Uncovering false positives on a virtual screening search for cruzain inhibitors

Some unexpected promiscuous inhibitors were observed in a virtual screening protocol applied to select cruzain inhibitors from the ZINC database. Physical-chemical and pharmacophore model filters were used to reduce the database size. The selected compounds were docked into the cruzain active site. Six hit compounds were tested as inhibitors. Although the compounds were designed to be nucleophilically attacked by the catalytic cysteine of cruzain, three of them showed typical promiscuous behavior, revealing that false positives are a prevalent concern in VS programs. (C) 2007 Elsevier Ltd. All rights reserved.

Search for methylation-sensitive amplification polymorphisms in mutant figs

Fig (Ficus carica) breeding programs that use conventional approaches to develop new cultivars are rare, owing to limited genetic variability and the difficulty in obtaining plants via gamete fusion. Cytosine methylation in plants leads to gene repression, thereby affecting transcription without changing the DNA sequence. Previous studies using random amplification of polymorphic DNA and amplified fragment length polymorphism markers revealed no polymorphisms among select fig mutants that originated from gamma-irradiated buds. Therefore, we conducted methylation-sensitive amplified polymorphism analysis to verify the existence of variability due to epigenetic DNA methylation among these mutant selections compared to the main cultivar 'Roxo-de-Valinhos'. Samples of genomic DNA were double-digested with either HpaII (methylation sensitive) or MspI (methylation insensitive) and with EcoRI. Fourteen primer combinations were tested, and on an average, non-methylated CCGG, symmetrically methylated CmCGG, and hemimethylated hmCCGG sites accounted for 87.9, 10.1, and 2.0%, respectively. MSAP analysis was effective in detecting differentially methylated sites in the genomic DNA of fig mutants, and methylation may be responsible for the phenotypic variation between treatments. Further analyses such as polymorphic DNA sequencing are necessary to validate these differences, standardize the regions of methylation, and analyze reads using bioinformatic tools. © FUNPEC-RP.

Efficient certification of feasibility and objective value of linear programs and its applications

The use of linear programming in various areas has increased with the significant improvement of specialized solvers. Linear programs are used as such to model practical problems, or as subroutines in algorithms such as formal proofs or branch-and-cut frameworks. In many situations a certified answer is needed, for example the guarantee that the linear program is feasible or infeasible, or a provably safe bound on its objective value. Most of the available solvers work with floating-point arithmetic and are thus subject to its shortcomings such as rounding errors or underflow, therefore they can deliver incorrect answers. While adequate for some applications, this is unacceptable for critical applications like flight controlling or nuclear plant management due to the potential catastrophic consequences. We propose a method that gives a certified answer whether a linear program is feasible or infeasible, or returns unknown'. The advantage of our method is that it is reasonably fast and rarely answers unknown'. It works by computing a safe solution that is in some way the best possible in the relative interior of the feasible set. To certify the relative interior, we employ exact arithmetic, whose use is nevertheless limited in general to critical places, allowing us to rnremain computationally efficient. Moreover, when certain conditions are fulfilled, our method is able to deliver a provable bound on the objective value of the linear program. We test our algorithm on typical benchmark sets and obtain higher rates of success compared to previous approaches for this problem, while keeping the running times acceptably small. The computed objective value bounds are in most of the cases very close to the known exact objective values. We prove the usability of the method we developed by additionally employing a variant of it in a different scenario, namely to improve the results of a Satisfiability Modulo Theories solver. Our method is used as a black box in the nodes of a branch-and-bound tree to implement conflict learning based on the certificate of infeasibility for linear programs consisting of subsets of linear constraints. The generated conflict clauses are in general small and give good rnprospects for reducing the search space. Compared to other methods we obtain significant improvements in the running time, especially on the large instances.

Parallel algorithm for solving integer linear programs

Linear programs, or LPs, are often used in optimization problems, such as improving manufacturing efficiency of maximizing the yield from limited resources. The most common method for solving LPs is the Simplex Method, which will yield a solution, if one exists, but over the real numbers. From a purely numerical standpoint, it will be an optimal solution, but quite often we desire an optimal integer solution. A linear program in which the variables are also constrained to be integers is called an integer linear program or ILP. It is the focus of this report to present a parallel algorithm for solving ILPs. We discuss a serial algorithm using a breadth-first branch-and-bound search to check the feasible solution space, and then extend it into a parallel algorithm using a client-server model. In the parallel mode, the search may not be truly breadth-first, depending on the solution time for each node in the solution tree. Our search takes advantage of pruning, often resulting in super-linear improvements in solution time. Finally, we present results from sample ILPs, describe a few modifications to enhance the algorithm and improve solution time, and offer suggestions for future work.

