gebhart/patrepeval huggingface dataset:
CARDIOVASCULAR DISEASE RISK FACTORS PRIOR TO THE DIAGNOSIS OF IMPAIRED GLUCOSE TOLERANCE AND NON-INSULIN-DEPENDENT DIABETES MELLITUS IN A COMMUNITY OF OLDER ADULTS (1990)

Cardiovascular disease risk factors were measured 10-15 years (mean, 11.9 years) prior to the diagnosis of impaired glucose tolerance and non-insulin-dependent diabetes mellitus in Rancho Bernardo, California. There were 1,847 men and women aged 40-79 years who had no known diabetes or fasting hyperglycemia at baseline (1972-1974). At the follow-up examination (1984-1987), 1,115 men and women (60.4%) had normal glucose tolerance, 513 (27.8%) had impaired glucose tolerance, and 219 (11.9%) had non-insulin-dependent diabetes mellitus as defined by World Health Organization criteria. Rates of impaired glucose tolerance and non-insulin-dependent diabetes mellitus increased with age, and impaired glucose tolerance was approximately twice as common as non-insulin-dependent diabetes mellitus. Those with non-insulin-dependent diabetes mellitus were older and more overweight and had higher levels of blood pressure, fasting plasma glucose, and triglyceride at baseline than those whose glucose tolerance remained normal; those with impaired glucose tolerance generally had intermediate levels of the same risk factors. When it was examined in a prospective fashion, in general, the age-adjusted risk of non-insulin-dependent diabetes mellitus increased with increasing quartile of each risk factor, and the risk of non-insulin-dependent diabetes mellitus in a given quartile was greater than that for impaired glucose tolerance. Logistic regression analyses showed these factors to be positively associated with a subsequent diagnosis of impaired glucose tolerance as well as non-insulin-dependent diabetes mellitus in women, and to a lesser degree in men, independent of baseline age and body mass index (weight (kg)/height (m)2). These data illustrate that a less favorable cardiovascular risk factor profile precedes the diagnosis of both non-insulin-dependent diabetes mellitus and impaired glucose tolerance.
Chloroquine attenuates hemorrhagic shock-induced suppression of Kupffer cell antigen presentation and major histocompatibility complex class II antigen expression through blockade of tumor necrosis factor and prostaglandin release (1991)

Hemorrhagic shock suppresses the ability of Kupffer cells (KC) to present antigen and express the major histocompatibility complex class II (Ia) antigen. These alterations are concomitant with an enhanced release of cytokines (tumor necrosis factor [TNF], interleukin-1 [IL- 1], IL-6) and prostaglandin E2 (PGE2) by KC after hemorrhagic shock. The aim of this study was to determine whether chloroquine (CQ) administration in vivo before or after hemorrhage affects the altered cytokine and PGE2 release by KC as well as the capacity of KC to present antigen and express Ia. To study this, C3H/HeN mice were bled to and maintained at a mean arterial blood pressure of 35 mm Hg for 60 minutes, followed by fluid resuscitation. Chloroquine (10 mg/kg body weight) was injected intramuscularly 2 hours before or during resuscitation following shock. The administration of CQ led to a significant reduction in the hemorrhage-induced elevation of TNF, IL-6, and PGE2 release by KC; however, IL-1 secretion was not affected by CQ. In addition, CQ treatment abolished the hemorrhage-induced increase in circulating TNF and IL-6. These changes in cytokine and PGE2 release following CQ administration correlated with a significant enhancement of the antigen-presenting capacity of KC. No differences were observed between pretreatment and posttreatment with CQ. Our data indicate that CQ selectively inhibits the release of TNF, IL-6, and PGE2 by KC, while IL-1 secretion was unaffected. Because the reduction of these inflammatory mediators was concomitant with a significant improvement of KC capacity to present antigen and express Ia, we propose that TNF, IL-6, and PGE2 play a pivotal role in the induction of posthemorrhage immunosuppression. Furthermore, the data suggest that the suppression of KC functions occurs during or after resuscitation, because posttreatment with CQ was as effective as pretreatment. Additional studies indicated that the survival of animals after hemorrhage and sepsis was significantly increased by posttreatment of hemorrhaged mice with CQ. Thus, CQ, because of its unique ability to selectively inhibit the release of inflammatory cytokines and prostaglandins, represents a potent immunomodulating agent in the treatment of conditions associated with increased cytokine release and for decreasing the mortality from sepsis after hemorrhage.
Phase II Trial of Doxorubicin and Paclitaxel Plus Granulocyte Colony-Stimulating Factor in Metastatic Breast Cancer: An Eastern Cooperative Oncology Group Study (1999)

