bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small-Molecule Fusion Inhibitors Bind the pH-Sensing Stable Signal Peptide-GP2 Subunit Interface of the Lassa Virus Envelope Glycoprotein
Authors: Shankar Sundaresh , Whitby Landon R. , Casquilho-Gray Hedi E. , York Joanne , Boger Dale L. , Nunberg Jack H. 
Published: May 2016

ABSTRACT
Arenavirus species are responsible for severe life-threatening hemorrhagic fevers in western Africa and South America. Without effective antiviral therapies or vaccines, these viruses pose serious public health and biodefense concerns. Chemically distinct small-molecule inhibitors of arenavirus entry have recently been identified and shown to act on the arenavirus envelope glycoprotein (GPC) to prevent membrane fusion. In the tripartite GPC complex, pH-dependent membrane fusion is triggered through a poorly understood interaction between the stable signal peptide (SSP) and the transmembrane fusion subunit GP2, and our genetic studies have suggested that these small-molecule inhibitors act at this interface to antagonize fusion activation. Here, we have designed and synthesized photoaffinity derivatives of the 4-acyl-1,6-dialkylpiperazin-2-one class of fusion inhibitors and demonstrate specific labeling of both the SSP and GP2 subunits in a native-like Lassa virus (LASV) GPC trimer expressed in insect cells. Photoaddition is competed by the parental inhibitor and other chemically distinct compounds active against LASV, but not those specific to New World arenaviruses. These studies provide direct physical evidence that these inhibitors bind at the SSP-GP2 interface. We also find that GPC containing the uncleaved GP1-GP2 precursor is not susceptible to photo-cross-linking, suggesting that proteolytic maturation is accompanied by conformational changes at this site. Detailed mapping of residues modified by the photoaffinity adducts may provide insight to guide the further development of these promising lead compounds as potential therapeutic agents to treat Lassa hemorrhagic fever.

IMPORTANCE
Hemorrhagic fever arenaviruses cause lethal infections in humans and, in the absence of licensed vaccines or specific antiviral therapies, are recognized to pose significant threats to public health and biodefense. Lead small-molecule inhibitors that target the arenavirus envelope glycoprotein (GPC) have recently been identified and shown to block GPC-mediated fusion of the viral and cellular endosomal membranes, thereby preventing virus entry into the host cell. Genetic studies suggest that these inhibitors act through a unique pH-sensing intersubunit interface in GPC, but atomic-level structural information is unavailable. In this report, we utilize novel photoreactive fusion inhibitors and photoaffinity labeling to obtain direct physical evidence for inhibitor binding at this critical interface in Lassa virus GPC. Future identification of modified residues at the inhibitor-binding site will help elucidate the molecular basis for fusion activation and its inhibition and guide the development of effective therapies to treat arenaviral hemorrhagic fevers.
Measurements of Intrahost Viral Diversity Are Extremely Sensitive to Systematic Errors in Variant Calling
Authors: McCrone John T. , Lauring Adam S. 
Published: May 2016

ABSTRACT

With next-generation sequencing technologies, it is now feasible to efficiently sequence patient-derived virus populations at a depth of coverage sufficient to detect rare variants. However, each sequencing platform has characteristic error profiles, and sample collection, target amplification, and library preparation are additional processes whereby errors are introduced and propagated. Many studies account for these errors by using
ad hoc
quality thresholds and/or previously published statistical algorithms. Despite common usage, the majority of these approaches have not been validated under conditions that characterize many studies of intrahost diversity. Here, we use defined populations of influenza virus to mimic the diversity and titer typically found in patient-derived samples. We identified single-nucleotide variants using two commonly employed variant callers, DeepSNV and LoFreq. We found that the accuracy of these variant callers was lower than expected and exquisitely sensitive to the input titer. Small reductions in specificity had a significant impact on the number of minority variants identified and subsequent measures of diversity. We were able to increase the specificity of DeepSNV to >99.95% by applying an empirically validated set of quality thresholds. When applied to a set of influenza virus samples from a household-based cohort study, these changes resulted in a 10-fold reduction in measurements of viral diversity. We have made our sequence data and analysis code available so that others may improve on our work and use our data set to benchmark their own bioinformatics pipelines. Our work demonstrates that inadequate quality control and validation can lead to significant overestimation of intrahost diversity.

