Accurate computational methods for two-electron atom-laser interactions

We discuss the application of quantitatively accurate computational methods to the study of laser-driven two-electron atoms in short intense laser pulses. The fundamental importance of such calculations to the subject area is emphasized. Calculations of single- and double-electron ionization rates at 390 nm are presented. (C) 2001 Optical Society of America.

Computational methods in the fractional calculus of variations and optimal control

The fractional calculus of variations and fractional optimal control are generalizations of the corresponding classical theories, that allow problem modeling and formulations with arbitrary order derivatives and integrals. Because of the lack of analytic methods to solve such fractional problems, numerical techniques are developed. Here, we mainly investigate the approximation of fractional operators by means of series of integer-order derivatives and generalized finite differences. We give upper bounds for the error of proposed approximations and study their efficiency. Direct and indirect methods in solving fractional variational problems are studied in detail. Furthermore, optimality conditions are discussed for different types of unconstrained and constrained variational problems and for fractional optimal control problems. The introduced numerical methods are employed to solve some illustrative examples.

Integrated X-ray crystallography, optical and computational methods in studies of structure and luminescence of new synthesized complexes of lanthanides with ligands derived from 2,6-diformylpyridine

The reaction of 2,6-diformylpyridine-bis(benzoylhydrazone) [dfpbbh] and 2,6-diformylpyridine-bis(4-phenylsemicarbazone) [dfpbpsc] with lanthanides salts yielded the new chelates complexes [Eu(dfpbpsc-H +) 2]NO 3 (1), [Dy(fbhmp) 2][Dy(dfpbbh-2H +) 2]·2EtOH·2H 2O (fbhmp = 2-formylbenzoylhydrazone-6-methoxide-pyridine; Ph = phenyl; Py = pyridine; Et = ethyl) and [Er 2(dfpbbh-2H +) 2(μ-NO 3)(H 2O) 2(OH)]·H 2O. X-ray diffraction analysis was employed for the structural characterization of the three chelate complexes. In the case of complex 1, optical, synthetic and computational methods were also exploited for ground state structure determinations and triplet energy level of the ligand and HOMO-LUMO calculations, as well as for a detailed study of its luminescence properties. © 2010 Elsevier Ltd. All rights reserved.

Computational methods for genome screening

Motivation An actual issue of great interest, both under a theoretical and an applicative perspective, is the analysis of biological sequences for disclosing the information that they encode. The development of new technologies for genome sequencing in the last years, opened new fundamental problems since huge amounts of biological data still deserve an interpretation. Indeed, the sequencing is only the first step of the genome annotation process that consists in the assignment of biological information to each sequence. Hence given the large amount of available data, in silico methods became useful and necessary in order to extract relevant information from sequences. The availability of data from Genome Projects gave rise to new strategies for tackling the basic problems of computational biology such as the determination of the tridimensional structures of proteins, their biological function and their reciprocal interactions. Results The aim of this work has been the implementation of predictive methods that allow the extraction of information on the properties of genomes and proteins starting from the nucleotide and aminoacidic sequences, by taking advantage of the information provided by the comparison of the genome sequences from different species. In the first part of the work a comprehensive large scale genome comparison of 599 organisms is described. 2,6 million of sequences coming from 551 prokaryotic and 48 eukaryotic genomes were aligned and clustered on the basis of their sequence identity. This procedure led to the identification of classes of proteins that are peculiar to the different groups of organisms. Moreover the adopted similarity threshold produced clusters that are homogeneous on the structural point of view and that can be used for structural annotation of uncharacterized sequences. The second part of the work focuses on the characterization of thermostable proteins and on the development of tools able to predict the thermostability of a protein starting from its sequence. By means of Principal Component Analysis the codon composition of a non redundant database comprising 116 prokaryotic genomes has been analyzed and it has been showed that a cross genomic approach can allow the extraction of common determinants of thermostability at the genome level, leading to an overall accuracy in discriminating thermophilic coding sequences equal to 95%. This result outperform those obtained in previous studies. Moreover, we investigated the effect of multiple mutations on protein thermostability. This issue is of great importance in the field of protein engineering, since thermostable proteins are generally more suitable than their mesostable counterparts in technological applications. A Support Vector Machine based method has been trained to predict if a set of mutations can enhance the thermostability of a given protein sequence. The developed predictor achieves 88% accuracy.

