Showing papers by "Virginia Tech published in 2014"

The SEED and the Rapid Annotation of microbial genomes using Subsystems Technology (RAST)

Abstract: In 2004, the SEED (http://pubseed.theseed.org/) was created to provide consistent and accurate genome annotations across thousands of genomes and as a platform for discovering and developing de novo annotations. The SEED is a constantly updated integration of genomic data with a genome database, web front end, API and server scripts. It is used by many scientists for predicting gene functions and discovering new pathways. In addition to being a powerful database for bioinformatics research, the SEED also houses subsystems (collections of functionally related protein families) and their derived FIGfams (protein families), which represent the core of the RAST annotation engine (http://rast.nmpdr.org/). When a new genome is submitted to RAST, genes are called and their annotations are made by comparison to the FIGfam collection. If the genome is made public, it is then housed within the SEED and its proteins populate the FIGfam collection. This annotation cycle has proven to be a robust and scalable solution to the problem of annotating the exponentially increasing number of genomes. To date, >12 000 users worldwide have annotated >60 000 distinct genomes using RAST. Here we describe the interconnectedness of the SEED database and RAST, the RAST annotation pipeline and updates to both resources.

Mechanism of Nitrogen Fixation by Nitrogenase: The Next Stage

Abstract: Brian M. Hoffman,* Dmitriy Lukoyanov, Zhi-Yong Yang,† Dennis R. Dean,*,‡ and Lance C. Seefeldt*,† †Department of Chemistry and Biochemistry, Utah State University, 0300 Old Main Hill, Logan, Utah 84322, United States ‡Department of Biochemistry, Virginia Tech, 900 West Campus Drive, Blacksburg, Virginia 24061, United States Departments of Chemistry and Molecular Biosciences, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States

Proteogenomic characterization of human colon and rectal cancer

Abstract: Extensive genomic characterization of human cancers presents the problem of inference from genomic abnormalities to cancer phenotypes. To address this problem, we analysed proteomes of colon and rectal tumours characterized previously by The Cancer Genome Atlas (TCGA) and perform integrated proteogenomic analyses. Somatic variants displayed reduced protein abundance compared to germline variants. Messenger RNA transcript abundance did not reliably predict protein abundance differences between tumours. Proteomics identified five proteomic subtypes in the TCGA cohort, two of which overlapped with the TCGA 'microsatellite instability/CpG island methylation phenotype' transcriptomic subtype, but had distinct mutation, methylation and protein expression patterns associated with different clinical outcomes. Although copy number alterations showed strong cis- and trans-effects on mRNA abundance, relatively few of these extend to the protein level. Thus, proteomics data enabled prioritization of candidate driver genes. The chromosome 20q amplicon was associated with the largest global changes at both mRNA and protein levels; proteomics data highlighted potential 20q candidates, including HNF4A (hepatocyte nuclear factor 4, alpha), TOMM34 (translocase of outer mitochondrial membrane 34) and SRC (SRC proto-oncogene, non-receptor tyrosine kinase). Integrated proteogenomic analysis provides functional context to interpret genomic abnormalities and affords a new paradigm for understanding cancer biology.

Slowing Amazon deforestation through public policy and interventions in beef and soy supply chains

Abstract: The recent 70% decline in deforestation in the Brazilian Amazon suggests that it is possible to manage the advance of a vast agricultural frontier Enforcement of laws, interventions in soy and beef supply chains, restrictions on access to credit, and expansion of protected areas appear to have contributed to this decline, as did a decline in the demand for new deforestation The supply chain interventions that fed into this deceleration are precariously dependent on corporate risk management, and public policies have relied excessively on punitive measures Systems for delivering positive incentives for farmers to forgo deforestation have been designed but not fully implemented Territorial approaches to deforestation have been effective and could consolidate progress in slowing deforestation while providing a framework for addressing other important dimensions of sustainable development

A comprehensive assessment of RNA-seq accuracy, reproducibility and information content by the Sequencing Quality Control Consortium

Abstract: We present primary results from the Sequencing Quality Control (SEQC) project, coordinated by the US Food and Drug Administration. Examining Illumina HiSeq, Life Technologies SOLiD and Roche 454 platforms at multiple laboratory sites using reference RNA samples with built-in controls, we assess RNA sequencing (RNA-seq) performance for junction discovery and differential expression profiling and compare it to microarray and quantitative PCR (qPCR) data using complementary metrics. At all sequencing depths, we discover unannotated exon-exon junctions, with >80% validated by qPCR. We find that measurements of relative expression are accurate and reproducible across sites and platforms if specific filters are used. In contrast, RNA-seq and microarrays do not provide accurate absolute measurements, and gene-specific biases are observed for all examined platforms, including qPCR. Measurement performance depends on the platform and data analysis pipeline, and variation is large for transcript-level profiling. The complete SEQC data sets, comprising >100 billion reads (10Tb), provide unique resources for evaluating RNA-seq analyses for clinical and regulatory settings.

