bluuebunny/crossref_metadata_2025_split huggingface dataset:
CUDAMPF: a multi-tiered parallel framework for accelerating protein sequence search in HMMER on CUDA-enabled GPU
Authors: Jiang Hanyu , Ganesan Narayan 
Published: February 2016

Abstract
Background
HMMER software suite is widely used for analysis of homologous protein and nucleotide sequences with high sensitivity. The latest version of hmmsearch in HMMER 3.x, utilizes heuristic-pipeline which consists of MSV/SSV (Multiple/Single ungapped Segment Viterbi) stage, P7Viterbi stage and the Forward scoring stage to accelerate homology detection. Since the latest version is highly optimized for performance on modern multi-core CPUs with SSE capabilities, only a few acceleration attempts report speedup. However, the most compute intensive tasks within the pipeline (viz., MSV/SSV and P7Viterbi stages) still stand to benefit from the computational capabilities of massively parallel processors.

Results
A Multi-Tiered Parallel Framework (CUDAMPF) implemented on CUDA-enabled GPUs presented here, offers a finer-grained parallelism for MSV/SSV and Viterbi algorithms. We couple SIMT (Single Instruction Multiple Threads) mechanism with SIMD (Single Instructions Multiple Data) video instructions with warp-synchronism to achieve high-throughput processing and eliminate thread idling. We also propose a hardware-aware optimal allocation scheme of scarce resources like on-chip memory and caches in order to boost performance and scalability of CUDAMPF. In addition, runtime compilation via NVRTC available with CUDA 7.0 is incorporated into the presented framework that not only helps unroll innermost loop to yield upto 2 to 3-fold speedup than static compilation but also enables dynamic loading and switching of kernels depending on the query model size, in order to achieve optimal performance.

Conclusions
CUDAMPF is designed as a hardware-aware parallel framework for accelerating computational hotspots within the hmmsearch pipeline as well as other sequence alignment applications. It achieves significant speedup by exploiting hierarchical parallelism on single GPU and takes full advantage of limited resources based on their own performance features. In addition to exceeding performance of other acceleration attempts, comprehensive evaluations against high-end CPUs (Intel i5, i7 and Xeon) shows that CUDAMPF yields upto 440 GCUPS for SSV, 277 GCUPS for MSV and 14.3 GCUPS for P7Viterbi all with 100 % accuracy, which translates to a maximum speedup of 37.5, 23.1 and 11.6-fold for MSV, SSV and P7Viterbi respectively. The source code is available at https://github.com/Super-Hippo/CUDAMPF.
Regularized logistic regression with network-based pairwise interaction for biomarker identification in breast cancer
Authors: Wu Meng-Yun , Zhang Xiao-Fei , Dai Dao-Qing , Ou-Yang Le , Zhu Yuan , Yan Hong 
Published: February 2016

AbstractBackgroudTo facilitate advances in personalized medicine, it is important to detect predictive, stable and interpretable biomarkers related with different clinical characteristics. These clinical characteristics may be heterogeneous with respect to underlying interactions between genes. Usually, traditional methods just focus on detection of differentially expressed genes without taking the interactions between genes into account. Moreover, due to the typical low reproducibility of the selected biomarkers, it is difficult to give a clear biological interpretation for a specific disease. Therefore, it is necessary to design a robust biomarker identification method that can predict disease-associated interactions with high reproducibility.ResultsIn this article, we propose a regularized logistic regression model. Different from previous methods which focus on individual genes or modules, our model takes gene pairs, which are connected in a protein-protein interaction network, into account. A line graph is constructed to represent the adjacencies between pairwise interactions. Based on this line graph, we incorporate the degree information in the model via an adaptive elastic net, which makes our model less dependent on the expression data. Experimental results on six publicly available breast cancer datasets show that our method can not only achieve competitive performance in classification, but also retain great stability in variable selection. Therefore, our model is able to identify the diagnostic and prognostic biomarkers in a more robust way. Moreover, most of the biomarkers discovered by our model have been verified in biochemical or biomedical researches.ConclusionsThe proposed method shows promise in the diagnosis of disease pathogenesis with different clinical characteristics. These advances lead to more accurate and stable biomarker discovery, which can monitor the functional changes that are perturbed by diseases. Based on these predictions, researchers may be able to provide suggestions for new therapeutic approaches.
HPG pore: an efficient and scalable framework for nanopore sequencing data
Authors: Tarraga Joaquin , Gallego Asunción , Arnau Vicente , Medina Ignacio , Dopazo Joaquin 
Published: February 2016

