Quantum clustering and network analysis of MD simulation trajectories to probe the conformational ensembles of protein-ligand interactions

In this article, we present a novel application of a quantum clustering (QC) technique to objectively cluster the conformations, sampled by molecular dynamics simulations performed on different ligand bound structures of the protein. We further portray each conformational population in terms of dynamically stable network parameters which beautifully capture the ligand induced variations in the ensemble in atomistic detail. The conformational populations thus identified by the QC method and verified by network parameters are evaluated for different ligand bound states of the protein pyrrolysyl-tRNA synthetase (DhPylRS) from D. hafniense. The ligand/environment induced re-distribution of protein conformational ensembles forms the basis for understanding several important biological phenomena such as allostery and enzyme catalysis. The atomistic level characterization of each population in the conformational ensemble in terms of the re-orchestrated networks of amino acids is a challenging problem, especially when the changes are minimal at the backbone level. Here we demonstrate that the QC method is sensitive to such subtle changes and is able to cluster MD snapshots which are similar at the side-chain interaction level. Although we have applied these methods on simulation trajectories of a modest time scale (20 ns each), we emphasize that our methodology provides a general approach towards an objective clustering of large-scale MD simulation data and may be applied to probe multistate equilibria at higher time scales, and to problems related to protein folding for any protein or protein-protein/RNA/DNA complex of interest with a known structure.

Determining Top K Nodes in Social Networks using the Shapley Value

In this paper, we consider the problem of selecting, for any given positive integer k, the top-k nodes in a social network, based on a certain measure appropriate for the social network. This problem is relevant in many settings such as analysis of co-authorship networks, diffusion of information, viral marketing, etc. However, in most situations, this problem turns out to be NP-hard. The existing approaches for solving this problem are based on approximation algorithms and assume that the objective function is sub-modular. In this paper, we propose a novel and intuitive algorithm based on the Shapley value, for efficiently computing an approximate solution to this problem. Our proposed algorithm does not use the sub-modularity of the underlying objective function and hence it is a general approach. We demonstrate the efficacy of the algorithm using a co-authorship data set from e-print arXiv (www.arxiv.org), having 8361 authors.

A Reliable method of obtaining Breakthrough Curves of ions in Soils using Transport Equation

Molecular diffusion plays a dominant role in transport of contaminants through fine-grained soils with low hydraulic conductivity. Attenuation processes occur while contaminants travel through the soils. Effective diffusion coefficient (De) is expected to take into consideration various attenuation processes. Effective diffusion coefficient has been considered to develop a general approach for modelling of contaminant transport in soils.The effective diffusion coefficient of sodium in presence of sulphate has been obtained using the column test.The reliability of De, has been checked by comparing theoretical breakthrough curves of sodium ion in soils obtained using advection diffusion equation with the experimental curve.

A DCT Based Filtering of Biomedical Images

Image filtering techniques have numerous potential applications in biomedical imaging and image processing. The design of filters largely depends on the a-priori knowledge about the type of noise corrupting the image and image features. This makes the standard filters to be application and image specific. The most popular filters such as average, Gaussian and Wiener reduce noisy artifacts by smoothing. However, this operation normally results in smoothing of the edges as well. On the other hand, sharpening filters enhance the high frequency details making the image non-smooth. An integrated general approach to design filters based on discrete cosine transform (DCT) is proposed in this study for optimal medical image filtering. This algorithm exploits the better energy compaction property of DCT and re-arrange these coefficients in a wavelet manner to get the better energy clustering at desired spatial locations. This algorithm performs optimal smoothing of the noisy image by preserving high and low frequency features. Evaluation results show that the proposed filter is robust under various noise distributions.

Design and Evaluation of Torsional Probes for Multifrequency Atomic Force Microscopy

Multifrequency atomic force microscopy is a powerful nanoscale imaging and characterization technique that involves excitation of the atomic force microscope (AFM) probe and measurement of its response at multiple frequencies. This paper reports the design, fabrication, and evaluation of AFM probes with a specified set of torsional eigen-frequencies that facilitate enhancement of sensitivity in multifrequency AFM. A general approach is proposed to design the probes, which includes the design of their generic geometry, adoption of a simple lumped-parameter model, guidelines for determination of the initial dimensions, and an iterative scheme to obtain a probe with the specified eigen-frequencies. The proposed approach is employed to design a harmonic probe wherein the second and the third eigen-frequencies are the corresponding harmonics of the first eigen-frequency. The probe is subsequently fabricated and evaluated. The experimentally evaluated eigen-frequencies and associated mode shapes are shown to closely match the theoretical results. Finally, a simulation study is performed to demonstrate significant improvements in sensitivity to the second-and the third-harmonic spectral components of the tip-sample interaction force with the harmonic probe compared to that of a conventional probe.

