Dissecting Nucleosome Free Regions by a Segmental Semi-Markov Model

BACKGROUND: Nucleosome free regions (NFRs) play important roles in diverse biological processes including gene regulation. A genome-wide quantitative portrait of each individual NFR, with their starting and ending positions, lengths, and degrees of nucleosome depletion is critical for revealing the heterogeneity of gene regulation and chromatin organization. By averaging nucleosome occupancy levels, previous studies have identified the presence of NFRs in the promoter regions across many genes. However, evaluation of the quantitative characteristics of individual NFRs requires an NFR calling method. METHODOLOGY: In this study, we propose a statistical method to identify the patterns of NFRs from a genome-wide measurement of nucleosome occupancy. This method is based on an appropriately designed segmental semi-Markov model, which can capture each NFR pattern and output its quantitative characterizations. Our results show that the majority of the NFRs are located in intergenic regions or promoters with a length of about 400-600bp and varying degrees of nucleosome depletion. Our quantitative NFR mapping allows for an investigation of the relative impacts of transcription machinery and DNA sequence in evicting histones from NFRs. We show that while both factors have significant overall effects, their specific contributions vary across different subtypes of NFRs. CONCLUSION: The emphasis of our approach on the variation rather than the consensus of nucleosome free regions sets the tone for enabling the exploration of many subtler dynamic aspects of chromatin biology

Perceptions and Expected Immediate Reactions to Severe Storm Displays

The National Weather Service has adopted warning polygons that more specifically indicate the risk area than its previous county-wide warnings. However, these polygons are not defined in terms of numerical strike probabilities (ps). To better understand people’s interpretations of warning polygons, 167 participants were shown 23 hypothetical scenarios in one of three information conditions—polygon-only (Condition A), polygon + tornadic storm cell (Condition B), and polygon + tornadic storm cell + flanking nontornadic storm cells (Condition C). Participants judged each polygon’s ps and reported the likelihood of taking nine different response actions. The polygon-only condition replicated the results of previous studies; ps was highest at the polygon’s centroid and declined in all directions from there. The two conditions displaying storm cells differed from the polygon-only condition only in having ps just as high at the polygon’s edge nearest the storm cell as at its centroid. Overall, ps values were positively correlated with expectations of continuing normal activities, seeking information from social sources, seeking shelter, and evacuating by car. These results indicate that participants make more appropriate ps judgments when polygons are presented in their natural context of radar displays than when they are presented in isolation. However, the fact that ps judgments had moderately positive correlations with both sheltering (a generally appropriate response) and evacuation (a generally inappropriate response) suggests that experiment participants experience the same ambivalence about these two protective actions as people threatened by actual tornadoes

Structural Descriptors of gp120 V3 Loop for the Prediction of HIV-1 Coreceptor Usage

HIV-1 cell entry commonly uses, in addition to CD4, one of the chemokine receptors CCR5 or CXCR4 as coreceptor. Knowledge of coreceptor usage is critical for monitoring disease progression as well as for supporting therapy with the novel drug class of coreceptor antagonists. Predictive methods for inferring coreceptor usage based on the third hypervariable (V3) loop region of the viral gene coding for the envelope protein gp120 can provide us with these monitoring facilities while avoiding expensive phenotypic tests. All simple heuristics (such as the 11/25 rule) as well as statistical learning methods proposed to date predict coreceptor usage based on sequence features of the V3 loop exclusively. Here, we show, based on a recently resolved structure of gp120 with an untruncated V3 loop, that using structural information on the V3 loop in combination with sequence features of V3 variants improves prediction of coreceptor usage. In particular, we propose a distance-based descriptor of the spatial arrangement of physicochemical properties that increases discriminative performance. For a fixed specificity of 0.95, a sensitivity of 0.77 was achieved, improving further to 0.80 when combined with a sequence-based representation using amino acid indicators. This compares favorably with the sensitivities of 0.62 for the traditional 11/25 rule and 0.73 for a prediction based on sequence information as input to a support vector machine and constitutes a statistically significant improvement. A detailed analysis and interpretation of structural features important for classification shows the relevance of several specific hydrogen-bond donor sites and aliphatic side chains to coreceptor specificity towards CCR5 or CXCR4. Furthermore, an analysis of side chain orientation of the specificity-determining residues suggests a major role of one side of the V3 loop in the selection of the coreceptor. The proposed method constitutes the first approach to an improved prediction of coreceptor usage based on an original integration of structural bioinformatics methods with statistical learning