Computational methods for the analysis of protein structure and function

The vast majority of known proteins have not yet been experimentally characterized and little is known about their function. The design and implementation of computational tools can provide insight into the function of proteins based on their sequence, their structure, their evolutionary history and their association with other proteins. Knowledge of the three-dimensional (3D) structure of a protein can lead to a deep understanding of its mode of action and interaction, but currently the structures of <1% of sequences have been experimentally solved. For this reason, it became urgent to develop new methods that are able to computationally extract relevant information from protein sequence and structure. The starting point of my work has been the study of the properties of contacts between protein residues, since they constrain protein folding and characterize different protein structures. Prediction of residue contacts in proteins is an interesting problem whose solution may be useful in protein folding recognition and de novo design. The prediction of these contacts requires the study of the protein inter-residue distances related to the specific type of amino acid pair that are encoded in the so-called contact map. An interesting new way of analyzing those structures came out when network studies were introduced, with pivotal papers demonstrating that protein contact networks also exhibit small-world behavior. In order to highlight constraints for the prediction of protein contact maps and for applications in the field of protein structure prediction and/or reconstruction from experimentally determined contact maps, I studied to which extent the characteristic path length and clustering coefficient of the protein contacts network are values that reveal characteristic features of protein contact maps. Provided that residue contacts are known for a protein sequence, the major features of its 3D structure could be deduced by combining this knowledge with correctly predicted motifs of secondary structure. In the second part of my work I focused on a particular protein structural motif, the coiled-coil, known to mediate a variety of fundamental biological interactions. Coiled-coils are found in a variety of structural forms and in a wide range of proteins including, for example, small units such as leucine zippers that drive the dimerization of many transcription factors or more complex structures such as the family of viral proteins responsible for virus-host membrane fusion. The coiled-coil structural motif is estimated to account for 5-10% of the protein sequences in the various genomes. Given their biological importance, in my work I introduced a Hidden Markov Model (HMM) that exploits the evolutionary information derived from multiple sequence alignments, to predict coiled-coil regions and to discriminate coiled-coil sequences. The results indicate that the new HMM outperforms all the existing programs and can be adopted for the coiled-coil prediction and for large-scale genome annotation. Genome annotation is a key issue in modern computational biology, being the starting point towards the understanding of the complex processes involved in biological networks. The rapid growth in the number of protein sequences and structures available poses new fundamental problems that still deserve an interpretation. Nevertheless, these data are at the basis of the design of new strategies for tackling problems such as the prediction of protein structure and function. Experimental determination of the functions of all these proteins would be a hugely time-consuming and costly task and, in most instances, has not been carried out. As an example, currently, approximately only 20% of annotated proteins in the Homo sapiens genome have been experimentally characterized. A commonly adopted procedure for annotating protein sequences relies on the "inheritance through homology" based on the notion that similar sequences share similar functions and structures. This procedure consists in the assignment of sequences to a specific group of functionally related sequences which had been grouped through clustering techniques. The clustering procedure is based on suitable similarity rules, since predicting protein structure and function from sequence largely depends on the value of sequence identity. However, additional levels of complexity are due to multi-domain proteins, to proteins that share common domains but that do not necessarily share the same function, to the finding that different combinations of shared domains can lead to different biological roles. In the last part of this study I developed and validate a system that contributes to sequence annotation by taking advantage of a validated transfer through inheritance procedure of the molecular functions and of the structural templates. After a cross-genome comparison with the BLAST program, clusters were built on the basis of two stringent constraints on sequence identity and coverage of the alignment. The adopted measure explicity answers to the problem of multi-domain proteins annotation and allows a fine grain division of the whole set of proteomes used, that ensures cluster homogeneity in terms of sequence length. A high level of coverage of structure templates on the length of protein sequences within clusters ensures that multi-domain proteins when present can be templates for sequences of similar length. This annotation procedure includes the possibility of reliably transferring statistically validated functions and structures to sequences considering information available in the present data bases of molecular functions and structures.

