bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemical vapor deposition of monolayer MoS2 directly on ultrathin Al2O3 for low-power electronics
Authors: Bergeron Hadallia , Sangwan Vinod K. , McMorrow Julian J. , Campbell Gavin P. , Balla Itamar , Liu Xiaolong , Bedzyk Michael J. , Marks Tobin J. , Hersam Mark C.
Published: January 2017

Monolayer MoS2 has recently been identified as a promising material for high-performance electronics. However, monolayer MoS2 must be integrated with ultrathin high-κ gate dielectrics in order to realize practical low-power devices. In this letter, we report the chemical vapor deposition (CVD) of monolayer MoS2 directly on 20 nm thick Al2O3 grown by atomic layer deposition (ALD). The quality of the resulting MoS2 is characterized by a comprehensive set of microscopic and spectroscopic techniques. Furthermore, a low-temperature (200 °C) Al2O3 ALD process is developed that maintains dielectric integrity following the high-temperature CVD of MoS2 (800 °C). Field-effect transistors (FETs) derived from these MoS2/Al2O3 stacks show minimal hysteresis with a sub-threshold swing as low as ∼220 mV/decade, threshold voltages of ∼2 V, and current ION/IOFF ratio as high as ∼104, where IOFF is defined as the current at zero gate voltage as is customary for determining power consumption in complementary logic circuits. The system presented here concurrently optimizes multiple low-power electronics figures of merit while providing a transfer-free method of integrating monolayer MoS2 with ultrathin high-κ dielectrics, thus enabling a scalable pathway for enhancement-mode FETs for low-power applications.
Conduction electrons as dissipation channel in friction experiments at the metal-metal transition of LSMO measured by contact-resonance atomic force microscopy
Authors: Pfahl V. , Phani M. K. , Büchsenschütz-Göbeler M. , Kumar A. , Moshnyaga V. , Arnold W. , Samwer K.
Published: January 2017

We report on friction measurements on a La0.6Sr0.4MnO3 (LSMO) thin film using atomic force microscopy cantilever contact-resonances. There is a contribution to the damping of the cantilever oscillations, which is caused by micro-sliding of the cantilever tip on the surface of the thin film. This frictional part decreases with temperature parallel to the increase in the resistivity of the thin film. The LSMO is well-known for a ferromagnetic to paramagnetic phase transition that occurs without changes in the rhombohedral (R-3c) crystalline structure. The magnetic transition at the Curie temperature TC ∼ 360 K is accompanied by a metal-to-metal transition with a large increase in electrical resistivity. The behavior of the cantilever damping constant demonstrates that there is a direct coupling between mechanical friction and the mobility of the electrons in the LSMO film.
Enhancement of voltage-controlled magnetic anisotropy through precise control of Mg insertion thickness at CoFeB|MgO interface
Authors: Li Xiang , Fitzell Kevin , Wu Di , Karaba C. Ty , Buditama Abraham , Yu Guoqiang , Wong Kin L. , Altieri Nicholas , Grezes Cecile , Kioussis Nicholas , Tolbert Sarah , Zhang Zongzhi , Chang Jane P. , Khalili Amiri Pedram , Wang Kang L.
Published: January 2017

We studied the impact of different insertion layers (Ta, Pt, and Mg) at the CoFeB|MgO interface on voltage-controlled magnetic anisotropy (VCMA) effect and other magnetic properties. Inserting a very thin Mg layer of 0.1–0.3 nm yielded a VCMA coefficient of 100 fJ/V-m, more than 3 times higher than the average values of around 30 fJ/V-m reported in Ta|CoFeB|MgO-based structures. Ta and Pt insertion layers also showed a small improvement, yielding VCMA coefficients around 40 fJ/V-m. Electrical, magnetic, and X-ray diffraction results reveal that a Mg insertion layer of around 1.2 nm gives rise to the highest perpendicular magnetic anisotropy, saturation magnetization, as well as the best CoFe and MgO crystallinity. Other Mg insertion thicknesses give rise to either under- or over-oxidation of the CoFe|MgO interface; a strong over-oxidation of the CoFe layer leads to the maximum VCMA effect. These results show that precise control over the Mg insertion thickness and CoFe oxidation level at the CoFeB|MgO interface is crucial for the development of electric-field-controlled perpendicular magnetic tunnel junctions with low write voltage.
Single laser modulated drive and detection of a nano-optomechanical cantilever
Authors: Sauer Vincent T. K. , Diao Zhu , Westwood-Bachman Jocelyn N. , Freeman Mark R. , Hiebert Wayne K.
Published: January 2017

To reduce the complexity in a nano-optomechanical system a pump and probe scheme using only a single input laser is used to both coherently pump and probe the nanomechanical device. The system operates similarly to the traditional two laser system, but instead of using a constant power to probe the device and a separate, modulated laser to drive it with an optical gradient force, a single laser is utilized for both functions. A model of the measurement scheme’s response is developed which matches the experimental data obtained in the optomechanical Doppler regime and low cavity power limit. As such, the unconventional response still yields useful device information such as the resonant frequency of the device and its mechanical quality factor. The device is driven with low noise and its frequency is tracked using a phase-locked loop. This demonstrates its potential use for dynamic frequency measurements such as nanomechanical inertial mass loading. In such a system, the estimated mass resolution of the device is 6 zg and consistent with other detection methods.
Protection of α-amylase from proteolysis by adsorption to feed components in vitro and in the porcine small intestine
Authors: Pluschke Anton M. , Jochems Paulus G. M. , Williams Barbara A. , Gidley Michael J.
Published: January 2017

