gebhart/patrepeval huggingface dataset:
ARACHnase:An Evaluation of a Positive Control for Platelet Neutralization Procedure Testing With Seven Commercial Activated Partial Thromboplastin Time Reagents (1993)

ARACHnase (Hemostasis Diagnostics International Co., Denver, CO) is a normal plasma that contains a venom extract from the brown recluse spider, Loxosceles reclusa, which mimics the presence of a lupus anticoagulant (LA). Seven activated partial thromboplastin time (APTT) reagents were used for platelet neutralization procedure (PNP) testing with ARACHnase: Automated APTT (Organon-Teknika, Durham, NC); Thrombofax and Thrombosil (Ortho, Raritan, NJ); Actin and Actin FSL (Dade, Aguado, PR); and Thromboscreen-Kontact and Thromboscreen-APTT LS (Pacific-Hemostasis, Ventura, CA). ARACHnase consistently displayed a positive PNP result of greater than 5 seconds correction of the initial baseline APTT. Thus, ARACHnase may provide a positive control for LA testing, regardless of the choice of APTT reagent and activator/phospholipid combination.
Distance Measurement between Tyr10 and Met35 in Amyloid β by Site‐Directed Spin‐Labeling ESR Spectroscopy: Implications for the Stronger Neurotoxicity of Aβ42 than Aβ40 (2007)

The neurotoxicity of the 42-mer and 40-mer amyloid beta peptides (Abeta42 and Abeta40) is closely related to the radicalization at both Tyr10 and Met35. Abeta42 is more neurotoxic than Abeta40. Our previous structural analyses of Abeta42 suggested that Tyr10 and Met35 are brought closer together by the turn at positions 22 and 23, and the S-oxidized radical cation at position 35, which is the ultimate toxic radical species, can be produced effectively through oxidation by the phenoxy radical at position 10. To verify this idea, their separation was measured by site-directed spin labeling (MTSSL) by using ESR spectroscopy. Among the three kinds of Abeta42 derivatives, which are doubly or singly spin-labeled at position 10 and 35, only 10,35-MTSSL-Abeta42 showed a clear dipole coupling in continuous-wave ESR; this suggests that the intramolecular spin labels at position 10 and 35 in Abeta42 are located within approximately 15 A. In contrast, 10,35-MTSSL-Abeta40 did not give such signals. The distance between Tyr10 and Met35 in 10,35-MTSSL-Abeta40, which was successfully measured by pulsed ESR spectroscopy was 30 A long. The difference in the distance between Abeta42 and Abeta40 could explain in part the stronger neurotoxicity of Abeta42 compared to Abeta40.
Hemi‐gap‐junction channels in solitary horizontal cells of the catfish retina. (1992)

1. Solitary horizontal cells were isolated from catfish retinas and their membrane current was recorded with a whole-cell voltage clamp. Reducing the extracellular Ca2+ concentration produced a current that could be suppressed by dopamine. This Ca(2+)- and dopamine-sensitive current is hereafter termed I gamma. The voltage dependence, cytoplasmic regulation, and permeability of the I gamma channel suggest that it is half of a gap-junction channel. 2. I gamma was voltage and time dependent. In the steady state, the current-voltage relation displayed outward rectification at voltages more depolarized than 0 mV and a negative resistance region at voltages more hyperpolarized than -15 mV. The reversal potential was 3.3 +/- 1.5 mV when NaCl was the predominant extracellular salt and potassium-D-aspartate was the predominant intracellular salt. 3. The size of I gamma depended on the extracellular Ca2+ concentration. I gamma was maximal at external Ca2+ concentrations below 10 microM, half-maximal at 220 microM-Ca2+, and reduced to less than 4% of its maximum amplitude at external Ca2+ concentrations above 1 mM. Increasing the extracellular Ca2+ concentration reduced the amplitude of I gamma without changing the shape of the current-voltage relation or the kinetics of inactivation. Thus, rectification does not result from a voltage-dependent block by extracellular Ca2+. 4. Patches of cell membrane were voltage clamped in both the cell-attached and excised-patch configurations. In the cell-attached configuration, the addition of dopamine to the solution outside the patch pipette blocked the opening of channels within the membrane patch. Thus, dopamine closes I gamma channels by initiating an intracellular messenger cascade. In the excised-patch configuration, a maximum conductance of 145 pS was measured while Cs+ and tetraethylammonium+ (TEA+) were the only monovalent cations on both sides of the membrane. 5. The ability of dopamine to suppress I gamma was blocked by introducing an inhibitor of the cyclic AMP-dependent protein kinase, PKI5-24, into the cytoplasm. Thus, the action of dopamine is mediated by a pathway that includes the activation of a cyclic AMP-dependent kinase. 6. I gamma was suppressed by nitroprusside, an agent which activates guanylate cyclase and increases the intracellular cyclic GMP concentration. The effect of nitroprusside was not altered by the intracellular application of PKI5-24. Thus, nitroprusside suppresses I gamma through a pathway that does not include the activation of a cyclic AMP-dependent kinase.(ABSTRACT TRUNCATED AT 400 WORDS)
Maintenance of growth factor signaling through Ras in human colon carcinoma cells containing K-ras mutations (1996)

