gebhart/patrepeval huggingface dataset:
Possible Existence of a Novel Receptor for Uridine Analogues in the Central Nervous System Using Two Isomers, N3-(S)-(+)- and N3-(R)-(-)-.ALPHA.-Hydroxy-.BETA.-phenethyluridines. (2001)

Uridine analogue binding sites, the so-called uridine receptor, were observed in the experiments on specific [3H]N3-phenacyluridine binding to bovine synaptic membranes using two isomers, N3-(S)-(+)- and N3-(R)-(-)-alpha-hydroxy-beta-phenethyluridine, as ligands. The potent hypnotic, N3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine, but not the (R)-isomer, strongly inhibited [3H]N3-phenacyluridine binding. The racemate had inhibitory activity intermediate between that of the two alpha-hydroxy-beta-phenethyluridines ((R)- or (S)-isomers). The inhibitory constants of these compounds were determined. The Ki values of N3-phenacyluridine, alpha-hydroxy-beta-phenethyluridine (racemate), N3-(R)-(-)-, and N3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine were 0.65, 397.4, 1908, and 10.2 nM, respectively. The present results indicate the existence of uridine receptors in the central nervous system in relation to their hypnotic activities reported previously.
Chemical and sensory stability of fried‐salted peanuts flavored with oregano essential oil and olive oil (2009)

Abstract BACKGROUND: Synthetic antioxidants, such as BHA, BHT and PG, are used in many foods to prevent rancidity. However, their health safety is questioned. There is renewed interest in the increased use of naturally occurring antioxidants such as essential oils from aromatic plants. The objective of this work was to evaluate the effect of oregano essential oil and olive oil on the oxidative stability of fried‐salted peanuts. RESULTS: Fried‐salted peanuts (FP), fried‐salted peanuts with oregano essential oil (FP‐O) and fried‐salted peanuts with oregano essential oil and olive oil (FP‐OO) were prepared. Peroxide value (PV), p ‐anisidine value (AV) and conjugated diene (CD) measurements, and descriptive analysis were analyzed on the products during 112 days of storage. FP‐OO showed higher stability during storage. PV and AV at the end of storage were lower in FP‐OO (57.70–7.77, respectively) followed by FP‐O (63.94–8.30) and FP (76.38–9.33, respectively). The oxidized and cardboard flavor intensities increased more in FP during storage than the other products while the roasted peanutty flavor also decreased more in FP. CONCLUSION: Oregano essential oil and olive oil showed protective effect against lipid oxidation in fried‐salted peanuts increasing the shelf‐life of this product. Copyright © 2009 Society of Chemical Industry
Correction: Human Umbilical Mesenchymal Stem Cells-Seeded Bladder Acellular Matrix Grafts for Reconstruction of Bladder Defects in a Canine Model (2013)

The goal of this study was to explore the feasibility of utilizing human umbilical mesenchymal stem cells (HUMSCs)-seeded Bladder acellular matrix graft (BAMG) for bladder reconstruction in a canine model.
Expression of FcγRIII defines distinct subpopulations of fetal liver B cell and myeloid precursors (1995)

We have isolated four distinct fetal liver (FL) populations based on the expression of AA4.1 and the low-affinity Fc gamma receptors type II and III (Fc gamma RII/III), and characterized them with respect to B cell, T cell, and myeloid precursor content. Polymerase chain reaction analysis revealed that the prevalent Fc gamma R isoform at this stage of FL development (day 12 of gestation) was Fc gamma RIII. Two of the four populations, one which expressed AA4.1 but little if any Fc gamma RII/III (AA4.1+), and one which expressed abundant levels of both markers (AA4.1+/FcR+), contained B cell precursors that grew and differentiated to generate VHDJH-rearranged B-lineage cells on S-17 stromal cells in the presence of IL-7. When cultured on FLST2 stromal cells only the AA4.1+ cells generated VHDJH-rearranged B-lineage cells. T cell precursors as assayed by their ability to repopulate fetal thymi in organ culture were found only in the AA4.1+ fraction. In contrast to the lymphoid precursors, myeloid precursors able to generate colonies in methyl cellulose cultures were found in all four fractions including the one which expressed Fc gamma RII/III but no AA4.1 (FcR+) and the one which expressed neither marker (AA4.1-/FcR-). The AA4.1+ population which contained both B cell and T cell precursors was enriched for precursors from many myeloid lineages including the most immature ones which generated multilineage colonies. In contrast, the AA4.1+/FcR+ population, which also contained B cell precursors, was almost devoid of myeloid precursors and the few that were detected were committed to the macrophage lineage. The population defined as FcR+ was also enriched for precursors; however, the majority of these were committed to the erythroid, the macrophage and the mast cell lineage. The fourth population which expressed neither marker (AA4.1-/FcR-) was enriched for relatively mature erythroid precursors which were not present in any of the other fractions. Together, these findings demonstrate that fractionation of FL cells on the basis of AA4.1 and Fc gamma RII/III expression distinguishes subpopulations of B cell and myeloid precursors and suggests that the low-affinity Fc gamma RIII could play a role in the development of early hematopoietic cells at this stage of ontogeny.
3'-O-(4-benzoyl)benzoylcytidine 5'-triphosphate. A substrate and photoaffinity label for CMP-N-acetylneuraminic acid synthetase. (1986)

