Miracle-dz/UniFAR-FTUs huggingface dataset:
Template/Primer Requirements and Single Nucleotide Incorporation by Hepatitis C Virus Nonstructural Protein 5B Polymerase

ABSTRACT Nonstructural protein 5B (NS5B) of hepatitis C virus (HCV) possesses an RNA-dependent RNA polymerase activity responsible for viral genome RNA replication. Despite several reports on the characterization of this essential viral enzyme, little is known about the reaction pathway of NS5B-catalyzed nucleotide incorporation due to the lack of a kinetic system offering efficient assembly of a catalytically competent polymerase/template/primer/nucleotide quaternary complex. In this report, specific template/primer requirements for efficient RNA synthesis by HCV NS5B were investigated. For intramolecular copy-back RNA synthesis, NS5B utilizes templates with an unstable stem-loop at the 3′ terminus which exists as a single-stranded molecule in solution. A template with a stable tetraloop at the 3′ terminus failed to support RNA synthesis by HCV NS5B. Based on these observations, a number of single-stranded RNA templates were synthesized and tested along with short RNA primers ranging from two to five nucleotides. It was found that HCV NS5B utilized di- or trinucleotides efficiently to initiate RNA replication. Furthermore, the polymerase, template, and primer assembled initiation-competent complexes at the 3′ terminus of the template RNA where the template and primer base paired within the active site cavity of the polymerase. The minimum length of the template is five nucleotides, consistent with a structural model of the NS5B/RNA complex in which a pentanucleotide single-stranded RNA template occupies a groove located along the fingers subdomain of the polymerase. This observation suggests that the initial docking of RNA on NS5B polymerase requires a single-stranded RNA molecule. A unique β-hairpin loop in the thumb subdomain may play an important role in properly positioning the single-stranded template for initiation of RNA synthesis. Identification of the template/primer requirements will facilitate the mechanistic characterization of HCV NS5B and its inhibitors.
Family circles.

The consultation in general practice has been portrayed as a dialogue between an analytical, perspicacious individual with a thorough know-ledge of the latest scientific developments-the patient - and a confused, harassed person struggling to come to grips with a multitude of diverse innovative therapies - the doctor. I offer to the latter an introduction to a technique which will permit him to utilize concepts from family therapy in his work with his patients.
Knockdown of Rap2B, a Ras Superfamily Protein, Inhibits Proliferation, Migration, and Invasion in Cervical Cancer Cells via Regulating the ERK1/2 Signaling Pathway

Rap2B, belonging to the Ras superfamily, has been implicated in cancer development and functions as a tumor promoter. However, the role of Rap2B in cervical cancer is unknown. In this study, we investigated the expression pattern and biological functions of Rap2B in cervical cancer. The results showed that Rap2B was overexpressed in cervical cancer tissues and cell lines. Knockdown of Rap2B inhibited the proliferation, migration, and invasion of cervical cancer cells. In addition, our tumorigenesis assay showed that Rap2B knockdown suppressed cervical cancer cell growth and metastasis in vivo. We also found that the ERK1/2 signaling pathway is involved in the inhibitory effect of Rap2B knockdown on cervical cancer development. In conclusion, we suggest that Rap2B is an oncogene and may be a promising therapeutic target for cervical cancer.
Influences of metrical structure and grouping on the kinematics of rhythmic finger tapping

We investigated whether metrical accentuation has obligatory effects on the kinematics of rhythmic finger tapping. Auditory rhythmic patterns were repeated cyclically, and participants first synchronized with each pattern and then reproduced it 10 times on a MIDI keyboard, which yielded measures of the timing and velocities of key depression and release. Experiment 1 used strongly and weakly metrical patterns from Povel and Essens (1985). Experiment 2 varied metrical structure independently of grouping structure by adding an explicit beat in different phases to rhythmic patterns. Strongly metrical sequences were produced with more precise and less variable timing (Exp. 1), and syncopation had some unexpected effects on timing (Exp. 2). However, metrically accented taps were similar in most respects to unaccented taps; only key release velocities tended to be faster for accented taps (Exp. 2). By contrast, grouping structure had strong effects on all movement parameters. The results suggest that, unlike rhythmic grouping, metrical structure (and metrical accentuation in particular) is not necessarily reflected in action. Repp & Saltzman: Meter and grouping 3
Thyroid functions after contrast agent administration for coronary angiography: a prospective observational study in euthyroid patients.

