Miracle-dz/UniFAR-FTUs huggingface dataset:
Receptor-Binding Domain of Severe Acute Respiratory Syndrome Coronavirus Spike Protein Contains Multiple Conformation-Dependent Epitopes that Induce Highly Potent Neutralizing Antibodies

The spike (S) protein of severe acute respiratory syndrome associated coronavirus (SARS-CoV) is a major antigenic determinant capable of inducing protective immunity. Recently, a small fragment on the SARS-CoV S protein (residues 318–510) was characterized as a minimal receptor-binding domain (RBD), which mediates virus binding to angiotensin-converting enzyme 2, the functional receptor on susceptible cells. In this study, we demonstrated that a fusion protein containing RBD linked to human IgG1 Fc fragment (designated RBD-Fc) induced high titer of RBD-specific Abs in the immunized mice. The mouse antisera effectively neutralized infection by both SARS-CoV and SARS pseudovirus with mean 50% neutralization titers of 1/15,360 and 1/24,737, respectively. The neutralization determinants on the RBD of S protein were characterized by a panel of 27 mAbs isolated from the immunized mice. Six groups of conformation-dependent epitopes, designated as Conf I–VI, and two adjacent linear epitopes were identified by ELISA and binding competition assays. The Conf IV and Conf V mAbs significantly blocked RBD-Fc binding to angiotensin-converting enzyme 2, suggesting that their epitopes overlap with the receptor-binding sites in the S protein. Most of the mAbs (23 of 25) that recognized the conformational epitopes possessed potent neutralizing activities against SARS pseudovirus with 50% neutralizing dose ranging from 0.005 to 6.569 μg/ml. Therefore, the RBD of SARS S protein contains multiple conformational epitopes capable of inducing potent neutralizing Ab responses, and is an important target site for developing vaccines and immunotherapeutics.
Evidence-based guidelines for cardiovascular disease prevention in women.

Copyright © 2004 American Heart Association. All rights reserved. Print ISSN: 0009-7322. Online 72514 Circulation is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX DOI: 10.1161/01.CIR. 0000114834.85476. 81 2004;109;672-693; originally published online Feb 4, 2004; Circulation K. Wenger and Christine L. Williams Nanette A. Sila, Sidney C. Smith, Jr, George Sopko, Anne L. Taylor, Brian W. Walsh, Pasternak, Vivian W. Pinn, Rose Marie Robertson, Karin Schenck-Gustafsson, Cathy Oparil, Pamela Ouyang, Mehmet C. Oz, Michael E. Mendelsohn, Richard C. Sharonne N. Hayes, Debra R. Judelson, Nora L. Keenan, Patrick McBride, Suzanne Chandra-Strobos, Rosalind P. Fabunmi, Deborah Grady, Constance K. Haan, Lori Mosca, Lawrence J. Appel, Emelia J. Benjamin, Kathy Berra, Nisha Evidence-Based Guidelines for Cardiovascular Disease Prevention in Women http://circ.ahajournals. org/cgi/content/full/109/5/672 located on the World Wide Web at: The online version of this article, along with updated information and services, is
Prospective evaluation of multilayered epithelium in Barrett's esophagus

OBJECTIVE:We recently identified a distinctive type of multilayered epithelium in two patients with Barrett's esophagus, which shows morphological characteristics of both squamous and columnar epithelium. This study was performed to prospectively evaluate the prevalence of multilayered epithelium in patients with Barrett's esophagus.METHODS:Mucosal biopsies were obtained from the squamocolumnar junction (Z-line) of 58 patients with endoscopic evidence of esophageal columnar epithelium and from the gastroesophageal junction in 21 patients without endoscopic evidence of esophageal columnar epithelium. Specimens were evaluated for the presence of multilayered epithelium and goblet cells.RESULTS:Twenty-four of 58 (41%) of the patients with endoscopic evidence of esophageal columnar epithelium had multilayered epithelium compared with only one of 21 patients (5%) in the control group (p = 0.005). Of the 58 patients in the study group, 43 had goblet cell metaplasia and 15 did not (p < 0.001). Only patients with goblet cell metaplasia had multilayered epithelium. Shorter lengths of columnar epithelium were noted in the 24 patients with goblet cells and multilayered epithelium compared with the 19 patients with goblet cells and no multilayered epithelium (p < 0.05). CONCLUSIONS:Multilayered epithelium is strongly associated with goblet cell metaplasia in patients with endoscopic evidence of esophageal columnar epithelium. These data support the hypothesis that multilayered epithelium may represent a transitional stage in the development of Barrett's esophagus.
Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects.

