A method for stabilizing the cis prolyl peptide bond: influence of an unusual n -> pi* interaction in 1,3-oxazine and 1,3-thiazine containing peptidomimetics

The cis/trans isomer ratios of the Xaa-Pyr (Pyr = pyrrolidine) 3 degrees amide bonds are significantly high (similar to 90% cis) in the novel peptidomimetics where Pyr contains 1,3-oxazine (Oxa) or 1,3-thiazine (Thi) at its 2 position. We find that an unusual n -> pi(i-1)* interaction, selectively stabilizes the cis conformer and the n X n repulsion destabilizes the trans conformer of these molecules. Both these electronic effects oppose the steric effects in the 3 degrees amide bond. The structural requirements for manifestation of these electronic effects are determined. (c) 2012 Elsevier Ltd. All rights reserved.

Suite of tools for statistical N-gram language modeling for pattern mining in whole genome sequences

Genome sequences contain a number of patterns that have biomedical significance. Repetitive sequences of various kinds are a primary component of most of the genomic sequence patterns. We extended the suffix-array based Biological Language Modeling Toolkit to compute n-gram frequencies as well as n-gram language-model based perplexity in windows over the whole genome sequence to find biologically relevant patterns. We present the suite of tools and their application for analysis on whole human genome sequence.

Statistical Methods for Accelerated Life Testing with Particular Reference to Resin Impregnated Paper Bushings

Electrical failure of insulation is known to be an extremal random process wherein nominally identical pro-rated specimens of equipment insulation, at constant stress fail at inordinately different times even under laboratory test conditions. In order to be able to estimate the life of power equipment, it is necessary to run long duration ageing experiments under accelerated stresses, to acquire and analyze insulation specific failure data. In the present work, Resin Impregnated Paper (RIP) a relatively new insulation system of choice used in transformer bushings, is taken as an example. The failure data has been processed using proven statistical methods, both graphical and analytical. The physical model governing insulation failure at constant accelerated stress has been assumed to be based on temperature dependent inverse power law model.

Device oriented statistical modeling method for process variability in 45nm analog CMOS technology

With the rapid scaling down of the semiconductor process technology, the process variation aware circuit design has become essential today. Several statistical models have been proposed to deal with the process variation. We propose an accurate BSIM model for handling variability in 45nm CMOS technology. The MOSFET is designed to meet the specification of low standby power technology of International Technology Roadmap for Semiconductors (ITRS).The process parameters variation of annealing temperature, oxide thickness, halo dose and title angle of halo implant are considered for the model development. One parameter variation at a time is considered for developing the model. The model validation is done by performance matching with device simulation results and reported error is less than 10%.© (2012) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

Computational interrogation of cis-regulatory elements of genes that are common targets of luteotropin and luteolysin in the primate corpus luteum

The rapid recent increase in microarray-based gene expression studies in the corpus luteum (CL) utilizing macaque models gathered increasing volume of data in publically accessible microarray expression databases. Examining gene pathways in different functional states of CL may help to understand the factors that control luteal function and hence human fertility. Co-regulation of genes in microarray experiments may imply common transcriptional regulation by sequence-specific DNA-binding transcriptional factors. We have computationally analyzed the transcription factor binding sites (TFBS) in a previously reported macaque luteal microarray gene set (n = 15) that are common targets of luteotropin (luteinizing hormone (LH) and human chorionic gonadotropin (hCG)) and luteolysin (prostaglandin (PG) F-2 alpha). This in silico approach can reveal transcriptional networks that control these important genes which are representative of the interplay between luteotropic and luteolytic factors in the control of luteal function. Our computational analyses revealed 6 matrix families whose binding sites are significantly over-represented in promoters of these genes. The roles of these factors are discussed, which might help to understand the transcriptional regulatory network in the control of luteal function. These factors might be promising experimental targets for investigation of human luteal insufficiency. (C) 2012 Elsevier B.V. All rights reserved.

Crystal-structure analysis of cis-X-pro-containing peptidomimetics: understanding the steric interactions at cis X-pro amide bonds

Catch the twist: The cis Piv-Pro conformer (Piv=pivaloyl) of peptides is no longer inaccessible. Any cis X-Pro tertiary-amide-bond conformer can be stabilized in crystals of peptides by accommodating the unavoidable distortion of the dihedral angle of the peptide bond to the carbonyl group of the Pro residue (see picture), in this case through ni−1→πi* interactions. Steric clashes were not observed in the cis Piv-Pro rotamers studied.

