gebhart/patrepeval huggingface dataset:
A New Inhibitor of Plasmin and Trypsin from Porcine Leukocytes (1990)

A new intracellular inhibitor of plasmin and trypsin was isolated from porcine leukocytes by ion exchange chromatography and affinity chromatography. In dodecyl sulphate gel electrophoresis a single protein band with an apparent molecular mass of 15 kDa was found under reducing conditions. On isoelectric focusing three protein bands with isoelectric points between pH 4.0 and 4.5 were found. The association rate constants and the inhibition constants were determined for porcine plasmin and bovine trypsin. The inhibitor shows no immunologic cross-reactivity with any of the tested leukocyte inhibitors. On the basis of its N-terminal amino-acid sequence a great degree of similarity to Kunitz-type inhibitors was observed.
Cloning and expression of the tumor-associated antigen L6. (1992)

The L6 cell surface antigen, which is highly expressed on lung, breast, colon, and ovarian carcinomas, has attracted attention as a therapeutic target for murine monoclonal antibodies and their humanized counterparts. Its molecular nature has, however, remained elusive. Here we describe the expression cloning of a cDNA encoding the L6 antigen. COS cells transfected with this cDNA direct the expression of an approximately 24-kDa surface protein that reacts with the two anti-L6 monoclonal antibodies available. The predicted L6 peptide sequence is 202 amino acids long and contains three predicted NH2-terminal hydrophobic transmembrane regions, which are followed by a hydrophilic region containing two potential N-linked glycosylation sites and a COOH-terminal hydrophobic transmembrane region. The L6 antigen is related to a number of cell surface proteins with similar predicted membrane topology that have been implicated in cell growth. Two other members of this family of proteins, CD63 (ME491) and CO-029, are also highly expressed on tumor cells. The present findings should make it possible to further study the role of the L6-defined antigen in normal and neoplastic cells and to construct animal models for development of improved agents for active and passive cancer immunotherapy.
Highly ordered high-molecular weight alternating polysilylene copolymer prepared by anionic polymerization of masked disilene (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleHighly ordered high-molecular weight alternating polysilylene copolymer prepared by anionic polymerization of masked disileneKenkichi Sakamoto, Masaru Yoshida, and Hideki SakuraiCite this: Macromolecules 1990, 23, 20, 4494–4496Publication Date (Print):October 1, 1990Publication History Published online1 May 2002Published inissue 1 October 1990https://doi.org/10.1021/ma00222a031RIGHTS & PERMISSIONSArticle Views213Altmetric-Citations56LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (337 KB) Get e-Alerts Get e-Alerts
Pathogenesis of Mycobacterium avium complex in the SIV/macaque model of AIDS (2004)

The prevalence of benzodiazepine abuse was estimated among gynecological outpatients at a general hospital in New Delhi, India. Approximately 8% of respondents abuse benzodiazepines, with Diazepam being the most popular drug. Abuse was more common among younger and more educated women.
Dimethyl disulfide derivatives of long chain alkenes, alkadienes, and alkatrienes for gas chromatography/mass spectrometry (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDimethyl disulfide derivatives of long chain alkenes, alkadienes, and alkatrienes for gas chromatography/mass spectrometryDavid A. Carlson, Chin Shyan. Roan, Richard A. Yost, and Julio. HectorCite this: Anal. Chem. 1989, 61, 14, 1564–1571Publication Date (Print):July 15, 1989Publication History Published online1 May 2002Published inissue 15 July 1989https://doi.org/10.1021/ac00189a019Request reuse permissionsArticle Views1201Altmetric-Citations148LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (901 KB) Get e-Alertsclose Get e-Alerts
Preparation of Casein Phosphopeptides from Casein Micelles by Ultrafiltration (1995)

Casein phosphopeptides (CPPs), which inhibit the precipitation of calcium phosphate in the intestines, were prepared as CPP-calcium phosphate complexes from casein micelles by the ultrafiltration method. The prepared CPPs hardly contained any other peptides, so there was no need to treat with active carbon to remove the bitter peptides. The sum of alpha s1-CN-5P(f59-79) and beta-CN-4P(f1-25) comprised 60% of the CPP composition by an analysis of the elution pattern from a Q-Sepharose FF column. The content of alpha s1-CN-5P(f59-79), which has high retention ability for calcium phosphate, was the highest in the CPPs.
N-Heterocyclic Carbenes: A New Concept in Organometallic Catalysis (2002)

