Quantitative metabolic profiling of NMR spectral signatures of branched chain amino acids in blood serum

Branched Chain Amino Acids (BCAAs) are related to different aspects of diseases like pathogenesis, diagnosis and even prognosis. While in some diseases, levels of all the BCAAs are perturbed; in some cases, perturbation occurs in one or two while the rest remain unaltered. In case of ischemic heart disease, there is an enhanced level of plasma leucine and isoleucine but valine level remains unaltered. In `Hypervalinemia', valine is elevated in serum and urine, but not leucine and isoleucine. Therefore, identification of these metabolites and profiling of individual BCAA in a quantitative manner in body-fluid like blood plasma/serum have long been in demand. H-1 NMR resonances of the BCAAs overlap with each other which complicates quantification of individual BCAAs. Further, the situation is limited by the overlap of broad resonances of lipoprotein with the resonances of BCAAs. The widely used commercially available kits cannot differentially estimate the BCAAs. Here, we have achieved proper identification and characterization of these BCAAs in serum in a quantitative manner employing a Nuclear Magnetic Resonance-based technique namely T-2-edited Correlation Spectroscopy (COSY). This approach can easily be extended to other body fluids like bile, follicular fluids, saliva, etc.

A hybrid method for stochastic response analysis of a vibrating structure

Response analysis of a linear structure with uncertainties in both structural parameters and external excitation is considered here. When such an analysis is carried out using the spectral stochastic finite element method (SSFEM), often the computational cost tends to be prohibitive due to the rapid growth of the number of spectral bases with the number of random variables and the order of expansion. For instance, if the excitation contains a random frequency, or if it is a general random process, then a good approximation of these excitations using polynomial chaos expansion (PCE) involves a large number of terms, which leads to very high cost. To address this issue of high computational cost, a hybrid method is proposed in this work. In this method, first the random eigenvalue problem is solved using the weak formulation of SSFEM, which involves solving a system of deterministic nonlinear algebraic equations to estimate the PCE coefficients of the random eigenvalues and eigenvectors. Then the response is estimated using a Monte Carlo (MC) simulation, where the modal bases are sampled from the PCE of the random eigenvectors estimated in the previous step, followed by a numerical time integration. It is observed through numerical studies that this proposed method successfully reduces the computational burden compared with either a pure SSFEM of a pure MC simulation and more accurate than a perturbation method. The computational gain improves as the problem size in terms of degrees of freedom grows. It also improves as the timespan of interest reduces.

Spectral Clustering with Jensen-type kernels and their multi-point extensions

Motivated by multi-distribution divergences, which originate in information theory, we propose a notion of `multipoint' kernels, and study their applications. We study a class of kernels based on Jensen type divergences and show that these can be extended to measure similarity among multiple points. We study tensor flattening methods and develop a multi-point (kernel) spectral clustering (MSC) method. We further emphasize on a special case of the proposed kernels, which is a multi-point extension of the linear (dot-product) kernel and show the existence of cubic time tensor flattening algorithm in this case. Finally, we illustrate the usefulness of our contributions using standard data sets and image segmentation tasks.

Lower Bound Axisymmetric Limit Analysis Using Drucker-Prager Yield Cone and Simulation with Mohr-Coulomb Pyramid

This paper presents a lower bound limit analysis approach for solving an axisymmetric stability problem by using the Drucker-Prager (D-P) yield cone in conjunction with finite elements and nonlinear optimization. In principal stress space, the tip of the yield cone has been smoothened by applying the hyperbolic approximation. The nonlinear optimization has been performed by employing an interior point method based on the logarithmic barrier function. A new proposal has also been given to simulate the D-P yield cone with the Mohr-Coulomb hexagonal yield pyramid. For the sake of illustration, bearing capacity factors N-c, N-q and N-gamma have been computed, as a function of phi, both for smooth and rough circular foundations. The results obtained from the analysis compare quite well with the solutions reported from literature.