The interactions between digestive enzymes and non-substrate feed components, and the impacts these have on enzyme activity, have rarely been studied. The aim of the present study was to determine the ability of granular wheat starch and whole porcine diets to protect porcine pancreatic α-amylase from proteolysis by trypsin both in vitro and in vivo. Granular wheat starch protected α-amylase from degradation in vitro by adsorbing trypsin and reducing its proteolytic activity. This protection was also found for a complete pig diet and corresponded to undetectable soluble-trypsin activity in the presence of the diet. Pancreatic α-amylase from small intestinal digesta of pigs was active from the duodenum to the ileum (~200–330 U/mL) irrespective of the addition of a protease inhibitor immediately after sampling, most likely due to binding with other food components protecting it from proteolysis. We conclude that non-specific binding between pancreatic digestive enzymes and food components may be competitive with enzyme–substrate complex formation, and therefore important in determining differences in the rate of digestion of macronutrients along the small intestine.
Trapped in a moral order
Authors: Patiño-Santos Adriana
Published: January 2017

This paper focuses on the forms of reflexivity that emerge in the conversational narratives of Latin American teenage school girls co-produced during sociolinguistic interviews, in a multicultural school in the centre of Madrid. The narratives about confrontation at school portray the girls’ actions and ways of making sense of such behaviours, in the course of their migrant life trajectories. Understanding narratives as communicative repertoires (Rymes 2014) of an interactive and situated nature makes them suitable discursive spaces for revealing the moral identity constructed, and the moral order evoked in these narratives. Herein we analyse stories recounting conflicts with three different groups of opponents: female peers, teachers and parents. It is in recounting and evaluating moments of conflict that social actors call upon their systems of beliefs and values. The failure of the girls’ secondary school and all the negative repercussions of such failure are central to the ethnographic circumstances in which their narratives are produced. Some attention will be given to the researcher’s reflexivity, as a co-teller of the narratives gathered, but also in the interpretations made of the data in the light of expectations built up over time regarding the social actors’ academic trajectories.
Research meets practice
Authors: Han ZhaoHong
Published: January 2017

At the recent CLTA-S2 conference, a spirited debate occurred between critics of second language acquisition (SLA) research and researchers who embraced it. Fascinating as it was, neither camp appeared to have convinced the other, but, more important, the debate left much of the audience flummoxed. In this paper, I intend to provide a follow-up, attempting to clarify a) the relationship between research and teaching in the context of Chinese as a second language (CSL), b) misunderstandings on the part of critics over research findings, and c) potential pitfalls in interpreting the SLA literature. My goal is to encourage, as well as contribute to, further communication between the two camps, for the ultimate good of CSL instruction and learning.
Examining rating criteria used to assess U.S. college students’ Chinese oral performance
Authors: Chen Guangyan
Published: January 2017

This study empirically examines the rating criteria used to assess U.S. college students’ CSL (Chinese as a Second Language) oral performance by analyzing teachers’ assessment of these performances at different proficiency levels. The researcher videotaped ten speeches, and three ACTFL-trained raters assessed oral performance in these samples. The researcher then selected three samples (Samples 1, 2, and 3) to represent Novice High, Intermediate High, and Advanced Low levels. The researcher developed 20 rating items through interviewing ten experienced CSL teachers and running an Exploratory Factor Analysis (EFA) on teachers’ assessments of speech samples. After that, 104 CSL teachers used these rating items to assess the aforementioned samples. The EFAs of teachers’ assessments led to three corresponding rating criteria models (Models 1, 2, and 3). Both Models 2 and 3 for Samples 2 and 3, respectively, were five-criterion models, consisting of fluency, conceptual understanding, content richness, communication appropriateness, and communication clarity. Model 1 for Sample 1 was a four-criterion model, in which the items in communication appropriateness and content richness showed high correlations, and therefore were merged into one category; the other three criteria remained the same. Comparisons of the three models demonstrated that the criteria were constant. The ANOVAs showed that the proficiency levels of these oral performances differed significantly across all five rating criteria. This study empirically supports CSL teachers’ use of constant rating criteria to assess different levels of oral performance. It also provides Chinese teachers with rating criteria they can use to assess U.S. college students’ CSL oral performance.
“Today I know, we know, that these sacrifices are heavy, but necessary”
Authors: Polymeneas George
Published: January 2017

This study attempts an analysis of political discourse during the current Greek debt crisis at the beginning of 2010, when the size of the debt became apparent. It draws upon both the critical discourse analysis tradition and corpus linguistics in order to examine the relationship between discourse and group “knowledge” in speeches of the then Prime Minister, George Papandreou, and the Minister of Finance, George Papakonstantinou. It is argued that political knowledge on the crisis is a matter of “truth” between contesting political groups. The Greek government talked and wrote about the crisis so as to establish their “truth”, by transforming their beliefs and interpretations on how the crisis can be converted into knowledge.
Golden Dawn in the media during the Greek crisis
Authors: Mouka Effie , Saridakis Ioannis E.
Published: January 2017

