gebhart/patrepeval huggingface dataset:
Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus (2015)

Middle East Respiratory Syndrome (MERS) is a highly lethal pulmonary infection caused by a previously unidentified coronavirus (CoV), likely transmitted to humans by infected camels. There is no licensed vaccine or antiviral for MERS, therefore new prophylactic and therapeutic strategies to combat human infections are needed. In this study, we describe, for the first time, to our knowledge, the isolation of a potent MERS-CoV-neutralizing antibody from memory B cells of an infected individual. The antibody, named LCA60, binds to a novel site on the spike protein and potently neutralizes infection of multiple MERS-CoV isolates by interfering with the binding to the cellular receptor CD26. Importantly, using mice transduced with adenovirus expressing human CD26 and infected with MERS-CoV, we show that LCA60 can effectively protect in both prophylactic and postexposure settings. This antibody can be used for prophylaxis, for postexposure prophylaxis of individuals at risk, or for the treatment of human cases of MERS-CoV infection. The fact that it took only 4 mo from the initial screening of B cells derived from a convalescent patient for the development of a stable chinese hamster ovary (CHO) cell line producing neutralizing antibodies at more than 5 g/L provides an example of a rapid pathway toward the generation of effective antiviral therapies against emerging viruses.
Mutational analysis and an alternatively spliced product of B7 defines its CD28/CTLA4-binding site on immunoglobulin C-like domain. (1995)

Costimulatory molecules B7 and B7-2 interact with T cell surface receptors CD28/CTLA4 and deliver a costimulatory signal essential for T cell growth. However, the structure basis of this interaction is not known. B7 and B7-2 are members of immunoglobulin (Ig) superfamily and their extracellular portion consists of an IgV- and IgC-like domain. Here we report that a naturally occurring, alternatively spliced form of B7 reveals that exon 3-encoded IgC domain is essential for CD28/CTLA4 binding. Mutational analysis of B7 demonstrates a critical role of several amino acids around loops between strands B and C and D and E, for binding CTLA4/CD28. These amino acids are clustered to form a single binding site centered at 201Y. A comparison of the effects of mutations on the binding of CD28 and CTLA4 reveals that CD28 and CTLA4 binds to the same site on B7. These results have important implications on the role of CTLA4 and CD28 in T cell costimulation. The structure of the CD28/CTLA4-binding site also provides valuable information for immune intervention targeted at the B7/B7-2-CD28/CTLA4 interactions.
Biracial Population Study of Mortality in Mild Cognitive Impairment and Alzheimer Disease (2009)

The presence and severity of MCI and AD are associated with reduced survival among African Americans, and these effects are comparable to those seen among whites.
Design and synthesis of a CD4 beta-turn mimetic that inhibits human immunodeficiency virus envelope glycoprotein gp120 binding and infection of human lymphocytes. (1992)

Poor bioavailability, rapid degradation, antigenicity, and high cost often limit the use of proteinaceous pharmaceuticals. One goal of structural biochemistry is the reduction of complex molecules to small functional units that are amenable to high-resolution structural analysis and rapid modification. The dissection of complex proteins into small synthetic conformationally restricted components is an important step in the design of low molecular weight nonpeptides that mimic the activity of the native protein. We have developed a reverse-turn mimetic system to explore peptide and protein structure-function relationships. We now report the design and synthesis of a small molecule (M(r) 810, as its trifluoroacetate salt), water soluble, proteolytically stable mimetic of residues Gln40-Thr45 of the complementarity-determining 2-like region of CD4. This mimetic has a low micromolar Kd for human T-lymphotropic virus type IIIB gp120 and reduces syncytium formation.
Hepatitis B virus large surface protein is not secreted but is immunogenic when selectively expressed by recombinant vaccinia virus (1986)