Sequencing Effects and Loss Aversion in a Delay Discounting Task

abstract: The attractiveness of a reward depends in part on the delay to its receipt, with more distant rewards generally being valued less than more proximate ones. The rate at which people discount the value of delayed rewards has been associated with a variety of clinically and socially relevant human behaviors. Thus, the accurate measurement of delay discounting rates is crucial to the study of mechanisms underlying behaviors such as risky sex, addiction, and gambling. In delay discounting tasks, participants make choices between two alternatives: one small amount of money delivered immediately versus a large amount of money delivered after a delay. After many choices, the experimental task will converge on an indifference point: the value of the delayed reward that approximates the value of the immediate one. It has been shown that these indifference points are systematically biased by the direction in which one of the alternatives adjusts. This bias is termed a sequencing effect. The present research proposed a reference-dependent model of choice drawn from Prospect Theory to account for the presence of sequencing effects in a delay discounting task. Sensitivity to reference frames and sequencing effects were measured in two computer tasks. Bayesian and frequentist analyses indicated that the reference-dependent model of choice cannot account for sequencing effects. Thus, an alternative, perceptual account of sequencing effects that draws on a Bayesian framework of magnitude estimation is proposed and furnished with some preliminary evidence. Implications for future research in the measurement of delay discounting and sensitivity to reference frames are discussed.Dissertation/ThesisMasters Thesis Psychology 201

Language and Discounting Behavior

Subjective devaluation of hypothetical outcomes is a widely used metric in the fields of behavioral economics and the experimental analysis of behavior to detect the presence of impulsive behavioral characteristics. While discounting trends are long assumed to be relatively stable patterns of behavior, recent evidence suggests that discounting curves are subject to contextual conditions, either inherent within the experimental task or the surrounding environment. Researchers note that the frame of the task is vitally important to the results obtained from the procedure, but few have examined or manipulated the functional verbal relations present in these tasks. The present dissertation describes a series of investigations on how discounting behavior varies as a function of the language used to describe the task. New measurement methodologies are described, and a program of study is articulated for single-subject analysis of delay discounting

Enabling the “Easy Button” for Broad, Parallel Optimization of Functions Evaluated by Simulation

Java Optimization by Simulation (JOBS) is presented: an open-source, object-oriented Java library designed to enable the study, research, and use of optimization for models evaluated by simulation. JOBS includes several novel design features that make it easy for a simulation modeler, without extensive expertise in optimization or parallel computation, to define an optimization model with deterministic and/or stochastic constraints, choose one or more metaheuristics to solve it and run, using massively parallel function evaluation to reduce wall-clock times. JOBS is supported by a new language independent, application programming interface (API) for remote simulation model evaluation and a serverless computing environment to provide massively parallel function evaluation, on demand. Dynamic loop scheduling methods are evaluated in the serverless environment with the opportunity for significant resource contention for master node computing power and network bandwidth. JOBS implements several population-based and single-solution improvement metaheuristics (solvers) for real, discrete, and mixed problems. The object-oriented design is extendible with classes that drastically reduce the amount of code required to implement a new solver and encourage re-use of solvers as building blocks for creating new multi-stage solvers or memetic algorithms

Micro/Nano Manufacturing

Micro- and nano-scale manufacturing has been the subject of ever more research and industrial focus over the past 10 years. Traditional lithography-based technology forms the basis of micro-electro-mechanical systems (MEMS) manufacturing, but also precision manufacturing technologies have been developed to cover micro-scale dimensions and accuracies. Furthermore, these fundamentally different technology platforms are currently combined in order to exploit the strengths of both platforms. One example is the use of lithography-based technologies to establish nanostructures that are subsequently transferred to 3D geometries via injection molding. Manufacturing processes at the micro-scale are the key-enabling technologies to bridge the gap between the nano- and the macro-worlds to increase the accuracy of micro/nano-precision production technologies, and to integrate different dimensional scales in mass-manufacturing processes. Accordingly, this Special Issue seeks to showcase research papers, short communications, and review articles that focus on novel methodological developments in micro- and nano-scale manufacturing, i.e., on novel process chains including process optimization, quality assurance approaches and metrology