gebhart/patrepeval huggingface dataset:
Industrial Organic Chemistry (1997)

This book describes current industrial applications of organic chemistry and offers an excellent overview of industrial organic chemistry. It covers the manufacture of the most important precursors and intermediates and their use in the development of commercial products. It details chemical and physical data, aspects of energy and raw materials supply, and the production of chemicals in different countries. It also describes the possibilities for future developments in the manufacture of various chemicals.
GRP78 expression correlates with histologic differentiation and favorable prognosis in neuroblastic tumors (2004)

Glucose-regulated protein 78 (GRP78), an endoplasmic reticulum protein, is essential for the differentiation of neuroblastoma cells and is selectively induced when the cells are undergoing apoptosis. These findings suggest that GRP78 may affect the tumor behavior of neuroblastoma. Our study evaluates the association of clinicopathologic factors and patient survival with the expression of GRP78 in patients with neuroblastoma. GRP78 expression in 68 neuroblastic tumors was investigated semiquantitatively by immunohistochemistry. GRP78 mRNA and protein levels in 7 tumor tissues were also quantified by real-time PCR and Western blot respectively and correlated well with the immunohistochemical results. Forty (58.8%) of the 68 neuroblastic tumors showed positive GRP78 expression. The percentage of positive GRP78 immunostaining increased as the tumor histology became differentiated (p = 0.001). Furthermore, positive GRP78 expression strongly correlated with early clinical stages (P = 0.002) but inversely correlated with MYCN amplification (p = 0.001). Kaplan-Meier analysis showed that patients with positive GRP78 expression did have better survival than those with negative expression (5-year survival rate, 72.9% and 23.4% respectively, p < 0.001). Multivariate analysis further showed that GRP78 expression was an independent prognostic factor. Moreover, GRP78 expression predicted better survival in patients with either undifferentiated or differentiated histologies. GRP78 expression still had significant prognostic value when the analysis was restricted to tumors of advanced stages or without MYCN amplification. Thus, GRP78 can serve as a novel independent favorable prognostic factor for patients with neuroblastoma.
Renal oxygenation and haemodynamics in acute kidney injury and chronic kidney disease (2012)

Acute kidney injury (AKI) is a major burden on health systems and may arise from multiple initiating insults, including ischaemia-reperfusion injury, cardiovascular surgery, radiocontrast administration and sepsis. Similarly, the incidence and prevalence of chronic kidney disease (CKD) continues to increase, with significant morbidity and mortality. Moreover, an increasing number of AKI patients survive to develop CKD and end-stage renal disease. Although the mechanisms for the development of AKI and progression to CKD remain poorly understood, initial impairment of oxygen balance likely constitutes a common pathway, causing renal tissue hypoxia and ATP starvation that, in turn, induce extracellular matrix production, collagen deposition and fibrosis. Thus, possible future strategies for one or both conditions may involve dopamine, loop diuretics, atrial natriuretic peptide and inhibitors of inducible nitric oxide synthase, substances that target kidney oxygen consumption and regulators of renal oxygenation, such as nitric oxide and heme oxygenase-1.
Dihydroxy acid dehydratase from spinach contains a [2Fe-2S] cluster. (1988)

Dihydroxy acid dehydratase, the third enzyme in the branched-chain amino acid biosynthetic pathway, has been purified to homogeneity (5000-fold) from spinach leaves. The molecular weights of dihydroxy acid dehydratase as determined by sodium dodecyl sulfate and native gel electrophoresis are 63,000 and 110,000, respectively, suggesting the native enzyme is a dimer. 2 moles of iron were found per mol of protein monomer. Chemical analyses of iron and labile sulfide gave an Fe/S2- ratio of 0.95. The EPR spectrum of dithionite-reduced enzyme (gavg = 1.91) is similar to spectra characteristic of Rieske Fe-S proteins and has a spin concentration of 1 spin/1.9 irons. These results strongly suggest that dihydroxy acid dehydratase contains a [2Fe-2S] cluster, a novel finding for enzymes of the hydrolyase class. In contrast to the Rieske Fe-S proteins, the redox potential of the Fe-S cluster is quite low (-470 mV). Upon addition of substrate, the EPR signal of the reduced enzyme changes to one typical of 2Fe ferredoxins (gavg = 1.95), and the visible absorption spectrum of the native enzyme shows substantial changes between 400 and 600 nm. Reduction of the Fe-S cluster decreases the enzyme activity by 6-fold under Vmax conditions. These results suggest the direct involvement of the [2Fe-2S] cluster of dihydroxy acid dehydratase in catalysis. Similar conclusions have been reached for the catalytic involvement of the [4Fe-4S] cluster of the hydrolyase aconitase (Emptage, M. H., Kent, T. A., Kennedy, M. C., Beinert, H., and Münck, E. (1983) Proc. Natl. Acad. Sci. U. S. A. 80, 4674-4678).
The endoribonuclease Regnase-1: key molecule in inflammatory and immune responses (2019)

