bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complex folding and misfolding effects of deer-specific amino acid substitutions in the β2-α2 loop of murine prion protein
Authors: Agarwal Sonya , Döring Kristina , Gierusz Leszek A. , Iyer Pooja , Lane Fiona M. , Graham James F. , Goldmann Wilfred , Pinheiro Teresa J. T. , Gill Andrew C. 
Published: October 2015

AbstractThe β2–α2 loop of PrPC is a key modulator of disease-associated prion protein misfolding. Amino acids that differentiate mouse (Ser169, Asn173) and deer (Asn169, Thr173) PrPC appear to confer dramatically different structural properties in this region and it has been suggested that amino acid sequences associated with structural rigidity of the loop also confer susceptibility to prion disease. Using mouse recombinant PrP, we show that mutating residue 173 from Asn to Thr alters protein stability and misfolding only subtly, whilst changing Ser to Asn at codon 169 causes instability in the protein, promotes oligomer formation and dramatically potentiates fibril formation. The doubly mutated protein exhibits more complex folding and misfolding behaviour than either single mutant, suggestive of differential effects of the β2–α2 loop sequence on both protein stability and on specific misfolding pathways. Molecular dynamics simulation of protein structure suggests a key role for the solvent accessibility of Tyr168 in promoting molecular interactions that may lead to prion protein misfolding. Thus, we conclude that ‘rigidity’ in the β2–α2 loop region of the normal conformer of PrP has less effect on misfolding than other sequence-related effects in this region.
Zebrafish Models for Human Acute Organophosphorus Poisoning
Authors: Faria Melissa , Garcia-Reyero Natàlia , Padrós Francesc , Babin Patrick J. , Sebastián David , Cachot Jérôme , Prats Eva , Arick Mark , Rial Eduardo , Knoll-Gellida Anja , Mathieu Guilaine , Le Bihanic Florane , Escalon B. Lynn , Zorzano Antonio , Soares Amadeu M. V. M , Raldúa Demetrio 
Published: October 2015

AbstractTerrorist use of organophosphorus-based nerve agents and toxic industrial chemicals against civilian populations constitutes a real threat, as demonstrated by the terrorist attacks in Japan in the 1990 s or, even more recently, in the Syrian civil war. Thus, development of more effective countermeasures against acute organophosphorus poisoning is urgently needed. Here, we have generated and validated zebrafish models for mild, moderate and severe acute organophosphorus poisoning by exposing zebrafish larvae to different concentrations of the prototypic organophosphorus compound chlorpyrifos-oxon. Our results show that zebrafish models mimic most of the pathophysiological mechanisms behind this toxidrome in humans, including acetylcholinesterase inhibition, N-methyl-D-aspartate receptor activation and calcium dysregulation as well as inflammatory and immune responses. The suitability of the zebrafish larvae to in vivo high-throughput screenings of small molecule libraries makes these models a valuable tool for identifying new drugs for multifunctional drug therapy against acute organophosphorus poisoning.
Chromium exposure and incidence of metabolic syndrome among American young adults over a 23-year follow-up: the CARDIA Trace Element Study
Authors: Bai Jianling , Xun Pengcheng , Morris Steve , Jacobs David R. , Liu Kiang , He Ka 
Published: October 2015

AbstractStudies suggest that chromium deficiency is associated with elevated levels of fasting blood glucose, circulating insulin, cholesterol and triglycerides and decreased proportion of lean body mass. However, data directly relating chromium levels to metabolic syndrome (MetS) risk are lacking. A total of 3,648 American adults from the Coronary Artery Risk Development in Young Adults (CARDIA) study, aged 20–32 years, were prospectively examined for the incidence of MetS and its five components from 1987–88 to 2010–11. Baseline toenail chromium levels were measured with instrumental neutron-activation analysis. Incident MetS was defined by the NCEP-ATP III criteria. During the 23-year follow-up, 878 incident MetS cases were identified. Baseline toenail chromium was inversely associated with incidence of MetS as well as its blood lipid components. The multivariable-adjusted hazard ratio (HR) (95% confidence interval [CI]) of MetS comparing the highest to the lowest quartiles of toenail chromium levels was 0.80 (0.66–0.98; Plinear trend = 0.006). The adjusted HRs were 0.82 (0.68–0.98; Ptrend = 0.045) for having abnormal triglycerides levels and 0.75 (0.64–0.88; Ptrend  = 0.030) for having abnormal HDL cholesterol levels. Toenail chromium levels were inversely and longitudinally associated with incidence of MetS in American young adults. This inverse association was mainly explained by its relation to blood lipids.
Stepwise work hardening induced by individual grain boundary in Cu bicrystal micropillars
Authors: Li L. L. , Zhang Z. J. , Tan J. , Jiang C. B. , Qu R. T. , Zhang P. , Yang J. B. , Zhang Z. F. 
Published: October 2015