This is a corpus-driven study of the perception of Golden Dawn and its discourse by the Greek and European mainstream Press. More specifically, we examine the main traits attributed to Golden Dawn by eleven Greek and European newspapers, the causes to which its rise is linked, expecially with respect to the current crisis, and the suggested ways of addressing the phenomenon. Key lexemes are analysed and their co-articulation into meaningful discourse units is critically and contrastively discussed in the journalistic corpus. Overall, the study attempts to address the question of how the traits and political aims of Golden Dawn, as well as its discourse, are perceived by society through media.
Making sense of the Greek crisis
Authors: Goutsos Dionysis , Hatzidaki Ourania
Published: January 2017

The epilogue to this volume summarizes its relevance and contribution as far as the synergy between critical discourse analysis and corpus linguistics is concerned. It further discusses the issue of quantification, which seems to be the critical parameter in this synergy, and proposes the concept of discourse-driven quantification to complement the conventional corpus-driven quantification usually followed in corpus studies. Finally, it draws several conclusions on the basis of the individual chapters of the volume, which mainly concern the importance of genre as well as the viewpoint of various agents (discourse producers and receivers) as to how the Greek crisis is construed in diverse kinds of texts.
Grounds and ‘Grounds’
Authors: Rettler Bradley
Published: January 2017

In this paper, I offer a new theory of grounding. The theory has is that grounding is a job description that is realized by different properties in different contexts. Those properties play the grounding role contingently, and grounding is the property that plays the grounding role essentially. On this theory, grounding is monistic, but ‘grounding’ refers to different relations in different contexts. First, I argue against Kit Fine’s monist univocalism. Next, I argue against Jessica Wilson’s pluralist multivocalism. Finally, I introduce monist multivocalism, explicate three versions of it, and show its advantages.
Electrodeposition of multilayer Ni–W and Ni–W–alumina nanocomposite coatings
Authors: Allahyarzadeh M. , Aliofkhazraei M. , Rouhaghdam A. S. , Torabinejad V.
Published: January 2017

Multilayer Ni–W and Ni–W–Al2O3 coatings with intermittent low and high concentrations of tungsten and alumina were electrodeposited through alternative variation of pulse parameters. Microstructural studies and elemental analyses of the coatings were carried out using scanning electron microscopy and energy dispersive X-ray spectroscopy, respectively. Profilometry and atomic force microscopy were employed to investigate the surface roughness at two different scales. Pin-on-disc wear test was used to evaluate the tribological properties. The corrosion resistance was also studied using potentiodynamic polarisation and electrochemical impedance spectroscopy methods. Results revealed that at lower duty cycles, more incorporation of alumina and more co-deposition of tungsten are achieved. Results indicated variable and alternative microhardness values corresponding to the different concentrations of tungsten and alumina in each specific layers. Wear tests demonstrated the descending trend of the wear rate as a function of sliding distance. It was found that alumina nanoparticles enhanced the corrosion resistance.

GRAPHICAL ABSTRACT
A question of faith? Islamists and secularists fight over the post-Mubarak state
Authors: Utvik Bjørn Olav
Published: January 2017

Since the military coup of July 3, 2013, guns and batons have, broadly speaking, taken the place of open debate and elections in deciding the political future of Egypt. How can the political struggle be understood with regard to the shape and content of the reformed post-Mubarak state that took place during the period of relative free debate and of tentative steps towards a democratic system between February 11, 2011 and July 3, 2013. In light of the deepening polarization between the Muslim Brothers and the more secular political tendencies that characterized the period, the conflict is often portrayed by the media and by some researchers as between a project of Islamization and a secularist agenda. To what extent does this hold true? In this article I will argue (1) that what took place was rather a power struggle involving competing elites as well as what is sometimes termed the ‘deep state’, i.e., the entrenched power holders from Mubarak’s time, especially in the military, the police and the judiciary; and (2) to the extent that secularization was at stake, in some important aspects Islamists turned out to be, if anything, more secularizing than their secularist competitors. What follows is nothing near a full treatment of the transitional period. Neither is it a formal study of constitutional issues, although it does dwell on some important aspects of the new constitution finalized in 2012. The primary interest here is what the struggle over the new constitution, and more broadly over the path to be followed in the transition process, can tell us about the main forces at work at the heart of the intense political conflict that developed.
Suppression of lethal autoimmunity by regulatory T cells with a single TCR specificity
Authors: Levine Andrew G. , Hemmers Saskia , Baptista Antonio P. , Schizas Michail , Faire Mehlika B. , Moltedo Bruno , Konopacki Catherine , Schmidt-Supprian Marc , Germain Ronald N. , Treuting Piper M. , Rudensky Alexander Y.
Published: January 2017

The regulatory T cell (T reg cell) T cell receptor (TCR) repertoire is highly diverse and skewed toward recognition of self-antigens. TCR expression by T reg cells is continuously required for maintenance of immune tolerance and for a major part of their characteristic gene expression signature; however, it remains unknown to what degree diverse TCR-mediated interactions with cognate self-antigens are required for these processes. In this study, by experimentally switching the T reg cell TCR repertoire to a single T reg cell TCR, we demonstrate that T reg cell function and gene expression can be partially uncoupled from TCR diversity. An induced switch of the T reg cell TCR repertoire to a random repertoire also preserved, albeit to a limited degree, the ability to suppress lymphadenopathy and T helper cell type 2 activation. At the same time, these perturbations of the T reg cell TCR repertoire led to marked immune cell activation, tissue inflammation, and an ultimately severe autoimmunity, indicating the importance of diversity and specificity for optimal T reg cell function.
The discovery of the prokaryotic cytoskeleton: 25th anniversary
Authors: Erickson Harold P.
Published: January 2017

