gebhart/patrepeval huggingface dataset:
Stereospecific Olefin Polymerization with Chiral Metallocene Catalysts (1995)

Abstract Current studies on novel, metallocenebased catalysts for the polymerization of α‐olefins have far‐reaching implications for the development of new materials as well as for the understanding of basic reaction mechanisms responsible for the growth of a polymer chain at a catalyst center and the control of its stereoregularity. In contrast to heterogeneous Ziegler–Natta catalysts, polymerization by a homogeneous, metallocene‐based catalyst occurs principally at a single type of metal center with a defined coordination environment. This makes it possible to correlate metallocene structures with polymer properties such as molecular weight, stereochemical microstructure, crystallization behavior, and mechanical properties. Homogeneous catalyst systems now afford efficient control of regio‐ and stereoregularities, molecular weights and molecular weight distributions, and comonomer incorporation. By providing a means for the homo‐ and copolymerization of cyclic olefins, the cyclopolymerization of dienes, and access even to functionalized polyolefins, these catalysts greatly expand the range and versatility of technically feasible types of polyolefin materials. For corrigendum see DOI: 10.1002/anie.199513681
L‐Theanine: properties, synthesis and isolation from tea (2011)

Theanine is a non-protein amino acid that occurs naturally in the tea plant (Camellia sinensis) and contributes to the favourable taste of tea. It is also associated with effects such as the enhancement of relaxation and the improvement of concentration and learning ability. It is also linked with health benefits including the prevention of certain cancers and cardiovascular disease, the promotion of weight loss and enhanced performance of the immune system. Thus, there has been a significant rise in the demand for theanine. While theanine has been chemically and biologically synthesised, techniques to isolate theanine from natural sources remain an important area of research. In this review article, the properties and health benefits of theanine are summarised and the synthesis and isolation of theanine are reviewed and discussed. Future perspectives for the isolation of theanine from natural sources are also outlined.
Using speech recognition technology to assess foreign speakers' pronunciation of Dutch (1997)

Every year in the Netherlands lots of foreigners take part in examinations aimed at testing their proficiency in Dutch. In order to achieve greater efficiency and lower costs, attempts are being made to automate at least part of the testing procedure. Automatic testing of receptive skills such as reading and listening appears to be relatively simple, because the response tasks that are often used-multiple choice, matching
Evidence for Multiple Thyroxine-binding Sites in Human Prealbumin (1971)

Abstract The binding of thyroxine, triiodothyronine, and diiodothyronine to prealbumin, and to the prealbumin-retinol-binding protein (RBP) complex has been investigated by measurements of the quenched tryptophan fluorescence and by equilibrium rate dialysis. Fluorescence quenching revealed a single site of high affinity for prealbumin and the prealbumin-RBP complex. The binding constants under physiological conditions for the combination of prealbumin with a single molecule of thyroxine, triiodothyronine, and diiodothyronine were 1.1 x 107 m-1, 1.3 x 106 m-1, and 6.2 x 104 m-1, respectively. At pH 7.4, the binding of thyroxine to prealbumin was less sensitive to temperature changes within the range 2–40° than the binding between triiodothyronine and prealbumin. The calculated thermodynamic constants were compatible with the difference in ionization of thyroxine and triiodothyronine at pH 7.4. The phenolic hydroxyl group of thyroxine, bound to prealbumin, is highly ionized at this pH, whereas the phenolic hydroxyl group of triiodothyronine is essentially un-ionized. Variations of pH exerted a marked influence on the association constants for the thyroid hormones and prealbumin. Thus an increase in the binding strength under conditions promoting ionization of the phenolic hydroxyls indicated that this group participates in the binding with prealbumin. Reduced and carboxymethylated prealbumin did not show any binding to thyroxine but retained completely its affinity for the retinol-binding protein. The binding of thyroxine and triiodothyronine to prealbumin and to the prealbumin-RBP complex were also investigated over a wide range of ligand to protein ratios by means of equilibrium rate dialysis. Identical results were obtained for both hormones irrespective of whether prealbumin was free or in complex with RBP. A single site of high affinity, and three sites of weaker affinity were revealed. The differences in binding characteristics between the sites of high and low affinities would be most easily explained by assuming a negative homotropic effect of the thyroid hormone binding.
Dehydroepiandrosterone and Dihydrotestosterone Recognition by Human Estrogenic 17β-Hydroxysteroid Dehydrogenase (2000)

