gebhart/patrepeval huggingface dataset:
Genotype: A Crucial but Not Unique Factor Affecting the Clinical Phenotypes in Fabry Disease (2016)

Numerous α-galactosidase A (α-gal A) gene (GLA) mutations have been identified in Fabry disease (FD), but studies on genotype-phenotype correlation are limited. This study evaluated the features of GLA gene mutations and genotype-phenotype relationship in Chinese FD patients. Gene sequencing results, demographic information, clinical history, and laboratory findings were collected from 73 Chinese FD patients. Totally 47 mutations were identified, including 23 novel mutations which might be pathogenic. For male patients, those with frameshift and nonsense mutations presented the classical FD, whereas those with missense mutations presented both of classical and atypical phenotypes. Interestingly, two male patients with missense mutation p.R356G from two unrelated families, and two with p.R301Q from one family presented different phenotypes. A statistically significant association was found between the levels of α-gal A enzyme activity and ocular changes in males, though no significant association was found between residual enzyme activity level and genotype or clinical phenotypes. For female patients, six out of seven with frameshift mutations and one out of nine with missense mutation presented the classical FD, and α-gal A activity in those patients was found to be significantly lower than that of patients with atypical phenotypes (13.73 vs. 46.32 nmol/ml/h/mg). Our findings suggest that the α-gal A activity might be associated with the clinical severity in female patients with FD. But no obvious associations between activity level of α-gal A and genotype or clinical phenotypes were found for male patients.
Structure of the glucocorticoid receptor in intact cells in the absence of hormone. (1992)

The nonactivated glucocorticoid receptor (Mr approximately 330,000, Strokes radius = 82 A) contained in cell extracts and complexed with a steroidal ligand was previously investigated by chemical cross-linking. It was identified as a heterotetramer composed of one receptor polypeptide, two molecules of the 90-kDa heat shock protein hsp90, and one 59-kDa protein subunit (Rexin, M., Busch, W., and Gehring, U. (1991) J. Biol. Chem. 266, 24601-24605). We now have used the cross-linking technique to investigate the receptor structure in intact WEHI-7 mouse lymphoma cells at 37 degrees C and under steroid-free conditions. Using immunochemical methods we show that the receptor present in whole cells likewise exists as a high molecular weight structure of Strokes radius 82 A. It has a subunit composition identical to that of the nonactivated receptor-steroid complex in cell extracts. This is the first account of a steroid hormone receptor in its native state as it is contained in target cells under physiological conditions and before a hormonal signal is received.
Molecular characterization of the humoral response to the 41-kilodalton flagellar antigen of Borrelia burgdorferi, the Lyme disease agent (1991)

The earliest humoral response in patients infected with Borrelia burgdorferi, the agent of Lyme disease, is directed against the spirochete's 41-kDa flagellar antigen. In order to map the epitopes recognized on this antigen, 11 overlapping fragments spanning the flagellin gene were cloned by polymerase chain reaction and inserted into an Escherichia coli expression vector which directed their expression as fusion proteins containing glutathione S-transferase at the N terminus and a flagellin fragment at the C terminus. Affinity-purified fusion proteins were assayed for reactivity on Western blots (immunoblots) with sera from patients with late-stage Lyme disease. The same immunodominant domain was bound by sera from 17 of 18 patients. This domain (comprising amino acids 197 to 241) does not share significant homology with other bacterial flagellins and therefore may be useful in serological testing for Lyme disease.
Structure–function studies of ω‐atracotoxin, a potent antagonist of insect voltage‐gated calcium channels (1999)

