ALBERT

Beschreibung: The predicted effect of effective population size on the distribution of fitness effects and substitution rate is critically dependent on the relationship between sequence and fitness. This highlights the importance of using models that are informed by the molecular biology, biochemistry, and biophysics of the evolving systems. We describe a computational model based on fundamental aspects of biophysics, the requirement for (most) proteins to be thermodynamically stable. Using this model, we find that differences in population size have minimal impact on the distribution of population-scaled fitness effects, as well as on the rate of molecular evolution. This is because larger populations result in selection for more stable proteins that are less affected by mutations. This reduction in the magnitude of the fitness effects almost exactly cancels the greater selective pressure resulting from the larger population size. Conversely, changes in the population size in either direction cause transient increases in the substitution rate. As differences in population size often correspond to changes in population size, this makes comparisons of substitution rates in different lineages difficult to interpret.

Beschreibung: A proper orthogonal decomposition (POD) method is used to interpolate the flow around an airfoil for various Mach numbers and angles of attack in the transonic regime. POD uses a few numerical simulations, called snapshots, to create eigenfunctions. These eigenfunctions are combined using weighting coefficients to create a new solution for different values of the input parameters. Since POD methods are linear, their interpolation capabilities are quite limited when dealing with flow presenting nonlinearities, such as shocks. In order to improve their performance for cases involving shocks, a new method is proposed using variable fidelity. The main idea is to use POD to interpolate the difference between the CFD solution obtained on two different grids, a coarse one and a fine one. Then, for any new input parameter value, a coarse grid solution is computed using CFD and the POD interpolated difference is added to predict the fine grid solution. This allows some nonlinearities associated with the flow to be introduced. Results for various Mach numbers and angles of attack are compared to full CFD results. The variable fidelity-based POD method shows good improvement over the classical approach.

Beschreibung: O -GlcNAcylation is an inducible, highly dynamic and reversible post-translational modification, mediated by a unique enzyme named O -linked N -acetyl- d -glucosamine ( O -GlcNAc) transferase (OGT). In response to nutrients, O -GlcNAc levels are differentially regulated on many cellular proteins involved in gene expression, translation, immune reactions, protein degradation, protein–protein interaction, apoptosis and signal transduction. In contrast to eukaryotic cells, little is known about the role of O -GlcNAcylation in the viral life cycle. Here, we show that the overexpression of the OGT reduces the replication efficiency of Kaposi's sarcoma-associated herpesvirus (KSHV) in a dose-dependent manner. In order to investigate the global impact of O -GlcNAcylation in the KSHV life cycle, we systematically analyzed the 85 annotated KSHV-encoded open reading frames for O -GlcNAc modification. For this purpose, an immunoprecipitation (IP) strategy with three different approaches was carried out and the O -GlcNAc signal of the identified proteins was properly controlled for specificity. Out of the 85 KSHV-encoded proteins, 18 proteins were found to be direct targets for O -GlcNAcylation. Selected proteins were further confirmed by mass spectrometry for O -GlcNAc modification. Correlation of the functional annotation and the O -GlcNAc status of KSHV proteins showed that the predominant targets were proteins involved in viral DNA synthesis and replication. These results indicate that O -GlcNAcylation plays a major role in the regulation of KSHV propagation.

Beschreibung: Galectins are potent adhesion/growth-regulatory effectors with characteristic expression profiles. Understanding the molecular basis of gene regulation in each case requires detailed information on copy number of genes and sequence(s) of their promoter(s). Our report reveals plasticity in this respect between galectins and species. We here describe occurrence of a two-gene constellation for human galectin (Gal)-7 and define current extent of promoter-sequence divergence. Interestingly, cross-species genome analyses also detected single-copy display. Because the regulatory potential will then be different, extrapolations of expression profiles are precluded between respective species pairs. Gal-4 coding in chromosomal vicinity was found to be confined to one gene, whereas copy-number variation also applied to Gal-9. The example of rat Gal-9 teaches the lesson that the presence of multiple bands in Southern blotting despite a single-copy gene constellation is attributable to two pseudogenes. The documented copy-number variability should thus be taken into consideration when studying regulation of galectin genes, in a species and in comparison between species.

Beschreibung: In studying the molecular basis for the potent immune activity of previously described gamma and delta inulin particles and to assist in production of inulin adjuvants under Good Manufacturing Practice, we identified five new inulin isoforms, bringing the total to seven plus the amorphous form. These isoforms comprise the step-wise inulin developmental series amorphous -〉 alpha-1 (AI-1) -〉 alpha-2 (AI-2) -〉 gamma (GI) -〉 delta (DI) -〉 zeta (ZI) -〉 epsilon (EI) -〉 omega (OI) in which each higher isoform can be made either by precipitating dissolved inulin or by direct conversion from its precursor, both cases using regularly increasing temperatures. At higher temperatures, the shorter inulin polymer chains are released from the particle and so the key difference between isoforms is that each higher isoform comprises longer polymer chains than its precursor. An increasing trend of degree of polymerization is confirmed by end-group analysis using 1 H nuclear magnetic resonance spectroscopy. Inulin isoforms were characterized by the critical temperatures of abrupt phase-shifts (solubilizations or precipitations) in water suspensions. Such (aqueous) "melting" or "freezing" points are diagnostic and occur in strikingly periodic steps reflecting quantal increases in noncovalent bonding strength and increments in average polymer lengths. The (dry) melting points as measured by modulated differential scanning calorimetry similarly increase in regular steps. We conclude that the isoforms differ in repeated increments of a precisely repeating structural element. Each isoform has a different spectrum of biological activities and we show the higher inulin isoforms to be more potent alternative complement pathway activators.

Beschreibung: The methylotrophic yeast, Pichia pastoris , is an important organism used for the production of therapeutic proteins. Previously, we have reported the glycoengineering of this organism to produce human-like N -linked glycans but up to now no one has addressed engineering the O -linked glycosylation pathway. Typically, O -linked glycans produced by wild-type P. pastoris are linear chains of four to five α-linked mannose residues, which may be capped with β- or phospho-mannose. Previous genetic engineering of the N-linked glycosylation pathway of P. pastoris has eliminated both of these two latter modifications, resulting in O -linked glycans which are linear α-linked mannose structures. Here, we describe a method for the co-expression of an α-1,2-mannosidase, which reduces these glycans to primarily a single O -linked mannose residue. In doing so, we have reduced the potential of these glycans to interact with carbohydrate-binding proteins, such as dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin. Furthermore, the introduction of the enzyme protein- O -linked-mannose β-1,2- N -acetylglucosaminyltransferase 1, resulted in the capping of the single O -linked mannose residues with N -acetylglucosamine. Subsequently, this glycoform was extended into human-like sialylated glycans, similar in structure to α-dystroglycan-type glycoforms. As such, this represents the first example of sialylated O -linked glycans being produced in yeast and extends the utility of the P. pastoris production platform beyond N -linked glycosylated biotherapeutics to include molecules possessing O -linked glycans.

Beschreibung: Neurons and other cells require intracellular transport of essential components for viability and function. Previous work has shown that while net amyloid precursor protein (APP) transport is generally anterograde, individual vesicles containing APP move bi-directionally. This discrepancy highlights our poor understanding of the in vivo regulation of APP-vesicle transport. Here, we show that reduction of presenilin (PS) or suppression of gamma-secretase activity substantially increases anterograde and retrograde velocities for APP vesicles. Strikingly, PS deficiency has no effect on an unrelated cargo vesicle class containing synaptotagmin, which is powered by a different kinesin motor. Increased velocities caused by PS or gamma-secretase reduction require functional kinesin-1 and dynein motors. Together, our findings suggest that a normal function of PS is to repress kinesin-1 and dynein motor activity during axonal transport of APP vesicles. Furthermore, our data suggest that axonal transport defects induced by loss of PS-mediated regulatory effects on APP-vesicle motility could be a major cause of neuronal and synaptic defects observed in Alzheimer's Disease (AD) pathogenesis. Thus, perturbations of APP/PS transport could contribute to early neuropathology observed in AD, and highlight a potential novel therapeutic pathway for early intervention, prior to neuronal loss and clinical manifestation of disease.

Beschreibung: With age, muscle mass and integrity are progressively lost leaving the elderly frail, weak and unable to independently care for themselves. Defined as sarcopenia, this age-related muscle atrophy appears to be multifactorial but its definite cause is still unknown. Mitochondrial dysfunction has been implicated in this process. Using a novel transgenic mouse model of mitochondrial DNA (mtDNA) double-strand breaks (DSBs) that presents a premature aging-like phenotype, we studied the role of mtDNA damage in muscle wasting. We caused DSBs in mtDNA of adult mice using a ubiquitously expressed mitochondrial-targeted endonuclease, mito- Pst I. We found that a short, transient systemic mtDNA damage led to muscle wasting and a decline in locomotor activity later in life. We found a significant decline in muscle satellite cells, which decreases the muscle's capacity to regenerate and repair during aging. This phenotype was associated with impairment in acetylcholinesterase (AChE) activity and assembly at the neuromuscular junction (NMJ), also associated with muscle aging. Our data suggests that systemic mitochondrial dysfunction plays important roles in age-related muscle wasting by preferentially affecting the myosatellite cell pool.