AbstractVast experiments have demonstrated that the external specimen size makes a large difference in the deformation behavior of crystalline materials. However, as one important kind of internal planar defects, the role of grain boundary (GB) in small scales needs to be clarified in light of the scarce and inconsistent experimental results at present. Through compression of Cu bicrystal and its counterpart monocrystal micropillars, it is found that, in contrast to the monocrystals, the bicrystals are characterized by work hardening with discrete strain bursts. Interestingly, the stress rise between two adjacent strain bursts of the bicrystals increases with the decrease of specimen size. The results suggest that GBs play a critical role in the work hardening of materials in small scales, which may provide important implications to further understand the general work hardening behaviors of materials in the future.
Evolution of the dense packings of spherotetrahedral particles: from ideal tetrahedra to spheres
Authors: Jin Weiwei , Lu Peng , Li Shuixiang 
Published: October 2015

AbstractParticle shape plays a crucial role in determining packing characteristics. Real particles in nature usually have rounded corners. In this work, we systematically investigate the rounded corner effect on the dense packings of spherotetrahedral particles. The evolution of dense packing structure as the particle shape continuously deforms from a regular tetrahedron to a sphere is investigated, starting both from the regular tetrahedron and the sphere packings. The dimer crystal and the quasicrystal approximant are used as initial configurations, as well as the two densest sphere packing structures. We characterize the evolution of spherotetrahedron packings from the ideal tetrahedron (s = 0) to the sphere (s = 1) via a single roundness parameter s. The evolution can be partitioned into seven regions according to the shape variation of the packing unit cell. Interestingly, a peak of the packing density Φ is first observed at s ≈ 0.16 in the Φ-s curves where the tetrahedra have small rounded corners. The maximum density of the deformed quasicrystal approximant family (Φ ≈ 0.8763) is slightly larger than that of the deformed dimer crystal family (Φ ≈ 0.8704) and both of them exceed the densest known packing of ideal tetrahedra (Φ ≈ 0.8563).
Ultra‐wideband short‐pulse power divider based on coplanar waveguide and slotline structure
Authors: Zhao Hongxin , Yang Mei 
Published: October 2015

An ultra‐wideband (UWB) short‐pulse power divider with a novel structure utilising the coplanar waveguide (CPW) and the slotline transmission line is presented. The novelty of the proposed design can be manifested by that the electromagnetic energy propagates along the two slots of CPW can be naturally divided into the two slotlines of the output ports. The resistors bridging the two slotlines are applied for good isolation and return loss performance. The simulated and measured results for the fabricated prototype present an ultra‐wide frequency band from 0.65 to 7 GHz, where return loss at all the ports and the isolation between output ports are better than 10 dB. The performance of the proposed power divider is also characterised by time‐domain short pulses, which shows that the power divider is featured by very high fidelity and low dispersion for short‐pulse applications.
Quantifying operating reserves with wind power: towards probabilistic–dynamic approaches
Authors: Rahmann Claudia , Heinemann Antonia , Torres Rigoberto 
Published: October 2015

