bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a Functionally Relevant Adeno-Associated Virus Rep68 Oligomeric Interface
Authors: Bardelli Martino , Zárate-Pérez Francisco , Agúndez Leticia , Linden R. Michael , Escalante Carlos R. , Henckaerts Els
Published: May 2016

The life cycle of the human parvovirus adeno-associated virus (AAV) is orchestrated by four Rep proteins. The large Rep proteins, Rep78 and Rep68, are remarkably multifunctional and display a range of biochemical activities, including DNA binding, nicking, and unwinding. Functionally, Rep78 and Rep68 are involved in transcriptional regulation, DNA replication, and genomic integration. Structurally, the Rep proteins share an AAA
+
domain characteristic of superfamily 3 helicases, with the large Rep proteins additionally containing an N-terminal origin-binding domain (OBD) that specifically binds and nicks DNA. The combination of these domains, coupled with dynamic oligomerization properties, is the basis for the remarkable multifunctionality displayed by Rep68 and Rep78 during the AAV life cycle. In this report, we describe an oligomeric interface formed by Rep68 and demonstrate how disruption of this interface has drastic effects on both the oligomerization and functionality of the Rep proteins. Our results support a role for the four-helix bundle in the helicase domain of Rep68 as a bona fide oligomerization domain (OD). We have identified key residues in the OD that are critical for the stabilization of the Rep68-Rep68 interface; mutation of these key residues disrupts the enzymatic activities of Rep68, including DNA binding and nicking, and compromises viral DNA replication and transcriptional regulation of the viral promoters. Taken together, our data contribute to our understanding of the dynamic and substrate-responsive Rep78/68 oligomerization that is instrumental in the regulation of the DNA transitions that take place during the AAV life cycle.

IMPORTANCE
The limited genome size of small viruses has driven the evolution of highly multifunctional proteins that integrate different domains and enzymatic activities within a single polypeptide. The Rep68 protein from adeno-associated virus (AAV) combines a DNA binding and endonuclease domain with a helicase-ATPase domain, which together support DNA replication, transcriptional regulation, and site-specific integration. The coordination of the enzymatic activities of Rep68 remains poorly understood; however, Rep68 oligomerization and Rep68-DNA interactions have been suggested to play a crucial role. We investigated the determinants of Rep68 oligomerization and identified a hydrophobic interface necessary for Rep68 activity during the AAV life cycle. Our results provide new insights into the molecular mechanisms underlying the regulation of the versatile Rep proteins. Efficient production of AAV-based gene therapy vectors requires optimal Rep expression levels, and studies such as the one presented here could contribute to further optimization of AAV production schemes.
p53 Is a Host Cell Regulator during Herpes Simplex Encephalitis
Authors: Maruzuru Yuhei , Koyanagi Naoto , Takemura Naoki , Uematsu Satoshi , Matsubara Daisuke , Suzuki Yutaka , Arii Jun , Kato Akihisa , Kawaguchi Yasushi
Published: May 2016

p53 is a critical host cell factor in the cellular response to a broad range of stress factors. We recently reported that p53 is required for efficient herpes simplex virus 1 (HSV-1) replication in cell culture. However, a defined role for p53 in HSV-1 replication and pathogenesis
in vivo
remains elusive. In this study, we examined the effects of p53 on HSV-1 infection
in vivo
using p53-deficient mice. Following intracranial inoculation, p53 knockout reduced viral replication in the brains of mice and led to significantly reduced rates of mortality due to herpes simplex encephalitis. These results suggest that p53 is an important host cell regulator of HSV-1 replication and pathogenesis in the central nervous system (CNS).

IMPORTANCE
HSV-1 causes sporadic cases of encephalitis, which, even with antiviral therapy, can result in severe neurological defects and even death. Many host cell factors involved in the regulation of CNS HSV-1 infection have been investigated using genetically modified mice. However, most of these factors are immunological regulators and act via immunological pathways in order to restrict CNS HSV-1 infection. They therefore provide limited information on intrinsic host cell regulators that may be involved in the facilitation of CNS HSV-1 infection. Here we demonstrate that a host cell protein, p53, which has generally been considered a host cell restriction factor for various viral infections, is required for efficient HSV-1 replication and pathogenesis in the CNS of mice. This is the first report showing that p53 positively regulates viral replication and pathogenesis
in vivo
and provides insights into its molecular mechanism, which may suggest novel clinical treatment options for herpes simplex encephalitis.
Mutations in Encephalomyocarditis Virus 3A Protein Uncouple the Dependency of Genome Replication on Host Factors Phosphatidylinositol 4-Kinase IIIα and Oxysterol-Binding Protein
Authors: Dorobantu Cristina M. , Albulescu Lucian , Lyoo Heyrhyoung , van Kampen Mirjam , De Francesco Raffaele , Lohmann Volker , Harak Christian , van der Schaar Hilde M. , Strating Jeroen R. P. M. , Gorbalenya Alexander E. , van Kuppeveld Frank J. M.
Published: May 2016