The doxorubicin/paclitaxel regimen that we used is unlikely to produce an objective response rate of more than 70% and a complete response rate of more than 20% in patients with metastatic breast cancer, and proved to be excessively cardiotoxic for use in the adjuvant setting.
Functional Inactivation of Endogenous MDM2 and CHIP by HSP90 Causes Aberrant Stabilization of Mutant p53 in Human Cancer Cells (2011)

The tight control of wild-type p53 by mainly MDM2 in normal cells is permanently lost in tumors harboring mutant p53, which exhibit dramatic constitutive p53 hyperstabilization that far exceeds that of wild-type p53 tumors. Importantly, mutant p53 hyperstabilization is critical for oncogenic gain of function of mutant p53 in vivo. Current insight into the mechanism of this dysregulation is fragmentary and largely derived from ectopically constructed cell systems. Importantly, mutant p53 knock-in mice established that normal mutant p53 tissues have sufficient enzymatic reserves in MDM2 and other E3 ligases to maintain full control of mutant p53. We find that in human cancer cells, endogenous mutant p53, despite its ability to interact with MDM2, suffers from a profound lack of ubiquitination as the root of its degradation defect. In contrast to wild-type p53, the many mutant p53 proteins which are conformationally aberrant are engaged in complexes with the HSP90 chaperone machinery to prevent its aggregation. In contrast to wild-type p53 cancer cells, we show that in mutant p53 cancer cells, this HSP90 interaction blocks the endogenous MDM2 and CHIP (carboxy-terminus of Hsp70-interacting protein) E3 ligase activity. Interference with HSP90 either by RNA interference against HSF1, the transcriptional regulator of the HSP90 pathway, or by direct knockdown of Hsp90 protein or by pharmacologic inhibition of Hsp90 activity with 17AAG (17-allylamino-17-demethoxygeldanamycin) destroys the complex, liberates mutant p53, and reactivates endogenous MDM2 and CHIP to degrade mutant p53. Of note, 17AAG induces a stronger viability loss in mutant p53 than in wild-type p53 cancer cells. Our data support the rationale that suppression of mutant p53 levels in vivo in established cancers might achieve clinically significant effects.
Pyrazolopyridine Inhibitors of B-RafV600E. Part 1: The Development of Selective, Orally Bioavailable, and Efficacious Inhibitors (2011)

The V600E mutation of B-Raf kinase results in constitutive activation of the MAPK signaling pathway and is present in approximately 7% of all cancers. Using structure-based design, a novel series of pyrazolopyridine inhibitors of B-Raf(V600E) was developed. Optimization led to the identification of 3-methoxy pyrazolopyridines 17 and 19, potent, selective, and orally bioavailable agents that inhibited tumor growth in a mouse xenograft model driven by B-Raf(V600E) with no effect on body weight. On the basis of their in vivo efficacy and preliminary safety profiles, 17 and 19 were selected for further preclinical evaluation.
Low Molecular Mass Gelators of Organic Liquids and the Properties of Their Gels (1997)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTLow Molecular Mass Gelators of Organic Liquids and the Properties of Their GelsPierre Terech and Richard G. WeissView Author Information Laboratoire Physico-Chimie Moléculaire, UMR 585, Département de Recherche Fondamentale sur la Matière Condensée, C.E.A.-Grenoble, 17, Rue des Martyrs, 38054 Grenoble Cédex 09, France, and Department of Chemistry, Georgetown University, Washington, DC 20057-1227 Cite this: Chem. Rev. 1997, 97, 8, 3133–3160Publication Date (Web):December 18, 1997Publication History Received10 March 1997Revised2 July 1997Published online18 December 1997Published inissue 1 December 1997https://pubs.acs.org/doi/10.1021/cr9700282https://doi.org/10.1021/cr9700282research-articleACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views17869Altmetric-Citations2857LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Aggregation,Gelation,Gels,Liquids,Molecules Get e-Alerts
IspH Protein ofEscherichiacoli:  Studies on Iron−Sulfur Cluster Implementation and Catalysis (2004)