Abstract
Background
The use of nanopore technologies is expected to spread in the future because they are portable and can sequence long fragments of DNA molecules without prior amplification. The first nanopore sequencer available, the MinION™ from Oxford Nanopore Technologies, is a USB-connected, portable device that allows real-time DNA analysis. In addition, other new instruments are expected to be released soon, which promise to outperform the current short-read technologies in terms of throughput. Despite the flood of data expected from this technology, the data analysis solutions currently available are only designed to manage small projects and are not scalable.

Results
Here we present HPG Pore, a toolkit for exploring and analysing nanopore sequencing data. HPG Pore can run on both individual computers and in the Hadoop distributed computing framework, which allows easy scale-up to manage the large amounts of data expected to result from extensive use of nanopore technologies in the future.

Conclusions
HPG Pore allows for virtually unlimited sequencing data scalability, thus guaranteeing its continued management in near future scenarios. HPG Pore is available in GitHub at http://github.com/opencb/hpg-pore.
Hepatitis C virus-cross-reactive TCR gene-modified T cells: a model for immunotherapy against diseases with genomic instability
Authors: Spear Timothy T , Riley Timothy P , Lyons Gretchen E , Callender Glenda G , Roszkowski Jeffrey J , Wang Yuan , Simms Patricia E , Scurti Gina M , Foley Kendra C , Murray David C , Hellman Lance M , McMahan Rachel H , Iwashima Makio , Garrett-Mayer Elizabeth , Rosen Hugo R , Baker Brian M , Nishimura Michael I 
Published: February 2016

Abstract
A major obstacle hindering the development of effective immunity against viral infections, their associated disease, and certain cancers is their inherent genomic instability. Accumulation of mutations can alter processing and presentation of antigens recognized by antibodies and T cells that can lead to immune escape variants. Use of an agent that can intrinsically combat rapidly mutating viral or cancer-associated antigens would be quite advantageous in developing effective immunity against such disease. We propose that T cells harboring cross-reactive TCRs could serve as a therapeutic agent in these instances. With the use of hepatitis C virus, known for its genomic instability as a model for mutated antigen recognition, we demonstrate cross-reactivity against immunogenic and mutagenic nonstructural protein 3:1406-1415 and nonstructural protein 3:1073-1081 epitopes in PBL-derived, TCR-gene-modified T cells. These single TCR-engineered T cells can CD8-independently recognize naturally occurring and epidemiologically relevant mutant variants. TCR-peptide MHC modeling data allow us to rationalize how TCR structural properties accommodate recognition of certain mutated epitopes and how these substitutions impact the requirement of CD8 affinity enhancement for recognition. A better understanding of such TCRs’ promiscuous behavior may allow for exploitation of these properties to develop novel, adoptive T cell-based therapies for viral infections and cancers exhibiting similar genomic instability.
IFN-α promotes rapid human Treg contraction and late Th1-like Treg decrease
Authors: Pacella Ilenia , Timperi Eleonora , Accapezzato Daniele , Martire Carmela , Labbadia Giancarlo , Cavallari Eugenio N , D’Ettorre Gabriella , Calvo Ludovica , Rizzo Fabiana , Severa Martina , Coccia Eliana M , Vullo Vincenzo , Barnaba Vincenzo , Piconese Silvia 
Published: February 2016