IMPORTANCE
Advances in sequencing technology have made it feasible to sequence patient-derived viral samples at a level sufficient for detection of rare mutations. These high-throughput, cost-effective methods are revolutionizing the study of within-host viral diversity. However, the techniques are error prone, and the methods commonly used to control for these errors have not been validated under the conditions that characterize patient-derived samples. Here, we show that these conditions affect measurements of viral diversity. We found that the accuracy of previously benchmarked analysis pipelines was greatly reduced under patient-derived conditions. By carefully validating our sequencing analysis using known control samples, we were able to identify biases in our method and to improve our accuracy to acceptable levels. Application of our modified pipeline to a set of influenza virus samples from a cohort study provided a realistic picture of intrahost diversity and suggested the need for rigorous quality control in such studies.
Model Error in Filtering Random Compressible Flows Utilizing Noisy Lagrangian Tracers
Authors: Chen Nan , Majda Andrew J. 
Published: May 2016

AbstractLagrangian tracers are drifters and floaters that collect real-time information of fluid flows. This paper studies the model error in filtering multiscale random rotating compressible flow fields utilizing noisy Lagrangian tracers. The random flow fields are defined through random amplitudes of Fourier eigenmodes of the rotating shallow-water equations that contain both incompressible geostrophically balanced (GB) flows and rotating compressible gravity waves, where filtering the slow-varying GB flows is of primary concern. Despite the inherent nonlinearity in the observations with mixed GB and gravity modes, there are closed analytical formulas for filtering the underlying flows. Besides the full optimal filter, two practical imperfect filters are proposed. An information-theoretic framework is developed for assessing the model error in the imperfect filters, which can apply to a single realization of the observations. All the filters are comparably skillful in a fast rotation regime (Rossby number ). In a moderate rotation regime (), significant model errors are found in the reduced filter containing only GB forecast model, while the computationally efficient 3D-Var filter with a diagonal covariance matrix remains skillful. First linear then nonlinear coupling of GB and gravity modes is introduced in the random Fourier amplitudes, while linear forecast models are retained to ensure the filter estimates have closed analytical expressions. All the filters remain skillful in the regime. In the regime, the full filter with a linear forecast model has an acceptable filtering skill, while large model errors are shown in the other two imperfect filters.
Setting Single or Multiple Goals for Diet and Physical Activity Behaviors Improves Cardiovascular Disease Risk Factors in Adults With Type 2 Diabetes
Authors: Swoboda Christine M. , Miller Carla K. , Wills Celia E. 
Published: May 2016

Purpose The purpose of this study was to evaluate a 4-month telephone-based goal-setting and decision support intervention among adults with type 2 diabetes mellitus (T2DM) and multiple risk factors for cardiovascular disease (CVD). Methods A randomized pretest-posttest control group design was employed. Overweight or obese adults aged 40 to 75 years with T2DM and ≥1 additional CVD risk factor were provided with individualized CVD risk information. At baseline and each biweekly telephone call, the multiple-goal group self-selected both diet- and physical activity–related goals, the single goal group set a single goal, and the control group received information about community health resources. Dietary intake was assessed via a food frequency questionnaire, physical activity via questionnaire, and A1C and blood lipids via fasting fingerstick sample. Between-group differences for clinical (ie, A1C, blood pressure, and blood lipids), physical activity, and dietary variables were evaluated using Kruskal-Wallis, Mann-Whitney U, analysis of variance, and t tests. Results From pre- to postintervention, the single-goal group demonstrated significant improvement in systolic blood pressure and intake of servings of fruits, vegetables, and refined grains (all P < .05). The multiple-goal group reported significant reduction in percent energy from total, saturated, monounsaturated, and trans fat intake and significant increase in leisure time walking (all P < .05). Conclusion A multiple-goal approach over 4 months can improve dietary and physical activity outcomes, while a single-goal approach may facilitate improvement in one behavioral domain. Additional research is needed to evaluate maintenance of the achieved changes.
Involvement of Women in Natural Resource Collection in Rural Jharkhand, India
Authors: De Utpal Kumar , Ghosh Bhola Nath 
Published: May 2016