Positive-strand RNA viruses modulate lipid homeostasis to generate unique, membranous “replication organelles” (ROs) where viral genome replication takes place. Hepatitis C virus, encephalomyocarditis virus (EMCV), and enteroviruses have convergently evolved to hijack host phosphatidylinositol 4-kinases (PI4Ks), which produce PI4P lipids, to recruit oxysterol-binding protein (OSBP), a PI4P-binding protein that shuttles cholesterol to ROs. Consistent with the proposed coupling between PI4K and OSBP, enterovirus mutants resistant to PI4KB inhibitors are also resistant to OSBP inhibitors. Here, we show that EMCV can replicate without accumulating PI4P/cholesterol at ROs, by acquiring point mutations in nonstructural protein 3A. Remarkably, the mutations conferred resistance to PI4K but not OSBP inhibitors, thereby uncoupling the levels of dependency of EMCV RNA replication on PI4K and OSBP. This work may contribute to a deeper understanding of the roles of PI4K/PI4P and OSBP/cholesterol in membrane modifications induced by positive-strand RNA viruses.
Cemento-ossifying fibroma of the jaw
Authors: Katti Girish , Khan Mohammed Munnawarulla , Chaubey Shashi Shanker , Amena Mehroz
Published: May 2016

Cemento-ossifying fibroma is a benign growth, considered to originate from the periodontal ligament. It is often encapsulated and predominantly located in the mandible, and presents as a slow-growing lesion, but may cause deformity if left untreated. The definitive diagnosis of these lesions requires integration of its clinical, radiological and histological features. We present a case of cemento-ossifying fibroma in relation to the lower left one-third of the face, and its management.
Jackhammer oesophagus in a case of linitis plastica
Authors: Chaudhry Naueen Akbar , Zahid Kamran , Coman Roxana , Zhang Qing
Published: May 2016

A 52-year-old Caucasian woman presented with progressive nausea and vomiting, weight loss, and burning epigastric and chest pain. Initial oesophagogastroduodenoscopy (OGD) with biopsies demonstrated gastritis in absence ofHelicobacter pylori. A gastric emptying study, CT scan with pancreatic protocol and a colonoscopy revealed no concerning findings. Calcium channel blockers and proton pump inhibitors offered little improvement. A high-resolution oesophageal impedance manometry was performed, which was significant for jackhammer oesophagus with maximum distal contractile index 11 052 mm Hg-s-cm. Another OGD was carried out for Botox injection to oesophagogastric junction. Repeat gastric biopsies reported gastric adenocarcinoma, further diagnosed as stage 4 linitis plastica with metastatic peritoneal carcinomatosis. To the best of our knowledge, this is the only case of linitis plastica associated with jackhammer oesophagus.
Factors predicting a change in diagnosis in patients hospitalised through the emergency room: a prospective observational study
Authors: Hautz Stefanie C , Schuler Luca , Kämmer Juliane E , Schauber Stefan K , Ricklin Meret E , Sauter Thomas C , Maier Volker , Birrenbach Tanja , Exadaktylos Aristomenis , Hautz Wolf E
Published: May 2016

Introduction

Emergency rooms (ERs) generally assign a preliminary diagnosis to patients, who are then hospitalised and may subsequently experience a change in their lead diagnosis (cDx). In ERs, the cDx rate varies from around 15% to more than 50%. Among the most frequent reasons for diagnostic errors are cognitive slips, which mostly result from faulty data synthesis. Furthermore, physicians have been repeatedly found to be poor self-assessors and to be overconfident in the quality of their diagnosis, which limits their ability to improve. Therefore, some of the clinically most relevant research questions concern how diagnostic decisions are made, what determines their quality and what can be done to improve them. Research that addresses these questions is, however, still rare. In particular, field studies that allow for generalising findings from controlled experimental settings are lacking. The ER, with its high throughput and its many simultaneous visits, is perfectly suited for the study of factors contributing to diagnostic error. With this study, we aim to identify factors that allow prediction of an ER's diagnostic performance. Knowledge of these factors as well as of their relative importance allows for the development of organisational, medical and educational strategies to improve the diagnostic performance of ERs.

Methods and analysis

We will conduct a field study by collecting diagnostic decision data, physician confidence and a number of influencing factors in a real-world setting to model real-world diagnostic decisions and investigate the adequacy, validity and informativeness of physician confidence in these decisions. We will specifically collect data on patient, physician and encounter factors as predictors of the dependent variables. Statistical methods will include analysis of variance and a linear mixed-effects model.

Ethics and dissemination

The Bern ethics committee approved the study under KEK Number 197/15. Results will be published in peer-reviewed scientific medical journals. Authorship will be determined according to ICMJE guidelines.

Trial registration number

The study protocol Version 1.0 from 17 May 2015 is registered in the Inselspital Research Database Information System (IRDIS) and with the IRB (‘Kantonale Ethikkomission’) Bern under KEK Number 197/15.
Molecular clonality assessment shows high performance to predict malignant B-cell non-Hodgkin's lymphoma using cytological smears
Authors: Roepman Paul , Boots Cecile-Marie , Scheidel Karen C , Sprong Tobias , de Bruin Peter , de Weerdt Okke , Groenen Patricia J T A , Kummer J Alain
Published: May 2016

Aims

Molecular PCR-based clonality analysis is helpful for identification of monoclonal B-cell or T-cell populations and to distinguish malignant lymphoma from reactive lymphoid hyperplasia. Typically, clonality assessment on fine-needle aspiration cytology (FNAC) requires freshly obtained aspirates, but the collection and processing of these samples are often challenging in daily practice. In this study, we assessed the routine diagnostic value of the EuroClonality/BIOMED-2 assay for B-cell clonality on air-dried archived Giemsa-stained smears.