OBJECTIVE To review the basic scientific status of repair in articular cartilage tissue and to assess the efficiency of current clinical therapies instigated for the treatment of structural lesions generated therein as a result of trauma or during the course of various diseases, notably osteoarthritis (OA). Current scientific trends and possible directions for the future will also be discussed. DESIGN A systematic and critical analysis is undertaken, beginning with a description of the spontaneous repair responses in different types of lesion. Surgical interventions aimed at inducing repair without the use of active biologics will then be considered, followed by those involving active biologics and those drawing on autogenic and allogeneic tissue transplantation principles. Cell transplantation approaches, in particular novel tissue engineering concepts, will be critically presented. These will include growth-factor-based biological treatments and gene transfection protocols. A number of technical problems associated with repair interventions, such as tissue integration, tissue retention and the role of mechanical factors, will also be analysed. RESULTS A critical analysis of the literature reveals the existence of many novel and very promising biologically-based approaches for the induction of articular cartilage repair, the vast majority of which are still at an experimental phase of development. But prospective, double-blinded clinical trials comparing currently practiced surgical treatments have, unfortunately, not been undertaken. CONCLUSION The existence of many new and encouraging biological approaches to cartilage repair justifies the future investment of time and money in this research area, particularly given the extremely high socio-economic importance of such therapeutic strategies in the prevention and treatment of these common joint diseases and traumas. Clinical epidemiological and prospective trials are, moreover, urgently needed for an objective, scientific appraisal of current therapies and future novel approaches.
N-(4-Hydroxy-3-methoxybenzyl)benzamide

In the molecular structure of the title compound, C15H15NO3, the two benzene rings are twisted with respect to each other, making a dihedral angle of 75.11 (10)°. In the amide fragment, the C=O and C—N bond distances are 1.248 (3) and 1.321 (3) Å, respectively, indicating electron delocalization. A partially ovelapped arrangement between parallel hydroxymethoxybenzene rings is observed in the crystal structure, and the face-to-face distance of 3.531 (16) Å suggests the existence of weak π–π stacking. N—H⋯O and O—H⋯O hydrogen bonding is also present in the crystal structure.
Overlapping Roles of the Cytoplasmic and Mitochondrial Redox Regulatory Systems in the Yeast Saccharomyces cerevisiae

ABSTRACT Thioredoxins are small, highly conserved oxidoreductases which are required to maintain the redox homeostasis of the cell. Saccharomyces cerevisiae contains a cytoplasmic thioredoxin system (TRX1, TRX2, and TRR1) as well as a complete mitochondrial thioredoxin system, comprising a thioredoxin (TRX3) and a thioredoxin reductase (TRR2). In the present study we have analyzed the functional overlap between the two systems. By constructing mutant strains with deletions of both the mitochondrial and cytoplasmic systems (trr1 trr2 and trx1 trx2 trx3), we show that cells can survive in the absence of both systems. Analysis of the redox state of the cytoplasmic thioredoxins reveals that they are maintained independently of the mitochondrial system. Similarly, analysis of the redox state of Trx3 reveals that it is maintained in the reduced form in wild-type cells and in mutants lacking components of the cytoplasmic thioredoxin system (trx1 trx2 or trr1). Surprisingly, the redox state of Trx3 is also unaffected by the loss of the mitochondrial thioredoxin reductase (trr2) and is largely maintained in the reduced form unless cells are exposed to an oxidative stress. Since glutathione reductase (Glr1) has been shown to colocalize to the cytoplasm and mitochondria, we examined whether loss of GLR1 influences the redox state of Trx3. During normal growth conditions, deletion of TRR2 and GLR1 was found to result in partial oxidation of Trx3, indicating that both Trr2 and Glr1 are required to maintain the redox state of Trx3. The oxidation of Trx3 in this double mutant is even more pronounced during oxidative stress or respiratory growth conditions. Taken together, these data indicate that Glr1 and Trr2 have an overlapping function in the mitochondria.
Partial discharge diagnostics in power and instrument transformer based on acoustic emission method