Abstract
Type I IFNs are pleiotropic cytokines that exert concerted activities in the development of antiviral responses. Regulatory T cells represent a physiologic checkpoint in the balance between immunity and tolerance, requiring fine and rapid controls. Here, we show that human regulatory T cells are particularly sensitive to the sequential effects of IFN-α. First, IFN-α exerts a rapid, antiproliferative and proapoptotic effect in vitro and in vivo, as early as after 2 d of pegylated IFN/ribavirin therapy in patients with chronic hepatitis C. Such activities result in the decline, at d 2, in circulating regulatory T cell frequency and specifically of the activated regulatory T cell subset. Later, IFN-based therapy restrains the fraction of regulatory T cells that can be polarized into IFN-γ-producing Th1-like regulatory T cells known to contribute to chronic immune activation in type 1 inflammation. Indeed, Th1-like regulatory T cell frequency significantly declines after 30 d of therapy in vivo in relation to the persistent decline of relevant IL-12 sources, namely, myeloid and 6-sulfo LacNAc-expressing dendritic cells. This event is recapitulated by experiments in vitro, providing evidence that it may be attributable to the inhibitory effect of IFN-α on IL-12-induced, Th1-like regulatory T cell polarization. In summary, our results suggest that IFN-α-driven, early regulatory T cell depletion contributes to the development of antiviral immunity, ultimately resulting in the resolution of type 1 inflammation.
Analysis of Transpulmonary Thermodilution Data Confirms the Influence of Renal Replacement Therapy on Thermodilution Hemodynamic Measurements
Authors: Schmidt Sven , Westhoff Timm , Schlattmann Peter , Zidek Walter , Compton Friederike 
Published: February 2016

BACKGROUND:
Transpulmonary thermodilution (TPTD) is used frequently in the intensive care unit to determine cardiac index (CI), intrathoracic blood volume index (ITBVI), and extravascular lung volume index (EVLWI). Renal replacement therapy (RRT) influences TPTD results, but the underlying mechanisms are not completely understood. We hypothesized that RRT blood flow induces errors in TPTD measurements.

METHODS:
We analyzed TPTD data available from the PiCCO® plus hemodynamic measurement device on a personal computer using a proprietary Pulsion Medical Systems software. By using the dialysis catheter to inject the thermal indicator, 20 measurement series were performed in 12 intensive care unit patients determining CI, ITBVI, and EVLWI during RRT with the blood pump stopped, and at flows of 100 and 200 mL/min, respectively.

RESULTS:
Data export was successful in 17 measurement series and showed a significant decrease in measured CI (6.5 ± 2.5 vs 5.4 ± 1.9 L/min/m2, P < 0.001) and ITBVI (1358.8 ± 274.5 vs 1132.8 ± 218.3 mL/m2, P < 0.001) with RRT and a significant increase in EVLWI (8.6 ± 4.4, 10.2 ± 4.5 mL/kg, P < 0.001). Blood temperature before and the temperature decrease after injection of the thermal indicator were unchanged by RRT. Mean transit time and downslope time of the thermodilution curve, however, were both increased with the RRT blood pump running (P ≤ 0.001).

CONCLUSIONS:
Analysis of TPTD data shows that thermodilution curve forms are modified with RRT, resulting in an erroneous calculation of thermodilution-derived hemodynamic parameters.
Legislating Weight Loss: Are Antiobesity Public Health Policies Making an Impact?
Authors: Essington Malana , Hertelendy Attila J. 
Published: February 2016

Abstract
Obesity affects America's children both in childhood and into their adult years. Unfortunately, a long history of public policy has done little to effectively reduce obesity among children. Federal programs including the National School Lunch Program, School Breakfast Program, and the School Meals Initiative for Healthy Children have proven to be less than effective in reducing obesity rates among school-aged children. Studies find that children participating in these programs are more likely to be overweight than their brown-bag peers while nutritional targets are missed. Various iterations of school-based nutrition programs have proven to be ineffective and wasteful, yet policy leaders continue to consume tax dollars with their implementation. Although strict guidelines for evaluating scientific evidence were historically used to ensure rigorous reviews were conducted, recent relaxation of those guidelines jeopardizes the integrity of the scientific platform. Consequently, recommendations that were once rooted in science may be less reliable due to a compromise of the scientific literature review process, and the conclusions drawn by the Dietary Guidelines Advisory Committee may be somewhat questionable. Public policy must be augmented by scientific evidence and any further obesity reduction initiatives must be well-grounded in research that has been rigorously reviewed and evaluated.
Stem-cell-specific endocytic degradation defects lead to intestinal dysplasia in Drosophila
Authors: Nagy Péter , Kovács Laura , Sándor Gyöngyvér O. , Juhász Gábor 
Published: February 2016