Methods

This study comprised a retrospective analysis of a consecutive diagnostic cohort of 192 FNAC samples from 184 patients with at least 2-year follow-up. The results from the clonality assay were integrated with cytomorphological assessment and evaluated for their accuracy in detecting malignant disease. EuroClonality expert re-evaluation was performed for all cases with ambiguous results and for cases in which the diagnosis did not match the follow-up data.

Results

The clonality assay showed a high accuracy of 93% for detection of malignancy, with a sensitivity of 93% and a specificity of 92%. All 64 cases with monoclonal Ig heavy chain (IGH)/Ig kappa chain (IGK) rearrangements were confirmed malignant by histology or clinical follow-up. Expert re-evaluation changed the definite diagnosis for five cases (3%), mainly because of low signals or no proper duplicate results. We discuss and elucidate all cases for which the clonality results did not match the disease follow-up.

Conclusions

This study showed that EuroClonality/BIOMED-2 assay can successfully be performed on cytological Giemsa-stained smears and inclusion in daily practice can assist in better identification of malignant lymphoma.
Time to spontaneous ductus arteriosus closure in full-term neonates
Authors: Nagasawa Hiroyuki , Hamada Chikuma , Wakabayashi Masashi , Nakagawa Yuki , Nomura Satoshi , Kohno Yoshinori
Published: May 2016

Objective

The mean closure time of the ductus arteriosus (DA) in full-term neonates is presumed to be 1–2 days after birth; however, whether this rate is accurate throughout the neonatal period is still unclear. In addition, the clinical determinants that influence DA closure remain unknown.

Methods

Echocardiography was performed 1826 times (897 in boys, 929 in girls) in 1442 participants (732 boys, 710 girls). An iE33 colour Doppler echocardiograph supplied by Philips Electronics was employed to examine DA flow. Data regarding sex, birth date, examination date, method of delivery, mother's age, past deliveries, neonatal body weight and body height were also collected. The Statistical Analysis System makes statistical clarification of these queries possible. We examined the persistence of DA in full-term neonates and appropriate for gestational age (AGA) neonates in the early neonatal period using colour Doppler echocardiography, and a subsequent analysis with SAS.

Results

After performing multivariable analyses, the median DA persistency times were 27.42 and 45.10 h after birth in boys and girls, respectively. A statistically significant sex difference was observed (p<0.0001). Additionally, significant time differences were observed between vaginal and scheduled caesarean deliveries, at 26.97 and 28.93 h, respectively (p=0.0245). No significant differences were observed in the other variables.

Conclusions

Spontaneous DA closure time curves were clarified for the first time throughout the early neonatal period in full-term and AGA neonates. It was revealed that both sex and delivery method play important roles in time to DA closure.
Comparison of relationship between histopathological, serological and biochemical parameters in patients with chronic hepatitis B infection
Authors: Diktas Husrev , Karacaer Zehra , Özturk I Ilker , Cicek Huseyin
Published: May 2016

Objective

To demonstrate the relationship between liver histology, alanine aminotransferase (ALT)/aspartate aminotransferase (AST) and hepatitis B virus (HBV) DNA levels based on hepatitis B e antigen (HBeAg) seropositivity status in naive patients with chronic hepatitis B (CHB).

Materials and method

Naive patients with CHB admitted to our hospital between January 2012 and April 2014 were evaluated retrospectively. The patients were allocated into one of two groups based on HBeAg-seropositivity status.

Results

Two hundred and fourteen patients were enrolled in the study. Of these 214 patients, 103 (48.1%) were HBeAg-positive and 111 (51.9%) were HBeAg-negative. In the HBeAg-positive group, positive correlations were found between histologic activity index (HAI) scores and ALT (t=3.3, r=0.31, p=0.001), AST (t=2.8, r=0.27, p=0.005) and HBV DNA load (t=2.5, r=0.24, p=0.014). Additionally, in this group, fibrosis scores had positive correlations with ALT (t=3.3, r=0.32, p=0.001) and AST (t=2.7, r=0.26, p=0.008). In the HBeAg-negative group, positive correlations were found between HAI scores and ALT (t=3, r=0. 28, p=0.003), AST (t=3, r=0. 28, p=0.003) and HBV DNA (t=5.3, r=0. 45, p=0). In this same group, fibrosis scores had a positive correlation with HBV DNA (t=2.2, r=0. 21, p=0.024). Multivariate logistic regression analysis showed a positive relationship between fibrosis and ALT in the HBeAg-positive group and a positive relationship between fibrosis and HBV DNA load in the HBeAg-negative group.

Conclusions

This study showed that HBV DNA load is an independent predictive factor for evaluating HAI and fibrosis in the HBeAg-negative group. Also, ALT is an independent predictive factor for evaluating fibrosis in the HBeAg-positive group.
Surgical treatment of a bilateral patellar fracture in a young adult dog
Authors: Cabon Quentin , Cachon Thibaut
Published: May 2016

A 15‐month‐old female Belgian Malinois presented with an inability to ambulate on its pelvic limbs after running away. Orthopaedic examination revealed painful stifles, crepitus and a bilateral lack of patellar continuity. Radiographs confirmed bilateral patellar fractures showing a similar fracture pattern on both sides, with three parts divided in the shape of a ‘Y’. Surgical treatment consisted of fracture stabilisation using pins and wires protected by a tibio‐patellar prosthesis and type Ia external fixator. Bone healing occurred and a satisfactory level of function was observed at long‐term follow‐up. This report describes the original presentation of bilateral patellar fractures in a dog. The bilateral presentation and similar fracture pattern on both sides potentially support the notion that failure of the patellar secondary ossification centres to unite caused fragility of both patellae.
Synergistic and additive effects of drought stress and simulated herbivory on two goldenrods, Solidago altissima and S. gigantea
Authors: Shibel Zoryana , Heard Stephen B.
Published: May 2016

