gebhart/patrepeval huggingface dataset:
Design, Synthesis, and Antiviral Activity of α-Nucleosides:  d- and l-Isomers of Lyxofuranosyl- and (5-Deoxylyxofuranosyl)benzimidazoles (1998)

Several 2-substituted alpha-D- and alpha-L-lyxofuranosyl and 5-deoxylyxofuranosyl derivatives of 5,6-dicholro-2-(isopropylamino)-1-(beta-L-ribofuranosyl) benzimidazole (1263W94) and 2,5,6-trichloro-1(beta-D-ribofuranosyl)benzimidazole (TCRB) were synthesized and evaluated for activity against two herpesviruses (HSV-1 and HCMV) and for their cytotoxicity against HFF and KB cells. Condensation of 1,2,3,5-tetra-O-acetyl-L-lyxofuranose (2a) with 2,5,6-trichlorobenzimidazole (1) yielded the alpha-nucleoside 3a. The 2-bromo derivative and 2-methylamino derivative were prepared by treatment of 3a with HBr followed by deprotection or from methylamine, respectively. Compound 3a was deprotected and the resultant nucleoside used to prepare the 2-cyclopropylamino and 2-isopropylamino derivatives. The 2-alkylthio nucleosides were prepared by condensing 2a with 5,6-dichlorobenzimidazole-2-thione followed by deprotection. Alkylation of this adduct gave the 2-methylthio and 2-benzylthio derivatives. Condensation of 5-deoxy-1,2,3-tri-O-acetyl-L-lyxofuranosyl, prepared from L-lyxose, with 1 or 2-bromo-5,6-dichlorobenzimidazole (15), followed by deprotection, gave the 2-chloro or 2-bromo-5'-deoxylyxo-furanosyl derivative, respectively. The cyclopropylamino derivative was prepared from the 2-chloro derivative. All D-isomers were prepared in an analogous fashion from D-lyxose. Either compounds were inactive against HSV-1 or weak activity was poorly separated from cytotoxicity. In contrast, the 2-halogen derivatives in both the alpha-lyxose and 5-deoxy-alpha-lyxose series were active against the Towne strain of HCMV. The 5-deoxy alpha-L analogues were the most active, IC50's = 0.2-0.4 microM, plaque assay; IC90's = 0.2-2 microM, yield reduction assay. All of the 2-isopropylamino or 2-cyclopropylamino derivatives were less active (IC50's = 60-100 microM, plaque assay; IC90's = 17-100 microM, yield reduction assay) and were not cytotoxic. The methylamino, thio, and methylthio derivatives were neither active nor cytotoxic. The benzylthio derivatives were weakly active, but this activity was poorly separated from cytotoxicity. The alpha-lyxose L-isomers were more active in a plaque assay against the AD169 strain of HCMV compared to the Towne strain, thereby providing additional evidence of antiviral specificity.
Rimonabant, a CB1 antagonist, blocks nicotine-conditioned place preferences (2004)

The effects of Rimonabant (SR141716), an antagonist at cannabinoid CB1 receptors, were evaluated in animal models for subjective and rewarding effects of nicotine. Acute administration of 1 or 3 mg/kg SR141716 blocked expression of nicotine-induced conditioned place preferences. SR141716 (0.3-3 mg/kg) was also studied in rats trained to discriminate nicotine from saline under a fixed-ratio schedule of food delivery. In contrast to nicotine replacement therapy and bupropion, SR141716 did not have nicotine-like discriminative effects and did not alter the dose-response curve for nicotine discrimination. These findings support the proposed use of SR141716 for smoking cessation and indicate that it would selectively reduce the influence of environmental stimuli that contribute to persistent smoking behavior, without affecting subjective responses to nicotine.
Coordinated multipoint transmission and reception in LTE-advanced: deployment scenarios and operational challenges (2012)

3GPP has completed a study on coordinated multipoint transmission and reception techniques to facilitate cooperative communications across multiple transmission and reception points (e.g., cells) for the LTE-Advanced system. In CoMP operation, multiple points coordinate with each other in such a way that the transmission signals from/to other points do not incur serious interference or even can be exploited as a meaningful signal. The goal of the study is to evaluate the potential performance benefits of CoMP techniques and the implementation aspects including the complexity of the standards support for CoMP. This article discusses some of the deployment scenarios in which CoMP techniques will likely be most beneficial and provides an overview of CoMP schemes that might be supported in LTE-Advanced given the modern silicon/DSP technologies and backhaul designs available today. In addition, practical implementation and operational challenges are discussed. We also assess the performance benefits of CoMP in these deployment scenarios with traffic varying from low to high load.
The Fate of the Cyclic Nitramine Explosive RDX in Natural Soil (2001)

