gebhart/patrepeval huggingface dataset:
Applications of mass spectrometry to DNA fingerprinting and DNA sequencing (1993)

DNA fingerprinting and sequencing rely on polyacrylamide gel electrophoresis to determine the sizes of the DNA fragments. Innovative altematives to polyacrylamide gel electrophoresis are under investigation for characterization of such fingerprinting and sequencing. One method uses stable isotopes of tin and other elements to label the DNAwhereas other procedures do not require labels. The detectors in each case are mass spectrometers that detect either the stable isotopes or the DNA fragments themselves. If successful, these methods will speed up the rate of DNA analysis by one or two orders of magnitude.
Ranitidine Bismuth Citrate Can Help to Overcome Helicobacter pylori Resistance to Clarithromycin In Vivo (2000)

A synergy between RBC and clarithromycin may exist in vivo and, while clarithromycin resistance is increasing, it is an argument for using RBC in triple therapies.
Selective killing of target cells by antibody-ricin A chain or antibody-gelonin hybrid molecules: comparison of cytotoxic potency and use in immunoselection procedures. (1983)

Ricin A chain and gelonin, two plant proteins that can powerfully reduce the protein synthetic capacity of ribosome preparations, were covalently coupled to a monoclonal anti-Thy-1.2 antibody. Two conjugates were prepared by using N-succinimidyl-3-2(-pyridyldithio)propionate, which generates a disulfide linkage between the component molecules. Both conjugates specifically killed Thy-1.2 antigen-bearing EL-4 cells, but had no effect on Thy-1.2- BW5147 cells. The cytotoxic potency of both reagents was determined by comparing the cloning efficiency of E1-4 target cells after treatment with the conjugate. The frequency of cells surviving treatment with 45 micrograms/10(6) cells of the gelonin conjugate was 1/72, whereas this frequency was 1/836 after exposure to 7 micrograms of the Ricin A chain conjugate. Both reagents could be successfully used to select Thy-1.2- cells from cell mixtures consisting of Thy-1.2+ and Thy-1.2- cells.
Complete Regression of Metastatic Renal Cell Carcinoma by Multiple Injections of Engineered Mesenchymal Stem Cells Expressing Dodecameric TRAIL and HSV-TK (2012)

Sequential combination gene therapy using MSC/dTRAIL-TK achieved long-term remission of metastatic RCC without noticeable toxicity. Our findings provide an innovative therapeutic approach to completely eradicate metastatic tumors by simple, repeated administrations of MSC/dTRAIL-TK.
The angular structure of ONC201, a TRAIL pathway-inducing compound, determines its potent anti-cancer activity (2014)

We previously identified TRAIL-inducing compound 10 (TIC10), also known as NSC350625 or ONC201, from a NCI chemical library screen as a small molecule that has potent anti-tumor efficacy and a benign safety profile in preclinical cancer models. The chemical structure that was originally published by Stahle, et. al. in the patent literature was described as an imidazo[1,2-a]pyrido[4,3-d]pyrimidine derivative. The NCI and others generally accepted this as the correct structure, which was consistent with the mass spectrometry analysis outlined in the publication by Allen et. al. that first reported the molecule's anticancer properties. A recent publication demonstrated that the chemical structure of ONC201 material from the NCI is an angular [3,4-e] isomer of the originally disclosed, linear [4,3-d] structure. Here we confirm by NMR and X-ray structural analysis of the dihydrochloride salt form that the ONC201 material produced by Oncoceutics is the angular [3,4-e] structure and not the linear structure originally depicted in the patent literature and by the NCI. Similarly, in accordance with our biological evaluation, the previously disclosed anti-cancer activity is associated with the angular structure and not the linear isomer. Together these studies confirm that ONC201, produced by Oncoceutics or obtained from the NCI, possesses an angular [3,4-e] structure that represents the highly active anti-cancer compound utilized in prior preclinical studies and now entering clinical trials in advanced cancers.
Human Leucocyte Elastase (HLE) Preferentially Cleaves the Heavy Chain H2of Inter-α-Trypsin Inhibitor (ITI) (1993)