Fifty percent of human colon carcinomas contain activating mutations in the K-ras gene. However, whether these alterations in K-ras affect the function of Ras proteins in growth factor (GF) signal transduction is now known. Here we have characterized a previously defined human colon carcinoma cell model system for K-ras gene mutations and for altered levels of Ras protein expression and have examined whether these alterations affect Ras function in GF signal transduction. Sequence analysis of PCR-amplified K-ras gene fragments indicated that among the more aggressive cell lines, four had a normal K-ras sequence, whereas 3 others (isolated from the same human tumor) contained a mutation at codon 13. In contrast, all 7 of the less aggressive cell lines contained a mutation at either codon 12 or 13. In addition to the presence of a K-ras mutation, one cell line expressed higher levels of the K-Ras protein and displayed elevated Ras-GTP loading (in the absence of GF addition) compared with the other cell lines examined. Despite these alterations, the mitogenic GF combination epidermal growth factor + insulin + transferrin resulted in an activation of Ras and extracellular signal-regulated kinase 2. Collectively, our results indicate that the malignant phenotype of the cell lines was not correlated with the presence of K-ras mutations or with higher levels of Ras protein expression. Furthermore, K-ras mutations, high levels of K-Ras protein expression, and elevated Ras-GTP loading, as they occur naturally in human colon carcinomas, do not abolish the function of Ras in GF signaling.
Poisoning of human DNA topoisomerase I by ecteinascidin 743, an anticancer drug that selectively alkylates DNA in the minor groove (1999)

Ecteinascidin 743 (Et743, National Service Center 648766) is a potent antitumor agent from the Caribbean tunicate Ecteinascidia turbinata. Although Et743 is presently in clinical trials for human cancers, the mechanisms of antitumor activity of Et743 have not been elucidated. Et743 can alkylate selectively guanine N2 from the DNA minor groove, and this alkylation is reversed by DNA denaturation. Thus, Et743 differs from other DNA alkylating agents presently in the clinic (by both its biochemical activities and its profile of antitumor activity in preclinical models). In this study, we investigated cellular proteins that can bind to DNA alkylated by Et743. By using an oligonucleotide containing high-affinity Et743 binding sites and nuclear extracts from human leukemia CEM cells, we purified a 100-kDa protein as a cellular target of Et743 and identified it as topoisomerase I (top1). Purified top1 was then tested and found to produce cleavage complexes in the presence of Et743, whereas topoisomerase II had no effect. DNA alkylation was essential for the formation of top1-mediated cleavage complexes by Et743, and the distribution of the drug-induced top1 sites was different for Et743 and camptothecin. top1-DNA complexes were also detected in Et743-treated CEM cells by using cesium chloride gradient centrifugation followed by top1 immunoblotting. These data indicate that DNA minor groove alkylation by Et743 induces top1-mediated protein-linked DNA breaks and that top1 is a target for Et743 in vitro and in vivo.
Outcomes of Long-Term Testosterone Replacement in Older Hypogonadal Males: A Retrospective Analysis (1997)

