gebhart/patrepeval huggingface dataset:
The Cbl family of ubiquitin ligases: critical negative regulators of tyrosine kinase signaling in the immune system (2002)

The Cbl family of proteins are evolutionarily conserved negative regulators of activated tyrosine kinase-coupled receptors. Antigen receptors are prominent targets of negative regulation by the Cbl family members, Cbl and Cbl-b, which proteins function as ubiquitin ligases. Cbl and Cbl-b contain substrate recognition domains that interact specifically with activated protein tyrosine kinases of the Src and Syk/ZAP-70 families. Cbl-mediated ubiquitination of these kinases leads to their degradation, resulting in attenuation of receptor signals. Cbl may also control activation-induced monoubiquitination of antigen receptors, thus facilitating their delivery to lysosomes for subsequent degradation. Finally, the interactions of Cbl proteins with downstream targets of tyrosine kinases, such as PI-3-kinase and Vav, could provide an additional mechanism to attenuate receptor signaling. By targeting multiple components of antigen receptor signaling for degradation, the Cbl protein family provides a critical mechanism to ensure an appropriate immune response. The hyperresponsiveness of Cbl(-/-) and Cbl-b(-/-) lymphocytes and the autoimmune phenotype of Cbl-b(-/-) mice lend strong support for this proposal. The ability to control early receptor signals through regulated protein degradation provides a novel paradigm of immunoregulation.
Ultrastable, Highly Luminescent Organic–Inorganic Perovskite–Polymer Composite Films (2016)

A simple yet general swelling-deswelling microencapsulation strategy has been developed to achieve well dispersed and intimately passivated crystalline organic-inorganic perovskites nanoparticles within polymer matrixes and results in a series of highly luminescent CH<sub>3</sub> NH<sub>3</sub> PbBr<sub>3</sub> (MAPbBr<sub>3</sub> )-polymer composite films with unprecedented water and thermal stabilities and superior color purity.
Towards Automated Training of Legal Problem Solving. (1994)

An examination of Dutch research on legal case solving revealed that few law students get systematic instruction or testing in the technique of legal problem solving. The research being conducted at the Department of Computer Science and Law at the University of Amsterdam focuses on identifying the different functions in legal reasoning tasks in order to develop computational models which realize these functions. The major assumptions of the theory are: (1) in artificial legal reasoning, a separation should be made between reasoning about events in the world and reasoning about leul consequences; and (2) the real legal reasoning (when no reasoning about the world is conceived) should be viewed as a process of rule application and conflict resolution, rather than drawing logical inferences. The consequences of these assumptions for knowledge representation are, that in representing regulation knowledge, knowledge about the actions, agents, and objects should be separated from the representation of the regulation. In an intelligent tutoring system (ITS), the system and the student perform the task simultaneously; the way the system reasons has to be functional for educational purposes. The domain under study is administrative procedural law. The main educational goal of a student solving a case is to learn to handle the theoretical concepts in a specific field of law, to learn to find and apply the specific body of norms, to learn to olan the courses of action and to learn to construct a solution which is legally correct. A conceptual model of assessment, a typical task in the domain of law, is under development as part of the library of interpretation models; an interpretation model is an abstract conceptual model of a set of problem solving methods in terms of inference steps. The model can be used in i:he process of acquiring knowledge for building artificial legal problem solvers. (AEF) Towards automated training of legal problem solving Antoinette J. Muntjewerff Department of Computer Science and Law 00 Faculty of Law, University of Amsterdam Klovensersburgwal 72, 1012 CZ Amsterdam, The Netherlands 00 00 e-mail antoi@lrijur.uva.nl
Clinical significance of arginase in colorectal cancer (1992)