The envelope region of the hepatitis B virus (HBV) genome contains an open reading frame that begins upstream of the major surface protein gene. The two minor proteins that are initiated within this pre-s segment are immunogenic and may be involved in virus attachment to hepatocytes. We have constructed a recombinant vaccinia virus that contains the predicted coding segment for the large surface protein (LS) under control of a vaccinia virus that contains the predicted coding segment for the large surface protein (LS) under control of a vaccinia virus promoter. Cells infected with the recombinant virus synthesized HBV polypeptides of 39 and 42 kilodaltons, corresponding to the unglycosylated and glycosylated forms of LS, respectively. The presence of pre-s epitopes in the 39- and 42-kilodalton polypeptides was demonstrated by binding of antibody prepared against a synthetic peptide. Synthesis of the 42-kilodalton species was specifically inhibited by tunicamycin, suggesting that it is N-glycosylated. Despite apparent glycosylation, LS was not secreted into the medium of infected cells. Nevertheless, rabbits vaccinated with the purified recombinant virus made antibodies that recognized s and pre-s epitopes. Antibody to the NH2 terminus of LS appeared before or simultaneously with antibody that bound to the major surface protein. The additional immunogenicity provided by expression of LS may be advantageous for the development of an HBV vaccine.
Low-frequency transient electric and magnetic fields coupling to child body (2007)

Much of the research related to residential electric and magnetic field exposure focuses on cancer risk for children. But until now only little knowledge about coupling of external transient electric and magnetic fields with the child's body at low frequency transients existed. In this study, current densities, in the frequency range from 50 Hz up to 100 kHz, induced by external electric and magnetic fields to child and adult human body, were investigated, as in residential areas, electric and magnetic fields become denser in this frequency band. For the calculations of induced fields and current density, the ellipsoidal body models are used. Current density induced by the external magnetic field (1 microT) and external electric field (1 V/m) is estimated. The results of this study show that the transient electric and magnetic fields would induce higher current density in the child body than power frequency fields with similar field strength.
A cartilage catabolic factor from synovium (1979)

Porcine synovium in organ culture produces a factor that causes chondrocytes to degrade their matrix. A quantitative assay for the factor, for which the cartilage of bovine nasal septum is used, is described. Evidence is presented that the catabolic factor is a protein.
Regulation of vascular integrins [published erratum appears in Blood 1994 Apr 1;83(7):2013] (1993)

T with the vascular endothelium, and with the subendothelial matrix are essential for a number of physiologic and pathologic processes such as lymphocyte migration, wound healing, inflammation, hemostasis, and thrombosis. These attachments require the concerted actions of a number of cell adhesion molecules. One family of cell surface adhesion receptors, the integrins, plays a prominent role in mediating these diverse cell-cell and cell-extracellular matrix attachments. This review summarizes several of the principal mechanisms that regulate integrin binding function and that govern many of the physiologic responses of blood cells.
Non-intrusive appliance load monitoring based on an optical sensor (2004)

With the help of the optical sensor described in this paper, a NIALM system can be integrated with little expense in the existing electrical installation of households for analysing and optimising the active electric power consumption. The monitoring system requires as input device the electromechanical three-phase electricity meter (Ferraris meter) installed in the most of the German households. The active power consumption can be measured with time resolution down to second. The measured data constitute the basis for an autonomous NIALM approach which can without manual initialisation phase extract the switching sequence structures of the chief consumer load devices in the household, from the total load trace. The focus of the analysis lies on the automatic controlled on-off consumer loads. The analytical procedure consists of an approach based on certain rules for recognising repetitive patterns. In the decomposition of the total load as a function of time into switching events, simple on-off consumer loads and combinations of these patterns are investigated. The recognised patterns can be stored in a neural network. The network is updated daily and weekly. The results of the analysis are evaluated with regard to the potential for demand optimisation or for controlling the energy consumption of individual electric consumer devices.
BI-97C1, an Optically Pure Apogossypol Derivative as Pan-Active Inhibitor of Antiapoptotic B-Cell Lymphoma/Leukemia-2 (Bcl-2) Family Proteins (2010)