Citation Searching: Search Smarter & Find More

At the University of Connecticut, we have been enticing graduate students to join graduate student trainers to learn how to answer the following questions and improve the breadth of their research: Do you need to find articles published outside your primary discipline? What are some seminal articles in your field? Have you ever wanted to know who cited an article you wrote? We are participating in Elsevier's Student Ambassador Program (SAmP) in which graduate students train their peers on "citation searching" research using Scopus and Web of Science, two tremendous citation databases. We are in the fourth semester of these training programs, and they are wildly successful: We have offered more than 30 classes and taught more than 350 students from March 2007 through March 2008.

Systematic review of worksite-based behavior change programs that target metabolic syndrome risk factors

Approximately one-third of US adults have metabolic syndrome, the clustering of cardiovascular risk factors that include hypertension, abdominal adiposity, elevated fasting glucose, low high-density lipoprotein (HDL)-cholesterol and elevated triglyceride levels. While the definition of metabolic syndrome continues to be much debated among leading health research organizations, the fact is that individuals with metabolic syndrome have an increased risk of developing cardiovascular disease and/or type 2 diabetes. A recent report by the Henry J. Kaiser Family Foundation found that the US spent $2.2 trillion (16.2% of the Gross Domestic Product) on healthcare in 2007 and cited that among other factors, chronic diseases, including type 2 diabetes and cardiovascular disease, are large contributors to this growing national expenditure. Bearing a substantial portion of this cost are employers, the leading providers of health insurance. In lieu of this, many employers have begun implementing health promotion efforts to counteract these rising costs. However, evidence-based practices, uniform guidelines and policy do not exist for this setting in regard to the prevention of metabolic syndrome risk factors as defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III). Therefore, the aim of this review was to determine the effects of worksite-based behavior change programs on reducing the risk factors for metabolic syndrome in adults. Using relevant search terms, OVID MEDLINE was used to search the peer-reviewed literature published since 1998, resulting in 23 articles meeting the inclusion criteria for the review. The American Dietetic Association's Evidence Analysis Process was used to abstract data from selected articles, assess the quality of each study, compile the evidence, develop a summarized conclusion, and assign a grade based upon the strength of supporting evidence. The results revealed that participating in a worksite-based behavior change program may be associated in one or more improved metabolic syndrome risk factors. Programs that delivered a higher dose (>22 hours), in a shorter duration (<2 years) using two or more behavior-change strategies were associated with more metabolic risk factors being positively impacted. A Conclusion Grade of III was obtained for the evidence, indicating that studies were of weak design or results were inconclusive due to inadequate sample sizes, bias and lack of generalizability. These results provide some support for the continued use of worksite-based health promotion and further research is needed to determine if multi-strategy, intense behavior change programs targeting multiple risk factors are able to sustain health improvements in the long-term.^

U.S. school based sealant programs: Review of their most common characteristics

In the United States, dental caries is the most common chronic illness in children, occurring five to eight times as frequently as asthma. 11 Dental caries is an unmet health need, disproportionately affecting minority groups and individuals with low socio-economic status.15,34,36 School-Based Sealant Programs were developed to target children at risk, to provide dental services in a closer geographic area, to offer low cost preventive dental services, and to educate families about oral health and prevention.1 There is scientific, evidence based literature that shows the effectiveness of dental sealants preventing dental decay. 13^ Currently, there is no central source for cataloging School-Based Sealant Programs (SBSPs). Information is scattered around publications and documents. For instance, the National Health and Nutrition Examination Survey (NHANES) does not have information about all the existing SBSPs. ^ This literature review determined which are the most common characteristics of SBSPs in the U.S. and determined the extent to which these programs provide sealants to children of low socio-economic status. The method utilized was an electronic database search. Pubmed and EBESCO host databases were searched with Mesh terms like “dental school sealant programs”, “community dentistry”, “school based sealant programs” and “oral preventive programs”. Results were organized in terms of location, population served, providers, funding source and data shared. ^ The searches produced 77 studies, from which 40 were included in this work. Only 18 U.S. states were represented in the results; however these findings are very consistent with the Best Practice Approach – School Based Sealant Programs3. Most of the SBSPs provide their services to children from low income families, and utilized the lower labor cost providers permitted by their state regulations. The author intends that this thesis work will become an aide in the development of future programs, and as evidence for the sustainability of these programs.^

Parallel execution of Prolog programs: a survey

Since the early days of logic programming, researchers in the field realized the potential for exploitation of parallelism present in the execution of logic programs. Their high-level nature, the presence of nondeterminism, and their referential transparency, among other characteristics, make logic programs interesting candidates for obtaining speedups through parallel execution. At the same time, the fact that the typical applications of logic programming frequently involve irregular computations, make heavy use of dynamic data structures with logical variables, and involve search and speculation, makes the techniques used in the corresponding parallelizing compilers and run-time systems potentially interesting even outside the field. The objective of this article is to provide a comprehensive survey of the issues arising in parallel execution of logic programming languages along with the most relevant approaches explored to date in the field. Focus is mostly given to the challenges emerging from the parallel execution of Prolog programs. The article describes the major techniques used for shared memory implementation of Or-parallelism, And-parallelism, and combinations of the two. We also explore some related issues, such as memory management, compile-time analysis, and execution visualization.