Immune responses are accompanied by dynamic changes in gene expression. Many transcription factors including NF-κB and AP-1 are involved in induction of genes involved in inflammatory and immune responses. However, recent studies have revealed that control of gene expression at the mRNA level is as important as transcriptional control in the immune response. We have shown that Regnase-1 encoded by the Zc3h12a gene is an endoribonuclease involved in destabilization of a variety of mRNAs including IL-6,IL-12, and Regnase-1 itself mRNAs via the stem loop structure present in the 3'UTR of these genes
Therapeutic proteins : pharmacokinetics and pharmacodynamics (1993)

Detailing recent advances in therapeutic proteins, this text focuses on a critical stage in the development of proteins for therapeutic use - the evaluation of the pharmacokinetic and pharmacodynamic aspects of protein/peptide drugs. Written by both industrial and academic researchers, the book explores the key components of the protein therapeutics industry, from basic research to drug development to drug applications. Therapeutic Proteins examines some of the major protein/peptide drugs recently licensed or currently being developed. The book reviews the basic principles involved in evaluating toxicity and efficacy, discusses industry standards for protein drug evaluation and provides state-of-the-art guidelines for designing and interpreting protein pharmacokinetic and pharmacodynamic studies.
Synthesis and biological activities of chloroethylurea, methylurea, and nitrosourea analogs of N-deacetylmethylthiocolchicine (1980)

A series of urea and nitrosourea analogues of N-deacetylmethylthiocolchicine (1) has been synthesized, and their antineoplastic and antiviral activities were evaluated. The objective for combination of two active moieties, such as thiocolchicine and nitrosourea, into one molecule was the generation of compounds with potential improved biological and pharmacological properties. The ED50 for 2, 3, 4, and 5 was 1.6, 1.2, 3.3, and 1.8 X 10(-8) M for L1210 cells and 3.0, 2.7, 2.9, and 2.6 X 10(-8) M for S-180 cells, respectively. The synthesis and cytotoxic and antiviral properties of these compounds are discussed.
A nitric oxide donor induces neurogenesis and reduces functional deficits after stroke in rats (2001)

The adult rodent brain is capable of generating neuronal progenitor cells in the subventricular zone, and in the dentate gyrus of the hippocampus, throughout the life of the animal. Signals that regulate progenitor cell proliferation, differentiation, and migration are not well known. We report that administration of a nitric oxide donor, (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) aminio]diazen-1-ium-1,2-diolate (DETA/NONOate), to young adult rats significantly increases cell proliferation and migration in the subventricular zone and the dentate gyrus. Treatment with DETA/ NONOate also increases neurogenesis in the dentate gyrus. Furthermore, administration of DETA/NONOate to rats subjected to embolic middle cerebral artery occlusion significantly increases cell proliferation and migration in the subventricular zone and the dentate gyrus, and these rats exhibit significant improvements of neurological outcome during recovery from ischemic stroke. Administration of DETA/NONOate significantly increases cortical levels of guanosine monophosphate both in ischemic and nonischemic rats, supporting the role of nitric oxide in promoting cell proliferation and neurogenesis. Thus, our data indicate that nitric oxide is involved in the regulation of progenitor cells and neurogenesis in the adult brain. This suggests that nitric oxide delivered to the brain well after stroke may have therapeutic benefits.
Rapid flow cytofluorometric analysis of mammalian cell cycle by propidium iodide staining. (1975)

