gebhart/patrepeval huggingface dataset:
Identification of cis- and trans-Active Factors Regulating Human Islet Amyloid Polypeptide Gene Expression in Pancreatic β-Cells (1997)

Islet amyloid polypeptide is expressed almost exclusively in pancreatic beta- and delta-cells. Here we report that beta cell-specific expression of the human islet amyloid polypeptide gene is principally regulated by promoter proximal sequences. The sequences that control tissue-specific expression were mapped between nucleotides -2798 and +450 of the human islet amyloid polypeptide (IAPP) gene using transgenic mice. To localize the cis-acting elements involved in this response, we examined the effects of mutations within these sequences using transfected islet amyloid polypeptide promoter expression constructs in pancreatic beta cell lines. The sequences between -222 and +450 bp were found to be necessary for beta cell-specific expression. Linker-scanning mutations of the 5'-promoter proximal region defined several key distinct control elements, including a negative-acting element at -111/-102 base pairs (bp), positive-acting elements like the basic helix-loop-helix-like binding site at -138/-131 bp, and the three A/T-rich, homeobox-like sites at -172/-163, -154/-142, and -91/-84 bp. Mutations within any one of these elements eliminated transcriptional expression by the promoter. Gel mobility shift assays revealed that the PDX-1 homeobox factor, which is required for insulin gene transcription in beta cells, interacted specifically at the -154/-142- and -91/-84-bp sites. Since PDX-1 is highly enriched in beta and delta cells, these results suggest that this factor plays a principal role in defining islet beta cell- and delta cell-specific expression of the IAPP gene.
Tracking adhesion factors in Staphylococcus caprae strains responsible for human bone infections following implantation of orthopaedic material (1999)

Ten Staphylococcus caprae strains isolated from four patients and responsible for bone infections following implantation of orthopaedic material were compared to four S. caprae strains collected from milk samples of healthy goats. The following characteristics were investigated: Smal patterns, hybridization patterns with pBA2 (ribotypes), slime production, adhesion to matrix proteins (fibrinogen, fibronectin, collagen) and the staphylococcal adhesion genes (fnbA, clfA, cna, atlE, ica, fbe). None of the characteristics enabled us to distinguish the human strains from the goat strains. Slime was occasionally produced by S. caprae strains but all of them carried nucleotide sequences hybridizing at low stringency with the following genes: atlE encoding a S. epidermidis autolysin binding vitronectin and responsible for the primary adhesion to polystyrene, ica operon involved in the biosynthesis of a S. epidermidis extracellular polysaccharide, and the part of clfA encoding the serine-aspartate repeated region of a S. aureus cell-wall fibrinogen-binding protein.
Catalytic Cycle of Rhodium-Catalyzed Asymmetric 1,4-Addition of Organoboronic Acids. Arylrhodium, Oxa-π-allylrhodium, and Hydroxorhodium Intermediates (2002)

The catalytic cycle of asymmetric 1,4-addition of phenylboronic acid to an alpha,beta-unsaturated ketone catalyzed by a rhodium-binap complex was established by use of RhPh(PPh(3))(binap) as a key intermediate. The reaction proceeds through three intermediates, phenylrhodium, oxa-pi-allylrhodium, and hydroxorhodium complexes, all of which were observed in NMR spectroscopic studies. The transformations between the three intermediates, that is, insertion, hydrolysis, and transmetalation, were also observed. On the basis of the catalytic cycle, a more active chiral catalyst, [Rh(OH)(binap)](2), was found and used successfully for the asymmetric 1,4-addition reactions.
Development of IVM‐IVF produced 8‐cell bovine embryos in simple, serum‐free media after conditioning or Co‐culture with buffalo rat liver cells (1994)

Development of 8-cell bovine embryos derived from in vitro matured/in vitro fertilized (IVM/IVF) oocytes was evaluated in two simple, serum-free media (CZB and SOM) with buffalo rat liver cells co-culture (BRLC) or after conditioning compared to a commonly used, serum-supplemented complex medium TCM-199. In a 3 x 4 factorial design, 578 eight-cell embryos were randomly assigned to 12 treatment groups. The factors were: first, type of culture medium (M199/FBS, CZBg and SOM), and second, the use of BRLC (as co-culture or to condition media for 24 hr and 48 hr) and unconditioned media. Development to morula was not affected by the type of medium, but co-culture and 48 hr conditioning within media type resulted in better development when compared to the 24-hr conditioned or unconditioned groups. Blastocyst development in SOM (38.9%) was different (P < 0.05) than in CZBg (46.6%) and M199/FBS (48.7%) and was lowest in the unconditioned group (27.8%) followed by 24 hr conditioned (33.3%), 48 hr (56.3%), and co-culture (59.6%). No blastocyst expansion was observed with unconditioned media and 24 hr conditioned SOM. Significant differences (P < 0.05) were found among all treatment groups except the co-culture and 48-hr conditioned groups. Hatching occurred only with co-culture and 48-hr conditioned groups of M199/FBS and CZBg media. These data show that CZB with glucose conditioned by BRLC monolayers for 48 hr can support the development of IVM/IVF produced bovine embryos to blastocyst compared to culture in TCM-199 with serum.
Preparation and characterization of sustained-release microspheres of chlorpromazine (1998)

