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 the nuclear overhauser effect noe is the transfer of nuclear spin polarization from one nuclear spin population to another via cross relaxation it is a common phenomenon observed by nuclear magnetic resonance nmr spectroscopy the theoretical basis for the noe was described and experimentally verified by anderson and in the noe is an extension of the seminal work of american physicist albert overhauser who in proposed that nuclear spin polarization could be enhanced by the microwave irradiation of the conduction electrons in certain metals the general overhauser effect was first demonstrated experimentally by t r carver and c p slichter also in another early explanation and experimental observation of the noe was by in in an nmr experiment where the spin polarization was transferred from one population of nuclear spins to another rather than from electrons spins to nuclear spins however the theoretical basis and the applicable solomon equations had already been published by solomon in subsequent to its discovery the noe was shown to be highly useful in nmr spectroscopy for characterizing and organic chemical structures in this application the noe differs from the application of spin spin coupling in that the noe occurs through space not through chemical bonds thus atoms that are in close to each other can give a noe whereas spin coupling is observed only when the atoms are connected by chemical bonds the inter atomic distances derived from the observed noe can often help to confirm a precise molecular conformation i e the three dimensional structure of a molecule in was awarded the nobel prize in chemistry for demonstrating that the noe could be using two dimensional nmr spectroscopy to determine the three dimensional structures of biological macromolecules in solution 
 a quantum solvent is essentially a superfluid a quantum liquid used to another chemical species any superfluid can theoretically act as a quantum solvent however in practice the only viable superfluid medium that can currently be used is helium and it has been successfully accomplished in controlled conditions such solvents are currently under investigation for use in spectroscopic techniques in the field of analytical chemistry due to their kinetic properties any matter or otherwise suspended in the superfluid will to aggregate together in by a quantum solvation shell due to the totally nature of the superfluid medium the entire object then proceeds to act very much like a ball allowing effectively complete rotational freedom of the chemical species a quantum solvation shell consists of a region of non superfluid helium atoms that the molecule s and exhibit following around the centre of gravity of the as such the kinetics of an effectively molecule can be studied without the need to use an actual gas which can be impractical or impossible it is necessary to make a small to the rotational constant of the chemical species being examined in order to compensate for the higher mass by the quantum solvation shell quantum solvation has so far been achieved with a number of organic and compounds and it has been that as well as the obvious use in the field of spectroscopy quantum solvents could be used as tools in chemical engineering perhaps to components for use in nanotechnology 
 coupling is a coupled rotational and vibrational excitation of a molecule it is different from coupling which involves a change in all of electronic vibrational and rotational states simultaneously rotational vibrational spectroscopy generally vibrational transitions occur in conjunction with rotational transitions consequently it is possible to observe both rotational and vibrational transitions in the vibrational spectrum although many methods are available for observing vibrational spectra the two most common methods are infrared spectroscopy and raman spectroscopy formula where formula is the vibrational quantum number formula is the rotational quantum number h is planck s constant formula is the frequency of the vibration formula is the speed of light and formula is the rotational constant spectra the selection rule for the absorption of dipole radiation the strongest component of light is that formula this is because of the vector addition properties of quantum mechanical angular momenta and because light particles photons have angular momenta of in spectroscopy the transitions where formula are referred to as the p branch transitions with formula are referred to as q branch and formula as r branch for linear molecules the most commonly observed case is that only transitions with formula are observed this is only possible when the molecule has a ground state that is there are no unpaired electron spins in the molecule for molecules that do have unpaired electrons q branches see below are commonly observed the gap between the r and p branches is known as the q branch a peak would appear here for a vibrational transition in which the rotational energy did not change formula however according to the quantum mechanical rigid rotor model upon which rotational spectroscopy is based there is a spectroscopic selection rule that requires that formula this selection rule explains the p and r branches are observed but not the q branch as well as branches for which formula formula etc the positions of the peaks in the spectrum can be predicted using the rigid rotor model one prediction of the rigid rotor model is that the space between each of the peaks should be formula where formula is the rotational constant for a given molecule experimentally it is observed that the spacing between the r branch peaks decreases as the frequency increases similarly the spacing between the p branch peaks increases as the frequency decreases this variation in the spacing results from the bonds between the atoms in a molecule not being rigid formula formula rotational vibrational spectra will also show some fine structure due to the presence of different isotopes in the spectrum in the spectrum shown above all of the rotational peaks are slightly into two peaks one peak corresponds to and the other to the ratio of the peak intensities corresponds to the natural abundance of these two isotopes 
 in physics an effective field theory is as any effective theory an approximate theory usually a quantum field theory that includes appropriate degrees of freedom to describe physical phenomena occurring at a chosen length scale while and degrees of freedom at shorter distances or at higher energies the renormalization group presently effective field theories are discussed in the context of the renormalization group rg where the process of out short distance degrees of freedom is made systematic although this method is not sufficiently to allow the actual construction of effective field theories the understanding of their becomes clear through a rg analysis this method also to the main technique of effective field theories through the analysis of symmetries if there is a single mass scale m in the microscopic theory then the effective field theory can be seen as an expansion in m the construction of an effective field theory accurate to some power of m requires a new set of free parameters at each order of the expansion in m this technique is useful for scattering or other processes where the maximum momentum scale k satisfies the condition k since effective field theories are not valid at small length scales they need not be renormalizable indeed the ever expanding number of parameters at each order in m required for an effective field theory means that they are generally not renormalizable in the same sense as quantum electrodynamics which requires only the renormalization of three parameters examples of effective field theories fermi theory of beta this theory a interaction between the four fermions involved in these reactions the theory had great success and was eventually understood to arise from the gauge theory of interactions which forms a part of the standard model of particle physics in this more fundamental theory the interactions are by a changing gauge boson the the success of the fermi theory was because the w particle has mass of about gev whereas the early experiments were all done at an energy scale of less than mev such a separation of scales by over orders of magnitude has not been met in any other situation as yet bcs theory of superconductivity another famous example is the bcs theory of superconductivity here the underlying theory is of electrons in a metal interacting with lattice vibrations called phonons the phonons cause attractive interactions between some electrons causing them to form pairs the length scale of these pairs is much larger than the wavelength of phonons making it possible to neglect the dynamics of phonons and construct a theory in which two electrons effectively interact at a point this theory has had remarkable success in describing and predicting the results of experiments other examples presently effective field theories are written for many situations 
 chemical physics is a of chemistry and physics that phenomena using techniques from atomic and molecular physics and condensed matter physics it is the branch of physics that studies chemical processes from the point of view of physics while at the interface of physics and chemistry chemical physics is distinct from physical chemistry in that it focuses more on the characteristic elements and theories of physics meanwhile physical chemistry studies the physical nature of chemistry the distinction between the two fields is and workers often practice in each field during the course of their research 
 a rotational transition is an change in angular momentum in quantum physics like all other properties of a quantum particle angular momentum is quantized meaning it can only equal certain discrete values which correspond to different rotational energy states when a particle angular momentum it is said to have to a lower rotational energy state likewise when a particle gains angular momentum a positive rotational transition is said to have occurred rotational transitions are important in physics due to the unique spectral lines that result because there is a net gain or loss of energy during a transition electromagnetic radiation of a particular frequency must be absorbed or emitted this forms spectral lines at that frequency which can be detected with a as in rotational spectroscopy or raman spectroscopy 
 dynamic nuclear polarization dnp results from spin polarization from electrons to nuclei aligning the nuclear spins to the extent that electron spins are aligned note that the alignment of electron spins at a given magnetic field and temperature is described by the boltzmann distribution under the thermal equilibrium see figure it is also possible that those electrons are aligned to a higher degree of order by other of electron spin order such as chemical reactions leading to chemical induced dnp optical and spin dnp is considered one of several techniques for when electron spin polarization from its thermal equilibrium value polarization between electrons and nuclei can occur spontaneously through electron nuclear cross relaxation and or spin state mixing among electrons and nuclei for example the polarization transfer is after a chemical reaction on the other hand when the electron spin system is in a thermal equilibrium the polarization transfer requires continuous microwave irradiation at a frequency close to the corresponding electron paramagnetic resonance epr frequency in particular mechanisms for the microwave driven dnp processes are into the overhauser effect the solid effect the cross effect and thermal mixing the first dnp experiments were performed in the early at low magnetic fields but until recently the technique was of limited applicability for high frequency high field nmr spectroscopy because of the lack of microwave sources operating at the appropriate frequency today such sources are available as turn key instruments making dnp a valuable and indispensable method especially in the field of structure determination by high resolution solid state nmr spectroscopy dnp mechanisms the overhauser effect dnp was first realized using the concept of the overhauser effect which is the perturbation of nuclear spin level populations observed in metals and free radicals when electron spin transitions are by the microwave irradiation this effect relies on stochastic interactions between an electron and a nucleus the dynamic initially to highlight the time dependent and random interactions in this polarization transfer process the dnp phenomenon was theoretically predicted by albert overhauser in and initially some criticism from ramsey and other renowned physicists of the time on the grounds of being the experimental by carver and slichter as well as an from ramsey both reached overhauser in the same year the so called electron nucleus cross relaxation which is responsible for the dnp phenomenon is caused by rotational and translational modulation of the electron nucleus hyperfine coupling the theory of this process is based essentially on the second order time dependent perturbation theory solution of the von equation for the spin density matrix while the overhauser effect relies on time dependent electron nuclear interactions the remaining polarizing mechanisms rely on time independent electron nuclear and electron electron interactions the solid effect the solid effect occurs when the electron nucleus mutual flip transition in an electron nucleus two spin system is excited by microwave irradiation this polarizing mechanism is optimal when the exciting microwave frequency shifts up or down by the nuclear larmor frequency from the electron larmor frequency in the discussed two spin system the direction of frequency shifts corresponds to the sign of dnp enhancements therefore to the between positive and negative dnp enhancements it requires that the linewidth of the epr spectrum of involved unpaired electrons is smaller than the nuclear larmor frequency note that the transition moment for the above microwave excitation results from a second order effect of the electron nuclear interactions and thus requires stronger microwave power to be significant and its intensity is by an increase of the external magnetic field as a result the dnp enhancement from the solid effect scales as the cross effect the cross effect requires two unpaired electrons as the source of high polarization while the underlying physics is still of second order nature with respect to the electron electron and electron nuclear interactions the polarizing efficiency can be improved with the optimized epr frequency separation of the two electrons close to the nuclear larmor frequency as a result the strength of microwave irradiation is less than that in the solid effect in practice the correct epr frequency separation is accomplished through random orientation of paramagnetic species with g anisotropy depending on the probability of desired frequency separation from an broadened epr lineshape whose linewidth is than the nuclear larmor frequency therefore as this linewidth is proportional to external magnetic field the overall dnp efficiency or the enhancement of nuclear polarization scales as thermal mixing thermal mixing is an energy exchange phenomena between the electron spin ensemble and the nuclear spin which can be thought of as using multiple electron spins to provide nuclear polarization note that the electron spin ensemble acts as a whole because of stronger inter electron interactions the strong interactions lead to a broadened epr lineshape of the involved paramagnetic species the linewidth is optimized for polarization transfer from electrons to nuclei when it is close to the nuclear larmor frequency the optimization is related to an three spin electron electron nucleus process that the coupled three spins under the energy conservation mainly of the zeeman interactions due to the inhomogeneous component of the associated epr lineshape the dnp enhancement by this mechanism also scales as 
 the knight shift is a shift in the nuclear magnetic resonance frequency of a paramagnetic first published in by the american physicist walter david knight the knight shift refers to the relative shift k in nmr frequency for atoms in a metal e g sodium compared with the same atoms in a nonmetallic environment e g sodium chloride the observed shift reflects the local magnetic field produced at the sodium nucleus by the of the conduction electrons the average local field in sodium the applied resonance field by approximately one part per in nonmetallic sodium chloride the local field is negligible in comparison the knight shift is due to the conduction electrons in metals they an extra effective field at the nuclear site due to the spin of the conduction electrons in the presence of an external field this is responsible for the shift observed in the nuclear magnetic resonance the shift from two sources one is the pauli paramagnetic spin susceptibility the other is the s component at the nucleus depending on the electronic structure the knight shift may be temperature dependent however in metals which normally have a broad electronic density of states knight shifts are temperature independent 
 is the measure of the change in a molecule s electron distribution in response to an applied electric field which can also be induced by electric interactions with solvents or ionic it is a property of matter polarizabilities determine the dynamical response of a bound system to external fields and provide insight into a molecule s internal structure electric polarizability definition electric polarizability is the relative tendency of a charge distribution like the electron cloud of an atom or molecule to be distorted from its normal shape by an external electric field which is applied typically by the molecule in a charged parallel plate but may also be caused by the presence of a nearby ion or dipole the electronic polarizability formula is defined as the ratio of the induced dipole moment formula of an atom to the electric field formula that produces this dipole moment formula polarizability has the units of but is more often expressed as polarizability volume with units of or in formula where formula is the vacuum the polarizability of individual particles is related to the average electric susceptibility of the medium by the relation note that the polarizability formula as defined above is a scalar quantity this implies that the applied electric fields can only produce polarization components parallel to the field for example an electric field in the formula direction can only produce an formula component in formula however it can that an electric field in the formula direction produces a formula or formula component in the vector formula in this case formula is described as a tensor of rank which is represented with respect to a given system of axes frame of reference by a formula matrix generally polarizability increases as volume occupied by electrons increases in atoms this occurs because larger atoms have more loosely held electrons in contrast to smaller atoms with tightly bound electrons on rows of the periodic table polarizability therefore decreases from left to right polarizability increases down on columns of the periodic table likewise larger molecules are generally more polarizable than smaller ones though water is a very polar molecule alkanes and other hydrophobic molecules are more polarizable alkanes are the most polarizable molecules although and are expected to have larger polarizability than alkanes because of their higher reactivity compared to alkanes alkanes are in fact more polarizable this results because of s and s more electronegative carbons to the s less electronegative carbons it is important to note that ground state electron configuration models are often in studying the polarizability of bonds because dramatic changes in molecular structure occur in a reaction magnetic polarizability magnetic polarizability defined by spin interactions of nucleons is an important parameter of and in particular measurement of tensor polarizabilities of nucleons yields important information about spin dependent nuclear forces the method of spin amplitudes uses quantum mechanics to more easily describe spin dynamics vector and tensor polarization of particle nuclei with spin are specified by the unit polarization vector formula and the polarization tensor p additional of products of three or more spin matrices are needed only for the description of polarization of particles nuclei with spin polarizability of the nucleon the polarizabilities belong to the fundamental structure constants of the nucleon in addition to the mass the electric charge the spin and the magnetic moment the to measure the polarizabilities back to the two experimental options were considered i compton scattering by the proton and ii the scattering of slow neutrons in the coulomb field of heavy nuclei the idea was that the nucleon with its pion cloud obtains an electric dipole moment under the action of an electric field vector which is proportional to the electric polarizability after the discovery of the of the resonance it became obvious that the nucleon also should have a strong paramagnetic polarizability because of a virtual spin flip transition of one of the constituent quarks due to the magnetic field vector provided by a real photon in a compton scattering experiment however experiments showed that this expected strong paramagnetism is not observed apparently a strong diamagnetism exists which the expected strong paramagnetism though this explanation is it remained unknown how it may be understood in terms of the structure of the nucleon a solution of this problem was found very recently when it was shown that the diamagnetism is a property of the structure of the constituent quarks in this is not a because constituent quarks generate their mass mainly through interactions with the vacuum via the exchange of a meson this is predicted by the linear model on the quark level which also predicts the mass of the meson to be mev the meson has the capability of interacting with two photons being in parallel planes of linear polarization we will show in the following that the meson as part of the constituent quark structure therefore provides the part of the electric polarizability and the total diamagnetic polarizability definition of electromagnetic polarizabilities a nucleon in an electric field e and a magnetic field h obtains an electric dipole moment d and magnetic dipole moment m given by in a unit system where the electric charge formula is given by formula the proportionality constants formula and formula are denoted as the electric and magnetic polarizabilities respectively these polarizabilities may be understood as a measure of the response of the nucleon structure to the fields provided by a real or virtual photon and it is evident that we need a second photon to measure the polarizabilities this may be expressed through the relations where formula is the energy change in the electromagnetic field due to the presence of the nucleon in the field the definition implies that the polarizabilities are measured in units of a volume i e in units of formula m modes of two photon reactions and experimental methods electric fields of sufficient strength are provided by the coulomb field of heavy nuclei therefore the electric polarizability of the neutron can be measured by scattering slow neutrons in the electric field e of a pb nucleus the neutron has no electric charge therefore two simultaneously interacting electric field vectors two virtual photons are required to produce a deflection of the neutron then the electric polarizability can be obtained from the differential cross section measured at a small deflection angle a further possibility is provided by compton scattering of real photons by the nucleon where during the scattering process two electric and two magnetic field vectors simultaneously interact with the nucleon in the following we discuss the experimental options we have to measure the polarizabilities of the nucleon as above two photons are needed which simultaneously interact with the electrically charged parts of the nucleon these photons may be in parallel or perpendicular planes of linear polarization and in these two modes measure the polarizabilities formula formula or spinpolarizabilities formula respectively the is only for particles having a spin case corresponds to the measurement of the electric polarizability formula via two parallel electric field vectors e these parallel electric field vectors may either be provided as photons by the coulomb field of a heavy nucleus or by compton scattering in the forward direction or by reflecting the photon by real photons simultaneously provide electric e and magnetic h field vectors this means that in a compton scattering experiment linear combinations of electric and magnetic polarizabilities and linear combinations of electric and magnetic spinpolarizabilities are measured the combination of case and case measures formula and is observed in forward direction compton scattering the combination of case and case measures formula and is observed in backward direction compton scattering the combination of case and case measures formula and is observed in forward direction compton scattering the combination of case and case measures formula and is observed in backward direction compton scattering compton scattering experiments exactly in the forward direction and exactly in the backward direction are not possible from a technical point of view therefore the respective quantities have to be extracted from compton scattering experiments carried out at intermediate angles experimental results the experimental polarizabilities of the proton p and the neutron n may be as follows the experimental spinpolarizabilities of the proton p and neutron n are the experimental polarizabilities of the proton have been obtained as an average from a larger number of compton scattering experiments the experimental electric polarizability of the neutron is the average of an experiment on electromagnetic scattering of a neutron in the coulomb field of a pb nucleus and a compton scattering experiment on a neutron i e a neutron separated from a deuteron during the scattering process the two results are see furthermore there are experiments at the university of lund sweden where the electric polarizability of the neutron is determined through compton scattering by the deuteron calculation of polarizabilities recently great progress has been made in disentangling the total photoabsorption cross section into parts separated by the spin the and the parity of the intermediate state using the meson amplitudes of et al the spin of the intermediate state may be formula or formula depending on the spin directions of the photon and the nucleon in the initial state the parity change during the from the ground state to the intermediate state is formula for the multipoles formula and formula for the multipoles formula calculating the respective partial cross from photo meson data the following sum rules can be where formula is the photon energy in the lab frame the sum rules for formula and formula depend on nucleon structure degrees of freedom only whereas the sum rules for formula and formula have to be supplemented by the quantities formula and formula respectively these are formula channel contributions which may be interpreted as contributions of scalar and pseudoscalar mesons being parts of the constituent quark structure the sum rule for formula depends on the total photoabsorption cross section and therefore does not require a disentangling with respect to quantum numbers the sum rule for formula requires a disentangling with respect to the parity change of the transition the sum rule for formula requires a disentangling with respect to the spin of the intermediate state the sum rule for formula requires a disentangling with respect to spin and parity change the formula channel contributions depend on those scalar and pseudoscalar mesons which i are part of the structure of the constituent quarks and ii are capable of coupling to two photons these are the mesons formula formula and formula in case of formula and the mesons formula formula and formula in case of formula the are dominated by the formula and the formula whereas the other mesons only lead to small corrections results of calculation the electric polarizabilities formula and formula are dominated by a smaller component due to the pion cloud nucleon and a larger component due to the formula meson as part of the constituent quark structure const quark the magnetic polarizabilities formula and formula have a large paramagnetic part due to the spin structure of the nucleon nucleon and an only slightly smaller diamagnetic part due to the formula meson as part of the constituent quark structure const quark the contributions of the formula meson are supplemented by small corrections due to formula and formula mesons the spinpolarizabilities formula and formula are dominated by interfering components from the pion cloud and the spin structure of the nucleon the different obtained for the proton and the neutron are due to this destructive interference the spinpolarizabilities formula and formula have a minor component due to the structure of the nucleon nucleon and a major component due to the pseudoscalar mesons formula formula and formula as structure components of the constituent quarks const quark the agreement with the experimental data is excellent in all eight cases in the we have shown that the polarizabilities of the nucleon are well understood from previous the structure of the constituent quark is essential for the and the general properties of the polarizabilities 
 an anisotropic liquid is a liquid which has and where the molecules have an average structural order relative to each other along their molecular axis that ordinary do not have liquid are examples of anisotropic liquids 
