gebhart/patrepeval huggingface dataset:
The CD39 molecule defines distinct cytotoxic subsets within alloactivated human CD8‐positive cells (1992)

Lymphocyte activation induces or increases the expression of several surface structures, none of which is characteristic of an activated cell subset. In particular, structures such as CD45RO, CD25, CD26, CD49b, CD54, CD71 are expressed by the vast majority of lymphocytes at various times following in vitro activation. CD39 molecules were originally identified on activated B lymphocytes and have recently been described on activated T cell clones. In the present report, we have characterized phenotypically and functionally defined cell subsets generated during an in vitro allostimulation. Results indicated that the percentage of CD39+ cells reached a maximum at day 6 and remained stable thereafter. We demonstrate that CD39 expression allows the identification within the allosensitized CD8+ cytotoxic cells of distinct subsets of cells mediating allo cytotoxic T lymphocyte or natural killer (NK)-like reactivity. More precisely, CD8+CD39+ alloactivated cells mainly mediate specific killer activity, whereas CD8+CD39- alloactivated cells predominantly exhibit NK-like reactivity. Further, we show a high functional correlation associated with the lack of CD39 expression on NK-like alloactivated CD8+ cells, while there is no association with CD56 or CD57 NK-associated structures.
Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study (2013)

Saudi Arabian Ministry of Health, Wellcome Trust, European Community, and National Institute of Health Research University College London Hospitals Biomedical Research Centre.
A Multidrug Resistance Regulatory Chromosomal Locus Is Widespread among Enteric Bacteria (1993)

Constitutive expression of the mar operon (marRAB) in Escherichia coli produces a multiple antibiotic resistance phenotype mediated by the expression of multiple genetic loci in response to regulatory proteins in the operon. A mar-specific DNA probe was used to search for the operon in bacterial strains representing 53 species and 27 genera. Among these, 6 other Enterobacteriaceae, Salmonella, Shigella, Klebsiella, Citrobacter, Hafnia, and Enterobacter species, contained DNA sequences that hybridized to the probe under high-stringency conditions. By use of a selection protocol developed to obtain multiple antibiotic resistant mutants of E. coli, multiply resistant mutants that showed increased expression of mar-specific RNA were obtained from Enterobacter agglomerans and Salmonella species.
Visual and Auditory Neurotoxicity in Patients Receiving Subcutaneous Deferoxamine Infusions (1986)

Of 89 patients receiving nightly subcutaneous deferoxamine for transfusion-dependent thalassemia major or Diamond-Blackfan anemia, 13 presented with visual loss or deafness of acute onset or both. Detailed ophthalmologic, audiologic, and evoked-potential studies uncovered abnormalities caused by neurotoxicity in 27 more. Four patients with visual loss had optic neuropathy, with a marked decrease in acuity, loss of color vision, and delayed visual evoked potentials. Five asymptomatic patients had changes in the pigment of the retinal epithelium. The hearing loss was characterized by a high-frequency sensorineural deficit, which necessitated hearing aids in six patients. When deferoxamine was stopped, recovery of vision was complete in 2 patients and partial in 2, and in 22 patients with abnormal audiograms, reversal of the hearing deficit was complete in 4 and partial in 1. An analysis of the clinical data showed that members of the affected group were younger, had lower serum ferritin values, and were self-administering higher doses of deferoxamine per kilogram of body weight. Significantly lower doses of deferoxamine were being taken by patients without abnormalities than by those with visual symptoms, abnormal audiograms, or prolonged evoked potentials (P less than 0.001, less than 0.006, and less than 0.04, respectively). The data implicate high-dose deferoxamine as a central factor in the pathogenesis of the neurotoxicity. We strongly recommend careful regulation of the deferoxamine dosage and serial audiovisual monitoring in all patients receiving the drug.
Bone Marrow-Derived Progenitor Cells Are Important for Lung Repair after Lipopolysaccharide-Induced Lung Injury (2004)