Steric and Electronic Interactions Controlling the cis/trans Isomer Equilibrium at X-Pro Tertiary Amide Motifs in Solution

A systematic understanding of the noncovalent interactions that influence the structures of the cis conformers and the equilibrium between the cis and the trans conformers, of the X-Pro tertiary amide motifs, is presented based on analyses of H-1-, C-13-NMR and FTIR absorption spectra of two sets of homologous peptides, X-Pro-Aib-OMe and X-Pro-NH-Me (where X is acetyl, propionyl, isobutyryl and pivaloyl), in solvents of varying polarities. First, this work shows that the cis conformers of any X-Pro tertiary amide motif, including Piv-Pro, are accessible in the new motifs X-Pro-Aib-OMe, in solution. These conformers are uniquely observable by FTIR spectroscopy at ambient temperatures and by NMR spectroscopy from temperatures as high as 273 K. This is made possible by the persistent presence of n(i-1i)* interactions at Aib, which also influence the disappearance of steric effects at these cis X-Pro rotamers. Second, contrary to conventional understanding, the energy contribution of steric effects to the cis/trans equilibrium at the X-Pro motifs is found to be nonvariant (0.54 +/- 0.02 kcal/mol) with increase in steric bulk on the X group. Third, the current studies provide direct evidence for the weak intramolecular interactions namely the n(i-1i)*, the N-Pro center dot center dot center dot Hi+1 (C(5)a), and the C-7 hydrogen bond that operate and influence the structures, stabilities, and dynamics between different conformational states of X-Pro tertiary amide motifs. NMR and IR spectral data suggest that the cis conformers of X-Pro motifs are ensembles of short-lived rotamers about the C-X-N-Pro bond. (c) 2013 Wiley Periodicals, Inc. Biopolymers 101: 66-77, 2014.

Conformational Diversity in Contryphans from Conus Venom: cis-trans Isomerisation and Aromatic/Proline Interactions in the 23-Membered Ring of a 7-Residue Peptide Disulfide Loop

Conformational diversity or shapeshifting in cyclic peptide natural products can, in principle, confer a single molecular entity with the property of binding to multiple receptors. Conformational equilibria have been probed in the contryphans, which are peptides derived from Conus venom possessing a 23-membered cyclic disulfide moiety. The natural sequences derived from Conus inscriptus, GCV(D)LYPWC* (In936) and Conus loroisii, GCP(D)WDPWC* (Lo959) differ in the number of proline residues within the macrocyclic ring. Structural characterisation of distinct conformational states arising from cis-trans equilibria about Xxx-Pro bonds is reported. Isomerisation about the C2-P3 bond is observed in the case of Lo959 and about the Y5-P6 bond in In936. Evidence is presented for as many as four distinct species in the case of the synthetic analogue V3P In936. The Tyr-Pro-Trp segment in In936 is characterised by distinct sidechain orientations as a consequence of aromatic/proline interactions as evidenced by specific sidechain-sidechain nuclear Overhauser effects and ring current shifted proton chemical shifts. Molecular dynamics simulations suggest that Tyr5 and Trp7 sidechain conformations are correlated and depend on the geometry of the Xxx-Pro bond. Thermodynamic parameters are derived for the cis trans equilibrium for In936. Studies on synthetic analogues provide insights into the role of sequence effects in modulating isomerisation about Xxx-Pro bonds.

Photocurrent spectroscopic studies of diketopyrrolopyrrole-based statistical copolymers

Diketopyrrolopyrrole (DPP) containing copolymers have gained a lot of interest in organic optoelectronics with great potential in organic photovoltaics. In this work, DPP based statistical copolymers, with slightly different bandgap energies and a varying fraction of donor-acceptor ratio are investigated using monochromatic photocurrent spectroscopy and Fourier-transform photocurrent spectroscopy (FTPS). The statistical copolymer with a lower DPP fraction, when blended with a fullerene derivative, shows the signature of an inter charge transfer complex state in photocurrent spectroscopy. Furthermore, the absorption spectrum of the blended sample with a lower DPP fraction is seen to change as a function of an external bias, qualitatively similar to the quantum confined Stark effect, from where we estimate the exciton binding energy. The statistical copolymer with a higher DPP fraction shows no signal of the inter charge transfer states and yields a higher external quantum efficiency in a photovoltaic structure. In order to gain insight into the origin of the observed charge transfer transitions, we present theoretical studies using density-functional theory and time-dependent density-functional theory for the two pristine DPP based statistical monomers.