The sorption-desorption behavior and long-term fate of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) was examined in sterilized and nonsterilized topsoil. Results of this study indicate that although RDX is not extensively sorbed by the topsoil (Ks(d) of 0.83 L/kg), sorption is nearly irreversible. Furthermore, there was no difference in the sorption behavior for sterile and nonsterile topsoil. However, over the longterm, RDX completely disappeared within 5 weeks in nonsterile topsoil, and hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX), hexahydro-1,3-dinitroso-5-nitro-1,3,5-triazine (DNX), and hexahydro-1,3,5-trinitroso-1,3,5-triazine (TNX) metabolites formed in the aqueous phase. Over the same period, recovery of RDX from sterile topsoil was high (55-99%), and the nitroso metabolites were not detected. Only traces of RDX were mineralized to CO2 and N2O by the indigenous microorganisms in nonsterile topsoil. Of the RDX that was mineralized to N2O, one N originated from the ring and the other from the nitro group substituent, as determined using N15 ring-labeled RDX. However, N2O from RDX represented only 3% of the total N2O that formed from the process of nitrification/denitrification.
Human Action Recognition Based on AdaBoost Algorithm for Feature Extraction (2014)

A novel action recognition method based on AdaBoost algorithm is proposed in this paper. The method can select the most discriminative sample subset from a large amount of raw features of training data, so it can reduce the recognition computational complexity with high accuracy. The histogram of oriented gradient feature (HOG) descriptor is utilized to represent raw feature data. In order to select the most discriminative samples, Gadabouts algorithm is used to extract the raw feature data. The nearest neighbor classifier algorithm is utilized to test the proposed method on the UCF Sports database. Experiment results show that the method not only achieve the better recognition rate but also greatly improve the speed of recognition.
Keys to successful organ procurement: An experience-based review of clinical practices at a high-performing health-care organization (2017)

Organ procurement (OP) from donors after brain death and circulatory death represents the primary source of transplanted organs. Despite favorable laws and regulations, OP continues to face challenges for a number of reasons, including institutional, personal, and societal barriers. This focused review presents some of the key components of a successful OP program at a large, high-performing regional health network. This review focuses on effective team approaches, aggressive resuscitative strategies, optimal communication, family support, and community outreach efforts.
Formation of glycosidases in batch and continuous culture of Bacteroides fragilis (1978)

Nine strains of bacteroides fragilis were cultivated in stirred fermentors and tested for their ability to produce glycosidases. B. fragilis subsp. vulgatus B70 was used for optimizing the production of glycosidases. The highest bacterial yield was obtained in proteose peptone-yeast extract medium. The optimum pH for maximal bacterial yield was 7.0, and the optimum temperature for growth was 37 degrees C. The formation of glycosidases was optimal between pH 6.5 and 7.5, and the optimum temperature for synthesis of glycosidases was between 33 and 37 degrees C. Culture under controlled conditions in fermentors gave more reproducible production of glycosidases than static cultures in bottles. The strain was also grown in continuous culture at a dilution rate of 0.1 liter/h at pH 7.0 and 37 degrees C with a yield of 2.0 mg of dry weight per ml in the complex medium. The formation of glycosidases remained constant during the entire continuous process.
Cytokines as positive and negative regulators of tumor promotion and progression. (1992)

Cytokines can have both negative and positive effects on cells undergoing carcinogenesis. The promotion and progression phases of carcinogenesis may be affected by autocrine loops involving cytokines with growth factor activities such as IL-1, IL-2, low molecular weight B cell growth factor, TNF, IL-3, GM-CSF, M-CSF and IL-9. Aberrations in cytokine receptors such as the truncated EGF receptor present in v-erB promotes the growth of neoplastic cells. Aberrant signaling mechanisms, as found with spleen focus-forming virus, which mimics the ligand that activates the erythropoietin receptor, can also contribute to proliferation of preneoplastic and neoplastic cells. In contrast, cytokines such as interferons, LIF, TGF-beta, TNF and leukoregulin, with antiproliferative or differentiating activities, are sometimes capable of inhibiting carcinogenesis. Transfection of tumor cells with cytokine genes, such as IL-2, IL-4 and TNF, can cause suppression of in vivo tumor cell growth by mobilizing host immune and inflammatory cell responses. Thus cytokines and their receptors may play a direct role in early stages of tumor cell development and growth.
Safety and Immunogenicity of UBI HIV-1 MN Octameric V3 Peptide Vaccine Administered by Subcutaneous Injection (1997)