Multiple Spectral Peak Tracking for Heart Rate Monitoring from Photoplethysmography Signal During Intensive Physical Exercise

We propose a multiple initialization based spectral peak tracking (MISPT) technique for heart rate monitoring from photoplethysmography (PPG) signal. MISPT is applied on the PPG signal after removing the motion artifact using an adaptive noise cancellation filter. MISPT yields several estimates of the heart rate trajectory from the spectrogram of the denoised PPG signal which are finally combined using a novel measure called trajectory strength. Multiple initializations help in correcting erroneous heart rate trajectories unlike the typical SPT which uses only single initialization. Experiments on the PPG data from 12 subjects recorded during intensive physical exercise show that the MISPT based heart rate monitoring indeed yields a better heart rate estimate compared to the SPT with single initialization. On the 12 datasets MISPT results in an average absolute error of 1.11 BPM which is lower than 1.28 BPM obtained by the state-of-the-art online heart rate monitoring algorithm.

Spectral characterizations and photophysical properties of one-step synthesized blue fluorescent 4 `-aryl substituted 2,2 `:6 `,2 `'-terpyridine for OLEDs application

We have synthesized a series of 4'-aryl substituted 2,2':6',2 `'-terpyridine (terpy) derivatives, namely 4'-(4-methylphenyl)-2,2':6',2 `'-terpyridine (C-1), 4'-(2-furyl)-2,2':6'2 `'-terpyridine (C-2), and 4'-(3,4,5-trimethoxyphenyl)-2,2':6',2 `'-terpyridine (C-3). The synthesized terpy compounds were characterized by elemental analyses, FTIR, NMR (H-1 and C-13), and ESI-Mass spectrometry. Photophysical, electrochemical and thermal properties of terpy compounds were systematically studied. Maximum excitation band was observed between 240 and 330 nm using UV-visible spectra, and maximum emission peaks from PL spectra were observed at 385, 405 and 440 nm for C-1, C-2 and C-3 respectively. Fluorescence lifetime (tau) of the fluorophores was found to be 035 and 1.55 ns at the excitation wavelength of 406 nm for C-1 and C-2 respectively, and tau value for C-3 was found to be 0.29 ns at the excitation wavelength of 468 nm. We noticed that the calculated values of HOMO energy levels were increased from 5.96 (C-1) to 6.08 (C-3) eV, which confirms that C-3 derivative is more electrons donating in nature. The calculated electrochemical band gaps were 2.95, 2.82 and 3.02 eV for C-1, C-2 and C-3 respectively. These blue fluorescent emitter derivatives can be used as an electron transport and electroluminescent material to design the blue fluorescent organic light emitting diode (OLED) applications. (C) 2015 Elsevier B.V: All rights reserved.

Spectral intensity distribution of trapped

To calculate static response properties of a many-body system, local density approximation (LDA) can be safely applied. But, to obtain dynamical response functions, the applicability of LDA is limited bacause dynamics of the system needs to be considered as well. To examine this in the context of cold atoms, we consider a system of non-interacting spin4 fermions confined by a harmonic trapping potential. We have calculated a very important response function, the spectral intensity distribution function (SIDF), both exactly and using LDA at zero temperature and compared with each other for different dimensions, trap frequencies and momenta. The behaviour of the SIDF at a particular momentum can be explained by noting the behaviour of the density of states (DoS) of the free system (without trap) in that particular dimension. The agreement between exact and LDA SIDFs becomes better with increase in dimensions and number of particles.

Spectral solutions to the Korteweg-de-Vries and nonlinear Schrodinger equations

In this paper, we present the solutions of 1-D and 2-D non-linear partial differential equations with initial conditions. We approach the solutions in time domain using two methods. We first solve the equations using Fourier spectral approximation in the spatial domain and secondly we compare the results with the approximation in the spatial domain using orthogonal functions such as Legendre or Chebyshev polynomials as their basis functions. The advantages and the applicability of the two different methods for different types of problems are brought out by considering 1-D and 2-D nonlinear partial differential equations namely the Korteweg-de-Vries and nonlinear Schrodinger equation with different potential function. (C) 2015 Elsevier Ltd. All rights reserved.