The ispH gene of Escherichia coli specifies an enzyme catalyzing the conversion of 1-hydroxy-2-methyl-2-(E)-butenyl diphosphate into a mixture of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) in the nonmevalonate isoprenoid biosynthesis pathway. The implementation of a gene cassette directing the overexpression of the isc operon involved in the assembly of iron-sulfur clusters into an Escherichia coli strain engineered for ispH gene expression increased the catalytic activity of IspH protein anaerobically purified from this strain by a factor of at least 200. For maximum catalytic activity, flavodoxin and flavodoxin reductase were required in molar concentrations of 40 and 12 microM, respectively. EPR experiments as well as optical absorbance indicate the presence of a [3Fe-4S](+) cluster in IspH protein. Among 4 cysteines in total, the 36 kDa protein carries 3 absolutely conserved cysteine residues at the amino acid positions 12, 96, and 197. Replacement of any of the conserved cysteine residues reduced the catalytic activity by a factor of more than 70 000.
Compression of femtosecond optical pulses with dielectric multilayer interferometers (1986)

The group velocity dispersion of a multilayer thin film Gires-Tournois interferometer used for reflection of ultrashort optical pulses can be continuously tuned from positive to negative values at an extremely low loss in pulse energy. Thus, this device can be applied for compression of femtosecond pulses independent of the sign of the frequency chirp by simple angle tuning of the interferometer. This has been demonstrated with up-chirped 210 fs pulses which have been compressed to an almost transform-limited duration of 115 fs.
Identification and functional importance of tyrosine sulfate residues within recombinant factor VIII (1992)

Sulfated tyrosine residues within recombinant human factor VIII were identified by [35S]sulfate biosynthetic labeling of Chinese hamster ovary cells which express human recombinant factor VIII. Alkaline hydrolysis of purified [35S]sulfate-labeled factor VIII showed that greater than 95% of the [35S]sulfate was incorporated into tyrosine. [3H]Tyrosine and [35S]sulfate double labeling was used to quantify the presence of 6 mol of tyrosine sulfate per mole of factor VIII. Amino acid sequence analysis of thrombin and tryptic peptides isolated from [35S]sulfate-labeled factor VIII demonstrated tyrosine sulfate at residue 346 in the factor VIII heavy chain and at residues 1664 and 1680 in the factor VIII light chain. In addition, the carboxyl-terminal half of the A2 domain contained three tyrosine sulfate residues, likely at positions 718, 719, and 723. Interestingly, all sites of tyrosine sulfation border thrombin cleavage sites. The functional importance of tyrosine sulfation was examined by treatment of cells expressing factor VIII with sodium chlorate, a potent inhibitor of tyrosine sulfation. Increasing concentrations of sodium chlorate inhibited sulfate incorporation into factor VIII without affecting its synthesis and/or secretion. However, factor VIII secreted in the presence of sodium chlorate exhibited a 5-fold reduction in procoagulant activity, although the protein was susceptible to thrombin cleavage. These results suggest that tyrosine sulfation is required for full factor VIII activity and may affect the interaction of factor VIII with other components of the coagulation cascade.
Interferon-gamma depresses binding of ligand by C3b and C3bi receptors on cultured human monocytes, an effect reversed by fibronectin. (1986)

