gebhart/patrepeval huggingface dataset:
Therapy with statins in patients with refractory rheumatic diseases: a preliminary study (2003)

We have explored the therapeutic potential of statins in patients with different inflammatory rheumatic diseases refractory to conventional therapy. We found that simvastatin (80mg o.d. for eight days) induced a rapid and significant reduction in proteinuria levels in three systemic lupus erythematosus (SLE) patients. A similar kind of therapy had a marked beneficial effect in a patient with Wegener's granulomatosis and a patient with erythema nodosum. On the other hand, five patients with rheumatoid arthritis (RA) who received atorvastatin for eight days (20mg/day) showed reduction in C-reactive protein levels and a clinical improvement that was classified as an ACR20 response. Prior to the administration of statins, all these patients had received aggressive conventional therapy with no satisfactory response. A significant reduction in spontaneous apoptosis of peripheral blood lymphocytes and expression of CD69 and HLA-DR was observed in SLE patients after simvastatin therapy. These results prompted us to perform a pilot short-time comparative (simvastatin versus chloroquine) open clinical trial in 15 patients with RA who were receiving methotrexate as a single disease modifying antirheumatic drug with no satisfactory response. Most patients (9/10) who received simvastatin (40mg/day) showed an ACR50 or better response after eight weeks, whereas such a response was not observed in any patient (0/5) treated with chloroquine. Our preliminary results indicate that statins may be an important therapeutic tool for the treatment of inflammatory rheumatic diseases.
Real-Time Conformational Changes and Controlled Orientation of Native Proteins Inside a Protein Nanoreactor (2017)

Protein conformations play crucial roles in most, if not all, biological processes. Here we show that the current carried through a nanopore by ions allows monitoring conformational changes of single and native substrate-binding domains (SBD) of an ATP-Binding Cassette importer in real-time. Comparison with single-molecule Förster Resonance Energy Transfer and ensemble measurements revealed that proteins trapped inside the nanopore have bulk-like properties. Two ligand-free and two ligand-bound conformations of SBD proteins were inferred and their kinetic constants were determined. Remarkably, internalized proteins aligned with the applied voltage bias, and their orientation could be controlled by the addition of a single charge to the protein surface. Nanopores can thus be used to immobilize proteins on a surface with a specific orientation, and will be employed as nanoreactors for single-molecule studies of native proteins. Moreover, nanopores with internal protein adaptors might find further practical applications in multianalyte sensing devices.
Expression Cloning of a Human GT3 Synthase (1996)

Gangliosides of the C series such as GT3 are polysialylated glycosphingolipids whose synthesis is developmentally regulated. Here we report the expression cDNA cloning and characterization of GT3 synthase that adds the second alpha-2,8-sialic acid to GD3, NeuNAcalpha2-->8NeuNAcalpha2-->3Galbeta1-->4Glc-->Cer, thus forming GT3, NeuNAcalpha2-->8NeuNAcalpha2-->8NeuNAc alpha2-->3Galbeta1--> 4Glc-->Cer. Unexpectedly, the cloned cDNA was found to be identical to the cDNA that encodes GD3 synthase. The newly identified enzyme was therefore named GD3/GT3 synthase (GD3/GT3ST). GD3/GT3ST synthesized GT3 most efficiently when GM3, NeuNAcalpha2-->3Galbeta1-->4Glc-->Cer, was incubated as an acceptor, indicating that GD3/GT3ST is a polysialyltransferase that can transfer more than one sialic acid residue via alpha-2,8 linkage to gangliosides. Moreover, a longer period of incubation of GD3 with GD3/GT3ST produced a significant amount of GT3 and higher polysialogangliosides. Among various cell lines expressing GD3/GT3ST, higher polysialogangliosides including GT3 were detected only in cell lines where the amount of GD3/GT3 mRNA is sufficiently high. The expression of GD3/GT3ST mRNA among human tissues is highly restricted to fetal and adult brains. The GD3/GT3ST gene was found to be located at chromosome 12, region p12. Taken together, these results indicate that C series polysialogangliosides are synthesized by a ganglioside-specific polysialyltransferase, GD3/GT3ST, that is specifically expressed in neural tissues.
Development of a Fungal Transformation System Based on Selection of Sequences with Promoter Activity (1987)

