bluuebunny/crossref_metadata_2025 huggingface dataset:
Study of hot cracking potential in a 6-ton steel ingot casting
Authors: Yang Jing’an , Liu Baicheng , Shen Houfa
Published: April 2018

A new hot cracking potential (HCP) criterion, for the appearance of hot tearing in steel ingot castings, is proposed. The maximum value of the first principal stress, divided by the dynamic yield strength in the brittle temperature range (BTR), was used to identify the HCP. Experiments were carried out on a 6-ton P91 steel ingot in which severe hot tearing was detected in the upper centerline. Another ingot, with a better heat preservation riser, and without hot tearing, was used for comparison. Samples were obtained from the area of the ingot body with hot tearing, and their morphologies were inspected by a X-ray high energy industrial computed tomography. The carbon and sulfur distributions around the hot tearing were characterized by an infrared spectrometry carbon and sulfur analyzer. High temperature mechanical properties were obtained by a Gleeble thermal simulation machine, under different strain rates. Then, thermo-mechanical simulations using an elasto-viscoplastic finite-element model were conducted to analyze the stress and strain evolution during ingot solidification. The results showed that the hot tearing area, which was rich in both carbon and sulfur, was under excessive tensile stress in the BTR, bearing the highest HCP.
Micro friction stir lap welding of AISI 430 ferritic stainless steel: a study on the mechanical properties, microstructure, texture and magnetic properties
Authors: Mostaan Hossein , Safari Mehdi , Bakhtiari Arash
Published: April 2018

In this study, the effect of friction stir welding of AISI 430 (X6Cr17, material number 1.4016) ferritic stainless steel is examined. Two thin sheets with dimensions of 0.4 × 50 × 200 mm3 are joined in lap configuration. Optical microscopy and field emission electron microscopy were used in order to microstructural evaluations and fracture analysis, respectively. Tensile test and microhardness measurements are employed in order to study the mechanical behaviors of welds. Also, vibrational sample magnetometry (VSM) is employed for characterizing magnetic properties of welded samples. Texture analysis is carried out in order to clarify the change mechanism of magnetic properties in the welded area. The results show that AISI 430 sheets are successfully joined considering both, the appearance of the welding bead and the strength of the welded joint. It is found that by friction stir welding of AISI 430 sheets, texture components with easy axes magnetization have been replaced by texture components with harder magnetization axes. VSM analysis showed that friction stir welding leads to increase in residual induction (Br) and coercivity (Hc). This increase is attributed to the grain refining due the friction stir welding and formation of texture components with harder axes of magnetizations.
Irradiation-Induced Palladium-Catalyzed Direct C–H Alkylation of Heteroarenes with Tertiary and Secondary Alkyl Bromides
Authors: Shang Rui , Fu Yao , Wang Guang-Zu
Published: April 2018

A palladium catalyst in combination with two types of phosphine ligands efficiently catalyzes direct C–H alkylation of heteroarenes with secondary and tertiary alkyl bromides under irradiation conditions. Irradiation of blue light-emitting diodes (blue LEDs) effectively excites phosphine-ligated palladium catalyst to facilitate oxidative addition with alkyl bromides, and also excites the alkylpalladium species to enable the generation of alkyl radicals to react with heteroarenes.
Changes in the Messenger RNA Expression of Toll-Like Receptors 2 and 4 in Healthy Infants According to Age
Authors: Galliano Ilaria , Garro Maria , Savino Andrea , Manzoni Paolo , Daprà Valentina , Montanari Paola , Bergallo Massimiliano , Savino Francesco
Published: April 2018

Background Toll-like receptors (TLRs) are potentially useful indicators of several pediatric disease states. Here, we explore the mechanisms by which inflammation is regulated by interactions between microbiota and the host. Little data are available regarding the expression of TLRs in postnatal healthy infants. TLR 2 and TLR4 are extracellular TLRs that act as innate immune receptors by recognizing a wide range of endogenous ligands and microorganisms.

Methods The aim of this study was to use real-time polymerase chain reaction to investigate the expression of the messenger RNAs (mRNAs) of TLR2 and TLR4 in blood samples obtained from healthy full-term infants and toddlers.

Results We analyzed the mRNA expression levels of TLRs in 88 healthy term children separated according to age. The median expression level of TLR2 was 1.49 ± 1.10 arbitrary units (AU) (n = 25) in infants younger than 3 months, 0.67 ± 0.72 AU (n = 25) in infants aged between 3 and 12 months, and 0.03 ± 0.02 AU (n= 38) in infants older than 12 months. The median expression level of TLR4 was 1.25 ± 0.79 AU (n = 25) in infants younger than 3 months, 0.75 ± 0.54 AU (n = 25) in infants aged 3 to 12 months, and 0.44 ± 0.28 AU (n = 38) in infants older than 12 months. There was difference in the mRNA expression level of TLR2 and TLR4 between infants aged 0 to 3 and 3 to 12 months and those aged more than 1 year (p < 0.0001 and p < 0.0001, respectively)