Beschreibung: Populations of widely distributed species encounter and must adapt to local environmental conditions. However, comprehensive characterization of the genetic basis of adaptation is demanding, requiring genome-wide genotype data, multiple sampled populations, and an understanding of population structure and potential selection pressures. Here, we used single-nucleotide polymorphism genotyping and data on numerous environmental variables to describe the genetic basis of local adaptation in 21 populations of teosinte, the wild ancestor of maize. We found complex hierarchical genetic structure created by altitude, dispersal events, and admixture among subspecies, which complicated identification of locally beneficial alleles. Patterns of linkage disequilibrium revealed four large putative inversion polymorphisms showing clinal patterns of frequency. Population differentiation and environmental correlations suggest that both inversions and intergenic polymorphisms are involved in local adaptation.

Beschreibung: Pupylation, one of the most important posttranslational modifications of proteins, typically takes place when prokaryotic ubiquitin-like protein (Pup) is attached to specific lysine residues on a target protein. Identification of pupylation substrates and their corresponding sites will facilitate the understanding of the molecular mechanism of pupylation. Comparing with the labor-intensive and time-consuming experiment approaches, computational prediction of pupylation sites is much desirable for their convenience and fast speed. In this study, a new bioinformatics tool named EnsemblePup was developed that used an ensemble of support vector machine classifiers to predict pupylation sites. The highlight of EnsemblePup was to utilize the Bi-profile Bayes feature extraction as the encoding scheme. The performance of EnsemblePup was measured with a sensitivity of 79.49%, a specificity of 82.35%, an accuracy of 85.43%, and a Matthews correlation coefficient of 0.617 using the 5-fold cross validation on the training dataset. When compared with other existing methods on a benchmark dataset, the EnsemblePup provided better predictive performance, with a sensitivity of 80.00%, a specificity of 83.33%, an accuracy of 82.00%, and a Matthews correlation coefficient of 0.629. The experimental results suggested that EnsemblePup presented here might be useful to identify and annotate potential pupylation sites in proteins of interest. A web server for predicting pupylation sites was developed.

Beschreibung: Not all calcite ballast is created equal: differing effects of foraminiferan and coccolith calcite on the formation and sinking of aggregates Biogeosciences Discussions, 10, 14861-14885, 2013 Author(s): K. Schmidt, C. L. De La Rocha, M. Gallinari, and G. Cortese Correlation between particulate organic carbon (POC) and calcium carbonate sinking through the deep ocean has led to the idea that ballast provided by calcium carbonate is important for the export of POC from the surface ocean. While this idea is certainly to some extent true, it is worth considering in more nuance, for example, examining the different effects on the aggregation and sinking of POC of small, non-sinking calcite particles like coccoliths and large, rapidly sinking calcite like planktonic foraminiferan tests. We have done that here in a simple experiment carried out in roller tanks that allow particles to sink continuously without being impeded by container walls. Coccoliths were efficiently incorporated into aggregates that formed during the experiment, increasing their sinking speed compared to similarly sized aggregates lacking added calcite ballast. The foraminiferan tests, which sank as fast as 700 m d −1 , became associated with only very minor amounts of POC. In addition, when they collided with other, larger, foraminferan-less aggregates, they fragmented them into two smaller, more slowly sinking aggregates. While these effects were certainly exaggerated within the confines of the roller tanks, they clearly demonstrate that calcium carbonate ballast is not just calcium carbonate ballast- different forms of calcium carbonate ballast have notably different effects on POC aggregation, sinking, and export.

Beschreibung: The problem of exponential stability for the uncertain neutral Markovian jump systems with interval time-varying delays and nonlinear perturbations is investigated in this paper. This study starts from the corresponding nominal systems with known and partially unknown transition rates, respectively. By constructing a novel augmented Lyapunov functional which contains triple-integral terms and fully utilizes the bound of the delay, the delay-range-dependent and rate-dependent exponential stability criteria are developed by the Lyapunov theory, reciprocally convex lemma, and free weighting matrices. Then, the results about nominal systems are extended to the uncertain case. Finally, numerical examples are given to demonstrate the effectiveness of the proposed methods.

Beschreibung: The local fractional Schrödinger equations in the one-dimensional Cantorian system are investigated. The approximations solutions are obtained by using the local fractional series expansion method. The obtained solutions show that the present method is an efficient and simple tool for solving the linear partial differentiable equations within the local fractional derivative.

Beschreibung: The present paper investigates the reliability analysis of industrial systems by using vague lambda-tau methodology in which information related to system components is uncertain and imprecise in nature. The uncertainties in the data are handled with the help of intuitionistic fuzzy set (IFS) theory rather than fuzzy set theory. Various reliability parameters are addressed for strengthening the analysis in terms of degree of acceptance and rejection of IFS. Performance as well as sensitivity analysis of the system parameter has been investigated for accessing the impact of taking wrong combinations on its performance. Finally results are compared with the existing traditional crisp and fuzzy methodologies results. The technique has been demonstrated through a case study of bleaching unit of a paper mill.

Beschreibung: A classical issue in many applied fields is to obtain an approximating surface to a given set of data points. This problem arises in Computer-Aided Design and Manufacturing (CAD/CAM), virtual reality, medical imaging, computer graphics, computer animation, and many others. Very often, the preferred approximating surface is polynomial, usually described in parametric form. This leads to the problem of determining suitable parametric values for the data points, the so-called surface parameterization. In real-world settings, data points are generally irregularly sampled and subjected to measurement noise, leading to a very difficult nonlinear continuous optimization problem, unsolvable with standard optimization techniques. This paper solves the parameterization problem for polynomial Bézier surfaces by applying the firefly algorithm, a powerful nature-inspired metaheuristic algorithm introduced recently to address difficult optimization problems. The method has been successfully applied to some illustrative examples of open and closed surfaces, including shapes with singularities. Our results show that the method performs very well, being able to yield the best approximating surface with a high degree of accuracy.

Beschreibung: The tension between the meaning of causality in science and law or public policy is well-known; however, defendants in product liability cases or industries that might be affected by a government regulation may try to convince the factfinder to require evidence of a causal relationship that meets the standards of science. From the perspective of public health, however, people may be exposed unnecessarily to a health risk during the time period between the establishment of reasonably strong evidence of a causal relationship and the overwhelming evidence required for scientific causality. The Bayesian paradigm enables one to update information from epidemiologic studies as they accumulate, providing estimates of the probability that the relative risk of a particular harm from exposure exceeds a threshold value, e.g. 2.0 or 4.0 that is sufficient to meet the preponderance of the evidence standard or to support a health initiative. In order to diminish the role of the initial prior distribution, which may be quite subjective, the first case-control study or an analysis of adverse event and case reports is used to determine two prior distributions. One is the most favourable to the defendant, or industry that might be regulated, which is consistent with the previous data. The other is centred on or near the estimated relative risk from the first study. The method is applied to the studies that linked aspirin use to Reye syndrome and demonstrates that the evidence of a causal association was sufficiently strong in 1982, when the Food and Drug Administration first proposed that the public be warned of the risk, to support the regulation. Thus, lives would have been saved had the warning been given at the end of 1982 rather than in early 1985.

Beschreibung: In law, inferences of causation are sometimes made through a structured process in which multiple participants play various roles, and make decisions concerning various logical components of the overall inference (such as legal rules, policy objectives, presumptions, evidence, burdens of proof and findings of fact). This article illustrates such a process using empirical research into compensation decisions in the USA for injuries allegedly caused by vaccinations. Empirical research into actual legal processes is essential, in order to discover how various players approach their sub-tasks of decision-making. It also provides insights for areas outside of law, such as non-monotonic logic, cognitive science, sociology and artificial intelligence.

Beschreibung: Situations of causal factual uncertainty are relatively common in law. The problems and difficulties regarding ‘factual causation’ in law point to the need of ‘evidence’ and ‘proof’ models that are adequate and capable to accommodate the tests and methodologies used to explain and demonstrate it in a legal context. Given the configuration of the situations of causal factual uncertainty and the available ‘evidence’ and ‘proof’ models, I argue that it is justified to use an ‘argumentative-narrative’ model for ‘proving causation’ in law. However, considering that each model of ‘evidence’ and ‘proof’ reveals a different kind of ‘rationality’ that can still be viewed in different ways, I also argue that we must try to match the perspective we have on the ‘rationality’ behind the chosen model of ‘evidence’ and ‘proof’ with the ‘rationality’ underlying ‘causation’ in law.