Implication of scaling hierarchy associated with nonequilibrium: field and particulate

The advent of nanotechnology has necessitated a better understanding of how material microstructure changes at the atomic level would affect the macroscopic properties that control the performance. Such a challenge has uncovered many phenomena that were not previously understood and taken for granted. Among them are the basic foundation of dislocation theories which are now known to be inadequate. Simplifying assumptions invoked at the macroscale may not be applicable at the micro- and/or nanoscale. There are implications of scaling hierrachy associated with in-homegeneity and nonequilibrium. of physical systems. What is taken to be homogeneous and equilibrium at the macroscale may not be so when the physical size of the material is reduced to microns. These fundamental issues cannot be dispensed at will for the sake of convenience because they could alter the outcome of predictions. Even more unsatisfying is the lack of consistency in modeling physical systems. This could translate to the inability for identifying the relevant manufacturing parameters and rendering the end product unpractical because of high cost. Advanced composite and ceramic materials are cases in point. Discussed are potential pitfalls for applying models at both the atomic and continuum levels. No encouragement is made to unravel the truth of nature. Let it be partiuclates, a smooth continuum or a combination of both. The present trend of development in scaling tends to seek for different characteristic lengths of material microstructures with or without the influence of time effects. Much will be learned from atomistic simulation models to show how results could differ as boundary conditions and scales are changed. Quantum mechanics, continuum and cosmological models provide evidence that no general approach is in sight. Of immediate interest is perhaps the establishment of greater precision in terminology so as to better communicate results involving multiscale physical events.

Language model combination and adaptation using weighted finite state transducers

In speech recognition systems language model (LMs) are often constructed by training and combining multiple n-gram models. They can be either used to represent different genres or tasks found in diverse text sources, or capture stochastic properties of different linguistic symbol sequences, for example, syllables and words. Unsupervised LM adaptation may also be used to further improve robustness to varying styles or tasks. When using these techniques, extensive software changes are often required. In this paper an alternative and more general approach based on weighted finite state transducers (WFSTs) is investigated for LM combination and adaptation. As it is entirely based on well-defined WFST operations, minimum change to decoding tools is needed. A wide range of LM combination configurations can be flexibly supported. An efficient on-the-fly WFST decoding algorithm is also proposed. Significant error rate gains of 7.3% relative were obtained on a state-of-the-art broadcast audio recognition task using a history dependently adapted multi-level LM modelling both syllable and word sequences. ©2010 IEEE.

Smoothed Particle Hydrodynamics (SPH): an Overview and Recent Developments

Smoothed particle hydrodynamics (SPH) is a meshfree particle method based on Lagrangian formulation, and has been widely applied to different areas in engineering and science. This paper presents an overview on the SPH method and its recent developments, including (1) the need for meshfree particle methods, and advantages of SPH, (2) approximation schemes of the conventional SPH method and numerical techniques for deriving SPH formulations for partial differential equations such as the Navier-Stokes (N-S) equations, (3) the role of the smoothing kernel functions and a general approach to construct smoothing kernel functions, (4) kernel and particle consistency for the SPH method, and approaches for restoring particle consistency, (5) several important numerical aspects, and (6) some recent applications of SPH. The paper ends with some concluding remarks.

Trapped ion magnetic resonance: concepts and designs

A novel spectroscopy of trapped ions is proposed which will bring single-ion detection sensitivity to the observation of magnetic resonance spectra. The approaches developed here are aimed at resolving one of the fundamental problems of molecular spectroscopy, the apparent incompatibility in existing techniques between high information content (and therefore good species discrimination) and high sensitivity. Methods for studying both electron spin resonance (ESR) and nuclear magnetic resonance (NMR) are designed. They assume established methods for trapping ions in high magnetic field and observing the trapping frequencies with high resolution (<1 Hz) and sensitivity (single ion) by electrical means. The introduction of a magnetic bottle field gradient couples the spin and spatial motions together and leads to a small spin-dependent force on the ion, which has been exploited by Dehmelt to observe directly the perturbation of the ground-state electron's axial frequency by its spin magnetic moment.