Conclusion We found that the expression levels of TLR2 and TLR4 were associated with age. In particular, we observed that their expression increased during the suckling period and then clearly decreased once the infants reached 1 year of age (p < 0.001). These findings could be related to microbial colonization and the immune system.
The Use of Dynamic Assist Orthosis for Muscle Reeducation following Brachial Plexus Injury and Reconstruction
Authors: Chinchalkar Shrikant , Larocerie-Salgado Juliana , Cepek Jeremy , Grenier Marie-Lyne
Published: April 2018

Therapeutic management of brachial plexus injuries remains complex. The impact of brachial plexus injuries on everyday human functioning should not be underestimated. Early active-assisted range of motion following such injuries may prevent myostatic contractures, minimize muscle atrophy, facilitate muscle fiber recruitment, and enable a faster return to baseline strength levels. The dynamic assist elbow flexion orthosis proposed is designed to provide patients with a graded system for muscle reeducation and function. No clinical data are currently available on the use of this orthosis design; however, this article presents a treatment option based on sound clinical reasoning to facilitate rehabilitation following this devastating injury.
Compliance on Mandatory Data Reporting in Registered Obstetrics Trials
Authors: Evans M. , Athale Abha , Jawhar Omar , Wright Micah , Bryant Kristine , Vassar Matt , Checketts Jake
Published: April 2018

Background The Food and Drug Administration's (FDA's) Amendments Act established a legal mandate requiring registration of certain drug, device, and biologics trials in ClinicalTrials.gov prior to patient enrollment. One provision of the act requires investigators to report trial results in ClinicalTrials.gov within 1 year of completion. Preliminary evidence suggests that overall compliance rates are inadequate, and rates specific to obstetrics have not been investigated.

Objective The purpose of this study was to examine the rate of compliance for mandatory reporting of results from obstetrics trials to ClinicalTrials.gov and to determine whether compliance rates were associated with funding type.

Study Design We performed a registry-based study of clinical trials pertaining to obstetrics. ClinicalTrials.gov was cross-referenced with Drugs@FDA to determine which trials required mandatory reporting. We used obstetrics trials registered on ClinicalTrials.gov with at least 1 US site. Phase 0, Phase 1, and trials not reporting a phase were excluded. Furthermore, only trials of interventions approved by the FDA were retained.

Results Our search returned 973 trials, of which 325 (33.4%) were screened for eligibility. Of the 325 completed trials, 74 (22.8% or 7.6% of the total) met all inclusion criteria and were evaluated for compliance. Thirty-seven of these trials (50%) did not list results, whereas the remaining 37 trials (50%) contained results on ClinicalTrials.gov. Trials funded by the National Institutes of Health (87.5%; ⅞) and industry (80%; 12/15) had higher rates of compliance than trials funded by other (43.9%; 18/41) or unspecified (0%; 0/10) sources.

Conclusion Half of all applicable obstetrics trials did not report results. Furthermore, rates of compliance appeared to vary by funding source, with trials funded by the National Institutes of Health or industry appearing to have a higher rate of compliance to mandatory data reporting. Greater awareness of federal regulations is needed, and changes should be implemented to increase reporting.
Auch ältere Frauen profitieren
Authors: Kretzschmar Alexander
Published: April 2018

Frauen ˃ 70 Jahre mit hormonsensiblem Mammakarzinom sprechen ebenso gut auf die Therapie mit CDK4/6-Inhibitoren an wie jüngere Patientinnen. Dies ergab eine von der US-Zulassungsbehörde durchgeführte exploratorische Metaanalyse von Daten aus zwei prospektiven Studien der in den USA und/oder der EU zugelassenen drei CDK4/6-Inhibitoren (Cyclin Dependent Kinases 4 and 6; CDK) – Abemaciclib, Palbociclib und Ribociclib.
Selbstlernende Algorithmen übertreffen Experten
Authors: Krome Susanne
Published: April 2018

Deep Learning basiert auf der Fähigkeit des Computers, aus Beispielen zu lernen. Grundlage sind umfangreiche, klassifizierte Datensätze und künstliche neuronale Netze mit vielen Ebenen, welche das menschliche Gehirn imitieren und die Automatisierung intelligenten Verhaltens ermöglichen. In CAMELYON16 traten zwölf erfahrene Pathologen in Wettbewerb mit 32 Algorithmen für die Detektion von Lymphknotenmetastasen bei Mammakarzinomen.
Verzicht auf Stammzelltransplantation ist möglich
Authors: Arnheim Katharina
Published: April 2018

Patienten mit akuter Promyelozyten-Leukämie (APL), die nach lang anhaltender kom-pletter Remission (CR) rezidivieren, profitieren laut einer retrospektiven Analyse von einer Erhaltungstherapie mit ATRA-ATO (all-trans-Retinsäure- Arsentrioxid).
Erhaltungstherapie als Alternative zur Stammzelltransplantation
Authors: Arnheim Katharina
Published: April 2018

Die Therapie mit dem bispezifischen Antikörper-Konstrukt Blinatumumab wurde in der TOWER-Studie bei rezidivierten und refraktären Patienten mit Philadelphia-Chromosom-negativer (Ph-) B-Vorläufer-ALL (Akute Lymphatische Leukämie) erfolgreich geprüft. Eine neue Auswertung der Studie zeigt jetzt, dass die Erhaltungstherapie mit Blimatumumab nach Erreichen einer kompletten hämatologischen Remission (CHR) für nicht stammzelltransplantierte Patienten aufgrund der Verlängerung des Gesamtüberlebens (OS) vorteilhaft ist.
The role of surface vorticity during unsteady separation
Authors: Melius Matthew S. , Mulleners Karen , Cal Raúl Bayoán
Published: April 2018

