bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Extrinsic Coagulation Pathway: a Biomarker for Suicidal Behavior in Major Depressive Disorder
Authors: Yang Yongtao , Chen Jin , Liu Chengyu , Fang Liang , Liu Zhao , Guo Jing , Cheng Ke , Zhou Chanjuan , Zhan Yuan , Melgiri Narayan D. , Zhang Liang , Zhong Jiaju , Chen Jianjun , Rao Chenglong , Xie Peng 
Published: September 2016

AbstractAlthough an association between major depressive disorder (MDD) and suicide exists, most depressed patients never attempt suicide. An improved understanding of the factors contributing to suicidal risk in MDD can provide direction for suicide predictor development. In MDD suicide attempters (MDD-SA), MDD non-attempters (MDD-NA), and healthy controls (HC) (n = 12 each group), complementary plasma proteomics identified 45 differential proteins mapped to coagulation and inflammation, 25 of which underwent Western blotting. In another cohort including antidepressant-treated patients (n = 49 each group), seven additional extrinsic pathway proteins were selected for ELISA. Two inflammatory proteins and eight coagulatory proteins demonstrated alterations in MDD-SA relative to MDD-NA and HC. Applying a relative mass-action ratio, MDD-SA subjects displayed a higher relative prothrombinase activity than MDD-NA subjects, while healthy controls displayed higher relative prothrombinase activity than both MDD-SA and MDD-NA subjects. Consistent with our human findings, we found that heparin treatment significantly increased forced swimming test (FST) immobility time in rodents. MDD, independent of suicidality, is associated with a proinflammatory state accompanied by a hypothrombotic state. Suicidal behavior in MDD is associated with a more pronounced proinflammatory and prothrombotic phenotype accompanied by extrinsic pathway activation, revealing an extrinsic pathway biomarker that can be applied in predicting and monitoring suicidal risk.
Incomplete immune response to coxsackie B viruses associates with early autoimmunity against insulin
Authors: Ashton Michelle P. , Eugster Anne , Walther Denise , Daehling Natalie , Riethausen Stephanie , Kuehn Denise , Klingel Karin , Beyerlein Andreas , Zillmer Stephanie , Ziegler Anette-Gabriele , Bonifacio Ezio 
Published: September 2016

AbstractViral infections are associated with autoimmunity in type 1 diabetes. Here, we asked whether this association could be explained by variations in host immune response to a putative type 1 etiological factor, namely coxsackie B viruses (CVB). Heterogeneous antibody responses were observed against CVB capsid proteins. Heterogeneity was largely defined by different binding to VP1 or VP2. Antibody responses that were anti-VP2 competent but anti-VP1 deficient were unable to neutralize CVB, and were characteristic of children who developed early insulin-targeting autoimmunity, suggesting an impaired ability to clear CVB in early childhood. In contrast, children who developed a GAD-targeting autoimmunity had robust VP1 and VP2 antibody responses to CVB. We further found that 20% of memory CD4+ T cells responding to the GAD65247-266 peptide share identical T cell receptors to T cells responding to the CVB4 p2C30-51 peptide, thereby providing direct evidence for the potential of molecular mimicry as a mechanism for GAD autoimmunity. Here, we highlight functional immune response differences between children who develop insulin-targeting and GAD-targeting autoimmunity, and suggest that children who lose B cell tolerance to insulin within the first years of life have a paradoxical impaired ability to mount humoral immune responses to coxsackie viruses.
Graphene-assisted multiple-input high-base optical computing
Authors: Hu Xiao , Wang Andong , Zeng Mengqi , Long Yun , Zhu Long , Fu Lei , Wang Jian 
Published: September 2016

AbstractWe propose graphene-assisted multiple-input high-base optical computing. We fabricate a nonlinear optical device based on a fiber pigtail cross-section coated with a single-layer graphene grown by chemical vapor deposition (CVD) method. An approach to implementing modulo 4 operations of three-input hybrid addition and subtraction of quaternary base numbers in the optical domain using multiple non-degenerate four-wave mixing (FWM) processes in graphene coated optical fiber device and (differential) quadrature phase-shift keying ((D)QPSK) signals is presented. We demonstrate 10-Gbaud modulo 4 operations of three-input quaternary hybrid addition and subtraction (A + B − C, A + C − B, B + C − A) in the experiment. The measured optical signal-to-noise ratio (OSNR) penalties for modulo 4 operations of three-input quaternary hybrid addition and subtraction (A + B − C, A + C − B, B + C − A) are measured to be less than 7 dB at a bit-error rate (BER) of 2 × 10−3. The BER performance as a function of the relative time offset between three signals (signal offset) is also evaluated showing favorable performance.
Purification, characterization, cytotoxicity and anticancer activities of L-asparaginase, anti-colon cancer protein, from the newly isolated alkaliphilic Streptomyces fradiae NEAE-82
Authors: El-Naggar Noura El-Ahmady , Deraz Sahar F. , Soliman Hoda M. , El-Deeb Nehal M. , El-Ewasy Sara M. 
Published: September 2016