Determinacy analysis for logic programs using mode and type information

We propose an analysis for detecting procedures and goals that are deterministic (i.e. that produce at most one solution), or predicates whose clause tests are mutually exclusive (which implies that at most one of their clauses will succeed) even if they are not deterministic (because they cali other predicates that can produce more than one solution). Applications of such determinacy information include detecting programming errors, performing certain high-level program transformations for improving search efñciency, optimizing low level code generation and parallel execution, and estimating tighter upper bounds on the computational costs of goals and data sizes, which can be used for program debugging, resource consumption and granularity control, etc. We have implemented the analysis and integrated it in the CiaoPP system, which also infers automatically the mode and type information that our analysis takes as input. Experiments performed on this implementation show that the analysis is fairly accurate and efncient.

Independence in constraint logic programs

Studying independence of literals, variables, and substitutions has proven very useful in the context of logic programming (LP). Here we study independence in the broader context of constraint logic programming (CLP). We show that a naive extrapolation of the LP definitions of independence to CLP is unsatisfactory (in fact, wrong) for two reasons. First, because interaction between variables through constraints is more complex than in the case of logic programming. Second, in order to ensure the efUciency of several optimizations not only must independence of the search space be considered, but also an orthogonal issue - "independence of constraint solving." We clarify these issues by proposing various types of search independence and constraint solver independence, and show how they can be combined to allow different independence-related optimizations, from parallelism to intelligent backtracking. Sufficient conditions for independence which can be evaluated "a-priori" at run-time are also proposed. Our results suggest that independence, provided a suitable definition is chosen, is even more useful in CLP than in LP.

B-LOG: A branch and bound methodology for the parallel execution of logic programs

We propose a computational methodology -"B-LOG"-, which offers the potential for an effective implementation of Logic Programming in a parallel computer. We also propose a weighting scheme to guide the search process through the graph and we apply the concepts of parallel "branch and bound" algorithms in order to perform a "best-first" search using an information theoretic bound. The concept of "session" is used to speed up the search process in a succession of similar queries. Within a session, we strongly modify the bounds in a local database, while bounds kept in a global database are weakly modified to provide a better initial condition for other sessions. We also propose an implementation scheme based on a database machine using "semantic paging", and the "B-LOG processor" based on a scoreboard driven controller.

Tools for Search Tree Visualization: The APT Tool

The control part of the execution of a constraint logic program can be conceptually shown as a search-tree, where nodes correspond to calis, and whose branches represent conjunctions and disjunctions. This tree represents the search space traversed by the program, and has also a direct relationship with the amount of work performed by the program. The nodes of the tree can be used to display information regarding the state and origin of instantiation of the variables involved in each cali. This depiction can also be used for the enumeration process. These are the features implemented in APT, a tool which runs constraint logic programs while depicting a (modified) search-tree, keeping at the same time information about the state of the variables at every moment in the execution. This information can be used to replay the execution at will, both forwards and backwards in time. These views can be abstracted when the size of the execution requires it. The search-tree view is used as a framework onto which constraint-level visualizations (such as those presented in the following chapter) can be attached.

Independence and search space preservation in dynamically scheduled constraint logic languages

This paper performs a further generalization of the notion of independence in constraint logic programs to the context of constraint logic programs with dynamic scheduling. The complexity of this new environment made necessary to first formally define the relationship between independence and search space preservation in the context of CLP languages. In particular, we show that search space preservation is, in the context of CLP languages, not only a sufficient but also a necessary condition for ensuring that both the intended solutions and the number of transitions performed do not change. These results are then extended to dynamically scheduled languages and used as the basis for the extension of the concepts of independence. We also propose several a priori sufficient conditions for independence and also give correctness and efficiency results for parallel execution of constraint logic programs based on the proposed notions of independence.

A Meta-Analysis of the Effectiveness of Military and Veterans Affairs (VA) Combat-Related PTSD Programs

A meta-analysis was conducted to examine the effectiveness of 55 treatment outcomes reported by military and Veterans Affairs (VA) treatment centers for combat-related posttraumatic stress disorder (PTSD). The analysis includes 46 tested treatment outcomes derived from 21 psychotherapy studies, and nine tested treatment outcomes derived from seven pharmacotherapy studies, which were obtained through PsychINFO and PsychARTICLES database searches, as well as a reference search. Analysis of all treatment outcomes suggested a statistically significant, and meaningful, decrease in PTSD symptoms between baseline and post-treatment time points, t(54) = 9.27, p < .001, d = 0.35. Additionally, analysis of outcomes between psychotherapy and pharmacotherapy treatments resulted in statistically significant differences in PTSD assessment scores at post-test, indicating a greater degree of change for psychotherapy than for pharmacotherapy.

A comprehensive search for cost-effectiveness data for highway safety countermeasures. Final report.

National Highway Traffic Safety Administration, Washington, D.C.