Beschreibung: At least in some cases, the values confronted in legal decision-making appear to be incommensurable. Some legal theorists resist incommensurability because they fear that this presents an overwhelming obstacle to rational decision-making. By offering a close analysis of proportionality and, more particularly, measures of proportional value satisfaction, I show that this fear is unfounded. Comparative measures of proportional value satisfaction do not require the values to be commensurable. However, assuming incommensurability presents us with the problem of public significance in the proportional satisfaction of values. When two values are commensurable, this public significance is provided by the mediating effects of the overarching third value that provides the common measure of the values. However, when this common measure is removed, then the public significance of value satisfaction must be otherwise achieved. This is why I propose an equal proportional value satisfaction as the most appropriate proportionality maximand. Under equal proportional value satisfaction, the proportional satisfaction of any one value has significance for each and every other value. This kind of public significance is interpersonal rather than impersonal (or second-personal rather than third-personal). The article then shows that the legal process that is most appropriate to equal proportionality is a process that implements defeasible legal rules.

Beschreibung: In order to allocate the risk between parties in legal adjudication, we use evidentiary techniques with the main device among them being the standard of proof (SoP). The traditional view holds the grade of probability to be the parameter that shifts when moving to different standards. However, as soon as we dig slightly deeper, an incoherent picture is being revealed. In this article, I challenge the accepted view and try to show that it faces insurmountable problems concerning the rationality, the grammatical consistency and the impact of the SoP for the acceptability of verdicts. At the end of the article, I shortly discuss the theory of epistemological contextualism and propose a framework that allows rational distinctions to be drawn between different standards of proof. In the second part of this project (forthcoming), I will defend a contextualist view according to which shifting parameter is not the grade of (aleatory) probability, but instead the Set of Epistemic Defeaters in play.

Beschreibung: This paper proposes a partial refactorization for faster nonlinear analysis based on sparse matrix solution, which is nowadays the default solution choice in finite element analysis and can solve finite element models up to millions degrees of freedom. Among various fill-in’s reducing strategies for sparse matrix solution, the graph partition is in general the best in terms of resultant fill-ins and floating-point operations and furthermore produces a particular graph of sparse matrix that prevents local change of entries from wide spreading in factorization. Based on this feature, an explicit partial triangular refactorization with local change is efficiently constructed with limited additional storage requirement in row-sparse storage scheme. The partial refactorization of the changed stiffness matrix inherits a big percentage of the original factor and is carried out only on partial factor entries. The proposed method provides a new possibility for faster nonlinear analysis and is mainly suitable for material nonlinear problems and optimization problems. Compared to full factorization, it can significantly reduce the factorization time and can make nonlinear analysis more efficient.

Beschreibung: Prediction of RNA structure is a useful process for creating new drugs and understanding genetic diseases. In this paper, we proposed a particle swarm optimization (PSO) and ant colony optimization (ACO) based framework (PAF) for RNA secondary structure prediction. PAF consists of crucial stem searching (CSS) and global sequence building (GSB). In CSS, a modified ACO (MACO) is used to search the crucial stems, and then a set of stems are generated. In GSB, we used a modified PSO (MPSO) to construct all the stems in one sequence. We evaluated the performance of PAF on ten sequences, which have length from 122 to 1494. We also compared the performance of PAF with the results obtained from six existing well-known methods, SARNA-Predict, RnaPredict, ACRNA, PSOfold, IPSO, and mfold. The comparison results show that PAF could not only predict structures with higher accuracy rate but also find crucial stems.

Beschreibung: The problem of robust fault tolerant control for continuous-time fractional-order (FO) systems with interval parameters and sensor faults of has been investigated. By establishing sensor fault model and state observer, an observer-based FO output feedback controller is developed such that the closed-loop FO system is asymptotically stable, not only when all sensor components are working well, but also in the presence of sensor components failures. Finally, numerical simulation examples are given to illustrate the application of the proposed design method.

Beschreibung: There is much interest in using high-throughput DNA sequencing methodology to monitor microorganisms, complex plant and animal communities. However, there are experimental and analytical issues to consider before applying a sequencing technology, which was originally developed for genome projects, to ecological projects. Many of these issues have been highlighted by recent microbial studies. Understanding how high-throughput sequencing is best implemented is important for the interpretation of recent results and the success of future applications. Addressing complex biological questions with metagenomics requires the interaction of researchers who bring different skill sets to problem solving. Educators can help by nurturing a collaborative interdisciplinary approach to genome science, which is essential for effective problem solving. Educators are in a position to help students, teachers, the public and policy makers interpret the new knowledge that metagenomics brings. To do this, they need to understand, not only the excitement of the science but also the pitfalls and shortcomings of methodology and research designs. We review these issues and some of the research directions that are helping to move the field forward.

Beschreibung: We believe that undergraduate biology students must acquire a foundational background in computing including how to formulate a computational problem; develop an algorithmic solution; implement their solution in software and then test, document and use their code to explore biological phenomena. Moreover, by learning these skills in the first year, students acquire a powerful tool set that they can use and build on throughout their studies. To address this need, we have developed a first-year undergraduate course that teaches students the foundations of computational thinking and programming in the context of problems in biology. This article describes the structure and content of the course and summarizes assessment data on both affective and learning outcomes.

Beschreibung: Bioinformatics is an integral part of modern life sciences. It has revolutionized and redefined how research is carried out and has had an enormous impact on biotechnology, medicine, agriculture and related areas. Yet, it is only rarely integrated into high school teaching and learning programs, playing almost no role in preparing the next generation of information-oriented citizens. Here, we describe the design principles of bioinformatics learning environments, including our own, that are aimed at introducing bioinformatics into senior high school curricula through engaging learners in scientifically authentic inquiry activities. We discuss the bioinformatics-related benefits and challenges that high school teachers and students face in the course of the implementation process, in light of previous studies and our own experience. Based on these lessons, we present a new approach for characterizing the questions embedded in bioinformatics teaching and learning units, based on three criteria: the type of domain-specific knowledge required to answer each question (declarative knowledge, procedural knowledge, strategic knowledge, situational knowledge), the scientific approach from which each question stems (biological, bioinformatics, a combination of the two) and the associated cognitive process dimension (remember, understand, apply, analyze, evaluate, create). We demonstrate the feasibility of this approach using a learning environment, which we developed for the high school level, and suggest some of its implications. This review sheds light on unique and critical characteristics related to broader integration of bioinformatics in secondary education, which are also relevant to the undergraduate level, and especially on curriculum design, development of suitable learning environments and teaching and learning processes.

Beschreibung: The aim of this paper is to study the relations between the Hausdorff dimensions of k -quasilines and the theory of extremal quasiconformal mappings. We show that there is an open and dense subset (Strebel points) of the universal Teichmüller space T (H) such that, for every [ f ] in the set, the Hausdorff dimension of the k -quasiline determined by [ f ] is strictly less than 1 + k 2 . We also show that there are some points [ f ] != [id] outside the open and dense set in the universal Teichmüller space such that the Hausdorff dimension of the quasiline determined by [ f ] is 1. Moreover, some results on the Hausdorff dimensions of the quasilines varying in the asymptotic Teichmüller space are also obtained.

Beschreibung: Next-generation sequencing (NGS) is increasingly being adopted as the backbone of biomedical research. With the commercialization of various affordable desktop sequencers, NGS will be reached by increasing numbers of cellular and molecular biologists, necessitating community consensus on bioinformatics protocols to tackle the exponential increase in quantity of sequence data. The current resources for NGS informatics are extremely fragmented. Finding a centralized synthesis is difficult. A multitude of tools exist for NGS data analysis; however, none of these satisfies all possible uses and needs. This gap in functionality could be filled by integrating different methods in customized pipelines, an approach helped by the open-source nature of many NGS programmes. Drawing from community spirit and with the use of the Wikipedia framework, we have initiated a collaborative NGS resource: The NGS WikiBook. We have collected a sufficient amount of text to incentivize a broader community to contribute to it. Users can search, browse, edit and create new content, so as to facilitate self-learning and feedback to the community. The overall structure and style for this dynamic material is designed for the bench biologists and non-bioinformaticians. The flexibility of online material allows the readers to ignore details in a first read, yet have immediate access to the information they need. Each chapter comes with practical exercises so readers may familiarize themselves with each step. The NGS WikiBook aims to create a collective laboratory book and protocol that explains the key concepts and describes best practices in this fast-evolving field.

Beschreibung: A new uniqueness result for a general n th order differential equation is obtained. We show that some previous results follow immediately from our theorem.