AbstractL-asparaginase is an important enzyme as therapeutic agents used in combination with other drugs in the treatment of acute lymphoblastic leukemia. A newly isolated actinomycetes strain, Streptomyces sp. NEAE-82, was potentially producing extracellular L-asparaginase, it was identified as Streptomyces fradiae NEAE-82, sequencing product was deposited in the GenBank database under accession number KJ467538. L-asparaginase was purified from the crude enzyme using ammonium sulfate precipitation, dialysis and ion exchange chromatography using DEAE Sepharose CL-6B. Further the kinetic studies of purified enzyme were carried out. The optimum pH, temperature and incubation time for maximum L-asparaginase activity were found to be 8.5, 40 °C and 30 min, respectively. The optimum substrate concentration was found to be 0.06 M. The Km and Vmax of the enzyme were 0.01007 M and 95.08 Uml−1min−1, respectively. The half-life time (T1/2) was 184.91 min at 50 °С, while being 179.53 min at 60 °С. The molecular weight of the subunits of L-asparaginase was found to be approximately 53 kDa by SDS–PAGE analysis. The purified L-asparaginase showed a final specific activity of 30.636 U/mg protein and was purified 3.338-fold. The present work for the first time reported more information in the production, purification and characterization of L-asparaginase produced by newly isolated actinomycetes Streptomyces fradiae NEAE-82.
Nedd4-2 haploinsufficiency causes hyperactivity and increased sensitivity to inflammatory stimuli
Authors: Yanpallewar Sudhirkumar , Wang Ting , Koh Dawn C. I. , Quarta Eros , Fulgenzi Gianluca , Tessarollo Lino 
Published: September 2016

AbstractNedd4-2 (NEDD4L in humans) is a ubiquitin protein ligase best known for its role in regulating ion channel internalization and turnover. Nedd4-2 deletion in mice causes perinatal lethality associated with increased epithelial sodium channel (ENaC) expression in lung and kidney. Abundant data suggest that Nedd4-2 plays a role in neuronal functions and may be linked to epilepsy and dyslexia in humans. We used a mouse model of Nedd4-2 haploinsufficiency to investigate whether an alteration in Nedd4-2 levels of expression affects general nervous system functions. We found that Nedd4-2 heterozygous mice are hyperactive, have increased basal synaptic transmission and have enhanced sensitivity to inflammatory pain. Thus, Nedd4-2 heterozygous mice provide a new genetic model to study inflammatory pain. These data also suggest that in human, SNPs affecting NEDD4L levels may be involved in the development of neuropsychological deficits and peripheral neuropathies and may help unveil the genetic basis of comorbidities.
Isolation, Co-Crystallization and Structure-Based Characterization of Anabaenopeptins as Highly Potent Inhibitors of Activated Thrombin Activatable Fibrinolysis Inhibitor (TAFIa)
Authors: Schreuder Herman , Liesum Alexander , Lönze Petra , Stump Heike , Hoffmann Holger , Schiell Matthias , Kurz Michael , Toti Luigi , Bauer Armin , Kallus Christopher , Klemke-Jahn Christine , Czech Jörg , Kramer Dan , Enke Heike , Niedermeyer Timo H. J. , Morrison Vincent , Kumar Vasant , Brönstrup Mark 
Published: September 2016