Computational Methods in Biophysics and Medicinal Chemistry: Applications and Challenges

In this thesis I described the theory and application of several computational methods in solving medicinal chemistry and biophysical tasks. I pointed out to the valuable information which could be achieved by means of computer simulations and to the possibility to predict the outcome of traditional experiments. Nowadays, computer represents an invaluable tool for chemists. In particular, the main topics of my research consisted in the development of an automated docking protocol for the voltage-gated hERG potassium channel blockers, and the investigation of the catalytic mechanism of the human peptidyl-prolyl cis-trans isomerase Pin1.

Computational Methods for Identification of Vibrating Structures

System identification deals with the problem of building mathematical models of dynamical systems based on observed data from the system" [1]. In the context of civil engineering, the system refers to a large scale structure such as a building, bridge, or an offshore structure, and identification mostly involves the determination of modal parameters (the natural frequencies, damping ratios, and mode shapes). This paper presents some modal identification results obtained using a state-of-the-art time domain system identification method (data-driven stochastic subspace algorithms [2]) applied to the output-only data measured in a steel arch bridge. First, a three dimensional finite element model was developed for the numerical analysis of the structure using ANSYS. Modal analysis was carried out and modal parameters were extracted in the frequency range of interest, 0-10 Hz. The results obtained from the finite element modal analysis were used to determine the location of the sensors. After that, ambient vibration tests were conducted during April 23-24, 2009. The response of the structure was measured using eight accelerometers. Two stations of three sensors were formed (triaxial stations). These sensors were held stationary for reference during the test. The two remaining sensors were placed at the different measurement points along the bridge deck, in which only vertical and transversal measurements were conducted (biaxial stations). Point estimate and interval estimate have been carried out in the state space model using these ambient vibration measurements. In the case of parametric models (like state space), the dynamic behaviour of a system is described using mathematical models. Then, mathematical relationships can be established between modal parameters and estimated point parameters (thus, it is common to use experimental modal analysis as a synonym for system identification). Stable modal parameters are found using a stabilization diagram. Furthermore, this paper proposes a method for assessing the precision of estimates of the parameters of state-space models (confidence interval). This approach employs the nonparametric bootstrap procedure [3] and is applied to subspace parameter estimation algorithm. Using bootstrap results, a plot similar to a stabilization diagram is developed. These graphics differentiate system modes from spurious noise modes for a given order system. Additionally, using the modal assurance criterion, the experimental modes obtained have been compared with those evaluated from a finite element analysis. A quite good agreement between numerical and experimental results is observed.

Computational Methods for Identifying Hypertrophic Cardiomyopathy using 12-lead ECG

Hypertrophic cardiomyopathy (HCM) is a cardiovascular disease where the heart muscle is partially thickened and blood flow is - potentially fatally - obstructed. It is one of the leading causes of sudden cardiac death in young people. Electrocardiography (ECG) and Echocardiography (Echo) are the standard tests for identifying HCM and other cardiac abnormalities. The American Heart Association has recommended using a pre-participation questionnaire for young athletes instead of ECG or Echo tests due to considerations of cost and time involved in interpreting the results of these tests by an expert cardiologist. Initially we set out to develop a classifier for automated prediction of young athletes’ heart conditions based on the answers to the questionnaire. Classification results and further in-depth analysis using computational and statistical methods indicated significant shortcomings of the questionnaire in predicting cardiac abnormalities. Automated methods for analyzing ECG signals can help reduce cost and save time in the pre-participation screening process by detecting HCM and other cardiac abnormalities. Therefore, the main goal of this dissertation work is to identify HCM through computational analysis of 12-lead ECG. ECG signals recorded on one or two leads have been analyzed in the past for classifying individual heartbeats into different types of arrhythmia as annotated primarily in the MIT-BIH database. In contrast, we classify complete sequences of 12-lead ECGs to assign patients into two groups: HCM vs. non-HCM. The challenges and issues we address include missing ECG waves in one or more leads and the dimensionality of a large feature-set. We address these by proposing imputation and feature-selection methods. We develop heartbeat-classifiers by employing Random Forests and Support Vector Machines, and propose a method to classify full 12-lead ECGs based on the proportion of heartbeats classified as HCM. The results from our experiments show that the classifiers developed using our methods perform well in identifying HCM. Thus the two contributions of this thesis are the utilization of computational and statistical methods for discovering shortcomings in a current screening procedure and the development of methods to identify HCM through computational analysis of 12-lead ECG signals.