 the rotating wave approximation is an approximation used in atom and magnetic resonance in this approximation terms in a hamiltonian which oscillate rapidly are neglected this is a valid approximation when the applied electromagnetic radiation is near resonance with an atomic resonance and the intensity is low terms in the which oscillate with frequencies formula are neglected while terms which oscillate with frequencies formula are kept where formula is the light frequency and formula is a transition frequency the name of the approximation from the form of the hamiltonian in the interaction picture as shown below by to this picture the evolution of an atom due to the corresponding atomic hamiltonian is absorbed into the system ket leaving only the evolution due to the interaction of the atom with the light field to consider it is in this picture that the rapidly oscillating terms mentioned previously can be neglected since in some sense the interaction picture can be thought of as rotating with the system ket only that part of the electromagnetic wave that approximately co rotates is kept the rotating component is mathematical formulation for consider a two level atomic system with ground and excited states formula and formula respectively using the notation let the energy difference between the states be formula so that formula is the transition frequency of the system then the hamiltonian of the atom can be written as suppose the atom an external classical electric field of frequency formula given by formula e g a plane wave propagating in space then under the dipole approximation the interaction hamiltonian between the atom and the electric field can be expressed as where formula is the dipole moment operator of the atom the total hamiltonian for the atom light system is therefore formula the atom does not have a dipole moment when it is in an energy so formula this means that defining formula allows the dipole operator to be written as making the approximation this is the point at which the rotating wave approximation is made the dipole approximation has been assumed and for this to remain valid the electric field must be near resonance with the atomic transition this means that formula and the complex formula and formula can be considered to be rapidly oscillating hence on any time scale the oscillations will quickly average to the rotating wave approximation is thus the claim that these terms may be neglected and thus the hamiltonian can be written in the interaction picture as at this point the rotating wave approximation is complete a common first step beyond this is to the remaining time dependence in the hamiltonian via another unitary transformation derivation given the above definitions the interaction hamiltonian is as stated the next step is to find the hamiltonian in the interaction picture formula the required unitary transformation is where the last step can be seen to follow e g from a series expansion and due to the of the states formula and formula we have the atomic hamiltonian was unaffected by the approximation so the total hamiltonian in the picture under the rotating wave approximation is 
 the rrkm theory is a theory of chemical reactivity it was developed by and in and in theory and into the rrkm theory in by who took the transition state theory developed by in into account these methods enable the computation of simple of the reaction rates from a few characteristics of the potential energy surface 
 a molecular vibration occurs when atoms in a molecule are in periodic motion while the molecule as a whole has constant translational and rotational motion the frequency of the periodic motion is known as a vibration frequency and the typical frequencies of molecular vibrations range from less than to approximately in general a molecule with n atoms has n normal modes of vibration but a linear molecule has n such modes as rotation about its molecular axis cannot be observed a diatomic molecule has one normal mode of vibration the normal modes of vibration of molecules are independent of each other but each normal mode will involve simultaneous vibrations of different parts of the molecule such as different chemical bonds a molecular vibration is excited when the molecule a quantum of energy e corresponding to the vibration s frequency according to the relation e where h is planck s constant a fundamental vibration is excited when one such quantum of energy is absorbed by the molecule in its ground state when two are absorbed the first overtone is excited and so on to higher overtones to a first approximation the motion in a normal vibration can be described as a kind of simple harmonic motion in this approximation the vibrational energy is a quadratic function with respect to the atomic and the first overtone has twice the frequency of the fundamental in reality vibrations are anharmonic and the first overtone has a frequency that is slightly lower than twice that of the fundamental excitation of the higher overtones involves less and less additional energy and eventually leads to dissociation of the molecule as the potential energy of the molecule is more like a morse potential the vibrational states of a molecule can be probed in a variety of ways the most direct way is through infrared spectroscopy as vibrational transitions typically require an amount of energy that corresponds to the infrared region of the spectrum raman spectroscopy which typically uses light can also be used to measure vibration frequencies directly the two techniques are complementary and comparison between the two can provide useful structural information such as in the case of the rule of mutual exclusion for molecules vibrational excitation can occur in conjunction with electronic excitation transition giving vibrational fine structure to electronic transitions particularly with molecules in the gas state simultaneous excitation of a vibration and gives rise to vibration rotation spectra vibrational coordinates the coordinate of a normal vibration is a combination of changes in the positions of atoms in the molecule when the vibration is excited the coordinate changes with a frequency the frequency of the vibration internal coordinates internal coordinates are of the following types with reference to the molecule in a rocking wagging or twisting coordinate the bond lengths within the groups involved do not change the angles do rocking is distinguished from wagging by the fact that the atoms in the group in the same plane in ethene there are internal coordinates c h stretching c c stretching h c h rocking wagging twisting note that the h c c angles cannot be used as internal coordinates as the angles at each carbon atom cannot all increase at the same time vibrations of a group in a molecule for illustration these do not represent the recoil of the c atoms which though necessarily present to balance the overall movements of the molecule are much smaller than the movements of the h atoms symmetry adapted coordinates symmetry adapted coordinates may be created by applying a projection operator to a set of internal coordinates the projection operator is constructed with the aid of the table of the molecular point group for example the four c h stretching coordinates of the molecule ethene are given by where are the internal coordinates for stretching of each of the four c h bonds of symmetry adapted coordinates for most small molecules can be found in normal coordinates the normal coordinates denoted as q refer to the positions of atoms away from their equilibrium positions with respect to a normal mode of vibration each normal mode is a single normal coordinate and so the normal coordinate refers to the progress along that normal mode at any given time formally normal modes are determined by solving a and then the normal coordinates over the normal modes can be expressed as a over the cartesian over the atom positions the advantage of working in normal modes is that they the matrix governing the molecular vibrations so each normal mode is an independent molecular vibration associated with its own spectrum of quantum mechanical states if the molecule symmetries it will belong to a point group and the normal modes will transform as an irreducible representation under that group the normal modes can then be determined by applying group theory and the irreducible representation onto the cartesian coordinates for example when this treatment is applied to it is found that the c o are not independent but rather there is a o c o symmetric stretch and an o c o stretch when two or more normal coordinates belong to the same irreducible representation of the molecular point group have the same symmetry there is mixing and the coefficients of the combination cannot be determined a for example in the linear molecule hydrogen the two stretching vibrations are the coefficients a and b are found by performing a full normal coordinate analysis by means of the gf method newtonian mechanics perhaps molecular vibrations can be treated using newtonian mechanics to calculate the correct vibration frequencies the basic is that each vibration can be treated as though it corresponds to a spring in the harmonic approximation the spring s law the force required to the spring is proportional to the extension the proportionality constant is known as a force constant k the anharmonic oscillator is considered elsewhere by second law of motion this force is also equal to a reduced mass times acceleration since this is one and the same force the ordinary differential equation follows the solution to this equation of simple harmonic motion is a is the maximum amplitude of the vibration coordinate q it remains to the reduced mass in general the reduced mass of a diatomic molecule is expressed in terms of the atomic masses and as the use of the reduced mass ensures that the centre of mass of the molecule is not affected by the vibration in the harmonic approximation the potential energy of the molecule is a quadratic function of the normal coordinate it follows that the force constant is equal to the second derivative of the potential energy when two or more normal vibrations have the same symmetry a full normal coordinate analysis must be performed see gf method the vibration frequencies i are obtained from the eigenvalues i of the matrix product gf g is a matrix of numbers derived from the masses of the atoms and the geometry of the molecule f is a matrix derived from force constant values details concerning the determination of the eigenvalues can be found in quantum mechanics in the harmonic approximation the potential energy is a quadratic function of the normal coordinates solving the wave equation the energy states for each normal coordinate are given by where n is a quantum number that can take values of the difference in energy when n changes by are therefore equal to the energy derived using classical mechanics see quantum harmonic oscillator for graphs of the first wave functions the wave functions certain selection rules can be formulated for example for a harmonic oscillator transitions are allowed only when the quantum number n changes by one but this does not apply to an anharmonic oscillator the observation of overtones is only possible because vibrations are anharmonic another consequence of is that transitions such as between states n and n have slightly less energy than transitions between the ground state and first excited state such a transition gives rise to a band intensities in an infrared spectrum the intensity of an absorption band is proportional to the derivative of the molecular dipole moment with respect to the normal coordinate the intensity of raman bands depends on polarizability 
 in combustion physics fuel mass fraction is the ratio of fuel mass flow to the total mass flow of a fuel if an air flow is fuel free the fuel mass fraction is zero in fuel without gases the ratio is unity as fuel is in a combustion process the fuel mass fraction is reduced 
 in molecular physics nanotechnology electrostatic deflection is the deformation of a beam like structure element bent by an electric field fig it can be due to interaction between electrostatic fields and net charge or electric polarization effects the beam like structure element is generally cantilevered at one of its ends in carbon nanotubes cnts are typical ones for electrostatic as show in fig when a material is brought into an electric field e the field tends to shift the positive charge in red and the negative charge in blue in opposite directions thus induced are created fig shows a beam like structure element in an electric field the interaction between the molecular dipole moment and the electric field results an induced torque t then this torque tends to align the beam toward the direction of field in case of a cantilevered cnt fig it would be bent to the field direction meanwhile the electrically induced torque and of the cnt against each other this deformation has been observed in experiments science and apl this property is an important characteristic for cnts promising nanoelectromechanical systems applications as well as for their separation and recently several nanoelectromechanical systems based on cantilevered cnts have been reported such as apl apl apl and feedback device apl which are designed for memory sensing or uses furthermore theoretical studies have been carried out to to get a full understanding of the electric deflection of carbon nanotubes z et al 
 the magic angle is a particular value of the collection angle of an electron microscope at which the measured energy loss spectrum becomes independent of the angle of the sample with respect to the beam direction the magic angle is not not uniquely defined for isotropic samples but the definition is unique in the typical case of small angle scattering on materials with a c axis such as the magic angle depends on both the incoming electron energy which is typically fixed and on the energy loss by the electron the ratio of the magic angle formula to the characteristic angle formula is roughly independent of the energy loss and more interestingly is roughly independent of the particular type of sample considered mathematical definition for the case of a relativistic incident electron the magic angle is defined by the of two different functions formula and math 
 the reactive empirical bond order rebo model is a widely used function for calculating the potential energy of bonds and the force in this model the total potential energy of system is a sum of nearest neighbour pair interactions which depend not only on the distance between atoms but also on their local atomic environment a bond order function was used to describe chemical pair interactions the early formulation and of rebo for carbon systems was done by tersoff in based on works of the tersoff s model could describe single double and triple bond energies in carbon structures such as in and a significant step was taken by brenner in he extended tersoff s potential function to radical and bonds by two additional terms into the bond order function compared to classical first principle and empirical approaches the rebo model is less time since only the and nearest neighbour interactions were considered this advantage of computational efficiency is especially for large scale atomic simulations from to atoms in recent years the rebo model has been widely used in the studies concerning mechanical and thermal properties of carbon nanotubes despite numerous successful applications of the first generation rebo potential function its several drawbacks have been reported e g its form is too to simultaneously fit equilibrium distances energies and force constants for all types of c c bonds the possibility of modeling processes involving atomic collisions is limited because both morse type terms go to finite values when the atomic distance decreases and the neglect of a separate pi bond leads to problems with the of radicals and a poor treatment of to these drawbacks an extension of brenner s potential was proposed by et al it is called the adaptive reactive bond order airebo potential in which both the and attractive pair interaction functions in rebo function are modified to fit bond properties and the long range atomic interactions and single bond interactions are included the airebo model has been used in recent studies using numerical simulations 
 photofragment ion imaging or more generally product imaging is an experimental technique for making measurements of the velocity of product molecules or particles following a chemical reaction or the photodissociation of a molecule the method uses a two dimensional detector usually a microchannel plate to record the arrival positions of state selected ions created by enhanced multi photon rempi the first experiment using photofragment ion imaging was performed by david w and in on the dynamics of methyl iodide background many problems in molecular reaction dynamics demand the simultaneous measurement of a particle s speed and angular direction the most demanding require the measurement of this velocity in coincidence with internal energy studies of molecular reactions energy transfer processes and photodissociation can only be understood completely if the internal energies and velocities of all products can be specified product imaging approaches this goal by determining the three dimensional velocity distribution of one state selected product of the reaction for a reaction producing two products because the speed of the sibling product is related to that of the measured product through conservation of momentum and energy the internal state of the sibling can often be example a simple example illustrates the principle ozone dissociates following ultraviolet excitation to yield an oxygen atom and an oxygen molecule although there are at least two possible channels the principle products are o and that is both the atom and the molecule are in their first excited electronic state see atomic term symbol and molecular term symbol for further explanation at a wavelength of the photon has enough energy to ozone to these two products to excite the to a maximum level of v and to provide some energy to the recoil velocity between the two fragments of course the more energy that is used to excite the vibrations the less will be available for the recoil rempi of the o atom in conjunction with the product imaging technique provides an image that can be used to determine the o three dimensional velocity distribution a slice through this cylindrically symmetric distribution is shown in the figure where an o atom that has zero velocity in the center of mass frame would arrive at the center of the figure note that there are four rings corresponding to four main groups of o speeds these correspond to production of the in the vibrational levels v and the ring corresponding to v is the outer one since production of the in this level the most energy for recoil between the o and thus the product imaging technique immediately shows the vibrational distribution of the note that the angular distribution of the o is not uniform more of the atoms toward the north or south pole than to the in this case the north south axis is parallel to the polarization direction of the light that the ozone ozone molecules that the polarized light are those in a particular alignment distribution with a line the end oxygen atoms in roughly parallel to the polarization because the ozone dissociates more rapidly than it rotates the o and products recoil along this polarization axis but there is more detail as well a close examination shows that the peak in the angular distribution is not actually exactly at the north or south pole but rather at an angle of about degrees this has to do with the polarization of the laser that the o and can be analyzed to show that the angular momentum of this atom which has units is aligned relative to the velocity of recoil more detail can be found elsewhere there are other dissociation channels available to ozone following excitation at this wavelength one produces o and that both the atom and molecule are in their ground electronic state the image above has no information on this channel since only the o is probed however by the ionization laser to the rempi wavelength of o one a completely different image that provides information about the internal energy distribution of the product imaging technique the original product imaging paper the positions of the ions are onto a two dimensional detector a photolysis laser dissociates methyl iodide while an ionization laser is used rempi to ionize a particular vibrational level of the product both lasers are and the ionization laser is at a delay short enough that the products have not moved because of an electron by the ionization laser does not change the recoil velocity of the fragment its position at any time following the photolysis is nearly the same as it would have been as a neutral the advantage of it to an ion is that by repelling it with a set of represented by the vertical solid lines in the figure one can project it onto a two dimensional detector the detector is a double microchannel plate of two glass with closely open channels several in diameter a high is placed across the plates as an ion hits inside a channel it secondary electrons that are then accelerated into the of the channel since multiple electrons are for each one that hits the wall the channels act as individual particle multipliers at the far end of the plates approximately electrons the channel for each ion that entered importantly they exit from a spot right behind where the ion entered the electrons are then accelerated to a phosphor screen and the spots of light are recorded with a charge coupled device ccd camera the image collected from each pulse of the lasers is then sent to a computer and the results of many thousands of laser are to provide an image such as the one for ozone shown previously in this position sensing version of product imaging the position of the ions as they hit the detector is recorded one can the ions produced by the dissociation and ionization lasers as expanding from the center of mass with a particular distribution of velocities it is this three dimensional object that we to detect since the ions created should be of the same mass they will all be accelerated toward the detector it takes very little time for the whole three dimensional object to be into the detector so the position of an ion on the detector relative to the center position is given simply by v where v is its velocity and is the time between when the ions were made and when they hit the detector the image is thus a two dimensional projection of the desired three dimensional velocity distribution for systems with an axis of cylindrical symmetry parallel to the surface of the detector the three dimensional distribution may be recovered from the two dimensional projection by the use of the inverse transform the cylindrical axis is the axis containing the polarization direction of the light it is important to note that the image is taken in the center of mass frame no transformation other than from time to speed is needed a final advantage of the technique should also be mentioned ions of different masses arrive at the detector at different times this differential arises because each ion is accelerated to the same total energy e as it the electric field but the acceleration speed vz varies as e thus vz varies as the reciprocal of the square root of the ion mass or the arrival time is proportional to the square root of the ion mass in a perfect experiment the ionization laser would ionize only the products of the dissociation and those only in a particular internal energy state but the ionization laser and perhaps the photolysis laser can create ions from other material such as or other the ability to detect a single mass by the detector is thus an important advantage in reducing noise to the product imaging technique velocity map imaging a major improvement to the product imaging technique was achieved by eppink and parker a difficulty that limits the resolution in the position sensing version is that the spot on the detector is no smaller than the cross sectional area of the ions excited for example if the volume of interaction of the molecular beam photolysis laser and ionization laser is say x x then the spot for an ion moving with a single velocity would still span x at the detector this is much larger than the limit of a channel width and is compared to the radius of a typical detector without some further improvement the velocity resolution for a position sensing apparatus would be limited to about one part in five eppink and parker found a way around this limit their version of the product imaging technique is called velocity map imaging velocity map imaging is based on the use of an lens to accelerate the ions toward the detector when the are properly adjusted this lens has the advantage that it focuses ions with the same velocity to a single spot on the detector regardless where the ion was created this technique thus overcomes the caused by the finite overlap of the laser and molecular beams three dimensional ion imaging and replaced the phosphor screen by a time delay line anode in order to be able to measure all three components of the initial product momentum vector simultaneously for each individual product particle at the detector this technique allows one to measure the three dimensional product momentum vector distribution without having to rely on mathematical reconstruction methods which require the investigated systems to be cylindrically symmetric later velocity mapping was added to imaging techniques have been used to characterize several elementary photodissociation processes and bimolecular chemical reactions chang et al realized that further increase in resolution could be gained if one carefully analyzed the results of each spot detected by the ccd camera under the microchannel plate typical in most laboratories each such spot was in diameter by a to each of up to spots per laser shot to determine the center of the distribution of each spot chang et al were able to further increase the velocity resolution to the equivalent of one pixel out of the pixel radius of the ccd slice imaging need to add this electron imaging product imaging of positive ions by rempi detection is only one of the areas where charged particle imaging has useful another area was in the detection of electrons the first ideas along these lines seem to have an early history et al were perhaps the first to a microscope they realized that trajectories of an electron emitted from an atom in different directions may again at a large distance from the atom and create an interference pattern they proposed building an apparatus to observe the predicted rings et al eventually realized such a and used it to study the of it was helm and co workers however who were the first to create an electron imaging apparatus the instrument is an improvement on previous photoelectron spectrometers in that it provides information on all energies and all angles of the for each shot of the laser helm and his co workers have now used this technique to investigate the ionization of and in more recent examples hayden and have pioneered the use of excitation and ionization to follow excited state dynamics in larger molecules coincidence imaging need to add a section here on work by hayden and others examples perhaps let people list examples of use here we need a good example of a bimolecular reaction or energy transfer another thought is to make a table here of the groups using this technique a reference the type of variation being used the type of application etc 
 a molecular beam is produced by allowing a gas at higher pressure to expand through a small into a chamber at lower pressure to form a beam of particles atoms free radicals molecules or ions moving at approximately equal velocities with very few collisions between the particles molecular beam is useful for thin in molecular beam and artificial structures such as quantum quantum and quantum molecular beams have also been applied as crossed molecular beams the molecules in the molecular beam can be by electrical fields and magnetic fields molecules can be in a decelerator or in a zeeman decelerator history the first to study molecular beams were h and f who in were in dipole moments and the deflection of beams of polar molecules in an inhomogeneous electric field their work indirectly the experiment that used not molecular beams but atomic beams the first to on the relationship between dipole moments and deflection in a beam using such as was in in a molecular beam magnetic resonance method in which two placed one after the other create a inhomogeneous magnetic field the method was used to measure the magnetic moment of several isotopes with molecular beams of and this method is a of nmr the of the in by and was made possible by a molecular beam of and a special electrostatic 
 mcconnell equation describes the proportional dependence of the hyperfine constant formula on the spin density formula the probability of an unpaired electron being on a particular atom in radical compounds such as radical formula formula formula is an empirical constant that can range from to history the equation is named after m mcconnell of stanford university who first presented it in in an article in the journal of chemical physics peter atkins de atkins physical chemistry oxford university press oxford 
 the zgb model is a statistical model most commonly to simulate catalytic reactions zgb in catalytic reactions the original paper presented zgb as a deviation from the classical approach to catalyst kinetics i e the tendency to consider only average concentrations of the adsorbed species and to write systems of differential equations of varying complexity with multiple parameters catalytic oxidation of carbon in the reactions above a molecule that is adsorbed on the catalyst surface when adsorbed the into two o atoms which occupy two separate catalyst surface sites the co molecule occupies a single surface site in the final step is produced and from the surface in the zgb simulation a trial with the random collision of a gas molecule on the square lattice that represents the catalyst surface the probability of the colliding molecule being co is expressed as yco while the probability of the colliding molecule being is expressed as yco 
