bluuebunny/crossref_metadata_2025_split huggingface dataset:
Statistical analysis and heuristic identification of unexpected interactions from the neurokinase‐inhibitor interactome in trigeminal neuralgia pharmacological intervention
Authors: Liu Lei , Chen Xiaobing , Liu Weiju , Yu Hui , Liu Fangming 
Published: April 2019

AbstractThe cell signaling pathways of human trigeminal neuralgia (TN) are orchestrated by a variety of protein kinase‐elicited phosphorylation events. However, a majority of TN‐related neurokinases have not yet been revealed and still remain largely unexplored. Here, a systematic kinase‐inhibitor interactome for 601 small‐molecule inhibitors across 51 human neurokinases is created via a high‐throughput molecular docking procedure; the inhibitors are reversible, ATP competitive, and commercially available, while the kinases are enriched by gene ontology (GO) to be semantically relevant with TN and have cocrystallized structures with their cognate ligands. Heuristic clustering and statistical analysis identify 35 hit inhibitors from the interactome profile, which are potential to target TN‐related kinases. The intermolecular interactions of four promising inhibitors with the array of 51 TN‐related kinases are investigated in detail at molecular level using dynamics simulation and energetics analysis. Consequently, a total of nine protein kinases are inferred as high‐affinity cotargets of these potent inhibitors, in which fours have already been established as sophisticated targets for TN therapy, while others are still unclear about their therapeutic implications underlying the disease. Some candidates are selected as representatives to perform kinase assay. It is found that some putative kinase targets can be inhibited effectively by noncognate inhibitors; the activity values are comparable with or even better than known cognate inhibitors. Structural examination of a potent kinase‐inhibitor complex identifies a number of noncovalent interactions such as hydrogen bonds, cation‐π stacking, and hydrophobic contacts at the tightly packed complex interface, conferring both stability and specificity to the complex recognition and interaction.
Mechanistic Insights into the Self‐Assembly of an Acid‐Sensitive Photoresponsive Supramolecular Polymer
Authors: Kartha Kalathil K. , Allampally Naveen Kumar , Yagai Shiki , Albuquerque Rodrigo Q. , Fernández Gustavo 
Published: April 2019

AbstractThe supramolecular polymerization of an acid‐sensitive pyridyl‐based ligand (L1) bearing a photoresponsive azobenzene moiety was elucidated by mechanistic studies. Addition of trifluoroacetic acid (TFA) led to the transformation of the antiparallel H‐bonded fibers of L1 in methylcyclohexane into superhelical braid‐like fibers stabilized by H‐bonding of parallel‐stacked monomer units. Interestingly, L1 dimers held together by unconventional pyridine–TFA N⋅⋅⋅H⋅⋅⋅O bridges represent the main structural elements of the assembly. UV‐light irradiation caused a strain‐driven disassembly and subsequent aggregate reconstruction, which ultimately led to short fibers. The results allowed to understand the mechanism of mutual influence of acid and light stimuli on supramolecular polymerization processes, thus opening up new possibilities to design advanced stimuli‐triggered supramolecular systems.
Antibacterial Small Molecules That Potently Inhibit Staphylococcus aureus Lipoteichoic Acid Biosynthesis
Authors: Naclerio George A. , Karanja Caroline W. , Opoku‐Temeng Clement , Sintim Herman O. 
Published: April 2019

AbstractThe rise of antibiotic resistance, especially in Staphylococcus aureus, and the increasing death rate due to multiresistant bacteria have been well documented. The need for new chemical entities and/or the identification of novel targets for antibacterial drug development is high. Lipoteichoic acid (LTA), a membrane‐attached anionic polymer, is important for the growth and virulence of many Gram‐positive bacteria, and interest has been high in the discovery of LTA biosynthesis inhibitors. Thus far, only a handful of LTA biosynthesis inhibitors have been described with moderate (MIC=5.34 μg mL−1) to low (MIC=1024 μg mL−1) activities against S. aureus. Herein we describe the identification of novel compounds that potently inhibit LTA biosynthesis in S. aureus, displaying impressive antibacterial activities (MIC as low as 0.25 μg mL−1) against methicillin‐resistant S. aureus (MRSA). Under similar in vitro assay conditions, these compounds are 4‐fold more potent than vancomycin and 8‐fold more potent than linezolid against MRSA.
Time‐critical data management in clouds: Challenges and a Dynamic Real‐Time Infrastructure Planner (DRIP) solution
Authors: Koulouzis Spiros , Martin Paul , Zhou Huan , Hu Yang , Wang Junchao , Carval Thierry , Grenier Baptiste , Heikkinen Jani , de Laat Cees , Zhao Zhiming 
Published: April 2019