Beschreibung: Consider a discrete uniformly elliptic divergence form equation on the d ≥3 dimensional lattice Z d with random coefficients. In Conlon and Spencer [ Trans. Amer. Math. Soc. , http://www.math.lsa.umich.edu/~conlon/paper/hom10.pdf ], rate of convergence results in homogenization and estimates on the difference between the averaged Green's function and the homogenized Green's function for random environments which satisfy a Poincaré inequality were obtained. Here, these results are extended to certain environments in which correlations can have arbitrarily small power law decay. These environments are simply related via a convolution to environments which do satisfy a Poincaré inequality.

Beschreibung: In this paper, we prove that, for any a , M N with ( a , M ) = 1, there are infinitely many Carmichael numbers m such that m a mod M .

Beschreibung: We give a topological analogue for openness of a criterion for flatness that originates with Auslander. Over a normal base of dimension n , failure of openness is detected by a vertical component in the n th fibred power of the morphism.

Beschreibung: Investigated are regular maps from real algebraic varieties into real Fermat varieties. It is proved that under some natural assumptions, all such maps are null homotopic.

Beschreibung: Let ( M , g ) be a complete non-compact Riemannian manifold. We consider operators of the form g + V , where g is the non-negative Laplacian associated with the metric g , and V a locally integrable function. Let be a Riemannian covering, with Laplacian g and potential . If the operator + V is non-negative on ( M , g ), then the operator is non-negative on . In this note, we show that the converse statement is true provided that is a co-amenable subgroup of 1 ( M ).

Beschreibung: Peak interpolation is concerned with a foundational kind of mathematical task: building functions in a fixed algebra A , which have prescribed values or behaviour on a fixed closed subset (or on several disjoint subsets). In this paper, we do the same but now A is an algebra of operators on a Hilbert space. We briefly survey this noncommutative peak interpolation , which we have studied with coauthors in a long series of papers, and whose basic theory now appears to be approaching its culmination. This programme developed from, and is based partly on, theorems of Hay and Read whose proofs were spectacular, but therefore inaccessible to an uncommitted reader. We give short proofs of these results, using recent progress in noncommutative peak interpolation, and conversely give examples of the use of these theorems in peak interpolation. For example, we prove a useful new noncommutative peak interpolation theorem.

Beschreibung: We show how a parameterized family of maps of the spine of a manifold can be used to construct a family of homeomorphisms of the ambient manifold which have the inverse limits of the spine maps as global attractors. We describe applications to unimodal families of interval maps, to rotation sets, and to the standard family of circle maps.

Beschreibung: For every prime p , we give infinitely many examples of torsors under abelian varieties over Q that are locally trivial but not divisible by p in the Weil–Châtelet group. We also give an example of a locally trivial torsor under an elliptic curve over Q that is not divisible by 4 in the Weil–Châtelet group. This gives a negative answer to a question of Cassels.

Beschreibung: We show that at least of the zeros of the Riemann zeta-function are simple, assuming the Riemann hypothesis. This was previously established by Conrey, Ghosh and Gonek [ Proc. London Math. Soc. 76 (1998) 497–522] under the additional assumption of the generalized Lindelöf hypothesis. We are able to remove this hypothesis by careful use of the generalized Vaughan identity.

Beschreibung: We construct an infinite family of hyperbolic, homologically thin knots that are not quasi-alternating. To establish the latter, we argue that the branched double-cover of each knot in the family does not bound a negative-definite 4-manifold with trivial first homology and bounded second Betti number. This fact depends in turn on information from the correction terms in Heegaard Floer homology, which we establish by way of a relationship to, and calculation of, the Turaev torsion.

Beschreibung: We observe that E -resultant of a very ample rank 2 vector bundle E on a real projective curve (with no real points) is nonnegative when restricted to the space of real sections. Moreover, we show that if E has a section vanishing at exactly two points and the degree d of E satisfies d ( d – 6) ≥ 4( g – 1), then this polynomial cannot be written as a sum of squares.

Beschreibung: Let G be one of the Ricci-flat holonomy groups SU( n ), Sp( n ), Spin(7) or G 2 , and M a compact manifold of dimension 2 n , 4 n , 8 or 7, respectively. We prove that the natural map from the moduli space of torsion-free G -structures on M to the moduli space of Ricci-flat metrics is open, and that the image is a smooth manifold. For the exceptional cases G = Spin(7) and G 2 , we extend the result to asymptotically cylindrical manifolds.

Beschreibung: We improve the results of Booker and Krishnamurthy ( Compos. Math. 147 (2011) 669–715) by allowing restricted sets of poles among the unramified twists. This allows for a clean statement of the GL(2) converse theorem which includes all cases of Eisenstein series.

Beschreibung: Let G be a solvable subgroup of the automorphism group Aut( X ) of a compact Kähler manifold X of complex dimension n , and let N ( G ) be the normal subgroup of G consisting of elements with null entropy. Let us denote by G * the image of G under the natural map from Aut( X ) to GL( V , R ), where V is the Dolbeault cohomology group H 1, 1 ( X , R ). Assume that the Zariski closure of G * in GL( V C ) is connected. The main aim of this paper is to show that, when the rank r ( G ) of the quotient group G / N ( G ) is equal to n – 1 and the identity component of Aut( X ) is trivial, then the normal subgroup N ( G ) of G is finite. This affirmatively answers a question in Invent. Math. posed by D.-Q. Zhang.

Beschreibung: It is widely accepted that tumorigenesis is a multistep process characterized by the sequential accumulation of genetic alterations. However, the molecular basis of genomic instability in cancer is still partially understood. The observation that hereditary cancers are often characterized by mutations in DNA repair and checkpoint genes suggests that accumulation of DNA damage is a major contributor to the oncogenic transformation. It is therefore of great interest to identify all the cellular pathways that contribute to the response to DNA damage. Recently, RNA processing has emerged as a novel pathway that may contribute to the maintenance of genome stability. In this review, we illustrate several different mechanisms through which pre-mRNA splicing and genomic stability can influence each other. We specifically focus on the role of splicing factors in the DNA damage response and describe how, in turn, activation of the DDR can influence the activity of splicing factors.

Beschreibung: We study the lattice dynamical system of a nonlinear Boussinesq equation. We first verify the Lipschitz continuity of the continuous semigroup associated with the system. Then, we provide an estimation of the tail of the difference between two solutions of the system. Finally, we obtain the existence of an exponential attractor of the system.

Beschreibung: A novel scheme for fault-tolerant control is proposed in this paper, in which model reference adaptive control method is incorporated with control allocation to cope with simultaneous actuator failures, input saturation, and model mismatch in the flight system. In order to reduce performance degradation caused by actuator failures, the proposed scheme redistributes the control signal to healthy actuators and updates the weighting matrix based on actuator effectiveness. Because of saturation errors resulting from actuator constraints and model mismatch caused by abnormal changes in the system, the original reference model may not be appropriate. Under this circumstance, an adaptive reference model which can also provide satisfactory performance is designed. Simulations of a flight control example are given to illustrate the effectiveness of the proposed scheme.

Beschreibung: A virtual channels scheduling algorithm with broad applicability based on movable boundary is proposed. According to the types of date sources, transmission time slots are divided into synchronous ones and asynchronous ones with a movable boundary between them. During the synchronous time slots, the virtual channels are scheduled with a polling algorithm; during the asynchronous time slots, the virtual channels are scheduled with an algorithm based on virtual channel urgency and frame urgency. If there are no valid frames in the corresponding VC at a certain synchronous time slot, a frame of the other synchronous VCs or asynchronous VCs will be transmitted through the physical channel. Only when there are no valid frames in all VCs would an idle frame be generated and transmitted. Experiments show that the proposed algorithm yields much lower scheduling delay and higher channel utilization ratio than those based on unmovable boundary or virtual channel urgency in many kinds of sources. Therefore, broad applicability can be achieved by the proposed algorithm.

Beschreibung: Self-localization is a basic skill for mobile robots in the dynamic environments. It is usually modeled as a state estimation problem for nonlinear system with non-Gaussian noise and needs the real-time processing. Unscented particle filter (UPF) can handle the state estimation problem for nonlinear system with non-Gaussian noise; however the computation of UPF is very high. In order to reduce the computation cost of UPF and meanwhile maintain the accuracy, we propose an adaptive unscented particle filter (AUPF) algorithm through relative entropy. AUPF can adaptively adjust the number of particles during filtering to reduce the necessary computation and hence improve the real-time capability of UPF. In AUPF, the relative entropy is used to measure the distance between the empirical distribution and the true posterior distribution. The least number of particles for the next step is then decided according to the relative entropy. In order to offset the difference between the proposal distribution, and the true distribution the least number is adjusted thereafter. The ideal performance of AUPF in real robot self-localization is demonstrated.