Arginase, a potent immune inhibitor, existed in much greater abundance in the cytoplasm of cancer cells than in normal cells. Serum arginase levels from 31 patients with colorectal adenocarcinoma were determined by using enzyme immunoassay (mean ± standard error = 18.96 f 4.83 ng/ml) and showed to be significantly higher than levels from control subjects (n = 115, 3.09 ± 0.22 ng/ml) (P < 0.005). Surgical samples of 15 patients were individually homogenized and assayed by the same method and revealed that the arginase level in tissues with colorectal cancer was two times greater than the level found in normal mucosal tissues (1.74 k 0.31 μg/g tissue versus 0.77 ± 0.09 μg/g tissue, P < 0.005). However, the serum arginase levels in patients with colorectal cancer were independent of their carcinoembryonic antigen (CEA) levels (n = 27, arginase 11.81 & 1.88 ng/ml, CEA 17.31 & 4.24 ng/ml, r = 0.084, P = 0.666). The results suggested that serum arginase level can be a valuable criterion for preoperative evaluation and possibly postoperative follow-up study. It can also combine with CEA determination to intensify the clinical assessment for colorectal cancer. Cancer 1992; 70:733–736.
Microbial production of methylketones: properties of purified yeast secondary alcohol dehydrogenase (1981)

Secondary alcohol dehydrogenase (SADH) was purified from extracts of a methanol-grown yeast, Pichia sp. The purified enzyme was homogeneous as judged by ultracentrifugation and by polyacrylamide gel electrophoresis. The purified SADH has a molecular weight of 98,000 as determined by gel filtration and 102,000 as determined by sedimentation equilibrium analysis. The sedimentation constant s/sub 20,w/ was 6.0. The subunit size of the SADH was 48,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, indicating that it consists of two subunits. The purified SADH contained two atoms of zinc per mole of enzyme protein. SADH catalyzed the oxidation of secondary alcohols. Primary alcohols (C/sub 1/ to C/sub 8/ tested) were not oxidized. The purified SADH and extracts of various yeasts and bacteria also catalyzed the reduction of methylketones to the corresponding secondary alcohols in the presence of reduced NAD/sup +/ as an electron donor. Both reactions (oxidation of secondary alcohols in the presence of NAD/sup +/ and reduction of methylketones in the presence of reduced NAD/sup +/) catalyzed by the purified SADH were inhibited by metal-chelating agents, thio reagent, and by antisera prepared against the purified enzyme. The apparent K/sub m/ values for NAD/sup +/, reduced NAD/sup +/, reduced NAD/sup +/,more » 2-butanol, and 2-butanone are 0.05, 0.1, 0.4, and 1 mM, respectively. The purified enzyme preferentially oxidized (-)-2-butanol and (-)-2-octanol, the rate of oxidation of (+)-2-butanol and (+)-2-octanol was 36% and 13% of that of 100% with (-)-2-butanol and (-)-2-octanol, respectively. The K/sub m/ values for (-)-2-butanol and (+)-2-butanol were 3.0 and 0.75 mM, respectively. Antisera prepared against purified Pichia SADH cross-reacted with the SADH derived from bacteria. This suggests difference in immunological properties between yeast and bacterial SADH.« less
Vancomycin pharmacokinetics in burn patients and intravenous drug abusers (1990)

The pharmacokinetics of vancomycin were evaluated in 34 patients (10 burn patients, 14 intravenous drug abusers [IVDA], and 10 controls). Multiple serum samples were drawn following a 1-h vancomycin infusion at steady state over an 8- to 12-h dosing interval. Pharmacokinetic parameters were derived by noncompartmental analysis. There were no significant differences among the groups with respect to age, weight, serum creatinine, volume of distribution, or protein binding. Burn patients had a significantly higher creatinine clearance than did IVDA or controls. Vancomycin clearances averaged 142.8, 98.0, and 67.7 ml/min in burn patients, IVDA, and controls, respectively. The renal clearance of vancomycin was also higher in burn patients than in the other groups. IVDA tended to have a higher vancomycin clearance (31% higher) than did controls, but the difference was not statistically significant. Vancomycin clearance was much higher in burn patients requiring dosage individualization and close monitoring. A considerable amount of vancomycin was eliminated through renal tubular secretion, making dosage predictions based on creatinine clearance more difficult. Further work with IVDA will be needed to determine if they represent a group requiring aggressive vancomycin dosages.
The binding of Pseudomonas aeruginosa pili to glycosphingolipids is a tip‐associated event involving the C‐terminal region of the structural pilin subunit (1994)