Steroid hormones share a very similar structure, but they behave distinctly. We present structures of human estrogenic 17beta-hydroxysteroid dehydrogenase (17beta-HSD1) complexes with dehydroepiandrosterone (DHEA) and dihydrotestosterone (DHT), providing the first pictures to date of DHEA and DHT bound to a protein. Comparisons of these structures with that of the enzyme complexed with the most potent estrogen, estradiol, revealed the structural basis and general model for sex hormone recognition and discrimination. Although the binding cavity is almost entirely composed of hydrophobic residues that can make only nonspecific interactions, the arrangement of residues is highly complementary to that of the estrogenic substrate. Relatively small changes in the shape of the steroid hormone can significantly affect the binding affinity and specificity. The K(m) of estrone is more than 1000-fold lower than that of DHEA and the K(m) of estradiol is about 10 times lower than that of DHT. The structures suggest that Leu-149 is the primary contributor to the discrimination of C-19 steroids and estrogens by 17beta-HSD1. The critical role of Leu-149 has been well confirmed by site-directed mutagenesis experiments, as the Leu-149 --> Val variant showed a significantly decreased K(m) for C-19 steroids while losing discrimination between estrogens and C-19 steroids. The electron density of DHEA also revealed a distortion of its 17-ketone toward a beta-oriented form, which approaches the transition-state conformation for DHEA reduction.
A Single Amino Acid Substitution, Gly117His, Confers Phosphotriesterase (Organophosphorus Acid Anhydride Hydrolase) Activity on Human Butyrylcholinesterase (1997)

The G117H mutant of human butyrylcholinesterase (EC 3.1.1.8) was expressed in Chinese hamster ovary cells. Substitution of Gly 117 with His to make the G117H mutant endowed butyrylcholinesterase with the ability to catalyze the hydrolysis of organophosphate esters. G117H was still able to hydrolyze butyrylthiocholine, benzoylcholine, and o-nitrophenyl butyrate, but in addition it had acquired the ability to hydrolyze the antiglaucoma drug echothiophate and the pesticide paraoxon. Wild-type butyrylcholinesterase was irreversibly inhibited by echothiophate and paraoxon, but G117H regained 100% activity within 2-3 min following reaction with these compounds. On a polyacrylamide gel, the same bands that stained for activity with butyrylthiocholine also stained for activity with echothiophate. G117H is the only enzyme known that hydrolyzes echothiophate. Diethoxyphosphorylated G117H aged with a half-time of 5.5 h, a rate 600 times slower than the rate of hydrolysis. Echothiophate and paraoxon were hydrolyzed with the same kcat of 0.75 min-1. This calculates to a rate acceleration of 100,000-fold for hydrolysis of echothiophate and paraoxon by the G117H mutant compared to the nonenzymatic rate.
Sodium cromoglycate in asthma: correlation between response and serum concentrations. (1988)

The clinical response to sodium cromoglycate treatment was compared with its concentration in serum. Twenty five children with asthma entered a 10 week trial of two baseline weeks followed by eight weeks of treatment by the inhalation of 20 mg of sodium cromoglycate spincaps four times a day. Individual clinical response was determined by the differences between baseline and treatment periods of: (a) percentage of symptomless days (delta score 0); (b) diary derived daily score for four symptoms (delta DS); and (c) peak expiratory flow rate (delta PEFR). At the end of the treatment period, patients inhaled a 20 mg spincap of sodium cromoglycate and the technique of inhalation was graded. Concentrations of sodium cromoglycate in serum were measured by radioimmunoassay in samples withdrawn 5 to 120 minutes after inhalation. Delta Score 0, delta DS, and delta PEFR correlated significantly with the area under the concentration time curve. Both the area under the sodium cromoglycate concentration time curve and clinical response correlated significantly with inhalation technique score. We suggest that response of children with asthma to inhalation treatment with sodium cromoglycate is correlated to its serum concentrations.
Discovery of 3-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), A Potent and Selective Inhibitor of the Fibroblast Growth Factor Receptor Family of Receptor Tyrosine Kinase (2011)