Beschreibung: Phenology as a strategy for carbon optimality: a global model Biogeosciences Discussions, 10, 15107-15152, 2013 Author(s): S. Caldararu, D. W. Purves, and P. I. Palmer Phenology is essential to our understanding of biogeochemical cycles and the climate system. We develop a global mechanistic model of leaf phenology based on the hypothesis that phenology is a strategy for optimal carbon gain at the canopy level so that trees adjust leaf gains and losses in response to environmental factors such as light, temperature and soil moisture, to achieve maximum carbon assimilation. We fit this model to five years of satellite observations of leaf area index (LAI) using a Bayesian fitting algorithm. We show that our model is able to reproduce phenological patterns for all vegetation types and use it to explore variations in growing season length and the climate factors that limit leaf growth for different biomes. Phenology in wet tropical areas is limited by leaf age physiological constraints while at higher latitude leaf seasonality is limited by low temperature and light availability. Leaf growth in grassland regions is limited by water availability but often in combination with other factors. This model will advance the current understanding of phenology for ecosystem carbon models and our ability to predict future phenological behaviour.

Beschreibung: This paper is the second in a series of papers considering symmetry properties of bosonic quantum systems over 2D graphs, with continuous spins, in the spirit of the Mermin-Wagner theorem. In the model considered here the phase space of a single spin is where is a -dimensional unit torus with a flat metric. The phase space of spins is , the subspace of formed by functions symmetric under the permutations of the arguments. The Fock space yields the phase space of a system of a varying (but finite) number of particles. We associate a space with each vertex of a graph satisfying a special bidimensionality property. (Physically, vertex represents a heavy “atom” or “ion” that does not move but attracts a number of “light” particles.) The kinetic energy part of the Hamiltonian includes (i) , the minus a half of the Laplace operator on , responsible for the motion of a particle while “trapped” by a given atom, and (ii) an integral term describing possible “jumps” where a particle may join another atom. The potential part is an operator of multiplication by a function (the potential energy of a classical configuration) which is a sum of (a) one-body potentials , , describing a field generated by a heavy atom, (b) two-body potentials , , showing the interaction between pairs of particles belonging to the same atom, and (c) two-body potentials , , scaled along the graph distance between vertices , which gives the interaction between particles belonging to different atoms. The system under consideration can be considered as a generalized (bosonic) Hubbard model. We assume that a connected Lie group acts on , represented by a Euclidean space or torus of dimension , preserving the metric and the volume in . Furthermore, we suppose that the potentials , , and are -invariant. The result of the paper is that any (appropriately defined) Gibbs states generated by the above Hamiltonian is -invariant, provided that the thermodynamic variables (the fugacity and the inverse temperature ) satisfy a certain restriction. The definition of a Gibbs state (and its analysis) is based on the Feynman-Kac representation for the density matrices.

Beschreibung: The genomes of related species contain valuable information on the history of the considered taxa. Great apes in particular exhibit variation of evolutionary patterns along their genomes. However, the great ape data also bring new challenges, such as the presence of incomplete lineage sorting and ancestral shared polymorphisms. Previous methods for genome-scale analysis are restricted to very few individuals or cannot disentangle the contribution of mutation rates and fixation biases. This represents a limitation both for the understanding of these forces as well as for the detection of regions affected by selection. Here, we present a new model designed to estimate mutation rates and fixation biases from genetic variation within and between species. We relax the assumption of instantaneous substitutions, modeling substitutions as mutational events followed by a gradual fixation. Hence, we straightforwardly account for shared ancestral polymorphisms and incomplete lineage sorting. We analyze genome-wide synonymous site alignments of human, chimpanzee, and two orangutan species. From each taxon, we include data from several individuals. We estimate mutation rates and GC-biased gene conversion intensity. We find that both mutation rates and biased gene conversion vary with GC content. We also find lineage-specific differences, with weaker fixation biases in orangutan species, suggesting a reduced historical effective population size. Finally, our results are consistent with directional selection acting on coding sequences in relation to exonic splicing enhancers.

Beschreibung: We prove a common fixed point theorem for two pairs of compatible and subsequentially continuous (alternately subcompatible and reciprocally continuous) mappings satisfying a general contractive condition in a metric space. Some illustrative examples are furnished to highlight the realized improvements. Our result improves the main result of Sedghi and Shobe (2007).

Beschreibung: Genetic control of male or female gonad development displays between different groups of organisms a remarkable diversity of "master sex-determining genes" at the top of the genetic hierarchies, whereas downstream components surprisingly appear to be evolutionarily more conserved. Without much further studies, conservation of sequence has been equalized to conservation of function. We have used the medaka fish to investigate the generality of this paradigm. In medaka, the master male sex-determining gene is dmrt1bY , a highly conserved downstream regulator of sex determination in vertebrates. To understand its function in orchestrating the complex gene regulatory network, we have identified targets genes and regulated pathways of Dmrt1bY. Monitoring gene expression and interactions by transgenic fluorescent reporter fish lines, in vivo tissue-chromatin immunoprecipitation and in vitro gene regulation assays revealed concordance but also major discrepancies between mammals and medaka, notably amongst spatial, temporal expression patterns and regulations of the canonical Hedgehog and R-spondin/Wnt/Follistatin signaling pathways. Examination of Foxl2 protein distribution in the medaka ovary defined a new subpopulation of theca cells, where ovarian-type aromatase transcriptional regulation appears to be independent of Foxl2. In summary, these data show that the regulation of the downstream regulatory network of sex determination is less conserved than previously thought.

Beschreibung: Timing of sea ice retreat can alter phytoplankton community structure in the western Arctic Ocean Biogeosciences Discussions, 10, 15153-15180, 2013 Author(s): given_name prefix surname suffix, A. Fujiwara, T. Hirawake, K. Suzuki, I. Imai, and S.-I. Saitoh This study assesses the response of phytoplankton assemblages to recent climate change, especially with regard to the shrinking of sea ice in the northern Chukchi Sea of the western Arctic Ocean. Distribution patterns of phytoplankton groups in the late summers of 2008–2010 were analyzed based on HPLC pigment signatures and, the following four major algal groups were inferred via multiple regression and cluster analyses: prasinophytes, diatoms, haptophytes and dinoflagellates. A remarkable interannual difference in the distribution pattern of the groups was found in the northern basin area. Haptophytes dominated and dispersed widely in warm surface waters in 2008, whereas prasinophytes dominated in cold water in 2009 and 2010. A difference in the onset date of sea ice retreat was evident among years – the sea ice retreat in 2008 was 1–2 months earlier than in 2009 and 2010. The spatial distribution of early sea ice retreat matched the areas in which a shift in algal community composition was observed. Steel-Dwass's multiple comparison tests were used to assess the physical, chemical and biological parameters of the four clusters. We found a statistically significant difference in temperature between the haptophyte-dominated cluster and the other clusters, suggesting that the change in the phytoplankton communities was related to the earlier sea ice retreat in 2008 and the corollary increase in sea surface temperatures. Longer periods of open water during the summer, which are expected in the future, may affect food webs and biogeochemical cycles in the western Arctic due to shifts in phytoplankton community structure.

Beschreibung: Continuous deployment of antifungals in treating infections caused by dimorphic opportunistic pathogen Candida albicans has led to the emergence of drug resistance resulting in cross-resistance to many unrelated drugs, a phenomenon termed multidrug resistance (MDR). Despite the current understanding of major factors which contribute to MDR mechanisms, there are many lines of evidence suggesting that it is a complex interplay of multiple factors which may be contributed by still unknown mechanisms. Coincidentally with the increased usage of antifungal drugs, the number of reports for antifungal drug resistance has also increased which further highlights the need for understanding novel molecular mechanisms which can be explored to combat MDR, namely, ROS, iron, hypoxia, lipids, morphogenesis, and transcriptional and signaling networks. Considering the worrying evolution of MDR and significance of C. albicans being the most prevalent human fungal pathogen, this review summarizes these new regulatory mechanisms which could be exploited to prevent MDR development in C. albicans as established from recent studies.

Beschreibung: Location estimation for object tracking is one of the important topics in the research of wireless sensor networks (WSNs). Recently, many location estimation or position schemes in WSN have been proposed. In this paper, we will propose the procedure and modeling of location estimation for object tracking in WSN. The designed modeling is a simple scheme without complex processing. We will use Matlab to conduct the simulation and numerical analyses to find the optimal modeling variables. The analyses with different variables will include object moving model, sensing radius, model weighting value α, and power-level increasing ratio k of neighboring sensor nodes. For practical consideration, we will also carry out the shadowing model for analysis.