Inter-alpha-trypsin inhibitor (ITI) is a complex protein containing two heavy polypeptide chains (H1 and H2) and a light chain, which in the free state is known as bikunin. In vitro cleavage of ITI with different proteases releases bikunin, but does not abolish the antitryptic activity. To study the mechanism of bikunin release, ITI was incubated with human leucocyte elastase (HLE). The resulting ITI fragments were characterized by (i) their electrophoretic and chromatographic behavior. (ii) their immunological reactivity towards antibodies specific for each of the heavy chains H1 and H2, and (iii) their N-terminal sequences. Our results demonstrate that the H2 heavy chain of ITI is particularly sensitive to HLE, and that early cleavage products (M(r)-values 120-150,000) consist of H1 linked to bikunin. A scheme is proposed for the mechanism for ITI degradation.
Transcription, Organization, and Sequence of an Auxin-Regulated Gene Cluster in Soybean (1989)

Bruce A. McClure, Gretchen Hagen, Christopher S. Brown, Melissa A. Gee, Tom J. Guilfoyle, Transcription, Organization, and Sequence of an Auxin-Regulated Gene Cluster in Soybean, The Plant Cell, Vol. 1, No. 2 (Feb., 1989), pp. 229-239
LazyFluids (2015)

In this paper we present a novel approach to appearance transfer for fluid animations based on flow-guided texture synthesis. In contrast to common practice where pre-captured sets of fluid elements are combined in order to achieve desired motion and look, we bring the possibility of fine-tuning motion properties in advance using CG techniques, and then transferring the desired look from a selected appearance exemplar. We demonstrate that such a practical work-flow cannot be simply implemented using current state-of-the-art techniques, analyze what the main obstacles are, and propose a solution to resolve them. In addition, we extend the algorithm to allow for synthesis with rich boundary effects and video exemplars. Finally, we present numerous results that demonstrate the versatility of the proposed approach.
Establishment of a Rescue System for Canine Distemper Virus (2000)

Canine distemper virus (CDV) has been rescued from a full-length cDNA clone. Besides Measles virus (MV) and Rinderpest virus, a third morbillivirus is now available for genetic analysis using reverse genetics. A plasmid p(+)CDV was constructed by sequential cloning using the Onderstepoort vaccine strain large-plaque-forming variant. The presence of a T7 promoter allowed transcription of full-length antigenomic RNA by a T7 RNA polymerase, which was provided by a host range mutant of vaccinia virus (MVA-T7). Plasmids expressing the nucleocapsid protein, the phosphoprotein, and the viral RNA-dependent RNA polymerase, also under control of a T7 promoter, have been generated. Infection of HeLa cells with MVA-T7 and subsequent transfection of p(+)CDV plus the helper plasmids led to syncytium formation and release of infectious recombinant (r) CDV. Comparison of the rescued virus with the parental virus revealed no major differences in the progression of infection or in the shape and size of syncytia. A genetic tag, consisting of two nucleotide changes within the coding region of the L protein, has been identified in the rCDV genome. Expression by rCDV of all the major viral structural proteins has been demonstrated by immunofluorescence.
Nucleotide sequence of the yeast STE14 gene, which encodes farnesylcysteine carboxyl methyltransferase, and demonstration of its essential role in a-factor export. (1994)

Eukaryotic proteins initially synthesized with a C-terminal CAAX motif (C is Cys, A is aliphatic, and X can be one of several amino acids) undergo a series of modifications involving isoprenylation of the Cys residue, proteolysis of AAX, and alpha-carboxyl methyl esterification of the newly formed isoprenyl cysteine. We have previously demonstrated that STE14 encodes the enzyme which mediates carboxyl methylation of the Saccharomyces cerevisiae CAAX proteins a-factor, RAS1, and RAS2. Here we report the nucleotide sequence of STE14, which indicates that STE14 encodes a protein of 239 amino acids, predicted to contain multiple membrane-spanning segments. Mapping data indicate that STE14 resides on chromosome IV, tightly linked to ADE8. By analysis of ste14 null alleles, we demonstrated that MATa ste14 mutants are unable to mate but are viable and exhibit no apparent growth defects. Additional analysis of ste14 ras 1 and ste14 ras2 double mutants, which grow normally, reinforces our previous conclusion that RAS function is not significantly influenced by its methylation status. We examine a-factor biogenesis in a ste14 null mutant by metabolic labeling and immunoprecipitation and demonstrate that although proteolytic processing and membrane localization of a-factor are normal, the ste14 null mutant exhibits a profound block in a-factor export. This observation suggests that the methyl group is likely to be a critical recognition determinant for the a-factor transporter, STE6, thus providing insight into the substrate specificity of STE6 and also supporting the hypothesis that carboxyl methylation can have a dramatic impact on protein-protein interactions.
Validation of a Metabolic Network for Saccharomyces cerevisiae Using Mixed Substrate Studies (1996)