A series of fundamental innovations is described m order to extend magnetic resonance to the higher masses of molecular ions (100 amu = 2x 10^5 electron masses) and smaller magnetic moments (nuclear moments = 10^(-3) of the electron moment). First, it is demonstrated how time-domain trapping frequency observations before and after magnetic resonance can be used to make cooling of the particle to its ground state unnecessary. Second, adiabatic cycling of the magnetic bottle off between detection periods is shown to be practical and to allow high-resolution magnetic resonance to be encoded pointwise as the presence or absence of trapping frequency shifts. Third, methods of inducing spindependent work on the ion orbits with magnetic field gradients and Larmor frequency irradiation are proposed which greatly amplify the attainable shifts in trapping frequency.

The dissertation explores the basic concepts behind ion trapping, adopting a variety of classical, semiclassical, numerical, and quantum mechanical approaches to derive spin-dependent effects, design experimental sequences, and corroborate results from one approach with those from another. The first proposal presented builds on Dehmelt's experiment by combining a "before and after" detection sequence with novel signal processing to reveal ESR spectra. A more powerful technique for ESR is then designed which uses axially synchronized spin transitions to perform spin-dependent work in the presence of a magnetic bottle, which also converts axial amplitude changes into cyclotron frequency shifts. A third use of the magnetic bottle is to selectively trap ions with small initial kinetic energy. A dechirping algorithm corrects for undesired frequency shifts associated with damping by the measurement process.

The most general approach presented is spin-locked internally resonant ion cyclotron excitation, a true continuous Stern-Gerlach effect. A magnetic field gradient modulated at both the Larmor and cyclotron frequencies is devised which leads to cyclotron acceleration proportional to the transverse magnetic moment of a coherent state of the particle and radiation field. A preferred method of using this to observe NMR as an axial frequency shift is described in detail. In the course of this derivation, a new quantum mechanical description of ion cyclotron resonance is presented which is easily combined with spin degrees of freedom to provide a full description of the proposals.

Practical, technical, and experimental issues surrounding the feasibility of the proposals are addressed throughout the dissertation. Numerical ion trajectory simulations and analytical models are used to predict the effectiveness of the new designs as well as their sensitivity and resolution. These checks on the methods proposed provide convincing evidence of their promise in extending the wealth of magnetic resonance information to the study of collisionless ions via single-ion spectroscopy.

I edo adikzio baten anatomia

[EN] This paper is devoted to i, the Basque dative case marker. In part I, the paper aims at presenting a general approach the locus of syntactic variation within Universal Grammar (sections 1.1 to 1.3). After an excursus on the use of minorized languages in science (1.4), a discussion on parameters is provided. In (1.5), the notion of macroparameter from the 80’s is critically discussed mainly but not along the lines of Newmeyer (2005). The last section (1.6)supports to focus on microparameters, along the lines of Kayne (2000, 2005), as the right way to properly understand and explain variation. Part II provides an analysis of the main properties of Basque datives (sections 2.1 and 2.2). Sections 2.3 and 2.4 are devoted to the nature of Basque inflectional morpheme (k)i, interpreted asan applicative morpheme which ‘applies’ dative object arguments to the structure. Finally, microcomparative analyses on Basque Differential Object Marking and Dative Displacement are presented in sections (2.6) and (2.7) respectively.

Cleavage of DNA by polyamide-seco-CBI conjugates

Small molecules that bind to any predetermined DNA sequence in the human genome are potentially useful tools for molecular biology and human medicine. Polyamides containing N-methylimidazole (Im) N-methylpyrrole (Py) are cell permeable small molecules that bind DNA according to a set of "pairing rules" with affinities and specificities similar to many naturally occurring DNA binding proteins. Py-Im polyamides offer a general approach to the chemical regulation of gene expression. We demonstrate here that polyamide containing a DNA alkylating moiety seco-CBI can specifically direct sequence specific DNA alkylation. We can also control the strand of DNA that is alkylated, depending on the enantiomer of seco-CBI used and the orientation of the polyamide relative to the alkylation site (Chapter 2). This class of molecules has been applied to a gene repair system in collaboration with the Baltimore group at Caltech (Chapter 3). Also reported are additional seco-CBI polyamide conjugates synthesized to study other systems (HIV-1 and COX-2) (Appendix 1).