Uncertainty Quantification in Ultrasonic Wave Based Detection of Delamination in Composite Structures

In this paper we consider the problem of guided wave scattering from delamination in laminated composite and further the problem of estimating delamination size and layer-wise location from the guided wave measurement. Damage location and region/size can be estimated from time of flight and wave packet spread, whereas depth information can be obtained from wavenumber modulation in the carrier packet. The key challenge is that these information are highly sensitive to various uncertainties. Variation in reflected and transmitted wave amplitude in a bar due to boundary/interface uncertainty is studied to illustrate such effect. Effect of uncertainty in material parameters on the time of flight are estimated for longitudinal wave propagation. To evaluate the effect of uncertainty in delamination detection, we employ a time domain spectral finite element (tSFEM) scheme where wave propagation is modeled using higher-order interpolation with shape function have spectral convergence properties. A laminated composite beam with layer-wise placement of delamination is considered in the simulation. Scattering due to the presence of delamination is analyzed. For a single delamination, two identical waveforms are created at the two fronts of the delamination, whereas waves in the two sub-laminates create two independent waveforms with different wavelengths. Scattering due to multiple delaminations in composite beam is studied.

Simulation of Effective Thermal Conductivity of Metal Hydride Packed Beds

Several mathematical models are available for estimation of effective thermal conductivity of nonreactive packed beds. Keeping in view the salient differences between metal hydride beds in which chemisorption of hydrogen takes place and conventional nonreactive packed beds, modified models are proposed here to predict the effective thermal conductivity. Variation in properties such as solid thermal conductivity and porosity during hydrogen absorption and desorption processes are incorporated. These extended models have been applied to simulate the effective thermal conductivity of the MmNi(4.5)Al(0.5) hydride bed and are compared with the experimental results. Applicability of the extended models for estimation of the effective thermal conductivity at different operating conditions such as pressure, temperature, and hydrogen concentration is discussed.

Learning-Based Fast Iterative Convergence of 3-D MoM via Eigen-AGMRES Method

Three-dimensional (3-D) full-wave electromagnetic simulation using method of moments (MoM) under the framework of fast solver algorithms like fast multipole method (FMM) is often bottlenecked by the speed of convergence of the Krylov-subspace-based iterative process. This is primarily because the electric field integral equation (EFIE) matrix, even with cutting-edge preconditioning techniques, often exhibits bad spectral properties arising from frequency or geometry-based ill-conditioning, which render iterative solvers slow to converge or stagnate occasionally. In this communication, a novel technique to expedite the convergence of MoMmatrix solution at a specific frequency is proposed, by extracting and applying Eigen-vectors from a previously solved neighboring frequency in an augmented generalized minimum residual (AGMRES) iterative framework. This technique can be applied in unison with any preconditioner. Numerical results demonstrate up to 40% speed-up in convergence using the proposed Eigen-AGMRES method.

Computationally efficient models for simulation of non-ideal DC-DC converters operating in continuous and discontinuous conduction modes

This paper discusses dynamic modeling of non-isolated DC-DC converters (buck, boost and buck-boost) under continuous and discontinuous modes of operation. Three types of models are presented for each converter, namely, switching model, average model and harmonic model. These models include significant non-idealities of the converters. The switching model gives the instantaneous currents and voltages of the converter. The average model provides the ripple-free currents and voltages, averaged over a switching cycle. The harmonic model gives the peak to peak values of ripple in currents and voltages. The validity of all these models is established by comparing the simulation results with the experimental results from laboratory prototypes, at different steady state and transient conditions. Simulation based on a combination of average and harmonic models is shown to provide all relevant information as obtained from the switching model, while consuming less computation time than the latter.