Transcranial focused ultrasound modulates the activity of primary somatosensory cortex in humans

Abstract: Improved methods of noninvasively modulating human brain function are needed. Here we probed the influence of transcranial focused ultrasound (tFUS) targeted to the human primary somatosensory cortex (S1) on sensory-evoked brain activity and sensory discrimination abilities. The lateral and axial spatial resolution of the tFUS beam implemented were 4.9 mm and 18 mm, respectively. Electroencephalographic recordings showed that tFUS significantly attenuated the amplitudes of somatosensory evoked potentials elicited by median nerve stimulation. We also found that tFUS significantly modulated the spectral content of sensory-evoked brain oscillations. The changes produced by tFUS on sensory-evoked brain activity were abolished when the acoustic beam was focused 1 cm anterior or posterior to S1. Behavioral investigations showed that tFUS targeted to S1 enhanced performance on sensory discrimination tasks without affecting task attention or response bias. We conclude that tFUS can be used to focally modulate human cortical function.

Distracted driving and risk of road crashes among novice and experienced drivers

Abstract: BackgroundDistracted driving attributable to the performance of secondary tasks is a major cause of motor vehicle crashes both among teenagers who are novice drivers and among adults who are experienced drivers MethodsWe conducted two studies on the relationship between the performance of secondary tasks, including cell-phone use, and the risk of crashes and near-crashes To facilitate objective assessment, accelerometers, cameras, global positioning systems, and other sensors were installed in the vehicles of 42 newly licensed drivers (163 to 170 years of age) and 109 adults with more driving experience ResultsDuring the study periods, 167 crashes and near-crashes among novice drivers and 518 crashes and near-crashes among experienced drivers were identified The risk of a crash or near-crash among novice drivers increased significantly if they were dialing a cell phone (odds ratio, 832; 95% confidence interval [CI], 283 to 2442), reaching for a cell phone (odds ratio, 705; 95% CI, 264 to 1883)

A survey of intrusion detection techniques for cyber-physical systems

Abstract: Pervasive healthcare systems, smart grids, and unmanned aircraft systems are examples of Cyber-Physical Systems (CPSs) that have become highly integrated in the modern world. As this integration deepens, the importance of securing these systems increases. In order to identify gaps and propose research directions in CPS intrusion detection research, we survey the literature of this area. Our approach is to classify modern CPS Intrusion Detection System (IDS) techniques based on two design dimensions: detection technique and audit material. We summarize advantages and drawbacks of each dimension’s options. We also summarize the most and least studied CPS IDS techniques in the literature and provide insight on the effectiveness of IDS techniques as they apply to CPSs. Finally, we identify gaps in CPS IDS research and suggest future research areas.

Consensus proposals for classification of the family Hepeviridae

Abstract: The family Hepeviridae consists of positive-stranded RNA viruses that infect a wide range of mammalian species, as well as chickens and trout. A subset of these viruses infects humans and can cause a self-limiting acute hepatitis that may become chronic in immunosuppressed individuals. Current published descriptions of the taxonomical divisions within the family Hepeviridae are contradictory in relation to the assignment of species and genotypes. Through analysis of existing sequence information, we propose a taxonomic scheme in which the family is divided into the genera Orthohepevirus (all mammalian and avian hepatitis E virus (HEV) isolates) and Piscihepevirus (cutthroat trout virus). Species within the genus Orthohepevirus are designated Orthohepevirus A (isolates from human, pig, wild boar, deer, mongoose, rabbit and camel), Orthohepevirus B (isolates from chicken), Orthohepevirus C (isolates from rat, greater bandicoot, Asian musk shrew, ferret and mink) and Orthohepevirus D (isolates from bat). Proposals are also made for the designation of genotypes within the human and rat HEVs. This hierarchical system is congruent with hepevirus phylogeny, and the three classification levels (genus, species and genotype) are consistent with, and reflect discontinuities in the ranges of pairwise distances between amino acid sequences. Adoption of this system would include the avoidance of host names in taxonomic identifiers and provide a logical framework for the assignment of novel variants.