Mechanics of deformable glacier beds

My focus in this thesis is to contribute to a more thorough understanding of the mechanics of ice and deformable glacier beds. Glaciers flow under their own weight through a combination of deformation within the ice column and basal slip, which involves both sliding along and deformation within the bed. Deformable beds, which are made up of unfrozen sediment, are prevalent in nature and are often the primary contributors to ice flow wherever they are found. Their granular nature imbues them with unique mechanical properties that depend on the granular structure and hydrological properties of the bed. Despite their importance for understanding glacier flow and the response of glaciers to changing climate, the mechanics of deformable glacier beds are not well understood.

Our general approach to understanding the mechanics of bed deformation and their effect on glacier flow is to acquire synoptic observations of ice surface velocities and their changes over time and to use those observations to infer the mechanical properties of the bed. We focus on areas where changes in ice flow over time are due to known environmental forcings and where the processes of interest are largely isolated from other effects. To make this approach viable, we further develop observational methods that involve the use of mapping radar systems. Chapters 2 and 5 focus largely on the development of these methods and analysis of results from ice caps in central Iceland and an ice stream in West Antarctica. In Chapter 3, we use these observations to constrain numerical ice flow models in order to study the mechanics of the bed and the ice itself. We show that the bed in an Iceland ice cap deforms plastically and we derive an original mechanistic model of ice flow over plastically deforming beds that incorporates changes in bed strength caused by meltwater flux from the surface. Expanding on this work in Chapter 4, we develop a more detailed mechanistic model for till-covered beds that helps explain the mechanisms that cause some glaciers to surge quasi-periodically. In Antarctica, we observe and analyze the mechanisms that allow ocean tidal variations to modulate ice stream flow tens of kilometers inland. We find that the ice stream margins are significantly weakened immediately upstream of the area where ice begins to float and that this weakening likely allows changes in stress over the floating ice to propagate through the ice column.

A multiple scattering problem

The present work deals with the problem of the interaction of the electromagnetic radiation with a statistical distribution of nonmagnetic dielectric particles immersed in an infinite homogeneous isotropic, non-magnetic medium. The wavelength of the incident radiation can be less, equal or greater than the linear dimension of a particle. The distance between any two particles is several wavelengths. A single particle in the absence of the others is assumed to scatter like a Rayleigh-Gans particle, i.e. interaction between the volume elements (self-interaction) is neglected. The interaction of the particles is taken into account (multiple scattering) and conditions are set up for the case of a lossless medium which guarantee that the multiple scattering contribution is more important than the self-interaction one. These conditions relate the wavelength λ and the linear dimensions of a particle a and of the region occupied by the particles D. It is found that for constant λ/a, D is proportional to λ and that |Δχ|, where Δχ is the difference in the dielectric susceptibilities between particle and medium, has to lie within a certain range.

The total scattering field is obtained as a series the several terms of which represent the corresponding multiple scattering orders. The first term is a single scattering term. The ensemble average of the total scattering intensity is then obtained as a series which does not involve terms due to products between terms of different orders. Thus the waves corresponding to different orders are independent and their Stokes parameters add.

The second and third order intensity terms are explicitly computed. The method used suggests a general approach for computing any order. It is found that in general the first order scattering intensity pattern (or phase function) peaks in the forward direction Θ = 0. The second order tends to smooth out the pattern giving a maximum in the Θ = π/2 direction and minima in the Θ = 0 , Θ = π directions. This ceases to be true if ka (where k = 2π/λ) becomes large (> 20). For large ka the forward direction is further enhanced. Similar features are expected from the higher orders even though the critical value of ka may increase with the order.

The first order polarization of the scattered wave is determined. The ensemble average of the Stokes parameters of the scattered wave is explicitly computed for the second order. A similar method can be applied for any order. It is found that the polarization of the scattered wave depends on the polarization of the incident wave. If the latter is elliptically polarized then the first order scattered wave is elliptically polarized, but in the Θ = π/2 direction is linearly polarized. If the incident wave is circularly polarized the first order scattered wave is elliptically polarized except for the directions Θ = π/2 (linearly polarized) and Θ = 0, π (circularly polarized). The handedness of the Θ = 0 wave is the same as that of the incident whereas the handedness of the Θ = π wave is opposite. If the incident wave is linearly polarized the first order scattered wave is also linearly polarized. The second order makes the total scattered wave to be elliptically polarized for any Θ no matter what the incident wave is. However, the handedness of the total scattered wave is not altered by the second order. Higher orders have similar effects as the second order.