Understanding the combined effects of stressors on plants is important for understanding how they will tolerate herbivory and other damage under unfavorable conditions. When two stresses have synergistic effects, plants may experience particularly strong impacts. We examined individual and combined effects of drought stress and clipping (simulated herbivory) on two species of goldenrods (Solidago altissima L. and S. gigantea Ait.). Each stress reduced production of most plant structures, with drought stress having stronger impacts than clipping. The effects of the two stresses were additive for S. gigantea but synergistic for S. altissima, at least for aboveground biomass and inflorescence biomass. Both species, when under stress, reallocated resources toward asexual reproduction (rhizomes) and away from sexual reproduction (inflorescences). Our results suggest that even closely related plants may tolerate damage differently when under abiotic stresses, and that predicting the additive vs. synergistic action of combined stresses will be difficult.
Characterization of InN nanoparticles prepared by laser as photodetector
Authors: Khashan Khawla S. , Abbas Sarah F.
Published: May 2016

Indium nitride (InN) nanoparticles (NPs) are a potentially important material for optoelectronic and high speed electronic devices. Using 1064 nm Nd:YAG laser, InN NPs suspension has been prepared by laser ablation of indium target submerged under ammonium hydroxide. FTIR determined the presence of In=N at 1114.8 cm[Formula: see text] symmetric stretching mode, and In–N bending vibration mode appears at 445.5 cm[Formula: see text]. X-ray diffraction (XRD) observed the peaks (101), (110), and (220) as a reflection formation cubic InN, with an average size of 2 nm. Scanning electron microscope (SEM) image shows that the NPs have a spherical shape with particle size in the range 2–20 nm. The transmission spectra of InN NPs suspension have the maximum optical transmission edge at 1378 nm with the band gap energy of 1.2 eV. The current–voltage characteristics of InN/Si heterojunction have a good rectifying property with a spectral responsivity of about 0.797 A/W at 750 nm wavelength.
On the dynamics of a time-dependent mesoscopic LC circuit with a negative inductance
Authors: Pedrosa I. A. , Nogueira E. , Guedes I.
Published: May 2016

We discuss the problem of a mesoscopic LC circuit with a negative inductance ruled by a time-dependent Hermitian Hamiltonian. Classically, we find unusual expressions for the Faraday’s law and for the inductance of a solenoid. Quantum mechanically, we solve exactly the time-dependent Schrödinger equation through the Lewis and Riesenfeld invariant operator method and construct Gaussian wave packet solutions for this time-dependent LC circuit. We also evaluate the expectation values of the charge and the magnetic flux in these Gaussian states, their quantum fluctuations and the corresponding uncertainty product.
Guiding Bug Triage through Developer Analysis in Bug Reports
Authors: Zhang Tao , Yang Geunseok , Lee Byungjeong , Chan Alvin T. S.
Published: May 2016

An important part of software maintenance is bug report analysis during bug-fixing, especially for large-scale software projects. Since bugs reported to the bug repository need to be fixed, triagers are responsible to identify appropriate developers to execute the fix. Previous research focused on optimizing this process, such as by duplicate detection and use of developer recommendations for reducing the workload of triagers. However, there were scant studies that analyzed developer roles (e.g. reporter and assignee) in the bug-fixing process. Therefore, in this paper, we perform an in-depth empirical study of the different roles that developers perform in bug resolution. By extracting the factors that affect bug resolution from the analysis results, we propose a novel bug triage algorithm to recommend the appropriate developers to fix a given bug. We implement the proposed recommendations on the Eclipse and Mozilla Firefox projects, with the results showing that the new bug triage algorithm can effectively recommend which experts should fix given bugs.
Configuration Management Model in Evolutionary Software Product Line
Authors: Farahani Elham Darmanaki , Habibi Jafar
Published: May 2016

In Software Product Line (SPL), Configuration Management (CM) is a multi-dimensional problem. On the one hand, the Core Assets that constitute a configuration need to be managed, and on the other hand, each product in the product line that is built using a configuration must be managed, and furthermore, the management of all these configurations must be coordinated under a single process. Therefore, CM for product lines is more complex than for single systems. The CM of any software system involves four closely related activities: Change Management (ChM), Version Management (VM), System Building (SB) and Release Management (RM) [I. Sommerville, Software Engineering, 9th edn. (Addison-Wesley, 2010)]. The aim of this paper is to provide ChM and VM models for evolutionary-based SPL system development and maintenance. The proposed models support any level of aggregation in SPLs and have been applied to Mobile SPL as a case study.
Effective Social Productivity Measurements during Software Development — An Empirical Study
Authors: Yilmaz Murat , O'Connor Rory V. , Clarke Paul
Published: May 2016