Cultivation of human monocytes with recombinant IFN-gamma causes a 5-10-fold depression in their binding of EC3b or EC3bi. This effect is observed within 18 h and is expressed for 5 d in the presence of 100 U/ml IFN-gamma. The capacity of IFN-gamma-treated phagocytes to bind EC3b and EC3bi is fully restored if the phagocytes are allowed to spread for 45 min on surfaces coated with Fn. IFN-gamma-treated cells express normal levels of cell surface C3b and C3bi receptors as measured with monoclonal anti-receptor antibodies, and spreading on Fn does not alter receptor number. We conclude that cultivation with IFN-gamma causes a change in the nature of these receptors that prevents them from interacting with ligand. Immunoelectron microscopy shows that C3bi receptors are expressed on the apical surface of the IFN-gamma-treated MO and that these receptors exhibit normal capacity to migrate in the plane of the membrane. Thus, the nature of the change caused by IFN-gamma is not related to changes in receptor number, location, or mobility. While spreading of IFN-gamma-treated cells on Fn enables C3 receptors to bind ligand, it does not enable them to promote phagocytosis. Treatment of cells with PMA alone does not affect binding or phagocytosis, but treatment of cells with both Fn and PMA enables cells to phagocytose EC3b and EC3bi. These data indicate that the binding and signaling activities of C3 receptors are separately regulated. Fn enables receptors to bind ligand and PMA enables them to signal phagocytosis.
Carbon deposition in a Bosch process using a cobalt and nickel catalyst (1980)

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1980.
Ergotamine Gangrene in Various Inflammatory Conditions (1971)

Given in subtoxic doses to the rat, ergotamine produced tail gangrene in not more than 20% of animals. The incidence rate of ergotamine gangrene was not influenced by acute Mammation (carrageenin, dextran oedema). However, when inflammation was produced by immersing the tail of the rat in dimethyl sulfoxide, the incidence rate of ergotamine gangrene was greatly increased. The gangrene-inducing effect of ergotamine was significantly increased in rats with adjuvant arthritis or 6-sulphanylamido-indazole arthritis. Like arthritic rats, rats with lathyrism due to chronic treatment with aminoacetonitrile were also more sensitive to the gangrene-inducing effect of ergotamine. Ergotamine-induced tail gangrene in adjuvant arthritic rats is a good model for use in research for drugs which are effective against the vascular complications of ‘collagen’ diseases.
Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra- and extrahepatic cholestasis (2003)

Farnesoid X receptor (FXR) is a bile acid-activated transcription factor that is a member of the nuclear hormone receptor superfamily. Fxr-null mice exhibit a phenotype similar to Byler disease, an inherited cholestatic liver disorder. In the liver, activation of FXR induces transcription of transporter genes involved in promoting bile acid clearance and represses genes involved in bile acid biosynthesis. We investigated whether the synthetic FXR agonist GW4064 could protect against cholestatic liver damage in rat models of extrahepatic and intrahepatic cholestasis. In the bile duct-ligation and alpha-naphthylisothiocyanate models of cholestasis, GW4064 treatment resulted in significant reductions in serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase, as well as other markers of liver damage. Rats that received GW4064 treatment also had decreased incidence and extent of necrosis, decreased inflammatory cell infiltration, and decreased bile duct proliferation. Analysis of gene expression in livers from GW4064-treated cholestatic rats revealed decreased expression of bile acid biosynthetic genes and increased expression of genes involved in bile acid transport, including the phospholipid flippase MDR2. The hepatoprotection seen in these animal models by the synthetic FXR agonist suggests FXR agonists may be useful in the treatment of cholestatic liver disease.
Analysis of a dual magnetoresistive head (1992)

