Miracle-dz/UniFAR-FTUs huggingface dataset:
Gene expression in skeletal muscle in response to stretch and force generation.

Striated muscle is a tissue in which gene expression is influenced to a large extent by mechanical signals. This includes the regulation of gene expression-associated muscle fiber phenotype determination, which depends on which protein isoform genes are transcribed, as well as muscle fiber mass accretion, which appears to involve some translational regulation. Although muscle synthesizes a set of highly specialized proteins it has a remarkable ability to adapt by expressing different isoforms of the same protein so that it acquires the appropriate contractile characteristics. Our work has focused on the myosin heavy chain (HC) genes as these encode the myosin cross bridge, which is responsible for muscle intrinsic velocity of contraction and economy of force development. RNA analyses after cast immobilization of the limb with the muscle in the lengthened or shortened position and/or with electrical stimulation were used to determine the effects of altered mechanical signals on gene transcription. When the soleus muscle was immobilized in the shortened position in the young animal it did not fully differentiate into a slow postural-type muscle. Even in the adult, the soleus muscle if deprived of stretch and contractile activity switches back to transcribing the fast myosin HC gene. The converse was true when the fast rabbit tibialis anterior was subjected to immobilization in the lengthened position and/or electrical stimulation. Both stretch alone and stimulation alone caused repression of the fast type and activation of the slow myosin genes. The reprogramming of the fast muscle was more complete when the stretch was combined with stimulation. (ABSTRACT TRUNCATED AT 250 WORDS)
Herpesvirus infections of laboratory macaques

Non-human primates (NHPs), primarily macaques, are commonly used as non-rodent species in pre-clinical safety assessment studies. The use of macaques in such studies is increasing largely due to the development of biopharmaceutical and immunomodulatory therapies that necessitates extensive safety testing. Macaques, commonly available for use in such studies, are infected by a rich flora of herpesviruses that cause persistent, latent, life-long infections. Primary infection of immune competent macaques is typically subclinical with very little associated morbidity and mortality only in very rare cases. A life-long consequence of herpesvirus infection is periodic stochastic and frequently asymptomatic recurrences from latency throughout an infected macaque’s lifetime. With immune modulation or suppression, however, immune control of herpesvirus infections can be lost, resulting in significant disease and even death of the affected animals. Since macaques undergo primary infection with herpesviruses starting around 4-6 months-of-age when maternally-derived antibody begins to wane, it is difficult and costly to derive animals that are herpesvirus-free. Further, the herpesvirus flora and prevalence of infection in laboratory macaques mirrors that of the adult human population making the herpesvirus-infected macaque a reasonable model of the general human population. This review is intended to familiarize toxicologists performing preclinical drug safety studies with the basic biology, disease pathogenesis and consequences of immune suppression in herpesvirus-infected laboratory macaques.
Cytomorphology of gastric and duodenal epithelium and reactivity to B72.3: A baseline for comparison to pancreatic lesions aspirated by EUS‐FNAB