In our continued attempts to identify novel and effective pan-Bcl-2 antagonists, we have recently reported a series of compound 2 (Apogossypol) derivatives, resulting in the chiral compound 4 (8r). We report here the synthesis and evaluation on its optically pure individual isomers. Compound 11 (BI-97C1), the most potent diastereoisomer of compound 4, inhibits the binding of BH3 peptides to Bcl-X(L), Bcl-2, Mcl-1, and Bfl-1 with IC(50) values of 0.31, 0.32, 0.20, and 0.62 microM, respectively. The compound also potently inhibits cell growth of human prostate cancer, lung cancer, and lymphoma cell lines with EC(50) values of 0.13, 0.56, and 0.049 microM, respectively, and shows little cytotoxicity against bax(-/-)bak(-/-) cells. Compound 11 displays in vivo efficacy in transgenic mice models and also demonstrated superior single-agent antitumor efficacy in a prostate cancer mouse xenograft model. Therefore, compound 11 represents a potential drug lead for the development of novel apoptosis-based therapies against cancer.
Hypoxia-inducible factor 1α promotes primary tumor growth and tumor-initiating cell activity in breast cancer (2012)

These results demonstrate that HIF-1α plays a key role in promoting primary mammary tumor growth and metastasis, in part through regulation of TICs. HIF-1α regulates expression of several members of the Notch pathway, CD133 and markers of the basal lineage in mammary tumors. Our results suggest that CD133, which has not been profiled extensively in breast cancer, may be a useful marker of TICs in the PyMT mouse model. These data reveal for the first time that HIF-1α directly regulates breast TIC activity in vivo.
Macrocycles. 21. Role of Ring−Ring Equilibria in Thermodynamically Controlled Polycondensations (2003)

A new hypothesis is presented saying that an ideal thermodynamically controlled polycondensation is characterized by the following three aspects: first, the ring−chain equilibria automatically include ring−ring equilibria which become decisive for the thermodynamical properties of the system at high conversions. Second, at 100% conversion, all reaction products are cycles. Third, the chain growth is limited by the thermodynamical properties of the ring−ring equilibrium. The following polycondensations were discussed: base-catalyzed transesterification of ethyl cholate and combinations of Bu2Sn(OMe)2 with α,ω-poly(ethylene glycol)s, with poly(tetrahydrofuran)diols or with two oligosiloxane diols. Moreover, equilibrations of oligo- and polysiloxanes and polycondensations of Bu2Sn bisacetate with various aliphatic dicarboxylic acids are discussed. Furthermore, polycondensations of pentaerythritol and its oligoether derivatives with Bu2Sn(OMe)2 yielding spirocycles are discussed. It is demonstrated by a variety of chemical or analytical methods that Sn-containing polymers were never formed and that cycles were the only reaction products. These results clearly support the above formulated modifications of the Jacobson−Stockmayer theory and of the Carothers−Flory theory.
The Xenopus homeobox gene Twin mediates Wnt induction of Goosecoid in establishment of Spemann’s organizer (1997)

We describe the isolation of the Xenopus homeobox gene twin (Xtwn), which was identified in an expression cloning screen for molecules with dorsalizing activities. Injection of synthetic Xtwn mRNA restores a complete dorsal axis in embryos lacking dorsal structures and induces a complete secondary dorsal axis when ectopically expressed in normal embryos. The sequence homology, expression pattern and gain-of-function phenotype of Xtwn is most similar to the previously isolated Xenopus homeobox gene siamois (Xsia) suggesting that Xtwn and Xsia comprise a new subclass of homeobox genes important in dorsal axis specification. We find that Xtwn is able to activate the Spemann organizer-specific gene goosecoid (gsc) via direct binding to a region of the gsc promoter previously shown to mediate Wnt induction. Since Xtwn expression is strongly induced in ectodermal (animal cap) cells in response to overexpression of a dorsalizing Wnt molecule, we examined the possibility that Xtwn might be a direct target of a Wnt signal transduction cascade. First, we demonstrate that purified LEF1 protein can interact, in vitro, with consensus LEF1/TCF3-binding sites found within the Xtwn promoter. Second, these binding sites were shown to be required for Wnt-mediated induction of a Xtwn reporter gene containing these sites. As LEF1/TCF3 family transcription factors have previously been shown to directly mediate Wnt signaling, these results suggest that Xtwn induction by Wnt may be direct. Finally, in UV-hyperventralized embryos, expression of endogenous Xtwn is confined to the vegetal pole and a Xtwn reporter gene is hyperinduced vegetally in a LEF1/TCF3-binding-site-dependent manner. These results suggest that cortical rotation distributes Wnt-like dorsal determinants to the dorsal side of the embryo, including the dorsal marginal zone, and that these determinants may directly establish Spemann's organizer in this region.
Clara Cell Secretory Protein Deficiency Alters Clara Cell Secretory Apparatus and the Protein Composition of Airway Lining Fluid (2002)