The year 2017 marks the 25th anniversary of the discovery of homologues of tubulin and actin in prokaryotes. Before 1992, it was largely accepted that tubulin and actin were unique to eukaryotes. Then three laboratories independently discovered that FtsZ, a protein already known as a key player in bacterial cytokinesis, had the “tubulin signature sequence” present in all α-, β-, and γ-tubulins. That same year, three candidates for bacterial actins were discovered in silico. X-ray crystal structures have since confirmed multiple bacterial proteins to be homologues of eukaryotic tubulin and actin. Tubulin and actin were apparently derived from bacterial precursors that had already evolved a wide range of cytoskeletal functions.
The Impact of Broadband on U.S. Agriculture: An Evaluation of the USDA Broadband Loan Program
Authors: Kandilov Amy M.G. , Kandilov Ivan T. , Liu Xiangping , Renkow Mitch
Published: January 2017

We evaluate the impact that the USDA’s low‐cost broadband loan programs have on the U.S. agricultural sector. The broadband loan programs increase access to high‐speed Internet in recipient communities, which can raise farm sales by increasing both farm output and prices received by producers. Further, high‐speed Internet may drive down costs by providing information on cheaper inputs and better management practices, leading to an overall improvement in farm profits. Using U.S. county‐level data on farm sales and expenditures in 2000 and 2007, we employ an inverse probability weighting technique to control for endogenous selection in an econometric model that also accounts for spatial dependence. We find that the two USDA broadband loan programs have had positive causal impacts on farm sales, expenditures, and profits in a subset of rural counties—those adjacent to metropolitan counties—but not in other types of counties.
Addressing Participant Inattention in Federal Programs: A Field Experiment with the Conservation Reserve Program
Authors: Wallander Steven , Ferraro Paul , Higgins Nathaniel
Published: January 2017

Voluntary land conservation programs depend upon the willingness of land owners to participate. Since participation requires commitment to long‐term contracts, most studies on participation focus on changes to the pecuniary incentives facing land owners. This study presents a large‐scale field experiment within the USDA's Conservation Reserve Program (CRP) that examines whether informational outreach, including behavioral nudges, could improve land owners’ willingness to participate. The experiment evaluates the impact of three types of reminder letters on the rate at which land is offered into the CRP. We find that for the most well‐informed group, farms with expiring CRP contracts, the reminder letters did improve participation. We interpret this result as evidence of inattentive behavior. We do not detect any differences in the estimated treatment effects among the basic reminder letter and the letters augmented with peer comparisons and social norm messaging, nor do we detect any treatment effect among currently unenrolled farms. From a policy perspective, these results imply that the USDA can generate additional CRP offers among farms with expiring contracts at an average cost of $39 per additional offer. Assuming a twenty‐five million acre program, reminder letters sent during every sign‐up period would result in re‐enrollment offers from an additional 420,000 acres. Using simulations based on offers from prior CRP sign‐ups, we estimate that these additional offers in the CRP auction would reduce program costs. Depending on the year of simulation, the outreach effort achieves a benefit‐cost ratio of between 20:1 and 90:1.
Tools for the Precision Medicine Era: How to Develop Highly Personalized
Treatment Recommendations From Cohort and Registry Data Using Q-Learning
Authors: Krakow Elizabeth F , Hemmer Michael , Wang Tao , Logan Brent , Arora Mukta , Spellman Stephen , Couriel Daniel , Alousi Amin , Pidala Joseph , Last Michael , Lachance Silvy , Moodie Erica E M
Published: January 2017

Q-learning is a method of reinforcement learning that employs backwards stagewise estimation to identify sequences of actions that maximize some long-term reward. The method can be applied to sequential multiple-assignment randomized trials to develop personalized adaptive treatment strategies (ATSs)—longitudinal practice guidelines highly tailored to time-varying attributes of individual patients. Sometimes, the basis for choosing which ATSs to include in a sequential multiple-assignment randomized trial (or randomized controlled trial) may be inadequate. Nonrandomized data sources may inform the initial design of ATSs, which could later be prospectively validated. In this paper, we illustrate challenges involved in using nonrandomized data for this purpose with a case study from the Center for International Blood and Marrow Transplant Research registry (1995–2007) aimed at 1) determining whether the sequence of therapeutic classes used in graft-versus-host disease prophylaxis and in refractory graft-versus-host disease is associated with improved survival and 2) identifying donor and patient factors with which to guide individualized immunosuppressant selections over time. We discuss how to communicate the potential benefit derived from following an ATS at the population and subgroup levels and how to evaluate its robustness to modeling assumptions. This worked example may serve as a model for developing ATSs from registries and cohorts in oncology and other fields requiring sequential treatment decisions.
Recent Advances in Immunity and Hypertension
Authors: Lopez Gelston Catalina A. , Mitchell Brett M.
Published: January 2017