In this study, the economic benefits of using a probabilistic‐dynamic approach (PDA) in the quantification of operating reserves are investigated and compared with more traditional quantification rules in power systems with high penetration levels of wind power. To do this, a comprehensive methodology to quantify different operating reserves categories within the real‐time system operation is proposed. The quantification is based on an iterative process where the total costs of the system are minimised, that is the sum of the operating costs (including the additional costs of partially loading generating units due to operating reserves) and the costs of the expected energy not supplied. The PDA considers conventional generation outages; load and wind forecast uncertainty on an hourly basis as well as load and wind variability in a 10 min time frame. The authors use the Chilean power system to demonstrate the efficiency and advantages of the proposed reserve quantification approach.
Transcriptomic characterization of fibrolamellar hepatocellular carcinoma
Authors: Simon Elana P. , Freije Catherine A. , Farber Benjamin A. , Lalazar Gadi , Darcy David G. , Honeyman Joshua N. , Chiaroni-Clarke Rachel , Dill Brian D. , Molina Henrik , Bhanot Umesh K. , La Quaglia Michael P. , Rosenberg Brad R. , Simon Sanford M. 
Published: October 2015

SignificanceFibrolamellar hepatocellular carcinoma (FLHCC) is a rare pediatric liver cancer. A deletion of ∼400 kb in one copy of chromosome 19 results in a chimeric protein, an activated protein kinase A. No other deletions, amplifications, mutations, or structural variants were found. This strongly implicates the chimera as the driving mutation. This paper examines gene expression in FLHCC. The results establish FLHCC as a single disease distinct from other cancers, including hepatocellular carcinoma. The results help explain some of the known pathophysiology: the collagen fibers that give fibrolamellar its name and the gynecomastia reported in young male patients. Finally, this work identifies oncogenes whose expression is increased and that may serve as targets for therapeutic intervention.
An intrinsic mechanism of secreted protein aging and turnover
Authors: Yang Won Ho , Aziz Peter V. , Heithoff Douglas M. , Mahan Michael J. , Smith Jeffrey W. , Marth Jamey D. 
Published: October 2015

SignificanceIn the blood, secreted proteins have different life spans that determine their abundance and function. Measurements of plasma protein composition and biological activities remain important for many clinical diagnoses. However the molecular mechanisms by which secreted proteins age and turnover have remained unidentified. The findings of this research have established an intrinsic and constitutive mechanism of secreted protein aging and turnover. This mechanism involves multiple factors including circulating glycosidases that progressively remodel the N-glycan linkages attached to most secreted proteins. N-glycan remodeling with time exposes glycan ligands of various endocytic lectin receptors that then eliminate these aged secreted proteins. This mechanism thereby determines the life spans and abundance of secreted proteins, and modulates the pathogenesis and outcomes of disease.
Effects of Water Temperature and Fish Size on Predation Vulnerability of Juvenile Humpback Chub to Rainbow Trout and Brown Trout
Authors: Ward David L. , Morton‐Starner Rylan 
Published: October 2015

AbstractPredation on juvenile native fish by introduced Rainbow Trout and Brown Trout is considered a significant threat to the persistence of endangered Humpback Chub Gila cypha in the Colorado River in the Grand Canyon. Diet studies of Rainbow Trout and Brown Trout in Glen and Grand canyons indicate that these species do eat native fish, but impacts are difficult to assess because predation vulnerability is highly variable, depending on prey size, predator size, and the water temperatures under which the predation interactions take place. We conducted laboratory experiments to evaluate how short‐term predation vulnerability of juvenile native fish changes in response to fish size and water temperature using captivity‐reared Humpback Chub, Bonytail, and Roundtail Chub. Juvenile chub 45–90 mm total length (TL) were exposed to adult Rainbow and Brown trouts at 10, 15, and 20°C to measure predation vulnerability as a function of water temperature and fish size. A 1°C increase in water temperature decreased short‐term predation vulnerability of Humpback Chub to Rainbow Trout by about 5%, although the relationship is not linear. Brown Trout were highly piscivorous in the laboratory at any size > 220 mm TL and at all water temperatures we tested. Understanding the effects of predation by trout on endangered Humpback Chub is critical in evaluating management options aimed at preserving native fishes in Grand Canyon National Park.
Influence of Hydrographic Conditions on the Distribution of Spiny Lobster Larvae off the West Coast of Baja California
Authors: Funes‐Rodríguez René , Ruíz‐Chavarría José A. , González‐Armas Rogelio , Durazo Reginaldo , Guzmán‐del Proó Sergio A. 
Published: October 2015