Unsteady flow separation in rotationally augmented flow fields plays a significant role in a variety of fundamental flows. Through the use of time-resolved particle image velocimetry, vorticity accumulation and vortex shedding during unsteady separation over a three-dimensional airfoil are examined. The results of the study describe the critical role of surface vorticity accumulation during unsteady separation and reattachment. Through evaluation of the unsteady characteristics of the shear layer, it is demonstrated that the buildup and shedding of surface vorticity directly influence the dynamic changes of the separation point location. The quantitative characterization of surface vorticity and shear layer stability enables improved aerodynamic designs and has a broad impact within the field of unsteady fluid dynamics.
Self-assembled InN quantum dots on side facets of GaN nanowires
Authors: Bi Zhaoxia , Ek Martin , Stankevic Tomas , Colvin Jovana , Hjort Martin , Lindgren David , Lenrick Filip , Johansson Jonas , Wallenberg L. Reine , Timm Rainer , Feidenhans'l Robert , Mikkelsen Anders , Borgström Magnus T. , Gustafsson Anders , Ohlsson B. Jonas , Monemar Bo , Samuelson Lars
Published: April 2018

Self-assembled, atomic diffusion controlled growth of InN quantum dots was realized on the side facets of dislocation-free and c-oriented GaN nanowires having a hexagonal cross-section. The nanowires were synthesized by selective area metal organic vapor phase epitaxy. A 3 Å thick InN wetting layer was observed after growth, on top of which the InN quantum dots formed, indicating self-assembly in the Stranski-Krastanow growth mode. We found that the InN quantum dots can be tuned to nucleate either preferentially at the edges between GaN nanowire side facets, or directly on the side facets by tuning the adatom migration by controlling the precursor supersaturation and growth temperature. Structural characterization by transmission electron microscopy and reciprocal space mapping show that the InN quantum dots are close to be fully relaxed (residual strain below 1%) and that the c-planes of the InN quantum dots are tilted with respect to the GaN core. The strain relaxes mainly by the formation of misfit dislocations, observed with a periodicity of 3.2 nm at the InN and GaN hetero-interface. The misfit dislocations introduce I1 type stacking faults (…ABABCBC…) in the InN quantum dots. Photoluminescence investigations of the InN quantum dots show that the emissions shift to higher energy with reduced quantum dot size, which we attribute to increased quantum confinement.
Optimization of gas-filled quartz capillary discharge waveguide for high-energy laser wakefield acceleration
Authors: Qin Zhiyong , Li Wentao , Liu Jiansheng , Liu Jiaqi , Yu Changhai , Wang Wentao , Qi Rong , Zhang Zhijun , Fang Ming , Feng Ke , Wu Ying , Ke Lintong , Chen Yu , Wang Cheng , Li Ruxin , Xu Zhizhan
Published: April 2018

A hydrogen-filled capillary discharge waveguide made of quartz is presented for high-energy laser wakefield acceleration (LWFA). The experimental parameters (discharge current and gas pressure) were optimized to mitigate ablation by a quantitative analysis of the ablation plasma density inside the hydrogen-filled quartz capillary. The ablation plasma density was obtained by combining a spectroscopic measurement method with a calibrated gas transducer. In order to obtain a controllable plasma density and mitigate the ablation as much as possible, the range of suitable parameters was investigated. The experimental results demonstrated that the ablation in the quartz capillary could be mitigated by increasing the gas pressure to ∼7.5–14.7 Torr and decreasing the discharge current to ∼70–100 A. These optimized parameters are promising for future high-energy LWFA experiments based on the quartz capillary discharge waveguide.
Accurate detection of hierarchical communities in complex networks based on nonlinear dynamical evolution
Authors: Zhuo Zhao , Cai Shi-Min , Tang Ming , Lai Ying-Cheng
Published: April 2018

One of the most challenging problems in network science is to accurately detect communities at distinct hierarchical scales. Most existing methods are based on structural analysis and manipulation, which are NP-hard. We articulate an alternative, dynamical evolution-based approach to the problem. The basic principle is to computationally implement a nonlinear dynamical process on all nodes in the network with a general coupling scheme, creating a networked dynamical system. Under a proper system setting and with an adjustable control parameter, the community structure of the network would “come out” or emerge naturally from the dynamical evolution of the system. As the control parameter is systematically varied, the community hierarchies at different scales can be revealed. As a concrete example of this general principle, we exploit clustered synchronization as a dynamical mechanism through which the hierarchical community structure can be uncovered. In particular, for quite arbitrary choices of the nonlinear nodal dynamics and coupling scheme, decreasing the coupling parameter from the global synchronization regime, in which the dynamical states of all nodes are perfectly synchronized, can lead to a weaker type of synchronization organized as clusters. We demonstrate the existence of optimal choices of the coupling parameter for which the synchronization clusters encode accurate information about the hierarchical community structure of the network. We test and validate our method using a standard class of benchmark modular networks with two distinct hierarchies of communities and a number of empirical networks arising from the real world. Our method is computationally extremely efficient, eliminating completely the NP-hard difficulty associated with previous methods. The basic principle of exploiting dynamical evolution to uncover hidden community organizations at different scales represents a “game-change” type of approach to addressing the problem of community detection in complex networks.
Physics-informed machine learning for inorganic scintillator discovery
Authors: Pilania G. , McClellan K. J. , Stanek C. R. , Uberuaga B. P.
Published: April 2018