Women living in rural areas are very close to the natural environment. Most poor families are dependent on nature for their survival, grazing cattle, collecting water and fuelwood and similar tasks, which are considered inferior and suitable for women and children, are not remunerative. Adult males and some women work outside for a livelihood. The life of rural women, particularly tribal women, is so much intertwined with the environment, that the whole ecosystem revolves around them and they cannot even think of their survival without it. However, significant intra-household differences in the distribution of such activities between male and female members of the families exist, varying with socioeconomic background, cultural and religious beliefs and underlying attitudes towards women and children. This article examines to what extent women in rural Jharkhand are involved in such natural resource collection and management activities. We tried to unearth the impact of cultural and economic factors on women’s role in different economic sections and social groups. The analysis reveals that income, occupation and status of the families have a significant inverse link with the involvement of women and also of girl children at the cost of their educational prospects. Religious and cultural beliefs also determine the extent of women and children’s involvement in resource collection. The study indicates the low empowerment level of rural women in the area.
Influence of Biochemical and Anthropometric Factors on the Presence of Insulin Resistance in Adolescents
Authors: González-Jiménez Emilio , Schmidt-RioValle Jacqueline , Montero-Alonso Miguel A. , Padez Cristina , García-García Carmen J. , Perona Javier S. 
Published: May 2016

Background: Insulin resistance plays a determinant role in the development of metabolic syndrome in adolescents. The objective of the present study was to determine the influence of factors commonly associated with insulin resistance in a sample of adolescents. Methods: This cross-sectional study included 976 adolescents from southeast Spain. Anthropometric and biochemical measurements were performed, and insulin resistance was assessed using the homeostasis model assessment–insulin resistance (HOMA-IR). Results: Subjects with abnormal HOMA-IR values had significantly higher body mass index (BMI), body fat content, waist circumference, and systolic blood pressure (BP) than those with normal values. Furthermore, levels of glucose, insulin, glycosylated hemoglobin, total cholesterol, triglycerides, low-density lipoprotein-cholesterol, homocysteine, nonesterified fatty acids, and ceruloplasmin were higher in subjects with abnormal HOMA-IR values. Multivariate logistic regression analysis showed the highest odds ratio ( OR) for BMI and that combinations of BMI with body fat content or systolic BP can increase the risk of insulin resistance 7-fold. Discussion: Anthropometric indicators have different levels of influence on the risk of insulin resistance in adolescents, and a combination of two of these indicators is enough to increase the risk 7-fold. Since the highest OR was observed for BMI, the greatest effort should be directed to reducing this parameter in adolescents. An adequate understanding by nursing personnel of factors associated with insulin resistance is a key factor in the prevention of this pathophysiological condition and its complications in adolescents.
Modern sedation aspects at endoscopic examination
Authors: Киреев  , Kireev V. , Китиашвили  , Kitiashvili D. 
Published: May 2016