To determine the complications, toxicities, and compliance of long term testosterone replacement in hypogonadal males, we retrospectively assessed 45 elderly hypogonadal men receiving testosterone replacement therapy and 27 hypogonadal men taking testosterone. Hypogonadism was defined as a bioavailable testosterone serum concentration of 72 ng/dL or less. Both groups received baseline physical examinations and blood tests. The testosterone-treated group received 200 mg testosterone enanthate or cypionate im every 2 weeks, and follow-up examinations and blood samplings were performed every 3 months. The control group had a single follow-up blood test and physical examination. There was no significant difference in the initial blood tests in the two groups. At 2 yr follow-up, only the hematocrit showed a statistically significant increase in the testosterone-treated group compared to the control group (P < 0.001). A decrease in the urea nitrogen to creatinine ratio and an increase in the prostate-specific antigen concentration was not statistically significant. Eleven (24%) of the testosterone-treated subjects developed polycythemia sufficient to require phlebotomy or the temporary withholding of testosterone, one third of which occurred less than 1 yr after starting testosterone treatment. There was no significant difference in the incidence of new illness in the two groups during the 2-yr follow-up. Although self-assessment of libido was dramatically improved in the testosterone-treated group (P < 0.0001), approximately one third of the subjects discontinued therapy. In conclusion, testosterone replacement therapy appears to be well tolerated by over 84% of the subjects. Long term testosterone replacement to date appears to be a safe and effective means of treating hypogonadal elderly males, provided that frequent follow-up blood tests and examinations are performed.
Synthesis of mono-, di- and tetra-alkyne functionalized calix[4]arenes: Reactions of these multipodal ligands with dicobalt octacarbonyl to give complexes which contain up to eight cobalt atoms (2009)

The functionalized mono-alkyne cone-monopropargyl p-tert-butylcalix[4]arene was synthesized by the reaction of p-tert-butylcalix[4]arene with K(2)CO(3) and 3-bromo-1-propyne. More prolonged reaction times led to the formation of the 1,3 cone bis(propargyl)calix[4]arene . The tetra-alkyne species cone-tetrapropargyl p-tert-butylcalix[4]arene and its conformational isomer, 1,3-alternate-tetrapropargylcalix[4]arene may both be prepared via related reaction sequences. The structures of the molecules and were both re-determined by single crystal X-ray diffraction studies. All four functionalized calixarenes react rapidly with dicobalt octacarbonyl to give [(calix[4]arene).{Co(2)(CO)(6)}(n)] species (n = 1, 2 or 4) in which the alkyne functionalities of the propargylcalix[4]arenes are ligated to one or more [Co(2)(CO)(6)] groups. Two products could be harvested from the reaction of [Co(2)(CO)(8)] with the bis-propargyl-calixarene , depending on the reaction conditions and relative molar quantities of the reactants: complex , [1,3-cone bis(propargyl)calix[4]arene.{Co(2)(CO)(6)}(2)], in which each alkyne group is bonded to a [Co(2)(CO)(6)] group, and complex , [1,3-cone bis(propargyl)calix[4]arene.{Co(2)(CO)(6)}], which contains a unligated alkyne and an alkyne group bonded to a Co(2)(CO)(6) unit. The structures of the tetracobalt and octacobalt complexes and were established by single crystal X-ray diffraction studies.
The immune modulator Linomide prevents neuronal death in injured peripheral nerves of the mouse (1998)

Neuronal death after injury or disease could result from imbalanced cytokine expression. Linomide (LS-2616, quinoline-3-carboxamide), a synthetic immunomodulator with effects on cytokine production, suppresses autoimmune diseases of the nervous system. Here adult mice were pre-treated with 200 mg/kg/day of Linomide for 9 days, after which the sciatic nerves were crushed. After another 10 days of Linomide treatment the dorsal root ganglia were dissected out and stained for apoptosis, either immediately or after 2 days in culture, which increases cell death. Superior cervical ganglia were also cultured for 2 days. The Linomide pretreatment profoundly reduced (approximately 60-80%) the injury-induced apoptotic death of neurons and satellite cells in both systems. The results suggest that modulation of the inflammatory cytokine cascade is a promising road to nerve cell rescue.
Structure of the Calcium-Dependent Lectin Domain from a Rat Mannose-Binding Protein Determined by MAD Phasing (1991)