Applications of inorganic scintillators—activated with lanthanide dopants, such as Ce and Eu—are found in diverse fields. As a strict requirement to exhibit scintillation, the 4f ground state (with the electronic configuration of [Xe]4fn 5d0) and 5d1 lowest excited state (with the electronic configuration of [Xe]4fn−1 5d1) levels induced by the activator must lie within the host bandgap. Here we introduce a new machine learning (ML) based search strategy for high-throughput chemical space explorations to discover and design novel inorganic scintillators. Building upon well-known physics-based chemical trends for the host dependent electron binding energies within the 4f and 5d1 energy levels of lanthanide ions and available experimental data, the developed ML model—coupled with knowledge of the vacuum referred valence and conduction band edges computed from first principles—can rapidly and reliably estimate the relative positions of the activator’s energy levels relative to the valence and conduction band edges of any given host chemistry. Using perovskite oxides and elpasolite halides as examples, the presented approach has been demonstrated to be able to (i) capture systematic chemical trends across host chemistries and (ii) effectively screen promising compounds in a high-throughput manner. While a number of other application-specific performance requirements need to be considered for a viable scintillator, the scheme developed here can be a practically useful tool to systematically down-select the most promising candidate materials in a first line of screening for a subsequent in-depth investigation.
An atypical N-ethylmaleimide sensitive factor enables the viability of nematode-resistant
Rhg1
soybeans
Authors: Bayless Adam M. , Zapotocny Ryan W. , Grunwald Derrick J. , Amundson Kaela K. , Diers Brian W. , Bent Andrew F.
Published: April 2018

Significance

N-ethylmaleimide sensitive factor (NSF) and α-soluble NSF attachment protein (α-SNAP) are key components of vesicle trafficking systems and are conserved across eukaryotes. This study shows that these two essential housekeeping proteins have coevolved toward atypical forms in soybean to confer resistance to a highly damaging nematode pathogen while balancing plant fitness. We report discovery of a naturally occurring NSF variant carrying unusual polymorphisms that enhance interaction with and assuage the cytotoxicity of the
Rhg1
resistance-associated α-SNAPs. Pathogen selection pressure has apparently driven this rewiring of multiple components of the conserved SNARE recycling machinery. Useful introduction of the agriculturally valuable
Rhg1
resistance source into other plants is likely to require a cofunctional NSF protein partner.
OPQRST(U): Integrating Substance use Disorders or “Use” into the Medical History
Authors: Eloge Joshua , Napier T. Celeste , Dantz Bezalel
Published: April 2018

Substance use disorders (SUDs) are pervasive in the United States, with 20.1 million cases in 2016, of which only 19% receive treatment. SUDs permeate all medical specialties and should be considered in the differential diagnosis of every chief complaint. Acknowledging the salience of SUDs provides a unique opportunity for early identification and intervention. Thus, SUDs should be reflected prominently in the history of the present illness rather than in the social history. To this effect, we propose the inclusion of Use (U) in the history of present illness and incorporating “U” into the pedagogical mnemonic of OPQRST that is commonly used in medical training. Obtaining this history will help determine if and which abused substances may be contributing to the chief complaint. We also suggest the incorporation of an additional acronym, SORTED, to account for the various domains of Use, including Street (illicit drugs), OTCs (over-the-counter medications), Rx (prescriptions, including nonmedicinal use of pharmaceutical drugs), Tobacco (including e-cigarettes), EtOH (alcohol), and Dietary (caffeine, vitamins, and herbal supplements) agents. We discuss how utilizing OPQRSTU will help reshape the way medical students think about SUDs and will facilitate detection and diagnosis of all domains of SUDs.
Characterization of LAMP1-labeled nondegradative lysosomal and endocytic compartments in neurons
Authors: Cheng Xiu-Tang , Xie Yu-Xiang , Zhou Bing , Huang Ning , Farfel-Becker Tamar , Sheng Zu-Hang
Published: April 2018