OBJECTIVE This study aims to investigate long-term effects of iodinated radiographic contrast media used for coronary angiography (CAG) on the thyroid function in euthyroid patients. METHODS In a prospective observational cohort study, nonionic iodinated contrast material was electively used in 101 patients for coronary angiography. The patients were recruited without age restrictions and, at baseline, all had normal levels of free triiodothyronine (FT3), free thyroxine (FT4) and thyrotropin (TSH). The morphology of the thyroid was evaluated by thyroid ultrasonography (USG). Four and eight weeks after CAG, serum TSH, FT3 and FT4 levels were assessed. RESULTS Compared to a mean baseline level of 1.49 (25%-75%, range 13-2.21), follow-up TSH levels decreased significantly to 1.45 (25%-75%, range 1.98-0.92, p=0.017) and 1.40 (25%-75%, range 1.89-0.87, p=0.003) at 4 weeks and 8 weeks, respectively (p=0.008). No significant diffe-rence was observed in TSH levels between the 4th and 8th weeks (p=0.833). CONCLUSION Iodinated radiographic contrast agents may cause subclinical hyperthyroidism in euthyroid patients undergoing CAG.
Expression of early activation antigen (CD69) during human thymic development

The novel early activation antigen, EA1, has been shown to be induced by mitogens, antigens and the tumour promoter, phorbol myristate acetate (PMA), on human lymphocytes. This antigen has been designated to be CD69. EA1 has also been shown to be expressed on thymocytes without exogenous activation stimuli. In order to characterize further the expression of EA1 on thymocytes, the ontogeny of its expression was studied. EA1 appeared between 7 and 9.5 weeks of gestation, after colonization of the thymic rudiment with CD7+ T cell precursors, but before the onset of compartmentalization of the thymus into cortical and medullary zones. After cortico‐medullary differentiation, the majority of medullary thymocytes expressed EA1 while only a fraction of the cortical thymocytes expressed this antigen. In the fetal and post‐natal cortex, EA1 expression appeared to cluster in the subcapsular cortex. EA1+ cells were also scattered throughout the inner cortex. By two‐colour fluorocytometric analysis of post‐natal thymocytes, it was shown that EA1 was expressed on 30 to 65% of thymocytes. EA1 was expressed onCD4+ CD8+ as well as on the more immature CD4‐ CD8‐ thymocytes. In contrast to circulating T cells, thymocytes were much less responsive to PMA stimulation for the expression of EA1. Molecular characterization showed that EA1 on thymocytes had the same structure as that of activated peripheral T cells. In addition, thymic EA1 was constitutively phosphorylated. Thus, EA1 expression is acquired early during thymic development after colonization of the thymic rudiment by CD7+ T cell precursors. However, the specific role that EA1 may play in the activation and function of developing thymocytes remains to be determined.
Effective articulatory modeling for pronunciation error detection of L2 learner without non-native training data

For effective articulatory feedback in computer-assisted pronunciation training (CAPT) systems, we address effective articulatory models of second language (L2) learners' speech without using such data, which is difficult to collect and annotate in a large scale. Context-dependent articulatory attributes (placement and manner of articulation) are modeled based on deep neural network (DNN). In order to efficiently train the non-native articulatory models, we exploit large speech corpora of native and target language to model inter-language phenomena. This multi-lingual learning is then combined with multi-task learning, which uses phone-classification as a sub-task. These methods are applied to Mandarin Chinese pronunciation learning by Japanese native speakers. Effects are confirmed in the native attribute classification and pronunciation error detection of non-native speech.
Molecular Aspects and Comparative Genomics of Bacteriophage Endolysins

ABSTRACT Phages are recognized as the most abundant and diverse entities on the planet. Their diversity is determined predominantly by their dynamic adaptation capacities when confronted with different selective pressures in an endless cycle of coevolution with a widespread group of bacterial hosts. At the end of the infection cycle, progeny virions are confronted with a rigid cell wall that hinders their release into the environment and the opportunity to start a new infection cycle. Consequently, phages encode hydrolytic enzymes, called endolysins, to digest the peptidoglycan. In this work, we bring to light all phage endolysins found in completely sequenced double-stranded nucleic acid phage genomes and uncover clues that explain the phage-endolysin-host ecology that led phages to recruit unique and specialized endolysins.
Multiresolution for SAT Checking