Endoscopic ultrasound‐guided fine‐needle aspiration biopsy (EUS‐FNAB) has become a widely used method of pre‐operatively evaluating pancreatic masses. This technique introduces gastrointestinal contamination into the specimen, which poses a diagnostic pitfall. The cytomorphologic features of these contaminants have not been fully characterized. The current study was designed to systematically document the cytomorphology of gastric and duodenal epithelium on fixed and air‐dried smears, as well as ThinPrep® (TP) preparations, and to assess the reactivity of the epithelial cells to the tumor marker B72.3 so as to establish a baseline for future comparative studies with EUS‐FNAB of the pancreas. Air‐dried and fixed smears and TP specimens were obtained using a cytobrush from gastric (GM) and duodenal (DM) mucosa from 14 Whipple specimens. Cytologic features of cell architecture, cellular features and smear background were analysed. Immunocytochemical staining with B72.3 was performed in 10/14 cases. Mucin was present in all preparations except one case from the duodenum. It was consistently present as isolated thick to thin clumps but never as diffuse ‘colloid–type’ mucin; it was most prominent on air‐dried smears, and most abundant from the GM. Epithelial cells were admixed with mucin, but degenerated cells and inflammation were not present within the mucin. Mucin on TP appeared as fragmented wisps of pale blue staining material. Background inflammation and debris were not significant findings. The epithelial cells were arranged in large and small monolayered sheets. Smaller groups were more common from GM on smears and more abundant on TP than smears. Luminal edges (DM>GM) were a prominent feature, with a brush border noted in DM. The nuclei of GM and DM were round, evenly spaced and without atypia, and dense, non‐vacuolated cytoplasm was the rule, with the exception of goblet cells and occasional gastric foveolar cells noted in one case. In both GM and DM, B72.3 stained goblet cells with a strong, coarsely granular pattern and stained epithelial cells focally in a finely granular, punctate, perinuclear distribution; mucin also stained strongly in all cases. These baseline characteristics provide a template for assessing mucin and epithelial GM and DM contamination on pancreatic EUS‐FNAB specimens. Diagn. Cytopathol. 2005;33:381–386. © 2005 Wiley‐Liss, Inc.
The Exocyst is a multiprotein complex required for exocytosis in Saccharomyces cerevisiae.

In the yeast Saccharomyces cerevisiae, the products of at least 15 genes are involved specifically in vesicular transport from the Golgi apparatus to the plasma membrane. Previously, we have shown that three of these genes, SEC6, SEC8 and SEC15, encode components of a multisubunit complex which localizes to the tip of the bud, the predominant site of exocytosis in S. cerevisiae. Mutations in three more of these genes, SEC3, SEC5 and SEC10, were found to disrupt the subunit integrity of the Sec6‐Sec8‐Sec15 complex, indicating that these genes may encode some of the remaining components of this complex. To examine this possibility, we cloned and sequenced the SEC5 and SEC10 genes, disrupted them, and either epitope tagged them (Sec5p) or prepared polyclonal antisera (Sec10p) to them for co‐immunoprecipitation studies. Concurrently, we biochemically purified the remaining unidentified polypeptides of the Sec6‐Sec8‐Sec15 complex for peptide microsequencing. The genes encoding these components were identified by comparison of predicted amino acid sequences with those obtained from peptide microsequencing of the purified complex components. In addition to Sec6p, Sec8p and Sec15p, the complex contains the proteins encoded by SEC3, SEC5, SEC10 and a novel gene, EXO70. Since these seven proteins function together in a complex required for exocytosis, and not other intracellular trafficking steps, we have named it the Exocyst.
The Immediate-Early 63 Protein of Varicella-Zoster Virus: Analysis of Functional Domains Required for Replication In Vitro and for T-Cell and Skin Tropism in the SCIDhu Model In Vivo