SummaryThe increasing volume of data being produced, curated, and made available by research infrastructures in the environmental science domain require services that are able to optimize the delivery and staging of data for researchers and other users of scientific data. Specialized data services for managing data life cycle, for creating and delivering data products, and for customized data processing and analysis all play a crucial role in how these research infrastructures serve their communities, and many of these activities are time‐critical—needing to be carried out frequently within specific time windows. We describe our experiences identifying the time‐critical requirements of environmental scientists making use of computational research support environments. We present a microservice‐based infrastructure optimization suite, the Dynamic Real‐Time Infrastructure Planner, used for constructing virtual infrastructures for research applications on demand. We provide a case study whereby our suite is used to optimize runtime service quality for a data subscription service provided by the Euro‐Argo using EGI Federated Cloud and EUDAT's B2SAFE services, and to consider how such a case study relates to other application scenarios.
Non‐blocking two‐phase commit using blockchain
Authors: Ezhilchelvan Paul , Aldweesh Amjad , van Moorsel Aad 
Published: April 2019

SummaryThe two‐phase commit (2PC) protocol has long been known to have a provably inevitable vulnerability to blocking or non‐progress amidst server crashes, even when the distributed database system guarantees the most demanding timing‐related or “synchrony” requirements. Our aim here is to eliminate this vulnerability by using a blockchain for coordinating 2PC execution. We present the impossibilities, the possibilities, the cost, and the trade‐offs in this blockchain‐based approach to blocking‐free management of distributed transactions. We prove that a non‐blocking and blockchain‐coordinated 2PC protocol can exist only if both the blockchain and distributed database systems meet synchrony requirements; otherwise, although blocking remains eliminated, transactions can unnecessarily abort. We present a blockchain‐coordinated 2PC protocol and provide rigorous arguments for its correctness under the synchrony requirements. We then implement this protocol on the Ethereum Testnet and demonstrate, through our experiments, that the monetary cost of executing smart contracts is quite small, that the protocol performance slows down when using a public blockchain like Ethereum, and that even major violations of synchrony requirements lead only to relatively small increases in unnecessary aborts. We thus identify a trade‐off between improving protocol performance and admitting a risk that transactions could occasionally abort unnecessarily.
Integrated positioning algorithm based on GPS/WLAN
Authors: Li Dengao , Wei Zheng , Zhao Jumin , Cheng Junbing , Ma Zhiying 
Published: April 2019

SummaryIn complex urban environment, GPS signals are susceptible to occlusion and interference; the positioning accuracy will be reduced or even impossible to locate. Today, Wireless Local Area Network (WLAN) localization technology can effectively supplement the blind spot of GPS signals. However, due to the instability of received signal strength (RSS), the positioning accuracy of WLAN is seriously affected. To solve the aforementioned problems, a GPS/WLAN integrated location algorithm based on particle filter is proposed. In our method, the federated Kalman filter is used to fuse the location information of GPS and WLAN, and then the important sampling function of the particle filter is generated by the fusion result. The updating of the particle weights is accomplished by the results of federated Kalman filter and map information. With the complementary characteristics of GPS and WLAN positioning technology, the experimental results show that our algorithm can effectively improves the coverage rate of GPS and the positioning accuracy of pedestrians in complex urban environment. Compared with GPS and WLAN single system and traditional fusion algorithm, the positioning accuracy of the proposed algorithm is significantly improved.
In Situ Synthesis of NiCoP Nanoparticles Supported on Reduced Graphene Oxide for the Catalytic Hydrolysis of Ammonia Borane
Authors: Yang Chenlu , Men Yana , Xu Yuezhi , Liang Lijing , Cai Ping , Luo Wei 
Published: April 2019