Much of contemporary scientific discussion regarding factors that influence software development productivity is undertaken in various domains where there is an insufficient empirical basis for exploring socio-technical factors of productivity that are specific to a software development organization. The purpose of the study is to characterize the multidimensional nature of software development productivity and its social aspects as a set of latent constructs (i.e. variables that are not directly observed) for a medium-sized software company. To this end, we designed an exploratory in-depth field study based on the hypothesized productivity constructs, which were modeled by a set of factors identified from literature reviews, and later refined by industrial focus groups. In order to demonstrate the applicability of our approach, we conducted confirmatory factor analysis with the data attained from a questionnaire with 216 participants. To investigate factors of influence further, we analyzed the impact of selected team-based variables over the latent constructs of productivity. Taken together, our findings confirm that such an approach can be used to explore the quantifiable influence of socio-technical factors that would affect productivity of a particular software development organization. Ultimately, the resulting model provides guidance to explore the comparative importance of a set of firm-specific factors that may help to improve the productivity of the organization.
Aspect Oriented Re-engineering of Legacy Software Using Cross-Cutting Concern Characterization and Significant Code Smells Detection
Authors: Shaikh Mohsin , Lee Chan-Gun
Published: May 2016

Although object-oriented programming (OOP) methodologies immensely promote reusable and well-factored decomposition of complex source code, legacy software systems often show symptoms of deteriorating design over time due to lack of maintenance. Software systems may have different business and application contexts, but most of these systems require similar maintenance mechanism of understanding, analysis and transformation. As a consequence, intensive re-engineering efforts based on the model driven approach can be effective ensuring that best practices are followed during maintenance and eventually reducing the development cost. In this paper, we suggest detailed framework of re-engineering which includes: (i) rigorous and automated source code analysis technique for identification, characterization and prioritization of most prominent and threatening design flaws in legacy software, (ii) migration of existing the code to aspect-oriented programming (AOP) code by exploiting current state of art for aspect mining mechanism and incorporating behavioral knowledge of cross-cutting concerns. To exemplify how the approach works a case study has been conducted to experimentally validate the idea and analyze the effect of process on specific software quality spectrum. An explicit analysis of prevalent work on the subject and their critical reviews are also presented to further enhance the recognition of proposed re-engineering framework.
IDENTIFYING OPEN INNOVATION PARTNERS: A METHODOLOGY FOR STRATEGIC PARTNER SELECTION
Authors: GUERTLER MATTHIAS R. , LINDEMANN UDO
Published: May 2016

By opening a company’s innovation process, and allowing purposeful collaboration with external partners, Open Innovation (OI) offers several advantages, such as the use of external expertise, shorter time-to-market and reduced failure rates. However, the success of OI projects is directly linked to the selection of suitable partners, who operationally or strategically contribute to reach the goal of the OI project. Despite this relevance of OI-partner selection, methodical support has hitherto been limited — it is either too abstract to be helpful in practice, or too focused on single aspects. This paper presents a methodical approach to close this gap by combining identification and selection approaches from different fields, such as stakeholder analysis, lead-user identification and systems engineering. The methodology was evaluated in an industrial OI-project with an SME from plant manufacturing.
IMPROVING INNOVATION CAPABILITIES BY COOPERATION: EXAMINING EFFECTS OF CORE NETWORK MANAGEMENT FUNCTIONS AND RELATIONAL MECHANISMS IN THE INDUSTRIAL GOODS SECTOR
Authors: WEBER BENJAMIN , HEIDENREICH SVEN
Published: May 2016

For companies, cooperation represents a way to innovate more effectively. Within this respect, past literature stresses the importance of core network management functions and relational mechanisms for the effectiveness of interorganisational cooperation. However, it is still unclear whether and how core network management functions and relational mechanisms improve a firm’s innovation capability from interorganisational cooperation. Based on data of 154 industrial companies, the results from structural equation modelling provide evidence that core network management functions significantly enhance innovation capability improvement of individual firms by interorganisational cooperation. Furthermore, both formal and informal relational mechanisms partially mediate the impact of core network management functions on innovation capability improvement. With regard to informal relational mechanisms, companies should foster trust, guarantee equal power distribution and ascribe high importance to their cooperation. With regard to formal relational mechanisms, companies should provide organisational support to their cooperation, continuously share knowledge with their partners and also meet and communicate on regular basis.
Deletion of novel protein TMEM35 alters stress-related functions and impairs long-term memory in mice
Authors: Kennedy Bruce C. , Dimova Jiva G. , Dakoji Srikanth , Yuan Li-Lian , Gewirtz Jonathan C. , Tran Phu V.
Published: May 2016

The mounting of appropriate emotional and neuroendocrine responses to environmental stressors critically depends on the hypothalamic-pituitary-adrenal (HPA) axis and associated limbic circuitry. Although its function is currently unknown, the highly evolutionarily conserved transmembrane protein 35 (TMEM35) is prominently expressed in HPA circuitry and limbic areas, including the hippocampus and amygdala. To investigate the possible involvement of this protein in neuroendocrine function, we generated tmem35 knockout (KO) mice to characterize the endocrine, behavioral, electrophysiological, and proteomic alterations caused by deletion of the tmem35 gene. While capable of mounting a normal corticosterone response to restraint stress, KO mice showed elevated basal corticosterone accompanied by increased anxiety-like behavior. The KO mice also displayed impairment of hippocampus-dependent fear and spatial memories. Given the intact memory acquisition but a deficit in memory retention in the KO mice, TMEM35 is likely required for long-term memory consolidation. This conclusion is further supported by a loss of long-term potentiation in the Schaffer collateral-CA1 pathway in the KO mice. To identify putative molecular pathways underlying alterations in plasticity, proteomic analysis of synaptosomal proteins revealed lower levels of postsynaptic molecules important for synaptic plasticity in the KO hippocampus, including PSD95 and N-methyl-d-aspartate receptors. Pathway analysis (Ingenuity Pathway Analysis) of differentially expressed synaptic proteins in tmem35 KO hippocampus implicated molecular networks associated with specific cellular and behavioral functions, including decreased long-term potentiation, and increased startle reactivity and locomotion. Collectively, these data suggest that TMEM35 is a novel factor required for normal activity of the HPA axis and limbic circuitry.
CETP Lowers TLR4 Expression Which Attenuates the Inflammatory Response Induced by LPS and Polymicrobial Sepsis
Authors: Venancio Tatiana Martins , Machado Roberta Marcondes , Castoldi Angela , Amano Mariane Tami , Nunes Valeria Sutti , Quintao Eder Carlos Rocha , Camara Niels Olsen Saraiva , Soriano Francisco Garcia , Cazita Patrícia Miralda
Published: May 2016