The article highlights the issue of improving the quality of endoscopy in patients are treated at the department of anesthesiology and intensive care unit.
Endoscopic study was the bronchoscopy, the gastroscopy, the colonoscopy. It was revealed the necessity of sedation during endoscopy in patients in the intensive care unit. The authors analyzed the characteristics of the use of drugs for sedation during endoscopic study. Clinical evaluation of their impact on the psycho-emotional status of the patient was carried out. The substantiation of the advantages of the Dexmedetomidine (Deksdor) as sedation analgesia over other drugs was proven. Controlled sedation with the Deksdor allows to stop pain with the absence of central nervous system depression, respiratory depression and danger emotional pain perception. After the sedation and endoscopy, the vegetative changes do not require medical treatment due to the subsequent tendency to vegetative equilibrium in post-endoscopic period. Based on the obtained data, it was proven the clinical efficacy of the proposed method of sedation in endoscopic studies, the relationship with the improvement of the current study, a decrease in the number and severity of complications.
Surgical treatment and improvement recovery processes in patients with the musculoskeletal tumors by the application of new methods of immunodiagnostics and immunocorrection
Authors: Антонов  , Antonov A. 
Published: May 2016

In recent years there has been a marked increase in the number of patients with primary and metastatic tumors of the musculoskeletal system. Skeletal system is one of the most affected in various cancer diseases, such as breast, prostate, kidney, thyroid, lung cancer, gastro-intestinal tract.
The authors use the individual metal-polymer express-endoprosthesis for replacement of bone defects in primary and secondary tumors of the musculoskeletal system and spine.
The purpose and the objectives of this study were to present the possibilities of proposed surgical technique and to increase its effectiveness by the use of the new immunodiagnostic methods. The essence of immunodiagnostics was assessment the state of natural immunity to the definition of autoantibody levels only in the affected organs, as well as immune correction in the early postoperative period using immunoglobulins, fast adaptogens, immunomodulators &#34;Vitavis&#34; and powerful antioxidant neutral Anolyte produced at the facility Stela NPO &#34;Screen&#34; of the Medical and Technical Academy.
Use of the fast adaptogens, immunomodulators, neutral Anolyte, immunoglobulins allows to optimize postoperative dynamics of biochemical and immune parameters, to reduce the risk of complications and to accelerate wound healing, to speed up the &#34;engraftment&#34; implants, to reduce the postoperative period.
A new approach to the evaluation of the immune status at the level of oncological diseases of autoimmunity allows to identify the affected tumor process bodies (lesions, microlesions, metastases, hidden metastases), to detect the presence of systemic activation or suppression of the immune system, which is the justification for the use of immunosuppressive or immunostimulatory therapy.
Identifying systemic immunosuppression by humoral type allows to use new methods of immunotherapy of oncological diseases - Ig-therapy, as well as to select individual regimens according to the degree of immunosuppression.
Reviews
Authors: Pennacchia Maddalena , Poore Benjamin 
Published: May 2016

Abstract
RECLAIMING ROMEO AND JULIET: ITALIAN TRANSLATIONS FOR PAGE, STAGE AND SCREEN, VINCENZA MINUTELLA (2013) Amsterdam and New York: Rodopi, 264 pp., ISBN: 9789042037342, p/bk, £49.41
ADAPTATION, INTERMEDIALITY AND THE BRITISH CELEBRITY BIOPIC, MÁRTA MINIER AND MADDALENA PENNACCHIA (EDS) (2014) UK: Ashgate, 234 pp., ISBN: 9781409461265, h/bk, £95.00
The sweetheart factor: Tracing translation in Martin Crimp’s writing for theatre
Authors: Brodie Geraldine 
Published: May 2016

Abstract
Martin Crimp’s activity as a playwright includes the translation and adaptation of the theatrical works of other writers. This article considers how Crimp’s theoretical and practical engagement with translation is manifested in his writing for the stage. Crimp’s voice on and in translation is analysed: first, from the perspective of translation theory, in particular as it relates to Crimp’s discussions on translation and adaptation; and second, in a study of Crimp’s use of the word ‘sweetheart’ in his various writings, including his translations and adaptations of works by other playwrights. I conclude that Crimp’s authorial presence exists throughout his work, whether self-authored, translated or adapted, while simultaneously operating to recognize the plurality of voices within a translated text.
A study of legal translation from the perspective of error analysis
Authors: Hu Pi-Chan , Cheng Le 
Published: May 2016