Sustained release microspheres of chlorpromazine were prepared from Eudragit RS 100 by an emulsion-solvent evaporation method using a six-baffled vessel. The morphology of microspheres was characterized by scanning electron microscopy (SEM). In the presence of aluminium tristearate (5%), microspheres were spherical in shape and uniform. The release of chlorpromazine from microspheres was pH-independent. With increasing amount of aluminium tristearate and increasing ratio of Eudragit RS 100/drug from 1:1 to 9:1, the particle size of chlorpromazine microspheres was reduced and the release rate decreased. The microspheres prepared with the polymer/drug ratio of 9:1 produced a 12-h sustained release pattern.
IL-1RI deficiency ameliorates early experimental renal interstitial fibrosis (2009)

IL-1/IL-1RI interactions are profibrotic in renal fibrosis. IL-1RI(-/-) mice were more protected at an early stage, associated with changes in TGF-beta and downstream mediators of fibrosis, but independent of the presence of infiltrating macrophages.
Localization of intravenously administered verocytotoxins (Shiga-like toxins) 1 and 2 in rabbits immunized with homologous and heterologous toxoids and toxin subunits (1997)

Rabbits challenged intravenously with Shiga toxin or with Escherichia coli verocytotoxin 1 or 2 (VT1 or VT2) are known to develop diarrhea, paralysis, and death, which can be prevented by immunization with a toxoid. The pathological effects of VT1 in the central nervous system and the gastrointestinal tract of unimmunized rabbits correlate with the localization of 125I-VT1 in these tissues, whereas in immunized animals, localization of 125I-VT1 in target tissues is inhibited and labeled toxin is cleared by the liver and spleen. By using the approach described above in this study, rabbits immunized with VT1 toxoid, VT2 toxoid, or with the A or B subunit of each toxin were challenged with intravenous 125I-VT1 or 125I-VT2. After 2 h, the animals were sacrificed, and selected tissues were analyzed for uptake of labeled toxin. It was found that animals immunized with either VT1 toxoid or VT2 toxoid were protected from target tissue uptake of both 125I-VT1 and 125I-VT2. Rabbits immunized with either the VT1 A or VT2 A subunit were also protected from target tissue uptake of both the homologous and heterologous 125I-labeled holotoxins. In contrast, in animals immunized with the toxin B subunits, protection extended only against challenge by the homologous toxin. These results provide evidence of VT1 and VT2 cross-neutralization in vivo in the rabbit model and indicate that the in vivo cross-neutralization is a function, mainly, of antibodies directed to the VT A subunits. This suggests that the VT1 A or VT2 A subunit may be a suitable immunogen for immunizing humans against systemic VT-mediated disease.
Complement analysis in children with idiopathic membranoproliferative glomerulonephritis: A long‐term follow‐up (2001)

Fifty children with idiopathic membranoproliferative glomerulonephritis (MPGN), aged 2-14 years at apparent onset, were monitored for the presence of C3 nephritic factor (C3 NeF) and signs of complement activation in serum. In addition, C3 allotyping was performed in 32 patients. Observation time ranged from 2 to 20 (median 11) years. C3 NeF activity was detected at least once in 60% of the patients (in 11 of 26 with type I, in 15 of 17 with type II, and in four of seven with type III). C3 NeF-positive patients had significantly reduced levels of CH50 and C3 and elevated levels of C3dg/C3d. During follow-up, C3 levels were persistently normal in 62% of the patients with MPGN type I and in 43% with type III but in only 18% with type II. C3 allotype frequencies differed from those found in healthy controls with a significant shift to the C3F/C3FS variants in C3 NeF-positive patients. C3b(Bb)P as a marker for alternative pathway activation was not increased in C3 NeF-positive patients. Despite the presence of C3 NeF activity, C3 levels remained normal in six patients throughout the observation period. C3 NeF became undetectable in six patients, whereas seven developed C3 NeF activity during follow-up. There was no significant difference in renal survival probability in patients with or without C3 NeF activity. Neither C3 variants nor continuous low C3 or low CH50 levels had any prognostic value for the clinical outcome. No factor H deficiency was detected.
Infections due to group A streptococcus: new concepts and potential treatment strategies. (1997)