Pili are one of the adhesins of Pseudomonas aeruginosa that mediate adherence to epithelial cell-surface receptors. The pili of P. aeruginosa strains PAK and PAO were examined and found to bind gangliotetraosyl ceramide (asialo-GM1) and, to a lesser extend, II3N-acetylneuraminosylgangliotetraosyl ceramide (GM1) in solid-phase binding assays. Asialo-GM1, but not GM1, inhibited both PAK and PAO pili binding to immobilized asialo-GM1 on the microtitre plate. PAO pili competitively inhibited PAK pili binding to asialo-GM1, suggesting the presence of a structurally similar receptor-binding domain in both pilus types. The interaction between asialo-GM1 and pili occurs at the pilus tip as asialo-GM1 coated colloidal gold only decorates the tip of purified pili. Three sets of evidence suggest that the C-terminal disulphide-bonded region of the Pseudomonas pilin is exposed at the tip of the pilus: (i) immunocytochemical studies indicate that P. aeruginosa pili have a basal-tip structural differentiation where the monoclonal antibody (mAb) PK3B recognizes an antigenic epitope displayed only on the basal ends of pili (produced by shearing) while the mAb PK99H, whose antigenic epitope resides in residues 134-140 (Wong et al., 1992), binds only to the tip of PAK pili; (ii) synthetic peptides, PAK(128-144)ox-OH and PAO(128-144)ox-OH, which correspond to the C-terminal disulphide-bonded region of Pseudomonas pilin are able to bind to asialo-GM1 and inhibit the binding of pili to the glycolipid; (iii) PK99H was shown to block PAK pilus binding to asialo-GM1.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of Feed and Bleed Rate on Hybridoma Cells in an Acoustic Perfusion Bioreactor: Metabolic Analysis (2007)

For the development of optimal perfusion processes, insight into the effect of feed and bleed rate on cell growth, productivity, and metabolism is essential. In the here presented study the effect of the feed and bleed rate on cell metabolism was investigated using metabolic flux analysis. Under all tested feed and bleed rates the biomass concentration as calculated from the nitrogen balance (biomass-nitrogen) increased linearly with an increase in feed rate, as would be expected. However, depending on the size of the feed and bleed rate, this increase was attained in two different ways. At low feed and bleed rates (Region I) the increase was obtained through an increase in viable-cell concentration, while the cellular-nitrogen content remained constant. At high feed and bleed rates (Region II) the increase was attained through an increase in cellular-nitrogen content, while the cell concentration remained constant. Per gram biomass-nitrogen, the specific consumption and production rates of the majority of the nutrients and products were identical in both regions, as were most of the fluxes. The major difference between the two regions was an increased flux from pyruvate to lactate and a decreased flux of pyruvate toward citrate in region II. The decreased in-flux at the level of citrate can either be balanced by a decreased out-flux toward lipid biosynthesis leading to a lower fraction of lipids in the cell, by a decreased out-flux toward the citric acid cycle resulting in a decreased energy generation, or by a combination of these. Finally, the specific productivity increases less than the nitrogen content per cell in region II, which implies that for obtaining maximum production rates it is important to increase the cell density and not only the biomass density.
A novel, rapid method for the isolation of terminal sequences from yeast artificial chromosome (YAC) clones (1990)

The recent development of yeast artificial chromosome (YAC) vectors has provided a system for cloning fragments that are over ten times larger than those that can be cloned in more established systems. We have developed a method for the rapid isolation of terminal sequences from YAC clones. The YAC clone is digested with a range of restriction enzymes, a common linker is ligated to the DNA fragments and terminal sequences are amplified using a vector specific primer and a linker specific primer. Sequence data derived from these terminal specific products can be used to design primers for a further round of screening to isolate overlapping clones. The method also provides a convenient method of generating Sequence Tagged Sites for the mapping of complex genomes.
Lewis Acid-Promoted Hetero Diels−Alder Cycloaddition of α-Acetoxynitroso Dienophiles (2004)

[reaction: see text] alpha-Acetoxynitroso compound 3 has been prepared as a new stable, isolable, and reactive dienophile in nitroso Diels-Alder reactions. The yield of the [4 + 2] cycloaddition of alpha-acetoxynitroso dienophile with 1,3-dienes could be enhanced in the presence of 20 mol % Lewis acid. An unexpected retro hetero-Michael reaction from 26 was observed, leading to the cleavage of the N-O bond of the cycloadduct. This tandem nitroso Diels-Alder/retro hetero-Michael sequence has been used with cyclic and acyclic 1,3-dienes.
Sensitized Detection of Inhibitory Fragments and Iterative Development of Non‐Peptidic Protease Inhibitors by Dynamic Ligation Screening (2008)