AbstractIn this research, we established a small scale corpus with abstracts in English and Chinese from the law reviews of Taiwan. We identified problems found in these abstracts and classified them into several categories. After analyzing the problems, we found that translators are faced with numerous problems when translating legal texts: the influence of ordinary language, lack of reliable reference tools, insufficiency of legal knowledge, deficiency in the target language or source language, and the peculiar characteristics of legal language. These problems simply render the task of translating even more intricate. Strategies will be proposed to enhance the ability of legal translators and to help them to overcome these obstacles.
CAPITAL MARKET’S REACTION TOWARDS 2014 WORKING CABINET ANNOUNCEMENT (INDONESIAN CASE STUDY)
Authors: Ardiansari Anindya , Saputra Arif 
Published: May 2016

The purpose of this study is to examine the market reaction regarding the announcement of working cabinet following the election of Jokowi as the President of Indonesia. Political events such as presidential election, government change, cabinet announcement, and other events are very influential towards price and trade volume at the stock exchange since the political events are closely related to the state economy stability. The Sample in this study is stock which was listed as issuers in Indonesia Stock Exchange (IDX) which included in LQ45 company group during this research period from 20 October– 3 November 2014. The result shows that there was significant effect towards abnormal return difference before and after the cabinet announcement on the companies listed in LQ 45. The existence of this significant difference means that market reacted with the cabinet announcement event.
Epistasis and the Dynamics of Reversion in Molecular Evolution
Authors: McCandlish David M , Shah Premal , Plotkin Joshua B 
Published: May 2016

AbstractRecent studies of protein evolution contend that the longer an amino acid substitution is present at a site, the less likely it is to revert to the amino acid previously occupying that site. Here we study this phenomenon of decreasing reversion rates rigorously and in a much more general context. We show that, under weak mutation and for arbitrary fitness landscapes, reversion rates decrease with time for any site that is involved in at least one epistatic interaction. Specifically, we prove that, at stationarity, the hazard function of the distribution of waiting times until reversion is strictly decreasing for any such site. Thus, in the presence of epistasis, the longer a particular character has been absent from a site, the less likely the site will revert to its prior state. We also explore several examples of this general result, which share a common pattern whereby the probability of having reverted increases rapidly at short times to some substantial value before becoming almost flat after a few substitutions at other sites. This pattern indicates a characteristic tendency for reversion to occur either almost immediately after the initial substitution or only after a very long time.
“Is There No One Here Who Speaks to Me?” Performing Ethnic Encounter in Bohemia and Moravia at the Turn of the 17th Century
Authors: Edwards Scott L. 
Published: May 2016

This article investigates the musical performance of ethnic encounter following the transfer of the imperial court of Rudolf II from Vienna to Prague in 1583. As the Bohemian capital more than tripled in size in the following decades, musical culture began to reflect the international make up of the city with ramifications that could be felt across Bohemia and Moravia. Musical forms such as the multilingual quodlibet and the messanza responded to the newfound cultural preeminence of Italian music as well as a rapidly expanding Italian diaspora, while exposing the communicative challenges unique to the region’s multilingual environment.
Une scène en Bohême : mobilités et performances artistiques dans la ville d’eau de Teplitz au tournant des xviiie et xixe siècles
Authors: Magne Matthieu 
Published: May 2016

À la fois seigneurie des princes de Clary-Aldringen et ville d’eau renommée de Bohême du Nord, les domaines de Teplitz connaissent une fréquentation sans précédent à partir des années 1790. Le théâtre du château aménagé en 1751 pour la famille ouvre ses portes aux compagnies professionnelles engagées pour jouer en allemand devant un public mobile et varié, sans que le théâtre de société francophone donné à huis clos ne cesse pour autant. Différents fonds d’archives permettent ainsi de ressaisir la manière dont les arts de la scène s’organisent à Teplitz, où l’attractivité mondaine et thermale se conjugue au renouveau des logiques mécénales dans le premier xixe siècle.