Power and instrument transformers represent important components of electric power transmission and distribution stations. An important indicator of the condition of the insulation of such equipment is the evolution of the partial discharge (PD) level, since an increase of this level usually indicates the development of a fault affecting the insulation quality. Detection of partial discharges in the early stages reduces the risk of decommissioning of such equipment. A well known method for detecting and locating of partial discharges is the acoustic emission method. This article is an overview of the thirty years' experience of the use of this method in ICMET, which resulted in the development of the necessary equipment for monitoring and location of partial discharges in power and instrument transformers.
Heart rate versus %VO2max: age, sex, race, initial fitness, and training response--HERITAGE.

PURPOSE In the HERITAGE Family Study, heart rate (HR) associated with various percentages of maximal oxygen intake (VO2max) was used to prescribe exercise intensity. When fitness improved, HR at the same power output (PO) decreased, and PO was increased to produce the prescribed HR. Although we assumed that subjects were again working at the same %VO2max, there were no studies with a large heterogeneous population to determine whether this was correct. METHODS Therefore, 653 subjects with complete data were classified by age, sex, race, initial VO2max, and VO2max response after 20 wk of training. RESULTS All groups had a significant increase in VO2max and a significant decrease in HR at the same absolute PO after training but no difference in HR at the same relative intensity. CONCLUSIONS Training does not affect HR at a given %VO2max in a heterogeneous population of men and women, blacks and whites aged 17-65 yr with different initial VO2max values and different responses to training.
Structural basis for autoinhibition and activation of Auto, a virulence‐associated peptidoglycan hydrolase of Listeria monocytogenes

During a bacterial infection, each successive step is orchestrated by a dedicated set of virulence factors. In Gram‐positive bacteria, the presentation or release of such factors is crucially dependent on the continual remodelling of the cell wall. We have investigated the autolysin or peptidoglycan hydrolase Auto (Lmo1076) from the human pathogen Listeria monocytogenes to structurally and biochemically underpin its role in host cell invasion. We demonstrate that Auto is an N‐acetylglucosaminidase, that it is autoinhibited when newly secreted but activated by proteolytic cleavage, that it has an acidic pH optimum and that it preferentially cleaves acetylated over de‐acetylated peptidoglycan. The crystal structure of Auto, the first for glycoside hydrolase family 73, and the first for a listerial autolysin, indicates that autoinhibition is due to an N‐terminal α‐helix unique to Auto that physically blocks the substrate‐binding cleft. We identify Glu122 and Glu156 as the two catalytically essential carboxylate groups. The physical properties of Auto as well as its localization to lipoteichoic acid by its four C‐terminal GW modules imply cell wall degradation by Auto to be highly co‐ordinated. Its spatio‐temporally controlled activation and localized activity in an acidified environment indicate that it facilitates remodelling of the cell wall and may be involved in co‐ordinating the release of virulence factors at specific stages of an infection.
ENDOTHELIAL PROGENITOR CELLS AND RESPONSE TO RANIBIZUMAB IN AGE-RELATED MACULAR DEGENERATION