Persistent immune system activation plays an important role in the development of various forms of hypertension. Activation of the innate immune system, inflammation, and subsequent adaptive immune system response causing end-organ injury and dysfunction ultimately leads to hypertension and its associated sequelae including coronary artery disease, heart failure, stroke, and chronic kidney disease. In this review, we will provide updates on the innate and adaptive immune cells involved in hypertension, the current understanding of how the immune system gets activated, and examine the recently discovered mechanisms involved in several forms of experimental hypertension.
Correlated mutations select misfolded from properly folded proteins
Authors: Wozniak P P , Vriend G , Kotulska M
Published: January 2017

Motivation

The recently developed direct coupling analysis (DCA) method has greatly improved the accuracy with which residue–residue contacts can be predicted from multiple sequence alignments. Contact prediction accuracy, though, is still often not sufficient for complete ab initio protein structure prediction. DCA can, however, support protein structure studies in several ways.

Results

We show that DCA can select the better structure from among properly folded and misfolded variants. This idea was tested by comparing obsolete PDB files with their more correctly folded successors and by the comparison of structures with deliberately misfolded decoy models from the Decoys ′R′ Us database. The DCA method systematically predicts more contacts for properly folded structures than for misfolded ones. The method works much better for X-ray structures than for NMR structures.

Availability and Implementation

All data are available from http://comprec-lin.iiar.pwr.edu.pl/dcaVSmisfolds/ and http://swift.cmbi.ru.nl/dcaVSmisfolds/.

Supplementary information

Supplementary data are available at Bioinformatics online.
annoPeak: a web application to annotate and visualize peaks from ChIP-seq/ChIP-exo-seq
Authors: Tang Xing , Srivastava Arunima , Liu Huayang , Machiraju Raghu , Huang Kun , Leone Gustavo
Published: January 2017

We developed annoPeak, a web application to annotate, visualize and compare predicted protein-binding regions derived from ChIP-seq/ChIP-exo-seq experiments using human and mouse cells. Users can upload peak regions from multiple experiments onto the annoPeak server to annotate them with biological context, identify associated target genes and categorize binding sites with respect to gene structure. Users can also compare multiple binding profiles intuitively with the help of visualization tools and tables provided by annoPeak. In general, annoPeak will help users identify patterns of genome wide transcription factor binding profiles, assess binding profiles in different biological contexts and generate new hypotheses.

Availability and Implementation

The web service is freely accessible through URL: https://apps.medgen.iupui.edu/rsc/content/19/. Source code is available at https://github.com/XingTang2014/annoPeak.

Supplementary information

Supplementary data are available at Bioinformatics online.
HIPred: an integrative approach to predicting haploinsufficient genes
Authors: Shihab Hashem A , Rogers Mark F , Campbell Colin , Gaunt Tom R
Published: January 2017

Motivation

A major cause of autosomal dominant disease is haploinsufficiency, whereby a single copy of a gene is not sufficient to maintain the normal function of the gene. A large proportion of existing methods for predicting haploinsufficiency incorporate biological networks, e.g. protein-protein interaction networks that have recently been shown to introduce study bias. As a result, these methods tend to perform best on well-studied genes, but underperform on less studied genes. The advent of large genome sequencing consortia, such as the 1000 genomes project, NHLBI Exome Sequencing Project and the Exome Aggregation Consortium creates an urgent need for unbiased haploinsufficiency prediction methods.

Results

Here, we describe a machine learning approach, called HIPred, that integrates genomic and evolutionary information from ENSEMBL, with functional annotations from the Encyclopaedia of DNA Elements consortium and the NIH Roadmap Epigenomics Project to predict haploinsufficiency, without the study bias described earlier. We benchmark HIPred using several datasets and show that our unbiased method performs as well as, and in most cases, outperforms existing biased algorithms.

Availability and Implementation

HIPred scores for all gene identifiers are available at: https://github.com/HAShihab/HIPred.

Supplementary information

Supplementary data are available at Bioinformatics online.
Dscam1 web server: online prediction of Dscam1 self- and hetero-affinity
Authors: Marini Simone , Nazzicari Nelson , Biscarini Filippo , Wang Guang-Zhong
Published: January 2017

Motivation

Formation of homodimers by identical Dscam1 protein isomers on cell surface is the key factor for the self-avoidance of growing neurites. Dscam1 immense diversity has a critical role in the formation of arthropod neuronal circuit, showing unique evolutionary properties when compared to other cell surface proteins. Experimental measures are available for 89 self-binding and 1722 hetero-binding protein samples, out of more than 19 thousands (self-binding) and 350 millions (hetero-binding) possible isomer combinations.

Results

We developed Dscam1 Web Server to quickly predict Dscam1 self- and hetero- binding affinity for batches of Dscam1 isomers. The server can help the study of Dscam1 affinity and help researchers navigate through the tens of millions of possible isomer combinations to isolate the strong-binding ones.

Availability and Implementation

Dscam1 Web Server is freely available at: http://bioinformatics.tecnoparco.org/Dscam1-webserver. Web server code is available at https://gitlab.com/ne1s0n/Dscam1-binding.