The omega-atracotoxins are a family of 36 to 37-residue peptide neurotoxins that block insect but not mammalian voltage-gated calcium channels. The high phylogenetic specificity of these toxins recommends them as lead compounds for targeting insects that have developed resistance to chemical pesticides. We have begun to examine structure-function relationships in the omega-atracotoxins in order to explore the molecular basis of their activity and phylogenetic specificity. By probing the venom of the Blue Mountains funnel-web spider, Hadronyche versuta, for insecticidal toxins with masses close to that of omega-atracotoxin-Hv1a (omega-ACTX-Hv1a), we have isolated and sequenced five additional omega-atracotoxins. Five of the six omega-atracotoxins isolated from the venom of H. versuta (omega-ACTX-Hv1a to -Hv1e) differ from one another by only 1-3 residues and have similar insecticidal potencies. In contrast, omega-ACTX-Hv1f differs from the other toxins by up to 10 residues and it has markedly reduced insecticidal potency, thus providing information on key functional residues. The new atracotoxin sequences have revealed that the three N-terminal residues are highly conserved. Despite the fact that these residues are structurally disordered in solution we show here, by a series of N-terminal truncations, that they contribute significantly to insecticidal potency. However, loss of activity does not correlate with deletion of highly conserved residues, which leads us to propose that the disposition of the N-terminal charge, rather than the chemical properties of the N-terminal residues themselves, may be critical for the activity of omega-atracotoxin on insect calcium channels.
Activation of soluble splenic cell guanylate cyclase by prostaglandin endoperoxides and fatty acid hydroperoxides (1978)

Purified prostaglandin endoperoxides (PGG2 and PGH2) and hydroperoxides (15-OOH-PGE2) as well as fatty acid hydroperoxides (12-OOH-20:4, 15-00H-20:4, and 13-OOH-18:2) were examined as effectors of soluble splenic cell guanylate cyclase activity. The procedures described (in the miniprint supplement) for the preparation, purification, and characterization of these components circumvented the use of diethyl ether which obscured effects of lipid effectors because of contaminants presumed to be ether peroxides which were stimulatory to the cyclase. Addition of prostaglandin endoperoxides or fatty acid hydroperoxides to the reaction mixture led to a time-dependent activation of guanylate cyclase activity; 2.5- to 5-fold stimulation was seen during the first 6 min. The degree of stimulation and rate of activation were dependent on the concentration of the fatty acid effector; when initial velocities (6 min) were assessed half-maximal stimulation was achieved in the range of 2 to 3 micrometer. However, by extending the incubation time to 90 min similar maximal increases in specific activity could be achieved with 3 or 10 micrometer PGG2 or PGH2. Activation of guanylate cyclase upon addition of prostaglandin endoperoxides or fatty acid hydroperoxides was prevented or reversed by the thiol reductants dithiothreitol (3 to 5 mM) or glutathione (10 to 15 mM). Na2S2O4, not known as an effective reducing agent of disulfides, prevented but was relatively ineffective in reversing activation after it had been induced by PGG2. Pretreatment of the enzyme preparation with increasing concentrations of N-ethylmaleimide in the range of 0.01 to 1.0 mM prevented activation by PGG2 without affecting basal guanylate cyclase activity. These observations indicate that fatty acid hydroperoxides and prostaglandin endoperoxides promote activation of the cyclase by oxidation of enzyme-related thiol functions. In contrast PGE2, PGF2a, hydroxy fatty acids (13-OH-18:2, 12-OH-20:4) as well as saturated (18:0) monoenoic (18:1), dienoic (18:2), and tetraenoic (20:4) fatty acids were ineffective in promoting cyclase activation in the range of 1 to 10 micrometer. Studies to identify the species of the rapidly metabolized prostaglandin endoperoxides that serve as effectors of the cyclase indicated that PGG2 but not 15-OOH-PGE2 (the major buffer-rearrangement product of PGG2) is most likely an activator. In the case of PGH2, a rapidly generated (30 s) metabolite of PGH2 was found which contained a hydroperoxy or endoperoxy functional group and was equally as effective as PGH2 as an apparent activator of the enzyme. The combined effects of PGG2 and dehydroascorbic acid, another class of activator, exhibited additivity with respect to the rate at which the time-dependent activation was induced. These results suggest that activation of soluble guanylate cyclase from splenic cells can be achieved by the oxidation of sulfhydryl groups that may be associated with specific hydrophobic sites of the enzyme or a related regulatory component.
[D-TRP32]Neuropeptide Y: A Competitive Antagonist of NPY in Rat Hypothalamus (1994)