A novel strategy was used to develop a transformation system for the plant pathogenic fungus Cochliobolus heterostrophus. Sequences capable of driving the expression of a gene conferring resistance to the antibiotic hygromycin B in C. heterostrophus were selected from a library of genomic DNA fragments and used, with the selectable marker, as the basis for transformation. The library of random 0.5- to 2.0-kilobase-pair fragments of C. heterostrophus genomic DNA was inserted at the 5' end of a truncated, promoterless Escherichia coli hygromycin B phosphotransferase gene (hygB) whose product confers resistance to hygromycin B. C. heterostrophus protoplasts were transformed with the library and selected for resistance. Resistant colonies arose at low frequency. Each colony contained a transformation vector stably integrated into chromosomal DNA. When the transforming DNA was recovered from the genome and introduced into C. heterostrophus, resistant colonies appeared at higher frequency. We determined the sequences of two of the C. heterostrophus DNA fragments which had been inserted at the 5' end of hygB in the promoter library and found that both made translational fusions with hygB. One of the two fusions apparently adds 65 and the other at least 86 amino acids to the N-terminus of the hygB product. Plasmids containing hygB-C. heterostrophus promoter fusions can be used unaltered to drive hygB expression in several other filamentous ascomycetes. This approach to achieving transformation may have general utility, especially for organisms with relatively undeveloped genetics.
Learning Internal Representations by Error Propagation (1985)

This chapter contains sections titled: The Problem, The Generalized Delta Rule, Simulation Results, Some Further Generalizations, Conclusion
Dosimetry for 252Cf neutron emitting brachytherapy sources: Protocol, measurements, and calculations (1999)

The mixed-field dosimetry for 252Cf Applicator Tube (AT) type medical sources available from Oak Ridge National Laboratory (ORNL) has been characterized using ionization chambers, a GM counter, and Monte Carlo methods. Unlike the AAPM Task Group No. 43 (TG-43), specification of dose to muscle instead of water is recommended for clinical dosimetry of 252Cf medical sources. A dosimetry protocol similar to ICRU 45 was formulated with parameters determined specifically for 252Cf brachytherapy. Comparisons of experimental and calculative dosimetry results with Colvett et al. [Phys. Med. Biol. 17, 356-364 (1972)] and Krishnaswamy [Phys. Med. Biol. 17, 56-63 (1972)] were performed, and correction factors were determined to compare the different dosimetry formalisms. Using a Maxwellian model for the 252Cf neutron energy spectrum, kerma relative to muscle was determined for a variety of materials, and compared with relative kermas for external neutron beams of three different energies. Neutron isodose distributions and data necessary for clinical implementation of 252Cf AT sources are also presented.
Intradermal implantation of bovine collagen. Humoral immune responses associated with clinical reactions (1984)

• A special collagen implant (Zyderm) (ZCI) is a biomaterial used for the correction of dermal contour deformities. Although infrequent, reactions believed to be of an immunologic nature have followed treatment. To investigate whether humoral immunity is associated with these reactions, we studied 40 patients for the presence of anti-ZCI antibodies using an enzyme-linked immunosorbent assay. Ten patients who had had adverse treatment reactions uniformly exhibited circulating anti-ZCI antibodies. Twenty-nine of 30 control patients, including nine who had received ZCI without adverse reaction, failed to produce the high levels of antibodies found in all clinical reactors. This difference was statistically significant. Additional investigations confirmed that the antibodies studied were directed primarily against the bovine collagen component of the ZCI. These data suggest that the humoral immune system is capable of recognizing ZCI and that the presence of antibodies to the ZCI correlates with the occurrence of adverse reactions. (<i>Arch Dermatol</i>1984;120:183-187)
IKK/NF- B signaling: balancing life and death - a new approach to cancer therapy (2005)

IkappaB kinase/NF-kappaB (IKK/NF-kappaB) signaling pathways play critical roles in a variety of physiological and pathological processes. One function of NF-kappaB is promotion of cell survival through induction of target genes, whose products inhibit components of the apoptotic machinery in normal and cancerous cells. NF-kappaB can also prevent programmed necrosis by inducing genes encoding antioxidant proteins. Regardless of mechanism, many cancer cells, of either epithelial or hematopoietic origin, use NF-kappaB to achieve resistance to anticancer drugs, radiation, and death cytokines. Hence, inhibition of IKK-driven NF-kappaB activation offers a strategy for treatment of different malignancies and can convert inflammation-induced tumor growth to inflammation-induced tumor regression.
Medical management of stable coronary artery disease. (2011)