 in chemistry the empirical formula of a chemical compound is the simplest positive integer ratio of atoms of each element present in a compound an empirical formula makes no reference to structure or absolute number of atoms the empirical formula is used as standard for most ionic compounds such as and for macromolecules such as empirical formula gives the simplest ratio of the atoms in a molecule or a compound in contrast the molecular formula identifies the number of each type of atom in a molecule and the structural formula also shows the structure of the molecule for example the chemical compound n hexane has the structural formula which shows that it has carbon atoms in a chain and hydrogen atoms hexane s molecular formula is and its empirical formula is showing a c h ratio of different compounds can have the same empirical formula for example formaldehyde acetic acid and glucose have the same empirical formula this is the actual molecular formula for formaldehyde but acetic acid has double the number of atoms and glucose has six times the number of atoms definition empirical formula a formula that gives the simplest whole number ratio of atoms in a compound 
 the pauli effect is a term referring to the apparently failure of technical equipment in the presence of certain people the term was coined using the name of the austrian theoretical physicist wolfgang pauli the pauli effect is not to be confused with the pauli exclusion principle which is a physical phenomenon history since the century the work of physics research has been divided between theorists and experimentalists see scientific method only a few physicists such as fermi have been successful in both roles an or interest in experimental work many theorists have a for breaking experimental equipment pauli was in this regard it was said that he was such a good that any experiments would simply because he was in the vicinity for fear of the pauli effect the experimental physicist pauli from his laboratory in despite their an incident occurred in the physics laboratory at the university of an expensive measuring device for no working although pauli was in fact james the director of the institute reported the incident to his pauli in with the that at least this time pauli was however it out that pauli on a to in about the time of failure the incident is reported in s years that physics where it is also claimed the effect to be stronger as the theoretical physicist is more the pauli effect if it were real would be classified as a macro phenomenon wolfgang pauli was that the effect named after him was real as pauli considered of serious investigation this would fit with his to this end pauli with hans and jung on the concept of in pauli saw a failure of his car during a with his second as proof of a real pauli effect since it occurred without an obvious external cause in february when he was at princeton university the and he asked if this to such a pauli effect named after him the pauli effect at the foundation of the c g jung institute caused pauli to write his article background physics in which he tries to find complementary between physics and depth psychology 
 the slac national accelerator laboratory originally named stanford linear accelerator center is a united states department of energy national laboratory operated by stanford university under the direction of the u s department of energy office of science the slac research program on experimental and theoretical research in elementary particle physics using electron beams and a broad program of research in atomic and solid state physics chemistry biology and medicine using synchrotron radiation history founded in as the stanford linear accelerator center the facility is located on square kilometers of stanford university land on road in of the university s main campus the main accelerator is miles longest linear accelerator in the has been operational since slac s meeting facilities also provided a venue for the computer and other of the home computer revolution of the late and early in the laboratory was named a national engineering landmark and an ieee slac developed and in december began the first server outside of europe in the early to mid the stanford linear collider slc investigated the properties of the z boson using the stanford large detector as of slac over people some of which are physicists with degrees and serves over researchers operating particle for high energy physics and the stanford synchrotron radiation laboratory ssrl for synchrotron light radiation research which was indispensable in the research leading to the nobel prize in chemistry in october the department of energy announced that the center s name would be changed to slac national accelerator laboratory the reasons given include a better representation of the new direction of the lab and the ability to trademark the laboratory s name stanford university had legally the department of energy s attempt to trademark stanford linear accelerator center components accelerator the main accelerator is an linear accelerator that can accelerate electrons and positrons up to gev at miles about kilometers long the accelerator is the longest linear accelerator in the world and is claimed to be the world s object the main accelerator is about below ground and underneath highway the above ground the is the longest building in the united states stanford linear collider the stanford linear collider was a linear accelerator that electrons and positrons at slac the center of mass energy was about gev equal to the mass of the z boson which the accelerator was designed to study student d discovered the first z event on april while over the previous day s computer data from the mark ii detector the bulk of the data was collected by the slac large detector which came online in although largely by the large electron positron collider at cern which began running in the highly polarized electron beam at slc close to made certain unique measurements possible presently no beam the south and north arcs in the machine which leads to the final focus therefore this section is to run beam into the section from the beam slac large detector the slac large detector sld was the main detector for the stanford linear collider it was designed primarily to detect z produced by the accelerator s electron positron collisions the sld operated from to pep ii from to the main purpose of the linear accelerator was to electrons and positrons into the pep ii accelerator an electron positron collider with a pair of storage rings miles in pep ii was host to the experiment one of the so called b experiments studying charge parity symmetry stanford synchrotron radiation lightsource the stanford synchrotron radiation lightsource ssrl is a synchrotron light user facility located on the slac campus originally built for particle physics it was used in experiments where the j meson was discovered it is now used for materials science and biology experiments which take advantage of the high intensity synchrotron radiation emitted by the stored electron beam to study the structure of molecules in the early an independent electron was built for this storage ring allowing it to operate independently of the main linear accelerator kipac the institute for particle astrophysics and kipac is partially on the grounds of slac in addition to its presence on the main stanford campus lcls the coherent light source lcls is a free electron laser facility located at slac the lcls is partially a reconstruction of the last of the original linear accelerator at slac and can extremely x ray radiation for research in a number of areas it achieved first in april the laser uses x rays times the relative of traditional x rays in order to take of objects on the nearly atomic level before samples the laser s wavelength is similar in width to an atom providing extremely detailed images on a scale previously additionally the laser is capable of capturing images with a speed measured in or of a second necessary because the intensity of the beam is such that it nearly its subject 
 image laws in latin thumb right newton s first and second laws in latin from the original principia mathematica law thumb walter explains newton s first law and reference frames mit physics physics i classical mechanics fall video mit course the three laws of motion were first compiled by sir isaac newton in his work naturalis principia mathematica first published in newton used them to explain and investigate the motion of many physical objects and systems for example in the third volume of the newton showed that these laws of motion combined with his law of universal gravitation explained kepler s laws of motion overview newton s laws are applied to bodies objects which are considered or idealized as a particle in the sense that the extent of the body is neglected in the evaluation of its motion i e the object is small compared to the distances involved in the analysis or the deformation and rotation of the body is of no importance in the analysis therefore a planet can be idealized as a particle for analysis of its motion around a in their original form newton s laws of motion are not to characterize the motion of rigid bodies and deformable bodies euler in introduced a generalization of newton s laws of motion for rigid bodies called the euler s laws of motion later applied as well for deformable bodies assumed as a continuum if a body is represented as an assemblage of discrete particles each governed by laws of motion then laws can be derived from laws laws can however be taken as axioms describing the laws of motion for extended bodies independently of any particle structure newton s laws hold only with respect to a certain set of frames of reference called newtonian or inertial reference frames some authors the first law as defining what an inertial reference frame is from this point of view the second law only holds when the observation is made from an inertial reference frame and therefore the first law cannot be as a special case of the second other authors do treat the first law as a of the second the explicit concept of an inertial frame of reference was not developed until long after newton s death in the given interpretation mass acceleration momentum and most importantly force are assumed to be defined quantities this is the most common but not the only interpretation one can consider the laws to be a definition of these quantities newtonian mechanics has been by special relativity but it is still useful as an approximation when the speeds involved are much than the speed of light newton s first law newton s laws are valid only in an inertial reference frame any reference frame that is in uniform motion with respect to an inertial frame is also an inertial frame i e galilean invariance or the principle of newtonian relativity newton s first law is a of the law of inertia which galileo had already described and newton gave credit to galileo had the view that all objects have a natural place in the universe that heavy objects like wanted to be at rest on the earth and that light objects like wanted to be at rest in the and the stars wanted to remain in the he thought that a body was in its natural state when it was at rest and for the body to in a straight line at a constant speed an external was needed to it otherwise it would stop moving galileo however realized that a force is necessary to change the velocity of a body i e acceleration but no force is needed to maintain its velocity this insight leads to newton s first force means no acceleration and hence the body will maintain its velocity the law of inertia apparently occurred to several different natural and scientists independently including thomas in his the century also formulated the law although he did not perform any experiments to confirm it newton s second law where since the law is valid only for constant mass systems the mass can be taken outside the differentiation operator by the constant factor rule in differentiation thus where f is the net force applied m is the mass of the body and a is the body s acceleration thus the net force applied to a body produces a proportional acceleration in other words if a body is accelerating then there is a force on it any mass that is gained or by the system will cause a change in momentum that is not the result of an external force a different equation is necessary for variable mass systems see below consistent with the first law the time derivative of the momentum is non zero when the momentum changes direction even if there is no change in its magnitude such is the case with uniform circular motion the relationship also implies the conservation of momentum when the net force on the body is zero the momentum of the body is constant any net force is equal to the rate of change of the momentum newton s second law requires modification if the effects of special relativity are to be taken into account because at high speeds the approximation that momentum is the product of rest mass and velocity is not accurate impulse an impulse j occurs when a force f acts over an interval of time t and it is given by since force is the time derivative of momentum it follows that this relation between impulse and momentum is to newton s wording of the second law impulse is a concept frequently used in the analysis of collisions and impacts variable mass systems variable mass systems like a rocket fuel and spent gases are not closed and cannot be directly treated by making mass a function of time in the second law where is the total external force on the system m is the total mass of the system and acm is the acceleration of the center of mass of the system where u is the relative velocity of the or incoming mass with respect to the center of mass of the body under some the quantity m d t on the left hand side known as the is defined as a force the force on the body by the changing mass such as rocket and is included in the quantity f then by the definition of acceleration the equation becomes history the sense or senses in which newton used his and how he understood the second law and intended it to be understood have been extensively discussed by of science along with the relations between newton s formulation and modern newton s third law in the above as motion is newton s name for momentum hence his distinction between motion and velocity the third law means that all forces are interactions between different bodies and thus that there is no such as a force or a force that acts on only one body whenever a first body exerts a force f on a second body the second body exerts a force on the first body f and are equal in magnitude and opposite in direction this law is sometimes referred to as the action reaction law with f called the action and the reaction the action and the reaction are simultaneous as shown in the diagram opposite the forces on each other are equal in magnitude but act in opposite directions although the forces are equal the are not the less massive will have a greater acceleration due to newton s second law the two forces in newton s third law are of the same type e g if the road exerts a forward frictional force on an accelerating car s tires then it is also a frictional force that newton s third law predicts for the tires backward on the road put very simply a force acts between a pair of objects and not on a single object so each and every force has two ends each of the two ends is the same except for being opposite in direction the ends of a force are mirror images of each other one might say from a mathematical point of view newton s third law is a one dimensional vector equation which can be stated as follows given two objects a and b each a force on the other where newton used the third law to derive the law of conservation of momentum however from a conservation of momentum is the more fundamental idea derived via s from galilean invariance and holds in cases where newton s third law appears to for instance when force fields as well as particles momentum and in quantum mechanics importance and range of validity newton s laws were verified by experiment and observation for over years and they are excellent approximations at the scales and speeds of everyday life newton s laws of motion together with his law of universal gravitation and the mathematical techniques of provided for the first time a quantitative explanation for a wide range of physical phenomena these three laws hold to a good approximation for macroscopic objects under everyday conditions however newton s laws combined with universal gravitation and classical electrodynamics are for use in certain most notably at very small scales very high speeds in special relativity the lorentz factor must be included in the expression for momentum along with rest mass and velocity or very strong gravitational fields therefore the laws cannot be used to explain phenomena such as conduction of electricity in a optical properties of errors in non systems and superconductivity explanation of these phenomena requires more physical theories including general relativity and quantum field theory in quantum mechanics concepts such as force momentum and position are defined by linear operators that operate on the quantum state at speeds that are much lower than the speed of light newton s laws are just as exact for these operators as they are for classical objects at speeds comparable to the speed of light the second law holds in the original form which says that the force is the derivative of the momentum of the object with respect to time but some of the newer versions of the second law such as the constant mass approximation above do not hold at relativistic velocities relationship to the conservation laws in modern physics the laws of conservation of momentum energy and angular momentum are of more general validity than newton s laws since they apply to both light and matter and to both classical and non classical physics this can be stated simply momentum energy and angular momentum cannot be created or destroyed because force is the time derivative of momentum the concept of force is redundant and to the conservation of momentum and is not used in fundamental theories e g quantum mechanics quantum electrodynamics general relativity etc the standard model explains in detail how the three fundamental forces known as gauge forces out of exchange by virtual particles other forces such as gravity and fermionic pressure also arise from the momentum conservation indeed the conservation of momentum in inertial motion via space time results in what we call gravitational force in general relativity theory application of space derivative which is a momentum operator in quantum mechanics to overlapping wave functions of pair of fermions particles with half integer spin results in shifts of of compound away from each other which is observable as of fermions newton stated the third law within a world view that assumed instantaneous action at a distance between material particles however he was for philosophical criticism of this action at a distance and it was in this context that he stated the famous i no hypotheses in modern physics action at a distance has been completely eliminated except for effects involving quantum however in modern engineering in all practical applications involving the motion of vehicles and the concept of action at a distance is used extensively conservation of energy was discovered nearly two centuries after newton s the long delay occurring because of the difficulty in understanding the role of microscopic and forms of energy such as heat and red light 
 uncertainty is a term used in different ways in a number of fields including physics philosophy statistics insurance psychology engineering and information science it applies to predictions of future events to physical measurements already made or to the unknown concepts uncertainty for example if you do not know whether it will rain tomorrow then you have a state of uncertainty if you apply probabilities to the possible outcomes using or even just a probability assessment you have quantified the uncertainty suppose you quantify uncertainty as a chance of if you are planning a major costly event for tomorrow then you have risk since there is a chance of rain and rain would be furthermore if this is a business event and you would lose if it then you have quantified the risk a chance of losing these situations can be made even more realistic by light rain vs heavy rain the cost of vs etc some may represent the risk in this example as the expected opportunity loss eol or the chance of the loss multiplied by the amount of the loss that is useful if the of the event is risk neutral which most people are not most would be willing to pay a to avoid the loss an insurance company for example would compute an eol as a minimum for any insurance coverage then add on to that other operating costs and profit since many people are willing to insurance for many reasons then clearly the eol is not the value of avoiding the risk quantitative uses of the terms uncertainty and risk are consistent from fields such as probability theory science and information theory some also create new terms without changing the definitions of uncertainty or risk for example is a variation on uncertainty sometimes used in information theory but outside of the more mathematical uses of the term usage may vary widely in cognitive psychology uncertainty can be real or just a matter of such as expectations etc or ambiguity are sometimes described as second order uncertainty where there is uncertainty even about the definitions of uncertain states or outcomes the difference here is that this uncertainty is about the human definitions and concepts not an objective fact of nature it has been that ambiguity however is avoidable while uncertainty of the first order kind is not necessarily avoidable uncertainty may be purely a consequence of a lack of knowledge of obtainable facts that is you may be uncertain about whether a new rocket design will work but this uncertainty can be removed with further analysis and experimentation at the level however uncertainty may be a fundamental and property of the universe in quantum mechanics the heisenberg uncertainty principle limits on how much an can ever know about the position and velocity of a particle this may not just be ignorance of obtainable facts but that there is no fact to be found there is some in physics as to whether such uncertainty is an irreducible property of nature or if there are hidden variables that would describe the state of a particle even more exactly than heisenberg s uncertainty principle allows measurements the middle notation is used when the error is not about the value for example formula this can occur when using a scale for example the latter notation is used for example by in the atomic mass of elements there the uncertainty given in applies to the least significant figure s of the number prior to the value i e from to left for instance stands for while stands for often the uncertainty of a measurement is found by the measurement enough times to get a good estimate of the standard deviation of the values then any single value has an uncertainty equal to the standard deviation however if the values are then the mean measurement value has a much smaller uncertainty equal to the standard error of the mean which is the standard deviation divided by the square root of the number of measurements when the uncertainty represents the standard error of the measurement then about of the time the true value of the measured quantity within the stated uncertainty range for example it is likely that for of the atomic mass values given on the list of elements by atomic mass the true value outside of the stated range if the width of the interval is doubled then probably only of the true values lie outside the doubled interval and if the width is tripled probably only lie outside these values follow from the properties of the normal distribution and they apply only if the measurement process produces normally distributed errors in that case the standard errors are easily to one sigma two sigma or three sigma in this context uncertainty depends on both the accuracy and precision of the measurement instrument the lower the accuracy and precision of an instrument the larger the measurement uncertainty is notice that precision is often determined as the standard deviation of the repeated measures of a given value using the same method described above to assess measurement uncertainty however this method is correct only when the instrument is accurate when it is inaccurate the uncertainty is larger than the standard deviation of the repeated measures and it appears evident that the uncertainty does not depend only on instrumental precision uncertainty and the media uncertainty in science and science in general is often interpreted much differently in the public sphere than in the scientific community this is due in part to the diversity of the public audience and the tendency for scientists to and therefore not communicate ideas clearly and effectively one example is explained by the information model also in the public there are often many scientific giving on a single topic for example depending on how an issue is reported in the public sphere between outcomes of multiple scientific studies due to differences could be interpreted by the public as a lack of consensus in a situation where a consensus does in fact exist this interpretation may even been as scientific uncertainty may be to reach certain goals for example global warming took the of to frame global warming as an issue of scientific uncertainty which was a precursor to the frame used by journalists when reporting the issue can be loosely said to apply to situations in which not all the parameters of the system and their interactions are fully known whereas ignorance refers to situations in which it is not known what is not known these indeterminacy and ignorance that exist in science are often into uncertainty when reported to the public in order to make issues more since scientific indeterminacy and ignorance are difficult concepts for scientists to without losing conversely uncertainty is often interpreted by the public as ignorance the transformation of indeterminacy and ignorance into uncertainty may be related to the of uncertainty as ignorance journalists often either inflate uncertainty making the science seem more uncertain than it really is or downplay uncertainty making the science seem more certain than it really is one way that journalists inflate uncertainty is by describing new research that past research without providing context for the change other times journalists give scientists with views equal weight as scientists with majority views without describing or explaining the state of scientific consensus on the issue in the same journalists often give non scientists the same amount of attention and importance as scientists journalists may downplay uncertainty by carefully chosen wording and by losing these the information is and presented as more certain and than it really also stories with a single source or without any context of previous research mean that the subject at hand is presented as more definitive and certain than it is in reality there is often a over approach to science that too in the of finally and most notably for this investigation when science is framed by journalists as a uncertainty is framed as and some media routines and organizational factors affect the of uncertainty other media routines and organizational factors help inflate the of an issue because the general public in the united states generally scientists when science stories are covered without from special interest organizations groups environmental organization etc they are often covered in a business related sense in an economic development frame or a social progress frame the nature of these frames is to downplay or uncertainty so when economic and scientific are focused on early in the issue cycle as has happened with coverage of plant biotechnology and nanotechnology in the united states the matter in question seems more definitive and certain sometimes too or will pressure a media organization to promote the business aspects of a scientific issue and therefore any uncertainty that may the business are or eliminated applications in financial such as the market 