Current status and future advances for wind speed and power forecasting

Abstract: This paper presents an overview of existing research on wind speed and power forecasting. It first discusses state-of-the-art wind speed and power forecasting approaches. Then, forecasting accuracy is presented based on variable factors. Finally, potential techniques to improve the accuracy of forecasting models are reviewed. A full survey on all existing models is not presented, but attempts to highlight the most promising body of knowledge concerning wind speed and power forecasting.

An overview of load balancing in hetnets: old myths and open problems

Abstract: Matching the demand for resources (?load?) with the supply of resources (?capacity?) is a basic problem occurring across many fields of engineering, logistics, and economics, and has been considered extensively in both the Internet and wireless networks. The ongoing evolution of cellular communication networks into dense, organic, and irregular heterogeneous networks (HetNets) has elevated load awareness to a central problem, and introduces many new subtleties. This article explains how several long-standing assumptions about cellular networks need to be rethought in the context of a load-balanced HetNet: we highlight these as three deeply entrenched myths that we then dispel. We survey and compare the primary technical approaches to HetNet load balancing: (centralized) optimization, game theory, Markov decision processes, and the newly popular cell range expansion (a.k.a. biasing), and draw design lessons for OFDMA-based cellular systems. We also identify several open areas for future exploration.

Microbial source tracking markers for detection of fecal contamination in environmental waters: relationships between pathogens and human health outcomes

Abstract: Microbial source tracking (MST) describes a suite of methods and an investigative strategy for determination of fecal pollution sources in environmental waters that rely on the association of certain fecal microorganisms with a particular host. MST is used to assess recreational water quality and associated human health risk, and total maximum daily load allocations. Many methods rely on signature molecules (markers) such as DNA sequences of host-associated microorganisms. Human sewage pollution is among the greatest concerns for human health due to (1) the known risk of exposure to human waste and (2) the public and regulatory will to reduce sewage pollution; however, methods to identify animal sources are receiving increasing attention as our understanding of zoonotic disease potential improves. Here, we review the performance of MST methods in initial reports and field studies, with particular emphasis on quantitative PCR (qPCR). Relationships among human-associated MST markers, fecal indicator bacteria, pathogens, and human health outcomes are presented along with recommendations for future research. An integrated understanding of the advantages and drawbacks of the many MST methods targeting human sources advanced over the past several decades will benefit managers, regulators, researchers, and other users of this rapidly growing area of environmental microbiology.

Secure Deduplication with Efficient and Reliable Convergent Key Management

Abstract: Data deduplication is a technique for eliminating duplicate copies of data, and has been widely used in cloud storage to reduce storage space and upload bandwidth. Promising as it is, an arising challenge is to perform secure deduplication in cloud storage. Although convergent encryption has been extensively adopted for secure deduplication, a critical issue of making convergent encryption practical is to efficiently and reliably manage a huge number of convergent keys. This paper makes the first attempt to formally address the problem of achieving efficient and reliable key management in secure deduplication. We first introduce a baseline approach in which each user holds an independent master key for encrypting the convergent keys and outsourcing them to the cloud. However, such a baseline key management scheme generates an enormous number of keys with the increasing number of users and requires users to dedicatedly protect the master keys. To this end, we propose Dekey , a new construction in which users do not need to manage any keys on their own but instead securely distribute the convergent key shares across multiple servers. Security analysis demonstrates that Dekey is secure in terms of the definitions specified in the proposed security model. As a proof of concept, we implement Dekey using the Ramp secret sharing scheme and demonstrate that Dekey incurs limited overhead in realistic environments.

The Behavioral Economics of Substance Use Disorders: Reinforcement Pathologies and Their Repair

Abstract: The field of behavioral economics has made important inroads into the understanding of substance use disorders through the concept of reinforcer pathology. Reinforcer pathology refers to the joint effects of (a) the persistently high valuation of a reinforcer, broadly defined to include tangible commodities and experiences, and/or (b) the excessive preference for the immediate acquisition or consumption of a commodity despite long-term negative outcomes. From this perspective, reinforcer pathology results from the recursive interactions of endogenous person-level variables and exogenous environment-level factors. The current review describes the basic principles of behavioral economics that are central to reinforcer pathology, the processes that engender reinforcer pathology, and the approaches and procedures that can repair reinforcement pathologies. The overall goal of this review is to present a new understanding of substance use disorders as viewed by recent advances in behavioral economics.