ABSTRACT
UV radiation resistance-associated gene (UVRAG) is a tumor suppressor involved in autophagy, endocytosis and DNA damage repair, but how its loss contributes to colorectal cancer is poorly understood. Here, we show that UVRAG deficiency in Drosophila intestinal stem cells leads to uncontrolled proliferation and impaired differentiation without preventing autophagy. As a result, affected animals suffer from gut dysfunction and short lifespan. Dysplasia upon loss of UVRAG is characterized by the accumulation of endocytosed ligands and sustained activation of STAT and JNK signaling, and attenuation of these pathways suppresses stem cell hyperproliferation. Importantly, the inhibition of early (dynamin-dependent) or late (Rab7-dependent) steps of endocytosis in intestinal stem cells also induces hyperproliferation and dysplasia. Our data raise the possibility that endocytic, but not autophagic, defects contribute to UVRAG-deficient colorectal cancer development in humans.
Conditional mutation of Smc5 in mouse embryonic stem cells perturbs condensin localization and mitotic progression
Authors: Pryzhkova Marina V. , Jordan Philip W. 
Published: February 2016

ABSTRACT
Correct duplication of stem cell genetic material and its appropriate segregation into daughter cells are requisites for tissue, organ and organism homeostasis. Disruption of stem cell genomic integrity can lead to developmental abnormalities and cancer. Roles of the Smc5/6 structural maintenance of chromosomes complex in pluripotent stem cell genome maintenance have not been investigated, despite its important roles in DNA synthesis, DNA repair and chromosome segregation as evaluated in other model systems. Using mouse embryonic stem cells (mESCs) with a conditional knockout allele of Smc5, we showed that Smc5 protein depletion resulted in destabilization of the Smc5/6 complex, accumulation of cells in G2 phase of the cell cycle and apoptosis. Detailed assessment of mitotic mESCs revealed abnormal condensin distribution and perturbed chromosome segregation, accompanied by irregular spindle morphology, lagging chromosomes and DNA bridges. Mutation of Smc5 resulted in retention of Aurora B kinase and enrichment of condensin on chromosome arms. Furthermore, we observed reduced levels of Polo-like kinase 1 at kinetochores during mitosis. Our study reveals crucial requirements of the Smc5/6 complex during cell cycle progression and for stem cell genome maintenance.
The mechanical regulation of integrin–cadherin crosstalk organizes cells, signaling and forces
Authors: Mui Keeley L. , Chen Christopher S. , Assoian Richard K. 
Published: February 2016

ABSTRACT
Cadherins and integrins are intrinsically linked through the actin cytoskeleton and share common signaling molecules. Although mechanosensing by the integrin–actin axis has long been appreciated, a growing body of literature now demonstrates that cadherins also transduce and respond to mechanical forces. Mounting evidence shows that mechanically driven crosstalk between integrins and cadherins regulates the spatial distribution of these receptors, their signaling intermediates, the actin cytoskeleton and intracellular forces. This interplay between integrins and cadherins can control fibronectin matrix assembly and signaling, and a fine balance between traction forces at focal adhesions and intercellular tension at adherens junctions is crucial for directional collective cell migration. In this Commentary, we discuss two central ideas: (1) how the dynamic interplay between integrins and cadherins regulates the spatial organization of intracellular signals and the extracellular matrix, and (2) the emerging consensus that intracellular force is a central mechanism that dictates cell behavior, guides tissue development and ultimately drives physiology.
Odd Cycle Zero Forcing Parameters and the Minimum Rank of Graph Blowups
Authors: Lin Jephian Chin-Hung 
Published: February 2016

The minimum rank problem for a simple graph G and a given field F is to determine the smallest possible rank among symmetric matrices over F whose i, j-entry, i â j, is nonzero whenever i is adjacent to j, and zero otherwise; the diagonal entries can be any element in F. In contrast, loop graphs \mathscr{G} go one step further to restrict the diagonal i, i-entries as nonzero whenever i has a loop, and zero otherwise. When char F â 2, the odd cycle zero forcing number and the enhanced odd cycle zero forcing number are introduced as bounds for loop graphs and simple graphs, respectively. A relation between loop graphs and simple graphs through graph blowups is developed, so that the minimum rank problem of some families of simple graphs can be reduced to that of much smaller loop graphs.
A modified Adomian decomposition method for singular initial value Emden-Fowler type equations
Authors: Biazar Jafar , Hosseini Kamyar 
Published: February 2016