AbstractMature thrombin activatable fibrinolysis inhibitor (TAFIa) is a carboxypeptidase that stabilizes fibrin clots by removing C-terminal arginines and lysines from partially degraded fibrin. Inhibition of TAFIa stimulates the degradation of fibrin clots and may help to prevent thrombosis. Applying a lead finding approach based on literature-mining, we discovered that anabaenopeptins, cyclic peptides produced by cyanobacteria, were potent inhibitors of TAFIa with IC50 values as low as 1.5 nM. We describe the isolation and structure elucidation of 20 anabaenopeptins, including 13 novel congeners, as well as their pronounced structure-activity relationships (SAR) with respect to inhibition of TAFIa. Crystal structures of the anabaenopeptins B, C and F bound to the surrogate protease carboxypeptidase B revealed the binding modes of these large (~850 Da) compounds in detail and explained the observed SAR, i.e. the strong dependence of the potency on a basic (Arg, Lys) exocyclic residue that addressed the S1’ binding pocket, and a broad tolerance towards substitutions in the pentacyclic ring that acted as a plug of the active site.
Higher-dimensional performance of port-based teleportation
Authors: Wang Zhi-Wei , Braunstein Samuel L. 
Published: September 2016

AbstractPort-based teleportation (PBT) is a variation of regular quantum teleportation that operates without a final unitary correction. However, its behavior for higher-dimensional systems has been hard to calculate explicitly beyond dimension d = 2. Indeed, relying on conventional Hilbert-space representations entails an exponential overhead with increasing dimension. Some general upper and lower bounds for various success measures, such as (entanglement) fidelity, are known, but some become trivial in higher dimensions. Here we construct a graph-theoretic algebra (a subset of Temperley-Lieb algebra) which allows us to explicitly compute the higher-dimensional performance of PBT for so-called “pretty-good measurements” with negligible representational overhead. This graphical algebra allows us to explicitly compute the success probability to distinguish the different outcomes and fidelity for arbitrary dimension d and low number of ports N, obtaining in addition a simple upper bound. The results for low N and arbitrary d show that the entanglement fidelity asymptotically approaches N/d2 for large d, confirming the performance of one lower bound from the literature.
Statins affect ETS1-overexpressing triple-negative breast cancer cells by restoring DUSP4 deficiency
Authors: Jung Hae Hyun , Lee Soo-Hyeon , Kim Ji-Yeon , Ahn Jin Seok , Park Yeon Hee , Im Young-Hyuck 
Published: September 2016

AbstractWe investigated the molecular mechanisms underlying statin-induced growth suppression of triple-negative breast cancer (TNBC) that overexpress the transcription factor ets proto-oncogene 1(ets-1) and downregulate dual specific protein phosphatase 4(dusp4) expression. We examined the gene expression of BC cell lines using the nCounter expression assay, MTT viability assay, cell proliferation assay and Western blot to evaluate the effects of simvastatin. Finally, we performed cell viability testing in TNBC cell line-transfectedDUSP4. We demonstrated thatETS1mRNA and protein were overexpressed in TNBC cells compared with other BC cell lines (P = <0.001) andDUSP4mRNA was downregulated (P = <0.001). MTT viability assay showed that simvastatin had significant antitumor activity (P = 0.002 in 0.1 μM). In addition, simvastatin could restore dusp4 deficiency and suppress ets-1 expression in TNBC. Lastly, we found that si-DUSP4 RNA transfection overcame the antitumor activity of statins. MAPK pathway inhibitor, U0126 and PI3KCA inhibitor LY294002 also decreased levels of ets-1, phosphor-ERK and phosphor-AKT on Western blot assay. Accordingly, our study indicates that simvastatin potentially affects the activity of transcriptional factors such as ets-1 and dusp4 through the MAPK pathway. In conclusion, statins might be potential candidates for TNBC therapy reducing ets-1 expression via overexpression of dusp4.
Exploration and detection of potential regulatory variants in refractive error GWAS
Authors: Liao Xuan , Lan ChangJun , Liao Dan , Tian Jing , Huang XiuQi 
Published: September 2016