Setting up a metabolic network model for respiratory growth of Saccharomyces cerevisiae requires the estimation of only two (energetic) stoichiometric parameters: (1) the operational PO ratio and (2) a growth-related maintenance factor k. It is shown, both theoretically and practically, how chemostat cultivations with different mixtures of two substrates allow unique values to be given to these unknowns of the proposed metabolic model. For the yeast and model considered, an effective PO ratio of 1.09 mol of ATP/mol of O (95% confidence interval 1.07-1.11) and a k factor of 0.415 mol of ATP/C-mol of biomass (0.385-0.445) were obtained from biomass substrate yield data on glucose/ethanol mixtures. Symbolic manipulation software proved very valuable in this study as it supported the proof of theoretical identifiability and significantly reduced the necessary computations for parameter estimation. In the transition from 100% glucose to 100% ethanol in the feed, four metabolic regimes occur. Switching between these regimes is determined by cessation of an irreversible reaction and initiation of an alternative reaction. Metabolic network predictions of these metabolic switches compared well with activity measurements of key enzymes. As a second validation of the network, the biomass yield of S. cerevisiae on acetate was also compared to the network prediction. An excellent agreement was found for a network in which acetate transport was modeled with a proton symport, while passive diffusion of acetate gave significantly higher yield predictions.
Efficiency of the salt flotation technique in the recovery ofAscaris lumbricoideseggs from the soil (1995)

The efficacy of the salt flotation technique using saturated solutions of sodium nitrate (specific gravity 1.30) and zinc sulphate (specific gravity 1.16) for separating Ascaris lumbricoides eggs from clay, loamy and sandy soils has been investigated. Ten samples of each of the egg concentrations of 100, 500, 2500, 5000 and 10,000 eggs/25 g of soil were used for each soil type. Using T-test and ANOVA, the number of eggs recovered from sand was significantly higher than from loam and the number from loam significantly higher than from clay. With sodium nitrate, the maximum egg recovery rate was 25.04% from sandy soil at a concentration of 500 eggs/25 g soil while with zinc sulphate it was 13.88% also from sandy soil and concentration of 500 eggs/25 g soil. While the number of eggs recovered increased with soil egg concentration, the percentage of eggs recovered is inversely proportional to egg concentration. The number of eggs recovered with sodium nitrate was significantly higher than with zinc sulphate solution in the three soil types.
Cyclic Peptides as Non-carboxyl-terminal Ligands of Syntrophin PDZ Domains (1998)

Syntrophins, a family of intracellular peripheral membrane proteins of the dystrophin-associated protein complex (DAPC), each contain a single PDZ domain. Syntrophin PDZ domains bind C-terminal peptide sequences with the consensus R/K-E-S/T-X-V-COOH, an interaction that mediates association of skeletal muscle sodium channels with the DAPC. Here, we have isolated cyclic peptide ligands for syntrophin PDZ domains from a library of combinatorial peptides displayed at the N terminus of protein III of bacteriophage M13. Affinity selection from a library of X10C peptides yielded ligands with the consensus X-(R/K)-E-T-C-L/M-A-G-X-Psi-C, where Psi represents any hydrophobic amino acid. These peptides contain residues (underlined) similar to the C-terminal consensus sequence for binding to syntrophin PDZ domains and bind to the same site on syntrophin PDZ domains as C-terminal peptides, but do not bind to other closely related PDZ domains. PDZ binding is dependent on the formation of an intramolecular disulfide bond in the peptides, since treatment with dithiothreitol, or substitution of either of the two cysteines with alanines, eliminated this activity. Furthermore, amino acid replacements revealed that most residues in the phage-selected peptides are required for binding. Our results define a new mode of binding to PDZ domains and suggest that proteins containing similar conformationally constrained sequences may be ligands for PDZ domains.
Development ofAspergillus oryzae thiApromoter as a tool for molecular biological studies (2005)