Tissue repair often occurs in organs damaged by an inflammatory response. Inflammatory stimuli induce a rapid and massive release of inflammatory cells including neutrophils from the bone marrow. Recently, many studies suggested that bone marrow cells have the potential to differentiate into a variety of cell types. However, whether inflammatory stimuli induce release of bone marrow-derived progenitor cells (BMPCs), or how much impact the suppression of BMPCs has on the injured organ is not clear. Here we show that LPS, a component of Gram-negative bacterial cell walls, in the lung airways, induces a rapid mobilization of BMPCs into the circulation in mice. BMPCs accumulate within the inflammatory site and differentiate to become endothelial and epithelial cells. Moreover, the suppression of BMPCs by sublethal irradiation before intrapulmonary LPS leads to disruption of tissue structure and emphysema-like changes. Reconstitution of the bone marrow prevents these changes. These data suggest that BMPCs are important and required for lung repair after LPS-induced lung injury.
Characterization of membrane bound carbonic anhydrase IV (CA IV) located on the external surface of lung pulmonary endothelial cells (1995)

Conference Article| May 01 1995 Characterization of membrane bound carbonic anhydrase IV (CA IV) located on the external surface of lung pulmonary endothelial cells ISABELLE MAHIEU; ISABELLE MAHIEU 1Medical Genetics Unit, St George's Hospital Medical School, London SW17 ORE Search for other works by this author on: This Site PubMed Google Scholar AUDRA BENJAMIN; AUDRA BENJAMIN 2Department of Child Health, St George's Hospital Medical School, London SW17 ORE Search for other works by this author on: This Site PubMed Google Scholar RICHARD STEPHENS; RICHARD STEPHENS 2Department of Child Health, St George's Hospital Medical School, London SW17 ORE Search for other works by this author on: This Site PubMed Google Scholar DAFYDD WALTERS; DAFYDD WALTERS 2Department of Child Health, St George's Hospital Medical School, London SW17 ORE Search for other works by this author on: This Site PubMed Google Scholar NICK CARTER NICK CARTER 1Medical Genetics Unit, St George's Hospital Medical School, London SW17 ORE Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1995) 23 (2): 320S. https://doi.org/10.1042/bst023320s Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation ISABELLE MAHIEU, AUDRA BENJAMIN, RICHARD STEPHENS, DAFYDD WALTERS, NICK CARTER; Characterization of membrane bound carbonic anhydrase IV (CA IV) located on the external surface of lung pulmonary endothelial cells. Biochem Soc Trans 1 May 1995; 23 (2): 320S. doi: https://doi.org/10.1042/bst023320s Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 1995 Biochemical Society1995 Article PDF first page preview Close Modal You do not currently have access to this content.
Degradation of fructose-1,6-bisphosphate aldolase by cathepsin B (1980)

The mechanism of degradation of fructose-1,6-bisphosphate aldolase from rabbit muscle by the lysosomal proteinase cathepsin B was determined. Treatment of aldolase with cathepsin B destroys up to 90% of activity with fructose 1,6-bisphosphate as substrate, but activity with fructose 1-phosphate is slightly increased. Cathepsin L, another lysosomal thiol proteinase, and papain are also potent inactivators of aldolase, whereas inactivation is not caused by cathepsins D or H even at high concentrations, or by cathepsin B inhibited by leupeptin or iodoacetate. The cathepsin-B-treated aldolase shows no detectable change in subunit molecular weight, oligomer molecular weight or subunit interactions. Cathepsin B cleaves dipeptides from the C-terminus of th aldolase subunits. Four dipeptides are released sequentially: Ala-Tyr, Asn-His, Ile-Ser and Leu-Phe, and a maximum of five additional dipeptides may be released. There are indications that this peptidyldipeptidase activity of cathepsin B may be an important aspect of its action on protein substrates generally.
Fractal Analysis of the Vascular Tree in the Human Retina (2004)