Clara cells represent the predominant secretory cell within distal conducting airways of mammals and exhibit functional alterations with chronic lung disease. We previously demonstrated that Clara cell secretory protein (CCSP) deficiency results in enhanced susceptibility to environmental agents. The present study was undertaken to define changes in Clara cell secretory function associated with CCSP deficiency in knockout mice. Comparative morphometry of Clara cell ultrastructure revealed dramatic alterations in secretory apparatus between wild-type (WT) and CCSP knockout (CCSP-/-) mice. Secretory granules, which occupy greater than 2% of Clara cell cytoplasmic volume in WT mice, were completely absent among Clara cells of CCSP-/- mice. Moreover, Clara cells of CCSP-/- mice exhibited a > 95% reduction in rough endoplasmic reticulum and alterations to Golgi apparatus, relative to WT controls. Ultrastructural perturbations to Clara cells were associated with altered protein composition of airway lining fluid as revealed by two-dimensional gel analysis of bronchoalveolar lavage proteins, but were not associated with altered abundance or secretion of CC26, another Clara cell secretory protein. We conclude that CCSP is required for the appearance of Clara cell secretory granules and that functional changes to Clara cells that result from CCSP deficiency lead to alterations in the composition of epithelial lining fluid.
Evaluation of a ribosomal RNA gene probe for the identification of species and subspecies within the genus Staphylococcus (1992)

To evaluate a 16S rRNA gene probe for the identification of staphylococcal species and subspecies, we have augmented previous studies involving 12 staphylococcal species by analysing the remaining 16 species currently classified in the genus Staphylococcus. HindIII- and EcoRI-restricted DNA of isolates from validly described species of Staphylococcus was probed with radiolabelled plasmid pBA2 containing 16S rDNA from Bacillus subtilis. The Dice coefficient was used to assess similarity between the 74 HindIII- and the 81 EcoRI-hybridization patterns obtained from a total of 271 isolates belonging to 31 staphylococcal taxa (28 species, of which three include two subspecies). The use of HindIII yielded a better discrimination of the staphylococci than the use of EcoRI. All of the isolates belonging to the same species or subspecies, except S. hyicus isolates, were recovered as homogeneous clusters using their HindIII hybridization patterns. The phenotypically close taxa were clearly distinguished. Thus, the method presented in this study constitutes a powerful tool for the identification of taxa within the genus Staphylococcus.
Validation of Changes in Extracellular Volume Measured During Hemodialysis Using a Segmental Bioimpedance Technique (1998)

