1,057 research outputs found
A Polyglot Approach to Bioinformatics Data Integration: Phylogenetic Analysis of HIV-1
RNA-interference has potential therapeutic use against HIV-1 by targeting highly-functional mRNA sequences that contribute to the virulence of the virus. Empirical work has shown that within cell lines, all of the HIV-1 genes are affected by RNAi-induced gene silencing. While promising, inherent in this treatment is the fact that RNAi sequences must be highly specific. HIV, however, mutates rapidly, leading to the evolution of viral escape mutants. In fact, such strains are under strong selection to include mutations within the targeted region, evading the RNAi therapy and thus increasing the virus’ fitness in the host. Taking a phylogenetic approach, we have examined 4000+ HIV-1 strains obtained from NCBI’S database for each of the HIV genes, identifying conserved regions at each hypothetical and operational taxonomical unit within the tree. Integrating the wealth of information available from each genome’s record, we are able to observe how conserved regions vary with respect to their distribution throughout the world. This was made possible through the development of a new software tool, developed such that similar analyses can be conducted for any species or gene of interest, not just HIV-1. In addition to the phylogenetic signal which we can recognize from the HIV-1 genomes examined, we can also identify how selection varies across the genome. Taking this evolutionary approach, we have detected regions ideal for targeting by RNAi treatment.
The software system mentioned above provides access to the National Center for Biotechnology Information\u27s (NCBI) GenBank in multiple ways: It converts GenBank data to the FASTA format for for analysis using desktop tools, and it exposes the data in the form of a RESTful web service. We have implemented this system using polyglot approach involving multiple languages (Python and Scala), libraries (Flask and BioJavaX), and persistence mechanisms (text files and MongoDB NoSQL databases)
Cooperative action in eukaryotic gene regulation: physical properties of a viral example
The Epstein-Barr virus (EBV) infects more than 90% of the human population,
and is the cause of several both serious and mild diseases. It is a
tumorivirus, and has been widely studied as a model system for gene
(de)regulation in human. A central feature of the EBV life cycle is its ability
to persist in human B cells in states denoted latency I, II and III. In latency
III the host cell is driven to cell proliferation and hence expansion of the
viral population, but does not enter the lytic pathway, and no new virions are
produced, while the latency I state is almost completely dormant. In this paper
we study a physico-chemical model of the switch between latency I and latency
III in EBV. We show that the unusually large number of binding sites of two
competing transcription factors, one viral and one from the host, serves to
make the switch sharper (higher Hill coefficient), either by cooperative
binding between molecules of the same species when they bind, or by competition
between the two species if there is sufficient steric hindrance.Comment: 7 pages, 6 figures, 1 tabl
A Polyglot Approach to Bioinformatics Data Integration: a Phylogenetic Analysis of HIV-1
As sequencing technologies continue to drop in price and increase in throughput, new challenges emerge for the management and accessibility of genomic sequence data. We have developed a pipeline for facilitating the storage, retrieval, and subsequent analysis of molecular data, integrating both sequence and metadata. Taking a polyglot approach involving multiple languages, libraries, and persistence mechanisms, sequence data can be aggregated from publicly available and local repositories. Data are exposed in the form of a RESTful web service, formatted for easy querying, and retrieved for downstream analyses. As a proof of concept, we have developed a resource for annotated HIV-1 sequences. Phylogenetic analyses were conducted for \u3e6,000 HIV-1 sequences revealing spatial and temporal factors influence the evolution of the individual genes uniquely. Nevertheless, signatures of origin can be extrapolated even despite increased globalization. The approach developed here can easily be customized for any species of interest
Enantioselective and Enantiospecific Transition-Metal-Catalyzed Cross-Coupling Reactions of Organometallic Reagents To Construct C–C Bonds
The stereocontrolled construction of C−C bonds remains one of the foremost challenges in organic synthesis. At the heart of any chemical synthesis of a natural product or designed small molecule is the need to orchestrate a series of chemical reactions to prepare and functionalize a carbon framework. The advent of transition-metal catalysis has provided chemists with a broad range of new tools to forge C−C bonds and has resulted in a paradigm shift in synthetic strategy planning. The impact of these methods was recognized with the awarding of the 2010 Nobel Prize in Chemistry to Richard Heck, Ei-ichi Negishi, and Akira Suzuki for their seminal contributions to the development of Pd-catalyzed cross-coupling
Optical Coherence Tomography in the UK Biobank Study - Rapid Automated Analysis of Retinal Thickness for Large Population-Based Studies
PURPOSE:
To describe an approach to the use of optical coherence tomography (OCT) imaging in large, population-based studies, including methods for OCT image acquisition, storage, and the remote, rapid, automated analysis of retinal thickness.
METHODS:
In UK Biobank, OCT images were acquired between 2009 and 2010 using a commercially available “spectral domain” OCT device (3D OCT-1000, Topcon). Images were obtained using a raster scan protocol, 6 mm x 6 mm in area, and consisting of 128 B-scans. OCT image sets were stored on UK Biobank servers in a central repository, adjacent to high performance computers. Rapid, automated analysis of retinal thickness was performed using custom image segmentation software developed by the Topcon Advanced Biomedical Imaging Laboratory (TABIL). This software employs dual-scale gradient information to allow for automated segmentation of nine intraretinal boundaries in a rapid fashion.