N-Heterocyclic carbenes have become universal ligands in organometallic and inorganic coordination chemistry. They not only bind to any transition metal, be it in low or high oxidation states, but also to main group elements such as beryllium, sulfur, and iodine. Because of their specific coordination chemistry, N-heterocyclic carbenes both stabilize and activate metal centers in quite different key catalytic steps of organic syntheses, for example, C-H activation, C-C, C-H, C-O, and C-N bond formation. There is now ample evidence that in the new generation of organometallic catalysts the established ligand class of organophosphanes will be supplemented and, in part, replaced by N-heterocyclic carbenes. Over the past few years, this chemistry has been the field of vivid scientific competition, and yielded previously unexpected successes in key areas of homogeneous catalysis. From the work in numerous academic laboratories and in industry, a revolutionary turning point in oraganometallic catalysis is emerging.
Protein disulfide isomerase inhibition blocks thrombin generation in humans by interfering with platelet factor V activation (2017)

<b>BACKGROUND</b>: Protein disulfide isomerase (PDI) is required for thrombus formation. We previously demonstrated that glycosylated quercetin flavonoids such as isoquercetin inhibit PDI activity and thrombus formation in animal models, but whether extracellular PDI represents a viable anticoagulant target in humans and how its inhibition affects blood coagulation remain unknown. <b>METHODS</b>: We evaluated effects of oral administration of isoquercetin on platelet-dependent thrombin generation in healthy subjects and patients with persistently elevated anti-phospholipid antibodies. <b>RESULTS</b>: Following oral administration of 1,000 mg isoquercetin to healthy adults, the measured peak plasma quercetin concentration (9.2 μM) exceeded its IC<sub>50</sub> for inhibition of PDI by isoquercetin in vitro (2.5 ± 0.4 μM). Platelet-dependent thrombin generation decreased by 51% in the healthy volunteers compared with baseline (<i>P</i> = 0.0004) and by 64% in the anti-phospholipid antibody cohort (<i>P</i> = 0.015) following isoquercetin ingestion. To understand how PDI affects thrombin generation, we evaluated substrates of PDI identified using an unbiased mechanistic-based substrate trapping approach. These studies identified platelet factor V as a PDI substrate. Isoquercetin blocked both platelet factor Va and thrombin generation with an IC<sub>50</sub> of ~5 μM. Inhibition of PDI by isoquercetin ingestion resulted in a 53% decrease in the generation of platelet factor Va (<i>P</i> = 0.001). Isoquercetin-mediated inhibition was reversed with addition of exogenous factor Va. <b>CONCLUSION</b>: These studies show that oral administration of isoquercetin inhibits PDI activity in plasma and diminishes platelet-dependent thrombin generation predominantly by blocking the generation of platelet factor Va. These pharmacodynamic and mechanistic observations represent an important step in the development of a novel class of antithrombotic agents targeting PDI. <b>TRIAL REGISTRATION</b>: Clinicaltrials.gov (NCT01722669) <b>FUNDING</b>: National Heart, Lung, and Blood Institute (U54 HL112302) and Quercegen Pharma.
Parabrachial nucleus lesions impair feeding response elicited by 2,5-anhydro-D-mannitol (1995)

Systemic injection of the fructose analogue 2,5-anhydro-D-mannitol (2,5-AM) elicits a feeding response and induces c-fos activity in the parabrachial nuclei (PBN). We used bilateral ibotenic acid lesions of PBN to determine whether the activation inferred from c-fos activity was causally related to the feeding response. The relationship between the PBN lesion and feeding behavior was also examined with the glucose analogue 2-deoxy-D-glucose (2-DG). The PBN lesions interfered with the feeding response to 2,5-AM but spared the feeding response to 2-DG. Rats were also tested in a conditioned taste-aversion paradigm. Differences were observed in the relationship between lesion extent and behavioral deficit for feeding responses to 2,5-AM and taste-guided intake after taste-aversion conditioning. These data provide the first demonstration that central lesions can disrupt feeding responses to peripherally acting 2,5-AM. The results suggest that the neural substrate for this response differs from that mediating taste-aversion conditioning and from that involved in the feeding response to 2-DG.
A type-checking preprocessor for Cilk 2, a multithreaded C language (1995)

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1995.
Social class and coronary heart disease. (1981)

Over the past 40 years in England and Wales the rise in mortality from coronary heart disease has continued unabated among working-class men, whereas among professional men the rate has changed little for the past 20 years. As a result it is now 26 per cent higher in social class V compared with social class I. The difference in women is larger (+ 152%), and it has been present for at least 40 years. The social class gradient for men was confirmed in a survey of 17530 London civil servants aged between 40 and 64 (the Whitehall Study). When men in the lowest employment grade were compared with those in the top (administrative) grade, the age-adjusted prevalence rate was 53 per cent higher for angina, 77 per cent higher for ischaemic-type electrocardiographic abnormalities, and 75 per cent higher for the prevalence of electrocardiographic abnormality among men with angina. At follow-up, the seven-and-a-half year coronary mortality was 3.6 times higher in the lowest than in the top grade. This social class difference was partly explained by known coronary risk factors: men in the lower grades smoked more and exercised less, they were shorter and more overweight, and they had higher blood pressures and lower levels of glucose tolerance. Most of the difference, however, remains unexplained. It seems that there are major risk factors yet to be identified, and that these may throw light on how it is possible for members of a highly-placed social group to have a relatively low risk of coronary heart disease.
Dimerization and DNA binding of auxin response factors (1999)