Despite widespread distribution of LAMP1 and the heterogeneous nature of LAMP1-labeled compartments, LAMP1 is routinely used as a lysosomal marker, and LAMP1-positive organelles are often referred to as lysosomes. In this study, we use immunoelectron microscopy and confocal imaging to provide quantitative analysis of LAMP1 distribution in various autophagic and endolysosomal organelles in neurons. Our study demonstrates that a significant portion of LAMP1-labeled organelles do not contain detectable lysosomal hydrolases including cathepsins D and B and glucocerebrosidase. A bovine serum albumin–gold pulse–chase assay followed by ultrastructural analysis suggests a heterogeneity of degradative capacity in LAMP1-labeled endolysosomal organelles. Gradient fractionation displays differential distribution patterns of LAMP1/2 and cathepsins D/B in neurons. We further reveal that LAMP1 intensity in familial amyotrophic lateral sclerosis–linked motor neurons does not necessarily reflect lysosomal deficits in vivo. Our study suggests that labeling a set of lysosomal hydrolases combined with various endolysosomal markers would be more accurate than simply relying on LAMP1/2 staining to assess neuronal lysosome distribution, trafficking, and functionality under physiological and pathological conditions.
A gene–phenotype relationship extraction pipeline from the biomedical literature using a representation learning approach
Authors: Xing Wenhui , Qi Junsheng , Yuan Xiaohui , Li Lin , Zhang Xiaoyu , Fu Yuhua , Xiong Shengwu , Hu Lun , Peng Jing
Published: April 2018

Motivation

The fundamental challenge of modern genetic analysis is to establish gene-phenotype correlations that are often found in the large-scale publications. Because lexical features of gene are relatively regular in text, the main challenge of these relation extraction is phenotype recognition. Due to phenotypic descriptions are often study- or author-specific, few lexicon can be used to effectively identify the entire phenotypic expressions in text, especially for plants.

Results

We have proposed a pipeline for extracting phenotype, gene and their relations from biomedical literature. Combined with abbreviation revision and sentence template extraction, we improved the unsupervised word-embedding-to-sentence-embedding cascaded approach as representation learning to recognize the various broad phenotypic information in literature. In addition, the dictionary- and rule-based method was applied for gene recognition. Finally, we integrated one of famous information extraction system OLLIE to identify gene-phenotype relations. To demonstrate the applicability of the pipeline, we established two types of comparison experiment using model organism Arabidopsis thaliana. In the comparison of state-of-the-art baselines, our approach obtained the best performance (F1-Measure of 66.83%). We also applied the pipeline to 481 full-articles from TAIR gene-phenotype manual relationship dataset to prove the validity. The results showed that our proposed pipeline can cover 70.94% of the original dataset and add 373 new relations to expand it.

Availability and implementation

The source code is available at http://www.wutbiolab.cn: 82/Gene-Phenotype-Relation-Extraction-Pipeline.zip.

Supplementary information

Supplementary data are available at Bioinformatics online.
A powerful approach reveals numerous expression quantitative trait haplotypes in multiple tissues
Authors: Ying Dingge , Li Mulin Jun , Sham Pak Chung , Li Miaoxin
Published: April 2018

Motivation

Recently many studies showed single nucleotide polymorphisms (SNPs) affect gene expression and contribute to development of complex traits/diseases in a tissue context-dependent manner. However, little is known about haplotype’s influence on gene expression and complex traits, which reflects the interaction effect between SNPs.

Results

In the present study, we firstly proposed a regulatory region guided eQTL haplotype association analysis approach, and then systematically investigate the expression quantitative trait loci (eQTL) haplotypes in 20 different tissues by the approach. The approach has a powerful design of reducing computational burden by the utilization of regulatory predictions for candidate SNP selection and multiple testing corrections on non-independent haplotypes. The application results in multiple tissues showed that haplotype-based eQTLs not only increased the number of eQTL genes in a tissue specific manner, but were also enriched in loci that associated with complex traits in a tissue-matched manner. In addition, we found that tag SNPs of eQTL haplotypes from whole blood were selectively enriched in certain combination of regulatory elements (e.g. promoters and enhancers) according to predicted chromatin states. In summary, this eQTL haplotype detection approach, together with the application results, shed insights into synergistic effect of sequence variants on gene expression and their susceptibility to complex diseases.

Availability and implementation

The executable application ‘eHaplo’ is implemented in Java and is publicly available at http://grass.cgs.hku.hk/limx/ehaplo/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Covariate-adjusted heatmaps for visualizing biological data via correlation decomposition
Authors: Wu Han-Ming , Tien Yin-Jing , Ho Meng-Ru , Hwu Hai-Gwo , Lin Wen-chang , Tao Mi-Hua , Chen Chun-houh
Published: April 2018

Motivation

Heatmap is a popular visualization technique in biology and related fields. In this study, we extend heatmaps within the framework of matrix visualization (MV) by incorporating a covariate adjustment process through the estimation of conditional correlations. MV can explore the embedded information structure of high-dimensional large-scale datasets effectively without dimension reduction. The benefit of the proposed covariate-adjusted heatmap is in the exploration of conditional association structures among the subjects or variables that cannot be done with conventional MV.

Results

For adjustment of a discrete covariate, the conditional correlation is estimated by the within and between analysis. This procedure decomposes a correlation matrix into the within- and between-component matrices. The contribution of the covariate effects can then be assessed through the relative structure of the between-component to the original correlation matrix while the within-component acts as a residual. When a covariate is of continuous nature, the conditional correlation is equivalent to the partial correlation under the assumption of a joint normal distribution. A test is then employed to identify the variable pairs which possess the most significant differences at varying levels of correlation before and after a covariate adjustment. In addition, a z-score significance map is constructed to visualize these results. A simulation and three biological datasets are employed to illustrate the power and versatility of our proposed method.