Background: Choroidal neovascularization (CNV) is the main cause of vision loss in age-related macular degeneration (AMD). In experimental CNV, endothelial progenitor cells (EPCs) contribute to the formation of new vessels. The aim of this study was to investigate whether the behavior of EPCs in patients with AMD supports a role for EPCs in human CNV. Methods: The number of circulating EPCs that are considered pure endothelial precursors and EPCs with monocytic characteristics, and the plasma levels of regulatory cytokines were evaluated in 23 patients with AMD with active CNV and 20 matched controls. In the patients, this profile was re-evaluated after ranibizumab. Results: When compared with controls, the patients with AMD showed a lower number of both EPC types (P = 0.03) and higher plasma levels (P = 0.03) of stromal cell–derived factor 1. Three monthly injections of ranibizumab returned to control levels the number of circulating EPCs considered pure endothelial precursors and of stromal cell–derived factor 1, but not of monocytic EPCs. Conclusion: The observations indicate responsiveness of circulating EPCs to the CNV process in AMD. They suggest the hypothesis that increased stromal cell–derived factor 1 production at the CNV site (reflected in higher plasma levels) recruits EPCs from the circulation, and that antivascular endothelial growth factor therapy selectively decreases the recruitment of cells to be incorporated into new vessels.
Life events and stress in patients with functional dyspepsia compared with patients with duodenal ulcer and healthy controls.

BACKGROUND Life events and stress may be important for functional dyspepsia and duodenal ulcer. METHODS The perception of life events in the preceding 6 months was recorded in 100 patients with functional dyspepsia, 100 patients with duodenal ulcer, and 100 healthy controls. In addition, psychologic and social factors were assessed. RESULTS Patients with functional dyspepsia experienced significantly more life events than patients with duodenal ulcer and healthy controls. The difference in life events between the groups was due to the difference in stressful life events. The patients with functional dyspepsia had higher levels of state-trait anxiety, general psychopathology, and depression than patients with duodenal ulcer and healthy controls. CONCLUSION Patients with functional dyspepsia had higher scores on negative life events than patients with duodenal ulcer and healthy controls. This may be causally related to the higher levels of anxiety, depression, and general psychopathology in these patients.
Stability-Indicating Method and LC-MS-MS Characterization of Forced Degradation Products of Sofosbuvir.

Sofosbuvir is a novel direct acting antiviral agent against hepatitis C virus. In the present work, a rapid, specific and reproducible isocratic reversed phase high performance liquid chromatography (RP-HPLC) method has been developed and validated for the determination of sofosbuvir in the presence of its stressed degradation products. Sobosbuvir was subjected to hydrolysis (acidic, alkaline and neutral), oxidation, photolysis and thermal stress, as per international conference on harmonization (ICH) conditions. The drug showed degradation under oxidative, photolysis, acid and base hydrolysis stress conditions. However, it was stable under thermal and neutral hydrolysis stress conditions. Chromatographic separation of the drug from its degradation products was performed on Inertsil ODS-3 C18 (250 mm × 4.6 mm i.d., 5 µm) column using a green mobile phase of methanol:water 70:30 (v/v). The degradation products were characterized by LC-MS-MS and the fragmentation pathways were proposed. The developed method was validated as per ICH guidelines. No previous method was reported regarding the degradation behavior of sofosbuvir.
Participation in ECEC programs: equity, diversity and educational disadvantage

There is a consensus among researchers that children benefit from high quality early childhood education and that these beneficial effects are most salient for children at risk for developmental delays. However, different studies have also shown that children from poor families are over-represented in early childhood education of poor quality. Policies that favor funding by local or central authorities are more effective in enhancing accessibility than market-oriented policies. Further, we discuss what quality may mean in contexts of diversity. Child-centered curricula that take into account children’s and families’ diverse perspectives are more successful in creating profitable learning spaces. This asks for reflective practitioners that document their educational practices and that strive for belonging and involvement, rather than for parents’ participation.
Onde está o Wally? (In)visibilidades sobre mulheres e política nas práticas de receção jornalística