The retinal circulation of the normal human retinal vasculature is statistically self-similar and fractal. Studies from several groups present strong evidence that the fractal dimension of the blood vessels in the normal human retina is approximately 1.7. This is the same fractal dimension that is found for a diffusion-limited growth process, and it may have implications for the embryological development of the retinal vascular system. The methods of determining the fractal dimension for branching trees are reviewed together with proposed models for the optimal formation (Murray Principle) of the branching vascular tree in the human retina and the branching pattern of the human bronchial tree. The limitations of fractal analysis of branching biological structures are evaluated. Understanding the design principles of branching vascular systems and the human bronchial tree may find applications in tissue and organ engineering, i.e., bioartificial organs for both liver and kidney.
Use of Inteins for the In Vivo Production of Stable Cyclic Peptide Libraries in E. coli (2003)

Advances and opportunities in drug discovery and functional genomics have put methods for generating molecular diversity at a premium. Both chemical and biological approaches for the production of compound libraries have been pursued. Combinatorial chemistry has been used to synthesize molecular libraries in vitro, while molecular biology has been exploited to biosynthesize molecular libraries within cells. Unlike synthetic methods, which have largely focused on the production of libraries of small molecules, biosynthetic libraries must contend with the catabolic machinery of the host cell. Thus, variable segments are typically embedded within or fused to large biomolecules (1). The resulting random sequences have been described as peptides, but they display the physical characteristic of the scaffold biopolymer.
Diffractive optical element for mode shaping of a Nd:YAG laser (1994)

A diffractive laser cavity mirror is described that can customize the amplitude and phase of a laser mode. The design of this diffractive element is shown for a square, flat-topped fundamental mode. The laser cavity has a theoretical fundamental mode loss of only 0.08% and a second-order mode loss of 48.2%, resulting in high modal discrimination. The fabricated mirror is tested in a Nd:YAG laser system. The resulting square flat-topped mode has an rms variation of 1.5% over the two-dimensional flat-topped region and a large discrimination against higher-order modes.
T-cell clones can be rendered specific for CD19: toward the selective augmentation of the graft-versus-B–lineage leukemia effect (2003)

Relapse of B-lineage acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (HSCT) commonly results from the failure of a graft-versus-leukemia (GVL) effect to eradicate minimal residual disease. Augmenting the GVL effect by the adoptive transfer of donor-derived B-ALL-specific T-cell clones is a conceptually attractive strategy to decrease relapse rates without exacerbating graft-versus-host disease (GVHD). Toward this end, we investigated whether a genetic engineering approach could render CD8(+) cytotoxic T lymphocytes (CTLs) specific for tumor cells that express the B-cell lineage cell surface molecule CD19. This was accomplished by the genetic modification of CTLs to express a chimeric immunoreceptor composed of a CD19-specific single-chain immunoglobulin extracellular targeting domain fused to a CD3-zeta intracellular signaling domain. CD19-redirected CTL clones display potent CD19-specific lytic activity and chimeric immunoreceptor-regulated cytokine production and proliferation. Because B-ALL cells can evade T-cell/natural killer- cell recognition by down-regulation of cell surface accessory molecules that participate in the formation of a functional immunologic synapse, we compared the CD19-specific effector function of genetically modified CD8(+) CTLs toward CD19(+) cells with disparate levels of intercellular adhesion molecule 1 (ICAM-1), leukocyte function-associated antigen 1 (LFA-1), and LFA-3. We observed that recognition of B-lineage tumor lines by CD19-specific CTLs was not impaired by low levels of ICAM-1, LFA-1, and LFA-3 cell surface expression, a functional attribute that is likely a consequence of our high-affinity CD19-specific chimeric immunoreceptor. Furthermore, the CD19-specific CTLs could lyse primary B-ALL blasts. These preclinical observations form the basis for implementing clinical trials using donor-derived CD19-specific T-cell clones to treat or prevent relapse of B-ALL after allogeneic HSCT.
A CRISPR CASe for high-throughput silencing (2013)

Manipulation of gene expression on a genome-wide level is one of the most important systematic tools in the post-genome era. Such manipulations have largely been enabled by expression cloning approaches using sequence-verified cDNA libraries, large-scale RNA interference libraries (shRNA or siRNA) and zinc finger nuclease technologies. More recently, the CRISPR (clustered regularly interspaced short palindromic repeats) and CRISPR-associated (Cas)9-mediated gene editing technology has been described that holds great promise for future use of this technology in genomic manipulation. It was suggested that the CRISPR system has the potential to be used in high-throughput, large-scale loss of function screening. Here we discuss some of the challenges in engineering of CRISPR/Cas genomic libraries and some of the aspects that need to be addressed in order to use this technology on a high-throughput scale.
Chiral Compounds Synthesized by Biocatalytic Reductions [New Synthetic Methods (51)] (1985)