All patients with stable coronary artery disease require medical therapy to prevent disease progression and recurrent cardiovascular events. Three classes of medication are essential to therapy: lipid-lowering, antihypertensive, and antiplatelet agents. Lipid-lowering therapy is necessary to decrease low-density lipoprotein cholesterol to a target level of less than 100 mg per dL, and physicians should consider a goal of less than 70 mg per dL for very high-risk patients. Statins have demonstrated clear benefits in morbidity and mortality in the secondary prevention of coronary artery disease; other medications that can be used in addition to statins to lower cholesterol include ezetimibe, fibrates, and nicotinic acid. Blood pressure therapy for patients with coronary artery disease should start with beta blockers and angiotensin-converting enzyme inhibitors. If these medications are not tolerated, calcium channel blockers or angiotensin receptor blockers are acceptable alternatives. Aspirin is the first-line antiplatelet agent except in patients who have recently had a myocardial infarction or undergone stent placement, in which case clopidogrel is recommended. Anginal symptoms of coronary artery disease can be treated with beta blockers, calcium channel blockers, nitrates, or any combination of these. Familiarity with these medications and with the evidence supporting their use is essential to reducing morbidity and mortality in patients with coronary artery disease.
Studies on VIV Fatigue Behavior in SCRS of Hybrid Riser Systems (2002)

The main objective of this work is to demonstrate the application of an analysis methodology for hybrid riser configurations. Such configurations are based on submerged buoys that are connected by jumpers to a floating production unit (a FPSO vessel for instance), and by risers to the seabottom. The focus is on VIV-induced fatigue behavior of the steel catenary risers that connect the buoy to the seabottom. The methodology employs numerical tools for the nonlinear static analysis, modal analysis, VIV and fatigue behaviour. The application of the methodology is illustrated with the analysis of a practical case study located in Campos Basin.
Autonomic Neural Control of Intrathoracic Airways (2012)

Autonomic neural control of the intrathoracic airways aids in optimizing air flow and gas exchange. In addition, and perhaps more importantly, the autonomic nervous system contributes to host defense of the respiratory tract. These functions are accomplished by tightly regulating airway caliber, blood flow, and secretions. Although both the sympathetic and parasympathetic branches of the autonomic nervous system innervate the airways, it is the later that dominates, especially with respect to control of airway smooth muscle and secretions. Parasympathetic tone in the airways is regulated by reflex activity often initiated by activation of airway stretch receptors and polymodal nociceptors. This review discusses the preganglionic, ganglionic, and postganglionic mechanisms of airway autonomic innervation. Additionally, it provides a brief overview of how dysregulation of the airway autonomic nervous system may contribute to respiratory diseases.
INFLUENCE OF OXYGEN-DERIVED FREE RADICAL SCAVENGERS ON ISCHEMIC LIVERS (1985)

It has been hypothesized that the formation of oxygen-derived free radicals may play an important part in ischemically induced tissue injury. Using a canine ischemic liver model, we have assessed the role of two oxygen-free radical scavengers, catalase (CAT) and superoxide dismutase (SOD), used alone and in combination, on the recovery of ischemic livers. Liver ischemia was induced in adult mongrel dogs by cross-clamping of the portal vein and hepatic artery for 40 min. Hepatectomy was then performed, and livers were tested in an isolated perfusion model with 500 ml of an albumin-mannitol solution at 37 degrees C for 3 hr. Liver function tests were performed hourly during the perfusion period. Biopsies and 99m-Tc-HIDA scans were also done at the end of perfusion. Livers in group 1 (n = 6) served as controls and were not pretreated prior to ischemic injury. Livers in group 2 (n = 6), group 3 (n = 6), and group 4 (n = 6) were pretreated, respectively, with CAT (5000 U/kg), SOD (5000 U/kg), and SOD and CAT in combination (5000 U/kg) each. The results indicated that the oxygen-derived free radical scavengers, CAT and SOD, were able to provide partial protection against the free radicals accumulated during ischemic damage. These studies offer some potential avenues for the protection of livers prior to and after transplantation.
Use of the Glu-Glu-Phe C-terminal epitope for rapid purification of the catalytic domain of normal and mutant ras GTPase-activating proteins (1991)