Supplementary information

Supplementary data are available at Bioinformatics online.
FIT: statistical modeling tool for transcriptome dynamics under fluctuating field conditions
Authors: Iwayama Koji , Aisaka Yuri , Kutsuna Natsumaro , Nagano Atsushi J
Published: January 2017

Motivation

Considerable attention has been given to the quantification of environmental effects on organisms. In natural conditions, environmental factors are continuously changing in a complex manner. To reveal the effects of such environmental variations on organisms, transcriptome data in field environments have been collected and analyzed. Nagano et al. proposed a model that describes the relationship between transcriptomic variation and environmental conditions and demonstrated the capability to predict transcriptome variation in rice plants. However, the computational cost of parameter optimization has prevented its wide application.

Results

We propose a new statistical model and efficient parameter optimization based on the previous study. We developed and released FIT, an R package that offers functions for parameter optimization and transcriptome prediction. The proposed method achieves comparable or better prediction performance within a shorter computational time than the previous method. The package will facilitate the study of the environmental effects on transcriptomic variation in field conditions.

Availability and Implementation

Freely available from CRAN (https://cran.r-project.org/web/packages/FIT/).

Supplementary information

Supplementary data are available at Bioinformatics online
CHRR: coordinate hit-and-run with rounding for uniform sampling of constraint-based models
Authors: Haraldsdóttir Hulda S , Cousins Ben , Thiele Ines , Fleming Ronan M.T , Vempala Santosh
Published: January 2017

In constraint-based metabolic modelling, physical and biochemical constraints define a polyhedral convex set of feasible flux vectors. Uniform sampling of this set provides an unbiased characterization of the metabolic capabilities of a biochemical network. However, reliable uniform sampling of genome-scale biochemical networks is challenging due to their high dimensionality and inherent anisotropy. Here, we present an implementation of a new sampling algorithm, coordinate hit-and-run with rounding (CHRR). This algorithm is based on the provably efficient hit-and-run random walk and crucially uses a preprocessing step to round the anisotropic flux set. CHRR provably converges to a uniform stationary sampling distribution. We apply it to metabolic networks of increasing dimensionality. We show that it converges several times faster than a popular artificial centering hit-and-run algorithm, enabling reliable and tractable sampling of genome-scale biochemical networks.

Availability and Implementation

https://github.com/opencobra/cobratoolbox.

Supplementary information

Supplementary data are available at Bioinformatics online.
Efficient computation of transfer free energies of amino acids in beta-barrel membrane proteins
Authors: Tian Wei , Lin Meishan , Naveed Hammad , Liang Jie
Published: January 2017

Motivation

Transmembrane beta-barrel proteins (TMBs) serve a multitude of essential cellular functions in Gram-negative bacteria, mitochondria and chloroplasts. Transfer free energies (TFEs) of residues in the transmembrane (TM) region provides fundamental quantifications of thermodynamic stabilities of TMBs, which are important for the folding and the membrane insertion processes, and may help in understanding the structure–function relationship. However, experimental measurement of TFEs of TMBs is challenging. Although a recent computational method can be used to calculate TFEs, the results of which are in excellent agreement with experimentally measured values, this method does not scale up, and is limited to small TMBs.

Results

We have developed an approximation method that calculates TFEs of TM residues in TMBs accurately, with which depth-dependent transfer free energy profiles can be derived. Our results are in excellent agreement with experimental measurements. This method is efficient and applicable to all bacterial TMBs regardless of the size of the protein.

Availability and Implementation

An online webserver is available at http://tanto.bioe.uic.edu/tmb-tfe.

Supplementary information

Supplementary data are available at Bioinformatics online.
Assessment of phagocytic activity in live macrophages-tumor cells co-cultures by Confocal and Nomarski Microscopy
Authors: Martinez-Marin Dalia , Jarvis Courtney , Nelius Thomas , Filleur Stéphanie
Published: January 2017

Macrophages have been recognized as the main inflammatory component of the tumor microenvironment. Although often considered as beneficial for tumor growth and disease progression, tumor-associated macrophages have also been shown to be detrimental to the tumor depending on the tumor microenvironment. Therefore, understanding the molecular interactions between macrophages and tumor cells in relation to macrophages functional activities such as phagocytosis is critical for a better comprehension of their tumor-modulating action. Still, the characterization of these molecular mechanisms in vivo remains complicated due to the extraordinary complexity of the tumor microenvironment and the broad range of tumor-associated macrophage functions. Thus, there is an increasing demand for in vitro methodologies to study the role of cell–cell interactions in the tumor microenvironment. In the present study, we have developed live co-cultures of macrophages and human prostate tumor cells to assess the phagocytic activity of macrophages using a combination of Confocal and Nomarski Microscopy. Using this model, we have emphasized that this is a sensitive, measurable, and highly reproducible functional assay. We have also highlighted that this assay can be applied to multiple cancer cell types and used as a selection tool for a variety of different types of phagocytosis agonists. Finally, combining with other studies such as gain/loss of function or signaling studies remains possible. A better understanding of the interactions between tumor cells and macrophages may lead to the identification of new therapeutic targets against cancer.
Performance of hospitals according to the ESC ACCA quality indicators and 30-day mortality for acute myocardial infarction: national cohort study using the United Kingdom Myocardial Ischaemia National Audit Project (MINAP) register
Authors: Bebb Owen , Hall Marlous , Fox Keith A. A. , Dondo Tatendashe B. , Timmis Adam , Bueno Hector , Schiele François , Gale Chris P.
Published: January 2017

Aims

To investigate the application of the European Society of Cardiology Acute Cardiovascular Care Association quality indicators (QI) for acute myocardial infarction for the study of hospital performance and 30-day mortality.