 in physics and engineering a ripple tank is a shallow glass tank of water used in and to demonstrate the basic properties of waves it is a specialized form of a wave tank the ripple tank is usually illuminated from above so that the light through the water some small ripple fit onto the top of an overhead i e they are illuminated from below the ripples on the water show up as on the screen underneath the tank all the basic properties of waves including reflection refraction interference and diffraction can be demonstrated ripples may be generated by a piece of wood that is suspended above the tank on elastic bands so that it is just the surface to wood is a motor that has an off centre weight attached to the axle as the axle rotates the motor the wood and generating ripples demonstrating wave properties a number of wave properties can be demonstrated with a ripple tank these include plane waves reflection refraction interference and diffraction circular waves when the rippler is attached with a point ball and lowered so that it just touches the surface of the water circular waves will seen to be produced plane waves when the rippler is lowered so that it just touches the surface of the water plane waves will seen to be produced in the illustration the brown is the rippler reflection demonstrating reflection and focusing of by a metal bar in the tank and the bar a pulse of three of four ripples can be sent towards the metal bar the ripples reflect from the bar if the bar is placed at an angle to the wavefront the reflected waves can be seen to the law of reflection the angle of incidence and angle of reflection will be the same if a obstacle is used a plane wave pulse will on a point after reflection this point is the focal point of the mirror circular waves can be produced by a single drop of water into the ripple tank if this is done at the focal point of the mirror plane waves will be reflected back refraction if a of glass is placed in the tank the depth of water in the tank will be over the glass than elsewhere the speed of a wave in water depends on the depth so the ripples slow down as they pass over the glass this causes the wavelength to decrease if the between the and shallow water is at an angle to the wavefront the waves will refract in the diagram above the waves can be seen to towards the normal the normal is shown as a line the line is the direction that the waves would travel if they had not met the piece of glass in practice showing refraction with a ripple tank is quite to do diffraction if a small obstacle is placed in the path of the ripples and a slow frequency is used there is no shadow area as the ripples refract around it as shown below on the left a faster frequency may result in a shadow as shown below on the right if a large obstacle is placed in the tank a shadow area will probably be observed if an obstacle with a small gap is placed in the tank the ripples emerge in an almost pattern if the gap is large however the diffraction is much more limited small in this context means that the size of the obstacle is comparable to the wavelength of the ripples see also s principle diffraction from a grid a phenomenon identical to the x ray diffraction of x rays from an atomic crystal lattice can also be seen thus demonstrating the principles of crystallography if one a grid of obstacles into the water with the spacing between the obstacles roughly corresponding to the wavelength of the water waves one will see diffraction from the grid at certain angles between the grid and the waves the waves will appear to reflect off the grid at other angles the waves will pass through similarly if the frequency wavelength of the waves is altered the waves will also pass through or be reflected depending on the precise relationship between spacing orientation and wavelength interference interference can be produced by the use of two that are attached to the main ripple bar in the below on the left the light areas represent of waves the black areas represent notice the grey areas they are areas of destructive interference where the waves from the two sources one another out to the right is a of two point interference generated in a circular ripple tank 
 particle induced x ray emission or proton induced x ray emission pixe is a technique used in the determining of the elemental make up of a material or sample when a material is to an ion beam atomic interactions occur that give off radiation of in the x ray part of the electromagnetic spectrum specific to an element pixe is a powerful yet non destructive elemental analysis technique now used routinely by and others to help questions of and the technique was first proposed in by johansson of lund university sweden and developed over the next few years with his and thomas b johansson recent of pixe using tightly focused beams down to gives the additional capability of microscopic analysis this technique called micropixe can be used to determine the distribution of trace elements in a wide range of samples a related technique particle induced ray emission can be used to detect some light elements theory x ray emission quantum theory states that electrons of an atom must occupy discrete energy levels in order to be stable with ions of sufficient energy usually mev protons produced by an ion accelerator will cause inner shell ionization of atoms in a outer shell electrons drop down to inner shell however only certain transitions are allowed x rays of a characteristic energy of the element are emitted an energy detector is used to record and measure these x rays only elements than can be detected the lower detection limit for a pixe beam is given by the ability of the x rays to pass through the between the chamber and the x ray detector the upper limit is given by the ionisation cross section the probability of the k electron shell ionisation this is maximal when the velocity of the proton the velocity of the electron of the speed of light therefore mev proton beams are optimal proton backscattering protons can also interact with the nucleus of the atoms in the sample through elastic collisions backscattering often repelling the proton at angles close to degrees the give information on the sample thickness and composition the bulk sample properties allow for the correction of x ray photon loss within the sample proton transmission the transmission of protons through a sample can also be used to get information about the sample protein analysis protein analysis using micropixe allow for the determination of the elemental composition of liquid and crystalline proteins micropixe can quantify the metal content of protein molecules with a relative accuracy of between and the advantage of micropixe is that given a protein of known sequence the x ray emission from sulfur can be used as an internal standard to calculate the number of metal atom per protein because only relative concentrations are calculated there are only minimal systematic errors and the results are totally consistent the relative concentrations of dna to protein and metals can also be measured using the groups of the bases as an internal data analysis analysis of the data collected can be performed by the programs the end to limitations in order to get a meaningful sulfur signal from the analysis the buffer should not contain sulfur i e no or compounds excessive amounts of in the buffer should also be this will overlap with the sulfur peak and are suitable advantages there are many advantages to using a proton beam over an electron beam there is less crystal from radiation although there is some from the emission of electrons there is significantly less than if the primary beam was itself an electron beam because of the higher mass of protons relative to electrons there is less lateral deflection of the beam this is important for proton beam writing applications scanning two dimensional maps of elemental can be generated by scanning the micropixe beam across the target cell and tissue analysis whole cell and tissue analysis is possible using a micropixe beam this method is also referred to as nuclear artifact analysis micropixe is a useful technique for the non destructive analysis of and although it provides only an elemental analysis it can be used to and measure layers within the thickness of an artifact proton beam writing proton beams can be used for writing proton beam writing through either the of a by proton induced cross or through the of a proton sensitive material this may have important effects in the field of nanotechnology 
 within the field of physics experimental physics is the category of disciplines and sub disciplines concerned with the observation of physical phenomena in order to data about the universe methods vary from discipline to discipline from simple experiments and observations such as the experiment to more complicated ones such as the large collider overview experimental physics all the disciplines of physics that are concerned with data acquisition data acquisition methods and the detailed beyond simple thought experiments and of laboratory experiments it is often put in contrast with theoretical physics which is more concerned with predicting and explaining the physical behaviour of nature than the acquisition of knowledge about it although experimental and theoretical physics are concerned with different aspects of nature they both share the same goal of understanding it and have a relation the former provides data about the universe which can then be analyzed in order to be understood while the latter provides for the data and thus offers insight on how to better data and on how to set up experiments theoretical physics can also offer insight on what data is needed in order to gain a better understanding of the universe and on what experiments to in order to obtain it history as a distinct field experimental physics was established in early modern europe during what is known as the scientific revolution by physicists such as galileo huygens johannes kepler and sir isaac newton in the early century galileo made extensive use of experimentation to physical theories which is the key idea in the modern scientific method galileo formulated and successfully tested several results in dynamics in particular the law of inertia which later became the first law in newton s laws of motion in galileo s two new sciences a between the and discuss the motion of a ship as a moving frame and how that ship s is to its motion huygens used the motion of a along a dutch to an early form of the conservation of momentum experimental physics is considered to have with the publication of the naturalis principia mathematica in by sir isaac newton in newton published the principia two comprehensive and successful physical theories newton s laws of motion from which arise classical mechanics and newton s law of universal gravitation which describes the fundamental force of gravity both theories well with experiment the principia also included several theories in fluid dynamics from the late century thermodynamics was developed by physicist and boyle young and many others in used statistical with classical mechanics to derive thermodynamic results the field of statistical mechanics in demonstrated the of mechanical work into heat and in stated the law of conservation of energy in the form of heat as well as mechanical energy boltzmann in the nineteenth century is responsible for the modern form of statistical mechanics classical mechanics and thermodynamics another great field of experimental within physics was the nature of electricity observations in the and century by scientists such as boyle and created a foundation for later work these observations also established our basic understanding of electrical charge and current by had discovered that atoms of different elements have different and proposed the modern theory of the atom it was hans who first proposed the between electricity and magnetism after observing the deflection of a by a nearby electric current by the early michael faraday had demonstrated that magnetic fields and electricity could generate each other in james maxwell presented to the society a set of equations that described this relationship between electricity and magnetism maxwell s equations also predicted correctly that light is an electromagnetic wave starting with astronomy the principles of natural philosophy into fundamental laws of physics which were and improved in the centuries by the century the sciences had into multiple fields with specialized researchers and the field of physics although pre no longer could claim of the entire field of scientific research method experimental physics uses two main methods of experimental research controlled experiments and natural experiments controlled experiments are often used in laboratories as laboratories can offer a controlled environment natural experiments are used for example in astrophysics when observing objects where control of the variables in effect is impossible experimental techniques some well known experimental techniques include timelines see the timelines below for of physics experiments 
 in physics two experimental techniques are often called complementary if they investigate the same subject in two different ways such that two different ideally non overlapping properties or aspects can be investigated for example x ray scattering and neutron scattering experiments are often said to be complementary because the former information about the electron density of the atoms in the target but gives no information about the nuclei because they are too small to affect the x rays significantly while the latter allows you to investigate the nuclei of the atoms but cannot you about their electron because the neutrons being neutral do not interact with the charged electrons scattering experiments are sometimes also called complementary when they investigate the same physical property of a system from two complementary view points in the sense of for example time resolved and energy resolved experiments are said to be complementary the former uses a pulse which is well defined in time its position is well known at a given time the latter uses a pulse well defined in energy its frequency is well known 
 the elevator paradox to a hydrometer placed on an elevator or vertical that by moving to different changes the pressure in this classic demonstration the hydrometer remains at an equilibrium position essentially a hydrometer measures specific gravity of liquids independent of barometric pressure this is because the change in air pressure is applied to the entire hydrometer flask the portion of the flask receives a force through the liquid thus no portion of the apparatus receives a net force resulting from a change in air pressure this is a paradox if the buoyancy of the hydrometer is said to depend on the weight of the liquid that it displaces at a higher barometric pressure the liquid occupies a slightly smaller volume and thus more dense might be considered to have a higher specific gravity however the hydrometer also displaces air and the weight of the liquid and the air are affected equally by cartesian a cartesian diver on the other hand has an internal space that unlike a hydrometer is not rigid and thus can change its as increasing external air pressure the air in the diver if the diver instead of being placed in the classic were in a flask on an elevator the diver would to a change in air pressure similarly a non rigid like a will be affected as will the cage of a human diver and such systems will vary in buoyancy a glass hydrometer is rigid under normal pressure for all practical purposes the hydrometer in an accelerating frame of reference the or downward acceleration of the elevator as long as the net force is directed downward will not change the equilibrium point of the hydrometer either the force due to acceleration acts on the hydrometer exactly as it would on an equal mass of water or other liquid 
 a wave tank is a laboratory for observing the behavior of surface waves the typical wave tank is a box filled with liquid usually water leaving open or air filled space on top at one end of the tank an generates waves the other end usually has a wave surface a similar device is the ripple tank which is flat and shallow and used for observing patterns of surface waves from above a wave is a wave tank which has a width and length of comparable magnitude often used for testing structures and three dimensional models of and their another type of wave tank is the wave which is in width and often has windows for observing the wave motion as well as the physical model being tested in literature in the novel state of fear a wave tank was to simulate a made 
 classical newtonian physics has formally been replaced by quantum mechanics on the small scale and relativity on the large scale because most humans continue to think in terms of the kind of events we in the human scale of daily life it became necessary to provide a new philosophical interpretation of classical physics classical mechanics worked extremely well within its domain of observation but made inaccurate predictions at very small scale atomic scale systems and when objects moved very fast or were very massive through the lens of quantum mechanics or relativity we can now see that classical physics from the world of our everyday experience includes for which there is no actual evidence for example one commonly held idea is that there exists one absolute time shared by all another is the idea that electrons are discrete entities like that circle the nucleus in definite orbits the correspondence principle says that classical accounts are approximations to quantum mechanics that are for all practical purposes equivalent to quantum mechanics when with macro scale events various problems occur if classical mechanics is used to describe quantum systems such as the ultraviolet in black body radiation the paradox and the lack of a zero point for entropy since classical physics corresponds more closely to ordinary language than modern physics does this subject is also a part of the philosophical interpretation of ordinary language which has other aspects as well the measurement process in classical mechanics it is assumed that given properties speed or mass of a particle temperature of a gas etc can in principle be measured to any degree of accuracy desired study of the problem of measurement in quantum mechanics has shown that measurement of any object involves interactions between the measuring apparatus and that object that affect it in some way at the scale of particles this effect is necessarily large on the everyday macroscopic scale the effect can be made small furthermore the classical of a property simply being measured the fact that measurement of a property temperature of a gas by say involves a pre existing account of the behavior of the measuring device when effort was to working out the operational definitions involved in precisely determining position and momentum of scale entities physicists were required to provide such an account for measuring to be used at that scale the key thought experiment in this regard is known as heisenberg s microscope the problem for the individual is how to properly characterize a part of reality of which one has no direct sense experience our into the quantum domain find most it is that happens in between the events by means of which we obtain our only information our accounts of the quantum domain are based on interactions of macro domain instruments and sense with physical events and those interactions give us some but not all of the information we seek we then seek to derive further information from series of those experiments in an way we can say that physics is a part of science and as such aims at a description and understanding of nature any kind of understanding scientific or not depends on our language on the communication of ideas every description of phenomena of experiments and their results upon language as the only means of communication the words of this language represent the concepts of daily life which in the scientific language of physics may be refined to the concepts of classical physics these concepts are the only tools for an unambiguous communication about events about the setting up of experiments and about their results if therefore the atomic physicist is asked to give a description of what really happens in his experiments the words description and really and happens can only refer to the concepts of daily life or of classical physics as soon as the physicist gave up this basis he would lose the means of unambiguous communication and could not continue in his science therefore any statement about what has actually happened is a statement in terms of the classical concepts and because of thermodynamics and of the uncertainty relations by its very nature incomplete with respect to the details of the atomic events involved the demand to describe what happens in the quantum theoretical process between two successive observations is a in since the describe refers to the use of the classical concepts while these concepts cannot be applied in the space between the observations they can only be applied at the points of observation primacy of observation in quantum mechanics and special relativity both quantum mechanics and special relativity begin their divergence from classical mechanics by on the primacy of observations and a to entities thus special relativity the absolute assumed by classical mechanics and quantum mechanics does not one to of properties of the system exact position say other than those that can be connected to macro scale observations position and momentum are not waiting for us to rather they are the results that are obtained by performing certain 
 x ray crystal truncation rod scattering is a powerful method in surface science based on analysis of surface x ray diffraction patterns from a crystalline surface for an crystal the diffracted pattern is in delta function like bragg peaks presence of crystalline surfaces results in additional structure along so called truncation rods linear regions in momentum space normal to the surface crystal truncation rod ctr measurements allow detailed determination of atomic structure at the surface especially useful in cases of oxidation growth and adsorption studies on crystalline surfaces theory a particle incident on a crystalline surface with momentum formula will undergo scattering through a momentum change of formula if formula and formula represent directions in the plane of the surface and formula is perpendicular to the surface then the scattered intensity as a function of all possible values of formula is given by i mathbf q frac sin left tfrac n xa x right sin left tfrac q xa x right frac sin left tfrac n ya y right sin left tfrac q ya y right frac alpha z alpha n z cos left n zc right alpha alpha cos left q zc right math where formula is the defined as the ratio of x ray amplitudes scattered from successive planes of atoms in the crystal and formula formula and formula are the lattice in the x y and z directions respectively in the case of perfect adsorption formula and the intensity becomes independent of formula with a maximum for any formula the component of formula parallel to the crystal surface that satisfies the condition in reciprocal space mathbf q parallel mathbf g h mathbf a x k mathbf a y math for formula and formula this condition results in rods of intensity in reciprocal space oriented perpendicular to the surface and passing through the reciprocal lattice points of the surface as in fig these rods are known as diffraction rods or crystal truncation rods when formula is allowed to vary from the intensity along the rods varies according to fig note that in the limit as formula approaches unity the x rays are fully and the scattered intensity approaches a periodic delta function as in bulk diffraction this calculation has been done according to the single scattering approximation this has been shown to be accurate to within a factor of formula of the peak intensity dynamical multiple scattering to the model can result in even more accurate predictions of ctr intensity to obtain high quality data in x ray ctr measurements it is that the detected intensity be on the order of at least formula to achieve this level of output the x ray source must typically be a synchrotron source more traditional sources such as rotating anode sources provide orders of magnitude less x ray flux and are only suitable for studying high atomic number materials which return a higher diffracted intensity the maximum diffracted intensity is roughly proportional to the square of the atomic number formula anode x ray sources have been successfully used to study formula for example when doing x ray measurements of a surface the sample is held in ultra high vacuum and the x rays pass into and out of the chamber through windows there are approaches to chamber and diffractometer design that are in use in the first method the sample is fixed relative to the vacuum chamber which is kept as small and light as possible and mounted on the diffractometer in the second method the sample is rotated within the chamber by coupled to the outside this approach avoids a large mechanical on the diffractometer making it easier to maintain fine angular resolution one of many is that the sample must be moved in order to use other surface analysis methods such as or and after moving the sample back into the x ray diffraction position it must be in some the sample chamber can be from the diffractometer without breaking vacuum allowing for other users to have access for examples of x ray ctr diffractometer apparatus see in ctr for a given incidence angle of x rays onto a surface only the of the crystal truncation rods with the ewald sphere can be observed to measure the intensity along a ctr the sample must be rotated in the x ray beam so that the origin of the ewald sphere is and the sphere the rod at a different location in reciprocal space performing a in this way requires accurate motion of the sample and the detector along different axes to achieve this motion the sample and detector are mounted in an apparatus called a four circle diffractometer the sample is rotated in the plane the incoming and diffracted beam and the detector is moved into the position necessary to the diffracted ctr intensity surface structures surface features in a material produce variations in the ctr intensity which can be measured and used to evaluate what surface structures may be present two examples of this are shown in fig in the case of a at an angle formula a second set of rods is produced in reciprocal space called superlattice rods from the regular lattice rods by the same angle formula the x ray intensity is strongest in the region of between the lattice rods grey and superlattice rods black lines in the case of ordered steps the ctr intensity is into segments as shown in real materials the of surface features will be so regular but these two examples show the way in which surface and are in the obtained diffraction patterns 
 the faraday cup electrometer is the simplest form of an electrical aerosol instrument used in aerosol studies it consists of an electrometer and a filter inside a faraday cage charged particles collected by the filter generate an electric current which is measured by the electrometer principle according to law the charge collected on the faraday cup is the induced charge that means that the filter does not need to be a it is typically used to measure particles of charge which are particles with a net charge concentration that the charge concentration of or negatively charged particles with an aerosol electrometer the transportation of charge by electrical charged aerosol particles can be measured as electric current in a metal faraday cup a particle filter is mounted on an a faraday cup is a detector that measures the current in a beam of charged aerosol particles faraday are used e g in mass spectrometers being an alternative to secondary electron multipliers the advantage of the faraday cup is its and the possibility to measure the ion or electron stream furthermore the is constant by time and not mass dependent the form is the following a faraday detector consists of a metal cup that is placed in the path of the particle beam the aerosol has to pass the filter inside the cup the filter has to be isolated it is connected to the electrometer circuit which measures the current 
 a line source is a source of air noise water or electromagnetic radiation that from a linear one dimensional geometry the most prominent linear sources are roadway air pollution air emissions roadway noise certain types of water pollution sources that over a range of river extent rather than from a discrete point elongated light tubes certain models in medical physics and electromagnetic while point sources of pollution were studied since the late nineteenth century linear sources did not receive much attention from scientists until the late when environmental for highways and began to emerge at the same time computers with the processing power to accommodate the data processing of the computer models required to tackle these one dimensional sources became more available in addition this era of the saw the first of environmental scientists who the disciplines required to these studies for example and computer scientists in the air pollution field were required to build complex models to address roadway air modeling prior to the these to work within their own disciplines but with the advent of the air act the noise control act in the usa and other seminal the era of multidisciplinary environmental science had for electromagnetic linear sources the early advances in computer modeling arose in the and usa when the end of world war ii and the war were partially by progress in electronic including the technologies of active arrays linear air pollution source air pollution levels near major highways and urban are in violation of u s national air quality standards where millions of or work even the interior of a building does not really protect from adverse exterior air quality since the exterior air is the supply and it is well known that air quality is typically than exterior air a roadway by motor vehicles can be idealized by a line source emitting air pollutants this mathematical problem was first solved in by a collaboration of physics mathematics and computer science the original theory assumed state traffic conditions and meteorology on a straight roadway currently the models have to treat variable meteorology time variant traffic operations and complex geometries current technology allows highway and city planners to analyze alternative roadway development plans and assess air quality impacts the same basic model theory can be applied to operations since the linear source is an line in the early these esl models were refined into area source models to account for the finite width of the roadway linear noise source roadway noise is the most important example of a linear noise source since it about of the environmental noise for humans worldwide in the when computer modeling of this phenomenon was the first applications of linear source noise modeling became systematic after of the national environmental policy act and noise control act the demand for detailed analysis and makers began to to scientists for the planning of new roadways and the design of noise mitigation the intensity of roadway noise is governed by the following variables traffic operations speed age of roadway surface type types roadway and the geometry of area structures due to the complexity of the variables a line source acoustic model must be a computer model that can analyze sound levels in the vicinity of roadways the first meaningful models arose in the late and early two of the leading research teams were in boston and esl of california both of these groups developed complex mathematical models to allow the study of roadway designs traffic operations and noise mitigation strategies in an arbitrary setting later model alterations have come into use among state of transportation and city planners but the accuracy of early models has had little change in years generally line source acoustic models trace sound ray and calculate loss along with ray divergence or from phenomena diffraction is usually addressed by secondary at any points of or such as noise or building surfaces meteorology can be addressed in a statistical manner allowing for actual wind and wind speed statistics along with data water pollution line source less common are line source applications in the field of water pollutant this phenomenon generally arises when surface runoff soil from upper soil layers and these pollutants to a linear water such as a river the underlying land management which lead to such sources of water pollution are application construction and activity and urban runoff again computer models are needed to address the complexity of such an extended linear into a dynamic medium such as water the resulting surface runoff water pollutants may be considered a line source into a river or stream the chemical composition of this surface runoff may be by a surface runoff model such as the runoff algorithm while the may be analyzed by a dynamic river pollutant model such as light emission line source in the study of illumination a variety of sources are linear in nature most commonly the fluorescent tube during the process of interior design it is important to calculate the light intensity at work or other user areas not only to sufficient light is present but more importantly to avoid over illumination and its energy as well as adverse health effects thus the scientists involved in light transmission calculations employ computer models that linear sources when fluorescent are used in a typical setting there may be hundreds of finite length light sources that comprise the light output in an office environment a related concept are the ultraviolet tubes used in where output radiation from the tube can be accurately modeled by treating the tube as a line source on a larger scale an illuminated roadway may act as a line source of light pollution 