<p>Traditional Adomian decomposition method (ADM) usually fails to solve singular initial value problems of Emden-Fowler type. To overcome this shortcoming, a new and effective modification of ADM that only requires calculation of the first Adomian polynomial is formally proposed in the present paper. Three singular initial value problems of Emden-Fowler type with alpha=1, 2, and &gt;2, have been selected to demonstrate the efficiency of the method. </p>
σ2-Adaptin Facilitates Basal Synaptic Transmission and Is Required for Regenerating Endo-Exo Cycling Pool Under High-Frequency Nerve Stimulation in Drosophila
Authors: Choudhury Saumitra Dey , Mushtaq Zeeshan , Reddy-Alla Suneel , Balakrishnan Sruthi S , Thakur Rajan S , Krishnan Kozhalmannom S , Raghu Padinjat , Ramaswami Mani , Kumar Vimlesh 
Published: February 2016

Abstract
The functional requirement of adapter protein 2 (AP2) complex in synaptic membrane retrieval by clathrin-mediated endocytosis is not fully understood. Here we isolated and functionally characterized a mutation that dramatically altered synaptic development. Based on the aberrant neuromuscular junction (NMJ) synapse, we named this mutation angur (a Hindi word meaning “grapes”). Loss-of-function alleles of angur show more than twofold overgrowth in bouton numbers and a dramatic decrease in bouton size. We mapped the angur mutation to σ2-adaptin, the smallest subunit of the AP2 complex. Reducing the neuronal level of any of the subunits of the AP2 complex or disrupting AP2 complex assembly in neurons phenocopied the σ2-adaptin mutation. Genetic perturbation of σ2-adaptin in neurons leads to a reversible temperature-sensitive paralysis at 38°. Electrophysiological analysis of the mutants revealed reduced evoked junction potentials and quantal content. Interestingly, high-frequency nerve stimulation caused prolonged synaptic fatigue at the NMJs. The synaptic levels of subunits of the AP2 complex and clathrin, but not other endocytic proteins, were reduced in the mutants. Moreover, bone morphogenetic protein (BMP)/transforming growth factor β (TGFβ) signaling was altered in these mutants and was restored by normalizing σ2-adaptin in neurons. Thus, our data suggest that (1) while σ2-adaptin facilitates synaptic vesicle (SV) recycling for basal synaptic transmission, its activity is also required for regenerating SVs during high-frequency nerve stimulation, and (2) σ2-adaptin regulates NMJ morphology by attenuating TGFβ signaling.
TRX-1 Regulates SKN-1 Nuclear Localization Cell Non-autonomously in Caenorhabditis elegans
Authors: McCallum Katie C , Liu Bin , Fierro-González Juan Carlos , Swoboda Peter , Arur Swathi , Miranda-Vizuete Antonio , Garsin Danielle A 
Published: February 2016

Abstract
The Caenorhabditis elegans oxidative stress response transcription factor, SKN-1, is essential for the maintenance of redox homeostasis and is a functional ortholog of the Nrf family of transcription factors. The numerous levels of regulation that govern these transcription factors underscore their importance. Here, we add a thioredoxin, encoded by trx-1, to the expansive list of SKN-1 regulators. We report that loss of trx-1 promotes nuclear localization of intestinal SKN-1 in a redox-independent, cell non-autonomous fashion from the ASJ neurons. Furthermore, this regulation is not general to the thioredoxin family, as two other C. elegans thioredoxins, TRX-2 and TRX-3, do not play a role in this process. Moreover, TRX-1-dependent regulation requires signaling from the p38 MAPK-signaling pathway. However, while TRX-1 regulates SKN-1 nuclear localization, classical SKN-1 transcriptional activity associated with stress response remains largely unaffected. Interestingly, RNA-Seq analysis revealed that loss of trx-1 elicits a general, organism-wide down-regulation of several classes of genes; those encoding for collagens and lipid transport being most prevalent. Together, these results uncover a novel role for a thioredoxin in regulating intestinal SKN-1 nuclear localization in a cell non-autonomous manner, thereby contributing to the understanding of the processes involved in maintaining redox homeostasis throughout an organism.