Auxin response factors (ARFs) are transcription factors that bind with specificity to TGTCTC auxin response elements (AuxREs) found in promoters of primary/early auxin response genes. ARFs are encoded by a multi-gene family, consisting of more than 10 genes. Ten ARFs have been analyzed by Northern analysis and were found to be expressed in all major plant organs and suspension culture cells of Arabidopsis. The predicted amino acid sequences indicate that the 10 ARFs contain a novel amino-terminal DNA binding domain and a carboxyl-terminal dimerization domain, with the exception of ARF3 which lacks this dimerization domain. All ARFs tested bind with specificity to the TGTCTC AuxRE, but there are subtle variations in the sequence requirements at positions 5 (T) and 6 (C) of the AuxRE. While the amino-terminal domain of about 350 amino acids is sufficient for binding ARF1 to TGTCTC AuxREs, this domain is not sufficient for the binding of some other ARFs to palindromic AuxREs. Our results suggest that ARFs must form dimers on palindromic TGTCTC AuxREs to bind stably, and this dimerization may be facilitated by conserved motifs found in ARF carboxyl-terminal domains. Dimerization in at least some cases may dictate which ARF(s) are targeted to AuxREs.
A proposed operational model of thermotolerance based on effects of nutrients and the initial treatment temperature. (1980)

The phenomenon of thermotolerance in mammalian cells has been extensively documented in the literature. Because of its potential clinical importance as well as the fundamental biological interest, we pursued additional studies investigating pH and nutritional effects. Split-dose experiments were performed using plateau phase Chinese hamster HA-1 cells. The effects of the nutritional environment during the initial 43 degrees incubation and the second 43 degree treatment on the induction of thermotolerance were studied by comparing survival in full medium at pH 7.4 or in Hanks' balanced salt solution at pH 6.7. In additional experiments, we examined the effect on thermotolerance of changing the temperature of the initial treatment to 41 degrees. Thermotolerance was induced independently of the nutrient conditions of the first treatment. However, survival at the time of maximum expression of thermotolerance depended primarily on the duration and temperature of the initial treatment. Temperatures of 43 degrees or higher inhibited the development of thermotolerance during the first heat exposure. In contrast, if the initial exposure was at 41 degrees, thermotolerance was almost fully expressed by the end of this initial treatment. Changing pH in Hanks' balanced salt solution from 6.7 to 7.4 did not affect survival. On the basis of these and other data, we suggest that thermotolerance can be divided into three complementary and sometimes competing processes: an initial event ("trigger"); the expression of resistance ("development"); and its disappearance ("decay"). Trigger is induced at all hyperthermic temperatures while development requires a permissive temperature, i.e., less than 43 degrees for HA-1 cells. This model can provide plausible interpretations of several currently puzzling aspects of the survival kinetics of heat-exposed mammalian cells.
A method for difference cloning: gene amplification following subtractive hybridization. (1990)

We describe a procedure for genomic difference cloning, a method for isolating sequences present in one genomic DNA population ("tester") that is absent in another ("driver"). By subtractive hybridization, a large excess of driver is used to remove sequences common to a biotinylated tester, enriching the "target" sequences that are unique to the tester. After repeated subtractive hybridization cycles, tester is separated from driver by avidin/biotin affinity chromatography, and single-stranded target is amplified by the polymerase chain reaction, rendering it double-stranded and clonable. We model two situations: the gain of sequences that result from infection with a pathogen and the loss of sequences that result from a large hemizygous deletion. We obtain 100- to 700-fold enrichment of target sequences.
Transcriptional Properties of Genomic Transgene Integration Sites Marked by Electroporation or Retroviral Infection (2000)