A photoreactive, radiolabeled pyrimidine nucleotide, 3'-O-(4-benzoyl)benzoylcytidine 5'-triphosphate was synthesized from benzoylbenzoic acid and radiolabeled CTP. Benzoylbenzoyl-[5-3H]CTP could substitute for CTP, in an enzymatic reaction with N-acetylneuraminic acid catalyzed by Escherichia coli or rat liver CMP-NeuAc synthetase, to yield radiolabeled benzoyl-benzoyl-CMP-NeuAc. E. coli CMP-NeuAc synthetase could be specifically radiolabeled using benzoylbenzoyl-[alpha-32P]CTP as a photoaffinity label. This specific covalent binding occurred using enzyme preparations of different degrees of purity. These results suggest that benzoylbenzoic acid derivatives of pyrimidines should be of general use in the identification and active site mapping of pyrimidine-requiring proteins and enzymes. These include glycosyltransferases, sugar nucleotide synthetases, and transporters, and enzymes participating in the conjugation of bile acids and biosynthesis of nucleic acids and choline nucleotides.
Loss of MDA-7 Expression With Progression of Melanoma (2002)

PURPOSE: Ectopic transfer of the melanoma differentiation-associated gene-7 (mda-7) has been shown in vitro to suppress growth and induce apoptosis in a variety of human tumor cell lines; similar effects are not elicited in normal cells. Thus, the mda-7 gene seems to function as a novel tumor suppressor, and there is interest in the potential of mda-7 gene transfer as cancer therapy. The objective of this study was to determine if MDA-7 protein is lost during primary melanoma progression from superficial to invasive stages and from localized to metastatic tumor. As a secondary objective, we analyzed MDA-7 protein expression in primary melanomas for correlation with predictors of outcome and with survival. MATERIALS AND METHODS: MDA-7 protein expression was evaluated by immunohistochemistry in 41 primary melanomas and 41 metastases, including 24 paired samples. Each sample was scored for the percentage of positive cells and the overall intensity of immunolabeling. RESULTS: Significant decreases in MDA-7 immunostaining, reflected in both number and intensity scores, were observed when comparing the intraepidermal and superficially invasive portions with the deeply invasive portions of primary tumors. Significant differences were also observed when comparing primary tumors to paired metastases. CONCLUSION: Downregulation of MDA-7 expression in primary melanomas facilitates progression to invasive and metastatic stages. These data support the development of Ad-mda7 as gene therapy for advanced melanoma.
Variable heavy-chain gene analysis of follicular lymphomas: subclone selection rather than clonal evolution over time (2001)

To investigate B-cell receptor evolution in follicular lymphomas (FLs), immunoglobulin variable heavy chain (V(H)) gene regions of 3 FLs were analyzed at different time points. One FL with a high somatic mutation load and intraclonal V(H) gene diversity was investigated in situ. V(H) gene transcripts were amplified and sequenced from samples of approximately 50 tumor cells isolated from frozen tissue sections by laser microdissection. Interestingly, the mutation pattern of the prevalent subclone in the relapse biopsy was virtually identical to that of a subclone isolated by microdissection from the presentation biopsy 9 years earlier. In a second FL, proof was obtained that the subclone that dominated the relapse sample had already been present in the initial biopsy. The finding that subclones found in the relapses of these FLs had not evolved over time but were preexistent, challenges the concept of antigen-driven B-cell receptor evolution during disease course.
CLAVATA2, a regulator of meristem and organ development in Arabidopsis (1998)