AbstractThe distribution of phyllosoma of California spiny lobster Panulirus interruptus was investigated in relation to the seasonal variability of hydrographic conditions off the west coast of the Baja California Peninsula between 2006 and 2008. Early larval stages were recorded mostly from summer to fall, immediately following the reproductive period. The duration of larval development in plankton is variable (8–12 months), and hence, larvae are found at different times of the year; thus, intermediate and late stages did not show a well‐defined seasonal pattern. The highest phyllosoma density was associated with the relatively warm transitional water mass. However, the peak frequency of occurrence was observed in the colder subarctic water mass. A canonical correspondence analysis identified two distinct seasonal periods: (1) a warm period (summer–autumn), when the abundance of early and intermediate stages was highly correlated with a higher sea surface temperature, and (2) a cold period (winter–spring), when the most advanced stages were associated with a lower water temperature and higher dissolved oxygen. The distribution of larvae and the geostrophic flow patterns suggest that transport by the California Current and mesoscale eddies are the primary dispersal and retention mechanisms from the various breeding centers along the peninsula: northern (Ensenada–Punta Baja), central (Punta Eugenia), and southern (Golfo de Ulloa). In contrast, the data obtained suggest that the recruitment of late larval stages and pueruli in settlement areas might be regulated by the formation of meanders and poleward currents, in addition to the ability of pueruli (self‐recruitment) to reach settlement areas via swimming.
Hope and the Task of the Self
Authors: Bernier Mark 
Published: October 2015

AbstractThis chapter analyzes the notion of the task, and how this relates to the concept of hope. In the Kierkegaardian sense, a task always pertains to the self, as an attempt to have a meaningful life. Such a task has the following structure: one has a task when one has made one’s highest good one’s highest hope. One has made a total commitment. And just as there are two forms of hope, there are two forms of the task: (1) the central task of the self, which is constituted by a mundane hope for a mundane good; and (2) the authentic task, which is constituted by religious hope for a spiritual good. Communicating these results is one of the primary achievements of the study, since it sheds light on the role and importance of hope for the self—hope is essential to the self, since it constitutes the task.
Hope and the Knight of Faith
Authors: Bernier Mark 
Published: October 2015

AbstractIn this chapter, the second movement of faith is described, and its relation to hope analyzed. The primary example for the knight of faith is Abraham, who accepts the impossibility of keeping Isaac while simultaneously trusting God that Isaac will not be lost. Abraham’s movement is ‘absurd,’ in the sense that he grounds his belief in Isaac’s return on his trust in God, not his own judgment. He entrusts to God his highest good, and relinquishes control. He can only do this if there is a ‘teleological suspension of the ethical,’ which is to suspend his highest mundane good, and with it, his central task, for the sake of the higher spiritual good and the authentic task. Faith thus provides the ground for hope; for the possibility of the good. In trusting God, one is willing to hope, which stands in opposition to despair’s unwillingness to hope.
Transonic Flows
Authors: Ruban Anatoly I. 
Published: October 2015

Abstract
This chapter considers the far field in the two-dimensional flow past an arbitrary body, assuming that M∞ = 1 .The corresponding solution of the Euler equations can be found in a self-similar form. In this solution, the flow, that is subsonic in front of the body, experiences acceleration to become supersonic before it reaches a shock wave which makes it subsonic again downstream of the body. It is then assumed that the body is an aerofoil of a small thickness, and the chapter shows that in this case the Euler equations can be reduced to the Karman–Guderley equation. Though this equation is nonlinear and difficult to solve, it turns into the Tricomi equation if considered in the hodograph plane. The chapter presents two exact solutions of the Tricomi equation: the first describes the transonic flow separation at a corner of a rigid body contour, the second the flow accelerating into the Prandtl–Meyer expansion fan.
Hypersonic Flows
Authors: Ruban Anatoly I. 
Published: October 2015