Este artigo analisa o modo como os públicos jovens compreendem, interpretam e se posicionam em relação às representações mediáticas de mulheres que desempenham cargos políticos. Com base na análise do material que resultou da realização de grupos focais, este artigo mostra que a existência de assimetrias de género nos média informativos não é considerada pelos públicos (jovens) como uma questão relevante. A maioria das/os participantes adotou posicionamentos tranquilizadores relativamente à representação qualitativa de mulheres que exercem cargos políticos, tendo revelado a falta de consciência crítica sobre as consequências da manutenção de relações de poder desiguais no contexto mediático. Além disso, procurando explicar as causas subjacentes aos paradigmas representacionais identificados, as/os participantes raramente questionaram os fatores económicos, socioculturais e políticos que influem na produção noticiosa. Enformado por uma perspetiva feminista, este estudo sublinha, assim, a necessidade de promover a literacia crítica mediática juntos dos públicos com vista à desconstrução de assunções de género hegemónicas, bem como de se refletir sobre os eventuais impactos das representações mediáticas ao nível da (re)configuração do espaço político/público.
The South African truth and reconciliation commission as a therapeutic tool.

A Truth Commission is one of the institutions used in international law to investigate gross human rights violations within a specific country. In this article we examine claims that the South African Truth and Reconciliation Commission (TRC) was therapeutic. In the absence of empirical evidence, this examination will be guided by a theoretical framework that will reflect ways by which we believe international legal institutions can contribute tot he healing of the people of a country in which human rights abuses have taken place. We developed this framework with reference to the literature. Our conclusion is that the legislator's emphasis on truth, reconciliation, stability, and restorative justice enhanced the TRC's potential to promote healing, but that some features of this procedure and the enabling Act, the Promotion of National Unity and Reconciliation Act (1995), restricted its ability to be therapeutic. We conclude by looking at the role culture may have played in the success of the TRC.
Decision points in the treatment of transfusional iron overload in patients with myelodysplastic syndromes: why, when, and how to chelate

ABSTRACT Introduction: Patients with myelodysplastic syndromes (MDS) differ from those with other transfusion-dependent conditions (eg, thalassemia) as they are typically older, have comorbid conditions, and a generally shorter life expectancy. The underlying disease process in MDS and frequent use of red blood cell transfusions lead to iron accumulation and ultimately organ damage. Whether iron-reducing interventions such as chelation therapy can improve outcomes in this population is currently under investigation. Areas covered: We reviewed published English-language articles from PubMed on the topic of iron overload (IO) in MDS, and the use of iron chelation therapies (ICTs) to alleviate iron burden. Expert commentary: Data on IO-associated complications in MDS are derived largely from retrospective studies and there are limited data to guide clinicians on major treatment decisions. Although effective and well-tolerated oral ICTs are available, and general recommendations may be made regarding usage in MDS, guidance is not yet based on prospective data. The clinical endpoints and assessments for MDS may differ substantively from those used in patients with thalassemia, as an older population may have competing causes for morbidity. We expect that emergent data from clinical trials currently underway will define more appropriate endpoints/assessments for the MDS population in clinical trials.
Immunosuppressant Use Without Bone Loss—Implications for Bone Loss After Transplantation

Cyclosporine A (CsA) is associated with posttransplantation bone disease. Immunosuppressant drugs such as sirolimus (SRL), which are more potent and less deleterious than CsA, are being developed. Previous experiments have shown that SRL although immunosuppressive, is relatively bone sparing. The use of low doses of CsA and SRL in combination has displayed in vivo synergism. This study was initiated to examine the effect of low‐dose CsA and SRL on bone metabolism, thereby hopefully providing a bone sparing immunosuppressive regimen for transplant recipients. One hundred and nineteen rats were divided into groups: basal, vehicle, CsA high dose, CsA low dose, SRL low dose, and combination low‐dose CsA and SRL. The basal group was killed on day 0 for histomorphometry. The experimental groups were weighed and bled on days 0, 28, 56, and 84 and were killed on day 84 for histomorphometry. Serial assays for blood urea nitrogen (BUN), creatinine, and osteocalcin were performed. Osteocalcin was raised on days 28 and 56 in the high dose CsA group. Histomorphometry showed osteopenia with high‐dose CsA. Low‐dose CsA was relatively bone sparing, while low‐dose SRL and combined low‐dose CsA did not cause bone loss. In conclusion, the synergistic combination of low‐dose CsA and SRL has the potential of providing both bone sparing and immunosuppressive benefits.