Abstract It has been known for many decades that chiral compounds can be obtained by stereospecific biocatalytic reduction. Further significant methodological developments in this field have, however, only been made during the past ten years; they include the application of previously unused microorganisms and electron donors, the discovery of additional substrates for the known reductases, the development of methods for regenerating reduced pyridine nucleotides, and the discovery of new reductases which were sought for specific preparative purposes. Many chiral compounds can now be synthesized by microbial hydrogenation using H 2 and hydrogenase‐containing microorganisms as well as by electromicrobial or electroenzymatic reduction. In the two latter methods, anaerobic or aerobic organisms are supplied with electrons from electrochemically reduced, artificial mediators, e.g., methyl viologen. Reductases that do not require pyridine nucleotides and can accept electrons directly from reduced viologens are especially useful. Two examples of this type of enzyme are described which are of preparative interest. Many cells contain methyl viologen‐dependent NAD(P) reductases, a large number of which have still not been characterized. A productivity number is proposed which allows different methods of bioconversion with microorganisms to be compared. The productivity numbers of compounds synthesized by the methods described in this review are often 10‐ to 100‐fold higher than those of substances obtained by conventional techniques.
Fuzzy Logic Based Method for Improving Text Summarization (2009)

Text summarization can be classified into two approaches: extraction and abstraction. This paper focuses on extraction approach. The goal of text summarization based on extraction approach is sentence selection. One of the methods to obtain the suitable sentences is to assign some numerical measure of a sentence for the summary called sentence weighting and then select the best ones. The first step in summarization by extraction is the identification of important features. In our experiment, we used 125 test documents in DUC2002 data set. Each document is prepared by preprocessing process: sentence segmentation, tokenization, removing stop word, and word stemming. Then, we use 8 important features and calculate their score for each sentence. We propose text summarization based on fuzzy logic to improve the quality of the summary created by the general statistic method. We compare our results with the baseline summarizer and Microsoft Word 2007 summarizers. The results show that the best average precision, recall, and f-measure for the summaries were obtained by fuzzy method.
Tissue-specific Short Chain Fatty Acid Metabolism and Slow Metabolic Recovery after Ischemia from Hyperpolarized NMR in Vivo (2009)

Mechanistic details of mammalian metabolism in vivo and dynamic metabolic changes in intact organisms are difficult to monitor because of the lack of spatial, chemical, or temporal resolution when applying traditional analytical tools. These limitations can be addressed by sensitivity enhancement technology for fast in vivo NMR assays of enzymatic fluxes in tissues of interest. We apply this methodology to characterize organ-specific short chain fatty acid metabolism and the changes of carnitine and coenzyme A pools in ischemia reperfusion. This is achieved by assaying acetyl-CoA synthetase and acetyl-carnitine transferase catalyzed transformations in vivo. The fast and predominant flux of acetate and propionate signal into acyl-carnitine pools shows the efficient buffering of free CoA levels. Sizeable acetyl-carnitine formation from exogenous acetate is even found in liver, where acetyl-CoA synthetase and acetyl-carnitine transferase activities have been assumed sequestered in different compartments. In vivo assays of altered acetate metabolism were applied to characterize pathological changes of acetate metabolism upon ischemia. Coenzyme pools in ischemic skeletal muscle are reduced in vivo even 1 h after disturbing muscle perfusion. Impaired mitochondrial metabolism and slow restoration of free CoA are corroborated by assays employing fumarate to show persistently reduced tricarboxylic acid (TCA) cycle activity upon ischemia. In the same animal model, anaerobic metabolism of pyruvate and tissue perfusion normalize faster than mitochondrial bioenergetics.
Exploration of the P6/P7 Region of the Peptide-binding Site of the Human Class II Major Histocompatability Complex Protein HLA-DR1 (2003)