Important new information has been gained on the pathogenesis and treatment of life-threatening invasive infections caused by group A streptococci (GAS), i.e. the streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis (NF). Both STSS and NF lead to superantigen reactions with activation of up to 10% of the CD4+ lymphocytes and release of large amounts of cytokines; mainly tumour necrosing factor beta, interferon gamma, interleukin 1 and interleukin 6. Streptococcal products known to trigger the superantigen reactions are the pyrogenic exotoxins, spe A, spe B and spe C and the M-proteins. Therapeutically clindamycin has been shown to reduce mortality in animal experiments in comparison to penicillin treatment. A possible mechanism is the effect of clindamycin on protein synthesis which might decrease the production of superantigens. In man, the use of intravenous immunoglobulin has been shown to significantly reduce mortality in STSS and NF. The most probable mechanism is neutralisation of superantigens by antibodies in the immunoglobulin preparations used.
DeepCoder: Learning to Write Programs (2016)

We develop a first line of attack for solving programming competition-style problems from input-output examples using deep learning. The approach is to train a neural network to predict properties of the program that generated the outputs from the inputs. We use the neural network's predictions to augment search techniques from the programming languages community, including enumerative search and an SMT-based solver. Empirically, we show that our approach leads to an order of magnitude speedup over the strong non-augmented baselines and a Recurrent Neural Network approach, and that we are able to solve problems of difficulty comparable to the simplest problems on programming competition websites.
Testing recombinant adeno-associated virus-gene loading of dendritic cells for generating potent cytotoxic T lymphocytes against a prototype self-antigen, multiple myeloma HM1.24 (2003)

Recent studies demonstrate that recombinant adeno-associated virus (rAAV)-based antigen loading of dendritic cells (DCs) generates significant and rapid (one stimulation per week) cytotoxic T-lymphocyte (CTL) responses in vitro against viral antigens. As a more extensive analysis of the rAAV system, we have used a self-antigen, HM1.24, expressed in multiple myeloma (MM). Again, with one stimulation, significant major histocompatibility complex (MHC) class 1-restricted, anti-HM1.24-specific CTL killing was demonstrated against MM cells. Furthermore, higher expression of interferon-gamma (IFN-gamma) in T cells and higher expression levels of, in order of significance, CD80 (2.6- to 3.8-fold increase), CD86, and CD40 on DCs were also observed. The use of synthetic HM1.24-positive target cells further demonstrated the antigen specificity of these CTLs. There was also no evidence of natural killer cell involvement. These data extend our earlier studies and suggest that the rAAV-loading of DCs may be a particularly good protocol for generating CTLs against self-antigens, which may not otherwise be considered good targets because of their low immunogenicity. We also show that HM1.24 may be an effective antigen for targeting MM.
Cloning of genes coding for L-sorbose and L-sorbosone dehydrogenases from Gluconobacter oxydans and microbial production of 2-keto-L-gulonate, a precursor of L-ascorbic acid, in a recombinant G. oxydans strain (1997)

We have purified L-sorbose dehydrogenase (SDH) and L-sorbosone dehydrogenase (SNDH) from Gluconobacter oxydans T-100 that showed an ability to convert D-sorbitol to 2-keto-L-gulonate (2-KLGA). A genomic library of Gluconobacter oxydans T-100 was screened with a probe, a 180-bp PCR product which was obtained from degenerate oligodeoxyribonucleotides based on the elucidated sequence of the purified SDH (used as primers) and the genomic DNA of G. oxydans T-100 (used as a template). From sequencing of the DNA from a clone positive to the probe, the SNDH and the SDH were estimated to be coded in sequential open reading frames with 1,497 and 1,599 nucleotides, respectively, which was confirmed by expression of the DNA in Escherichia coli that showed both enzymatic activities. The DNA was introduced to a shuttle vector which was prepared from a plasmid of G. oxydans T-100 and pHSG298 to obtain an expression vector designated pSDH155. The production of 2-KLGA by pSDH155 in G. oxydans G624, an L-sorbose-accumulating strain, was improved to 230% compared to that of G. oxydans T-100. Chemical mutation of the host strain to suppress the L-idonate pathway and replacement of the original promoter with that of E. coli tufB resulted in improving the production of 2-KLGA. Consequently, high-level production from D-sorbitol to 2-KLGA (130 mg/ml) was achieved by simple fermentation of the recombinant Gluconobacter.
Human Sulfide:Quinone Oxidoreductase Catalyzes the First Step in Hydrogen Sulfide Metabolism and Produces a Sulfane Sulfur Metabolite (2012)