AbstractDeveloping highly efficient and stable noble‐metal‐free catalysts toward catalytic hydrolysis of ammonia borane (AB) for hydrogen storage is highly desirable, but still remains challenging. We report a simple and in situ co‐reduction approach to synthesize bimetallic NiCoP nanoparticles (NPs) supported on reduced graphene oxide (rGO). Thanks to the strong electronic interaction between Ni, Co, and P, the as‐synthesized Co89.8Ni10.2P11.7/rGO catalyst exhibits superior catalytic performance towards hydrolysis of AB, with the turnover frequency value (TOF) of 18.6 min−1, which is about 2.5 times higher than that of NiCo/rGO.
A Semitransparent Nitride Photoanode Responsive up to λ=600 nm Based on a Carbon Nanotube Thin Film Electrode
Authors: Akagi Daijiro , Kageshima Yosuke , Hashizume Yuta , Aoi Shigeki , Sasaki Yutaka , Kaneko Hiroyuki , Higashi Tomohiro , Hisatomi Takashi , Katayama Masao , Minegishi Tsutomu , Noda Suguru , Domen Kazunari 
Published: April 2019

AbstractThe development of semitransparent photoanodes is required for the construction of tandem photoelectrochemical (PEC) water splitting cells incorporating photocathodes. However, the poor stability of transparent conductive oxides at high temperatures hampers the growth of non‐oxide photoanodes with intense visible light absorption. In this work, semitransparent Ta3N5 thin film photoanodes were prepared on quartz glass substrates coated with carbon nanotubes (CNTs) by sputtering and thermal nitridation. This process makes use of the high thermal and chemical stability as well as the tunable conductivity and transmittance of CNT substrates. The photoanodic current produced by these Ta3N5 photoanodes at negative potentials is also enhanced by surface modification with Mg species. Conductive semitransparent CNT substrates such as these will assist in the development of new tandem PEC cells for water splitting.
A double‐blind, placebo‐controlled study of vortioxetine in the treatment of binge‐eating disorder
Authors: Grant Jon E. , Valle Stephanie , Cavic Elizabeth , Redden Sarah A. , Chamberlain Samuel R. 
Published: April 2019

AbstractBackgroundBinge‐eating disorder (BED) is associated with impaired quality of life and has a number of untoward public health associations. There are few established pharmacological treatments for BED, and available options are not suitable for all individuals. Vortioxetine is a recently developed pharmacological agent with effects on the serotonergic but also other neurochemical systems, which has yet to be evaluated in this context.MethodEighty adults with BED were recruited for a double‐blind, placebo‐controlled study. Participants received 12‐week treatment with vortioxetine (10 mg/day for 1 week, then increasing to 20 mg/day) or placebo in a parallel design. The primary efficacy outcome measures were binge‐eating frequency and weight. Safety data were collected. Effects of active versus placebo treatment were characterized using linear repeated measures models.ResultsBoth vortioxetine and placebo treatment were associated with significant reductions in binge‐eating frequency. Vortioxetine did not differentiate significantly from placebo on any efficacy measure. Frequency of adverse events did not differ between groups.DiscussionVortioxetine was not more effective than placebo in the treatment of BED. The ability to detect pharmacological treatment benefit may have been hindered by the relatively high placebo response and drop out. Future work should seek to better understand and predict placebo response in BED, with a view to more targeted treatment interventions and, potentially, sample enrichment.
Exploring the community phylogenetic structure along the slope aspect of subalpine meadows in the eastern Qinghai–Tibetan Plateau, China
Authors: Liu Minxia , Che Yingdi , Jiao Jiao , Li Lirong , Jiang Xiaoxuan 
Published: April 2019

AbstractExploring the community assembly has been important for explaining the maintenance mechanisms of biodiversity and species coexistence, in that it is a central issue in community ecology. Here, we examined patterns of the community phylogenetic structure of the subalpine meadow plant community along the slope gradient in the Qinghai–Tibetan Plateau of China. We surveyed all species and constructed the phylogenetic tree of the plant community based on data from the Angiosperm Phylogeny Group III. We selected the net relative index (NRI) and evaluated the community phylogenetic structure along the five slope plants communities. We found that the phylogenetic structure varied from phylogenetic clustering to phylogenetic overdispersion with the slope aspect from north to south. In the north slope, the community phylogenetically cluster indicated that the limiting similarity played a leading role in the community assembly and the maintenance of biodiversity. Community phylogenetic overdispersion in the east, southeast, and south slopes indicated that habitat filtration was the driving force for community assembly. The NRI index of the northeast slope was close to zero, implying random dispersion. But it may be driven by the neutral process or limiting similarity, in that the community assembly process was the result of a combination of several ecological factors and thus required further study.
Comparative genomics of 10 newCaenorhabditisspecies
Authors: Stevens Lewis , Félix Marie-Anne , Beltran Toni , Braendle Christian , Caurcel Carlos , Fausett Sarah , Fitch David , Frézal Lise , Gosse Charlie , Kaur Taniya , Kiontke Karin , Newton Matthew D. , Noble Luke M. , Richaud Aurélien , Rockman Matthew V. , Sudhaus Walter , Blaxter Mark 
Published: April 2019