Beschreibung: This paper investigates the stability analysis problem for a class of discrete-time networked control systems (NCSs) with random time delays and packet dropouts based on unified Markov jump model. The random time delays and packet dropouts existed in feedback communication link are modeled by two independent Markov chains; the resulting closed-loop system is described by a new Markovian jump linear system (MJLS) with Markov delays. Sufficient conditions of the stochastic stability for NCSs is obtained by constructing a novel Lyapunov functional, and the mode-dependent output feedback controller design method is presented based on linear matrix inequality (LMI) technique. A numerical example is given to illustrate the effectiveness of the proposed method.

Beschreibung: The rate-dependent hysteresis in giant magnetostrictive materials is a major impediment to the application of such material in actuators. In this paper, a relevance vector machine (RVM) model is proposed for describing the hysteresis nonlinearity under varying input current. It is possible to construct a unique dynamic model in a given rate range for a rate-dependent hysteresis system using the sinusoidal scanning signals as the training set input signal. Subsequently, a proportional integral derivative (PID) control scheme combined with a feedforward compensation is implemented on a giant magnetostrictive actuator (GMA) for real-time precise trajectory tracking. Simulations and experiments both verify the effectiveness and the practicality of the proposed modeling and control methods.

Beschreibung: Unlike its saturated counterparts, the mechanical behavior of an unsaturated soil depends not only upon its stress history but also upon its hydraulic history. In this paper, a soil-water characteristic relationship which is capable of describing the effect of capillary hysteresis is introduced to characterize the influence of hydraulic history on the skeletal deformation. The capillary hysteresis is viewed as a phenomenon associated with the internal structural rearrangements in unsaturated soils, which can be characterized by using a set of internal state variables. It is shown that both capillary hysteresis and plastic deformation can be consistently addressed in a unified theoretical framework. Within this context, a constitutive model of unsaturated soils is developed by generalizing the modified Cam-Clay model. A hardening function is introduced, in which both the matric suction and the degree of saturation are explicitly included as hardening variables, so that the effect of hydraulic history on the mechanical response can be properly addressed. The proposed model is capable of capturing the main features of the unsaturated soil behavior. The new model has a hierarchical structure, and, depending upon application, it can describe the stress-strain relation and the soil-water characteristics in a coupled or uncoupled manner.

Beschreibung: A new method for parameter sensitivity analysis of Lorenz equations is presented. The sensitivity equations are derived based on the staggered methods. Experimental results indicate that it is possible to determine effects of parameters on model variables so that we can eliminate the less effective ones. Robustness can also be verified in some confidence intervals by simply looking at the corresponding phase portraits. This enables us to control the system. Although the stability properties of the Lorenz equations are studied extensively, to the best knowledge of the authors, the PSA of Lorenz equations has not been considered which is the main goal of this paper.

Beschreibung: This paper addresses the problem of simultaneous identification of linear discrete time delay multivariable systems. This problem involves both the estimation of the time delays and the dynamic parameters matrices. In fact, we suggest a new formulation of this problem allowing defining the time delay and the dynamic parameters in the same estimated vector and building the corresponding observation vector. Then, we use this formulation to propose a new method to identify the time delays and the parameters of these systems using the least square approach. Convergence conditions and statistics properties of the proposed method are also developed. Simulation results are presented to illustrate the performance of the proposed method. An application of the developed approach to compact disc player arm is also suggested in order to validate simulation results.

Beschreibung: Boundary layer flow through a porous medium over a stretching porous wall has seen solved with analytical solution. It has been considered two wall boundary conditions which are power-law distribution of either wall temperature or heat flux. These are general enough to cover the isothermal and isoflux cases. In addition to momentum, both first and second laws of thermodynamics analyses of the problem are investigated. The governing equations are transformed into a system of ordinary differential equations. The transformed ordinary equations are solved analytically using homotopy analysis method. A comprehensive parametric study is presented, and it is shown that the rate of heat transfer increases with Reynolds number, Prandtl number, and suction to the surface.

Beschreibung: This study carries out numerical simulations to identify the magnitude of prestress force in a highway bridge by making use of the dynamic responses from moving vehicular loads. The prestressed bridges are modeled using four-node isoparametric flat shell element taking into account the transverse shearing deformation in the finite element model. The vehicle is modeled as a multiple degrees-of-freedom system. An approach based on dynamic response sensitivity-based finite element model updating is proposed to identify the elemental prestress force. The identified results are obtained iteratively with the penalty function method with regularization from the measured structural dynamic responses. A single-span prestressed Tee beam and two-span prestressed box-girder bridge are studied as two numerical examples. The effects of road surface roughness, measurement noise, and speed of moving vehicle on the identification results are investigated. Studies indicate that the proposed method is efficient and robust for prestress force identification. Good identified results can be obtained from several measured acceleration responses.

Beschreibung: This paper presents a novel way to formulate the triangular flat shell element. The basic analytical solutions of membrane and bending plate problem for anisotropy material are studied separately. Combining with the conforming displacement along the sides and hybrid element strategy, the triangular flat shell elements based on the analytical trial functions (ATF) for anisotropy material are formulated. By using the explicit integral formulae of the triangular element, the matrices used in proposed shell element are calculated efficiently. The benchmark examples showed the high accuracy and high efficiency.

Beschreibung: Considering the filtering problem of dynamic positioning (DP) ship for the slowly varying sea state, a multiple model adaptive observer (MMAO) for dynamic positioning ship is presented. The MMAO consists of a bank of nonlinear subobserver and a dynamic weighting signal generator, in which each sub-observer is designed based on different peak frequency of wave spectrum model. To improve the performance of the observer, subobserver using the measurement of position, velocity, and acceleration is used to update the estimated velocity of ship. The observer parameters are optimized using particle swarm optimization (PSO). Finally, the method is verified effective by the computer simulation.

Beschreibung: A dual fractal reservoir transient flow model was created by embedding a fracture system simulated by a tree-shaped fractal network into a matrix system simulated by fractal porous media. The dimensionless bottom hole pressure model was created using the Laplace transform and Stehfest numerical inversion methods. According to the model's solution, the bilogarithmic type curves of the dual fractal reservoirs are illustrated, and the influence of different fractal factors on pressure transient responses is discussed. This semianalytical model provides a practical and reliable method for empirical applications.

Beschreibung: This paper deals with the boundary control problems for the system described by first-order hyperbolic partial integro-differential equations with nonlocal boundary conditions by means of the deformation formulas. It is shown that the associated operator with nonlocal terms generates a C 0 -semigroup and the system defines an abstract boundary control system in L 2 -space. On the basis of the construction of integral kernel function, the ordinal and evolutional deformation formulas are established for a general class of Volterra integro-differential equations with nonlocal terms. By applying a special form of the formulas, a design of feedback boundary control law is given, which makes the scalar boundary control system null controllable in finite time. Furthermore, the null controllability result is extended to coupled nonsymmetric first-order hyperbolic systems by using appropriate linear transformations. Applications to physically important coupled systems are also given.

Beschreibung: An accelerated multilevel aggregation method is presented for calculating the stationary probability vector of an irreducible stochastic matrix in PageRank computation, where the vector extrapolation method is its accelerator. We show how to periodically combine the extrapolation method together with the multilevel aggregation method on the finest level for speeding up the PageRank computation. Detailed numerical results are given to illustrate the behavior of this method, and comparisons with the typical methods are also made.

Beschreibung: This paper numerically investigates the magnetohydrodynamic boundary layer flow with heat and mass transfer of an incompressible upper-convected Maxwell fluid over a stretching sheet in the presence of viscous dissipation and thermal radiation as well as chemical reaction. The governing partial differential equations are transformed into a system of ordinary differential equations by using suitable similarity transformations. The resultant highly nonlinear ordinary differential equations are then solved using spectral relaxation method. The results are obtained for velocity, temperature, concentration, skin friction, and Nusselt number. The effects of various material parameters on the flow with heat and mass transfer and the dimensionless variables are illustrated graphically and briefly discussed.

Beschreibung: Recently, in 2013, we proved that certain presentations present the Dunwoody -manifold groups. Since the Dunwoody -manifolds do not have a unique Heegaard diagram, we cannot determine a unique group presentation for the Dunwoody -manifolds. It is well known that every -knots in a lens space can be represented by the set of the 4-tuples (Cattabriga and Mulazzani (2004); S. H. Kim and Y. Kim (2012, 2013)). In particular, to determine a unique Heegaard diagram of the Dunwoody -manifolds, we proved the fact that the certain subset of representing all -bridge knots of -knots is determined completely by using the dual and mirror -decompositions (S. H. Kim and Y. Kim (2011)). In this paper, we show how to obtain the dual and mirror images of all elements in as the generalization of some results by Grasselli and Mulazzani (2001); S. H. Kim and Y. Kim (2011).

Beschreibung: The Exp-function method combined with -expansion method is employed to investigate the equation with -dependent coefficients. The solitary wave solutions and periodic wave solutions to the equation are constructed analytically under certain circumstances. The results presented in this paper improve the previous results.