A rapid method for the flow microfluorometric determination of the DNA content per cell is described. Incubation of cells in a hypotonic solution of propidium iodide results in disruption of the cell membrane and rapid staining of nuclear chromatin. DNA distribution histograms generated from cells stained by this method are identical to those generated after fixation and RNase digestion. In contrast to some earlier described methods, the present technique is rapid (5 min of processing), requires a minimal amount of material, and avoids formation of cell clumps.
Generalized eigenproblem algorithms and software for algebraic Riccati equations (1984)

Numerical issues related to the computational solution of the algebraic matrix Riccati equation are discussed. The approach presented uses the generalized eigenproblem formulation for the solution of general forms of algebraic Riccati equations arising in both continuous- and discrete-time applications. These general forms result from control and filtering problems for systems in generalized (or implicit or descriptor) state space form. A Newtontype iterative refinement procedure for the generalized Riccati solution is given. The issue of numerical condition of the Riccati problem is addressed. Balancing to improve numerical condition is discussed. An overview of a software package, RICPACK, coded in portable, reliable Fortran is given. Results of numerical experiments are reported.
Multimodal tracking and classification of audio-visual features (2002)

The surge of interest in multimedia and multimodal interfaces has prompted the need for novel estimation and classification techniques for data from different but coupled modalities. Unimodal techniques ported to this domain have only exhibited limited success. We propose a new framework for feature prediction and classification based on multimodal knowledge-constrained hidden Markov models (HMMs). The classical role of HMMs as statistical classifiers is enhanced by their new role as multimodal feature predictors. Moreover, by fusing the multimodal formulation with higher level knowledge we allow the influence of such knowledge to be reflected in feature prediction as well as in feature classification.
Docosahexaenoic acid, a major constituent of fetal serum and fish oil diets, inhibits IFN gamma-induced Ia-expression by murine macrophages in vitro. (1995)

Decreased Ia expression by macrophages may account for the increased susceptibility of fetuses and neonates to infection. We chose to investigate the role of docosahexaenoic acid (DHA), an omega-3 fatty acid, on Ia expression in vitro, because neonatal serum concentrations of DHA (100-150 microM) are approximately 50 times higher than in the adult. In addition, DHA is a major component of fish-oil diets that ameliorate some autoimmune diseases and prevent renal allograft rejection. DHA inhibited IFN-gamma-induced Ia expression with a half-maximal inhibitory concentration of 25 microM. The inhibition was not caused by nonspecific damage, because oxidative metabolism via the mitochondrial electron-transport chain was not inhibited. There were strict biochemical requirements for inhibition of Ia expression. Polyenoic fatty acids with 22 carbons were more inhibitory than those with 20 carbons. Among 22-carbon fatty acids, those with more double bonds, and, in particular, with a double bond in the omega-3 position, were more inhibitory. Although DHA is known to inhibit cyclooxygenase and thus the production of eicosanoids, indomethacin did not inhibit Ia expression. This indicated that inhibition of cyclooxygenase was not responsible for inhibition of Ia expression. We divided induction of Ia expression by IFN-gamma into four phases, with IFN-gamma being present only during the second phase. DHA was most inhibitory when given before or with the IFN-gamma. This indicated that DHA inhibited early steps in IFN-gamma-induced Ia expression. Consistent with this idea, we found that DHA inhibited the increase in mRNA transcripts for Ia beta b, as assayed by Northern blotting. In summary, we found that DHA, a major component of fetal and neonatal sera as well as fish-oil diets, inhibited IFN-gamma-induced macrophage Ia expression in vitro by preventing increases in Ia mRNA transcripts.
Synthesis and biological evaluation of novel 2‐(4‐O‐β‐D‐glucosidoxyphenyl)‐4,5‐disubstituted imidazoles (2010)