A review of bioactive glasses: Their structure, properties, fabrication and apatite formation

Abstract: Bioactive glass and glass-ceramics are used in bone repair applications and are being developed for tissue engineering applications. Bioactive glasses/Bioglass are very attractive materials for producing scaffolds devoted to bone regeneration due to their versatile properties, which can be properly designed depending on their composition. An important feature of bioactive glasses, which enables them to work for applications in bone tissue engineering, is their ability to enhance revascularization, osteoblast adhesion, enzyme activity and differentiation of mesenchymal stem cells as well as osteoprogenitor cells. An extensive amount of research work has been carried out to develop silicate, borate/borosilicate bioactive glasses and phosphate glasses. Along with this, some metallic glasses have also been investigated for biomedical and technological applications in tissue engineering. Many trace elements have also been incorporated in the glass network to obtain the desired properties, which have beneficial effects on bone remodeling and/or associated angiogenesis. The motivation of this review is to provide an overview of the general requirements, composition, structure-property relationship with hydroxyapatite formation and future perspectives of bioglasses.Attention has also been given to developments of metallic glasses and doped bioglasses along with the techniques used for their fabrication.

FGF21 is an endocrine signal of protein restriction

Abstract: Enhanced fibroblast growth factor 21 (FGF21) production and circulation has been linked to the metabolic adaptation to starvation. Here, we demonstrated that hepatic FGF21 expression is induced by dietary protein restriction, but not energy restriction. Circulating FGF21 was increased 10-fold in mice and rats fed a low-protein (LP) diet. In these animals, liver Fgf21 expression was increased within 24 hours of reduced protein intake. In humans, circulating FGF21 levels increased dramatically following 28 days on a LP diet. LP-induced increases in FGF21 were associated with increased phosphorylation of eukaryotic initiation factor 2α (eIF2α) in the liver, and both baseline and LP-induced serum FGF21 levels were reduced in mice lacking the eIF2α kinase general control nonderepressible 2 (GCN2). Finally, while protein restriction altered food intake, energy expenditure, and body weight gain in WT mice, FGF21-deficient animals did not exhibit these changes in response to a LP diet. These and other data demonstrate that reduced protein intake underlies the increase in circulating FGF21 in response to starvation and a ketogenic diet and that FGF21 is required for behavioral and metabolic responses to protein restriction. FGF21 therefore represents an endocrine signal of protein restriction, which acts to coordinate metabolism and growth during periods of reduced protein intake.

Drone Small Cells in the Clouds: Design, Deployment and Performance Analysis

Abstract: The use of drone small cells (DSCs) which are aerial wireless base stations that can be mounted on flying devices such as unmanned aerial vehicles (UAVs), is emerging as an effective technique for providing wireless services to ground users in a variety of scenarios. The efficient deployment of such DSCs while optimizing the covered area is one of the key design challenges. In this paper, considering the low altitude platform (LAP), the downlink coverage performance of DSCs is investigated. The optimal DSC altitude which leads to a maximum ground coverage and minimum required transmit power for a single DSC is derived. Furthermore, the problem of providing a maximum coverage for a certain geographical area using two DSCs is investigated in two scenarios; interference free and full interference between DSCs. The impact of the distance between DSCs on the coverage area is studied and the optimal distance between DSCs resulting in maximum coverage is derived. Numerical results verify our analytical results on the existence of optimal DSCs altitude/separation distance and provide insights on the optimal deployment of DSCs to supplement wireless network coverage.

TGF-β–induced epithelial-to-mesenchymal transition proceeds through stepwise activation of multiple feedback loops

Abstract: The process of epithelial-to-mesenchymal transition (EMT) is an essential type of cellular plasticity associated with a change from epithelial cells that function as a barrier consisting of a sheet of tightly connected cells to cells with properties of mesenchyme that are not attached to their neighbors and are highly motile. This phenotypic change occurs during development and also contributes to pathological processes, such as cancer progression. The molecular mechanisms controlling the switch between the fully epithelial and fully mesenchymal phenotypes and cells that have characteristics of both (partial EMT) are controversial, and multiple theoretical models have been proposed. To test these theoretical models, we systematically measured the changes in the abundance of proteins, mRNAs, and microRNAs (miRNAs) that represent the core regulators of EMT induced by transforming growth factor–β1 (TGF-β1) in the human breast epithelial cell line MCF10A at the population and single-cell levels. We provide experimental confirmation for a model of cascading switches in phenotypes associated with TGF-β1–induced EMT of MCF10A cells that involves two double-negative feedback loops: one between the transcription factor SNAIL1 and the miR-34 family and another between the transcription factor ZEB1 and the miR-200 family. Furthermore, our data showed that whereas the transition from epithelial to partial EMT was reversible for MCF10A cells, the transition from partial EMT to mesenchymal was mostly irreversible at high concentrations of TGF-β1.