Beschreibung: Recently, a new fruit fly optimization algorithm (FOA) is proposed to solve optimization problems. In this paper, we empirically study the performance of FOA. Six different nonlinear functions are selected as testing functions. The experimental results illustrate that FOA cannot solve complex optimization problems effectively. In order to enhance the performance of FOA, an improved FOA (named LGMS-FOA) is proposed. Simulation results and comparisons of LGMS-FOA with FOA and other metaheuristics show that LGMS-FOA can greatly enhance the searching efficiency and greatly improve the searching quality.

Beschreibung: A model of solid-water-air coupling in triphasic mixtures is compared with solid-water coupling in biphasic mixtures with an application to partially saturated porous media. Based on thermodynamics, the mathematical framework governing the behavior of a partially saturated soil is derived using balance equations, and the numerical implementation and drainage tests of a soil column are carried out to validate the obtained formulations. The role of the air phase in the hydro-mechanical behavior of triphasic mixtures can be analyzed from the interactions among multiple phases for the constitutive behavior of a solid skeleton, and the triphasic mixture model can be applied in geotechnical engineering problems, such as sequestration and air storage in aquifers.

Beschreibung: In the new decade, green investment decisions are attracting more interest in design supply chains due to the hidden economic benefits and environmental legislative barriers. In this paper, a supply chain network design problem with both economic and environmental concerns is presented. Therefore, a multiobjective optimization model that captures the trade-off between the total logistics cost and CO2 emissions is proposed. With regard to the complexity of logistic networks, a new multiobjective swarm intelligence algorithm known as a multiobjective Gravitational search algorithm (MOGSA) has been implemented for solving the proposed mathematical model. To evaluate the effectiveness of the model, a comprehensive set of numerical experiments is explained. The results obtained show that the proposed model can be applied as an effective tool in strategic planning for optimizing cost and CO2 emissions in an environmentally friendly automotive supply chain.

Beschreibung: This paper investigates the sampled-data stabilization problem of spacecraft relative positional holding with improved Lyapunov function approach. The classical Clohessy-Wiltshire equation is adopted to describe the relative dynamic model. The relative position holding problem is converted into an output tracking control problem using sampling signals. A time-dependent discontinuous Lyapunov functionals approach is developed, which will lead to essentially less conservative results for the stability analysis and controller design of the corresponding closed-loop system. Sufficient conditions for the exponential stability analysis and the existence of the proposed controller are provided, respectively. Finally, a simulation result is established to illustrate the effectiveness of the proposed control scheme.

Beschreibung: Cloud computing has become a popular topic for exploration in both academic and industrial research in recent years. In this paper, network behavior is analyzed to assess and compare the costs and risks associated with traditional local servers versus those associated with cloud computing to determine the appropriate deployment strategy. An analytic framework of a deployment strategy that involves two mathematical models and the analytical hierarchy process is proposed to analyze the costs and service level agreements of services involving using traditional local servers and platform as service platforms in the cloud. Two websites are used as test sites to analyze the costs and risks of deploying services in Google App Engine (GAE) (1) the website of Information and Finance of Management (IFM) at the National Chiao Tung University (NCTU) and (2) the NCTU website. If the examined websites were deployed in GAE, NCTU would save over 83.34% of the costs associated with using a traditional local server with low risk. Therefore, both the IFM and NCTU websites can be served appropriately in the cloud. Based on this strategy, a suggestion is proposed for managers and professionals.

Beschreibung: Meshing quality of the discrete model influences the accuracy, convergence, and efficiency of the solution for fractured network system in geological problem. However, modeling and meshing of such a fractured network system are usually tedious and difficult due to geometric complexity of the computational domain induced by existence and extension of fractures. The traditional meshing method to deal with fractures usually involves boundary recovery operation based on topological transformation, which relies on many complicated techniques and skills. This paper presents an alternative and efficient approach for meshing fractured network system. The method firstly presets points on fractures and then performs Delaunay triangulation to obtain preliminary mesh by point-by-point centroid insertion algorithm. Then the fractures are exactly recovered by local correction with revised dynamic grid deformation approach. Smoothing algorithm is finally applied to improve the quality of mesh. The proposed approach is efficient, easy to implement, and applicable to the cases of initial existing fractures and extension of fractures. The method is successfully applied to modeling of two- and three-dimensional discrete fractured network (DFN) system in geological problems to demonstrate its effectiveness and high efficiency.

Beschreibung: Motivation: Pyrosequencing technology provides an important new approach to more extensively characterize diverse sequence populations and detect low frequency variants. However, the promise of this technology has been difficult to realize, as careful correction of sequencing errors is crucial to distinguish rare variants (~1%) in an infected host with high sensitivity and specificity. Results: We developed a new approach, referred to as Indel and Carryforward Correction (ICC), to cluster sequences without substitutions and locally correct only indel and carryforward sequencing errors within clusters to ensure that no rare variants are lost. ICC performs sequence clustering in the order of (i) homopolymer indel patterns only, (ii) indel patterns only and (iii) carryforward errors only, without the requirement of a distance cutoff value. Overall, ICC removed 93–95% of sequencing errors found in control datasets. On pyrosequencing data from a PCR fragment derived from 15 HIV-1 plasmid clones mixed at various frequencies as low as 0.1%, ICC achieved the highest sensitivity and similar specificity compared with other commonly used error correction and variant calling algorithms. Availability and implementation: Source code is freely available for download at http://indra.mullins.microbiol.washington.edu/ICC . It is implemented in Perl and supported on Linux, Mac OS X and MS Windows. Contact: jmullins@uw.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Beschreibung: : Tiki proteins appear to antagonize Wnt signalling pathway by acting as Wnt proteases, thereby affecting Wnt solubility by its amino-terminal cleavage. Tiki1 protease activity was shown to be metal ion-dependent and was inhibited by chelating agents and thus was tentatively proposed to be a metalloprotease. Nevertheless, Tiki proteins exhibit no detectable sequence similarity to previously described metalloproteases, but instead have been reported as being homologues of TraB proteins (Pfam ID: PF01963), a widely distributed family of unknown function and structure. Here, we show that Tiki proteins are members of a new superfamily of domains contained not just in TraB proteins, but also in erythromycin esterase (Pfam ID: PF05139), DUF399 (domain of unknown function 399; Pfam ID: PF04187) and MARTX toxins that contribute to host invasion and pathogenesis by bacteria. We establish the core fold of this enzymatic domain and its catalytic residues. Contact: luis.sanchezpulido@dpag.ox.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.

Beschreibung: Motivation: The research area metabolomics achieved tremendous popularity and development in the last couple of years. Owing to its unique interdisciplinarity, it requires to combine knowledge from various scientific disciplines. Advances in the high-throughput technology and the consequently growing quality and quantity of data put new demands on applied analytical and computational methods. Exploration of finally generated and analyzed datasets furthermore relies on powerful tools for data mining and visualization. Results: To cover and keep up with these requirements, we have created MeltDB 2.0, a next-generation web application addressing storage, sharing, standardization, integration and analysis of metabolomics experiments. New features improve both efficiency and effectivity of the entire processing pipeline of chromatographic raw data from pre-processing to the derivation of new biological knowledge. First, the generation of high-quality metabolic datasets has been vastly simplified. Second, the new statistics tool box allows to investigate these datasets according to a wide spectrum of scientific and explorative questions. Availability: The system is publicly available at https://meltdb.cebitec.uni-bielefeld.de . A login is required but freely available. Contact: nkessler@cebitec.uni-bielefeld.de

Beschreibung: Motivation: High - throughput next - generation sequencing technologies enable increasingly fast and affordable sequencing of genomes and transcriptomes, with a broad range of applications. The quality of the sequencing data is crucial for all applications. A significant portion of the data produced contains errors, and ever more efficient error correction programs are needed. Results: We propose RACER (Rapid and Accurate Correction of Errors in Reads), a new software program for correcting errors in sequencing data. RACER has better error-correcting performance than existing programs, is faster and requires less memory. To support our claims, we performed extensive comparison with the existing leading programs on a variety of real datasets. Availability: RACER is freely available for non-commercial use at www.csd.uwo.ca/~ilie/RACER/ . Contact: ilie@csd.uwo.ca Supplementary information: Supplementary data are available at Bioinformatics online.