Sulfide:quinone oxidoreductase (SQOR) is a membrane-bound enzyme that catalyzes the first step in the mitochondrial metabolism of H(2)S. Human SQOR is successfully expressed at low temperature in Escherichia coli by using an optimized synthetic gene and cold-adapted chaperonins. Recombinant SQOR contains noncovalently bound FAD and catalyzes the two-electron oxidation of H(2)S to S(0) (sulfane sulfur) using CoQ(1) as an electron acceptor. The prosthetic group is reduced upon anaerobic addition of H(2)S in a reaction that proceeds via a long-wavelength-absorbing intermediate (λ(max) = 673 nm). Cyanide, sulfite, or sulfide can act as the sulfane sulfur acceptor in reactions that (i) exhibit pH optima at 8.5, 7.5, or 7.0, respectively, and (ii) produce thiocyanate, thiosulfate, or a putative sulfur analogue of hydrogen peroxide (H(2)S(2)), respectively. Importantly, thiosulfate is a known intermediate in the oxidation of H(2)S by intact animals and the major product formed in glutathione-depleted cells or mitochondria. Oxidation of H(2)S by SQOR with sulfite as the sulfane sulfur acceptor is rapid and highly efficient at physiological pH (k(cat)/K(m,H(2)S) = 2.9 × 10(7) M(-1) s(-1)). A similar efficiency is observed with cyanide, a clearly artificial acceptor, at pH 8.5, whereas a 100-fold lower value is seen with sulfide as the acceptor at pH 7.0. The latter reaction is unlikely to occur in healthy individuals but may become significant under certain pathological conditions. We propose that sulfite is the physiological acceptor of the sulfane sulfur and that the SQOR reaction is the predominant source of the thiosulfate produced during H(2)S oxidation by mammalian tissues.
Thermal antinociception after dexmedetomidine administration in cats: A comparison between intramuscular and oral transmucosal administration (2009)

Dexmedetomidine 40microg/kg was administered either intramuscularly (IM) or oral transmucosally (OTM) to 12 cats in a randomised cross-over study. Thermal nociceptive thresholds and visual analogue scale (VAS) sedation scores were obtained before and at regular intervals up to 24h after test drug administration. The summary measures of overall mean threshold, overall mean VAS sedation plus onset, offset and duration of analgesia were investigated using a univariate general linear model. There were no significant differences between treatment groups. Data are presented as mean+/-standard deviation: delta T mean increase over time (IM 6 degrees C+/-3 degrees C, OTM 6 degrees C+/-2 degrees C); overall mean VAS (IM 43+/-9 OTM 39+/-1); onset (IM 35+/-32 and OTM 30+/-40min); offset (IM 96+/-56 and OTM 138+/-135min); duration (IM 61+/-47 OTM 99+/-124min). Dexmedetomidine is well absorbed through the oral mucosa in cats since OTM and IM administration of dexmedetomidine 40microg/kg produced similar overall sedative and antinociceptive effects.
Full-waveform inversion of plane-wave seismograms in stratified acoustic media; theory and feasibility (1988)

Abstract We have implemented an inversion procedure for obtaining velocity and density profiles from multioffset data in a layered acoustic medium. Using an iterative modeling technique and the p-tau representation, the procedure is derived from the nonlinear least-squares formalism of Tarantola and Valette. The feasibility of this method depends upon obtaining Frechet derivatives during the modeling process and on vectorizing the Thompson-Haskell reflectivity algorithm. Test data sets for this study are gathers of two to four plane-wave synthetic seismograms which may contain both precritical and postcritical arrivals generated by a seismic wavelet. These examples demonstrate convergence to the correct velocity and density profiles with reasonable accuracy.
Enteral absorption of octreotide: absorption enhancement by polyoxyethylene‐24‐cholesterol ether (1993)