AbstractThe nematode Caenorhabditis elegans has been central to the understanding of metazoan biology. However, C. elegans is but one species among millions and the significance of this important model organism will only be fully revealed if it is placed in a rich evolutionary context. Global sampling efforts have led to the discovery of over 50 putative species from the genus Caenorhabditis, many of which await formal species description. Here, we present species descriptions for 10 new Caenorhabditis species. We also present draft genome sequences for nine of these new species, along with a transcriptome assembly for one. We exploit these whole-genome data to reconstruct the Caenorhabditis phylogeny and use this phylogenetic tree to dissect the evolution of morphology in the genus. We reveal extensive variation in genome size and investigate the molecular processes that underlie this variation. We show unexpected complexity in the evolutionary history of key developmental pathway genes. These new species and the associated genomic resources will be essential in our attempts to understand the evolutionary origins of the C. elegans model.
Induction therapy in acute myeloid leukemia: Is it time to put aside standard 3 + 7?
Authors: Ferrara Felicetto , Vitagliano Orsola 
Published: April 2019

AbstractFor more than 30 years after its introduction, the combination of an anthracycline, usually daunorubicin, given for 3 days with continuous infusion of cytarabine for 7 days (3 + 7) has been the standard induction regimen for patients with acute myeloid leukemia (AML). In the last decade, there has been a progressive understanding of the molecular pathogenesis of the disease, which has led to discovery of potential therapeutic targets, resulting in selective treatment approaches aimed at rational and personalized treatment strategies. In the last 2 years, different new agents for AML have become widely available for newly diagnosed or relapsing/refractory patients, and others are object of clinical investigation. For most treatment‐naïve patients, it is now evident that standard 3 + 7 represents undertreatment in that the addition of new compounds results in better quality of response and improved survival. Hopefully, within few years, no patients with AML will be given standard 3 + 7 in the daily practice and a personalized approach targeting driving mutations will be widely applied.
Association between the flap endonuclease 1 gene polymorphisms and cancer susceptibility: An updated meta‐analysis
Authors: Moazeni‐Roodi Abdolkarim , Ghavami Saeid , Ansari Hossein , Hashemi Mohammad 
Published: April 2019

AbstractFlap endonuclease 1 (FEN1) has emerged as an important enzyme in the maintenance of genomic instability and preventing carcinogenesis. The relationship between FEN1 −69G>A (rs174538)+4150G>T (rs4246215) polymorphisms and cancer susceptibility has been reported; however, results were inconclusive. In the present study, a meta‐analysis of data from eligible reports was carried out to summarize the possible relationship between FEN1 polymorphisms and cancer risk. A total of 11 articles, including 20 studies with 7366 cases and 9028 controls and 18 studies with 6649 cases and 8325 controls for FEN1 rs174538 and FEN1 rs4246215 polymorphisms, respectively, were recruited for meta‐analysis. Overall, meta‐analyses showed that FEN1 rs174538 and rs4246215 polymorphisms are significantly associated with the decreased risk of cancer. The stratified analysis proposed that both variants were associated with protection against gastrointestinal cancer, breast cancer, hepatocellular cancer, esophageal cancer, gastric cancer, colorectal cancer, and lung cancer. In conclusion, this meta‐analysis revealed an association between FEN1 polymorphisms and cancer risk. Additional studies in a larger study population that include subjects from a variety of ethnicities are warranted to further verify our findings.
Weighted gene coexpression network analysis identifies specific transcriptional modules and hub genes related to intramuscular fat traits in chicken breast muscle
Authors: Li Guoxi , Zhao Yinli , Li Yuanfang , Chen Yi , Jin Wenjiao , Sun Guirong , Han Ruili , Tian Yadong , Li Hong , Kang Xiangtao 
Published: April 2019