Twenty-four HIV-seronegative men, at high risk of HIV infection, were recruited into a phase I/II safety and immunogenicity trial of a prototype HIV vaccine. The immunogen was a synthetic, monovalent, octameric HIV-1MN V3 peptide in an aluminum hydroxide (alum) adjuvant. The vaccine had been evaluated previously using a standard 0-, 1-, 6-month intramuscular schedule and was found to stimulate neutralizing antibody in 60-90% of volunteers. Participants were randomized to receive either 500 micrograms (n = 10; high dose) or 100 micrograms (n = 10; low dose) of immunogen or placebo (alum alone; n = 4) at 0, 1, and 6 months by subcutaneous injection. Responses to the immunogen were evaluated by enzyme-linked immunosorbent assay (ELISA)-detectable antibody and by proliferative responses. Safety was monitored by both clinical assessment and regular review with a clinical psychologist. No serious adverse experiences were observed following administration of the assigned medication. One individual (placebo) seroconverted while on study, following exposure to HIV. After the vaccination course only four individuals (three high dose and one low dose) had ELISA-detectable antibody against the immunogen. In the evaluable samples, from 19 volunteers, only 7 vaccine recipients (3 high dose and 4 low dose) had demonstrable lymphoproliferative responses to preparations of the immunogen. Subcutaneous administration of its candidate vaccine was safe but did not result in uniform or robust immunological responses.
Humoral Responses to Peptides Correlate with Overall Survival in Advanced Cancer Patients Vaccinated with Peptides Based on Pre-existing, Peptide-Specific Cellular Responses (2004)

Abstract Purpose: The aim of this study is to find a laboratory marker for overall survival in advanced cancer patients who were vaccinated with peptides based on pre-existing, peptide-specific CTL precursors in the circulation. Experimental Design: A group of 113 patients with advanced cancer (28 colorectal, 22 prostate, 15 lung, 14 gastric, and 34 other cancers) was enrolled in a Phase I clinical study of peptide vaccination in which peptide-specific CTL precursors of prevaccination peripheral blood mononuclear cells were measured, followed by vaccination with these peptides (maximum of four). For cellular responses, pre and postvaccination (sixth) peripheral blood mononuclear cells were provided for measurement of both peptide-specific CTL precursors by IFN-γ release assay and tumor reactivity by 51Cr release assay. Delayed type hypersensitivity was also measured. For humoral response, pre and postvaccination (sixth) sera were provided for measurement of peptide-reactive IgG by an ELISA. Results: The median survival time and 1-year survival rate of the total cases were 346 ± 64.9 days and 44.6%, respectively, and those of patients vaccinated more than six times (n = 91) were 409 ± 15 days and 54.4%, respectively. In these 91 patients, the overall survival of patients whose sera showed increased levels of peptide-reactive IgG (n = 60) was significantly more prolonged (P = 0.0003) than that of patients whose sera did not (n = 31), whereas none of cellular responses correlated with overall survival. Conclusions: Peptide-specific IgG in postvaccination sera could be a suitable laboratory maker for the prediction of prolonged survival in advanced cancer patients vaccinated with peptides based on pre-existing CTL precursors.
Glucose‐based optimization of CHO‐cell perfusion cultures (2001)

Perfusion cultures of CHO cells producing t-PA were performed using acoustic filter cell retention. A robust off-line glucose analysis and predictive control protocol was developed to maintain the process within approximately 0.5 mM of the glucose set point, without the need for a more fallible on-line sensor. Glucose usage (the difference between the inlet and reactor glucose concentrations) provided an easily measured indicator of overall medium utilization for mapping acceptable ranges of operation, including the edge of failure. Earlier onset of perfusion with a ramping glucose set point (1.5 mM/d) resulted in improved growth and consistency during the perfusion culture start-up. At steady state, the t-PA concentration variability increased gradually with increasing glucose usage up to approximately 22 mM, then up to 24 mM the variability increased threefold. Peak t-PA concentrations of over 90 mg/L were obtained by controlling at a glucose usage of approximately 24 mM, but these t-PA levels were not sustainable for more than 3 days. A consistent t-PA concentration of 40 mg/L was obtained at a glucose usage of 21.5 mM.
Glycogen hyperphosphorylation underlies lafora body formation (2010)