The C-terminal catalytic domain (residues 704-1047) of the human ras GTPase-activating protein (GAP) has been engineered so as to incorporate the tripeptide, Glu-Glu-Phe, at its C terminus. This motif is recognized by the commercially available YL1/2 monoclonal antibody to alpha-tubulin and has previously been used for the immunoaffinity purification of HIV enzymes engineered to contain this epitope (Stammers, D. K., Tisdale, M., Court, S., Parmar, V., Bradley, C., and Ross, C. K. (1991) FEBS Lett. 283, 298-302). The engineered GAP catalytic domain (GAP-344) was obtained in high yield and purity from Escherichia coli extracts by means of a single affinity column of immobilized YL1/2, eluted under mild conditions with the dipeptide, Asp-Phe. The protein had similar activity to that previously described for full-length GAP, suggesting that the addition of the epitope did not grossly affect the activity. R903K and L902I mutants of GAP-344 were constructed, and the immunoaffinity purification procedure allowed their rapid characterization. The R903K mutant had less than 3% the activity of the normal protein, whereas the L902I substitution had less than 0.5% of normal activity, suggesting an important role for Leu-902 and Arg-903, residues absolutely conserved among GAP-related proteins. This work exemplifies the general utility of the C-terminal Glu-Glu-Phe motif for the rapid purification of proteins whose function is not altered by C-terminal modification.
Hybrid Antibacterials. DNA Polymerase−Topoisomerase Inhibitors (2006)

Novel Gram-positive (Gram+) antibacterial compounds consisting of a DNA polymerase IIIC (pol IIIC) inhibitor covalently connected to a topoisomerase/gyrase inhibitor are described. Specifically, 3-substituted 6-(3-ethyl-4-methylanilino)uracils (EMAUs) in which the 3-substituent is a fluoroquinolone moiety (FQ) connected by various linkers were synthesized. The resulting "AU-FQ" hybrid compounds were significantly more potent than the parent EMAU compounds as inhibitors of pol IIIC and were up to 64-fold more potent as antibacterials in vitro against Gram+ bacteria. The hybrids inhibited the FQ targets, topoisomerase IV and gyrase, with potencies similar to norfloxacin but 10-fold lower than newer agents, for example, ciprofloxacin and sparfloxacin. Representative hybrids protected mice from lethal Staphylococcus aureus infection after intravenous dosing, and one compound showed protective effect against several antibiotic-sensitive and -resistant Gram+ infections in mice. The AU-FQ hybrids are a promising new family of antibacterials for treatment of antibiotic-resistant Gram+ infections.
Kinetically Controlled Growth and Shape Formation Mechanism of Platinum Nanoparticles (1998)

Recently, we have been able to synthesize platinum colloidal nanoparticles of different shapes (Science, 1996, 272, 1924). In this report, we present transmission electron microscopic (TEM) results on the time-dependent shape distribution of platinum nanoparticles during the growth period and its dependence on the concentration of the capping polymer as well as the pH of the solution. The results suggest a shape-controlled growth mechanism in which the difference between the rate of the catalytic reduction process of Pt2+ on the {111} and {100} faces, the competition between the Pt2+ reduction and the capping process on the different nanoparticle surfaces, and the concentration-dependent buffer action of the polymer itself all control the final distribution of the different shapes observed.
A 0.15 μm NAND flash technology with 0.11 μm/sup 2/ cell size for 1 Gbit flash memory (2002)

A new 1 Gb NAND flash technology with high-aspect-ratio floating gate, tungsten bit line and poly-Si source line has been developed. It is fabricated using 0.15 /spl mu/m photolithography, shallow trench isolation (STI), highly selective gate etching, damascene and chemical-mechanical polishing (CMP) processes. Since thick poly-Si is deposited and its sidewall has an inclined profile by anisotropic etching, narrow floating gate space (/spl sim/80 nm) under the design rule and a high coupling ratio (/spl sim/0.75) are obtained. To interconnect the NAND cell array, the poly-Si source is connected to every string as a common line and the tungsten bit line is damascened over the entire string. These double-layer interconnections lead to simple process and reduced steps. Thus, for the first time, a prototype 1 Gb NAND flash memory with an extremely small cell size of 0.11 /spl mu/m/sup 2/ has been achieved.
Discovery of Novel Mesangial Cell Proliferation Inhibitors Using a Three-Dimensional Database Searching Method (2001)