ABSTRACT The immediate-early 63-kDa (IE63) protein of varicella-zoster virus (VZV) is a phosphoprotein encoded by open reading frame (ORF) ORF63/ORF70. To identify functional domains, 22 ORF63 mutations were evaluated for effects on IE63 binding to the major VZV transactivator, IE62, and on IE63 phosphorylation and nuclear localization in transient transfections, and after insertion into the viral genome with VZV cosmids. The IE62 binding site was mapped to IE63 amino acids 55 to 67, with R59/L60 being critical residues. Alanine substitutions within the IE63 center region showed that S165, S173, and S185 were phosphorylated by cellular kinases. Four mutations that changed two putative nuclear localization signal (NLS) sequences altered IE63 distribution to a cytoplasmic/nuclear pattern. Only three of 22 mutations in ORF63 were compatible with recovery of infectious VZV from our cosmids, but infectivity was restored by inserting intact ORF63 into each mutated cosmid. The viable IE63 mutants had a single alanine substitution, altering T171, S181, or S185. These mutants, rOKA/ORF63rev[T171], rOKA/ORF63rev[S181], and rOKA/ORF63rev[S185], produced less infectious virus and had a decreased plaque phenotype in vitro. ORF47 kinase protein and glycoprotein E (gE) synthesis was reduced, indicating that IE63 contributed to optimal expression of early and late gene products. The three IE63 mutants replicated in skin xenografts in the SCIDhu mouse model, but virulence was markedly attenuated. In contrast, infectivity in T-cell xenografts was not altered. Comparative analysis suggested that IE63 resembled the herpes simplex virus type 1 US1.5 protein, which is expressed colinearly with ICP22 (US1). In summary, most mutations of ORF63 made with our VZV cosmid system were lethal for infectivity. The few IE63 changes that were tolerated resulted in VZV mutants with an impaired capacity to replicate in vitro. However, the IE63 mutants were attenuated in skin but not T cells in vivo, indicating that the contribution of the IE63 tegument/regulatory protein to VZV pathogenesis depends upon the differentiated human cell type which is targeted for infection within the intact tissue microenvironment.
Merger Negotiations in the Shadow of Judicial Appraisal

The recent surge in appraisal litigation has sparked debate over the desirability of appraisal and how this remedy should be structured. Much of this debate is based on untested assertions about appraisal’s ex ante effect on the structure and pricing of takeovers. Systematically investigating this effect, we find evidence that target shareholders receive higher abnormal returns as the strength of the appraisal remedy increases. We find no evidence that bidders offer a lower up-front price as a means to pay off dissenting shareholders after a sale. Furthermore, threat of appraisal does not appear to limit takeover activity or impact the method of payment. Overall, our results suggest that appraisal provides an important ex ante protection for target-firm shareholders.
Interaction of genome-size DNA with phospholipid membrane in a cell-sized micro-watersphere as a model cellular system

It has been established that a long DNA molecule (> 20–30 kilo base-pairs) exhibits a conformational transition from a coiled state to a highly folded state under the presence of condensing agents such as polyamines. We have investigated these changes in conformation of long DNA molecules at a single-molecule level by directly observing conformation of individual DNA molecules in the bulk aqueous solution under fluorescence microscopy. In a cell, DNA is placed in a micrometer-scale space surrounded by phospholipid membrane. In this study, to get insights into the structural characteristics of the genome-size DNA under such a cellular environmental condition, we encapsulated giant DNA (bacteriophage T4 DNA, 166 kilo base-pairs) labeled with fluorescent dyes in a cell-sized (20–60 μm) microsphere coated with phospholipid membrane, and investigated the conformational characteristics and distribution of the DNA in the microsphere under fluorescence microscopy. In the microsphere, T4 DNAs were diffusely distributed within the aqueous phase and exhibited a coiled conformation, when the microsphere was composed of eggPC (phosphatidylcholine from egg yolk). On the other hand, in the microsphere composed of DOPE (1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine), the DNAs were located on the membrane surface in the presence of high concentrations of Mg2+. Single-molecule observation of the DNAs with high-magnification images showed that the DNA exhibited an extended coil conformation and underwent the intra-molecular chain motion on the membrane surface. Under the same experimental condition, a short linear DNA (6 kilo base-pairs) was not bound to the DOPE membrane surface and was present in the aqueous phase in the microsphere, which suggests that the adsorption to the DOPE membrane surface in the presence of Mg2+ is a distinctive characteristic of long DNAs. These results are interpreted in terms of the structural characteristic and its roles of DNA in the cellular environment.
Comparison of Bacterioneuston and Bacterioplankton Dynamics during a Phytoplankton Bloom in a Fjord Mesocosm