A novel series of N-aryl-N'-pyrimidin-4-yl ureas has been optimized to afford potent and selective inhibitors of the fibroblast growth factor receptor tyrosine kinases 1, 2, and 3 by rationally designing the substitution pattern of the aryl ring. On the basis of its in vitro profile, compound 1h (NVP-BGJ398) was selected for in vivo evaluation and showed significant antitumor activity in RT112 bladder cancer xenografts models overexpressing wild-type FGFR3. These results support the potential therapeutic use of 1h as a new anticancer agent.
Synthesis of nucleotide 5'-diphosphates from 5'-O-tosyl nucleosides (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of nucleotide 5'-diphosphates from 5'-O-tosyl nucleosidesV. Jo Davisson, Darrell R. Davis, Vyas M. Dixit, and C. Dale PoulterCite this: J. Org. Chem. 1987, 52, 9, 1794–1801Publication Date (Print):May 1, 1987Publication History Published online1 May 2002Published inissue 1 May 1987https://pubs.acs.org/doi/10.1021/jo00385a026https://doi.org/10.1021/jo00385a026research-articleACS PublicationsRequest reuse permissionsArticle Views2646Altmetric-Citations116LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Involvement of survival motor neuron (SMN) protein in cell death (2002)

Infantile spinal muscular atrophy (SMA) is caused by mutations in the survival motor neuron (SMN)1 gene. We investigated the role of human (h) SMN protein on cell death in PC12 and Rat-1 cells. hSMN prolonged cell survival in PC12 cells deprived of trophic support and in Rat-1 cells induced to die by activation of the proto-oncogene c-Myc, to similar magnitude as Bcl-2 or IAP-2. While hSMN was ineffective in inhibiting apoptosis induced by ultraviolet light (UV) or etoposide treatment in proliferating PC12 or Rat-1 cells, a protective effect was observed in terminally NGF/dBcAMP-differentiated PC12 cells. hSMN inhibited the onset of apoptosis in NGF/dBcAMP-deprived or UV-treated co-differentiated PC12 cells by preventing cytochrome c release and caspase-3 activation, indicating that its effects are through suppression of the mitochondrial apoptotic pathway. Expressing hSMN deleted for exon 7 (Delta7) or for exons 6 and 7 (Delta6/7), or with the SMA point mutant Y272C, resulted in loss of survival function. Moreover, these mutants also exhibited pro-apoptotic effects in Rat-1 cells. The localization pattern of full-length hSMN in PC12 and Rat-1 cells was similar to that of endogenous SMN: granular labelling in the cytoplasm and discrete fluorescence spots in the nucleus, some of which co-localized with p80 coilin, the characteristic marker of Cajal bodies. However, cytoplasmic and nuclear aggregates were often seen with hSMNDelta7, whereas the hSMNDelta6/7 mutant showed homogenous nuclear labelling that excluded the nucleolus. Thus, our results show that the C-terminal region is critical in suppression of apoptosis by SMN.
New antitumor antibiotic, LL-D05139.BETA.. Fermentation. isolation, structure determination and biological activities. (1987)

The LL-D05139 complex, containing LL-D05139 beta and azaserine, was recovered from the fermentation filtrate of Glycomyces harbinensis (NRRL 15337). A chemically defined medium was developed which favored the production of LL-D05139 beta. Antibiotic LL-D05139 beta was isolated from the fermentation filtrate by adsorption on granular carbon and further purified by chromatography on microcrystalline cellulose. Acid hydrolysis of LL-D05139 beta gave one molar equivalent each of alanine and serine. Both amino acids were found to have the L-configuration by GC analysis on a chiral column and alanine was assigned to be the N-terminal amino acid by Edman degradation. This information coupled with IR, UV, 1H NMR, 13C NMR and MS spectral data allowed us to assign the structure of LL-D05139 beta as alanylazaserine. LL-D05139 beta demonstrated greater antibacterial and biochemical induction assay activities than azaserine. The two drugs showed similar antitumor activities.
gp120 envelope glycoproteins of human immunodeficiency viruses competitively antagonize signaling by coreceptors CXCR4 and CCR5 (1998)