Methods and results

National cohort study (n = 118,075 patients, n = 211 hospitals, MINAP registry), 2012-13. Overall, 16 of the 20 QIs could be calculated. Eleven QIs had a significant inverse association with GRACE risk adjusted 30-day mortality (all P < 0.005). The association with the greatest magnitude was high attainment of the composite opportunity-based QI (80-100%) vs. zero attainment (odds ratio 0.04, 95% confidence interval 0.04-0.05, P < 0.001), increasing attainment from low (0.42, 0.37- 0.49, P < 0.001) to intermediate (0.15, 0.13-0.16, P < 0.001) was significantly associated with a reduced risk of 30-day mortality. A 1% increase in attainment of this QI was associated with a 3% reduction in 30-day mortality (0.97, 0.97-0.97, P < 0.001). The QI with the widest hospital variation was ′fondaparinux received among NSTEMI′ (interquartile range 84.7%) and least variation ′centre organisation′ (0.0%), with seven QIs depicting minimal variation (<11%). GRACE risk score adjusted 30-day mortality varied by hospital (median 6.7%, interquartile range 5.4-7.9%).

Conclusions

Eleven QIs were significantly inversely associated with 30-day mortality. Increasing patient attainment of the composite quality indicator was the most powerful predictor; a 1% increase in attainment represented a 3% decrease in 30-day standardised mortality. The ESC QIs for acute myocardial infarction are applicable in a large health system and have the potential to improve care and reduce unwarranted variation in death from acute myocardial infarction.
Sex hormones affect outcome in arrhythmogenic right ventricular cardiomyopathy/dysplasia: from a stem cell derived cardiomyocyte-based model to clinical biomarkers of disease outcome
Authors: Akdis Deniz , Saguner Ardan M. , Shah Khooshbu , Wei Chuanyu , Medeiros-Domingo Argelia , von Eckardstein Arnold , Lüscher Thomas F. , Brunckhorst Corinna , Chen H.S. Vincent , Duru Firat
Published: January 2017

Aims

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is characterized by fibrofatty infiltration of the myocardium and ventricular arrhythmias that may lead to sudden cardiac death. It has been observed that male patients develop the disease earlier and present with more severe phenotypes as compared to females. Thus, we hypothesized that serum levels of sex hormones may contribute to major arrhythmic cardiovascular events (MACE) in patients with ARVC/D.

Methods and results

The serum levels of five sex hormones, sex hormone-binding globulin, high sensitivity troponin T, pro-brain natriuretic peptide, cholesterol, triglycerides, insulin, and glucose were measured in 54 ARVC/D patients (72% male). Twenty-six patients (48%) experienced MACE. Total and free testosterone levels were significantly increased in males with MACE as compared to males with a favourable outcome, whereas estradiol was significantly lower in females with MACE as compared to females with a favourable outcome. Increased testosterone levels remained independently associated with MACE in males after adjusting for age, body mass index, Task Force criteria, ventricular function, and desmosomal mutation status. Furthermore, an induced pluripotent stem cell-derived ARVC/D cardiomyocyte model was used to investigate the effects of sex hormones. In this model, testosterone worsened and estradiol improved ARVC/D-related pathologies such as cardiomyocyte apoptosis and lipogenesis, strongly supporting our clinical findings.

Conclusions

Elevated serum testosterone levels in males and decreased estradiol levels in females are independently associated with MACE in ARVC/D, and directly influence disease pathology. Therefore, determining the levels of sex hormones may be useful for risk stratification and may open a new window for preventive interventions.
Determinants and clinical outcome of uptitration of ACE-inhibitors and beta-blockers in patients with heart failure: a prospective European study
Authors: Ouwerkerk W. , Voors A.A. , Anker S.D. , Cleland J.G. , Dickstein K. , Filippatos G. , van der Harst P. , Hillege H.L. , Lang C.C. , ter Maaten J.M. , Ng L.L. , Ponikowski P. , Samani N.J , van Veldhuisen D.J. , Zannad F. , Metra M. , Zwinderman A.H.
Published: January 2017

Introduction

Despite clear guidelines recommendations, most patients with heart failure and reduced ejection–fraction (HFrEF) do not attain guideline-recommended target doses. We aimed to investigate characteristics and for treatment-indication-bias corrected clinical outcome of patients with HFrEF that did not reach recommended treatment doses of ACE-inhibitors/Angiotensin receptor blockers (ARBs) and/or beta-blockers.