RESULTS:
67,321 participants (134,642 eyes) in UK Biobank underwent OCT imaging of both eyes as part of the ocular module. 134,611 images were successfully processed with 31 images failing segmentation analysis due to corrupted OCT files or withdrawal of subject consent for UKBB study participation. Average time taken to call up an image from the database and complete segmentation analysis was approximately 120 seconds per data set per login, and analysis of the entire dataset was completed in approximately 28 days.
CONCLUSIONS:
We report an approach to the rapid, automated measurement of retinal thickness from nearly 140,000 OCT image sets from the UK Biobank. In the near future, these measurements will be publically available for utilization by researchers around the world, and thus for correlation with the wealth of other data collected in UK Biobank. The automated analysis approaches we describe may be of utility for future large population-based epidemiological studies, clinical trials, and screening programs that employ OCT imaging
Soft systems methodology: a context within a 50-year retrospective of OR/MS
Soft systems methodology (SSM) has been used in the practice of operations research and management science OR/MS) since the early 1970s. In the 1990s, it emerged as a viable academic discipline. Unfortunately, its proponents consider SSM and traditional systems thinking to be mutually exclusive. Despite the differences claimed by SSM proponents between the two, they have been complementary. An extensive sampling of the OR/MS literature over its entire lifetime demonstrates the richness with which the non-SSM literature has been addressing the very same issues as does SSM
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New York City Energy-Water Integrated Planning: A Pilot Study
The New York City Energy-Water Integrated Planning Pilot Study is one of several projects funded by Sandia National Laboratories under the U.S. Department of Energy Energy-Water Nexus Program. These projects are intended to clarify some key issues and research needs identified during the Energy-Water Nexus Roadmapping activities. The objectives of the New York City Pilot Project are twofold: to identify energy-water nexus issues in an established urban area in conjunction with a group of key stakeholders and to define and apply an integrated energy and water decision support tool, as proof-of-concept, to one or more of these issues. During the course of this study, the Brookhaven National Laboratory project team worked very closely with members of a Pilot Project Steering Committee. The Steering Committee members brought a breadth of experience across the energy, water and climate disciplines, and all are well versed in the particular issues faced by an urban environment, and by New York City in particular. The first task was to identify energy-water issues of importance to New York City. This exercise was followed by discussion of the qualities and capabilities that an ideal decision support tool should display to address these issues. The decision was made to start with an existing energy model, the New York City version of the MARKAL model, developed originally at BNL and now used globally by many groups for energy analysis. MARKAL has the virtue of being well-vetted, transparent, and capable of calculating 'material' flows, such as water use by the energy system and energy requirements of water technology. The Steering Committee members defined five scenarios of interest, representing a broad spectrum of New York City energy-water issues. Brookhaven National Laboratory researchers developed a model framework (Water-MARKAL) at the desired level of detail to address the scenarios, and then attempted to gather the New York City-specific information required to analyze the scenarios using Water-MARKAL. This report describes the successes and challenges of defining and demonstrating the decision tool, Water-MARKAL. The issues that the stakeholders perceive for New York City are listed and the difficulties in gathering required information for Water-MARKAL to analyze these issues at the desired level of detail are described
Scoring schemes of palindrome clusters for more sensitive prediction of replication origins in herpesviruses
Many empirical studies show that there are unusual clusters of palindromes, closely spaced direct and inverted repeats around the replication origins of herpesviruses. In this paper, we introduce two new scoring schemes to quantify the spatial abundance of palindromes in a genomic sequence. Based on these scoring schemes, a computational method to predict the locations of replication origins is developed. When our predictions are compared with 39 known or annotated replication origins in 19 herpesviruses, close to 80% of the replication origins are located within 2% of the genome length. A list of predicted locations of replication origins in all the known herpesviruses with complete genome sequences is reported
Transition to forefoot strike reduces load rates more effectively than altered cadence
Background
Excessive vertical impacts at landing are associated with common running injuries. Two primary gait-retraining interventions aimed at reducing impact forces are transition to forefoot strike (FFS) and increasing cadence (CAD). The objective of this study was to compare the short- and long-term effects of 2 gait-retraining interventions aimed at reducing landing impacts.
Methods
A total of 39 healthy recreational runners using a rearfoot strike and a CAD of ≤170 steps/min were randomized into CAD or FFS groups. All participants performed 4 weeks of strengthening followed by 8 sessions of gait-retraining using auditory feedback. Vertical average load rates (VALR) and vertical instantaneous load rates were calculated from the vertical ground reaction force curve. Both CAD and foot strike angle were measured using 3-dimensional motion analysis and an instrumented treadmill at baseline and at 1 week, 1 month, and 6 months after retraining.
Results
Analysis of variance revealed that the FFS group had significant reductions in VALR (49.7%) and vertical instantaneous load rates (41.7%), and changes were maintained long term. Foot strike angle in the FFS group changed from 14.2° dorsiflexion at baseline to 3.4° plantarflexion, with changes maintained long term. The CAD group exhibited significant reduction only in VALR (16%) and only at 6 months. Both groups had significant and similar increases in CAD at all follow-ups (CAD, +7.2% to 173 steps/min; and FFS, +6.1% to 172 steps/min).
Conclusion
FFS gait-retraining resulted in significantly greater reductions in VALR and similar increases in CAD compared to CAD gait-retraining in the short and long term. CAD gait-retraining resulted in small reductions in VALR at only the 6-month follow-up
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