AbstractIntramuscular fat (IMF) traits are important factors that influence meat quality. However, the molecular regulatory mechanisms that underlie this trait in chickens are still poorly understood at the gene coexpression level. Here, we performed a weighted gene coexpression network analysis between IMF traits and transcriptome profile in breast muscle in the Chinese domestic Gushi chicken breed at 6, 14, 22, and 30 weeks. A total of 26 coexpressed gene modules were identified. Six modules, which included the dark gray, purple, cyan, pink, light cyan, and blue modules, showed a significant positive correlation (P < 0.05) with IMF traits. The strongest correlation was observed between the dark gray module and IMF content (r = 0.85; P = 4e‐04) and between the blue module and different fatty acid content (r = 0.87~0.91; P = 5e‐05~2e‐04). Enrichment analysis showed that the enrichment of biological processes, such as fatty acid metabolic process, fat cell differentiation, acylglycerol metabolic process, and glycerolipid metabolism were significantly different in the six modules. In addition, the 32, 24, 4, 7, 6, and 25 hub genes were identified from the blue, pink, light cyan, cyan, dark gray, and purple modules, respectively. These hub genes are involved in multiple links to fatty acid metabolism, phospholipid metabolism, cholesterol metabolism, diverse cellular behaviors, and cell events. These results provide novel insights into the molecular regulatory mechanisms for IMF‐related traits in chicken and may also help to uncover the formation mechanism for excellent meat quality traits in local breeds of Chinese chicken.
Upregulation of circular RNA circ_0034642 indicates unfavorable prognosis in glioma and facilitates cell proliferation and invasion via the miR‐1205/BATF3 axis
Authors: Yi Chao , Li Hongbin , Li Dan , Qin Xiangying , Wang Jun , Liu Yang , Liu Zengliang , Zhang Jiewen 
Published: April 2019

AbstractAccumulating studies demonstrate the critical role of circular RNAs (circRNAs) in the pathogenesis of various types of cancers. Previously, hsa_circ_0034642 has been found elevated in glioma tissues compared with the normal tissues, as proved by high‐throughput microarray. We further investigated its expression level in 52 paired tissues and different glioma cell lines by quantitative reverse transcription‐polymerase chain reaction. In addition, Fisher's exact test, Kaplan‐Meier curves, and Cox analyses were performed to elucidate the clinical significance of hsa_circ_0034642. For the part of functional assays, gain/loss‐of‐function assays were conducted to measure cell growth, apoptosis, and metastatic properties affected by hsa_circ_0034642. Furthermore, the mechanisms of hsa_circ_0034642 were investigated by dual‐luciferase reporter assays. As the results demonstrated, hsa_circ_0034642 was boosted in glioma tissues and cells. Overexpression of hsa_circ_0034642 was associated with clinical severity and poor prognosis. What is more, elevated hsa_circ_0034642 strikingly facilitated cell proliferation, migratory and invasive capacities, and decreased apoptotic cells. Mechanistically, hsa_circ_0034642 sponges miR‐1205. miR‐1205 regulates BATF3 level through targeting its 3′‐untranslated region. In summary, hsa_circ_0034642 might play a key role in this malignancy.
PE_PGRS62 promotes the survival of Mycobacterium smegmatis within macrophages via disrupting ER stress‐mediated apoptosis
Authors: Long Quanxin , Xiang Xiaohong , Yin Qingqin , Li Shuangjiang , Yang Wenmin , Sun Hang , Liu Qi , Xie Jianping , Deng Wanyan 
Published: April 2019

AbstractMycobacterium tuberculosis, the leading causative agent of tuberculosis, remains one of the most deadly infectious pathogens. PE_PGRS proteins become a new focus as their species specificity in mycobacteria, especially in pathogenic mycobacteria. Despite intensive research, PE_PGRS proteins are still a mysterious aspect of mycobacterial pathogenesis with unknown mechanism. Herein, we focused on a PE_PGRS member from M. tuberculosis, PE_PGRS62, characterized by a surface‐exposed protein function in disrupting phagolysosome maturation. Expression of PE_PGRS62 in Mycobacterium smegmatis, a nonpathogenic species naturally deficient in PE_PGRS genes, resulted in enhanced resistance to various in vitro stresses and cellular survival in macrophage. As a consequence, the cytokine profiles of macrophage were disturbed and cell apoptosis were inhibited via decreasing endoplasmic reticulum stress response.