Availability and implementation

GAP is available to readers and is free to non-commercial applications. The installation instructions, the user’s manual, and the detailed tutorials can be found at http://gap.stat.sinica.edu.tw/Software/GAP.

Supplementary information

Supplementary Data are available at Bioinformatics online.
lncFunTK: a toolkit for functional annotation of long noncoding RNAs
Authors: Zhou Jiajian , Huang Yile , Ding Yingzhe , Yuan Jie , Wang Huating , Sun Hao
Published: April 2018

Motivation

Thousands of long noncoding RNAs (lncRNAs) were newly identified from high throughput RNA-seq data. Functional annotation and prioritization of these lncRNAs for further experimental validation as well as the functional investigation is the bottleneck step for many noncoding RNA studies.

Results

Here we describe lncFunTK that can run either as standard application or webserver for this purpose. It integrates high throughput sequencing data (i.e. ChIP-seq, CLIP-seq and RNA-seq) to construct the regulatory network associated with lncRNAs. Through the network, it calculates the Functional Information Score (FIS) of each individual lncRNA for prioritizing and inferring its functions through Gene Ontology (GO) terms of neighboring genes. In addition, it also provides utility scripts to support the input data preprocessing and the parameter optimizing. We further demonstrate that lncFunTK can be widely used in various biological systems for lncRNA prioritization and functional annotation.

Availability and implementation

The lncFunTK standalone version is an open source package and freely available at http://sunlab.cpy.cuhk.edu.hk/lncfuntk under the MIT license. A webserver implementation is also available at http://sunlab.cpy.cuhk.edu.hk/lncfuntk/runlncfuntk.html.

Supplementary information

Supplementary data are available at Bioinformatics online.
High precision in protein contact prediction using fully convolutional neural networks and minimal sequence features
Authors: Jones David T , Kandathil Shaun M
Published: April 2018

Motivation

In addition to substitution frequency data from protein sequence alignments, many state-of-the-art methods for contact prediction rely on additional sources of information, or features, of protein sequences in order to predict residue–residue contacts, such as solvent accessibility, predicted secondary structure, and scores from other contact prediction methods. It is unclear how much of this information is needed to achieve state-of-the-art results. Here, we show that using deep neural network models, simple alignment statistics contain sufficient information to achieve state-of-the-art precision. Our prediction method, DeepCov, uses fully convolutional neural networks operating on amino-acid pair frequency or covariance data derived directly from sequence alignments, without using global statistical methods such as sparse inverse covariance or pseudolikelihood estimation.

Results

Comparisons against CCMpred and MetaPSICOV2 show that using pairwise covariance data calculated from raw alignments as input allows us to match or exceed the performance of both of these methods. Almost all of the achieved precision is obtained when considering relatively local windows (around 15 residues) around any member of a given residue pairing; larger window sizes have comparable performance. Assessment on a set of shallow sequence alignments (fewer than 160 effective sequences) indicates that the new method is substantially more precise than CCMpred and MetaPSICOV2 in this regime, suggesting that improved precision is attainable on smaller sequence families. Overall, the performance of DeepCov is competitive with the state of the art, and our results demonstrate that global models, which employ features from all parts of the input alignment when predicting individual contacts, are not strictly needed in order to attain precise contact predictions.

Availability and implementation

DeepCov is freely available at https://github.com/psipred/DeepCov.

Supplementary information

Supplementary data are available at Bioinformatics online.
TMCrys: predict propensity of success for transmembrane protein crystallization
Authors: Varga Julia K , Tusnády Gábor E
Published: April 2018

Motivation

Transmembrane proteins (TMPs) are crucial in the life of the cells. As they have special properties, their structure is hard to determine––the PDB database consists of 2% TMPs, despite the fact that they are predicted to make up to 25% of the human proteome. Crystallization prediction methods were developed to aid the target selection for structure determination, however, there is a need for a TMP specific service.

Results

Here, we present TMCrys, a crystallization prediction method that surpasses existing prediction methods in performance thanks to its specialization for TMPs. We expect TMCrys to improve target selection of TMPs.

Availability and implementation

https://github.com/brgenzim/tmcrys

Supplementary information

Supplementary data are available at Bioinformatics online.
Quantification of biases in predictions of protein stability changes upon mutations
Authors: Pucci Fabrizio , Bernaerts Katrien V , Kwasigroch Jean Marc , Rooman Marianne
Published: April 2018

Motivation

Bioinformatics tools that predict protein stability changes upon point mutations have made a lot of progress in the last decades and have become accurate and fast enough to make computational mutagenesis experiments feasible, even on a proteome scale. Despite these achievements, they still suffer from important issues that must be solved to allow further improving their performances and utilizing them to deepen our insights into protein folding and stability mechanisms. One of these problems is their bias toward the learning datasets which, being dominated by destabilizing mutations, causes predictions to be better for destabilizing than for stabilizing mutations.