Methods and results

BIOSTAT-CHF was specifically designed to study uptitration of ACE-inhibitors/ARBs and/or beta-blockers in 2516 heart failure patients from 69 centres in 11 European countries who were selected if they were suboptimally treated while initiation or uptitration was anticipated and encouraged. Patients who died during the uptitration period (n = 151) and patients with a LVEF > 40% (n = 242) were excluded. Median follow up was 21 months. We studied 2100 HFrEF patients (76% male; mean age 68 ±12), of which 22% achieved the recommended treatment dose for ACE-inhibitor/ARB and 12% of beta-blocker. There were marked differences between European countries. Reaching <50% of the recommended ACE-inhibitor/ARB and beta-blocker dose was associated with an increased risk of death and/or heart failure hospitalization. Patients reaching 50–99% of the recommended ACE-inhibitor/ARB and/or beta-blocker dose had comparable risk of death and/or heart failure hospitalization to those reaching ≥100%. Patients not reaching recommended dose because of symptoms, side effects and non-cardiac organ dysfunction had the highest mortality rate (for ACE-inhibitor/ARB: HR 1.72; 95% CI 1.43–2.01; for beta-blocker: HR 1.70; 95% CI 1.36–2.05).

Conclusion

Patients with HFrEF who were treated with less than 50% of recommended dose of ACE-inhibitors/ARBs and beta-blockers seemed to have a greater risk of death and/or heart failure hospitalization compared with patients reaching ≥100%.
Renal sodium avidity in heart failure: from pathophysiology to treatment strategies
Authors: Mullens Wilfried , Verbrugge Frederik Hendrik , Nijst Petra , Tang Wai Hong Wilson
Published: January 2017

Increased neurohumoral stimulation resulting in excessive sodium avidity and extracellular volume overload are hallmark features of decompensated heart failure. Especially in case of concomitant renal dysfunction, the kidneys often fail to elicit effective natriuresis. While assessment of renal function is generally performed by measuring serum creatinine–a surrogate for glomerular filtration-, this only represents part of the nephron’s function. Alterations in tubular sodium handling are at least equally important in the development of volume overload and congestion. Venous congestion and neurohumoral activation in advanced HF further promote renal sodium and water retention. Interestingly, early on, before clinical signs of heart failure are evident, intrinsic renal derangements already impair natriuresis. This clinical review discusses the importance of heart failure (HF) induced changes in different nephron segments. A better understanding of cardiorenal interactions which ultimately result in sodium avidity in HF might help to treat and prevent congestion in chronic and acute HF.
Duration of device-detected subclinical atrial fibrillation and occurrence of stroke in ASSERT
Authors: Van Gelder Isabelle C. , Healey Jeff S. , Crijns Harry J.G.M. , Wang Jia , Hohnloser Stefan H. , Gold Michael R. , Capucci Alessandro , Lau Chu-Pak , Morillo Carlos A. , Hobbelt Anne H. , Rienstra Michiel , Connolly Stuart J.
Published: January 2017

Background

ASSERT demonstrated that subclinical atrial fibrillation (SCAF) is common in pacemaker patients without prior AF and is associated with increased risk of ischemic stroke or systemic embolism. SCAF episodes vary in duration and little is known about the incidence of different durations of SCAF, or their prognosis.

Methods and results

ASSERT followed 2580 patients receiving a pacemaker or ICD, aged >65 years with hypertension, without prior AF. The effect of SCAF duration on subsequent risk of ischemic stroke or embolism was evaluated with time-dependent covariate Cox models. Patients in whom the longest SCAF was ≤6 min were excluded from the analysis (n=125). Among 2455 patients during mean follow-up of 2.5 years, the longest single episode of SCAF lasted >6 min to 6 h in 462 patients (18.8%), >6–24 h in 169 (6.9%), and >24 h in 262 (10.7%). SCAF duration >24 h was associated with a significant increased risk of subsequent stroke or systemic embolism (adjusted hazard ratio [HR] 3.24, 95% confidence interval [CI] 1.51–6.95, P=0.003). The risk of ischemic stroke or systemic embolism in patients with SCAF between 6 min and 24 h was not significantly different from patients without SCAF.

Conclusions

SCAF >24 h is associated with an increased risk of ischemic stroke or systemic embolism.
Une mémoire critique de la Fronde: formes et fonctions du pastiche dans les Mémoires apocryphes de Courtilz de Sandras
Authors: Tribout Bruno
Published: January 2017

Si la mémoire de la Fronde (1648
–
53) n’a pas fait l’objet d’une étude systématique, la critique s’est néanmoins beaucoup intéressée à la représentation de la guerre civile dans les Mémoires authentiques, écrits pour la plupart dans les premières décennies du règne de Louis XIV. Cet article se propose au contraire d’en étudier la représentation dans le genre des Mémoires apocryphes en vogue dans la seconde moitié du règne, en se penchant sur deux œuvres de Courtilz de Sandras (1644
–
1712): les
Mémoires de Mr. L. C. D. R.
(1687) et les
Mémoires de Mr. d’Artagnan
(1700). Ceux-ci permettent d’analyser la réception et la réécriture d’un premier ensemble de textes suscités par la Fronde. En abordant ces pseudo-Mémoires sous l’angle de l’imitation et du pastiche, on verra qu’ils font revivre une riche bibliothèque satirique où figurent, à côté des Mémoires authentiques, nombre de mazarinades et de romans historiques. La charge idéologique de cet intertexte conduira alors à s’interroger sur les fonctions du pastiche chez Courtilz de Sandras: on étudiera comment la réécriture pastichante de discours hétérogènes sur la Fronde sert moins ici une optique idéologique qu’une mise à distance ludique de l’histoire, promouvant des modes d’analyse critique du passé.