 the x ray standing wave technique the x ray standing wave xsw technique can be used to study the structure of surfaces and interfaces with high spatial resolution and chemical pioneered by b w in the the availability of synchrotron light has stimulated the application of this technique to a wide range of problems in surface science basic principles an x ray interference field created by bragg reflection provides the length scale against which atomic distances can be measured the spatial modulation of this field described by the dynamical theory of x ray diffraction a change when the sample is through the bragg condition due to a relative phase variation between the incoming and the reflected beam the planes of the xsw field shift by half a lattice constant depending on the position of the atoms within this wave field the element specific absorption of x rays varies in a characteristic way therefore measurement of the photo yield via x ray or photoelectron spectroscopy can reveal the position of the atoms relative to the lattice planes for a quantitative analysis the photo yield formula is described by y p r r f h cos pi p h math where formula is the and formula is the relative phase of the interfering beams the characteristic shape of formula can be used to derive precise structural information about the surface atoms because the two parameters formula coherent fraction and formula coherent position are directly related to the fourier representation of the atomic distribution function since the emitting atoms are located in the near field this technique does not from the phase problem of x ray crystallography therefore and with a sufficiently large number of fourier components being measured xsw data can be used to the distribution of the different atoms in the unit cell xsw imaging selected applications which require ultra high vacuum conditions which do not require ultra high vacuum conditions 
 a point source is a single localized source of something a point source has negligible extent it from other source geometries sources are called point sources because in mathematical modeling these sources can usually be approximated as a mathematical point to analysis the actual source need not be physically small if its size is negligible relative to other length scales in the problem for example in astronomy stars are routinely treated as point sources even though they are in much larger than the earth in three the density of something leaving a point source decreases in to the inverse square of the distance from the source if the distribution is in all directions and there is no absorption or other loss mathematics in mathematics a point source is a from which flux or flow is although such as this do not exist in the observable universe mathematical point sources are often used as approximations to reality in physics and other fields light generally a source of light can be considered a point source if the resolution of the imaging instrument is too low to its size or if the object is at a very great distance formula where formula is the wavelength of light and formula is the diameter radio waves radio wave sources which are smaller than one radio wavelength are also generally treated as point sources radio emissions generated by a fixed electrical circuit are usually polarized producing anisotropic radiation if the propagating medium is however the power in the radio waves at a given distance will still vary as the inverse square of the distance if the angle remains constant to the source polarization sound sound is an oscillating pressure wave as the pressure up and down an point source acts in turn as a fluid point source and then a fluid point sink such an object does not exist physically but is often a good simplified model for calculations heat in vacuum heat as radiation if the source remains stationary in a fluid such as air flow patterns can form around the source due to leading to an anisotropic pattern of heat loss the most common form of anisotropy is the formation of a thermal plume above the heat source fluid fluid point sources are commonly used in fluid dynamics and a point source of fluid is the inverse of a fluid point sink a point where fluid is removed whereas fluid exhibit complex rapidly changing behaviour such as is seen in vortices for example water running into a plug or generated at points where air is fluid sources generally produce simple flow patterns with stationary isotropic point sources generating an expanding sphere of new fluid if the fluid is moving such as wind in air or currents in water a plume is generated from the point source pollution sources of various types of pollution are often considered as point sources in large scale studies of pollution 
 the haas effect or the richardson effect after owen richardson is a physical phenomenon by albert einstein and wander johannes de haas in the mid s that a relationship between magnetism angular momentum and the spin of elementary particles wander johannes de haas rowan de haas was also a major to the theory applying its principles to the engineering industry specifically rowan s contributions had a effect on the industry in the early century description the effect corresponds to the mechanical rotation that is induced in a ferromagnetic material of cylindrical shape and originally at rest suspended with the aid of a thin inside a coil on driving an impulse of electric current through the coil to this mechanical rotation of the ferromagnetic material say iron is associated a mechanical angular momentum which by the law of conservation of angular momentum must be by an equally large and directed angular momentum inside the ferromagnetic material given the fact that an external magnetic field here generated by driving electric current through the coil leads to magnetisation of electron spins in the material or to reversal of electron spins in an already provided that the direction of the applied electric current is chosen the haas effect demonstrates that spin angular momentum is indeed of the same nature as the angular momentum of rotating bodies as in classical mechanics this is remarkable since electron spin being quantized cannot be described within the framework of classical mechanics einstein w j de haas proof of s molecular currents s hypothesis that magnetism is caused by the microscopic circular of electric the authors proposed a design to test lorentz s theory that the rotating particles are electrons the aim of the experiment was to measure the torque generated by a reversal of the magnetisation of an iron einstein w j de haas experimental proof of the of s molecular currents in einstein wrote three papers with wander j de haas on experimental work they did together on s molecular currents known as the haas effect he immediately wrote a correction to paper above when dutch physicist h a lorentz out an error in addition to the two papers above is and einstein and de haas a on paper later in the year for the same journal this topic was only indirectly related to einstein s interest in physics but as he wrote to his in old age i am developing a for experimentation calculations based on a model of electron spin as a electric charge this magnetic moment by a factor of approximately the g factor a correct description of this magnetic moment requires a treatment based on quantum electrodynamics 
 cern directors general typically serve year terms beginning on january during the cern had co directors 
 a fragment separator is an ion optical device used to focus and separate products from the collision of relativistic ion beams with thin targets selected products can then be studied individually fragment separators typically of a series of superconducting magnetic elements the thin target immediately before the separator allows the fragments produced through various reactions to the target material still at a very high velocity the products are forward focused because of the high velocity of the center of mass in the beam target interaction which allows fragment separators to collect a large fraction in some cases nearly all of the fragments produced in the target some examples of currently operating fragment separators are the at the at and at 
 physical systems such as fluid flow or mechanical vibrations behave in characteristic patterns known as modes in a flow for example one may think of a of vortices a big main vortex driving smaller secondary ones and so on most of the motion of such a system can be described using only a few of those patterns in a purely mathematical setting similar modes can be extracted form the governing equations using an eigenvalue decomposition but in many cases the mathematical model is very complicated or not available at all in an experiment the mathematical description is not at hand and one has to rely on the measured data only the dynamic mode decomposition dmd is a mathematical method to extract the relevant modes from experimental data without any to the governing equations it can thus be applied to any dynamic phenomenon where appropriate data is available it is similar but different from decomposition which has similar features but dynamical information about the data description a time physical situation may be approximated by the action of a linear operator formula to the instantaneous state vector the dynamic mode decomposition to approximate the evolution operator formula from a known sequence of observations formula the matrix s is small as compared to the sample data v therefore eigenvalues and can be computed with examples trailing edge of a profile the of an obstacle in the flow may develop a vortex the fig shows the shedding of a vortex behind the trailing edge of a profile the dmd analysis was applied to sequential entropy fields and yield an approximated eigenvalue spectrum as depicted below the analysis was applied to the numerical results without referring to the governing equations the profile is seen in white the white arcs are the processor since the computation was performed on a parallel computer using different computational blocks roughly a third of the spectrum was highly damped large negative formula and is not shown the shedding mode is shown in the following pictures the image to the left is the real part the image to the right the imaginary part of the eigenvector again the entropy eigenvector is shown in this pictures the acoustic of the same mode is seen in the half of the next the top half corresponds to the entropy mode as above example of a pattern the dmd analysis assumes a pattern of the form formula where formula is any of the independent variables of the problem but has to be selected in take for example the pattern with the time as the factor a sample is given in the following figure with formula formula and formula the left picture shows the pattern without the right with noise added the amplitude of the random noise is the same as that of the pattern a dmd analysis is performed with generated fields using a time interval formula limiting the analysis to formula the spectrum is symmetric and shows almost modes small negative real part whereas the other modes are heavily damped their numerical values are formula respectively the real one corresponds to the mean of the field whereas formula corresponds to the imposed pattern with formula a relative error of increasing the noise to times the signal value yields about the same error the real and imaginary part of one of the latter two is depicted in the following figure see also several other of experimental data exist if the governing equations are available an eigenvalue decomposition might be feasible 
 euler s laws of motion formulated by euler about years after isaac newton formulated his laws about the motion of particles them to rigid body motion overview euler s first law euler s first law states that the linear momentum of a body formula is equal to the product of the mass of the body and the velocity of its center of mass formula internal forces between the particles that make up a body do not contribute to changing the total momentum of the body the law is also stated as formula euler s second law euler s second law states that the rate of change of angular momentum about a point formula is equal to the sum of the external moments about that point formula for rigid bodies translating and rotating in only this can be expressed as formula where is the position vector of the center of mass with respect to the point about which moments are explanation and derivation the density of internal forces at every point in a deformable body are not necessarily equal i e there is a distribution of throughout the body this variation of internal forces throughout the body is governed by newton s second law of motion of conservation of linear momentum and angular momentum which normally are applied to a mass particle but are extended in continuum mechanics to a body of continuously distributed mass for continuous bodies these laws are called laws of motion if a body is represented as an assemblage of discrete particles each governed by laws of motion then equations can be derived from laws equations can however be taken as axioms describing the laws of motion for extended bodies independently of any particle structure the total body force applied to a continuous body with mass formula and volume formula is expressed as where formula is the body force density body forces and contact forces acting on the body lead to corresponding moments of force torques relative to a given point thus the total applied torque formula about the origin is given by where formula and formula indicate moments caused by body and contact forces respectively thus the sum of all applied forces and torques with respect to the origin of the coordinate system in the body can be given by let the coordinate system formula be an inertial frame of reference let formula be the position vector of a particle or point formula in the continuous body with respect to the origin of the coordinate system and formula the velocity vector of point formula first axiom or law law of balance of linear momentum or balance of forces states that in an inertial frame the time rate of change of linear momentum formula of an arbitrary portion of a continuous body is equal to the total applied force formula acting on the considered portion and it is expressed as second axiom or law law of balance of angular momentum or balance of torques states that in an inertial frame the time rate of change of angular momentum formula of an arbitrary portion of a continuous body is equal to the total applied torque formula acting on the considered portion and it is expressed as the derivatives of formula and formula are material derivatives 
 the fermilab holometer in is currently under construction and will be the world s most sensitive laser when complete the sensitivity of the and systems and theoretically able to detect holographic fluctuations in the holometer may be capable of meeting or the sensitivity required to detect the smallest units in the universe called planck units fermilab states is these days with the and images or sound transmission associated with poor internet bandwidth the holometer seeks to detect the equivalent or noise in reality itself associated with the frequency limit imposed by nature a particle at fermilab states about the experiment what for is when the lasers lose step with each other to detect the smallest unit in the universe this is really great a of old physics experiment where you know what the result will be experimental physicist of the max planck institute in germany states that although he is that the apparatus will successfully detect the holographic fluctuations if the experiment is successful it would be a very strong to one of the most open questions in fundamental physics it would be the first proof that space time the of the universe is quantized the hypothesis that holographic noise may be observed in this manner has been on the grounds that the theoretical framework used to derive the noise lorentz invariance lorentz invariance violation is however very already an issue that has been very addressed in the mathematical treatment 
 in condensed matter physics quantum oscillations describes an experimental technique to map the fermi surface of a metal in the presence of a strong magnetic field the technique is based on the principle of landau of fermions moving in a magnetic field for a gas of free fermions in a strong magnetic field the energy levels are quantized into bands called the landau levels whose separation is inversely proportional to the strength of the magnetic field in a quantum oscillations experiment the external magnetic field is varied which causes the landau levels to pass over the fermi surface which in turn results in oscillations of the hall resistance observation of quantum oscillations in a material is considered a signature of fermi liquid behaviour quantum oscillations have been used to study high temperature superconducting materials such as cuprates and studies using these experiments have showed that the ground state of underdoped cuprates behave similar to a fermi liquid and display characteristics such as landau quasiparticles experiment when a magnetic field is applied to a system of free fermions their energy states are quantized into the so called landau levels given by formula for integer formula where formula is the external magnetic field and formula are the charge and effective mass respectively when the external magnetic field formula is increased in an isolated system the landau levels expand and eventually fall off the fermi surface this leads to oscillations in the observed energy of the highest occupied level and hence in the hall the of these oscillations can be measured and in turn can be used to determine the cross sectional area of the fermi surface if the axis of the magnetic field is varied at constant magnitude similar oscillations are observed the oscillations occur whenever the landau orbits the fermi surface in this way the complete geometry of the fermi sphere can be underdoped cuprates studies of under compounds such as through probes such as arpes have that these show characteristics of non fermi liquids and in particular the absence of well defined landau quasiparticles however quantum oscillations have been observed in these materials at low if their superconductivity is by a sufficiently high magnetic field which is evidence for the presence of well defined quasiparticles with fermionic statistics these experimental results thus with those from arpes and other probes 
 bioinformatics is the application of computer science and information technology to the field of biology and medicine bioinformatics with algorithms databases and information systems web technologies artificial intelligence and soft computing information and computation theory software engineering data mining image processing modeling and simulation signal processing discrete mathematics control and system theory circuit theory and statistics bioinformatics generates new knowledge as well as the computational tools to create that knowledge commonly used software tools and technologies in this field include java perl c c python r cuda and microsoft introduction bioinformatics was applied in the creation and maintenance of a database to biological information at the beginning of the genomic revolution such as nucleotide sequences and amino acid sequences development of this type of database involved not only design issues but the development of complex interfaces researchers could access existing data as well as new or data the primary goal of bioinformatics is to increase the understanding of biological processes what sets it apart from other approaches however is its focus on developing and applying computationally intensive techniques to achieve this goal examples include pattern recognition data mining machine learning algorithms and visualization major research efforts in the field include sequence alignment gene finding genome assembly drug design drug discovery protein structure alignment protein structure prediction prediction of gene expression and interactions genome wide association studies and the modeling of evolution interestingly the term bioinformatics was coined before the genomic revolution and introduced the term in to refer to the study of information processes in systems this definition placed bioinformatics as a field parallel to biophysics or biochemistry biochemistry is the study of chemical processes in biological systems however its primary use since at least the late has been to describe the application of computer science and information sciences to the analysis of biological data particularly in those areas of genomics involving large scale dna sequencing bioinformatics now the creation and of databases algorithms computational and statistical techniques and theory to solve and practical problems arising from the management and analysis of biological data over the past few decades rapid developments in genomic and other molecular research technologies and developments in information technologies have combined to produce a amount of information related to molecular biology bioinformatics is the name given to these mathematical and computing approaches used to understanding of biological processes common activities in bioinformatics include mapping and analyzing dna and protein sequences aligning different dna and protein sequences to compare them and creating and d models of protein structures there are two fundamental ways of a biological system e g living cell both under bioinformatic approaches a broad sub category under bioinformatics is structural bioinformatics major research areas sequence analysis since the was sequenced in the dna sequences of thousands of organisms have been decoded and stored in databases this sequence information is analyzed to determine genes that encode proteins rna genes regulatory sequences structural motifs and repetitive sequences a comparison of genes within a species or between different species can show between protein functions or relations between species the use of molecular to construct with the growing amount of data it long ago became impractical to analyze dna sequences manually today computer programs such as are used daily to search sequences from more than organisms containing over nucleotides these programs can compensate for mutations or inserted bases in the dna sequence to identify sequences that are related but not identical a variant of this sequence alignment is used in the sequencing process itself the so called shotgun sequencing technique which was used for example by the institute for genomic research to sequence the first bacterial genome haemophilus influenzae does not produce entire chromosomes instead it generates the sequences of many thousands of small dna fragments ranging from to nucleotides long depending on the sequencing technology the ends of these fragments overlap and when aligned properly by a genome assembly program can be used to reconstruct the complete genome shotgun sequencing yields sequence data quickly but the task of assembling the fragments can be quite complicated for larger genomes for a genome as large as the human genome it may take many days of cpu time on large memory computers to assemble the fragments and the resulting assembly will usually contain numerous that have to be filled in later shotgun sequencing is the method of choice for virtually all genomes sequenced today and genome assembly algorithms are a critical area of bioinformatics research another of bioinformatics in sequence analysis is annotation this involves computational gene finding to search for protein coding genes rna genes and other functional sequences within a genome not all of the nucleotides within a genome are part of genes within the genomes of higher organisms large parts of the dna do not serve any obvious purpose this so called dna may however contain functional elements bioinformatics to the gap between genome and projects for example in the use of dna sequences for protein identification genome annotation in the context of genomics annotation is the process of the genes and other biological features in a dna sequence the first genome annotation software system was designed in by dr owen white who was part of the team at the institute for genomic research that sequenced and analyzed the first genome of a free living organism to be decoded the haemophilus influenzae dr white built a software system to find the genes places in the dna sequence that encode a protein the transfer rna and other features and to make initial of function to those genes most current genome annotation systems work similarly but the programs available for analysis of genomic dna are changing and computational evolutionary biology future work to reconstruct the now more complex of life the area of research within computer science that uses genetic algorithms is sometimes confused with computational evolutionary biology but the two areas are not necessarily related literature analysis the area of research from statistics and computational analysis of gene expression the expression of many genes can be determined by measuring mrna levels with multiple techniques including microarrays expressed cdna sequence tag sequencing serial analysis of gene expression tag sequencing parallel signature sequencing rna seq also known as whole transcriptome shotgun sequencing or various applications of in hybridization all of these techniques are extremely noise and or subject to in the biological measurement and a major research area in computational biology involves developing statistical tools to separate signal from noise in high throughput gene expression studies such studies are often used to determine the genes implicated in a disorder one might compare microarray data from cancerous cells to data from non cancerous cells to determine the transcripts that are up regulated and down regulated in a particular population of cancer cells analysis of regulation regulation is the complex of events starting with an signal such as a and leading to an increase or decrease in the activity of one or more proteins bioinformatics techniques have been applied to various steps in this process for example analysis involves the identification and study of sequence motifs in the dna the coding region of a gene these motifs influence the extent to which that region is transcribed into mrna expression data can be used to infer gene regulation one might compare microarray data from a wide variety of states of an organism to form hypotheses about the genes involved in each state in a single cell organism one might compare stages of the cell cycle along with various conditions heat shock etc one can then apply clustering algorithms to that expression data to determine which genes are co expressed for example the regions of co expressed genes can be for over represented regulatory elements analysis of protein expression protein microarrays and high throughput ht mass ms can provide a of the proteins present in a biological sample bioinformatics is very much involved in making sense of protein microarray and ht ms data the former approach similar problems as with microarrays targeted at mrna the latter involves the problem of matching large amounts of mass data against predicted masses from protein sequence databases and the complicated statistical analysis of samples where multiple but incomplete peptides from each protein are detected analysis of mutations in cancer in cancer the genomes of affected cells are in complex or even ways massive sequencing efforts are used to identify previously unknown point mutations in a variety of genes in cancer bioinformaticians continue to produce specialized systems to manage the volume of sequence data produced and they create new algorithms and software to compare the sequencing results to the growing collection of human genome sequences and new physical detection technologies are employed such as oligonucleotide microarrays to identify chromosomal gains and losses called comparative genomic hybridization and single nucleotide arrays to detect known point mutations these detection methods simultaneously measure several hundred thousand sites throughout the genome and when used in high throughput to measure thousands