A potential anti-SARS drug has been developed by dynamic ligation screening (DLS), by which nucleophilic fragments are directed to the protein's active site by reversible reaction with an aldehyde inhibitor. Their inhibitory effect is detected by competition with a fluorogenic enzyme substrate. With this concept, low-affinity fragments binding specifically to the active site are quickly identified in a functional enzyme assay.
Mucosal immunization with filamentous hemagglutinin protects against Bordetella pertussis respiratory infection (1992)

Mucosal immunization of mice with purified Bordetella pertussis filamentous hemagglutinin (FHA), by either the respiratory or the gut route, was found to protect against B. pertussis infection of the trachea and lungs. Intranasal immunization of BALB/c and (C57BL/6 x C3H/HeN)F1 adult female mice with FHA prior to B. pertussis aerosol challenge resulted in a 2 to 3 log reduction in number of bacteria recovered from the lungs and the tracheas of immunized mice in comparison to unimmunized controls. Intraduodenal immunization of adult mice with FHA before infection also resulted in approximately a 2 log reduction in the recovery of bacteria from the lungs and the tracheas of immunized mice in comparison to unimmunized controls. Immunoglobulin A and immunoglobulin G anti-FHA were both detected in bronchoalveolar lavage fluids of mucosally immunized mice. Limiting dilution analysis revealed a 60-fold increase in the frequency of FHA-specific B cells isolated from the lungs of mice immunized intranasally with FHA in comparison to unimmunized control mice. These data suggest that both gut and respiratory mucosal immunization with a major adhesin of B. pertussis generates a specific immune response in the respiratory tract that may serve as one means of mitigating subsequent B. pertussis respiratory infection.
Front and rear image generation module for depth-fused 3-D display (2006)

We have developed an image generation module for the depth-fused 3-D (DFD) display, which can show 3-D images using the DFD visual illusion. The module generates the front and rear images from the 2-D original image and depth-map image. The module uses a field programmable gate array (FPGA). This module shows 3-D images at the full video rate and easily provides a video interface for DFD display users
Unique Recognition of Activin and Inhibin by Polyclonal Antibodies to Inhibin Subunits (1996)

Inhibin-A is a glycoprotein composed of an alpha subunit containing a glycosylation site and a beta A subunit, whereas activin-A is a homodimer of two inhibin beta A subunits. We examined the recognition of activin-A and inhibin-A by several antisera to the alpha or beta A subunit, and factors affecting the recognition. A total of six polyclonal antibodies to inhibin subunits, i.e., two antisera to a peptide fragment of the alpha subunit [alpha (1-19) and alpha (1-26)], and four antisera to the beta A subunit [beta A (1-10), beta A (70-79), beta A (87-99), and beta A (94-105)], was generated. On Western blot analysis, the anti-beta A (87-99) and beta A (94-105) sera recognized recombinant human activin-A but not inhibin-A under non-reducing conditions. When inhibin-A was deglycosylated with N-glycosidase-F, inhibin-A could be recognized by the anti-beta A (87-99) and beta A (94-105) sera. In addition, when activin-A bound to a nitrocellulose membrane was pre-incubated with recombinant human follistatin, the recognition of activin-A by the anti- beta A (87-99) and beta A (94-105) sera was decreased. These results suggested that the lower affinity of follistatin to inhibin-A than to activin-A might be likely explained as reflecting a site associated with the glycosylation of inhibin-A. However, the exposure of amino acids 87-105 of the inhibin beta A subunit on the molecular surface through deglycosylation did not increase the affinity of inhibin-A for follistatin but rather resulted in poor binding with follistatin. The present data suggest that (1) amino acids 87-105 of the inhibin/activin beta A subunit are located on the molecular surface, although this region of inhibin-A is concealed by the carbohydrate chain of the alpha subunit, (2) the region responsible for follistatin binding within the activin beta A subunit is spanned by amino acids 87-105, and (3) the mode of binding of inhibin-A to follistatin is quite different from that of activin-A to follistatin, and the former may be influenced by glycosylation.
Selective formation of hydrogen bonded cocrystals between a sulfonamide and aromatic carboxylic acids in the solid state (1995)