In filamentous fungi, the repertoire of promoters available for exogenous gene expression is limited. Here, we report the development and application of the thiamine-regulatable thiA promoter (PthiA) in Aspergillus oryzae as a tool for molecular biological studies. When PthiA was used to express the enhanced green fluorescent protein (EGFP) reporter, the fluorescence in the mycelia was either repressed or induced in the presence or absence of thiamine in the culture media, respectively. In addition, the expression level from the thiA promoter can be controlled by the concentration of external thiamine. Thiamine content in the media did not affect mycelial morphology, making the thiA promoter more useful compared with alcA and amyB promoters that depend on carbon source for regulation. Moreover, as the A. oryzae thiA promoter was also regulated by thiamine in A. nidulans, this promoter can be further applied as an inducible promoter in other Aspergilli.
A family of receptor-linked protein tyrosine phosphatases in humans and Drosophila. (1989)

To understand the regulation of cell proliferation by tyrosine phosphorylation, characterization of protein tyrosine phosphatases (PTPase; protein-tyrosine-phosphate phosphohydrolase, EC 3.1.3.48) is essential. The human genes LCA (leukocyte common antigen) and LAR encode putative receptor-linked PTPases. By using consensus sequence probes, two additional receptor-linked PTPase genes, DLAR and DPTP, were isolated from Drosophila melanogaster. The extracellular segments of both DLAR and DPTP are composed of multiple immunoglobulin-like domains and fibronectin type III-like domains. The cytoplasmic region of DLAR and DPTP, as well as human LCA and LAR, are composed of two tandemly repeated PTPase domains. PTPase activities of immunoprecipitated LCA and LAR were demonstrated by measuring the release of phosphate from a 32P-labeled [Tyr(P)]peptide. Furthermore, the cytoplasmic domains of LCA, LAR, DLAR, and DPTP, expressed in Escherichia coli, have PTPase activity. Site-directed mutagenesis showed that a conserved cysteine residue is essential for PTPase activity.
The First Crystal and Molecular Structure of asyn-Acetato-Bridged Dinuclear Cyclometallated Complex [Pd{2,3,4-(MeO)3C6HC(H)=NCH2CH2OH}(μ-OAc)]2 (2002)

Treatment of the Schiff base ligands 2,3,4-(MeO)3C6H2C(H)=NR (R = CH2CH2OH, 1; R = Me, 17; R = Et, 18; R = Pr, 19; R = tBu, 20) with palladium(II) acetate in toluene gave the dinuclear cyclometallated complexes [Pd{2,3,4-(MeO)3C6HC(H)=NR}(μ-O2CMe)]2 (R = CH2CH2OH, 2; R = Me, 21; R = Et, 22; R = Pr, 23; R = tBu, 24), with the ligand bonded to the palladium atom through the imine nitrogen and the C6 carbon atoms. The 1H and 13C{1H} NMR spectra of the complexes showed the presence of the anti and syn isomers in solution. The anti/syn ratio varies with the solvent and the nature of the imine nitrogen substituent R. Complex 24 with the bulky tBu group showed a 28:1 ratio in chloroform whilst the less bulky substituted complexes showed lower ratios. The X-ray crystal structure of the syn isomer of complex 2 is described. Reaction of the acetato-bridged complex 2 with PPh3 gave the mononuclear complex 4, in a bridge-splitting reaction. Reaction of 2 with the diphosphanes dppm, dppp and dppb in a 1:1 molar ratio gave the dinuclear cyclometallated complexes 5, 6 and 7, respectively. Treatment of 2 with an aqueous solution of sodium chloride gave the chloro-bridged complex 3. Treatment of the cyclometallated chloro-bridged complex 3 with PPh3 in acetone yielded the mononuclear complex 8, and reaction of 3 with silver triflate gave the cyclometallated complex 9, with the palladium atom bonded to four different atoms C, N, O and P. Treatment of 3 with the tertiary diphosphanes dppp, dppb and dppf, in a 1:1 molar ratio gave the dinuclear complexes 10, 11 and 12, respectively, with terminal chloride ligands. However, reaction of 3 with the small "bite" diphosphane dppm gave 13, with a bridging chloride ligand. Reaction of 11 with silver triflate in acetone gave the new dinuclear complex 14, with the Schiff base ligand as [C,N,O] terdentate. Reaction of 3 with the diphosphane dppe in a 1:2 molar ratio, and silver perchlorate, gave the mononuclear complex 15. Treatment of 3 with the triphosphane bis(2-diphenylphosphanylethyl)phenylphosphane in a 1:2 molar ratio, followed by treatment with sodium perchlorate, gave 16, in which the palladium atom was bonded to the triphosphane through the three phosphorus atoms. The X-ray crystal structures of complexes 8, 9, 15 and 16 are also reported. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)
Proto-Oncogene c-fos Is Transcriptionally Regulated by Parathyroid Hormone (PTH) and PTH-Related Protein in a Cyclic Adenosine Monophosphate-Dependent Manner in Osteoblastic Cells (1997)