Signal transductions by the dual-function CXCR4 and CCR5 chemokine receptors/HIV type 1 (HIV-1) coreceptors were electrophysiologically monitored in Xenopus laevis oocytes that also coexpressed the viral receptor CD4 and a G protein-coupled inward-rectifying K+ channel (Kir 3.1). Large Kir 3.1-dependent currents generated in response to the corresponding chemokines (SDF-1alpha for CXCR4 and MIP-1alpha; MIP-1beta and RANTES for CCR5) were blocked by pertussis toxin, suggesting involvement of inhibitory guanine nucleotide-binding proteins. Prolonged exposures to chemokines caused substantial but incomplete desensitization of responses with time constants of 5-7 min and recovery time constants of 12-19 min. CXCR4 and CCR5 exhibited heterologous desensitization in this oocyte system, suggesting possible inhibition of a common downstream step in their signaling pathways. In contrast to chemokines, perfusion with monomeric or oligomeric preparations of the glycoprotein of Mr 120, 000 (gp120) derived from several isolates of HIV-1 did not activate signaling by CXCR4 or CCR5 regardless of CD4 coexpression. However, adsorption of the gp120 from a T-cell-tropic virus resulted in CD4-dependent antagonism of CXCR4 response to SDF-1alpha, whereas gp120 from macrophage-tropic viruses caused CD4-dependent antagonism of CCR5 response to MIP-1alpha. These antagonisms could be partially overcome by high concentrations of chemokines and were specific for coreceptors of the corresponding HIV-1 isolates, suggesting that they resulted from direct interactions of gp120-CD4 complexes with coreceptors and that they did not involve the desensitization pathway. These results indicate that monomeric or oligomeric gp120s specifically antagonize CXCR4 and CCR5 signaling in response to chemokines, but they do not exclude the possibility that gp120s might also function as weak agonists in some cells. The gp120-mediated disruption of CXCR4 and CCR5 signaling may contribute to AIDS pathogenesis.
A simple practice guide for dose conversion between animals and human (2016)

Understanding the concept of extrapolation of dose between species is important for pharmaceutical researchers when initiating new animal or human experiments. Interspecies allometric scaling for dose conversion from animal to human studies is one of the most controversial areas in clinical pharmacology. Allometric approach considers the differences in body surface area, which is associated with animal weight while extrapolating the doses of therapeutic agents among the species. This review provides basic information about translation of doses between species and estimation of starting dose for clinical trials using allometric scaling. The method of calculation of injection volume for parenteral formulation based on human equivalent dose is also briefed.
Analysis of Natural Allelic Variation of Arabidopsis Seed Germination and Seed Longevity Traits between the Accessions Landsberg erecta and Shakdara, Using a New Recombinant Inbred Line Population (2004)

Quantitative trait loci (QTL) mapping was used to identify loci controlling various aspects of seed longevity during storage and germination. Similar locations for QTLs controlling different traits might be an indication for a common genetic control of such traits. For this analysis we used a new recombinant inbred line population derived from a cross between the accessions Landsberg erecta (Ler) and Shakdara (Sha). A set of 114 F9 recombinant inbred lines was genotyped with 65 polymerase chain reaction-based markers and the phenotypic marker erecta. The traits analyzed were dormancy, speed of germination, seed sugar content, seed germination after a controlled deterioration test, hydrogen peroxide (H2O2) treatment, and on abscisic acid. Furthermore, the effects of heat stress, salt (NaCl) stress, osmotic (mannitol) stress, and natural aging were analyzed. For all traits one or more QTLs were identified, with some QTLs for different traits colocating. The relevance of colocation for mechanisms underlying the various traits is discussed.
Bragg gratings based on long-range surface plasmon-polariton waveguides: comparison of theory and experiment (2005)