Abstract magnified image A series of 2‐(4‐hydroxyphenyl)‐4,5‐disubstituted imidazoles ( 1a , 1b , 1c , 1d , 1e ) prepared from α‐diketones, ammonium acetate, and p ‐hydroxybenzaldehyde, which were glucosylated by using α‐acetobromoglucose to form 2‐(4‐ O ‐ β‐ D ‐2,3,4,6‐tetra‐ O ‐acetyl‐glucosidoxyphenyl)‐4,5‐disubstituted imidazoles ( 2a , 2b , 2c , 2d , 2e ) which on catalytic deacetylation with CH 3 ONa in methanol afforded the title compound 2‐(4‐ O ‐ β‐ D ‐glucosidoxyphenyl)‐4,5‐disubstituted imidazoles ( 3a , 3b , 3c , 3d , 3e ). Compounds were characterized by elemental analysis and by instrumental technique, similarly the title compounds were investigated for antimicrobial and antifungal activity. J. Heterocyclic Chem., (2010).
The Molecular Logic of Olfaction in Drosophila (2001)

Drosophila fruit flies display robust olfactory-driven behaviors with an olfactory system far simpler than that of vertebrates. Endowed with 1300 olfactory receptor neurons, these insects are able to recognize and discriminate between a large number of distinct odorants. Candidate odorant receptor molecules were identified by complimentary approaches of differential cloning and genome analysis. The Drosophila odorant receptor (DOR) genes encode a novel family of proteins with seven predicted membrane-spanning domains, unrelated to vertebrate or nematode chemosensory receptors. There are on the order of 60 or more members of this gene family in the Drosophila genome, far fewer than the hundreds to thousands of receptors found in vertebrates or nematodes. DOR genes are selectively expressed in small subsets of olfactory neurons, in expression domains that are spatially conserved between individuals, bilaterally symmetric and not sexually dimorphic. Double in situ RNA hybridization with a number of pairwise combinations of DOR genes fails to reveal any overlap in gene expression, suggesting that each olfactory neuron expresses one or a small number of receptor genes and is therefore functionally distinct. How is activation of such a subpopulation of olfactory receptor neurons in the periphery sensed by the brain? In the mouse, all neurons expressing a given receptor project with precision to two of 1800 olfactory bulb glomeruli, creating a spatial map of odor quality in the brain. We have employed DOR promoter transgenes that recapitulate expression of endogenous receptor to visualize the projections of individual populations of receptor neurons to subsets of the 43 glomeruli in the Drosophila antennal lobe. The results suggest functional conservation in the logic of olfactory discrimination from insects to mammals.
Fourth order sigma-delta modulator circuit for digital audio and ISDN applications (1989)

A fourth order switched capacitor sigma-delta modulator architecture is presented providing extremely high signal to quantization noise ratio with modest circuit level demands for digital audio specification. Tolerable nonidealities in subcircuits are specified by system level simulation. The subcircuits are designed to fulfil the digital audio specification. Five modulators are fabricated in order to investigate the 1/f-noise elimination. >
HAP1 and ROX1 Form a Regulatory Pathway in the Repression of HEM13 Transcription in Saccharomyces cerevisiae (1992)

HEM13 of Saccharomyces cerevisiae encodes coproporphyrinogen oxidase, an enzyme in the heme biosynthetic pathway. Expression of HEM13 is repressed by oxygen and heme. This study investigated the regulatory pathway responsible for the regulation of HEM13 expression. The transcriptional activator HAP1 is demonstrated to be required for the full-level expression of HEM13 in the absence of heme. It is also shown that the repression of HEM13 transcription caused by heme involves the HAP1 and ROX1 gene products; a mutation in either gene results in derepression of HEM13 expression. The heme-dependent expression of ROX1 was found to require functional HAP1, leading one to propose that repression of HEM13 results from a pathway involving HAP1-mediated regulation of ROX1 transcription in response to heme levels followed by ROX1-mediated repression of HEM13 transcription. In support of this model, expression of ROX1 under control of the GAL promoter was found to result in repression of HEM13 transcription in a hap1 mutant strain. The ability of ROX1 encoded by the galactose-inducible ROX1 construct to function in the absence of HAP1 indicates that the only role of HAP1 in repression of HEM13 is to activate ROX1 transcription.
Sex Differences in Plasmacytoid Dendritic Cell Levels of IRF5 Drive Higher IFN-α Production in Women (2015)