This paper presents a system based on new operators for handling sets of propositional clauses compactly represented by means of ZBDDs. The high compression power of such data structures allows efficient encodings of structured instances. A specialized operator for the distribution of sets of clauses is introduced and used for performing multiresolution on clause sets. Cut eliminations between sets of clauses of exponential size may then be performed using polynomial size data structures. The ZRES system, a new implementation of the Davis-Putnam procedure of 1960, solves two hard problems for resolution, that are currently out of the scope of the best SAT provers.
The Equine Herpesvirus 1 UL20 Product Interacts with Glycoprotein K and Promotes Egress of Mature Particles

ABSTRACT The aim of the present study was to identify and functionally characterize the equine herpesvirus 1 (EHV-1) UL20 protein (UL20p). Using a specific antiserum, UL20p was shown to be associated with membranes of infected cells, as well as with envelopes of purified virions. By Western blot analysis, UL20p was detected in two main forms exhibiting Mrs of 25,000 and 75,000. Both moieties did not enter the separating gel after heating of protein samples to 99°C. The slower-migrating form of UL20p contains N-linked carbohydrates, and its presence is dependent of that of other viral proteins. Infection of cells that either constitutively express UL20p or a gK-green fluorescent protein (GFP) fusion protein with various EHV-1 deletion mutants revealed a relatively stable hetero-oligomer containing gK and UL20p with an apparent Mr of 75,000. As demonstrated by confocal microscopy, UL20p distribution in Rk13 cells changed from a diffuse granular or netlike appearance to a pattern confined to the Golgi network when gK was coexpressed. Analysis of a UL20 deletion mutant of EHV-1 strain RacL11 indicated an involvement of UL20p in cell-to-cell spread, as well as in very late events in virus egress. Based on these and electron microscopic studies we suggest that the EHV-1 UL20 protein might be necessary to avoid fusion of mature virions with membranes of their transport vesicles.
New insights into regulated aquaporin-2 function

Purpose of reviewAquaporin-2 (AQP2) water channels in principal cells of the kidney collecting duct are essential for urine concentration. Due to application of modern technologies, progress in our understanding of AQP2 has accelerated in recent years. In this article, we highlight some of the new insights into AQP2 function that have developed recently, with particular focus on the cell biological aspects of AQP2 regulation. Recent findingsAQP2 is subjected to a number of regulated modifications, including phosphorylation and ubiquitination, which are important for AQP2 function, cellular localization and degradation. AQP2 is likely internalized via clathrin and non-clathrin-mediated endocytosis. Regulation of AQP2 endocytosis, in addition to exocytosis, is a vital mechanism in determining overall AQP2 membrane abundance. AQP2 is associated with regulated membrane microdomains. Studies using membrane cholesterol depleting reagents, for example statins, have supported the role of membrane rafts in regulation of AQP2 trafficking. Noncanonical roles for AQP2, for example in epithelial cell migration, are emerging. SummaryAQP2 function and thus urine concentration is dependent on a variety of cell signalling mechanisms, posttranslational modification and interplay between AQP2 and its lipid environment. This complexity of regulation allows fine-tuning of AQP2 function and thus body water homeostasis.
L'étude psychanalytique de la résolution des conflits dans les interactions internationales et la négociation

L’essence la plus profonde de l’homme est constituee de pulsions qui sont du meme ordre chez tous les etres humains, et qui visent la satisfaction de besoins primordiaux dans les conflits latents ou manifestes ininterrompus. Le processus de la civilisation mene necessairement de la famille a l’humanite, et est indissolublement lie au conflit inne de l’eternelle lutte entre l’amour et le desir de la mort. Conformement a cette idee et aux travaux de Freud, de Lacan, de Jung, de Binswanger et d’autres, notre these interroge le rapport entre les conflits qui existent en cinq niveaux (intrapersonnel, interpersonnel, intragroupal, intergroupal, international) et leur impact specifique sur les interactions internationales. La resolution de ces conflits est le choix entre deux ou plusieurs solutions possibles et parfois contradictoires (guerre ou paix, hostilites ou diplomatie, etc.). Ce choix se determine souvent dans les negociations internationales a travers des vecteurs psychanalytiques (enjeux identitaires, impact du bilinguisme et du plurilinguisme dans les interactions, discours politiques, etc.). L’enjeu de notre these est d’analyser le role et les consequences des negociations principales dans la resolution des conflits internationaux (avant, pendant la Seconde Guerre mondiale-1918-1945 et durant la guerre froide -1945-1991).
Analyzing Forty Years of Software Maintenance Models