Sepsis is a systemic inflammatory response to infection eliciting high mortality rate which is a serious health problem. Despite numerous studies seeking for therapeutic alternatives, the mechanisms involved in this disease remain elusive. In this study we evaluated the influence of cholesteryl ester transfer protein (CETP), a glycoprotein that promotes the transfer of lipids between lipoproteins, on the inflammatory response in mice. Human CETP transgenic mice were compared to control mice (wild type, WT) after polymicrobial sepsis induced by cecal ligation and puncture (CLP), aiming at investigating their survival rate and inflammatory profiles. Macrophages from the peritoneal cavity were stimulated with LPS in the presence or absence of recombinant CETP for phenotypic and functional studies. In comparison to WT mice, CETP mice showed higher survival rate, lower IL-6 plasma concentration, and decreased liver toll-like receptor 4 (TLR4) and acyloxyacyl hydrolase (AOAH) protein. Moreover, macrophages from WT mice to which recombinant human CETP was added decreased LPS uptake, TLR4 expression, NF-κB activation and IL-6 secretion. This raises the possibility for new therapeutic tools in sepsis while suggesting that lowering CETP by pharmacological inhibitors should be inconvenient in the context of sepsis and infectious diseases.
GC‐MS Analysis: In Vivo Hepatoprotective and Antioxidant Activities of the Essential Oil of Achillea biebersteinii Afan. Growing in Saudi Arabia
Authors: Al-Said Mansour S. , Mothana Ramzi A. , Al-Yahya Mohammed M. , Rafatullah Syed , Al-Sohaibani Mohammed O. , Khaled Jamal M. , Alatar Abdulrahman , Alharbi Naiyf S. , Kurkcuoglu Mine , Baser Husnu C.
Published: May 2016

Liver disease is a worldwide problem. It represents one of the main causes of morbidity and mortality in humans. Achillea biebersteinii is used as herbal remedy for various ailments including liver diseases. But the scientific basis for its medicinal use remains unknown. Thus, this research was undertaken to evaluate the efficiency of A. biebersteinii essential oil (ABEO) (0.2 mL/kg) in the amelioration of CCl4‐induced hepatotoxicity in rodent model. Moreover, the chemical content of the oil was investigated using GC and GC‐MS. The following biochemical parameters were evaluated: serum glutamic oxaloacetic transaminase (GOT), glutamic‐pyruvic transaminase (GPT), gamma‐glutamyl‐transpeptidase (γ‐GGT), alkaline phosphatase (ALP), and total bilirubin. Furthermore, lipid profile, malondialdehyde (MDA), nonprotein sulfhydryl (NP‐SH), and total protein (TP) contents in liver tissue were estimated. 44 components (92.0%) of the total oil have been identified by GC‐MS analysis where α‐terpinene and p‐cymene were the most abundant. The high serum enzymatic (GOT, GPT, GGT, and ALP) and bilirubin concentrations as well as the level of MDA, NP‐SH, and TP contents in liver tissues were significantly reinstated towards normalization by the ABEO. Histopathological study further confirmed these findings. In addition, ABEO showed mild antioxidant activity in 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical scavenging and β‐carotene‐linoleic acid assays.
Integration of HIV in the Human Genome: Which Sites Are Preferential? A Genetic and Statistical Assessment
Authors: Gonçalves Juliana , Moreira Elsa , Sequeira Inês J. , Rodrigues António S. , Rueff José , Brás Aldina
Published: May 2016

Chromosomal fragile sites (FSs) are loci where gaps and breaks may occur and are preferential integration targets for some viruses, for example, Hepatitis B, Epstein-Barr virus, HPV16, HPV18, and MLV vectors. However, the integration of the human immunodeficiency virus (HIV) in Giemsa bands and in FSs is not yet completely clear. This study aimed to assess the integration preferences of HIV in FSs and in Giemsa bands using anin silicostudy. HIV integration positions from Jurkat cells were used and two nonparametric tests were applied to compare HIV integration in dark versus light bands and in FS versus non-FS (NFSs). The results show that light bands are preferential targets for integration of HIV-1 in Jurkat cells and also that it integrates with equal intensity in FSs and in NFSs. The data indicates that HIV displays different preferences for FSs compared to other viruses. The aim was to develop and apply an approach to predict the conditions and constraints of HIV insertion in the human genome which seems to adequately complement empirical data.
A Tauberian Theorem for Double Cesàro Summability Method
Authors: Jena Bidu Bhusan , Paikray Susanta Kumar , Misra Umakanta
Published: May 2016