AbstractRefractive error (RE) is a complex multifactorial disease. Genome-wide association studies (GWAS) have provided significant insight into the genetic architecture and identified plenty of robust genetic variations or single nucleotide polymorphisms (SNPs) associated with complex disease. A major current challenge is to convert those resources into causal variants and target genes. We used RegulomeDB and HaploReg to annotate regulatory information onto associated SNPs derived from the two largest RE GWAS, and additional SNPs in linkage disequilibrium (LD) with GWAS significant SNPs. Overall 868 SNPs were investigated, out of which 662 returned RegulomeDB scores of 1 to 6. It was observed that 36 out of those SNPs show strong evidence of regulatory effects with a RegulomeDB score of 1, while only four of them were GWAS significant SNPs (CD55/rs1652333, CNDP2/rs12971120, RDH5/rs3138142 and rs3138144). The results encourage us to explore those putative pathogenic variants, both GWAS significant SNPs as well as the SNPs in LD, for future discernment of functional consequence. This study offers the attractive approach for prioritizing potential functional variants by combining ENCODE data and GWAS information, and provide further insights into the pathogenesis and mechanism and ultimately therapeutics.
The association between naturally acquired IgG subclass specific antibodies to the PfRH5 invasion complex and protection from Plasmodium falciparum malaria
Authors: Weaver Rupert , Reiling Linda , Feng Gaoqian , Drew Damien R. , Mueller Ivo , Siba Peter M. , Tsuboi Takafumi , Richards Jack S. , Fowkes Freya J. I. , Beeson James G. 
Published: September 2016

AbstractUnderstanding the targets and mechanisms of human immunity to malaria is important for advancing the development of highly efficacious vaccines and serological tools for malaria surveillance. The PfRH5 and PfRipr proteins form a complex on the surface of P. falciparum merozoites that is essential for invasion of erythrocytes and are vaccine candidates. We determined IgG subclass responses to these proteins among malaria-exposed individuals in Papua New Guinea and their association with protection from malaria in a longitudinal cohort of children. Cytophilic subclasses, IgG1 and IgG3, were predominant with limited IgG2 and IgG4, and IgG subclass-specific responses were higher in older children and those with active infection. High IgG3 to PfRH5 and PfRipr were significantly and strongly associated with reduced risk of malaria after adjusting for potential confounding factors, whereas associations for IgG1 responses were generally weaker and not statistically significant. Results further indicated that malaria exposure leads to the co-acquisition of IgG1 and IgG3 to PfRH5 and PfRipr, as well as to other PfRH invasion ligands, PfRH2 and PfRH4. These findings suggest that IgG3 responses to PfRH5 and PfRipr may play a significant role in mediating naturally-acquired immunity and support their potential as vaccine candidates and their use as antibody biomarkers of immunity.
Record-breaking warming and extreme drought in the Amazon rainforest during the course of El Niño 2015–2016
Authors: Jiménez-Muñoz Juan C. , Mattar Cristian , Barichivich Jonathan , Santamaría-Artigas Andrés , Takahashi Ken , Malhi Yadvinder , Sobrino José A. , Schrier Gerard van der 
Published: September 2016

AbstractThe El Niño-Southern Oscillation (ENSO) is the main driver of interannual climate extremes in Amazonia and other tropical regions. The current 2015/2016 EN event was expected to be as strong as the EN of the century in 1997/98, with extreme heat and drought over most of Amazonian rainforests. Here we show that this protracted EN event, combined with the regional warming trend, was associated with unprecedented warming and a larger extent of extreme drought in Amazonia compared to the earlier strong EN events in 1982/83 and 1997/98. Typical EN-like drought conditions were observed only in eastern Amazonia, whilst in western Amazonia there was an unusual wetting. We attribute this wet-dry dipole to the location of the maximum sea surface warming on the Central equatorial Pacific. The impacts of this climate extreme on the rainforest ecosystems remain to be documented and are likely to be different to previous strong EN events.
Deep sequencing reveals microbiota dysbiosis of tongue coat in patients with liver carcinoma
Authors: Lu Haifeng , Ren Zhigang , Li Ang , Zhang Hua , Jiang Jianwen , Xu Shaoyan , Luo Qixia , Zhou Kai , Sun Xiaoli , Zheng Shusen , Li Lanjuan 
Published: September 2016