Measured optical spectra are presented for a family of third-order uniform step-in-width Bragg gratings operating in the long-range surface plasmon-polariton mode supported by thin finite-width Au films in a homogeneous dielectric background. The spectra are compared quantitatively with theoretical predictions generated by a model proposed for the gratings. Physical measurements of critical features achieved on-wafer have been made and the results used in the theoretical model. The measured and modeled results are generally in good agreement. The largest reflectance measured among the set of gratings characterized is 47.4%, the bandwidths (full width at half maximum) measured range from 0.2 to 0.4 nm, and the measured Bragg wavelengths coincide to 1544.2 nm for all of the gratings.
Targeted delivery of platinum-based anticancer complexes (2013)

The most widely used anticancer drugs are platinum-based. Their efficacy might be improved by carriers which can transport large numbers of Pt centres, shield the drug from premature activation, and/or deliver Pt specifically to cancer cells using vectors which recognise specific targets. We describe recent progress using functionalized carbon nanotubes (CNTs) and nanorods, hollow Prussian blue (HPB), magnetic iron oxide and gold nanoparticles, liposomes, nanogels and polymers, as well as active targeting by conjugation to biodegradable proteins and peptides (e.g. EGF, heparin, herceptin, somatostatin and TAT). Spatially targeted activation of Pt(IV) prodrugs using light is also a promising approach. Interestingly, use of these new delivery and targeting systems for platinum drugs can lead to species with unusual reactivity which can kill cancer cells by new mechanisms.
Effect of introducing proline residues on the stability of Aspergillus awamori (1997)

In Aspergillus awamori glucoamylase, Ala27, Ala393, Ala435, Ser436 and Ser460 were replaced with proline residues, in order to stabilize the enzyme by forming more rigid peptide backbones. Specific activities were unaffected except for a decrease in Ser460-->Pro glucoamylase. Thermostability was increased in Ser436-->Pro glucoamylase, unchanged in Ala435-->Pro glucoamylase and decreased in Ala27-->Pro, Ala393-->Pro glucoamylases. As measured by circular dichroism, mutant glucoamylases Ala435-->Pro and Ser436-->Pro resisted unfolding caused by guanidine hydrochloride at pH 4.5 and 25 degrees C better than wild-type glucoamylase, whereas mutant glucoamylases Ala27-->Pro, Ala393-->Pro and Ser460-->Pro were more susceptible to unfolding than wild-type glucoamylase, reaching a level of 50% unfolded enzyme at guanidine hydrochloride concentrations 0.50-0.75 M lower than that of the wild-type enzyme. Mutations Ala435-->Pro and Ser436-->Pro are located in a non-regular structure, which is assumed to be stabilized by these mutations. The Ala27-->Pro residue is partially buried, which may result in unfavorable steric contact and/or regional strains; mutation Ala393-->Pro results in loss of a hydrogen bond, since the N of the proline residue does not have an extra hydrogen to act as donor; and mutation Ser480-->Pro eliminates an O-glycosylation site, which could explain how these mutations destabilized glucoamylase.
Repression of transcriptional activity at a distance by the evolutionary conserved KRAB domain present in a subfamily of zinc finger proteins (1994)

Sub-families of related zinc finger protein genes have been defined on the basis of evolutionarily conserved structural features found outside the C2-H2 finger repeats. Such elements include the FAX domain found in a large number of Xenopus ZFPs, the evolutionarily conserved KRAB (Krüppel-associated box) and the ZiN (zinc finger N-terminal) domains. Here we describe a new evolutionarily conserved motif within zinc finger proteins which we have named the leucine rich region (LeR). Since conserved modules in regulatory proteins may specify properties relevant to their action we have determined the functional capabilities of LeR and the KRAB domains in the regulation of gene transcription by fusing relevant regions to a heterologous DNA-binding domain (GAL4 DNA-binding domain). We found that the KRAB-A domain tethered to RNA polymerase II promoters by a GAL4 DNA-binding domain actively represses transcription in a distance-independent manner. KRAB-mediated repression is dependent on the dose of the GAL4-KRAB-A fusion protein and on the presence of GAL4 binding sites on the DNA. Conversely, the LeR domain did not modulate significantly the transcription. Our results indicate that the KRAB domain present in the non-finger region of many ZFP genes quenches transcription possibly due to specific protein-protein interactions between the KRAB-A domain and components of the proximal transcriptional apparatus.