We have generalized Littlewood Tauberian theorems for(C,k,r)summability of double sequences by using oscillating behavior and de la Vallée-Poussin mean. Further, the generalization of(C,r)summability from(C,k,r)summability is given as corollaries which were earlier established by the authors.
Interaction between Angiotensin II and Insulin/IGF-1 Exerted a Synergistic Stimulatory Effect on ERK1/2 Activation in Adrenocortical Carcinoma H295R Cells
Authors: Tong An-li , Wang Fen , Cui Yun-ying , Li Chun-yan , Li Yu-xiu
Published: May 2016

The cross talk between angiotensin II (Ang II) and insulin has been described mainly in cardiovascular cells, hepatocytes, adipocytes, and so forth, and to date no such cross talk was reported in adrenal. In this study, we examined the interaction between Ang II and insulin/IGF-1 in ERK and AKT signaling pathways and expression of steroidogenic enzymes in H295R cells. Compared to the control, 100 nM Ang II increased phospho-ERK1/2 approximately 3-fold. Insulin (100 nM) or IGF-1 (10 nM) alone raised phospho-ERK1/2 1.8- and 1.5-fold, respectively, while, after pretreatment with 100 nM Ang II for 30 min, insulin (100 nM) or IGF-1 (10 nM) elevated phospho-ERK1/2 level 8- and 7-fold, respectively. The synergistic effect of Ang II and insulin/IGF-1 on ERK1/2 activation was inhibited by selective AT1 receptor blocker, PKC inhibitor, and MEK1/2 inhibitor. Ang II marginally suppressed AKT activation under the basal condition, while it had no effect on phospho-AKT induced by insulin/IGF-1. Ang II significantly stimulated mRNA expression of CYP11B1 and CYP11B2, and such stimulatory effects were enhanced when cells were cotreated with insulin/IGF-1. We are led to conclude that Ang II in combination with insulin/IGF-1 had an evident synergistic stimulatory effect on ERK1/2 activation in H295R cells and the effect may be responsible for the enhanced steroid hormone production induced by Ang II plus insulin/IGF-1.
Clinical Scenarios for Discordant Anti-Xa
Authors: Vera-Aguilera Jesus , Yousef Hindi , Beltran-Melgarejo Diego , Teng Teng Hugh , Jan Ramos , Mok Mary , Vera-Aguilera Carlos , Moreno-Aguilera Eduardo
Published: May 2016

Anti-Xa testmeasuresthe activity ofheparinagainst the activity of activated coagulation factor X; significant variability of anti-Xa levels in common clinical scenarios has been observed.Objective. To review the most common clinical settings in which anti-Xa results can be bias.Evidence Review. Guidelines and current literature search: we used PubMed, Medline, Embase, and MEDION, from 2000 to October 2013.Results. Anti-Xa test is widely used; however the assay underestimates heparin concentration in the presence of significant AT deficiency, pregnancy, end stage renal disease, and postthrombolysis and in patients with hyperbilirubinemia; limited published data evaluating the safety and effectiveness of anti-Xa assays for managing UH therapy is available.Conclusions and Relevance. To our knowledge this is the first paper that summarizes the most common causes in which this assay can be affected, several “day to day” clinical scenarios can modify the outcomes, and we concur that these rarely recognized scenarios can be affected by negative outcomes in the daily practice.
Multiobjective Optimization Method for Multichannel Microwave Components of Active Phased Array Antenna
Authors: Wang Lu , Wang Zhihai , Wang Congsi , Li Guozhou , Yin Lei
Published: May 2016

Multichannel microwave components are widely used and the active phased array antenna is a typical representative. The high power generated from T/R modules in active phased array antenna (APAA) leads to the degradation of its electrical performances, which seriously restricts the development of high-performance APAA. Therefore, to meet the demand of thermal design for APAA, a multiobjective optimization design model of cold plate is proposed. Furthermore, in order to achieve temperature uniformity and case temperature restrictions of APAA simultaneously, optimization model of channel structure is developed. Besides, an airborne active phased array antenna was tested as an example to verify the validity of the optimization model. The valuable results provide important reference for engineers to enhance thermal design technology of antennas.
Association of Trabecular Bone Score with Inflammation and Adiposity in Patients with Psoriasis: Effect of Adalimumab Therapy
Authors: Hernández José L. , López-Mejías Raquel , Blanco Ricardo , Pina Trinitario , Ruiz Sheila , Sierra Isabel , Ubilla Begoña , Mijares Verónica , González-López Marcos A. , Armesto Susana , Corrales Alfonso , Pons Enar , Fuentevilla Patricia , González-Vela Carmen , González-Gay Miguel Á.
Published: May 2016

Studies on trabecular bone score (TBS) in psoriasis are lacking. We aim to assess the association between TBS and inflammation, metabolic syndrome features, and serum adipokines in 29 nondiabetic patients with psoriasis without arthritis, before and after 6-month adalimumab therapy. For that purpose, adjusted partial correlations and stepwise multivariable linear regression analysis were performed. No correlation was found between TBS and disease severity. TBS was negatively associated with weight, BMI, waist perimeter, fat percentage, and systolic and diastolic blood pressure before and after adalimumab. After 6 months of therapy, a negative correlation between TBS and insulin resistance (p=0.02) and leptin (p=0.01) and a positive correlation with adiponectin were found (p=0.01). The best set of predictors for TBS values at baseline were female sex (p=0.015), age (p=0.05), and BMI (p=0.001). The best set of predictors for TBS following 6 months of biologic therapy were age (p=0.001), BMI (p<0.0001), and serum adiponectin levels (p=0.027). In conclusion, in nondiabetic patients with moderate-to-severe psoriasis, TBS correlates with metabolic syndrome features and inflammation. This association is still present after 6 months of adalimumab therapy. Moreover, serum adiponectin levels seem to be an independent variable related to TBS values, after adalimumab therapy.
Aspects of Screening and Confinement in a Topologically MassiveU1W×U(1)YChern-Simons-Higgs Theory
Authors: Gaete Patricio , Helayël-Neto José A.
Published: May 2016