Increased IFN-α production contributes to the pathogenesis of infectious and autoimmune diseases. Plasmacytoid dendritic cells (pDCs) from females produce more IFN-α upon TLR7 stimulation than pDCs from males, yet the mechanisms underlying this difference remain unclear. In this article, we show that basal levels of IFN regulatory factor (IRF) 5 in pDCs were significantly higher in females compared with males and positively correlated with the percentage of IFN-α-secreting pDCs. Delivery of recombinant IRF5 protein into human primary pDCs increased TLR7-mediated IFN-α secretion. In mice, genetic ablation of the estrogen receptor 1 (Esr1) gene in the hematopoietic compartment or DC lineage reduced Irf5 mRNA expression in pDCs and IFN-α production. IRF5 mRNA levels furthermore correlated with ESR1 mRNA levels in human pDCs, consistent with IRF5 regulation at the transcriptional level by ESR1. Taken together, these data demonstrate a critical mechanism by which sex differences in basal pDC IRF5 expression lead to higher IFN-α production upon TLR7 stimulation in females and provide novel targets for the modulation of immune responses and inflammation.
Determination of Reduced Nicotinamide Adenine Dinucleotide Phosphate Concentration Using High-Performance Liquid Chromatography with Fluorescence Detection: Ratio of the Reduced Form as a Biomarker of Oxidative Stress (2009)

Reduced nicotinamide adenine dinucleotide phosphate (NADPH) is the principal source of reducing power in numerous processes of physiological importance. We examined the influence of oxidative stress on the relative amounts of NADPH in human red blood cells (RBCs). To determine the homeostasis of the NADPH existing in the reduced form following oxidation, we developed an improved method for measurement of NADPH in human RBCs using high-performance liquid chromatography (HPLC). The present method with fluorescent detection is reproducible and selective than enzymatic cycling method and HPLC methods with spectrometric detection. The calibration curve is linear over the range of 0.1-5.0 muM with a correlation coefficient of 0.999. The within-run precision of the assays for total NADPH (NADPH+NADP(+)) and NADPH concentrations in human RBC were 2.4% and 8.6%, respectively (n=5). After the RBC suspension was exposed to tert-butyl hydroperoxide (t-BHP), which is scavenged by glutathione peroxidase (GPX) along with NADPH consumption, a significant decrease in the NADPH ratio [(NADPH/(NADPH+NADP(+))] was observed after a transient decrease and rapid recovery of the reduced form of glutathione. The marked decrease in the NADPH ratio induced by t-BHP exposure was observed in the absence of glucose. However, the NADPH ratio was not decreased by t-BHP exposure after pre-treatment with a glutathione reductase inhibitor. This method may be useful for the measurement of small amounts of NADPH from various biological sources.
Next‐generation DNA barcoding: using next‐generation sequencing to enhance and accelerate DNA barcode capture from single specimens (2014)

DNA barcoding is an efficient method to identify specimens and to detect undescribed/cryptic species. Sanger sequencing of individual specimens is the standard approach in generating large-scale DNA barcode libraries and identifying unknowns. However, the Sanger sequencing technology is, in some respects, inferior to next-generation sequencers, which are capable of producing millions of sequence reads simultaneously. Additionally, direct Sanger sequencing of DNA barcode amplicons, as practiced in most DNA barcoding procedures, is hampered by the need for relatively high-target amplicon yield, coamplification of nuclear mitochondrial pseudogenes, confusion with sequences from intracellular endosymbiotic bacteria (e.g. Wolbachia) and instances of intraindividual variability (i.e. heteroplasmy). Any of these situations can lead to failed Sanger sequencing attempts or ambiguity of the generated DNA barcodes. Here, we demonstrate the potential application of next-generation sequencing platforms for parallel acquisition of DNA barcode sequences from hundreds of specimens simultaneously. To facilitate retrieval of sequences obtained from individual specimens, we tag individual specimens during PCR amplification using unique 10-mer oligonucleotides attached to DNA barcoding PCR primers. We employ 454 pyrosequencing to recover full-length DNA barcodes of 190 specimens using 12.5% capacity of a 454 sequencing run (i.e. two lanes of a 16 lane run). We obtained an average of 143 sequence reads for each individual specimen. The sequences produced are full-length DNA barcodes for all but one of the included specimens. In a subset of samples, we also detected Wolbachia, nontarget species, and heteroplasmic sequences. Next-generation sequencing is of great value because of its protocol simplicity, greatly reduced cost per barcode read, faster throughout and added information content.