Calcium-dependent (C-type) animal lectins participate in many cell surface recognition events mediated by protein-carbohydrate interactions. The C-type lectin family includes cell adhesion molecules, endocytic receptors, and extracellular matrix proteins. Mammalian mannose-binding proteins are C-type lectins that function in antibody-independent host defense against pathogens. The crystal structure of the carbohydrate-recognition domain of a rat mannose-binding protein, determined as the holmium-substituted complex by multiwavelength anomalous dispersion (MAD) phasing, reveals an unusual fold consisting of two distinct regions, one of which contains extensive nonregular secondary structure stabilized by two holmium ions. The structure explains the conservation of 32 residues in all C-type carbohydrate-recognition domains, suggesting that the fold seen here is common to these domains. The strong anomalous scattering observed at the Ho LIII edge demonstrates that traditional heavy atom complexes will be generally amenable to the MAD phasing method.
Biotechnology of Endophytic Fungi of Grasses (2018)

Detailing current research on grass endophytes, this work presents procedures for isolation, inoculation, fungus and plant tissue culturing, staining and molecular methodology. Chapters on the ecology of grass hosts document the benefits of endophytes to grass hosts and discuss this topic in terms of a mathematical model. Chemical constituents of infected grasses and methods to alleviate toxic effects are identified. The current use of endophytes to increase plant hardiness in turf and forage grasses is explained. Techniques for screening and selecting endophytes and for genetic modification of endophytes are described. The text discusses the impact of endophyte-infected grasses on the environment, looks at the response of endophyte-infected grasses and grasslands to increased atmospheric CO2 and radiation, and provides techniques and procedures for studying endophytes.
Angiotensin II induces cellular hypertrophy in cultured murine proximal tubular cells (1990)

In the present study we demonstrate that a murine proximal tubular cell line (MCT cells), expressing angiotensin II (ANG II) receptors [dissociation constant (Kd) = 0.89 nM; receptor density (R0) = 46,900 receptors/cell] in culture, can be induced to hypertrophy after the daily addition of exogenous ANG II (10(-8) M). This hypertrophic response was characterized by an increase in total cellular protein content, by an enhancement of [3H]leucine incorporation into precipitable proteins, and by an augmentation in cell size by cytofluorography. This ANG II effect producing MCT cell enlargement was demonstrable in the absence of cellular proliferation. Proliferation of MCT cells, however, could be induced by epidermal growth factor (EGF) or platelet-derived growth factor (PDGF), and pretreatment of rested MCT cells with ANG II further enhanced EGF-induced cell division. ANG II-induced hypertrophy in MCT cells was factor specific, in that it could be blocked with saralasin, and not induced by angiotensin I (ANG I). This hypertrophic response was also independent of prostaglandin E2 synthesis but was transducible by pertussis toxin-sensitive G proteins and involved, to some extent, the activation of Na(+)-H+ exchange. ANG II, as well as EGF and/or PDGF, moreover, could induce the cellular oncogenes c-fos, c-myc, c-N-ras, but not c-cis, which suggests that early gene activation is probably not a specific prerequisite for hypertrophy. Our findings demonstrate that ANG II, in culture, can be a single-factor event capable of inducing hypertrophy in proximal tubular cells.
Measurement of the accurate mass of a 50 MDa infectious virus (2016)

At over 50 MDa, phage P22 is the largest object with a well-defined molar mass to be analyzed by mass spectrometry. The narrow measured mass distribution indicates that the virions survive the transition into the gas phase intact. Copyright © 2016 John Wiley & Sons, Ltd.
Dominant Thermodynamic Role of the Third Independent Receptor Binding Site in the Receptor-Associated Protein RAP (2001)

The 39 kDa receptor-associated protein (RAP) is a three-domain escort protein in the secretory pathway for several members of the low-density lipoprotein receptor (LDLR) family of endocytic receptors, including the LDLR-related protein (LRP). The minimal functional unit of LRP required for efficient binding to RAP is composed of complement-type repeat (CR)-domain pairs, located in clusters on the extracellular part of LRP. Here we investigate the binding of full-length RAP and isolated RAP domains 1−3 to an ubiquitin-fused CR-domain pair consisting of the fifth and sixth CR domains of LRP (U-CR56). As shown by isothermal titration calorimetric analysis of simple RAP domains as well as adjoined RAP domains, all three RAP domains bind to this CR-domain pair in a noncooperative way. The binding of U-CR56 to RAP domains 1 and 2 is (at room temperature) enthalpically driven with an entropy penalty (KD = 2.77 × 10-6 M and 1.85 × 10-5 M, respectively), whereas RAP domain 3 binds with a substantially lower enthalpy, but is favored due to a positive entropic contribution (KD = 1.71 × 10-7 M). The heat capacity change for complex formation between RAP domain 1 and the CR-domain pair is −1.65 kJ K-1 mol-1. There is an indication of a conformational change in RAP domain 3 upon binding in the surface plasmon resonance analysis of the interaction. The different mechanisms of binding to RAP domains 1 and 3 are further substantiated by the different effects on binding of mutations of the Asp and Trp residues in the LRP CR5 or CR6 domains, which are important for the recognition of several ligands.
A hybrid approach for automated trading systems (2002)