By using the gauge-invariant but path-dependent variables formalism, we consider a recently proposed topologically massiveU1W×U(1)YChern-Simons-Higgs theory in2+1dimensions. In particular, we inspect the impact of a Chern-Simons mixing term between two Abelian gauge fields on physical observables. We pursue our investigation by analyzing the model in two different situations. In the first case, where we integrate the massive excitation and consider an effective model for the massless field, we show that the interaction energy contains a linear term leading to the confinement of static charge probes along with a screening contribution. In the second situation, where the massless field can be exactly integrated with its constraint duly taken into account, the interesting feature is that the resulting effective model describes a purely screening phase, without any trace of a confining regime.
Flow Characteristics Study of Wind Turbine Blade with Vortex Generators
Authors: Hu Hao , Li Xin-kai , Gu Bo
Published: May 2016

The blade root flow control is of particular importance to the aerodynamic characteristic of large wind turbines. The paper studies the feasibility of improving blade pneumatic power by applying vortex generators (VGs) to large variable propeller shaft horizontal axis wind turbines, with 2 MW variable propeller shaft horizontal axis wind turbine blades as research object. In the paper, three cases of VGs installation are designed; they are scattered in different chordwise position at the blade root, and then they are calculated, respectively, with CFD method. The results show that VGs installed in the separation line upstream, with the separation line of the blade root as a benchmark, show a better effect. Pneumatic power of blades increases by 0.6% by installing VGs. Although the effect on large wind turbines is not obvious, there is a space for optimization.
Analysis of Plant Breeding on Hadoop and Spark
Authors: Chen Shuangxi , Wu Chunming , Yu Yongmao
Published: May 2016

Analysis of crop breeding technology is one of the important means of computer-assisted breeding techniques which have huge data, high dimensions, and a lot of unstructured data. We propose a crop breeding data analysis platform on Spark. The platform consists of Hadoop distributed file system (HDFS) and cluster based on memory iterative components. With this cluster, we achieve crop breeding large data analysis tasks in parallel through API provided by Spark. By experiments and tests of Indica and Japonica rice traits, plant breeding analysis platform can significantly improve the breeding of big data analysis speed, reducing the workload of concurrent programming.
Piperine Plays an Anti‐Inflammatory Role in Staphylococcus aureus Endometritis by Inhibiting Activation of NF‐κB and MAPK Pathways in Mice
Authors: Zhai Wen-jun , Zhang Zhen-biao , Xu Nian-nian , Guo Ying-fang , Qiu Changwei , Li Cheng-ye , Deng Gan-zhen , Guo Meng-yao
Published: May 2016

Endometritis is commonly caused by pathogenic microorganisms, including Staphylococcus aureus (S. aureus). Piperine, which is a natural medicine, has shown a variety of biological activities. To explore the effect and mechanism of piperine on S. aureus endometritis, a mouse model of S. aureus endometritis was successfully established in the present study. Histopathological changes were observed with H&E staining, cytokines were analyzed by ELISA, mRNA was analyzed by qPCR, and proteins were detected by western blot. The results showed that piperine could significantly alleviate inflammatory injury in S. aureus endometritis. The qPCR and ELISA results showed that piperine effectively reduced the S. aureus‐induced overexpression of TNF‐α, IL‐1β, and IL‐6 but increased the expression of IL‐10. The S. aureus‐induced inflammation was related to TLR‐2 and TLR‐4 because the results showed that their expression was increased in S. aureus infection but then decreased with piperine treatment. To further confirm that piperine caused an anti‐inflammatory response by targeting NF‐κB and MAPKs, the expression of I‐κB, p65, p38, ERK, and JNK was measured. The phosphorylation of I‐κB, p65, p38, ERK, and JNK was inhibited by piperine in a dose‐dependent manner. All of the results indicated that piperine may be a potential anti‐inflammatory drug both in endometritis and in other S. aureus‐induced diseases.
Is Sexual Size Dimorphism Inherent in the ScallopPatinopecten yessoensis?
Authors: Silina Alla V.
Published: May 2016

Studies on sexual size dimorphism in Pectinidae are limited. This work deals with the mobile long-lived scallopPatinopecten yessoensis, a common (fished and cultured) species in the subtidal benthos of the Sea of Japan. A previously developed method of age determination inP. yessoensisallowed me to compare the parameters of same aged males and females in scallop populations. The shell growth rates and sizes of both sexes were similar; therefore, it was only possible to visually identify the sex of live specimens during the breeding period (May-June). Statistical analyses showed female-biased dimorphism in the gonad weight for age groups that are >4 years old. Gonad weight (in the prespawning period) increased with age, until a threshold age was attained, which varied between populations; and then gonad weight remained virtually unchanged. The fecundity advantage hypothesis forP. yessoensiswith group mating and external fertilization is at least partly realized by physiological mechanisms, which cause older females to have larger gonads than those of same aged males in the population in order to produce a larger brood. Gregarious settlement of this bivalve contributes to the reproductive success of the population so that the energetically costly ovaries may all be fertilized.