Neuropeptide Y (NPY) is a potent orexigenic peptide. Structure-activity studies have revealed that nearly the entire sequence of NPY is required to elicit feeding responses. Therefore, in order to develop antagonistic peptides for NPY-induced feeding, we synthesized full-length analogs of NPY, substituting D-Trp in the C-terminal receptor binding region, and screened their activity in rat hypothalamus. Although [D-Trp36]NPY and [D-Trp34]NPY inhibited isoproterenol-stimulated hypothalamic membrane adenylate cyclase activity, [D-Trp32]NPY exhibited no intrinsic activity. Furthermore, [D-Trp32]NPY inhibited [125I]NPY binding to rat hypothalamic membranes with a potency comparable to that of NPY. The presence of 30 and 300 nM concentrations of [D-Trp32]NPY shifted the inhibitory dose-response curve of NPY on isoproterenol-stimulated hypothalamic membrane adenylate cyclase activity parallel to the right with comparable KB values. Moreover, in vivo experiments in rats revealed that [D-Trp32]NPY (10 micrograms) significantly attenuated the 1-h feeding response induced by NPY (1 microgram). Several other substitutions at position 32 including 2-D-Nal resulted in agonist activity, suggesting that there are strict structural requirements to induce the antagonistic property in NPY. These findings confirm that [D-Trp32]NPY is a competitive antagonist of NPY in both in vitro and in vivo systems. Analogs based on [D-Trp32]NPY may have potential clinical application, since NPY has been implicated in the pathophysiology of a number of feeding disorders including obesity, anorexia, and bulimia.
Elastic and inelastic light scattering in flow cytometry (1983)

A review of the fundamental aspects of elastic light scattering suggests that information about the shape and internal structure may best be obtained from signals measured in the backscattering directions. Size information can be most readily extracted from forward scattering signals. Spectral analysis of scattered signals with incident white light is a subject that merits further study. Signals from cells that have been stained with fluorescent dyes are proportional to dye content in the usual flow-cytometric configuration except in the case of dense, strongly anisometric structures such as sperm cells. The recent discovery that Raman signals from molecules adsorbed on small silver particles are strongly enhanced suggests the possibility of utilizing this effect for identification of molecular species inside biological cells.
A video surveillance architecture for alarm generation and video sequences retrieval (2003)

This paper presents a system for automatic video surveillance applications. The system has been designed to monitor outdoor environments such as car parks or streets, providing the human operator with a symbolic description of the scene. The final task of the architecture is to automatically provide alarms when specific events of interest are detected. In this way the level of automation of the system is increased as well as overall performances. One of the main drawbacks of traditional video surveillance systems lies in the alarm generation. This task has to be visually performed by the human operators with intrinsic limitation. The possibility of having this process automated is here described within the design of an architecture capable of acquiring, processing and successfully storing data coming from one or more sensors.
YKL-40 Is a Differential Diagnostic Marker for Histologic Subtypes of High-Grade Gliomas (2005)

Glioblastomas show strikingly more YKL-40 expression than anaplastic oligodendrogliomas. Only 2 of 37 glioblastomas showed completely negative YKL-40 staining in both tumor cells and extracellular matrix, whereas 18 of 29 anaplastic oligodendrogliomas were completely negative in non-microgemistocytic tumor cells and extracellular matrix. Tumor cell staining intensity was also markedly different: 84% of glioblastomas showed strong staining intensities of 2+ or 3+ whereas 76% of anaplastic oligodendrogliomas either did not stain or stained at only 1+. YKL-40 staining provided a better class distinction of glioblastoma versus anaplastic oligodendroglioma than glial fibrillary acidic protein, the current standard immunohistochemical marker used to distinguish diagnostically challenging gliomas. Moreover, a combination of YKL-40 and glial fibrillary acidic protein immunohistochemistry afforded even greater diagnostic accuracy in anaplastic oligodendrogliomas.
Near-Infrared Acousto-Optic Filtered Spectroscopic Microscopy: A Solid-State Approach to Chemical Imaging (1992)