Automated trading systems have been proved to be very helpful to traders and investors. However, most of the existing systems implemented with any statistical or neural network approaches are incapable to give accurate advice because they cannot capture the off-market information for which most of it is non-numeric. In this paper, an automated trading system which integrates the techniques from technical analysis, pattern recognition, and knowledge-based system is presented. The numeric data from the stock is processed by both the statistical method and feature extraction. The intermediate results are then used by the rule-based system which captures the off-market information in form of facts and rules. After that, the advice can be generated through the inference with the data stored in the database. For resolving the inconsistencies among the intermediate results from different components of the system, concepts from the fuzzy set theories are employed. Further, some data from the past Hang Seng Index (HSI) is used for illustration.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Critical Role of O-Linked β-N-Acetylglucosamine Transferase in Prostate Cancer Invasion, Angiogenesis, and Metastasis (2012)

Cancer cells universally increase glucose and glutamine consumption, leading to the altered metabolic state known as the Warburg effect; one metabolic pathway, highly dependent on glucose and glutamine, is the hexosamine biosynthetic pathway. Increased flux through the hexosamine biosynthetic pathway leads to increases in the post-translational addition of O-linked β-N-acetylglucosamine (O-GlcNAc) to various nuclear and cytosolic proteins. A number of these target proteins are implicated in cancer, and recently, O-GlcNAcylation was shown to play a role in breast cancer; however, O-GlcNAcylation in other cancers remains poorly defined. Here, we show that O-GlcNAc transferase (OGT) is overexpressed in prostate cancer compared with normal prostate epithelium and that OGT protein and O-GlcNAc levels are elevated in prostate carcinoma cell lines. Reducing O-GlcNAcylation in PC3-ML cells was associated with reduced expression of matrix metalloproteinase (MMP)-2, MMP-9, and VEGF, resulting in inhibition of invasion and angiogenesis. OGT-mediated regulation of invasion and angiogenesis was dependent upon regulation of the oncogenic transcription factor FoxM1, a key regulator of invasion and angiogenesis, as reducing OGT expression led to increased FoxM1 protein degradation. Conversely, overexpression of a degradation-resistant FoxM1 mutant abrogated OGT RNAi-mediated effects on invasion, MMP levels, angiogenesis, and VEGF expression. Using a mouse model of metastasis, we found that reduction of OGT expression blocked bone metastasis. Altogether, these data suggest that as prostate cancer cells alter glucose and glutamine levels, O-GlcNAc modifications and OGT levels become elevated and are required for regulation of malignant properties, implicating OGT as a novel therapeutic target in the treatment of cancer.
Characterization of recombination intermediates from DNA injected into Xenopus laevis oocytes: evidence for a nonconservative mechanism of homologous recombination. (1991)

Homologous recombination between DNA molecules injected into Xenopus laevis oocyte nuclei is extremely efficient if injected molecules have overlapping homologous ends. Earlier work demonstrated that ends of linear molecules are degraded by a 5'----3' exonuclease activity, yielding 3' tails that participate in recombination. Here, we have characterized intermediates further advanced along the recombination pathway. The intermediates were identified by their unique electrophoretic and kinetic properties. Two-dimensional gel electrophoresis and hybridization with oligonucleotide probes showed that the intermediates had heteroduplex junctions within their homologous overlaps in which strands ending 3' were full length and those ending 5' were shortened. Additional characterization suggested that these intermediates had formed by the annealing of complementary 3' tails. Annealed junctions made in vitro were rapidly processed to products, indicating that they are on the normal recombination pathway. These results support a nonconservative, single-strand annealing mode of recombination. This recombination mechanism appears to be shared by many organisms, including bacteria, fungi, plants, and mammals.