of samples generate terabytes of data per experiment again the massive amounts and new types of data generate new opportunities for bioinformaticians the data is often found to contain considerable or noise and thus hidden markov model and change point analysis methods are being developed to infer real copy number changes another type of data that requires novel informatics development is the analysis of found to be recurrent among many tumors comparative genomics the core of comparative genome analysis is the of the correspondence between genes analysis or other genomic features in different organisms it is these maps that make it possible to trace the evolutionary processes responsible for the divergence of two genomes a of evolutionary events acting at various organizational levels shape genome evolution at the level point mutations affect individual nucleotides at a higher level large chromosomal segments undergo lateral transfer and whole genomes are involved in processes of hybridization and often leading to rapid the complexity of genome evolution many exciting challenges to developers of mathematical models and algorithms who have to a spectra of statistical and mathematical techniques ranging from exact heuristics fixed parameter and approximation algorithms for problems based on models to markov chain algorithms for bayesian analysis of problems based on models many of these studies are based on the homology detection and protein families computation modeling biological systems systems biology involves the use of computer simulations of cellular subsystems such as the networks of and enzymes which comprise metabolism signal pathways and gene regulatory networks to both analyze and the complex of these cellular processes artificial life or virtual evolution attempts to understand evolutionary processes via the computer simulation of simple artificial life forms structural bioinformatic approaches prediction of protein structure protein structure prediction is another important application of bioinformatics the amino acid sequence of a protein the so called primary structure can be easily determined from the sequence on the gene that for it in the vast majority of cases this primary structure uniquely determines a structure in its native environment of course there are such as the a k a disease knowledge of this structure is in understanding the function of the protein for lack of better terms structural information is usually classified as one of secondary tertiary and structure a viable general solution to such predictions remains an open problem as of now most efforts have been directed towards heuristics that work most of the time one of the key ideas in bioinformatics is the of homology in the genomic branch of bioinformatics homology is used to predict the function of a gene if the sequence of gene a whose function is known is homologous to the sequence of gene b whose function is unknown one could infer that b may share a s function in the structural branch of bioinformatics homology is used to determine which parts of a protein are important in structure formation and interaction with other proteins in a technique called homology modeling this information is used to predict the structure of a protein once the structure of a homologous protein is known this currently remains the only way to predict protein structures reliably one example of this is the similar protein homology between hemoglobin in humans and the hemoglobin in both serve the same purpose of oxygen in the organism though both of these proteins have completely different amino acid sequences their protein structures are virtually identical which reflects their near identical purposes other techniques for predicting protein structure include protein and de novo from physics based modeling see also structural and structural domain molecular interaction efficient software is available today for studying interactions among proteins ligands and peptides types of interactions most often in the field include including drug and molecular dynamic simulation of of atoms about bonds is the fundamental principle behind computational algorithms docking algorithms for studying molecular interactions see also interaction prediction docking algorithms in the last two decades tens of thousands of protein three dimensional structures have been determined by x ray crystallography and protein nuclear magnetic resonance spectroscopy protein nmr one central question for the biological scientist is whether it is practical to predict possible interactions only based on these without doing interaction experiments a variety of methods have been developed to tackle the docking problem though it seems that there is still much work to be done in this field software and tools software tools for bioinformatics range from simple line tools to more complex graphical programs and standalone web services available from various bioinformatics companies or public institutions open source bioinformatics software many free and open source software tools have and continued to grow since the the combination of a continued need for new algorithms for the analysis of emerging types of biological the potential for innovative in silico experiments and freely available open code bases have helped to create opportunities for all research groups to contribute to both bioinformatics and the range of open source software available regardless of their funding the open source tools often act as of ideas or community supported plug in commercial applications they may also provide de standards and shared object models for assisting with the challenge of integration the range of open source software packages includes such as taverna workbench and in order to maintain this and create further opportunities the non profit open bioinformatics foundation have supported the annual bioinformatics open source conference since web services in bioinformatics and rest based interfaces have been developed for a wide variety of bioinformatics applications allowing an application running on one computer in one part of the world to use algorithms data and computing resources on servers in other parts of the world the main advantages derive from the fact that end users do not have to deal with software and database maintenance basic bioinformatics services are classified by the into three sequence search services multiple sequence alignment and biological sequence analysis the availability of these service oriented bioinformatics resources demonstrate the applicability of web based bioinformatics solutions and range from a collection of standalone tools with a common data under a single standalone or web based interface to distributed and bioinformatics workflow management systems bioinformatics workflow management systems a bioinformatics workflow management system is a specialized form of a workflow management system designed specifically to and a series of computational or data steps or a workflow in a bioinformatics application such systems are designed to currently there are two platforms giving this service and taverna 
 computational biology involves the development and application of data analytical and theoretical methods mathematical modeling and computational simulation techniques to the study of biological behavioral and social systems the field is defined and includes foundations in computer science applied mathematics statistics biochemistry chemistry biophysics molecular biology genetics evolution neuroscience and visualization computational biomodeling computational biomodeling a field concerned with building computer models of biological systems computational genomics computational genomics a field within genomics which studies the genomes of cells and organisms high throughput genome sequencing produces of data which requires extensive processing sequence assembly and uses dna microarray technologies to perform statistical on the genes expressed in individual cell types this can help find genes of interest for certain diseases or conditions this field also studies the mathematical foundations of sequencing advances in many areas of genomics research are heavily rooted in engineering technology from the units used in large scale dna sequencing projects computational neuroscience computational neuroscience is the study of brain function in terms of the information processing properties of the structures that make up the system computational biology vs bioinformatics bioinformatics and computational biology are rooted in life sciences as well as computer and information sciences and technologies both of these approaches from specific disciplines such as mathematics physics statistics computer science and engineering biology and behavioral science bioinformatics and computational biology each maintain close interactions with life sciences to their full potential bioinformatics involves information theory and data management applying principles of information sciences and technologies to make the vast diverse and complex life sciences data more and useful computational biology on the other hand uses mathematical and computational approaches to directly address biological hypotheses both theoretical and experimental in nature although bioinformatics and computational biology are distinct there is also significant overlap and activity at their interface and they are consequently often confused by those outside of the discipline another way to the difference is that bioinformaticians build software while computational biologists use and the software to tackle their specific biological questions 
 folding home or f h is a distributed computing project for simulation of protein folding computational drug design and other molecular dynamics for disease research it primarily attempts to determine how proteins reach their final three dimensional structure which is of significant academic interest and has major implications for research into alzheimer s disease huntington s disease and many forms of cancer among other diseases to a certain extent folding home also tries to predict that final structure and to determine how other molecules may interact with it which has applications in drug design folding home is developed and operated by the pande laboratory at stanford university under the leadership of pande and is shared by various scientific institutions and research laboratories across the world in a collaboration known as the folding home folding home is by the processing resources of thousands of personal computers and playstation as part of the project s client server architecture these systems receive simulation work units complete them and return them to database servers where they are compiled into an overall simulation can track their contributions on the folding home website which can make participation and long term the project has pioneered the uses of gpus playstation and message passing interface used for computing on multi core processors for distributed computing and scientific research this large scale computing network has allowed folding home to simulate protein folding at timescales thousands of times longer than previously achieved the project uses simulation methodology that represents a paradigm shift from traditional computational approaches since its launch on october the pande lab has produced six scientific research papers as a direct result of the project folding home at approximately petaflops a higher computational performance than all distributed computing projects under boinc combined and it remains one of the world s fastest computing systems this computing power makes folding home the most powerful molecular dynamics and allows it to run computationally expensive atomic level simulations over biologically relevant timescales these simulations have demonstrated accuracy to observations in laboratory research which is a challenge in computational biology project significance proteins are an essential component to many biological functions and participate in virtually all processes within cells they often act as enzymes performing biochemical reactions including cell molecular transportation and cellular regulation as structural elements some proteins act as a type of for cells and as other proteins participate in the immune system before a protein can take on these roles it must fold into a functional three dimensional structure a process that often occurs spontaneously and is dependent on interactions within its amino acid sequence protein folding is driven by the search to find the most conformation of the protein i e its native state thus understanding protein folding is critical to understanding what a protein does and how it works and is considered a of computational biology despite folding occurring within a crowded cellular environment it typically proceeds however due to a protein s chemical properties or other factors proteins may that is fold down the and end up cellular mechanisms are capable of or refolding such misfolded proteins they can aggregate and cause a variety of diseases laboratory experiments studying these processes can be limited in scope and atomic detail leading scientists to use physics based computational models that when complementing experiments seek to provide a more complete picture of protein folding misfolding and aggregation due to the complexity of proteins conformation space and limitations in computational power all atom molecular dynamics simulations have been limited in the timescales which they can study while most proteins typically fold in the order of milliseconds prior to simulations could only reach to timescales general purpose supercomputers have been used to simulate protein folding but such systems are expensive and typically shared between many different research groups and because the in kinetic models are serial in nature strong scaling of traditional molecular simulations to these architectures is exceptionally difficult additionally as the protein folding process is stochastic a limited number of long simulations are not sufficient for comprehensive views of protein folding protein folding does not occur in a single step instead a significant portion of the folding time is spent waiting in various intermediate conformational states where each state represents a local free energy minimum in the protein s energy landscape folding home simulations from these states and the rates and probabilities of transitions between sets of in parallel this approach protein s phase space while avoiding much of the computation inside the local minimum state itself and achieves near linear parallelization leading to a significant in overall serial calculation time the conformational states and the short simulations between them are then compiled into a statistical markov state model msm which essentially serves as a map of the protein s energy landscape and kinetic and equilibrium thermodynamic properties once constructed each msm illustrates folding events and pathways and can represent its conformational states at an arbitrary resolution it can also reveal which transitions are limiting the model s accuracy which allows for specific follow up simulations to improve the of the model using this adaptive sampling technique the amount of time it takes to construct an accurate markov state model is inversely proportional to the number of parallel simulations run i e the number of processors available folding home has used these msms to simulate folding at biologically relevant timescales to reveal how proteins and to quantitatively compare simulations with experiments in folding home used markov state models to complete approximately a million cpu days of simulations over the span of several months and in msms another simulation that required an aggregate million cpu of computation in january folding home used msms to simulate the dynamics of the slow folding protein out to milliseconds a timescale that is a thousand times longer than previously achieved the model of many individual trajectories each two orders of magnitude shorter this was the first demonstration that msms were capable of capturing folding events that could not be seen by simulation methods in folding home researcher was awarded the thomas paradigm shift award from the american chemical society for the instrumental development of the software used to automatically build these msms and for quantitative agreement between theory and experiment for his work pande was awarded the michael and award for young investigators for developing field defining and field changing computational methods to produce leading theoretical models for protein and rna folding as well as the young award for his unique approach to advances in algorithms that make optimal use of distributed computing which places his efforts at the cutting edge of simulations the results have stimulated a examination of the meaning of both ensemble and single molecule measurements making dr efforts contributions to simulation methodology biomedical research protein misfolding is a component in the development of a variety of diseases including alpha alzheimer s disease cancer cell disease huntington s disease osteogenesis imperfecta s disease and type ii once it is understood how a protein misfolds therapeutic intervention can follow which can use molecules to the production of a certain protein to help a misfolded protein or to assist in the folding process cellular infection by viruses such as hiv and influenza also involve folding events within cellular computer assisted drug design has the potential to drug discovery the combination of computational molecular modeling and experimental analysis has the possibility of the future of molecular medicine and the rational design of even though simulations run on folding home are used in conjunction with laboratory experiments researchers can use folding home to study how folding in vitro differs from folding in native cellular in folding home continued simulations of folding inside a ribosomal exit tunnel to help scientists better understand how natural and might influence the folding process researchers can further use folding home to study aspects of folding misfolding and its relationship to disease that are exceptionally difficult to observe experimentally for example scientists typically employ chemical to proteins from their stable native state it is difficult to experimentally determine if these denatured states contain structures which may influence folding behavior but folding home has been used to study this denatured state and the mechanism folding home is dedicated to producing significant amounts of results about protein folding and the diseases that result from protein misfolding it is also used to develop novel computational methods for drug design the goal of the first five years of the project was to make significant advances in understanding folding while the current goal is to understand misfolding and related disease especially alzheimer s disease the pande lab is a non profit organization and does not the results generated by folding home the large data sets from the project are freely available for other researchers to use upon and some can be from the folding home website the pande lab has collaborated with other molecular dynamics systems such as the blue gene supercomputer they also share folding home s key software with other researchers so that the algorithms which folding home may aid other scientific areas in they released the open source software which is based on folding home s msm and other parallelization techniques and aims to significantly improve the efficiency and scaling of molecular simulations on large computer clusters or supercomputers of all of the scientific from folding home are posted on the folding home website after publication the full publications are available online from an academic library alzheimer s disease alzheimer s disease is an incurable form of which most often the its cause remains largely unknown but the disease is identified as a protein misfolding disease and is associated with toxic of the amyloid beta peptide a fragment of the larger amyloid precursor protein high concentrations of misfolded cause protein oligomer growth that in turn contribute to misfolding this process appears to be toxic and leads to the oligomer aggregates then collect into dense known as a of alzheimer s the of the disease depends not only on the amount of but also on how it misfolds however due to the nature of these aggregates experimental studies of the oligomer structure in atomic detail are difficult and simulations of oligomer aggregates are extremely computationally demanding due to their size and complexity in folding home simulated oligomerization in atomic detail over timescales of the order of tens of this was significant as previous simulations had been to use simplified models and been limited to several hundreds of microseconds six orders of magnitude short of experimentally relevant timescales this study helped prepare the pande lab for future aggregation studies and for further research to find a small peptide which may stabilize the aggregation process this is as a promising approach to the development of therapeutic drugs for treating alzheimer s the pande lab is focusing their research on alzheimer s with the goal of predicting the aggregate structure for drug design approaches as well as developing methods to stop the oligomerization process in folding home found several small drug which appear to the of in these drug leads from the test tube to testing on living tissue and in close with the center for protein folding continue to be refined in folding home simulations of several mutations that appear to stabilize the aggregate formation which could aid in the development of therapeutic drug approaches to the disease as well as greatly assisting with experimental nmr spectroscopy studies of the oligomers in the same year folding home began simulations of various fragments in order to determine how various natural enzymes affect the structure and folding of huntington s disease huntington s disease is a genetic disorder that is also associated with protein misfolding and aggregation excessive repeats of the amino acid at the n of the huntingtin protein cause aggregation and although the behavior of the repeats is not completely understood it does lead to the cognitive associated with the disease as with other aggregates there is difficulty in experimentally determining its structure scientists are using folding home to study huntingtin protein aggregate structure as well as to predict how the aggregate forms assisting with rational drug design approaches to stop the aggregate formation the fragment of the huntingtin protein this aggregation and while there have been several proposed mechanisms its exact role in this process remains largely unknown folding home has simulated this and other fragments in order to their roles in the disease since the pande lab has applied the drug design approaches used in alzheimer s disease to huntington s and in folding home researcher thomas proposed a novel therapeutic strategy for huntington s which may be funded by the national institutes of health this strategy could be used to the results from folding home directly to a therapeutic drug cancer more than half of all known cancers involve mutations of a tumor protein present in every cell which the cell cycle and for cell death in the event of to dna specific mutations in can these functions allowing an abnormal cell to continue growing resulting in the development of tumors these mutations may between the various types and locations of cancer and analysis of these mutations is important for understanding the root causes of related cancers in folding home was used to perform the first molecular dynamics study of the refolding of s protein in explicit water which revealed insights that were previously unobtainable and from it produced the first peer reviewed publication on cancer from a distributed computing project the following year they developed a method to identify the amino acids that are crucial for the of a given protein which was then used to study mutations of the method demonstrated success in cancer mutations and determined the effects of specific mutations which could not otherwise be measured experimentally following these studies the pande lab expanded their efforts to other related diseases folding home is also being used to study protein chaperones which act as heat shock proteins and assist with protein folding inside the crowded and environment and which have essential roles in cell rapidly growing cancer cells rely on specific chaperones for their function and some chaperones key roles in resistance these specific chaperones are seen as potential modes of action for efficient drugs or for reducing the of cancer using folding home and working closely with the protein folding center the pande lab hopes to find a drug which those chaperones involved in cancerous cells researchers are also using folding home to study other molecules related to cancer such as the enzyme and certain forms of the in folding home began simulations of the dynamics of the small protein which can identify in imaging by binding to surface of cancer cells from simulations of this protein they hope to accelerate research efforts to it to identify other diseases or to bind to drugs il is a protein which plays crucial roles in t cells of the immune system attack and tumors its use as a cancer treatment is due to serious side effects such as pulmonary il to these pulmonary cells differently than it does to t cells so il research involves understanding the differences between these binding mechanisms in folding home assisted with the discovery of a form of il which is three hundred times more effective in its immune system role but fewer side effects in experiments this altered form significantly outperformed natural il in tumor growth pharmaceutical companies have expressed interest in the molecule and the national institutes of health is testing it against a large variety of tumor models in the hopes of accelerating its development as a therapeutic osteogenesis imperfecta osteogenesis imperfecta also known as bone disease is a incurable genetic bone disorder which can be those with the disease are unable to make functional bone tissue this is most commonly due to a mutation in type i collagen which is the most abundant protein in and fulfills a variety of structural roles the mutation causes a deformation in collagen s triple structure which if not destroyed leads to abnormal and bone tissue in the pande lab produced a publication on a quantum mechanical technique that improved upon previous simulations methods and which may be useful for future computational studies of collagen although researchers have used folding home to study collagen folding and misfolding the interest stands as a pilot project compared to alzheimer s and huntington s research viruses the pande lab is using folding home to study certain viruses such as influenza and hiv with a focus on preventing the virus from the cell influenza in particular has been responsible for periodic high such as the which may have up to million people worldwide membrane fusion is an essential event for viral infection and involves conformational changes of viral fusion proteins and protein docking a virus may after this process or a virus may itself in the cell s membrane membrane fusion is also crucial to a wide range of biological functions and it has pharmaceutical implications but the exact molecular mechanisms behind fusion remain largely unknown fusion events may involve the interactions of over a half million atoms for hundreds of microseconds this complexity and timescale makes standard computer simulations exceptionally difficult which are typically limited to about thousand atoms over tens of a difference of several orders of magnitude such mechanisms are difficult to analyse experimentally however in scientists applied markov state models and the folding home network to gain detailed insights into the fusion process using folding home for detailed simulations of fusion in the pande lab introduced a new technique for measuring fusion intermediate in researchers used folding home to study mutations of influenza hemagglutinin a protein that a virus to its target cell and assists with viral mutations to hemagglutinin affect the binding to the cell surface of a target species which determines the of the virus to that species knowledge of the effects of hemagglutinin mutations assists in the development of drugs in folding home began simulations of the dynamics of the enzyme rnase h a key component of hiv in the hopes of designing drugs to deactivate it as of folding home to simulate the folding and interactions of hemagglutinin complementing experimental studies at the university of drug design drugs function by binding to specific locations on target molecules and causing a certain desired change such as a pathogen ideally a drug should act very specifically and bind only to its target without interfering with other biological functions however it is difficult to precisely determine where and how tightly two molecules will bind due to limitations in computational power current in silico approaches usually have to speed for accuracy e g use rapid protein docking methods instead of computationally expensive free energy calculations folding home allows researchers to use both to evaluate these techniques and to find ways to improve their efficiency an accurate prediction of these binding has the potential to significantly lower the development costs of new drugs folding home has been used to study binding locations on protein surfaces by testing the interactions of different molecules with known binding sites folding home took part in s experiment which assessed current computational protein and ligand modeling methods by having various researchers attempt to predict which of a set of ligands would to a target protein and to estimate their associated binding energies the pande lab has used folding home to study how bacteria develop an to an of last as well as to study the dynamics of beta a protein that plays important roles in drug resistance in the hope of being better able to design