The Physics of the B Factories

Abstract: This work is on the Physics of the B Factories. Part A of this book contains a brief description of the SLAC and KEK B Factories as well as their detectors, BaBar and Belle, and data taking related issues. Part B discusses tools and methods used by the experiments in order to obtain results. The results themselves can be found in Part C.

An open science resource for establishing reliability and reproducibility in functional connectomics

Abstract: Efforts to identify meaningful functional imaging-based biomarkers are limited by the ability to reliably characterize inter-individual differences in human brain function. Although a growing number of connectomics-based measures are reported to have moderate to high test-retest reliability, the variability in data acquisition, experimental designs, and analytic methods precludes the ability to generalize results. The Consortium for Reliability and Reproducibility (CoRR) is working to address this challenge and establish test-retest reliability as a minimum standard for methods development in functional connectomics. Specifically, CoRR has aggregated 1,629 typical individuals’ resting state fMRI (rfMRI) data (5,093 rfMRI scans) from 18 international sites, and is openly sharing them via the International Data-sharing Neuroimaging Initiative (INDI). To allow researchers to generate various estimates of reliability and reproducibility, a variety of data acquisition procedures and experimental designs are included. Similarly, to enable users to assess the impact of commonly encountered artifacts (for example, motion) on characterizations of inter-individual variation, datasets of varying quality are included.

Pathology of Second-Generation Everolimus-Eluting Stents Versus First-Generation Sirolimus- and Paclitaxel-Eluting Stents in Humans

Abstract: Background—Clinical trials have demonstrated that the second-generation cobalt-chromium everolimus-eluting stent (CoCr-EES) is superior to the first-generation paclitaxel-eluting stent (PES) and is noninferior or superior to the sirolimus-eluting stent (SES) in terms of safety and efficacy. It remains unclear whether vascular responses to CoCr-EES are different from those to SES and PES because the pathology of CoCr-EES has not been described in humans. Methods and Results—A total of 204 lesions (SES=73; PES=85; CoCr-EES=46) from 149 autopsy cases with duration of implantation >30 days and ≤3 years were pathologically analyzed, and comparison of vascular responses was corrected for duration of implantation. The observed frequency of late and very late stent thrombosis was less in CoCr-EES (4%) versus SES (21%; P=0.029) and PES (26%; P=0.008). Neointimal thickness was comparable among the groups, whereas the percentage of uncovered struts was strikingly lower in CoCr-EES (median=2.6%) versus SES (18.0%; P<...

Review of Collagen I Hydrogels for Bioengineered Tissue Microenvironments: Characterization of Mechanics, Structure, and Transport

Abstract: Type I collagen hydrogels have been used successfully as three-dimensional substrates for cell culture and have shown promise as scaffolds for engineered tissues and tumors. A critical step in the development of collagen hydrogels as viable tissue mimics is quantitative characterization of hydrogel properties and their correlation with fabrication parameters, which enables hydrogels to be tuned to match specific tissues or fulfill engineering requirements. A significant body of work has been devoted to characterization of collagen I hydrogels; however, due to the breadth of materials and techniques used for characterization, published data are often disjoint and hence their utility to the community is reduced. This review aims to determine the parameter space covered by existing data and identify key gaps in the literature so that future characterization and use of collagen I hydrogels for research can be most efficiently conducted. This review is divided into three sections: (1) relevant fabrication parameters are introduced and several of the most popular methods of controlling and regulating them are described, (2) hydrogel properties most relevant for tissue engineering are presented and discussed along with their characterization techniques, (3) the state of collagen I hydrogel characterization is recapitulated and future directions are proposed. Ultimately, this review can serve as a resource for selection of fabrication parameters and material characterization methodologies in order to increase the usefulness of future collagen-hydrogel-based characterization studies and tissue engineering experiments.