PTH and PTH-related protein (PTHrP) bind to the PTH-1 (PTH/PTHrP) receptor and produce anabolic and catabolic effects in bone. To investigate postreceptor mechanisms of action, MC3T3-E1 cells were induced to differentiate to optimize PTH-1 receptor expression, and differentiated MC3T3-E1 cells were treated with varying doses of PTH (1–34) for 1 h. Northern blot analysis revealed a dose-dependent stimulation of steady state c-fos messenger RNA (mRNA), with measurable expression at doses as low as 1 pm PTH. The time course of c-fos mRNA induction was rapid, with peak levels detected at 30–45 min. Increased steady state c-fos mRNA was due to increased transcription of the c-fos gene as demonstrated by nuclear run-on assays and was dependent on the temporal differentiation state of the MC3T3-E1 cells. Stimulation of c-fos mRNA was induced exclusively by N-terminal PTH and PTHrP (which is also responsible for cAMP activation), and did not occur with PTH (7–34), (53–84), or PTHrP (107–139). The effects of PTH (1–34) on c-fos stimulation were dependent on intracellular cAMP. Forskolin [a guanine-nucleotide-binding protein (Gα) agonist] stimulated c-fos mRNA, whereas 9-(tetrahydro-2-furyl) adenine (THFA) (a cAMP antagonist), 1,9 dideoxyforskolin (a cAMP independent analog of forskolin), and phorbol 12-myristate 13-acetate (a protein kinase C activator) did not. Furthermore, THFA inhibited the ability of PTH (1–34) to stimulate c-fos mRNA in a time-dependent manner. These findings indicate that c-fos is transcriptionally regulated by PTH (1–34) in osteoblastic cells, and that cAMP is a mediator of PTH-stimulated c-fos induction. Several known bone-associated proteins contain DNA binding sites in their promoter regions that recognize c-fos in conjunction with c-jun (AP-1 sites). Consequently, the induction of c-fos by PTH (1–34) in osteoblastic cells may be a sensitive indicator of PTH effects in vitro and in vivo, and provide valuable information regarding mechanisms of PTH action in bone.
Regorafenib for the treatment of unresectable hepatocellular carcinoma (2017)

Sorafenib is the standard of care for patients with advanced hepatocellular carcinoma (HCC) and well preserved liver function. However, until recent approval of regorafenib by the Food and Drug Administration (FDA), no effective therapeutic options were available for patients resistant to sorafenib. Areas covered: The present article reviews the preclinical and clinical data of regorafenib, putting them into the context of current and future landscape of treatment options for patients with HCC. Recently, the randomized, placebo-controlled, Phase III RESORCE trial, demonstrated a statistically and clinically significant increase in overall survival from 7.8 months with placebo to 10.6 months with regorafenib in patients progressing on sorafenib. Furthermore, the study showed a significant improvement in all the other efficacy endpoints. Main adverse events were hypertension, hand-foot skin reaction, fatigue and diarrhea, with no negative impact on quality of life. Expert commentary: Regorafenib is a recently approved treatment option for HCC patients who have been previously treated with sorafenib. The RESORCE trial demonstrates the beneficial effect of a sequential approach involving two multikinase inhibitors, namely sorafenib and regorafenib, whose antitumor activity extends beyond their antiangiogenic functions.
ChemInform Abstract: Studies on the Chemistry of Isoindoles and Isoindolenines. Part 39. Reactions of 2‐Alkyl‐4,5,6,7‐Rn‐2H‐isoindoles (Rn: tetramethyl, tetrachloro) with Activated C=C Dienophiles. (1992)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.