Results

We thoroughly analyzed the biases in the prediction of folding free energy changes upon point mutations (ΔΔG0) and proposed some unbiased solutions. We started by constructing a dataset Ssym of experimentally measured ΔΔG0s with an equal number of stabilizing and destabilizing mutations, by collecting mutations for which the structure of both the wild-type and mutant protein is available. On this balanced dataset, we assessed the performances of 15 widely used ΔΔG0 predictors. After the astonishing observation that almost all these methods are strongly biased toward destabilizing mutations, especially those that use black-box machine learning, we proposed an elegant way to solve the bias issue by imposing physical symmetries under inverse mutations on the model structure, which we implemented in PoPMuSiCsym. This new predictor constitutes an efficient trade-off between accuracy and absence of biases. Some final considerations and suggestions for further improvement of the predictors are discussed.

Supplementary information

Supplementary data are available at Bioinformatics online.

Note

The article 10.1093/bioinformatics/bty340/, published alongside this paper, also addresses the problem of biases in protein stability change predictions.
Trends in user ratings and reviews of a popular yet inaccurate blood pressure-measuring smartphone app
Authors: Plante Timothy B , O’Kelly Anna C , Macfarlane Zane T , Urrea Bruno , Appel Lawrence J , Miller III Edgar R , Blumenthal Roger S , Martin Seth S
Published: April 2018

Objective

To understand whether user reviews of Instant Blood Pressure (IBP), an inaccurate, unregulated BP-measuring app reflected IBP’s inaccuracy, to understand drivers for high and low ratings, and to understand if disclaimers prevented medical use.

Materials and Methods

All iTunes app reviews for IBP v1.2.3 were downloaded and assessed for themes by two reviewers. Summary statistics for themes were tabulated with their associated star ratings.

Results

Common themes included perceived accuracy (42% of all reviews, star rating mean 4.8, median 5), inaccuracy (10%, 2.0, 1), and convenience (34%, 4.7, 5). Nine percent documented IBP use in medical conditions (4.6, 5), and 2% mentioned IBP’s disclaimer (2.7, 3).

Discussion

User reviews and ratings of a popular, inaccurate BP-measuring app were positive and uncommonly commented on its inaccuracy. Disclaimers attempting to prevent medical use of the app were ineffective. These findings support the need for more rigorous regulatory review of apps prior to their release.
Predictors of viewing progress notes among users of VA’s electronic health portal who receive mental health care
Authors: Dobscha Steven K , Denneson Lauren M , Pisciotta Maura K , Bourne Donald S , Chen Jason I , Philipps-Moses David , Woods Susan S
Published: April 2018

Objective

Consistent with the OpenNotes movement, the Veterans Health Administration (VHA) offers patients online access to their clinical notes through the Blue Button feature in its electronic patient health portal, My HealtheVet. We identified demographic, diagnostic, and knowledge-related predictors of viewing clinical notes among veterans receiving VHA mental health care who recently used My HealtheVet.

Materials and Methods

Three hundred and thirty-eight patients receiving mental health care from 1 VHA medical center who had logged into My HealtheVet in the prior 6 months completed self-report questionnaires assessing their viewing of clinical notes. Additional data were extracted from VHA’s Patient Care Database. Multivariable logistic regression was used to examine predictors of viewing notes.

Results

Fifty percent of respondents reported having read their notes. In the final multivariable model, post-traumatic stress disorder (PTSD) diagnosis [odds ratio (OR) = 2.30 (1.31–4.07)], speaking with their mental health clinician about their ability to view notes [OR = 3.84 (1.69–8.72)], and being very or extremely confident in understanding the purpose and uses of Blue Button [OR = 9.80 (2.23–43.07) and OR = 13.36 (2.74–65.20), respectively] were associated with viewing notes.

Discussion

Patient recall of mental health clinicians speaking to them about their ability to view notes, and confidence in understanding the use and purposes of Blue Button, were stronger predictors of viewing notes than demographic variables. PTSD diagnosis was the only clinical characteristic associated with viewing notes.

Conclusion

The findings support the value of mental health clinicians openly discussing the availability of notes with patients if they wish to help them take advantage of their potential benefits.
Single-atom catalysis: a new field that learns from tradition
Authors: Ball Philip
Published: April 2018

Much of industrial chemical processing (in the petrochemicals industry, for example), and a great deal of laboratory chemical synthesis, involves catalysts that both lower the energy barrier to reaction and may help steer a reaction along a particular path. Traditionally, catalysts have come in two classes: heterogeneous, typically meaning that the catalyst is an extended solid; and homogeneous, where the catalyst is a small molecule that shares a solvent with the reactants. In heterogeneous catalysis, the reaction generally takes place on a surface, involving molecules attached there by covalent bonds. Homogeneous catalysts are often organometallic compounds, in which a metal atom or small cluster of atoms supplies the active site for reaction.

 In recent years, these distinctions have become somewhat blurred thanks to the advent of single-atom catalysis, where the catalytic site consists of a single atom (as in many homogeneous catalysts) attached to or embedded in a surface. The emergence of this field might be regarded as the logical conclusion of the use of ‘supported metal clusters’—small metal particles of nanometer scale and below, containing perhaps hundreds, tens or just a few atoms. It has became clear that such clusters can sometimes provide greater product selectivity and activity than macro-sized particles or powders of the same metal, partly because the active sites might be atoms at particular locations (such as edges and corners) in the nanoscale particles. By reducing their scale down to the level of single atoms, one can optimize these properties. At the same time, the potential uniformity of the atoms’ environments makes such catalysts more amenable to rational design and modeling to understand mechanism.