We identify a single common modification, glycogen hyperphosphorylation, as the root cause of Lafora body pathogenesis.
Human thrombomodulin: complete cDNA sequence and chromosome localization of the gene (1987)

A human umbilical vein endothelial cell cDNA library in lambda gt11 was screened for expression of thrombomodulin antigens with affinity-purified rabbit polyclonal anti-thrombomodulin immunoglobulin G (IgG) and mouse monoclonal anti-human thrombomodulin IgG. Among 7 million recombinant clones screened, 12 were recognized by both antibodies. Two of these, lambda HTm10 and lambda HTm12, were shown to encode thrombomodulin by comparison of the amino acid sequence deduced from the nucleotide sequence to the amino acid sequence determined directly from tryptic peptides of thrombomodulin. Thrombomodulin mRNA was estimated to be 3.7 kilobases in length by Northern blot analysis of endothelial cell and placental poly(A)+ RNA. Thrombomodulin mRNA was not detected in human brain, HepG2 hepatoma cells, or the monocytic U937 cell line. Additional cDNA clones were selected by hybridization with the 1.2-kilobase insert of lambda HTm10. One isolate, lambda HTm15, contained a 3693 base pair cDNA insert with an apparent 5'-noncoding region of 146 base pairs, an open reading frame of 1725 base pairs, a stop codon, a 3'-noncoding region of 1779 base pairs, and a poly(A) tail of 40 base pairs. The cDNA sequence encodes a 60.3-kDa protein of 575 amino acids. The predicted protein sequence includes a signal peptide of approximately 21 amino acids, an amino-terminal ligand-binding domain of approximately 223 amino acids, an epidermal growth factor (EGF) homology region of 236 amino acids, a serine/threonine-rich segment of 34 amino acids, a membrane-spanning domain of 23 amino acids, and a cytoplasmic tail of 38 amino acids. The EGF-homology region consists of six tandemly repeated EGF-like domains.(ABSTRACT TRUNCATED AT 250 WORDS)
Superior Efficacy and Selectivity of Novel Small-Molecule Kinase Inhibitors of T790M-Mutant EGFR in Preclinical Models of Lung Cancer (2017)

The clinical utility of approved EGFR small-molecule kinase inhibitors is plagued both by toxicity against wild-type EGFR and by metastatic progression in the central nervous system, a disease sanctuary site. Here, we report the discovery and preclinical efficacy of GNS-1486 and GNS-1481, two novel small-molecule EGFR kinase inhibitors that are selective for T790M-mutant isoforms of EGFR. Both agents were effective in multiple mouse xenograft models of human lung adenocarcinoma (T790M-positive or -negative), exhibiting less activity against wild-type EGFR than existing approved EGFR kinase inhibitors (including osimertinib). In addition, GNS-1486 showed superior potency against intracranial metastasis of EGFR-mutant lung adenocarcinoma. Our results offer a preclinical proof of concept for new EGFR kinase inhibitors with the potential to improve therapeutic index and efficacy against brain metastases in patients. <i>Cancer Res; 77(5); 1200-11. ©2017 AACR</i>.
Oral bioavailability of pantoprazole suspended in sodium bicarbonate solution (2003)

The bioavailability of pantoprazole when administered as a suspension in sodium bicarbonate solution and as the oral tablet was studied. In an open-label, randomized, two-period crossover study, healthy fasting subjects received either one enteric-coated 40-mg pantoprazole tablet by mouth with 240 mL of water or 20 mL of a suspension prepared from one crushed pantoprazole tablet and 840 mg of sodium bicarbonate solution and administered via a nasogastric tube. Treatments were separated by a 48-hour washout period. Blood samples were collected at intervals up to 24 hours after drug administration for measurement of pantoprazole concentration by high-performance liquid chromatography (HPLC) and estimation of pharmacokinetic values. A separate study was conducted to determine pantoprazole's stability in the suspension for up to three months at 25, 5, and -20 degrees C; concentrations were measured by HPLC. Twelve subjects completed the study. The suspension yielded pantoprazole Cmax values similar to those of the tablet formulation, but the drug was 25% less bioavailable. There was no lag time for the suspension. The suspension was stable for up to two weeks at 5 degrees C and up to three months at -20 degrees C. A suspension of pantoprazole in sodium bicarbonate solution yielded a Cmax similar to that of the tablet formulation, and the drug was quickly absorbed. However, bio-availability was slightly lower with the suspension than with the tablet.
Macrophages adhere to glucose-modified basement membrane collagen IV via their scavenger receptors. (1994)