Photocurrent spectroscopic studies of diketopyrrolopyrrole-based statistical copolymers

Diketopyrrolopyrrole (DPP) containing copolymers have gained a lot of interest in organic optoelectronics with great potential in organic photovoltaics. In this work, DPP based statistical copolymers, with slightly different bandgap energies and a varying fraction of donor-acceptor ratio are investigated using monochromatic photocurrent spectroscopy and Fourier-transform photocurrent spectroscopy (FTPS). The statistical copolymer with a lower DPP fraction, when blended with a fullerene derivative, shows the signature of an inter charge transfer complex state in photocurrent spectroscopy. Furthermore, the absorption spectrum of the blended sample with a lower DPP fraction is seen to change as a function of an external bias, qualitatively similar to the quantum confined Stark effect, from where we estimate the exciton binding energy. The statistical copolymer with a higher DPP fraction shows no signal of the inter charge transfer states and yields a higher external quantum efficiency in a photovoltaic structure. In order to gain insight into the origin of the observed charge transfer transitions, we present theoretical studies using density-functional theory and time-dependent density-functional theory for the two pristine DPP based statistical monomers.

Free turbulent shear layer in a point vortex gas as a problem in nonequilibrium statistical mechanics

This paper attempts to unravel any relations that may exist between turbulent shear flows and statistical mechanics through a detailed numerical investigation in the simplest case where both can be well defined. The flow considered for the purpose is the two-dimensional (2D) temporal free shear layer with a velocity difference Delta U across it, statistically homogeneous in the streamwise direction (x) and evolving from a plane vortex sheet in the direction normal to it (y) in a periodic-in-x domain L x +/-infinity. Extensive computer simulations of the flow are carried out through appropriate initial-value problems for a ``vortex gas'' comprising N point vortices of the same strength (gamma = L Delta U/N) and sign. Such a vortex gas is known to provide weak solutions of the Euler equation. More than ten different initial-condition classes are investigated using simulations involving up to 32 000 vortices, with ensemble averages evaluated over up to 10(3) realizations and integration over 10(4)L/Delta U. The temporal evolution of such a system is found to exhibit three distinct regimes. In Regime I the evolution is strongly influenced by the initial condition, sometimes lasting a significant fraction of L/Delta U. Regime III is a long-time domain-dependent evolution towards a statistically stationary state, via ``violent'' and ``slow'' relaxations P.-H. Chavanis, Physica A 391, 3657 (2012)], over flow time scales of order 10(2) and 10(4)L/Delta U, respectively (for N = 400). The final state involves a single structure that stochastically samples the domain, possibly constituting a ``relative equilibrium.'' The vortex distribution within the structure follows a nonisotropic truncated form of the Lundgren-Pointin (L-P) equilibrium distribution (with negatively high temperatures; L-P parameter lambda close to -1). The central finding is that, in the intermediate Regime II, the spreading rate of the layer is universal over the wide range of cases considered here. The value (in terms of momentum thickness) is 0.0166 +/- 0.0002 times Delta U. Regime II, extensively studied in the turbulent shear flow literature as a self-similar ``equilibrium'' state, is, however, a part of the rapid nonequilibrium evolution of the vortex-gas system, which we term ``explosive'' as it lasts less than one L/Delta U. Regime II also exhibits significant values of N-independent two-vortex correlations, indicating that current kinetic theories that neglect correlations or consider them as O(1/N) cannot describe this regime. The evolution of the layer thickness in present simulations in Regimes I and II agree with the experimental observations of spatially evolving (3D Navier-Stokes) shear layers. Further, the vorticity-stream-function relations in Regime III are close to those computed in 2D Navier-Stokes temporal shear layers J. Sommeria, C. Staquet, and R. Robert, J. Fluid Mech. 233, 661 (1991)]. These findings suggest the dominance of what may be called the Kelvin-Biot-Savart mechanism in determining the growth of the free shear layer through large-scale momentum and vorticity dispersal.

Dynamics of H-atom exchange in stable cis-dihydrogen/hydride complexes of ruthenium( II) bearing phosphine and N-N bidentate ligands

Synthesis and characterization of cis, trans-RuH(eta(2)-H-2)(PPh3)(2)(N-N)]OTf] (N-N = 2,2'-bipyridyl (bpy) 1a, 2,2'-bipyrimidine (bpm) 2a; OTf = trifluoromethane sulfonate (CF3SO3)) complexes are reported. The cis-H-2/hydride ligands are involved in H-atom site exchange between the two moieties. This dynamics was investigated by variable temperature NMR spectral studies based on which the mechanism of the exchange process was deduced. The Delta G(#) for the exchange of H-atoms between the eta(2)-H-2 and hydride ligands was determined to be around 8 and 13 kJ mol(-1), respectively, for 1a and 2a. The H-H distances (d(HH), A) in complexes 1a and 2a have been calculated from the T-1(minimum) and (1)J(H, D) and are found to be 1.07 A (slow) and 0.95 A for 1a and 1.04 A (slow) and 0.94 A for 2a, respectively. The molecular structure of 1a was determined by X-ray crystallography.