Software maintenance has dramatically evolved in the last four decades, to cope with the continuously changing software development models, and programming languages and adopting increasingly advanced prediction models. In this work, we present the initial results of a Systematic Literature Review (SLR), highlighting the evolution of the metrics and models adopted in the last forty years.
The use of genotoxicity biomarkers in molecular epidemiology: applications in environmental, occupational and dietary studies

Abstract Molecular epidemiology is an approach increasingly used in the establishment of associations between exposure to hazardous substances and development of disease, including the possible modulation by genetic susceptibility factors. Environmental chemicals and contaminants from anthropogenic pollution of air, water and soil, but also originating specifically in occupational contexts, are potential sources of risk of development of disease. Also, diet presents an important role in this process, with some well characterized associations existing between nutrition and some types of cancer. Genotoxicity biomarkers allow the detection of early effects that result from the interaction between the individual and the environment; they are therefore important tools in cancer epidemiology and are extensively used in human biomonitoring studies. This work intends to give an overview of the potential for genotoxic effects assessment, specifically with the cytokinesis blocked micronucleus assay and comet assay in environmental and occupational scenarios, including diet. The plasticity of these techniques allows their inclusion in human biomonitoring studies, adding important information with the ultimate aim of disease prevention, in particular cancer, and so it is important that they be included as genotoxicity assays in molecular epidemiology.
Incidence and risk factors for rectal pain after laparoscopic rectal cancer surgery

Objective This study was performed to investigate the incidence of and potential risk factors for rectal pain after laparoscopic rectal cancer surgery. Methods We retrospectively analyzed data from 300 patients who underwent laparoscopic rectal cancer surgery. We assessed the presence of rectal pain and categorized patients into Group N (no rectal pain) or Group P (rectal pain). Results In total, 288 patients were included. Of these patients, 39 (13.5%) reported rectal pain and 14 (4.9%) had rectal pain that persisted for >3 months. Univariate analysis revealed that patients in Group P had more preoperative chemoradiotherapy, more ileostomies, longer operation times, more anastomotic margins of <2 cm from the anal verge, more anastomotic leakage, and longer hospital stays. Multivariate analysis identified an anastomotic margin of <2 cm from the anal verge and a long operation time as risk factors. The presence of diabetes mellitus was a negative predictor of rectal pain. Conclusions In this study, the incidence of rectal pain after laparoscopic rectal cancer surgery was 13.5%. An anastomotic margin of <2 cm from the anal verge and a long operation time were risk factors for rectal pain. The presence of diabetes mellitus was a negative predictor of rectal pain. Thus, the possibility of postoperative rectal pain should be discussed preoperatively with patients with these risk factors.
CAUSAS DE ABANDONO DE LA PRÁCTICA CLÍNICA HOSPITALARIA DE ENFERMERÍA

En los centros hospitalarios de Chile se observa la tendencia en las enfermeras de abandonar la practica clinica hospitalaria tempranamente. Esto afecta el cuidado del paciente. Objetivo: Determinar las variables asociadas al abandono de las enfermeras de la practica clinica hospitalaria (PCH) en la Region Metropolitana. Material y metodo: A 1.000 enfermeras de la Region Metropolitana se enviaron encuestas via e-mail y se obtuvieron 164 respuestas de enfermeras que abandonaron y 75 de enfermeras que no han abandonado la practica hospitalaria. La encuesta consideraba variables asociadas a insatisfaccion laboral como causas de abandono recogidas en la literatura y de un focus group. Resultados: Las principales causas de abandono fueron: el sistema de turnos, las remuneraciones y el escaso reconocimiento organizacional. La vocacion aparece como la principal razon de permanencia en la practica clinica. Conclusiones: El modelo predictivo propuesto permite pronosticar la probabilidad de que una enfermera abandone la practica clinica. La insatisfaccion con elementos organizacionales lleva al abandono. Este estudio puede ser un aporte al management en salud.
Coexistence of conservative and dissipative behavior in reversible dynamical systems.