Differential binding of ppGpp and pppGpp to E-coli RNA polymerase: photo-labeling and mass spectral studies

(p) ppGpp, a secondary messenger, is induced under stress and shows pleiotropic response. It binds to RNA polymerase and regulates transcription in Escherichia coli. More than 25 years have passed since the first discovery was made on the direct interaction of ppGpp with E. coli RNA polymerase. Several lines of evidence suggest different modes of ppGpp binding to the enzyme. Earlier cross-linking experiments suggested that the beta-subunit of RNA polymerase is the preferred site for ppGpp, whereas recent crystallographic studies pinpoint the interface of beta'/omega-subunits as the site of action. With an aim to validate the binding domain and to follow whether tetra-and pentaphosphate guanosines have different location on RNA polymerase, this work was initiated. RNA polymerase was photo-labeled with 8-azido-ppGpp/8-azido-pppGpp, and the product was digested with trypsin and subjected to mass spectrometry analysis. We observed three new peptides in the trypsin digest of the RNA polymerase labeled with 8-azido-ppGpp, of which two peptides correspond to the same pocket on beta'-subunit as predicted by X-ray structural analysis, whereas the third peptide was mapped on the beta-subunit. In the case of 8-azido-pppGpp-labeled RNA polymerase, we have found only one cross-linked peptide from the beta'-subunit. However, we were unable to identify any binding site of pppGpp on the beta-subunit. Interestingly, we observed that pppGpp at high concentration competes out ppGpp bound to RNA polymerase more efficiently, whereas ppGpp cannot titrate out pppGpp. The competition between tetraphosphate guanosine and pentaphosphate guanosine for E. coli RNA polymerase was followed by gel-based assay as well as by a new method known as DRaCALA assay.

Differential dynamics of the serotonin(1A) receptor in membrane bilayers of varying cholesterol content revealed by all atom molecular dynamics simulation

The serotonin(1A) receptor belongs to the superfamily of G protein-coupled receptors (GPCRs) and is a potential drug target in neuropsychiatric disorders. The receptor has been shown to require membrane cholesterol for its organization, dynamics and function. Although recent work suggests a close interaction of cholesterol with the receptor, the structural integrity of the serotonin(1A) receptor in the presence of cholesterol has not been explored. In this work, we have carried out all atom molecular dynamics simulations, totaling to 3s, to analyze the effect of cholesterol on the structure and dynamics of the serotonin(1A) receptor. Our results show that the presence of physiologically relevant concentration of membrane cholesterol alters conformational dynamics of the serotonin(1A) receptor and, on an average lowers conformational fluctuations. Our results show that, in general, transmembrane helix VII is most affected by the absence of membrane cholesterol. These results are in overall agreement with experimental data showing enhancement of GPCR stability in the presence of membrane cholesterol. Our results constitute a molecular level understanding of GPCR-cholesterol interaction, and represent an important step in our overall understanding of GPCR function in health and disease.

New insight into the architecture of oxy-anion pocket in unliganded conformation of GAT domains: A MD-simulation study

Human Guanine Monophosphate Synthetase (hGMPS) converts XMP to GMP, and acts as a bifunctional enzyme with N-terminal ``glutaminase'' (GAT) and C-terminal ``synthetase'' domain. The enzyme is identified as a potential target for anticancer and immunosuppressive therapies. GAT domain of enzyme plays central role in metabolism, and contains conserved catalytic residues Cys104, His190, and Glu192. MD simulation studies on GAT domain suggest that position of oxyanion in unliganded conformation is occupied by one conserved water molecule (W1), which also stabilizes that pocket. This position is occupied by a negatively charged atom of the substrate or ligand in ligand bound crystal structures. In fact, MD simulation study of Ser75 to Val indicates that W1 conserved water molecule is stabilized by Ser75, while Thr152, and His190 also act as anchor residues to maintain appropriate architecture of oxyanion pocket through water mediated H-bond interactions. Possibly, four conserved water molecules stabilize oxyanion hole in unliganded state, but they vacate these positions when the enzyme (hGMPS)-substrate complex is formed. Thus this study not only reveals functionally important role of conserved water molecules in GAT domain, but also highlights essential role of other non-catalytic residues such as Ser75 and Thr152 in this enzymatic domain. The results from this computational study could be of interest to experimental community and provide a testable hypothesis for experimental validation. Conserved sites of water molecules near and at oxyanion hole highlight structural importance of water molecules and suggest a rethink of the conventional definition of chemical geometry of inhibitor binding site.