As a possible consequence of their survival strategy, proviruses are predominantly found in transcription-promoting genomic sites. For certain applications, these findings have led to the preferential use of retroviral vectors for the stable integration of transgenes. This study demonstrates that transcription levels of single-copy proviruses, which have been established either by infection or by single-copy transfection (electroporation), are rather comparable. Therefore, electroporation is suggested as an alternative gene transfer route in cases where the use of infectious retroviral vehicles is to be avoided due to safety considerations. A difference between clones derived from these two gene transfer routes concerns the inactivation pattern which, for electroporated clones, is an exclusive property of the low expressers. This difference may be due to the nature of the illegitimate recombination event which is thought to be less invasive if catalyzed by the retroviral integrase. Substantial differences between infection and Ca phosphate-mediated transfection that have been reported earlier are explained by the respective transfection parameters.
TUMOR NECROSIS, CACHEXIA, SHOCK, AND INFLAMMATION: A COMMON MEDIATOR (1988)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Fluorescence Energy Transfer as a Probe for Tetraplex Formation:  The i-Motif (1999)

The secondary structure of cytosine-rich oligodeoxynucleotides has been investigated with fluorescent probes. Intramolecular folding of an oligonucleotide into an i-DNA motif led to fluorescence excitation energy transfer between a donor (fluorescein) and an acceptor (tetramethylrhodamine) covalently attached to the 5' and 3' ends of the DNA, respectively, provided that a suitable linker was chosen. The conjugation of the dyes to the oligonucleotide had an influence on the thermodynamics of i-motif formation as well as on the kinetics of folding. Intramolecular folding was demonstrated from the concentration independence of FRET over a wide concentration range. Folding of the oligonucleotide was confirmed by UV absorption melting experiments. The folding of the i-motif could be followed at concentrations as low as 50 pM. Fluorescence energy transfer can thus be used to reveal the formation of multistranded DNA structures.
Lipid Oxidation Products Have Opposite Effects on Calcifying Vascular Cell and Bone Cell Differentiation (1997)

Atherosclerotic calcification and osteoporosis often coexist in patients, yielding formation of bone mineral in vascular walls and its simultaneous loss from bone. To assess the potential role of lipoproteins in both processes, we examined the effects of minimally oxidized low-density lipoprotein (MM-LDL) and several other lipid oxidation products on calcifying vascular cells (CVCs) and bone-derived preosteoblasts MC3T3-E1. In CVCs, MM-LDL but not native LDL inhibited proliferation, caused a dose-dependent increase in alkaline phosphatase activity, which is a marker of osteoblastic differentiation, and induced the formation of extensive areas of calcification. Similar to MM-LDL, oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (ox-PAPC) and the isoprostane 8-iso prostaglandin E2 but not PAPC or isoprostane 8-iso prostaglandin F2 alpha induced alkaline phosphatase activity and differentiation of CVCs. In contrast, MM-LDL and the above oxidized lipids inhibited differentiation of the MC3T3-E1 bone cells, as evidenced by their stimulatory effect on proliferation and their inhibitory effect on the induction of alkaline phosphatase and calcium uptake. These results suggest that specific oxidized lipids may be the common factors underlying the pathogenesis of both atherosclerotic calcification and osteoporosis.
Trial of C1-Esterase Inhibitor in Acute Relapses of Neuromyelitis Optica (P4.004) (2014)

OBJECTIVE: To minimize complement-mediated damage during acute relapses of neuromyelitis optica (NMO), we tested a complement inhibitor, purified C1-esterase inhibitor (Cinryze®), added to current standard of care. BACKGROUND: NMO is a relapsing autoimmune disease targeting the spinal cord and optic nerve leading to paralysis and blindness. The pathology of acute NMO lesions involves a robust humoral response with significant complement-mediated destruction. DESIGN/METHODS: We conducted an open-label phase 1b safety and proof-of-concept trial in 10 subjects with NMO-IgG seropositive NMO or NMO spectrum disease (NMOSD) who presented with acute transverse myelitis and/or optic neuritis. In addition to treating with 1 gram of daily intravenous methylprednisolone, we infused 2000 Units of C1-esterase inhibitor daily x3 days beginning on day 1 of hospitalization. The primary outcome measure was safety, and the secondary efficacy measure was change in Expanded Disability Scale Scores (EDSS). RESULTS: Ten NMO-IgG seropositive subjects were enrolled, 7 of whom presented with acute transverse myelitis and 3 with acute optic neuritis. C1-esterase inhibitor proved safe in all 10 NMO subjects with no serious adverse events reported. One subject had a headache during the first infusion. There were no thromboembolic events or related lab abnormalities in any of the subjects. EDSS scores dropped from a median of 4.5 on admission to 4.0 on discharge and then down to 2.5 on 30-day follow up. All but one subject returned to pre-attack EDSS and only one subject required escalation to plasmapheresis. CONCLUSIONS: C1-esterase inhibitor is a safe add-on therapy for NMO/NMOSD patients presenting with acute transverse myelitis and optic neuritis. Preliminary evidence suggests a promising benefit with C1-esterase inhibitor in reducing damage and improving outcomes. A placebo-controlled trial is necessary to confirm these findings. Study Supported by: Viropharma