A new instrumental approach for performing spectroscopic imaging microscopy is described. The instrument integrates an acousto-optic tunable filter (AOTF) and charge-coupled-device (CCD) detector with an infinity-corrected microscope for operation in the visible and near-infrared (NIR) spectral regions. Images at moderate spectral resolution (2 nm) and high spatial resolution (1 μim) can be collected rapidly. Data are presented containing 128 × 128 pixels, although images with significantly larger formats can be collected in approximately the same time. In operation, the CCD is used as a true imaging detector, while wavelength selectivity is provided by using the AOTF and quartz tungsten halogen lamp to create a tunable source. The instrument is entirely solid state, containing no moving parts, and can be readily configured for both absorption and reflectance spectroscopies. We present visible absorption spectral images of human epithelial cells, as well as NIR vibrational absorption images of a hydrated phospholipid suspension, to demonstrate the potential of the technique in the study of biological materials. Extensions and future applications of this work are discussed.
IL-23 induces human osteoclastogenesis via IL-17 in vitro, and anti-IL-23 antibody attenuates collagen-induced arthritis in rats (2007)

This study demonstrates that IL-23 stimulates the differentiation of human osteoclasts from peripheral blood mononuclear cells (PBMC). Furthermore, in vivo blockade of endogenous IL-23 activity by treatment with anti-IL-23 antibody attenuates collagen-induced arthritis in rats by preventing both inflammation and bone destruction. IL-23 induced human osteoclastogenesis in cultures of PBMC in the absence of osteoblasts or exogenous soluble-receptor activator of NF-kappaB ligand (RANKL). This IL-23-induced osteoclastogenesis was inhibited by osteoprotegerin, anti-IL-17 antibody, and etanercept, suggesting that RANKL, IL-17, and TNF-alpha are involved. In addition, we found the ratio of production levels of IL-17 to those of IFN-gamma from activated human T cells was elevated at 1 to 10 ng/ml IL-23. The inductive effect of IL-17 and the inhibitory effect of IFN-gamma on osteoclastogenesis indicate that the balance of these two cytokines is particularly important. We also demonstrated that IL-23 administered at a later stage significantly reduced paw volume in rats with collagen-induced arthritis, in a dose-dependent manner. Furthermore, anti-IL-23 antibody reduced synovial tissue inflammation and bone destruction in these rats. These findings suggest that IL-23 is important in human osteoclastogenesis and that neutralizing IL-23 after onset of collagen-induced arthritis has therapeutic potential. Thus, controlling IL-23 production and function could be a strategy for preventing inflammation and bone destruction in patients with rheumatoid arthritis.
THE USE OF RADIOLABELED ANTI-CD33 ANTIBODY TO AUGMENT MARROW IRRADIATION PRIOR TO MARROW TRANSPLANTATION FOR ACUTE MYELOGENOUS LEUKEMIA (1992)

Disease recurrence remains a major limitation to the use of marrow transplantation to treat leukemia. Previous transplant studies have demonstrated that higher doses of total-body irradiation result in less disease recurrence, but more toxicity. In this study, the possibility of delivering radiotherapy specifically to marrow using a radiolabeled anti-CD33 antibody (p67) was explored. Biodistribution studies were performed in nine patients using .05-.5 mg/kg p67 trace-labeled with 131I. In most patients initial specific uptake of 131I-p67 in the marrow was seen, but the half-life of the radiolabel in the marrow space was relatively brief, ranging from 9–41 hr, presumably due to modulation of the 131I-p67-CD33 complex with subsequent digestion and release of 131I from the marrow space. In four of nine patients these biodistribution studies demonstrated that with 131I-p67 marrow and spleen would receive more radiation than any normal nonhematopoietic organ, and therefore these four patients were treated with 110–330 mCi 131I conjugated to p67 followed by a standard transplant regimen of cyclophosphamide plus 12 Gy TBI. All four patients tolerated the procedure well and three of the four are alive in remission 195–477 days posttransplant. This study demonstrates the feasibility of using a radiolabeled antimyeloid antibody as part of a marrow transplant preparative regimen and also highlights a major limitation of using conventionally labeled anti-CD33—namely, the short residence time in marrow. Strategies to overcome this limitation include the use of alternative labeling techniques or the selection of cell surface stable antigens as targets.
Inducers of interferon and host resistance. II. Multistranded synthetic polynucleotide complexes. (1967)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Sero-Reactivity to Microbial Components in Crohn's Disease Is Associated with Disease Severity and Progression, but not NOD2/CARD15 Genotype (2004)