drugs to deactivate it approximately half of all known antibiotics with the of a bacteria s ribosome a large and complex biochemical machine that performs protein biosynthesis by translating rna into proteins antibiotics the ribosome s exit tunnel preventing of essential bacterial proteins in the pande lab received a grant to study and design new antibiotics in they used folding home to study the interior of this tunnel and how specific molecules may affect it the full structure of the ribosome has only been recently determined and folding home has also simulated ribosomal proteins as the functions of many of them remain largely unknown ribosomal research has helped the pande lab prepare for larger and more complex biomedical problems participation in addition to reporting active processors folding home also determines its computing performance as measured in flops based on the actual time of its calculations originally this was simply native flops that is the raw performance from each given type of processing hardware in march folding home began reporting the performance in both native and flops the latter being an of how many flops the calculation would take on the standard architecture which is commonly used as a performance reference specialized hardware such as gpus can efficiently perform certain complex functions in a single flop which would otherwise require multiple flops on the architecture this measurement attempts to even out these hardware differences despite using for the gpu and clients flops are much greater than their native flops and comprise a large majority of folding home s flop performance in folding home as the most powerful distributed computing network in the world as of may the project has about active cpus about active gpus and about active for a total of about native petaflops petaflops at the same time the combined efforts of all distributed computing projects under boinc petaflops from around active hosts using the markov state model approach folding home achieves strong scaling across its user base and gains a near linear speedup for every additional processor this large and powerful network allows folding home to do work not possible any other way active participation in folding home has since its launch in march google co launched google compute as add on for the google toolbar which allowed windows users to participate in the project although limited in functionality and scope it increased participation in folding home from up to about active cpus the program in october in of the official folding home clients and is no longer available for the toolbar folding home also gained participants from genome home another distributed computing project from the pande lab and a project to folding home the goal of genome home was protein design and associated applications but was officially concluded in march following its completion users were asked to computing power to folding home instead petaflops milestones on september due in large part to the participation of playstation the folding home project officially attained a sustained performance level higher than one native petaflops becoming the first computing system of any kind in the world to do so on may the project attained a sustained performance level higher than two native petaflops by the three and four native petaflops milestones on and september respectively it was the first computing project to do so then on february folding home achieved a performance level of just above five native petaflops most recently on november folding home crossed the six native petaflops with the equivalent of nearly eight petaflops points similarly to other distributed computing projects folding home quantitatively user computing contributions to the project through a credit system each user receives points for completing every work unit but for reliably and rapidly completing units which are exceptionally computationally demanding or are of great scientific priority users who in may be non awarded additional bonus points all units from a given protein project have uniform base credit which is determined by one or more work units from that project on an official reference machine before the project is released this generates a system of equal pay for equal work and attempts to align credit with the value of the scientific results the points can foster friendly between and teams to compute the most for the project users may receive credit for their work by clients on multiple machines users can use a to protect their contributions as they not only allow for the of bonus points but they also separate a user from any policy issues arising from another using that username users can their contributions under a team which the points of all their members a user can start their own team or they can join an existing team but existing points cannot be transferred to a new team or username in some cases a team may have their own community driven sources of help or such as an internet forum between teams benefit the folding community and members can have team for top spots individual and team statistics are posted on the folding home website software folding home software at the user s end involves three primary components work units cores and a client work units a work unit is the protein data that the client is asked to process work units are a fraction of the simulation calculating the rate of transitions between the states in a markov state model the client to a folding home server and a work unit and may also download an appropriate core depending on client settings operating system and underlying hardware architecture after the work unit has been completely processed it is returned and the respective credit points are awarded and this cycle then repeats automatically all work units have associated deadlines and if this deadline is the user may not get credit and the unit will be automatically to another as protein folding is serial in nature and many work units are generated from their predecessors this allows the overall simulation process to normally if one is not returned after a certain period of time due to these deadlines the minimum system for folding home is a cpu with or newer however work units for high performance clients have a much shorter deadline than those for the uniprocessor client as a major part of the scientific benefit is dependent on rapidly completing simulations before public release work units go through several quality steps to problematic ones from becoming fully available these stages include internal testing closed beta testing and open beta testing before a final full release across all of folding home folding home s work units are normally processed only once except in the event that errors occur during processing if this occurs for three different users it is automatically from distribution the folding home support forum can be used to between problematic hardware and a work unit cores specialized scientific computer programs referred to as and often cores perform the calculations on the work unit behind the scenes folding home s cores are modified and optimized versions of molecular dynamics programs including gromacs and most of folding home s cores use gromacs one of the fastest and most popular molecular dynamics software packages available which largely consists of manually optimized assembly code some of these cores perform explicit atom by atom molecular dynamics calculations while others perform solvation methods which treat atoms as a mathematical continuum while these cores use open source software folding home uses a closed source license and is not required to release the cores source code the same core can be used by various versions of the client and the core from the client enables their scientific methods to be updated automatically as needed without a client the cores also periodically create calculation so that if they are they can work from a upon client folding home participants client programs on their personal computer or on the playstation console the user interacts with the client which manages the other software components behind the scenes through the client the user may the folding process open an event the work progress or view personal statistics the clients run continuously in the background of the user s computer at an extremely low priority otherwise processing power so that normal computer usage is unaffected the maximum cpu utilization can also be adjusted through client settings computer clients to uniprocessor and multi core processors systems as well as graphics processing units while these latter clients use significantly more resources the diversity and power of each hardware architecture provides folding home with the ability to efficiently complete many different types of simulations in a manner in a few or months rather than years which is of significant scientific value together these clients allow researchers to study biomedical questions previously considered impossible to tackle computationally significant work into security issues in all of folding home s software for example clients can be only from the official folding home website or its commercial each client will upload and download data only from stanford s folding home data servers over with as an alternative using for verification and will only interact with folding home computer folding home s end user license agreement public access to the client source code for security and scientific reasons thus from a security it in a similar fashion to a web browser but is even more folding home s first client was a screensaver which would run folding home while the computer was not otherwise in use starting in the pande lab collaborated with david anderson to test a client on the open source boinc framework this client was released to closed beta in april however the approach became and was in june boinc s fixed architecture limits the types of project it can accommodate and thus was not appropriate for folding home graphics processing units the specialized hardware of gpus is designed to accelerate rendering of graphics applications such as video and can significantly cpus for certain types of calculations although limited in this makes gpus one of the most powerful and rapidly growing computational platforms as such general purpose gpu computing is the of many scientists and researchers however gpu hardware is difficult to utilize for non graphics tasks and usually requires significant algorithm and an advanced understanding of the underlying architecture such is challenging especially to researchers with limited software development resources to achieve hardware the pande lab s open source openmm library serves as a high level api allowing molecular simulation software to run efficiently on varying architectures without significant modification lower level interface the higher level api with the underlying platform this flexible approach performance nearly equal to hand gpu code and greatly cpu gpus remain folding home s most powerful platform in terms of flops as of may gpu clients account for of the entire project s flop throughput prior to the computational reliability of gpgpu hardware had remained largely unknown and evidence related to the lack of built in error detection and correction in gpu memory reliability the pande lab then the first large scale test of gpu scientific accuracy on over hosts on the folding home network soft errors were detected in the memory subsystems of two of the tested gpus the study found that the error rate was most dependent on board architecture but concluded that reliable gpgpu computing was very feasible as long as attention is to the hardware characteristics the first generation of folding home s windows gpu client was released to the public on october a speedup for certain calculations over its cpu based gromacs it was the first time gpus had been used for either distributed computing or major molecular dynamics calculations pande lab gained significant knowledge and experience with the development of gpgpu software but a need to improve scientific over it was succeeded by the second generation successor of the client on april following its introduction was officially on june compared to was more scientifically reliable and productive on and cuda enabled nvidia gpus and supported more advanced algorithms larger proteins and real time visualization of the protein simulation following this the third generation of folding home s gpu client was released on may while to is more stable and efficient is more flexible for additional scientific capabilities and uses openmm on top of an framework although the gpu client does not support the linux operating system it can be run under for users with nvidia graphics playstation folding home can also take advantage of the computing power of playstation at the time of its and for certain calculations its main cell processor a speed increase over processing power which could not be found on other systems such as the the s high speed and efficiency introduced other opportunities for and significantly changed the between computational efficiency and overall accuracy allowing for the utilization of more complex molecular models at little extra computational cost this allowed folding home to run biomedical calculations that would otherwise be computationally the also has the ability to stream data quickly to its gpu and is capable of real time atomic detail visualizations of the protein dynamics the client was developed in a collaborative effort between and the pande lab and was first released as a standalone client on march its release made folding home the first distributed computing project to utilize on september of the following year the client became a channel of life with playstation on its launch in terms of the types of calculations it can perform the client takes the middle ground between a cpu s flexibility and a gpu s speed however unlike cpus and gpus users cannot perform other activities on their while running folding home the s uniform console environment makes support easier and makes folding home more user friendly multi core processing client folding home can also utilize the parallel processing capabilities of modern multi core processors the ability to use several cpu cores simultaneously allows completion of the overall folding simulation much faster working together these cpu cores complete single work units faster than the standard uniprocessor client which reduces the traditional of scaling a large simulation to many processors while this approach is not only scientifically valuable the resulting publications would not have been possible without this computing power in november first generation symmetric smp clients were publicly released for open beta testing referred to as these clients used message passing interface mpi communication for parallel processing as at that time the gromacs cores were not designed to be used with multiple this was the first time a distributed computing project had utilized mpi as it had previously been only for supercomputers represented a landmark in the simulation of protein folding although the clients performed well in based operating systems such as linux and mac s os x they were particularly in windows on january the second generation of the smp clients and the successor to was released as an open beta and replaced the complex mpi with a more reliable based also supports a trial of a special category of bigadv work units designed for proteins that are large and computationally intensive but have a great scientific priority these units originally required a minimum of eight cpu cores but on february this was increased to cpu cores compared to standard units run on these also require more system resources such as and internet bandwidth but users who run these are with a increase over s bonus point system the bigadv category allows folding home to run particularly demanding simulations on long timescales that had previously required the use of supercomputing clusters and could not be performed on folding home the client is the and latest generation of the folding home client software and is a complete and of the previous clients for microsoft windows mac os x and linux operating systems like its predecessors can also run folding home in the background at a very low priority allowing other applications to use cpu resources as they need it is designed to make the start up and user friendly for as well as offers greater scientific flexibility than previous clients uses for managing its so that users can see its development process and provide feedback it was officially released on march consists of three elements the user interacts with s known as fahcontrol it has advanced and user interface modes and has the ability to monitor and control many folding clients from a single computer fahcontrol can monitor and direct which behind the scenes and in turn manages each or slot these act as for the previously distinct folding home computer clients as they may be of uniprocessor smp or gpu type each slot also contains a core and data associated with it and can download process and upload work units independently the function modeled after the s displays a real time rendering if available of the protein currently being processed comparison to other molecular systems rosetta home is a distributed computing project at protein structure prediction and is one of the most accurate tertiary structure available as rosetta only predicts the final folded state and not how proteins fold rosetta home and folding home address very different molecular questions the pande lab can use the conformational states from rosetta s software in a markov state model as starting points for folding home simulations conversely structure prediction algorithms can be improved from thermodynamic and kinetic models and the sampling aspects of protein folding simulations thus folding home and rosetta home perform complementary work anton is a special purpose supercomputer constructed for molecular dynamics simulations it is unique in its ability to produce individual ultra long molecular trajectories on biological timescales these simulations while computationally expensive contain more phase space than any one of folding home s many shorter trajectories like folding home it has also improved several long held theories of protein folding as of october anton and folding home are the two most powerful molecular dynamics systems and anton has also run individual simulations out to the range in the pande lab built a markov state model from a anton simulation the publication demonstrated that an msm built from serial data revealed folding information unobtainable with traditional approaches and that there was little difference between markov models constructed from anton s fewer long trajectories or one assembled from folding home s many shorter trajectories starting in june folding home began additional sampling of an anton simulation in an effort to better determine how its techniques compare to anton s more traditional methods it is that a combination of anton s and folding home s simulation methods would provide a well simulation over long timescales note supercomputer flop performance is assessed by running the linpack benchmark this short term testing has difficulty in accurately reflecting sustained performance on real world tasks because linpack more efficiently maps to supercomputer hardware computing systems also vary in architecture and design so direct comparison is difficult despite this flops remain the primary speed used in supercomputing folding home measures its work using wall time a more accurate method of determining actual performance 
 the term k mer or x mer where x can be virtually any of choice usually refers to a specific n or n of acid or amino acid sequences that can be used to identify certain regions within like dna e g for gene prediction or proteins either k mer as such can be used for finding regions of interest or k mer statistics giving discrete probability distributions of a number of possible k mer combinations or rather with are used specific short k mers are called oligomers or oligos for short 
 the journal of computational biology is a peer reviewed scientific journal dedicated to computational biology and bioinformatics the journal is published in issues per year by 
 foldit is an online puzzle video game about protein folding the game is part of an experimental research project and is developed by the university of washington s center for game science in collaboration with the department of biochemistry the objective of the game is to fold the structure of selected proteins to the best of the s ability using various tools provided within the game the highest solutions are by researchers who determine whether or not there is a native structural configuration or native state that can be applied to the relevant proteins in the real world scientists can then use such solutions to solve real world problems by and diseases and creating biological history rosetta david baker a protein research scientist at the university of washington is responsible for beginning the foldit project prior to the project s baker and his laboratory co workers upon another research project rosetta to predict the native structures of various proteins using special computer protein structure prediction algorithms the project was eventually extended to utilize the processing power of user s personal computers by developing a distributed computing program rosetta home the rosetta home program was made available for public download and was designed to display progress of a particular protein being worked on at the time as a screensaver the results of the program s prediction routines are sent to a central project server for verification some users of rosetta home became with the program when they realised they could see ways of solving the protein structures themselves but could not interact with the program when baker realised that humans could have considerable potential over computers to solve protein structures he david a computer scientist and a game designer studying at the same university to help and build an interactive program that would both to the public and assist in their efforts to find the native structures of proteins a game foldit many of the same people who created rosetta home worked on the construction of foldit the public beta version was released in may and has players since the foldit project has in critical assessment of techniques for protein structure prediction casp experiments its best solutions to targets based on unknown protein structures casp is an international experiment which aims to assess existing methods of protein structure prediction and highlight research that may be more productive toward solving protein structures goals protein structure prediction is important in several fields of science including bioinformatics molecular biology and medicine successful identification of the structural configuration of natural proteins enables scientists to study and understand proteins better this can lead toward the creation of novel proteins by design in the treatment of diseases and the development of solutions for other real world problems such as species and pollution the process by which living create the primary structure of proteins protein biosynthesis is well understood as is the means by which proteins are as dna determining how the primary structure of a protein into a three dimensional the molecule folds more difficult the general process is known but protein structure prediction is computationally demanding methods similar to rosetta home david baker and his team of co workers aim to use foldit as a means of native protein structures faster through a combination of crowdsourcing and distributed computing however there is a greater on crowdsourcing and community collaboration with the foldit project other methods such as virtual interaction and gamification were added creating a unique and innovative project environment with the potential to greatly assist the cause virtual interaction foldit attempts to apply the human brain s natural three dimensional pattern matching and spatial to help solve the problem of protein structure prediction current puzzles are based on well understood proteins by the ways in which humans approach these puzzles researchers hope to improve the algorithms employed by existing protein folding software foldit provides a series of in which the user simple protein like structures and a periodically updated set of puzzles based on real proteins the application displays a graphical representation of the protein s structure which the user is able to with the aid of a set of tools gamification rather than just building a useful science tool the developers of foldit focused on designing a program that the concept of gamification the aim was to make the program more and to a public audience in order to more people to the cause of protein folding this was especially true for those people that did not have a scientific education or background as the structure is modified a is calculated based on how well folded the protein is and a list of high scores for each puzzle is maintained foldit users may create and join groups and share puzzle solutions with each other a separate list of group high scores is maintained future development the is primarily for the design of protein molecules the game announced the plan to add the chemical building blocks with organic to enable the foldit players to design small molecules by 
 premier biosoft pb is a california united states based bioinformatics company the company in developing software for use in life science research in addition to developing software products the company offers for bioinformatics projects company background premier biosoft established in is one of the bioinformatics company founded by and brown with a mission to serve the life science research labs all over the world the mission statement for pb reads as follows research in life the company serves research labs core facilities and biotechnology companies with its products the company s first product primer premier was authored over years ago for designing pcr assays products and services after the launch of primer premier the company released a drawing and cloning simulation tool and designer for designing microarray probes the in the pcr market was soon towards a new and powerful technique called real time pcr premier biosoft up early and authored the most popular real time pcr the company later came out with a pathogen detection system called with support for real time pcr and microarray probe design for designing cross species species specific intron exon assays and variant microarrays the company has ventured into proteomics and research with the launch of primer primer design tool ms ms data analysis tool and characterization tool the company s latest offerings for and ion distribution in and for designs oligos for systems 