 This field represents an appealing blend of fundamental chemistry and physics—from the quantum-mechanical level upwards—and applied research aimed at producing many of the products vital to society, such as fuels and materials. Researchers in China have been strongly active in this field in recent years (see, for example, refs [1–5]). Jean Marie Basset of the King Abdullah University of Science and Technology in Thuwal, Saudi Arabia, is one of the leading practitioners in the area, and National Science Review spoke to him about the development and prospects of the field.
The formation of a Spitzer bubble RCW 79 triggered by a cloud–cloud collision
Authors: Ohama Akio , Kohno Mikito , Hasegawa Keisuke , Torii Kazufumi , Nishimura Atsushi , Hattori Yusuke , Hayakawa Takahiro , Inoue Tsuyoshi , Sano Hidetoshi , Yamamoto Hiroaki , Tachihara Kengo , Fukui Yasuo
Published: April 2018

Understanding the mechanism of O-star formation is one of the most important current issues in astrophysics. Also an issue of keen interest is how O stars affect their surroundings and trigger secondary star formation. An ${\rm H\,\small{II}}$ region RCW 79 is one of the typical Spitzer bubbles alongside RCW 120. New observations of CO J = 1–0 emission with Mopra and NANTEN2 revealed that molecular clouds are associated with RCW 79 in four velocity components over a velocity range of 20 km s−1. We hypothesize that two of the clouds collided with each other and the collision triggered the formation of 12 O stars inside the bubble and the formation of 54 low-mass young stellar objects along the bubble wall. The collision is supported by observational signatures of bridges connecting different velocity components in the colliding clouds. The whole collision process happened over a timescale of ∼3 Myr. RCW 79 has a larger size by a factor of 30 in the projected area than RCW 120 with a single O star, and the large size favored formation of the 12 O stars due to the greater accumulated gas in the collisional shock compression.
Baseline Sensitivity and Toxic Actions of Prochloraz to Sclerotinia sclerotiorum
Authors: Zhang Ran , Xu Qianru , Zhang Yuchao , Zhu Fuxing
Published: April 2018

The ergosterol biosynthesis inhibitor prochloraz is a broad-spectrum fungicide and has been registered in China since 2007 for control of the economically important necrotrophic pathogen Sclerotinia sclerotiorum. In this study, relative baseline sensitivity and toxic actions of prochloraz on S. sclerotiorum were investigated. The mean EC50 values (effective concentrations causing 50% mycelial growth inhibition) for isolates collected in 2008 (n = 73) and 2014 (n = 76) were 0.0463 and 0.0434 µg/ml, respectively. There was no significant difference (P = 0.348) in EC50 values between the two years. Both frequency distributions of EC50 values for 2008 and 2014 were unimodal. The curative efficacy of prochloraz was significantly higher (P < 0.05) than that of the reference fungicide carbendazim. Prochloraz in potato dextrose agar (PDA) at concentrations from 0.01 to 0.36 µg/ml had no significant (P = 0.574) effects on the weight of sclerotia, but the number of sclerotia per plate increased for treatments with prochloraz at 0.15 and 0.36 µg/ml. Light microscopic observations showed that prochloraz in PDA at 0.03 µg/ml increased the number of hyphal offshoots. Observations with a transmission electron microscope showed that the cell wall of the prochloraz-treated hyphae became thicker and darker than the nontreated control. Prochloraz at 0.01 and 0.04 µg/ml significantly (P < 0.001) reduced rather than increased cell membrane permeability. Prochloraz significantly (P = 0.041) increased the mannan content in the cell wall of S. sclerotiorum. The observed mycelial growth inhibitions for the mixtures of prochloraz at 0.03 µg/ml and Congo red at a dose range from 0.05 to 0.4% (w/v) were lower than the expected inhibitions, indicating prochloraz might reduce the content of chitin in S. sclerotiorum. These results demonstrate that prochloraz has significant effects on the morphology and components of the cell wall of S. sclerotiorum and thus will advance our understanding of the toxic actions of prochloraz on phytopathogenic fungi.
Ensuring Access to Quality Health Care in Vulnerable Communities
Authors: Bhatt Jay , Bathija Priya
Published: April 2018

For millions of Americans living in vulnerable rural and urban communities, their hospital is an important, and often their only, source of health care. As transformation in the hospital and health care field continues, some communities may be at risk of losing access to health care services and the opportunities and resources they need to improve and maintain their health. Integrated, comprehensive strategies to reform health care delivery and payment, within which vulnerable communities can make individual choices based on their needs, support structures, and preferences, are needed.

In this Invited Commentary, the authors outline characteristics and parameters of vulnerable communities as well as the essential health care services that hospitals should strive to maintain locally identified by the American Hospital Association Task Force on Ensuring Access in Vulnerable Communities. They also describe four of nine emerging strategies—recommended by the task force—to reform health care delivery and payment and allow hospitals to provide the essential health care services, along with implementation barriers and how to address them. While this Invited Commentary focuses on vulnerable communities, the four highlighted strategies (addressing the social determinants of health, adopting new and innovative virtual care strategies, designing global budgets, and using inpatient/outpatient transformation strategy), as well as the other five strategies, may have broader applicability for all communities.