Reactivity to microbial components is associated with severe CD characterized by small bowel involvement, frequent disease progression, longer disease duration, and greater need for intestinal surgery.
Cryptic plasmids in glutamic acid-producing bacteria. (1984)

(1984). Cryptic Plasmids in Glutamic Acid-producing Bacteria. Agricultural and Biological Chemistry: Vol. 48, No. 11, pp. 2901-2903.
Tutorial on high-level synthesis (1988)

High-level synthesis takes an abstract behavioral specification of a digital system and finds a register-transfer level structure that realizes the given behavior. In this tutorial we will examine the high-level synthesis task, showing how it can be decomposed into a number of distinct but not independent subtasks. Then we will present the techniques that have been developed for solving those subtasks. Finally, we will note those areas related to high-level synthesis that are still open problems.
LC-MS-MS analysis of 2-pyridylacetic acid, a major metabolite of betahistine: application to a pharmacokinetic study in healthy volunteers (2003)

1. A sensitive liquid chromatographic-tandem mass spectrometric assay was developed and validated to determine the major metabolite of betahistine, 2-pyridylacetic acid, in human plasma.2. The analyte was extracted from plasma samples by liquid–liquid extraction and analysed using liquid chromatography-tandem mass spectrometry with an electrospray ionization interface. The method has a lower limit of quantitation of 1 ng ml−1 for a 0.5-ml plasma aliquot. The intra- and interday precision (relative standard deviation), calculated from quality control (QC) samples, was less than 10%. Accuracy as determined from QC samples was within ±7%.3. The validated method was successfully applied to a pharmacokinetic study of betahistine in healthy volunteers. After oral administration of a single dose of 24 mg betahistine mesylate to 20 healthy Chinese male volunteers, Cmax was 339.4 ng ml−1 (range 77.3–776.4 ng ml−1). The t1/2 was 5.2 h (range 2.0−1−11.4 h). The AUC0−t obtained was 1153.5 ng ml−1 h (range 278.5–3150.8 ng ml−1 h). The disposition of the metabolite exhibited a marked interindividual variation.4. The plasma concentrations of the parent drug were less than 0.5 ng ml−1, suggesting that it undergoes almost complete first-pass metabolism. The reported two active metabolites were not detected in the plasma of any volunteer. Although there is no evidence that the major metabolite has pharmacological activity, the clinical importance of 2-pyridylacetic acid in humans should be reinvestigated.
Productivity loss in brainstorming groups: Toward the solution of a riddle. (1987)

We conducted four experiments to investigate free riding, evaluation apprehension, and production blocking as explanations of difference in brainstorming productivity typically observed between real and nominal groups. In Experiment 1, we manipulated assessment expectations in group and individual brainstorming. Although productivity was higher when subjects worked under personal rather than collective assessment instructions, type of session still had a major impact on brainstorming productivity under conditions that eliminated temptation to free ride. Experiment 2 demonstrated that inducing evaluation apprehension reduced productivity in individual brainstorming. However, failure to find an interaction between evaluation apprehension and type of session in Experiment 3 raises doubts about evaluation apprehension as a major explanation of productivity loss in brainstorming groups. Finally, by manipulating blocking directly, we determined in Experiment 4 that production blocking accounted for most of productivity loss of real brainstorming groups. The processes underlying production blocking are discussed, and a motivational interpretation of blocking is offered. In his influential book, Osborn (1957) suggested brainstorming as a method of group problem solving that considerably increases quality and quantity of ideas produced by group members. Brainstorming groups are traditionally given instructions designed to free individual members from inhibiting effects of self-criticism and criticism by others during problem-solving session. The rules behind brainstorming are as follows: keep in mind that more ideas better and wilder ideas better, improve or combine ideas already suggested; and do not be critical. Osborn (1957) claimed that if these rules are followed the average person can think up twice as many ideas when working with a group than when working alone (p. 229).