Co-grinding sulfadimidine [4-amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide] with several aromatic carboxylic acids in the solid state produces 1 : 1 hydrogen bonded cocrystals which are identical to those obtained from reaction between the components in solution. The kinetics of solid state formation of selected cocrystals have been measured using X-ray powder diffraction. Sulfadimidine selectively cocrystallizes with 2-aminobenzoic acid when the latter is present in binary mixtures of acids. Solid state reaction of the cocrystal sulfadimidine·2-hydroxybenzoic acid with 2-aminobenzoic acid results in elimination of 2-hydroxybenzoic acid and formation of the cocrystal sulfadimidine·2-aminobenzoic acid.
Palladium-Catalyzed Direct Synthesis of Carbazoles via One-Pot N-Arylation and Oxidative Biaryl Coupling: Synthesis and Mechanistic Study (2009)

An efficient catalytic system has been developed for the synthesis of carbazoles by one-pot N-arylation and oxidative biaryl coupling. A significant substituent effect of the diarylamine intermediate on oxidative coupling was observed. Mechanistic studies of oxidative coupling, including trapping of reaction intermediates and kinetic isotope effect experiments, are also presented.
[Clinical evaluation of serum NSE and CEA in primary lung cancer patients]. (1986)

The clinical value of serum neuron specific enolase (NSE) as a tumor marker was evaluated in comparison with simultaneously measured serum CEA, using 74 cases of lung cancers, 13 cases of non-tumorous and non-neurological disease and 28 normal volunteers. The results obtained were as follows: Thirty-five out of the 74 lung cancer cases showed positive serum NSE levels. However, none of the cases of non-tumorous, non-neurological disease and normal volunteers demonstrated more than 10ng/ml NSE which was significantly different from the results of lung cancer cases. We found a higher degree of NSE positiveness in cases of small cell carcinoma than in cases of other histological types. However, no obvious difference of CEA positiveness between any histological types was revealed. Both serum NSE and CEA showed an increase in positive rate in parallel with the progress of stages, including 80.4% of cases of stages III and IV disease which had positive serum levels of both or either of the two markers. However, we could not find any obvious correlation between serum NSE and CEA. The serum levels of both markers clearly decreased after surgery, serum CEA level being considered to be a better reflection of host tumor burden than NSE. In conclusion, the simultaneous testing of serum NSE and CEA is considered to be very useful for evaluating the clinical course or the effect of cancer therapy in lung cancer patients, with higher specificity and sensitivity.
TOR: a new orphan receptor expressed in the thymus that can modulate retinoid and thyroid hormone signals. (1995)

Vitamin A and other fat-soluble hormones and vitamins have important roles as modulators of essential biological processes such as homeostasis, development, differentiation, and oncogenesis and also as regulators of the immune system. The active form of vitamin A, retinoic acid, as well as vitamin D3 and thyroid hormones exert their actions by binding to specific nuclear receptors that represent one subfamily of the steroid/thyroid hormone receptor superfamily. To identify new members of the retinoid/thyroid hormone receptor subfamily that could play a role in the immune system, a screening of a T cell cDNA library was performed using a retinoid X receptor probe. A clone was isolated encoding a novel nuclear receptor expressed mainly in the thymus and T cell lines. This new receptor, TOR (thymus orphan receptor), is most closely related in both its DNA-binding domain and ligand-binding domain, 90% and 53%, respectively, to ROR alpha/RZR alpha and clusters with these two receptors and RZR beta in a phylogenetic tree, when both the DNA-binding domain and the ligand-binding domain sequences of nuclear receptors are compared. Thus, TOR is part of a subgroup of receptors, one of which has recently been reported to be activated by melatonin. TOR binds specifically to a direct repeat of the half-site sequence 5'-AGGTCA-3' with a four- or five-nucleotide spacer, DNA sequences that also serve as binding sites for thyroid hormone (TR), and retinoic acid receptors (RAR). In transient transfection experiments TOR does not activate a reporter gene carrying these sequences in the absence or the presence of any known nuclear receptor ligands. TOR, however, is able to repress TR and RAR activity on DR-4-TREs or DR-5-RAREs, respectively. Therefore, our data suggest that TOR, similar to COUP-TF, can negatively regulate retinoic acid and thyroid hormone signals. However, the response elements recognized by TOR and COUP-TF differ as do the expression patterns of these receptors. Thus, one important role of TOR could be to modulate retinoid and thyroid hormone signals in the thymus.