Abstract
The chapter starts its analysis with blunt-nosed bodies. In a supersonic flow, a blunt-nosed body produces a bow shock wave. The chapter shows that the shape of the shock and the entire flow between the shock and the body become independent of the Mach number, M∞, provided it is large enough. This result is known as the hypersonic stabilization principle. The chapter then presents the Newton–Busemann theory that exploits the fact that hypersonic flow undergoes significant compression in the bow shock. The chapter then turns to flows past thin bodies. These are characterized by the hypersonic interaction parameter, χ = M∞δ. If χ is small, then the Ackeret theory appears applicable. If χ is an order one quantity or large, then the flow can be studied using the so-called unsteady flow analogy. In particular, the effect of a rounded nose on the hypersonic flow past a thin body may be described using analogy with the blast wave.
An algorithm to detect and communicate the differences in computational models describing biological systems
Authors: Scharm Martin , Wolkenhauer Olaf , Waltemath Dagmar 
Published: October 2015

Abstract
Motivation: Repositories support the reuse of models and ensure transparency about results in publications linked to those models. With thousands of models available in repositories, such as the BioModels database or the Physiome Model Repository, a framework to track the differences between models and their versions is essential to compare and combine models. Difference detection not only allows users to study the history of models but also helps in the detection of errors and inconsistencies. Existing repositories lack algorithms to track a model’s development over time.
Results: Focusing on SBML and CellML, we present an algorithm to accurately detect and describe differences between coexisting versions of a model with respect to (i) the models’ encoding, (ii) the structure of biological networks and (iii) mathematical expressions. This algorithm is implemented in a comprehensive and open source library called BiVeS. BiVeS helps to identify and characterize changes in computational models and thereby contributes to the documentation of a model’s history. Our work facilitates the reuse and extension of existing models and supports collaborative modelling. Finally, it contributes to better reproducibility of modelling results and to the challenge of model provenance.
Availability and implementation: The workflow described in this article is implemented in BiVeS. BiVeS is freely available as source code and binary from sems.uni-rostock.de. The web interface BudHat demonstrates the capabilities of BiVeS at budhat.sems.uni-rostock.de.
Contact: martin.scharm@uni-rostock.de
Supplementary information: Supplementary data are available at Bioinformatics online.
Xtalk: a path-based approach for identifying crosstalk between signaling pathways
Authors: Tegge Allison N. , Sharp Nicholas , Murali T. M. 
Published: October 2015

AbstractMotivation: Cells communicate with their environment via signal transduction pathways. On occasion, the activation of one pathway can produce an effect downstream of another pathway, a phenomenon known as crosstalk. Existing computational methods to discover such pathway pairs rely on simple overlap statistics.Results: We present Xtalk, a path-based approach for identifying pairs of pathways that may crosstalk. Xtalk computes the statistical significance of the average length of multiple short paths that connect receptors in one pathway to the transcription factors in another. By design, Xtalk reports the precise interactions and mechanisms that support the identified crosstalk. We applied Xtalk to signaling pathways in the KEGG and NCI-PID databases. We manually curated a gold standard set of 132 crosstalking pathway pairs and a set of 140 pairs that did not crosstalk, for which Xtalk achieved an area under the receiver operator characteristic curve of 0.65, a 12% improvement over the closest competing approach. The area under the receiver operator characteristic curve varied with the pathway, suggesting that crosstalk should be evaluated on a pathway-by-pathway level. We also analyzed an extended set of 658 pathway pairs in KEGG and to a set of more than 7000 pathway pairs in NCI-PID. For the top-ranking pairs, we found substantial support in the literature (81% for KEGG and 78% for NCI-PID). We provide examples of networks computed by Xtalk that accurately recovered known mechanisms of crosstalk.Availability and implementation: The XTALK software is available at http://bioinformatics.cs.vt.edu/~murali/software. Crosstalk networks are available at http://graphspace.org/graphs?tags=2015-bioinformatics-xtalk.Contact: ategge@vt.edu, murali@cs.vt.eduSupplementary information: Supplementary data are available at Bioinformatics online.