If the medium is lossy the general approach employed for the lossless case is still valid. Only the algebra increases in complexity. It is found that the results of the lossless case are insensitive in the first order of k_imD where k_im = imaginary part of the wave vector k and D a linear characteristic dimension of the region occupied by the particles. Thus moderately extended regions and small losses make (k_imD)² ≪ 1 and the lossy character of the medium does not alter the results of the lossless case. In general the presence of the losses tends to reduce the forward scattering.

Análise global da estabilidade termodinâmica de misturas: um estudo com o método do conjunto gerador

O cálculo do equilíbrio de fases é um problema de grande importância em processos da engenharia, como, por exemplo, na separação por destilação, em processos de extração e simulação da recuperação terciária de petróleo, entre outros. Mas para resolvê-lo é aconselhável que se estude a priori a estabilidade termodinâmica do sistema, a qual consiste em determinar se uma dada mistura se apresenta em uma ou mais fases. Tal problema pode ser abordado como um problema de otimização, conhecido como a minimização da função distância do plano tangente à energia livre de Gibbs molar, onde modelos termodinâmicos, de natureza não convexa e não linear, são utilizados para descrevê-lo. Esse fato tem motivado um grande interesse em técnicas de otimização robustas e eficientes para a resolução de problemas relacionados com a termodinâmica do equilíbrio de fases. Como tem sido ressaltado na literatura, para proporcionar uma completa predição do equilíbrio de fases, faz-se necessário não apenas a determinação do minimizador global da função objetivo do teste de estabilidade, mas também a obtenção de todos os seus pontos estacionários. Assim, o desenvolvimento de metodologias para essa tarefa desafiadora tem se tornado uma nova área de pesquisa da otimização global aplicada à termodinâmica do equilíbrio, com interesses comuns na engenharia química e na engenharia do petróleo. O foco do presente trabalho é uma nova metodologia para resolver o problema do teste de estabilidade. Para isso, usa-se o chamado método do conjunto gerador para realizar buscas do tipo local em uma rede de pontos previamente gerada por buscas globais efetuadas com uma metaheurística populacional, no caso o método do enxame de partículas.Para se obter mais de um ponto estacionário, minimizam-se funções de mérito polarizadas, cujos pólos são os pontos previamente encontrados. A metodologia proposta foi testada na análise de quatorze misturas polares previamente consideradas na literatura. Os resultados mostraram que o método proposto é robusto e eficiente a ponto de encontrar, além do minimizador global, todos os pontos estacionários apontados previamente na literatura, sendo também capaz de detectar, em duas misturas ternárias estudadas, pontos estacionários não obtidos pelo chamado método de análise intervalar, uma técnica confiável e muito difundida na literatura. A análise do teste de estabilidade pela simples utilização do método do enxame de partículas associado à técnica de polarização mencionada acima, para a obtenção de mais de um ponto estacionário (sem a busca local feita pelo método do conjunto gerador em uma dada rede de pontos), constitui outra metodologia para a resolução do problema de interesse. Essa utilização é uma novidade secundária deste trabalho. Tal metodologia simplificada exibiu também uma grande robustez, sendo capaz de encontrar todos os pontos estacionários pesquisados. No entanto, quando comparada com a abordagem mais geral proposta aqui, observou-se que tal simplificação pode, em alguns casos onde a função de mérito apresenta uma geometria mais complexa, consumir um tempo de máquina relativamente grande, dessa forma é menos eficiente.

An assessment of discard mortality for two Alaskan crab species, Tanner crab (Chionoecetes bairdi) and snow crab (C. opilio), based on reflex impairment

Delayed mortality associated with discarded crabs and fishes has ordinarily been observed through tag and recovery studies or during prolonged holding in deck tanks, and there is need for a more efficient assessment method. Chionoecetes bairdi (Tanner crab) and C. opilio (snow crab) collected with bottom trawls in Bering Sea waters off Alaska were evaluated for reflexes and injuries and held onboard to track mortality. Presence or absence of six reflex actions was determined and combined to calculate a reflex impairment index for each species. Logistic regression revealed that reflex impairment provided an excellent predictor of delayed mortality in C. opilio (91% correct predictions). For C. bairdi, reflex impairment, along with injury score, resulted in 82.7% correct predictions of mortality, and reflex impairment alone resulted in 79.5% correct predictions. The relationships between reflex impairment score and mortality were independent of crab gender, size, and shell condition, and predicted mortality in crabs with no obvious external damage. These relationships provide substantial improvement over earlier predictors of mortality and will help to increase the scope and replication of fishing and handling experiments. The general approach of using reflex actions to predict mortality should be equally valuable for a wide range of crustacean species.