A three-dimensional pharmacophore model of mesangial cell (MC) proliferation inhibitors was generated from a training set of 4-(diethoxyphosphoryl)methyl-N-(3-phenyl-[1,2,4]thiadiazol-5-yl)benzamide, 2, and its derivatives using the Catalyst/HIPHOP software program. On the basis of the in vitro MC proliferation inhibitory activity, a pharmacophore model was generated as seven features consisting of two hydrophobic regions, two hydrophobic aromatic regions, and three hydrogen bond acceptors. Using this model as a three-dimensional query to search the Maybridge database, structurally novel 41 compounds were identified. The evaluation of MC proliferation inhibitory activity using available samples from the 41 identified compounds exhibited over 50% inhibitory activity at the 100 nM range. Interestingly, the newly identified compounds by the 3D database searching method exhibited the reduced inhibition of normal proximal tubular epithelial cell proliferation compared to a training set of compounds.
Robust analysis of feature spaces: color image segmentation (2002)

A general technique for the recovery of significant image features is presented. The technique is based on the mean shift algorithm, a simple nonparametric procedure for estimating density gradients. Drawbacks of the current methods (including robust clustering) are avoided. Feature space of any nature can be processed, and as an example, color image segmentation is discussed. The segmentation is completely autonomous, only its class is chosen by the user. Thus, the same program can produce a high quality edge image, or provide, by extracting all the significant colors, a preprocessor for content-based query systems. A 512/spl times/512 color image is analyzed in less than 10 seconds on a standard workstation. Gray level images are handled as color images having only the lightness coordinate.
FAP1, a homologue of human transcription factor NF‐X1, competes with rapamycin for binding to FKBP12 in yeast (2000)

The immunosuppressive drug rapamycin binds to the peptidyl-prolyl cis-trans isomerase FKBP12, and this complex arrests growth of yeast cells and activated T lymphocytes in the G1 phase of the cell cycle. In yeast, loss-of-function mutations in FPR1, the gene encoding FKBP12, or dominant gain-of-function mutations in TOR1 and TOR2, the genes encoding the physical targets of the FKBP12-rapamycin complex, confer rapamycin resistance. Here, we report the cloning and characterization of a novel gene, termed FAP1, which confers resistance to rapamycin by competing with the drug for binding to FKBP12. FAP1 encodes a member of an evolutionarily conserved family of putative transcription factors that includes human NF-X1, Drosophila melanogaster shuttle craft and previously undescribed homologues in Caenorhabditis elegans, Arabidopsis thaliana and Schizosaccharomyces pombe. We provide genetic and biochemical evidence that FAP1 interacts physically with FKBP12 in vivo and in vitro, and that it competes with rapamycin for interaction. Furthermore, mutations in the FKBP12 drug binding/active site or surface residues abolish binding to FAP1. Our results suggest that FAP1 is a physiological ligand for FKBP12 that is highly conserved from yeast to man. Furthermore, prolyl isomerases may commonly bind and regulate transcription factors.
Expérience de classe inversée en Seconde : simple inversion des espaces spatio-temporels ou levier de développement des apprentissages (2015)

La remise en cause des methodes pedagogiques prescrites est necessaire dans le metier d’enseignant. Suite a un questionnement autour des innovations pedagogiques, le dispositif de classe inversee, de par sa forte notoriete au sein de la communaute educative a naturellement emerge. Mais, ce dispositif favorise-t-il le developpement de certaines capacites chez les eleves ? L’experimentation conduite en dispositif de classe inversee visait a valider les hypotheses suivantes : les eleves presentent un haut niveau d’adhesion, il permet d’accroitre l’autonomie et enfin, il soutient le developpement de capacites d’un plus haut niveau cognitif. Le protocole retenu est base sur trois etapes, la premiere consiste pour les eleves a prendre connaissance des notions a distance et a rediger une synthese, une deuxieme phase permet de valider l’acquisition des notions par un questionnaire et une mise en application, et enfin durant la derniere etape, les eleves doivent produire collectivement une tâche complexe. Les resultats demontrent que si les eleves declarent un niveau d’adhesion eleve a ce dispositif, le developpement de l’autonomie n’est pas valide et dans une moindre mesure, la production de la tâche complexe n’est pas completement satisfaisante. Meme si son efficacite est relative, la classe inversee est un outil supplementaire a la disposition des enseignants.