 the international society for computational biology iscb is a society for researchers in computational biology and bioinformatics founded in the society s core mission is to contribute to the scientific understanding of living systems through computation iscb seeks to communicate the significance of computational biology to the larger scientific community to organizations and to the general public the society serves its members and internationally it provides for scientific publications meetings and information through multiple platforms iscb the intelligent systems for molecular biology ismb conference every year a growing number of smaller more or focused annual and bi annual conferences and has two official journals plos computational biology and bioinformatics the society two each year the overton prize and the by a scientist award and it to members that have distinguished themselves through contributions to the fields of computational biology and bioinformatics iscb leadership a president an executive committee and a board of directors comprise iscb s scientific leadership drawing on distinguished internationally renowned researchers who are elected for their term by the general society membership the executive leads the iscb staff and supports a diverse set of dedicated to specific issues that are important to the computational biology and bioinformatics community including education policy and publications aims iscb has the following aims conferences iscb grew out of the need for a stable organizational structure to support the planning and manage the finances of the intelligent systems for molecular biology ismb conference series which had its start in ismb is iscb s most prominent annual activity toward which a significant portion of resources are dedicated each year since when ismb is held in europe it is held with the european conference on computational biology eccb iscb began expanding its conference offerings with the introduction of the annual rocky mountain bioinformatics conference series in the annual conference on semantics in healthcare and life sciences cshals in the bi annual iscb africa asbcb conference on bioinformatics in and the bi annual iscb latin america conference in future plans include the development of an iscb asia conference in addition to iscb organized conferences the society supports other computational biology and bioinformatics conferences through and these include the annual pacific on or the annual international conference on research in computational molecular biology or the annual asia pacific bioinformatics network s international conference on computational biology or and the annual general meeting of the european molecular biology network or affiliated organizations africa asia europe and middle north america south america overview in the ismb conference committee thought it would be useful to start a scientific society focused on managing all scientific organizational and financial aspects of the ismb conference and to provide a forum for scientists to address the emerging role of computers in the biological sciences the international society for computational biology iscb was legally in the us in with currently director of the center for computational pharmacology at the university of colorado school of medicine and the university s computational program elected as its president by the members of the founding board of directors russ altman glasgow peter overton david david states and during the next few years the focus remained on management of the annual ismb conference whose attendance of approximately researchers had more than tripled by that year bioinformatics previously published as by oxford university press became the official journal of the iscb members of the society gained two of membership ismb conference registration and an online subscription to the journal the new brought in a new president in russ altman currently chair of stanford university s department of and director of the program in biomedical informatics and over attended ismb in san diego altman took steps to some of the and aspects of iscb before passing the in to e bourne currently professor in the department of pharmacology and school of and pharmaceutical sciences at the university of california san diego bourne gave iscb a more home at ucsd which included the university s to host the society through at least and its offer of staff support although bourne served as president for only one year he left his mark on the society by increasing the interaction with regional groups and conference organizers worldwide and through an improved web presence during his tenure membership grew to more than researchers and the ismb conference in canada over attendees in iscb vice president initiated the affiliated regional groups program to promote relationship building among bioinformatics groups worldwide the program offers a structure for mutual recognition and information exchange between the iscb and other bioinformatics groups so they can cross promote and events in the fall of the first european conference on computational biology eccb was held in germany which iscb supported through student travel and many iscb members and attended michael gribskov then at ucsd s san diego supercomputer department and now at the department of biological sciences at university was elected president in that year ismb took place in which was the first time the meeting was held outside north america or europe this phase brought many for the society when attendance to one half of expectations due to travel and related to of or the start of the war in and the location which with the pattern of north american and european venues although scientifically successful the financial losses of ismb left iscb for the first time in its history in part to iscb s dependence on ismb proceeds to the society s activities and annual overhead costs a pilot regional conference was in the us to gauge interest in smaller localized meetings in december the rocky mountain regional bioinformatics conference rocky was launched in colorado the meeting has been held ever since and now attendees from around the world in ismb eccb and genes proteins and computers for a joint conference in glasgow and included two parallel tracks of original paper for the first time as iscb s with the journal bioinformatics was drawing to a close the society moved to an online subscription plan for members since many scientists worked and studied at institutions that already held subscriptions therefore the need for individual subscriptions for all members that year also the launch of the iscb student council which opportunities of and young researchers working in computational biology and bioinformatics during an in phil bourne s lab while still a phd student now a scientist at the sanger institute developed the idea for a student council to give leadership opportunities and encourage among student members worldwide and was elected as its first council chair in in as part of the society s about the role of publications and the society s official journal by the advent of open access the iscb announced a partnership with the public library of science and launched a new open access journal plos computational biology the journal is intended to computational methods applied to living systems at all scales from molecular biology to populations and and which offer insight for experimentalists past president and past publications committee chair phil bourne served as the new publication s editor in and he remains in that role the first issue of the new journal with the day of ismb held in in ismb again ventured away from the pattern of north american and european venues by place in in collaboration with the association for bioinformatics and computational biology or once again the conference was a scientific success and included new tracks to encourage participation of experimentalists as well as computer scientists but attendance was approximately half of the previous year which negatively the society finances that had not yet recovered from the losses of membership for the year did not as as conference attendance which provided a strong sign for the successful of membership enrollment and conference registration burkhard rost then professor in the department of biochemistry and molecular biophysics at university and now the von professor and chair of bioinformatics and computational biology computational sciences at the technical university munich succeeded michael gribskov as president in and has been twice with a current term set for january under his tenure the ismb eccb conference in vienna austria chaired by thomas of the max planck institute for informatics and co chaired by burkhard rost and peter of the university of vienna was further expanded to include a total of eight parallel tracks and the conference attendance of approximately was back on track with expectations vienna as a and the austria center vienna were both so well received by the conference organizers and attendees that it was selected to host the conference as well which is a first for the ismb series that had before repeated a location in ismb chaired by burkhard rost and co chaired by jill mesirov of the broad institute of and mit and michal linial of the university of with thomas of the institute for cancer research serving as honorary co chair returned to canada this time attendance was strong membership enrollment continued to grow and the conference on semantics for healthcare and life sciences or cshals was created group of and incoming of iscb launched a new for the society that greatly enhanced the interactive functionality of the society s web presence for iscb members and improved access to information about computational biology and bioinformatics for the scientific community and general public in ismb eccb chaired by of the medical institute campus and co chaired by of with von of stockholm university serving as honorary co chair was held in stockholm sweden iscb membership reached a new high the student council initiated a regional student groups program to foster interactions between student groups around the world and iscb organized the first iscb africa asbcb joint conference on bioinformatics with the society for bioinformatics and computational biology in in ismb chaired by of princeton university and co chaired by jill mesirov and michal linial was held in boston usa the first iscb latin america chaired by a postdoc at the university of california san and then a phd candidate and now a postdoc at the university of was held in 
 the louis and beatrice laufer center for physical and quantitative biology is a multidisciplinary venue where research from such fields as biology biochemistry chemistry computer science engineering genetics mathematics and physics can come together and target medical and biological problems using both computation and experiment the laufer center is part of university the center s current director is dr a director is dr dr david f will head the multi training program for the center history the center was founded in by a from laufer laufer and their family in memory of louis and beatrice laufer on may the laufer center with a cutting 
 the law of maximum also known as law of the maximum is a principle developed by which states that total growth of a or a plant is proportional to about growth factors growth will not be greater than the aggregate values of the growth factors without the correction of the limiting growth factors and other are not fully or used resulting in resources applications hence the need to achieve maximal value for each factor is critical in order to obtain maximal growth of law of the the following demonstrates the law of the maximum for the various below one two or three factors were limiting while all the other factors were when two or three factors were simultaneously limiting predicted growth of the two or three factors was similar to the actual growth when the two or three factors were limits individually and then multiplied together 
 the enzyme function efi is a large scale collaborative project to develop and disseminate a robust strategy to determine enzyme function through an integrated sequence structure based approach the project was funded in may by the national institute of general medical sciences as a glue grant which supports the research of complex biological problems that cannot be solved by a single research group the efi was largely by the need to develop methods to identify the functions of the number proteins discovered through genomic sequencing projects the dramatic increase in genomic sequencing projects has caused the number of protein sequences deposited into public databases to grow to with the of sequences databases use computational predictions to annotate individual protein s functions while these computational methods offer the advantages of being extremely high throughput and generally provide accurate broad use has to a significant level of of enzyme function in protein databases thus although the information now available represents an opportunity to understand cellular metabolism across a wide variety of organisms which includes the ability to identify molecules and or reactions that may benefit human quality of life the potential has not been fully the biological community s ability to characterize discovered proteins has been by the rate of genome sequencing and the task of function is now considered the rate limiting step in understanding biological systems in detail integrated strategy for functional assignment the efi is developing an integrated sequence structure based strategy for functional assignment by predicting the specificities of unknown members of diverse enzyme superfamilies the approach conserved features within a given superfamily such as known chemistry of active site functional groups and composition of determining residues motifs or structures to predict function but on multidisciplinary expertise to and test the predictions the integrated sequence strategy under development will be generally applicable to the ligand specificities of any unknown protein organization by program glue grant must contain core resources and bridging projects the efi consists of six scientific cores which provide bioinformatic structural computational and data management expertise to functional predictions for enzymes of unknown function targeted by the efi these predictions are then tested by five bridging projects the amidohydrolase enolase gst had and isoprenoid synthase enzyme superfamilies scientific cores the superfamily genome core bioinformatic analysis by and complete sequence data sets generating sequence similarity networks and classification of superfamily members into and families for subsequent annotation transfer and evaluation as targets for functional characterization the protein core cloning expression and protein strategies for the enzymes targeted for study the structure core fulfills the structural biology component for efi by providing high resolution structures of targeted enzymes the computation core performs in silico docking to generate rank ordered of predicted substrates for targeted enzymes using both experimentally determined and or homology modeled protein structures the core in functions using genetic techniques and metabolomics to in vitro functions determined by the bridging projects the data and dissemination core two complementary public databases for bioinformatic structure function database and experimental data efi bridging projects the amidohydrolase superfamily contains evolutionarily related enzymes with a distorted fold which primarily catalyze metal assisted or reactions the enolase superfamily contains evolutionarily related enzymes with a fold which primarily catalyze metal assisted or of substrates the gst superfamily contains evolutionarily related enzymes with a modified fold and an additional all helical domain which primarily catalyze nucleophilic attack of reduced on substrates the had superfamily contains evolutionarily related enzymes with a fold with an inserted region which primarily catalyze metal assisted nucleophilic most frequently resulting in group transfer the isoprenoid synthase i superfamily contains evolutionarily related enzymes with a mostly all helical fold and primarily catalyze trans transfer reactions to form elongated or products investigators investigators with expertise in various disciplines make up the efi the efi s primary is development and dissemination of an integrated sequence structure strategy for functional assignment as the strategy is developed data and generated by the efi are made freely available via several online resources funding the efi was established in may with million in funding over a year period grant number project success and assessment of the glue grant funding mechanism the grant may be for an additional years in 
 the small rnas snornas represent an abundant group of small non coding rnas in with the of rnase all the snornas fall into two major families box c d and box h snornas on the basis of common sequence motifs and structural features they can be divided into and snornas according to the presence or absence of antisense sequence to or 
 sepp hochreiter in am is a computer scientist working in the fields of bioinformatics and machine learning since he has been head of the institute of bioinformatics at the johannes kepler university of linz before he was at the technical university of at the university of colorado at and at the technical university of munich he founded the program in bioinformatics at the johannes kepler university of linz where he is still the acting he founded the bioinformatics working group at the austrian computer society he is the of the university linz at the he is founding board member of different bioinformatics start up companies he was program chair of the conference bioinformatics research and development he is editor program committee member and for international journals and conferences scientific contributions microarray preprocessing and summarization sepp hochreiter developed factor analysis for robust microarray summarization farms farms has been designed for preprocessing and high density oligonucleotide dna microarrays at probe level to analyze rna gene expression farms is based on a factor analysis model which is optimized in a bayesian framework by the probability on in and other benchmark data farms outperformed all other methods a highly relevant feature of farms is its informative non informative i ni the i ni call is a bayesian technique which signal variance from noise variance the i ni call offers a solution to the main problem of high when analyzing microarray data by genes which are measured with high quality farms has been extended to farms for detecting dna structural variants like copy number variations with a low discovery rate biclustering sepp hochreiter developed factor analysis for bicluster acquisition fabia for biclustering that is simultaneously clustering rows and columns of a matrix a bicluster in data is a pair of a gene set and a sample set for which the genes are similar to each other on the samples and vice in drug design for example the effects of compounds may be similar only on a of genes fabia is a model that assumes realistic non signal distributions with heavy and utilizes well understood model selection techniques like a approach in the bayesian framework fabia the information content of each bicluster to separate biclusters from true biclusters support vector machines support vector machines svms are learning methods used for classification and regression analysis by patterns and in the data standard svms require a positive definite kernel to generate a kernel matrix from the data sepp hochreiter proposed the potential support vector machine psvm which can be applied to non square kernel matrices and can be used with that are not positive definite for psvm model selection he developed an efficient sequential minimal optimization algorithm the psvm a new objective which ensures theoretical on the generalization error and automatically features which are used for classification or regression feature selection sepp hochreiter applied the psvm to feature selection especially to gene selection for microarray data the psvm and standard support vector machines were applied to extract features that are indicative coil oligomerization low complex neural networks neural networks are different types of simplified mathematical models of biological neural networks like those in human brains if data mining is based on neural networks overfitting reduces the network s capability to correctly process future data to avoid overfitting sepp hochreiter developed algorithms for finding low complexity neural networks like flat minimum search which for a flat minimum a large connected region in the parameter space where the network function is constant thus the network parameters can be given with low precision which means a low complex network that avoids overfitting recurrent neural networks recurrent neural networks and process sequences and supply their results to the environment sepp hochreiter developed the long short term memory which overcomes the problem of previous recurrent networks to information about the sequence which was observed at the begin of the sequence lstm from training sequences to solve numerous tasks like automatic composition recognition learning and lstm was successfully applied to very fast protein homology detection without a sequence alignment 
 aureus sciences is a research based company which software to the pharmaceutical industry for drug development the company s range of products includes therapeutic target adme based databases and software applications aureus sciences was known as aureus products aureus software applications allow in silico prediction of drug absorption distribution metabolism and adme and potential drug drug interactions the scientific background to aureus process is detailed in recent publications 
 ieee acm on computational biology and bioinformatics is a peer reviewed scientific journal published it is a joint publication of the ieee computer society association for computing ieee computational intelligence society and the ieee engineering in medicine and biology society it research results related to the 
 the definition of the knotted protein a knot is defined as a of a three dimensional points to a circle according to this definition a knot only make senses for a closed loop however if we a point in space at distance and to the n and c respectively through a virtual bond the protein can be treated as a closed loop introduction of the knotted protein knotted proteins present one of the most challenging problems to both computational and experimental biologists despite an ever increasing number of knotted proteins deposited in pdb it is still not clear how a protein folds into a knotted conformation or how a protein s knot is related to its function though a number of computational methods have been developed for detecting protein knots there are still no completely automatic methods to detect protein knots without the necessary intervention due to the residues or chain in the x ray structures or the pdb at present there are types of knot identified in knot the knot the knot and the knot the web server to the knotted protein recently a number web servers were published providing service for knotted structures and analysis tools for detecting protein knots 
 biouml is an open source software platform for the analysis of data from omics sciences research and other advanced computational biology developed by scientists from the institute of systems biology in the platform is freely available online and used in research labs mostly in academic institutions for the discovery of disease and there is a commercial version available from bioinformatics services company which has some added features biouml is open source so is freely available online available versions the current release of biouml is version released in october and includes versions biouml server which offers access to data and analysis methods server side for biouml clients workbench and web edition over the internet biouml workbench this is a java application that can work standalone or as client for the biouml server edition biouml web edition this is a web browser based thin client for the biouml server edition and provides most of the functionality of the biouml workbench it utilizes and technology for interactive data and modeling the platform has been developed continuously since and offers data analysis and visualizations for scientists involved in complex molecular biology research the system allows for the description of biological systems structure and function including tools required to make related to genomics proteomics and metabolomics the biouml platform is built in a modular architecture which has allowed for the simple addition of new tools this has allowed the integration of many tools into the platform over the years it has been available application and usage biouml was used as the main workbench for s integrated database on cell cycle regulation and in next generation sequencing and other high throughput methods create data sets called big data in the region of terabytes biouml can disseminate analyse produce visualizations simulations allow for parameters and allow many other analysis techniques required to deal with such large amounts of raw data as research is typically shared between various institutions the storage delivery and of big data has been a technical challenge a typical genome data set might contain terabytes of data which may need to be shared often internationally using technology data mechanisms have been created by valex llc for the short read project that allows for the delivery of raw research data at speeds of up to to provide a full solution for such collaborative research the makers of biouml have developed a new hardware software system in partnership with valex llc this version of biouml is called biodatomics commercial versions biodatomics is a new available version of biouml which is a hardware and software solution for next generation and omics science researchers biodatomics is not open source but has the same modular architecture as biouml and is as a full hardware software platform as a service configuration as well as a standalone version of biouml platform in a software as a service configuration 
 de novo transcriptome assembly is the method of creating a transcriptome without the aid of a reference genome introduction before the development of de novo transcriptome assembly transcriptome information was only available for a of model organisms utilized by the international scientific research community since sequencing was very costly even just five years ago only transcriptomes of organisms that were of broad interest and to scientific research were sequenced with the advent of high throughput sequencing also called next generation sequencing technologies that are both cost and effective it is now possible to expand the range of organisms studied via these methods within the past few years transcriptomes have been created for as well as the brains of the the the and the red to name just a few non model organisms can provide novel insights into the mechanisms underlying the of that have enabled the abundance of life on planet earth in and the that cannot be examined in common model organisms include and de novo transcriptome assembly is often the method to studying non model organisms since it is and easier than building a genome and reference based methods are not possible without an existing genome the transcriptomes of these organisms can thus reveal novel proteins and their isoforms that are implicated in such unique biological phenomena de novo vs reference based assembly a set of assembled transcripts allows for initial gene expression studies prior to the development of transcriptome assembly computer programs transcriptome data were analyzed primarily by mapping on to a reference genome though genome alignment is a robust way of characterizing transcript sequences this method is by its to account for of structural alterations of mrna transcripts such as alternative splicing since a genome contains the sum of all introns and exons that may be present in a transcript spliced variants that align continuously along the genome may be as actual protein isoforms transcriptome vs genome assembly unlike genome sequence coverage levels which can vary as a result of content in non coding intron regions of dna transcriptome sequence coverage levels can be directly indicative of gene expression levels these repeated sequences also create ambiguities in the formation of contigs in genome assembly while ambiguities in transcriptome assembly contigs usually correspond to spliced isoforms or minor variation among members of a gene family method rna seq once mrna is extracted and from cells it is sent to a high throughput sequencing facility where it is first transcribed to create a cdna library this cdna can then be into various lengths depending on the platform used for sequencing each of the following platforms utilizes a different type of technology to sequence millions of short reads sequencing and solid assembly algorithms the cdna sequence reads are assembled into transcripts via a short read transcript assembly program most likely some amino acid variations among transcripts that are otherwise similar reflect different protein isoforms it is also possible that they represent different genes within the same gene family or even genes that share only a conserved domain depending on the degree of variation a number of assembly programs are available see assemblers although these programs have been generally successful in assembling genomes transcriptome assembly some unique challenges whereas high sequence coverage for a genome may indicate the presence of repetitive sequences and thus be for a transcriptome they may indicate abundance in addition unlike genome sequencing transcriptome sequencing can be specific due to the possibility of both sense and antisense transcripts finally it can be difficult to reconstruct and apart all splicing isoforms short read assemblers generally use one of two basic algorithms overlap graphs and de bruijn graphs overlap graphs are utilized for most assemblers designed for sanger sequenced reads the between each pair of reads is computed and compiled into a in which each represents a single sequence read this algorithm is more computationally intensive than de bruijn graphs and most effective in assembling fewer reads with a high degree of overlap de bruijn graphs align k mers usually based on k sequence conservation to create contigs the use of k mers which are shorter than the read lengths in de bruijn graphs reduces the computational intensity of this method functional annotation functional annotation of the assembled transcripts allows for insight into the particular molecular functions cellular components and biological processes in which the proteins are involved enables gene based data mining to annotate sequence data for which no go annotation is available yet it is a research tool often employed in functional genomics research on non model species it works by assembled contigs against a non redundant nucleotide database then them based on sequence similarity is another go annotation program specific for and plant gene products that works in a similar fashion it is part of the database of publicly of computational tools for go annotation and analysis following annotation of genes and genomes enables visualization of pathways and molecular interaction networks in the transcriptome in addition to being for go terms contigs can also be for open frames in order to predict the amino acid sequence of proteins derived from these transcripts another approach is to annotate protein domains and determine the presence of gene families rather than specific genes verification and quality control since a reference genome is not available the quality of computer assembled contigs may be verified by aligning the sequences of conserved gene domains found in mrna transcripts to transcriptomes or genomes of closely related species another method is to design pcr for predicted transcripts then attempt to them from the cdna library exceptionally short reads are out short sequences amino acids are to represent functional proteins as they are unable to fold independently and form hydrophobic cores assemblers the following is a partial of assembly software that has been used to generate transcriptomes and has also been in scientific literature velvet the velvet algorithm uses de bruijn graphs to assemble transcripts in simulations velvet can produce contigs up to kb length using data and kb in bacterial artificial chromosomes these transcripts are transferred to which uses paired end read and long read information to build transcript isoforms trans abyss abyss is a parallel paired end sequence trans abyss assembly by short sequences is a software pipeline written in python and perl for analyzing abyss assembled transcriptome contigs this pipeline can be applied to generated across a wide range of k values it first reduces the into smaller sets of non redundant contigs and identifies splicing events including exon novel exons introns novel introns and alternative splicing the trans abyss algorithms are also able to estimate gene expression levels identify potential sites as well as candidate gene fusion events