Beschreibung: : Interactions between various types of molecules that regulate crucial cellular processes are extensively investigated by high-throughput experiments and require dedicated computational methods for the analysis of the resulting data. In many cases, these data can be represented as a bipartite graph because it describes interactions between elements of two different types such as the influence of different experimental conditions on cellular variables or the direct interaction between receptors and their activators/inhibitors. One of the major challenges in the analysis of such noisy datasets is the statistical evaluation of the relationship between any two elements of the same type. Here, we present SICOP (significant co-interaction patterns), an implementation of a method that provides such an evaluation based on the number of their common interaction partners, their so-called co-interaction. This general network analytic method, proved successful in diverse fields, provides a framework for assessing the significance of this relationship by comparison with the expected co-interaction in a suitable null model of the same bipartite graph. SICOP takes into consideration up to two distinct types of interactions such as up- or downregulation. The tool is written in Java and accepts several common input formats and supports different output formats, facilitating further analysis and visualization. Its key features include a user-friendly interface, easy installation and platform independence. Availability: The software is open source and available at cna.cs.uni-kl.de/SICOP under the terms of the GNU General Public Licence (version 3 or later). Contact: agnes.horvat@iwr.uni-heidelberg.de or zweig@cs.uni-kl.de

Beschreibung: : Molecular recognition features (MoRFs) are small, intrinsically disordered regions in proteins that undergo a disorder-to-order transition on binding to their partners. MoRFs are involved in protein–protein interactions and may function as the initial step in molecular recognition. The aim of this work was to collect, organize and store all membrane proteins that contain MoRFs. Membrane proteins constitute ~30% of fully sequenced proteomes and are responsible for a wide variety of cellular functions. MoRFs were classified according to their secondary structure, after interacting with their partners. We identified MoRFs in transmembrane and peripheral membrane proteins. The position of transmembrane protein MoRFs was determined in relation to a protein’s topology. All information was stored in a publicly available mySQL database with a user-friendly web interface. A Jmol applet is integrated for visualization of the structures. mpMoRFsDB provides valuable information related to disorder-based protein–protein interactions in membrane proteins. Availability: http://bioinformatics.biol.uoa.gr/mpMoRFsDB Contact: shamodr@biol.uoa.gr

Beschreibung: : The signaling Petri net (SPN) simulator, designed to provide insights into the trends of molecules’ activity levels in response to an external stimulus, contributes to the systems biology necessity of analyzing the dynamics of large-scale cellular networks. Implemented into the freely available software, BioLayout Express 3D , the simulator is publicly available and easy to use, provided the input files are prepared in the GraphML format, typically using the network editing software, yEd, and standards specific to the software. However, analysis of complex networks represented using other systems biology formatting languages (on which popular software, such as CellDesigner and Cytoscape, are based) requires manual manipulation, a step that is prone to error and limits the use of the SPN simulator in BioLayout Express 3D . To overcome this, we present a Cytoscape plug-in that enables users to automatically convert networks for analysis with the SPN simulator from the standard systems biology markup language. The automation of this step opens the SPN simulator to a far larger user group than has previously been possible. Availability and implementation: Distributed under the GNU General Public License Version 3 at http://apps.cytoscape.org/apps/spnconverter . Contact: christine@picb.ac.cn

Beschreibung: Motivation: Conformational diversity is a key concept in the understanding of different issues related with protein function such as the study of catalytic processes in enzymes, protein-protein recognition, protein evolution and the origins of new biological functions. Here, we present a database of proteins with different degrees of conformational diversity. Conformational Diversity of Native State (CoDNaS) is a redundant collection of three-dimensional structures for the same protein derived from protein data bank. Structures for the same protein obtained under different crystallographic conditions have been associated with snapshots of protein dynamism and consequently could characterize protein conformers. CoDNaS allows the user to explore global and local structural differences among conformers as a function of different parameters such as presence of ligand, post-translational modifications, changes in oligomeric states and differences in pH and temperature. Additionally, CoDNaS contains information about protein taxonomy and function, disorder level and structural classification offering useful information to explore the underlying mechanism of conformational diversity and its close relationship with protein function. Currently, CoDNaS has 122 122 structures integrating 12 684 entries, with an average of 9.63 conformers per protein. Availability: The database is freely available at http://www.codnas.com.ar/ . Contact: gusparisi@gmail.com

Beschreibung: Motivation: Recent experimental advancements allow determining positions of nucleosomes for complete genomes. However, the resulting nucleosome occupancy maps are averages of heterogeneous cell populations. Accordingly, they represent a snapshot of a dynamic ensemble at a single time point with an overlay of many configurations from different cells. To study the organization of nucleosomes along the genome and to understand the mechanisms of nucleosome translocation, it is necessary to retrieve features of specific conformations from the population average. Results: Here, we present a method for identifying non-overlapping nucleosome configurations that combines binary-variable analysis and a Monte Carlo approach with a simulated annealing scheme. In this manner, we obtain specific nucleosome configurations and optimized solutions for the complex positioning patterns from experimental data. We apply the method to compare nucleosome positioning at transcription factor binding sites in different mouse cell types. Our method can model nucleosome translocations at regulatory genomic elements and generate configurations for simulations of the spatial folding of the nucleosome chain. Availability: Source code, precompiled binaries, test data and a web-based test installation are freely available at http://bioinformatics.fh-stralsund.de/nucpos/ Contact: gero.wedemann@fh-stralsund.de Supplementary Information: Supplementary data are available at Bioinformatics online.

Beschreibung: Ad hoc social networks are special social networks, such as ad hoc tactical social networks, ad hoc firefighter social networks, and ad hoc vehicular social networks. The social networks possess both the properties of ad hoc network and social network. One of the challenge problems in ad hoc social networks is opinion impact and consensus, and the opinion impact plays a key role for information fusion and decision support in ad hoc social networks. In this paper, consider the impact of physical and logical distance on the opinions of individuals or nodes in heterogeneous social networks; we present a general opinion impact model, discuss the local and global opinion impact models in detail, and point out the relationship between the local opinion impact model and the global opinion impact model. For understanding the opinion impact models easily, we use the general opinion impact model to ad hoc tactical social networks and discuss the opinion impact and opinion consensus for ad hoc tactical social networks in the end.

Beschreibung: Wolbachia , endosymbiotic bacteria of the order Rickettsiales, are widespread in arthropods but also present in nematodes. In arthropods, A and B supergroup Wolbachia are generally associated with distortion of host reproduction. In filarial nematodes, including some human parasites, multiple lines of experimental evidence indicate that C and D supergroup Wolbachia are essential for the survival of the host, and here the symbiotic relationship is considered mutualistic. The origin of this mutualistic endosymbiosis is of interest for both basic and applied reasons: How does a parasite become a mutualist? Could intervention in the mutualism aid in treatment of human disease? Correct rooting and high-quality resolution of Wolbachia relationships are required to resolve this question. However, because of the large genetic distance between Wolbachia and the nearest outgroups, and the limited number of genomes so far available for large-scale analyses, current phylogenies do not provide robust answers. We therefore sequenced the genome of the D supergroup Wolbachia endosymbiont of Litomosoides sigmodontis , revisited the selection of loci for phylogenomic analyses, and performed a phylogenomic analysis including available complete genomes (from isolates in supergroups A, B, C, and D). Using 90 orthologous genes with reliable phylogenetic signals, we obtained a robust phylogenetic reconstruction, including a highly supported root to the Wolbachia phylogeny between a (A + B) clade and a (C + D) clade. Although we currently lack data from several Wolbachia supergroups, notably F, our analysis supports a model wherein the putatively mutualist endosymbiotic relationship between Wolbachia and nematodes originated from a single transition event.

Beschreibung: Spatial competition plays important roles in economics, which attracts extensive research. This paper addresses spatial competitions along with horizontal product differentiations and entry deterrence. By the dynamic game theory model about one firm and a potential entrant with different cost in a linear city, this paper finds that both the higher fixed setup cost and the higher transportation cost deter entrants. To efficiently deter the entrants, the establisher is inclined to locating at the middle point of the linear city.

Beschreibung: We present several iterations for preconditioners introduced by Tarazaga and Cuellar (2009), and study the convergence of the method for solving a linear system whose coefficient matrix is positive definite matrices, and we also find that they complete very well with the SOR iteration, which is shown through numerical examples.

Beschreibung: With the rise in popularity of e-books, there is a growing need to reexamine the pricing strategy in the e-book supply chain. In this paper, we study two forms of pricing models widely used in the book industry: wholesale and agency pricing models. We first assume a stylized deterministic demand model in which the demand depends on the price, the degree of substitution, and the overall market potential. Subsequently, we employ the game theory to determine the price equilibriums and profit distribution under different pricing models. Finally, we explore the behavior of the publisher and the retailer under different preferences and degrees of substitution through a computational study. Our findings indicate that the e-book price will be lower under the agency pricing model than under the wholesale pricing model, which is counterintuitive. The publishers have higher incentives to adopt the agency pricing model than the wholesale pricing model. The agency pricing model benefits the whole system and can provide readers with books at lower prices. The degree of substitution between the two forms of books and the readers’ preference toward e-book will affect the books’ price and the profit distribution between the publisher and the retailers.