Externally injected class-B lasers are shown to be approximately described by a reversible three-dimensional flow. For critical values of the external field such a model displays symmetry-breaking bifurcations, where the structure of space changes from conservative to dissipative either in a continuous or discontinuous manner. As a consequence, the coexistence of the two behaviors is observed in suitable parameter ranges. Symmetry breaking is shown to explain the onset of the very stable periodic solutions exhibited by the physical system. Such bifurcations are then studied in the simpler context of two-dimensional flows and recognized as degenerate codimension-2 phenomena. Generic normal forms are finally introduced which describe the local bifurcation unfolding.
Void-Handling Techniques for Routing Protocols in Underwater Sensor Networks: Survey and Challenges

From the view of routing protocols in underwater sensor networks (UWSNs), the presence of communication void, where the packet cannot be forwarded further using the greedy mode, is perhaps the most challenging issue. In this paper, we review the state of the art of void-handling techniques proposed by underwater geographic greedy routing protocols. To this, we first review the void problem and its negative impact on the category of the geographic greedy routing protocols, which does not entail any void recovery technique. It is followed by a discussion about the constraints, challenges, and features associated with the design of void-handling techniques in UWSNs. Afterward, currently available void-handling techniques in UWSNs are classified and investigated. They can be classified into two main categories: 1) location-based and 2) depth-based techniques. The advantages and disadvantages of each technique along with the recent advances are then presented. Finally, we present a qualitative comparison of these techniques and also discuss some possible future directions.
Contents of the American Journal of Psychiatry

Regular Articles Is maternalsmokingduringpregnancya riskfactorfor attentiondeficithyperactivity disorderin children? SharonMilberger, Joseph Biederman.Stephen V. Faraone,Lisa Chenand JaniceJones 1138 Age-dependent declineof attentiondeficithyperactivity disorder. JohnC. HillandEugeneP. Schoener 1143 Six-week,double-blind,placebo-controlledstudy of desipraminefor adult attention deficithyperactivity disorder.TimothyE. Wilens, JosephBiederman, JeffersonPrince,ThomasJ. Spencer, StephenV.Faraone, Rebecca Warburton,David Schle@fer, Meg Harding, ColleenLine/Witand Daniel Geller 1147 Backward-masking deficitis adolescentswith schizophrenicdisordersor attentiondeficithyperactivity disorder. Bjern Rishovd Rund, Merete 0k and Kjetil Sundet 1154 Associationof abnormalsmoothpursuiteyemovementswiththe deficitsyndromein schizophrenicpatients. David E. Ross. GunvantK Thaker, Robert W. Buchanan,Adrienne C. Lahti, Deborah Medoff John J. Bartko, Marianne Moran and Julie Hartley 1158 Prenatal growth markers in schizophrenia: a monozygotic co-twin control study. James 0. Davis and H. Stefan Bracha 1166 Anticipation in schizophrenia: new light on a controversial problem. Philip Gorwood, Marion Leboyer, BrunoFalissar4MauriceJay, FrÃ©dÃ©ric RouillonandJosuÃ© Feingold 1173 Sex differencesin neuropsychologicalfunctioningamong schizophrenicpatients. Richard It J. Lewine, Elaine F. Walker, Rebecca Shureit, Jane Caudle and Catherine Haden 1178 Suicidal behavior in schizophrenia and its relationship to awareness of illness. Xavier F Amador, Jill Harkavy Friedman,ChrysoulaKasapis, Scott A. Yale, Michael Flaumand Jack M. Gorman 1185 Assessment of object relations and reality testing in methadone patients. Megan J. Rutherford, John S. Cacciola, Arthur I. Alterman and James It McKay 1189 PsychiatricResearch Interviewfor Substanceand Mental Disorders (PRISM): reliabilityfor substance abusers.DeborahS. Hasin,KristinD. Trautman, GloriaM Miele, SharonSamet,MelissaSmithand JeanEndicott 1195