1. The somatostatin octapeptide-analogue octreotide was absorbed as an intact peptide from the gastro-intestinal tract with an absolute bioavailability of about 0.3% in rats. Administration of octreotide in the presence of polyoxyethylene (24)-cholesterol-ether (POECE) resulted in an about 23 fold increase of bioavailability. 2. In vitro studies with Caco-2 cells showed a dose-dependent increase in octreotide permeation with increasing doses of coadministered POECE. The use of [3H]-polyethyleneglycol (PEG) 4000 as an extracellular marker also indicated that higher doses of POECE may partly enhance paracellular transport of macromolecules. 3. By means of fluorescence microscopy it was shown that transepithelial transport of the fluorescent octreotide analogue (4-nitrobenzo-2-oxa-1,3-diazol [NBD] labelled octreotide) was enhanced by the addition of POECE. Besides an increased enterocyte uptake, there was evidence of enhanced partition of NBD-octreotide into the intercellular space between enterocytes after co-administration of POECE. In addition, there appeared to be changes in the hepatic topographic disposition of NBD-octreotide when it was given together with POECE compared with its administration alone. 4. In a study in healthy volunteers, 16 mg POECE significantly enhanced by 8 fold the absorption of octreotide after oral administration.
Nucleic acid related compounds. 36. Synthesis of the 2′-O-methyl and 3′-O-methyl ethers of guanosine and 2-aminoadenosine and correlation of O′-methylnucleoside 13C nmr spectral shifts (1981)

A modified trimethylsilylation of guanosine (1) followed by in situ replacement of the 6-trimethylsilyloxy group with ammonia at 150 °C gave 2,6-diamino-9-β-D-ribofuranosylpurine (2) in 92% yield. Treatment of 2 with diazomethane in the presence of tin(II) chloride dihydrate gave the 2′-O-methyl (3) and 3′-O-methyl (4) ethers of 2 in 98% combined yield. The ratios of 3/4 could be varied from 51:47 to 34:64 by changing the amount of catalyst used. Treatment of 3 and 4 with adenosine deaminase resulted in clean conversion of these 2-aminoadenosine ethers to 2′-O-methylguanosine (5) and 3′-O-methylguanosine (6), respectively, in optimized yields of 40% and 54% overall from 1. The 13 C nmr data for six ribonucleosides and their isomeric methyl ether derivatives have been correlated to provide a convenient method of identification.
Characterization of a Soluble Vascular Endothelial Growth Factor Receptor-Immunoglobulin Chimera (1997)

To investigate the interaction between vascular endothelial growth factor (VEGF) and its receptor, we have constructed a chimeric protein consisting of the extracellular ligand-binding domain of the human VEGF receptor subtype KDR fused to a human IgG1 Fc domain (KDR-Fc). KDR-Fc was expressed in human 293 kidney epithelial cells as a 300-kDa secreted, dimeric glycoprotein that bound 125I-VEGF165 with high affinity (Kd = 150 pM). Unlike the full length cellular receptor, KDR-Fc did not require heparin for 125I-VEGF165 binding, although heparin did stimulate 125I-VEGF165 binding approximately 50 to 100%. Similar results were observed for KDR-Fc expressed in yeast cells. Since yeast do not synthesize heparan sulfate proteoglycans, we conclude that cellular heparan sulfates do not account for the lack of a heparin requirement for 125I-VEGF165 binding to KDR-Fc. The polycationic protein protamine, which inhibits (IC50 = 1 microgram/ml) 125I-VEGF165 binding to bovine aortic endothelial cells and other KDR-expressing cells by blocking heparin interactions, had no effect on the heparin independent component of 125I-VEGF165 binding to KDR-Fc. Protamine does inhibit (IC50 = 1 microgram/ml) the heparin dependent component of 125I-VEGF165 binding to KDR-Fc. KDR-Fc bound VEGF121 with the same affinity as VEGF165. Heparin had no effect on 125I-VEGF121 binding to KDR-Fc, indicating that heparin interaction with the 44 amino acids contained in VEGF165 but not VEGF121 allow for maximal VEGF165 binding. Deletion analysis of KDR-Fc demonstrated that the determinants required for high affinity VEGF binding are located in the three aminoterminal Ig-domains of the protein. Heparin had no effect on 125I-VEGF165 binding to the three Ig-domain receptor, suggesting that there are heparin binding determinants located in KDR Ig-domains 4 to 7.
Enhanced Fluorescence Imaging of Live Cells by Effective Cytosolic Delivery of Probes (2010)

We show the delivery of sufficient quantities of probes to the cytosol, allowing sustained functional imaging of live cells over time periods of days to weeks. Finally the combination of such effective staining with three-dimensional imaging by confocal laser scanning microscopy allows cell imaging in complex three-dimensional environments under both mono-culture and co-culture conditions. Thus cell migration and proliferation can be studied in models that are much closer to the in vivo situation.