ABSTRACT Mutations at the CLAVATA2 (CLV2) locus of Arabidopsis result in enlarged shoot and flower meristems, as well as alterations in the development of the gynoecia, flower pedicels, and stamens. The shoot and flower meristem phenotypes of clv2 mutants are similar to weak clv1 and clv3 mutants. We present genetic analysis that CLV2 may function in the same pathway as CLV1 and CLV3 in the regulation of meristem development, but function separately in the regulation of organ development. We also present evidence that clv2 phenotypes are altered when the mutants are grown under short-day light conditions. These alterations include flower-to-shoot transformations, as well as a nearly complete suppression of the flower phenotypes, indicating that the requirement for CLV2 changes in response to different physiological conditions. The stm-1 mutation dominantly suppresses clv2, and clv2 mutations suppress the strong stm-1 allele, but not the weak stm-2 allele.
Asymmetric Hydrogenations for the Synthesis of Boc-Protected 4-Alkylprolinols and Prolines (2003)

The utility of 4-substituted prolinols and their corresponding prolines in peptides, peptidomimetics, and natural products has motivated researchers to find new and efficient routes for their preparation. Herein, we report a general approach to the synthesis of Boc-protected 4-alkylprolinols and prolines via a divergent asymmetric hydrogenation strategy. Intermediate exocyclic olefins were prepared by Wittig-type reactions with ketone 6 and subjected to hydroxyl and sterically directed reductions. The Crabtree catalyst (Ir[COD]PyPCy(3)PF(6)) proved to be highly effective in diastereoselective hydrogenations to give trans-substituted pyrrolidines (9). Good facial selectivities were also observed in heterogeneous hydrogenations with Raney-nickel to obtain cis-substituted pyrrolidines (11). Employing this strategy, we describe the synthesis of novel prolinol and proline-based building blocks for incorporation into biologically relevant peptidomimetics.
Biochemical, neurophysiological, and behavioral effects of Wy‐45,233 and other identified metabolites of the antidepressant venlafaxine (1991)

Abstract Seven metabolites of venlafaxine, identified in several species, were examined for CNS pharmacological activity in rodents. The O‐desmethyl compound Wy‐45,233, which is the major metabolite in man, had the greatest preclinical activity. This metabolite exhibited an antidepressant profile (monoamine uptake blockade, reversal of reserpine hypothermia, induction of pineal β‐adrenergic subsensitivity) comparable to the parent drug, venlafaxine. This compound also inhibited serotonergic and noradrenergic firing rates like the parent compound, but with less potency. The cyclohexyl ring‐hydroxylated metabolite Wy‐47,877 and the N‐desmethyl metabolite Wy‐45, 494 were also active in reserpine hypothermia, but Wy‐45,494 was a weaker inhibitor of serotonin uptake and both metabolites were weaker inhibitors of norepinephrine uptake than Wy‐45,233. None of the seven metabolites tested exhibited significated binding at dopamine‐2, muscarinic cholinergic, α‐1‐adrenergic, histamine‐1, or opiate (μ) receptors. These results suggest that Wy‐45,233, the O‐desmethyl metabolite of venlafaxine, is an active metabolite which retains the benign side‐effect profile of venlafaxine.
Identification and Characterization of a Widely Expressed Form of Adenylyl Cyclase (1996)

A novel mammalian adenylyl cyclase was identified by reverse transcription-polymerase chain reaction amplification using degenerate primers based on a conserved region of previously described adenylyl cyclases (Premont, R. T. (1994) Methods Enzymol. 238, 116-127). The full-length cDNA sequence obtained from mouse brain predicts a 1353-amino acid protein possessing a 12-membrane span topology, and containing two regions of high similarity with the catalytic domains of adenylyl cyclases. Comparison of this novel adenylyl cyclase with the eight previously described mammalian enzymes indicates that this type 9 adenylyl cyclase sequence is the most divergent, defining a sixth distinct subclass of mammalian adenylyl cyclases. The AC9 gene has been localized to human chromosome band 16p13.3-13.2. The 8.5-kb mRNA encoding the type 9 adenylyl cyclase is widely distributed, being readily detected in all tissues tested, and is found at very high levels in skeletal muscle and brain. AC9 mRNA is found throughout rat brain but is particularly abundant in hippocampus, cerebellum, and neocortex. An antiserum directed against the carboxyl terminus of the type 9 adenylyl cyclase detects native and expressed recombinant AC9 protein in tissue and cell membranes. Levels of the AC9 protein are highest in mouse brain membranes. Characterization of expressed recombinant AC9 reveals that the protein is a functional adenylyl cyclase that is stimulated by Mg2+, forskolin, and mutationally activated Gsalpha. AC9 activity is not affected by Ca2+/calmodulin or by G protein betagamma-subunits. Thus AC9 represents a functional G protein-regulated adenylyl cyclase found in brain and in most somatic tissues.
The Abdominojugular Test: Technique and Hemodynamic Correlates (1988)