AbstractLiver carcinoma (LC) is a common malignancy worldwide, associated with high morbidity and mortality. Characterizing microbiome profiles of tongue coat may provide useful insights and potential diagnostic marker for LC patients. Herein, we are the first time to investigate tongue coat microbiome of LC patients with cirrhosis based on 16S ribosomal RNA (rRNA) gene sequencing. After strict inclusion and exclusion criteria, 35 early LC patients with cirrhosis and 25 matched healthy subjects were enrolled. Microbiome diversity of tongue coat in LC patients was significantly increased shown by Shannon, Simpson and Chao 1 indexes. Microbiome on tongue coat was significantly distinguished LC patients from healthy subjects by principal component analysis. Tongue coat microbial profiles represented 38 operational taxonomic units assigned to 23 different genera, distinguishing LC patients. Linear discriminant analysis (LDA) effect size (LEfSe) reveals significant microbial dysbiosis of tongue coats in LC patients. Strikingly, Oribacterium and Fusobacterium could distinguish LC patients from healthy subjects. LEfSe outputs show microbial gene functions related to categories of nickel/iron_transport, amino_acid_transport, energy produced system and metabolism between LC patients and healthy subjects. These findings firstly identify microbiota dysbiosis of tongue coat in LC patients, may providing novel and non-invasive potential diagnostic biomarker of LC.
Factors associated with Severe Fever with Thrombocytopenia Syndrome infection and fatal outcome
Authors: Sun Jimin , Gong Zhenyu , Ling Feng , Zhang Rong , Tong Zhendong , Chang Yue , Chen Enfu , Liu Qiyong , Lin Junfen , Chen Zhiping , Jiang Jianmin 
Published: September 2016

AbstractSevere fever with thrombocytopenia syndrome (SFTS) is emerging in China and the incidence increased year by year. In this study, we conducted case control study to explore factors associated with SFTS virus (SFTSV) infection and fatal outcome. In the study of factors associated with SFTSV infection, a total of 216 individuals participated the study, including 72 cases and 144 matched controls. There were significant differences in proportion of history of tick bite and breeding domestic animals between cases and controls. Of note, individuals who were unclear whether they had been bitten by ticks had the highest risk of SFTSV infection and odds ratio (OR) was 10.222. In the study of factors associated with SFTS fatal outcome, a total of 129 cases participated the study including 16 deaths and 113 survivors. Significant differences were observed in body mass index (BMI), intervals from illness onset to confirmation, and proportion of gingival hemorrhage between deaths and survivors, whose ORs of these factors were 3.903, 1.996, and 3.826, respectively. Our results suggest that all patients with fever, thrombocytopenia and leukocytopenia in SFTS endemic areas should be suspected of SFTS, even they don’t have history of tick bite, and more intense treatment should be administered to patients with abnormal BMI before laboratory parameters are detected.
Miniaturised equal/unequal SIW power divider with bandpass response loaded by CSRRs
Authors: Danaeian M. , Moznebi A.‐R. , Afrooz K. , Hakimi H. 
Published: September 2016

A miniaturised equal/unequal substrate integrated waveguide power divider with bandpass filtering response loaded by complementary split‐ring resonators (CSRRs) is proposed. The proposed structure is based on the theory of evanescent mode propagation. The use of the CSRRs enables the filtering function of the power divider and is able to reduce its size. By changing the orientations of the CSRRs, the equal/unequal power dividers are achieved. In the unequal power divider, the power ratio can be arbitrarily controlled by carefully tuning the parameters of the CSRRs and locations of the output ports. Three miniaturised filtering power divider samples with power division ratios of 1:1, 1:4 and 1:8 are fabricated and tested. These designs resonate at the frequency of 5.8 GHz covering WLAN. The sizes of the proposed power dividers (1:1, 1:4 and 1:8) are only 0.37 × 0.21λg2, 0.3 × 0.16λg2 and 0.3 × 0.15λg2, respectively.
Security constrained economic dispatch of wind‐integrated power system considering optimal system state selection
Authors: Ma Yanfeng , Hao Yi , Zhao Shuqiang , Bi Huijing 
Published: September 2016

The increasing penetration of wind power makes it a critical problem to maintain the security and economy in power system operations. This study proposes a security constrained economic dispatch (SCED) strategy that considers optimising system state selection and spinning reserve allocation. The system state selection is judged by the criterion of occurrence probability. Considering the impacts of wind power integration on the outage probability of system component, the over‐current protection outage model and voltage protection outage model are employed to calculate the operational outage probabilities of transmission lines and generators, respectively. The fast sorting technique is adopted to select all system states with higher‐occurrence probability than the system security threshold. Besides the traditional constraints on system demand and regulation range, the spinning reserve allocation additionally obeys the transmission constraints in the selected states to avoid transmission congestion in contingency situations. Benders decomposition is utilised to partition the SCED problem into the active power dispatch sub‐problem and the optimal reserve allocation sub‐problem for tractability. A numerical comparison with the traditional N−1 security assessment SCED is given to validate security and economic improvement of the proposed method.