Mono- and Dialkyne Insertion Reactions of Cyclopalladated N,N `,N `'-Triarylguanidines kappa(2)(C,N)Pd(mu-Br)](2) and cis-/trans-kappa(2)(C,N)Pd(Lewis Base)Br]. Scaffolds for Enlarged, Rearranged, and Zwitterionic Palladacycles through Ring Contraction cum Amine-Imine Tautomerization

Insertion reactions of six-membered cyclopalladated N,N',N''-triarylguanidines, kappa(2)(C,N)Pd(mu-Br)](2) with various alkynes in CH2Cl2 under ambient conditions afforded diinserted eight-membered palladacycles, (kappa(2)(C,N):eta(2)(C=C)-PdBr] (1-11), in high yield (76-96%), while insertion reactions of six-membered cyclopalladated N,N',N''-triarylguanidines, kappa(2)(C,N)Pd(Lewis base)Br] (VI-XI), with various alkynes under the aforementioned conditions afforded monoinserted six-membered palladacycles, kappa(2)(C,N)-Pd(Lewis base)Br] (12-21), in high yield (81-91%) except for 14 (23%). The insertion reaction of VI with 2 equiv of dimethyl acetylenedicarboxylate (DMAD) and the insertion reaction of 12 with 1 equiv of DMAD in CH2Cl2 under ambient conditions resulted in the formation of a diinserted zwitterionic five-membered palladacycle, kappa(2)(C,C)Pd(2,6-lutidine)Br] (22), in 76% and 70% yields, respectively. Palladacycle 22 upon reaction with AgOTf in wet MeCN afforded the ionic palladacycle kappa(2)(C,C)Pd(2,6-lutidine)(H2O)]OTf] (23) in 78% yield. The ring size of the ``kappa(2)(C,N)Pd]'' unit in the structurally characterized diinserted palladacycles (1 center dot 2CH(2)Cl(2)center dot H2O, 2, 5, and 7), and monoinserted palladacycles (17, 18, and 20 center dot C7H8 H2O) is smaller than that anticipated for mono- and diinserted palladacycles, and this feature is mainly ascribed to the proclivity of III-XI to undergo ring contraction cum amine-imine tautomerization upon alkyne insertion. Palladacycle 22 represents the first diinserted product obtained in alkyne insertion reactions of kappa(2)(C,N)Pd(Lewis base)X] type palladarycles. The molecular structure of 22 center dot H2O determined by X-ray diffraction indicates that the positive charge on the guanidinium moiety is balanced by the negative charge on the palladium atom and thus represents the first structurally characterized zwitterionic palladacycle to be reported in alkyne insertion chemistry. Plausible mechanisms of formation of 12-21 and 22 have been outlined. The presence of more than one species in solution for some of the palladacycles in the series 1-7 and 12-21 was explained by invoking the C-N single-bond rotation of the CN3 unit of the guanidine moiety, while this process in conjunction with Pd-N(lutidine) bond rotation was invoked to explain the presence of four isomers of 15, as studied with the aid of variable-concentration H-1 NMR experiments carried out for 14 and 15.

Development and Evaluation of Statistical Downscaling Models for Monthly Precipitation

Several statistical downscaling models have been developed in the past couple of decades to assess the hydrologic impacts of climate change by projecting the station-scale hydrological variables from large-scale atmospheric variables simulated by general circulation models (GCMs). This paper presents and compares different statistical downscaling models that use multiple linear regression (MLR), positive coefficient regression (PCR), stepwise regression (SR), and support vector machine (SVM) techniques for estimating monthly rainfall amounts in the state of Florida. Mean sea level pressure, air temperature, geopotential height, specific humidity, U wind, and V wind are used as the explanatory variables/predictors in the downscaling models. Data for these variables are obtained from the National Centers for Environmental Prediction-National Center for Atmospheric Research (NCEP-NCAR) reanalysis dataset and the Canadian Centre for Climate Modelling and Analysis (CCCma) Coupled Global Climate Model, version 3 (CGCM3) GCM simulations. The principal component analysis (PCA) and fuzzy c-means clustering method (FCM) are used as part of downscaling model to reduce the dimensionality of the dataset and identify the clusters in the data, respectively. Evaluation of the performances of the models using different error and statistical measures indicates that the SVM-based model performed better than all the other models in reproducing most monthly rainfall statistics at 18 sites. Output from the third-generation CGCM3 GCM for the A1B scenario was used for future projections. For the projection period 2001-10, MLR was used to relate variables at the GCM and NCEP grid scales. Use of MLR in linking the predictor variables at the GCM and NCEP grid scales yielded better reproduction of monthly rainfall statistics at most of the stations (12 out of 18) compared to those by spatial interpolation technique used in earlier studies.