Study Objective: To determine the hemodynamic correlates of a modified abdominojugular reflux test. Design: Case series. Setting: Referral-based cardiology practice in a university hospital. Patients: Two consecutive samples of 65 (group 1) and 21 (group 2) patients having both right and left heart catheterization. Interventions: Ten seconds of firm midabdominal pressure was applied by hand in all patients. In group 1 patients, right atrial pressures were recorded during this maneuver. In group 2 patients, simultaneous right atrial and pulmonary arterial wedge pressures were recorded during this maneuver. In group 2 patients, this abdominojugular test was also done at the bedside before cardiac catheterization by observing the changes in the jugular venous pressure. Measurements and Main Results: Positive results on an abdominojugular test, defined as an increase in the right atrial pressure during 10 seconds of firm midabdominal compression followed by an abrupt drop in pressure of at least 3 mm Hg (4 cm of blood) on pressure release, were found in patients who as a group had hemodynamic evidence of left ventricular failure. The patients with a positive response had lower left ventricular ejection fractions and stroke volumes, and higher left ventricular filling, higher mean pulmonary arterial, and higher right atrial pressures. The pulmonary arterial occluded or wedge pressures provided the clearest separation between patients with and without a positive response. The mean pulmonary arterial wedge pressure was 10.5 ±1 mm Hg in patients with a negative response and 19 ±3 mm Hg in patients with a positive response (P < 0.001). In all but one of the group 2 patients, midabdominal pressure produced similar directional changes in both the right atrial and pulmonary arterial wedge pressures. Conclusions: The abdominojugular test, when done in a standardized fashion, correlates best with the pulmonary arterial wedge pressure, and therefore, is probably a reflection of an increased central blood volume. In the absence of isolated right ventricular failure, seen in some patients with right ventricular infarction, a positive abdominojugular test suggests a pulmonary artery wedge pressure of 15 mm Hg or greater.
COX-2 inhibitors arrest prostate cancer cell cycle progression by down-regulation of kinetochore/centromere proteins (2014)

Our studies indicate that inhibition of COX-2 can arrest prostate cancer cell cycle progression through inactivation of the EP1 receptor signaling and down-regulation of kinetochore/centromere proteins.
A Deep Bag-of-Features Model for Music Auto-Tagging (2015)

Feature learning and deep learning have drawn great attention in recent years as a way of transforming input data into more effective representations using learning algorithms. Such interest has grown in the area of music information retrieval (MIR) as well, particularly in music audio classification tasks such as auto-tagging. In this paper, we present a two-stage learning model to effectively predict multiple labels from music audio. The first stage learns to project local spectral patterns of an audio track onto a high-dimensional sparse space in an unsupervised manner and summarizes the audio track as a bag-of-features. The second stage successively performs the unsupervised learning on the bag-of-features in a layer-by-layer manner to initialize a deep neural network and finally fine-tunes it with the tag labels. Through the experiment, we rigorously examine training choices and tuning parameters, and show that the model achieves high performance on Magnatagatune, a popularly used dataset in music auto-tagging.
Cancer Incidence and Survival among Children and Adolescents: United States SEER Program 1975-1995 (1999)

This DOI is not currently attached to any metadata records. DOIs can’t actually ever be deleted (they’re persistent), but sometimes our members create DOIs in error. We do have a process to approximate deletion which we follow only in rare cases where the DOI has been genuinely created in error, and most crucially, if the DOI has never been published anywhere online or in print and never otherwise distributed to or communicated with anyone (authors, readers, reviewers, etc.
Substituted 2-nitrobenzyltrichloroacetate esters for photodirected oligonucleotide detritylation in solid films (2008)