Computational methods for structural mechanics and dynamics : proceedings of a workshop ... held at NASA Langley Research Center, Hampton, Virginia, June 19-21, 1985 /

Includes bibliographical references.

Proceedings of Computational Methods for Coupled Problems in Science and Engineering

Computational Methods for Coupled Problems in Science and Engineering

Computational methods for traditional Chinese medicine:a survey

Traditional Chinese Medicine (TCM) has been actively researched through various approaches, including computational techniques. A review on basic elements of TCM is provided to illuminate various challenges and progresses in its study using computational methods. Information on various TCM formulations, in particular resources on databases of TCM formulations and their integration to Western medicine, are analyzed in several facets, such as TCM classifications, types of databases, and mining tools. Aspects of computational TCM diagnosis, namely inspection, auscultation, pulse analysis as well as TCM expert systems are reviewed in term of their benefits and drawbacks. Various approaches on exploring relationships among TCM components and finding genes/proteins relating to TCM symptom complex are also studied. This survey provides a summary on the advance of computational approaches for TCM and will be useful for future knowledge discovery in this area. © 2007 Elsevier Ireland Ltd. All rights reserved.

A Comparative Review of Computational Methods as Applied to Gold(I) Complexes and Mechanisms

In the last two decades, the field of homogeneous gold catalysis has been

extremely active, growing at a rapid pace. Another rapidly-growing field—that of

computational chemistry—has often been applied to the investigation of various gold-

catalyzed reaction mechanisms. Unfortunately, a number of recent mechanistic studies

have utilized computational methods that have been shown to be inappropriate and

inaccurate in their description of gold chemistry. This work presents an overview of

available computational methods with a focus on the approximations and limitations

inherent in each, and offers a review of experimentally-characterized gold(I) complexes

and proposed mechanisms as compared with their computationally-modeled

counterparts. No aim is made to identify a “recommended” computational method for

investigations of gold catalysis; rather, discrepancies between experimentally and

computationally obtained values are highlighted, and the systematic errors between

different computational methods are discussed.

Computational Methods for Identifying Hypertrophic Cardiomyopathy using 12-lead ECG

Hypertrophic cardiomyopathy (HCM) is a cardiovascular disease where the heart muscle is partially thickened and blood flow is - potentially fatally - obstructed. It is one of the leading causes of sudden cardiac death in young people. Electrocardiography (ECG) and Echocardiography (Echo) are the standard tests for identifying HCM and other cardiac abnormalities. The American Heart Association has recommended using a pre-participation questionnaire for young athletes instead of ECG or Echo tests due to considerations of cost and time involved in interpreting the results of these tests by an expert cardiologist. Initially we set out to develop a classifier for automated prediction of young athletes’ heart conditions based on the answers to the questionnaire. Classification results and further in-depth analysis using computational and statistical methods indicated significant shortcomings of the questionnaire in predicting cardiac abnormalities. Automated methods for analyzing ECG signals can help reduce cost and save time in the pre-participation screening process by detecting HCM and other cardiac abnormalities. Therefore, the main goal of this dissertation work is to identify HCM through computational analysis of 12-lead ECG. ECG signals recorded on one or two leads have been analyzed in the past for classifying individual heartbeats into different types of arrhythmia as annotated primarily in the MIT-BIH database. In contrast, we classify complete sequences of 12-lead ECGs to assign patients into two groups: HCM vs. non-HCM. The challenges and issues we address include missing ECG waves in one or more leads and the dimensionality of a large feature-set. We address these by proposing imputation and feature-selection methods. We develop heartbeat-classifiers by employing Random Forests and Support Vector Machines, and propose a method to classify full 12-lead ECGs based on the proportion of heartbeats classified as HCM. The results from our experiments show that the classifiers developed using our methods perform well in identifying HCM. Thus the two contributions of this thesis are the utilization of computational and statistical methods for discovering shortcomings in a current screening procedure and the development of methods to identify HCM through computational analysis of 12-lead ECG signals.