Crystal structures of the class II major histocompatibilty complex (MHC) protein, HLA-DR1, generally show a tight fit between MHC and bound peptide except in the P6/P7 region of the peptide-binding site. In this region, there is a shallow water-filled pocket underneath the peptide and between the pockets that accommodate the P6 and P7 side chains. We investigated the properties of this pocket with the idea of engineering substitutions into the corresponding region of peptide antigens to increase their binding affinity for HLA-DR1. We investigated d-amino acids and N-alkyl modifications at both the P6 and P7 positions of the peptide and found that binding of peptides to HLA-DR1 could be increased by incorporating an N-methyl substitution at position 7 of the peptide. The crystal structure of HLA-DR1 bound to a peptide containing a P7 N-methyl alanine was determined. The N-methyl group orients in the P6/P7 pocket, displacing one of the waters usually bound in this pocket. The structure shows that the substitution does not alter the conformation of the bound peptide, which adopts the usual polyproline type II helix. An antigenic peptide carrying the N-methyl modification is taken up by antigen-presenting cells and loaded onto endogenous class II MHC molecules for presentation, and the resultant MHC-peptide complexes activate antigen-specific T-cells. These results suggest a possible strategy for increasing the affinity of weakly immunogenic peptides that might be applicable to the development of vaccines and diagnostic reagents.
Congestion Pricing Using a Raffle-Based Scheme (2011)

International audience
Metabotropic GABAB Receptors New Challenges in Drug Design (2001)

The inhibitory neurotransmitter 4-aminobutanoic acid (GABA) is one of the most widespread transmitters in the mammalian brain, that regulates synaptic trans-mission and inhibits neuronal activity. Its actions are mediated by three types of recep-tors which are classified into ionotropic GABAA C receptors and G-protein-coupled metabotropic GABAB receptors. Activation of bicuculline-insensitive GABAB receptors reduces transmission at excitatory and inhibitory synapses, as a result of an increase in K+ conductance, or a decrease in voltage-dependent Ca 2+ currents. Some 30 years ago, baclofen was introduced into clinical practice for the treatment of spasticity associated with brain and spinal cord injuries, cerebral palsy, multiple sclerosis, tetanus, as well as dystonia. It remains to this date the classical prototypical agonist for GABAB receptors in experimental studies. Recently, remarkable progress has been achieved with the development of other more potent and selective agonists for GABAB receptors, which exert less tolerance than baclofen itself, reducing much of the known side-effects. The next significant progress came with the synthesis of high affinity antagonists that has enabled the initial expression cloning of the GABAB receptor at its most fundamental level, with the discovery of the amino acid sequences of GABAB R1a R1b splice variants, followed soon after by the characterization of a second class of receptors, the GABAB R2 receptors. This quantum leap in cloning studies can thus be attributed primarily to the availability of GABAB receptor antagonist ligands of strikingly high potencies. Once cloned, such new information on GABAB receptor molecular structure has become of paramount importance in light of the plethora of potential therapeutic drug targets that have emerged in areas such as drug addiction, nociception, cognition and absence seizures. The purpose of the present review is to address and highlight the remarkable advances on the development of a variety of novel and interesting compounds active at GABAB receptor sites. Keywords: GABAB Receptors, 4-aminobutanoic acid (GABA), PHACLOFEN, 2-OH-SACLOFEN, SACLOFEN, GABAB AGONISTS, BACLOFEN, SICLOFEN, GABAB ANTAGONISTS
Text Modeling for Real-Time Document Categorization (2005)

We report on experiments in adapting document categorization techniques to provide for implementation in high-speed hardware. Because resources are scarce, it is important to have a small set of robust and maximally informative variables over which learning can occur. We generate variables using information-theoretic clustering. The resulting performance is on par with general-purpose computing implementations which are able to take advantage of large amounts of time and memory. We conclude that custom high-speed hardware for document categorization can be made very accurate. We also believe that some of the strengths of information-theoretic data analysis techniques are brought out