Scavenger receptors have been reported to mediate macrophage adhesion to serum-coated plastic surfaces. We report here that scavenger receptors promote the divalent cation independent adhesion of human monocytes and macrophages to surfaces coated with non-enzymatically glycated collagen IV but not to surfaces coated with native collagen IV. Ligands for scavenger receptor types I and II blocked adhesion of monocytes and macrophages to non-enzymatically glycated collagen IV but had no effect on adhesion of these cells to albumin-coated surfaces. U937 human promonocyte-like cells transfected with cDNA encoding bovine scavenger receptor I or II adhered to surfaces coated with glycated-collagen IV but not to surfaces coated with native collagen IV. A synthetic peptide homologous to the domain of bovine scavenger receptor that binds modified low density lipoproteins (residues 327-343) inhibited the adhesion of U937 cells transfected with cDNA encoding bovine scavenger receptor II to glycated collagen IV, whereas a control peptide from the alpha helical domain of scavenger receptor II (residues 121-137) had no effect on adhesion of these cells. Macrophages plated on surfaces coated with glycated collagen IV were unable to endocytose acetylated low density lipoproteins from the medium, suggesting that their scavenger receptors were occupied in binding these cells to the substrate. These findings suggest new roles for scavenger receptors in the accelerated development of vascular lesions observed in diabetics.
PCR screening of 3-amino-5-hydroxybenzoic acid synthase gene leads to identification of ansamycins and AHBA-related antibiotic producers in Actinomycetes (2009)

The PCR screening of AHBA synthase gene represents a direct and sensitive molecular method for rapid detection of AHBA-related antibiotic-producing strains.
Sorbents in Acute Renal Failure and End-Stage Renal Disease: Middle Molecule and Cytokine Removal (2004)

Renal replacement therapy in acute renal failure (ARF) and chronic renal failure (end-stage renal disease; ESRD) has been based on the use of modifications of dialysis (continuous arteriovenous hemofiltration and hemodiafiltration) to remove middle-molecular-weight toxins, consisting of low-molecular-weight proteins and peptides (LMWP) and cytokines involved in inflammation. High-flux dialyzers are not efficient at removing LMWP, and for this reason, sorbents have been studied to augment or replace dialysis. Removal of LMWP such as beta2-microglobulin, leptin, complement factor D, angiogenin and cytokines such as interleukin (IL)-1, IL-6, IL-10, IL-18 and tumor necrosis factor-alpha has been established in animal models of sepsis and in ESRD patients using sorbents. Sorbent devices added to hemodialysis, or the use of such devices alone in inflammatory states, including sepsis, ARF, cardiopulmonary bypass, pre-explantation of donor organs and ESRD, are being studied.
Potential of tetracyclines to modify cartilage breakdown in osteoarthritis (1996)

For several decades, it has been recognized that an imbalance between activated matrix metalloproteinases, generated locally by both infiltrating and resident cells, and their endogenous inhibitors may play a role in the pathologic breakdown of the joint extracellular matrix in osteoarthritis. This understanding has stimulated the search for a number of synthetic matrix metalloproteinase inhibitors that could serve as potential therapeutic agents. Tetracycline analogues are currently on the threshold of approval as anti-matrix metalloproteinases for another extracellular matrix-destructive disease, periodontitis, and this application could be extended to osteoarthritis and rheumatoid arthritis therapy. In this regard, specially formulated low-dose regimens of a commercially available tetracycline, doxycycline, have been used in long-term clinical trials and were found to reduce extracellular matrix breakdown, including bone loss, in adult periodontitis. Matrix metalloproteinase inhibition by tetracycline analogues is now recognized as complex, and multiple mechanisms have been proposed. A series of recently discovered nonantimicrobial chemically modified tetracyclines are potent inhibitors of several classes of matrix metalloproteinases, preventing collagen breakdown and bone loss in a variety of animal models, although these analogues have not yet been approved for human use. Various tetracyclines have reduced the severity of osteoarthritis in animal models, indicating therapeutic potential for this class of compounds in the future.