Sum of segmental bioimpedance analysis (BIAs) has recently been introduced as a more accurate estimation of extracellular volume (ECV). The current study was designed to compare the changes in ECV estimated by whole body bioimpedance (BIA(W)) and BIAs and to determine whether BIAs could be used to accurately estimate changes in ECV compared with the ultrafiltration volume (UFV) as measured by the dialysis machine. Ten men (age, 49 +/- 10 years; dry weight, 78 +/- 13 kg) were studied during hemodialysis (HD). A multifrequency bioimpedance analyzer (BIS4000B; Xitron Technologies, San Diego, CA) and a digital switch developed by the authors were used to automatically collect data from three body segments (arm, trunk, and leg) and the whole body using the stated technique. There was a significant difference in delta ECV(W) and UFV at the end of the treatment (2.75 +/- 0.74 L vs 3.95 +/- 0.73 L, p < 0.05) because fluid removal from the trunk has almost no effect on whole body resistance. However, delta ECVs was not significantly different from UFV (3.76 +/- 0.65 L vs 3.95 +/- 0.73 L, p = NS). BIAs is a more accurate approach to monitor changes in ECV during HD than is BIA(W) because changes in local resistance can be allocated to segments with uniform geometry and resistivity. This is a prerequisite for future studies on dynamics of regional fluid distribution during hemodialysis.
Treatment of low‐grade non‐Hodgkin's lymphomas: Assessment of doxorubicin in a controlled trial (1990)

From 1981 to 1984 a randomized clinical trial was conducted to evaluate the role of doxorubicin in low grade malignancy non-Hodgkin's lymphoma (NHL). One hundred and thirteen patients were treated by an induction regimen including cyclophosphamide 400 mg/m2 day 1 and 8, vincristine 1.4 mg/m2 day 1 and 8, procarbazine 80 mg/m2 day 1 to 14, prednisone 60 mg/m2 day 1 to 5 (PCOP regimen) randomly associated to doxorubicin: 20 mg/m2 day 1 and 8 (PACOP regimen). Maintenance therapy consisted of 12 monthly courses of chlorambucil 10 mg/m2 for 5 days or association of cyclophosphamide 300 mg/m2 for 3 days, vincristine 1.4 mg/m2 day 1 and prednisone 60 mg/m2 for 5 days. Complete response (CR) was obtained in 51 patients (45 per cent), in 30 patients after induction regimen and in 21 patients after maintenance therapy, without difference according to regimens. Bone marrow involvement (p = 0.02) and number of involved nodal sites (p = 0.001) were found to influence probability of achieving CR. The median time to progression was estimated to 39 months without difference between regimens. Median overall survival is not reached with a median follow-up of 53 months. Multivariate regression analysis permits observation of negative influence on survival of three parameters: initial bone marrow involvement, age over 50 years and incomplete response to treatment. The initial adjunction of doxorubicin did not seem to influence the appearance of histologic progression.
IL-1 acts directly on CD4 T cells to enhance their antigen-driven expansion and differentiation (2009)

IL-1 causes a marked increase in the degree of expansion of naïve and memory CD4 T cells in response to challenge with their cognate antigen. The response occurs when only specific CD4 T cells can respond to IL-1beta, is not induced by a series of other cytokines and does not depend on IL-6 or CD-28. When WT cells are primed in IL-1R1(-/-) recipients, IL-1 increases the proportion of cytokine-producing transgenic CD4 T cells, especially IL-17- and IL-4-producing cells, strikingly increases serum IgE levels and serum IgG1 levels. IL-1beta enhances antigen-mediated expansion of in vitro primed Th1, Th2, and Th17 cells transferred to IL-1R1(-/-) recipients. The IL-1 receptor antagonist diminished responses to antigen plus lipopolysaccharide (LPS) by approximately 55%. These results indicate that IL-1beta signaling in T cells markedly induces robust and durable primary and secondary CD4 responses.
Planning, teaching and assessing the curriculum for pupils with learning difficulties: an introduction and overview (2001)

Non‐statutory guidelines for Planning, teaching and assessing the curriculum for pupils with learning difficulties have recently been published by QCA/DfEE (2001). The materials consist of 15 booklets which incorporate general guidelines on developing the school curriculum for pupils with learning difficulties, support material for developing skills across the curriculum, and support material for each National Curriculum subject, personal, social and health education (PSHE), and religious education (RE). This article, written by the research and development officers (RDOs) involved in the project, outlines the process of developing these guidelines and discusses some of the issues arising during the project. It focuses particularly on the development of the subject materials, using the subject of geography to illustrate points.