ABSTRACT The bacterioneuston is the community of Bacteria present in surface microlayers, the thin surface film that forms the interface between aquatic environments and the atmosphere. In this study we compared bacterial cell abundances and bacterial community structures of the bacterioneuston and the bacterioplankton (from the subsurface water column) during a phytoplankton bloom mesocosm experiment. Bacterial cell abundance, determined by flow cytometry, followed a typical bacterioplankton response to a phytoplankton bloom, with Synechococcus and high-nucleic acid content (HNA) bacterial cell numbers initially falling, probably due to selective protist grazing. Subsequently HNA and low-nucleic acid content bacterial cells increased in abundance, but Synechococcus cells did not. There was no significant difference between bacterioneuston and bacterioplankton cell abundances during the experiment. Conversely, distinct and consistent differences between the bacterioneuston and the bacterioplankton community structures were observed. This was monitored simultaneously by Bacteria 16S rRNA gene terminal restriction fragment length polymorphism and denaturing gradient gel electrophoresis. The conserved patterns of community structure observed in all of the mesocosms indicate that the bacterioneuston is distinctive and nonrandom.
HEALTH SYSTEMS INSTITUTIONAL CHARACTERISTICS: A SURVEY OF 29 OECD COUNTRIES

In 2008, the OECD launched a survey to collect information on the health systems characteristics of member countries. This paper presents the informaton provided by 29 of these countries in 2009. It describes country-specific arrangements to organise the population coverage against health risks and the financing of health spending. It depicts the organisation of health care delivery, focusing on the public/private mix of health care provision, provider payment schemes, user choice and competition among providers, as well as the regulation of heallth care suppply and prices. Finally, this document provides information on governnance and resource allocation in health systems (decentralisation in decisionmaking, nature of budget constraints and priority setting). En 2008, l’OCDE a lance une enquete aupres de ses pays membres pour recueillir une information sur les caracteristiques des systemes de sante. Ce document presente l’information fournie par 29 pays en 2009. Il decrit comment chaque pays organise la couverture de la population contre les risques lies a la sante et le financement des depenses de sante. Il depeint l’organisation des soins, a travers le caractere public/prive de l’offre de soins, les modes de paiement des prestataires, le choix de l’usager et la concurrence entre prestataires, ainsi que la regulation de l’offre et des prix. Finalement, il donne une information sur la gouvernance et l’allocation des ressources dans les systemes de sante (decentralisation, nature de la contrainte budgetaire et etablissement des priorites).
Measuring and Visualizing Students’ Behavioral Engagement in Writing Activities

Engagement is critical to the success of learning activities such as writing, and can be promoted with appropriate feedback. Current engagement measures rely mostly on data collected by observers or self-reported by the participants. In this paper, we describe a learning analytic system called Tracer, which derives behavioral engagement measures and creates visualizations of behavioral patterns of students writing on a cloud-based application. The tool records the intermediate stages of document development and uses this data to measure learners' behavioral engagement and derive three visualizations. Writers (N= 23 University students) participated in a controlled one-hour writing session in which they post-facto self-reported their level of behavioral engagement. Results show that the level of behavioral engagement automatically estimated by the system correlates with the level reported by the participants. Additionally, users stated that the visualizations were coherent with their writing activity and were useful to help them reflect on the writing process.
Vowel Categorization and the Critical Band

Using the concept formation paradigm, two series of experiments were conducted to test the hypothesis that the critical band (CB) was a factor in learning to make absolute discriminations of vowels. The specific hypothesis being examined was that the CB is a psychoacoustic boundary in learning to make vowel categorizations, and that learning absolute discriminations of pairs of vowels that differ in one of their formants by one bark or more is significantly easier than learning absolute discriminations of vowels that differ by less than one bark. Subjects were given the task of learning to identify paired sets of synthesized vowels that differed in either F1, or F2 by 0.4, 0.6, 0.8, 1.0, or 1.2 bark. The results of these experiments suggest that the critical bandwidth is not a natural psychoacoustic boundary in the learning of vowel categories, and also that subjects seem better able to learn distinctions involving differences in F1 than distinctions involving differences in F2. The discussion raises the possibility that vowels that differ by less than one bark may not be perceptually viable because of such factors as ambient noise, articulatory constraints, and coarticulatory influences. Some evidence from Dutch and French is presented in support of this conjecture.
Metrics to evalute fuctional quality: A sistematic review