Oligonucleotide microarray fabrication by chemical synthesis using photoacid generators in solid films could have advantages over existing methods, but has not matched the accuracy of conventional synthesis where detritylation is performed with acid solutions. To address this problem, we explored the kinetics and equilibria of nucleoside detritylation in solid films, using trichloroacetic acid (TCA) generated by photolysis from its esters with substituted 2-nitrobenzyl alcohols. We synthesised 25 such esters, all alpha-phenyl substituted, and assessed their potential as solid film photoacid generators. They included sets with (i) mono- or dimethoxy-, (ii) 5-halo-, (iii) alkyl- or aryl-substituted 5-amino-, or (iv) 5-aryl-substituents in the 2-nitro- or 2,6-dinitrobenzyl ring. Absorption maxima of their UV spectra ranged from 230 to 410 nm, with quantum yields at 365 nm from < 0.01 to nearly 1.0. The esters formed optically clear solid films on glass slides without added polymer. Kinetics of intrafilm photoacid generation, proton activity changes and detritylation were measured in situ. The most effective esters for light sensitivity and detritylation were 5-chloro-, 5-bromo-, 4,5-dimethoxy-, and 4- or 5-aryl-substituted 2,6-dinitrobenzyl esters. Photoacid-induced increases in proton activity and detritylation were severely inhibited by polymers containing electronegative heteroatoms, but not by polymers lacking them. In solid films, intrafilm detritylation with photogenerated TCA was fast, but stopped at an equilibrium well short of completion. Both experiment and theory emphasise the inadequacy of attempting to force detritylation with high intrafilm acid activity.
Concordance between Tramadol and Dextromethorphan Parent/Metabolite Ratios: The Influence of CYP2D6 and Non‐CYP2D6 Pathways on Biotransformation (2002)

Cytochrome P4502D6 (CYP2D6) activity has been shown to be a determinant of both the pharmacokinetics and pharmacodynamics of tramadol in adults. This study evaluated the association between CYP2D6 activity, as determined by dextromethorphan (DM) urinary metabolite ratio, and tramadol biotransformation in 13 children (7-16 years). CYP2D6 genotype was determined by XL-PCR and PCR/RFLP. Phenotype was assessed by HPLC quantitation of DM and its metabolites from a 12- to 24-hour urine collection following a single oral dose of DM. There was only a modest correlation between tramadol/M1 (metabolite 1) plasma concentration or AUC and the DM/dextrorphan (DX) urinary molar ratio in the study cohort; however, when subjects were segregated based on the number of functional CYP2D6 alleles, a much stronger relationship was observed for subjects with two functional alleles, with essentially no relationship evident in those individuals with one functional allele. Further evaluation of these data suggested that the CYP2D6-mediated metabolite (M1) is formed to a lesser extent, and the formation of the non-CYP2D6 product (M2) is more pronounced in subjects with one versus two functional alleles. Thus, the number of functional CYP2D6 alleles and the availability of alternative cytochromes P450 capable of metabolizing tramadol may explain the poor association between DM, a well-characterized CYP2D6 probe, and tramadol in a population of CYP2D6 extensive metabolizers.
Synthesis, Characterization, and Hydrolytic Degradation of Polylactide-Functionalized Polyoxanorbornenes (2007)

This paper describes the synthesis of polylactide-functionalized polyoxanorbornenes and their hydrolytic degradation behavior. Macromonomers with one or two exo-PLA chains as well with two endo,exo chains were prepared using tin(II) 2-ethylhexanoate as a catalyst in the presence of mono- or dialcohol derivatives of oxanorbornene. The well-characterized macromonomers were then subjected to ROMP by first, second, and modified second generation Grubbs ruthenium initiators. Investigation of these graft copolymers by SEC and NMR spectroscopy showed the presence of some uncapped PLA homopolymer, formed as a side product during the ROP of lactide. The degradation behavior showed that the presence of PLA homopolymer impurities in the graft copolymers significantly increases the rate of degradation of the final material. Therefore, a convenient procedure of graft copolymers purification to remove PLA homopolymer from the samples was developed. The degradation studies of graft copolymers with the same oxanorbornyl backbone length and different length of PLA grafts indicated that the degradation rate increased with increasing length of PLA grafts. The degradation behavior of material depends also on configuration of PLA side chains on polyoxanorbornene backbone chain. The fastest degradation was observed in the case of graft copolymers with one exo-PLA side chain.