Nowadays, quality assurance of software products is very important. To assure this quality, there exist several international standards like the standard ISO 25010. These standards define quality models, characteristics and sub-characteristics that must be taken into account in order to evaluate the quality of a software product. In this context, metrics are needed to evaluate quality objectively. This document shows a systematic review of the literature about the existing metrics that can be used to measure functional quality (as defined in the international standard ISO 25010) of a software product. As results of the conducted review, 23 metrics were found, most of them based on tests. The conclusions obtained from this study show that, although more metrics should be defined, there exists a enough number of metrics to measure all the functional quality characteristics defined in the international standard ISO 25010.
Risk factors for mortality in end-stage kidney disease patients under online-hemodiafiltration: three-year follow-up study

Abstract The aim of this work was to evaluate the predictors of mortality in a group of end-stage kidney disease (ESRD) patients under dialysis, by performing a three-year follow-up study. From the 236 patients included in this study, 54 patients died during the three-year follow-up period. Our data showed that the risk of death was higher in patients presenting lower levels of mean cell hemoglobin concentration, transferrin, and albumin. Our study showed that poor nutritional status and an inflammatory-induced iron depleted erythropoiesis are important factors for mortality in these patients.
Differential Contribution of Malic Enzymes during Soybean and Castor Seeds Maturation

Malic enzymes (ME) catalyze the decarboxylation of malate generating pyruvate, CO2 and NADH or NADPH. In some organisms it has been established that ME is involved in lipids biosynthesis supplying carbon skeletons and reducing power. In this work we studied the MEs of soybean and castor, metabolically different oilseeds. The comparison of enzymatic activities, transcript profiles and organic acid contents suggest different metabolic strategies operating in soybean embryo and castor endosperm in order to generate precursors for lipid biosynthesis. In castor, the malate accumulation pattern agrees with a central role of this metabolite in the provision of carbon to plastids, where the biosynthesis of fatty acids occurs. In this regard, the genome of castor possesses a single gene encoding a putative plastidic NADP-ME, whose expression level is high when lipid deposition is active. On the other hand, NAD-ME showed an important contribution to the maturation of soybean embryos, perhaps driving the carbon relocation from mitochondria to plastids to support the fatty acids synthesis in the last stages of seed filling. These findings provide new insights into intermediary metabolism in oilseeds and provide new biotechnological targets to improve oil yields.
The Geriatrics Excellence in Teaching Series: An Integrated Educational Skills Curriculum for Faculty and Fellows Development

Geriatricians need to acquire skills in teaching and curriculum development to educate physicians caring for the growing population of adults aged 65 and older. To meet this challenge, educators in the Duke University Center for the Study of Aging and Human Development introduced a monthly seminar series to promote the development of geriatrics faculty and fellows as clinician educators. Ten educational skills development seminars were incorporated into geriatrics grand rounds in the first year of the program. These sessions were implemented using a variety of active learning strategies to expose participants to innovative adult learning‐centered approaches for enhancing learning and instruction in medical education. Participants assessed all sessions using a feedback form and were surveyed at the end of the series to measure their overall satisfaction with the program and ascertain its effect on their roles as educators. Participants rated individual sessions highly, and respondents to the survey at the end of the course agreed that the Geriatrics Excellence in Teaching Series provided them with resources for use in their teaching practices and attested to having already applied knowledge and skills learned in the series in their teaching practices. Key elements for the program's success included an upfront needs assessment to prioritize topics, interactive sessions promoting skill development through actual practice of various strategies, open discussions to identify challenges and solutions, and a convenient and customary time slot. This format can be replicated with other geriatrics programs, providing a needed opportunity for faculty and fellows to learn about education principles.