A proposed dual magnetoresistive (DMR) reproduce head, consisting of two identical, adjacent MR stripes separated by a nonmagnetic spacer and connected electrically in parallel, was shown to have potential in very high density magnetic recording applications. The authors consider the micromagnetics of this device and derive approximate analytical expressions for the expected signal output as a function of linear recording density. The expression for the intrinsic reproduce sensitivity vs. recorded density, when including a proposed correction to account for the energy of traditionally neglected edge fringing fields, are shown to be in good agreement with more exact numerical results. The same form of equations is shown to be useful for deriving, via reciprocity, analogous and reasonably accurate analytical results for the shielded MR head.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Effects of single nucleotide polymorphisms on treatment outcomes and toxicity in patients treated with sunitinib. (2013)

Certain SNPs of KDR may affect treatment outcome and toxicity in patients treated with sunitinib.
Canadian Institutes of Health Research funds multi-year research program on chronic disease prevention in northern populations (2006)

The Canadian Institutes of Health Research (CIHR) has recently approved under its Team Grantsprogram the establishment of the CIHR Team in Circumpolar Chronic Disease Prevention, withfunding of $7.77 million CDN over 5 years. The team consists of principal investigators, co-investigatorsand collaborators from several academic research centres, regional health authorities, and indigenouspeoples’ organizations. The team leader is Prof. Kue Young of the University of Toronto.
Plant Breeding of Cannabis. Determination of Cannabinoids by High-Pressure Liquid Chromatography (1980)

Cannabinoids (CN) of CBDA stock, Tochishi No. 1 stock and crossed stock were determined on a high-pressure liquid chromatograph equipped with a LiChrosorb RP-18 column (25 cm×4 mm) by elution with a mixture of methanol and 0.02 N sulphuric acid (4 : 1). The CBDA stock was found to contain cannabidiolic acid (CBDA) and cannabichromenic acid (CBCA). Tochishi No. 1 stock was detected to have thtrahydrocannabinolic acid (THCA), CBCA and a small amount of CBDA. F1 was obtained by crossing CBDA stock (female) and Tochishi No. 1 stock (male). All 79 F1 specimens were found to contain CBDA, THCA and CBCA. Therefore F1 was designated the median type. F2 was then obtained by crossing F1 and out of 199 F2 specimens, 58, 40 and 101 stocks were designated as CBDA stock type, Tochishi No. 1 stock type and the median type by CN analysis, respectively. F3 was also gained by crossing CBDA stock type of F2 and all 166 F3 specimens were CBDA stock type. F4, which was obtained by crossing F3, was also CBDA stock type. In addition, the fibers of F4 were found to be better than those of the original CBDA stock, and F4 contained a negligible amount of THCA.
The anaphase-promoting complex is required in G1 arrested yeast cells to inhibit B-type cyclin accumulation and to prevent uncontrolled entry into S-phase (1997)

Inactivation of B-type cyclin dependent kinases due to ubiquitin-mediated cyclin proteolysis is necessary for the exit from mitosis. In Saccharomyces cerevisiae, proteolysis is initiated at the onset of anaphase and remains active until Cln1 and Cln2 cyclins appear in late G1 of the subsequent cell cycle. A large particle called the anaphase-promoting complex (APC) which is composed of the TPR proteins Cdc16p/Cdc23p/Cdc27p and other proteins is required for B-type cyclin ubiquitination in both anaphase and during G1 phase. The APC has an essential role for the separation of sister chromatids and for the exit from mitosis, but until now it was unclear whether the persistence of APC activity throughout G1 had any physiological role. We show here that the APC is needed in G1 arrested cells to inhibit premature appearance of B-type cyclins and to prevent unscheduled initiation of DNA replication. When pheromone arrested cells of cdc16 and cdc23 mutants were shifted to the restrictive temperature, they underwent DNA replication in the presence of pheromone. DNA replication also occurred in a G1 arrest induced by G1 cyclin (Cln) depletion, indicating that mutant cells with a defective APC initiate DNA replication without the Cln G1 cyclins, which are normally needed for the onset of S-phase. Degradation of Clb2p, Clb3p and Clb5p depends on the APC. This suggests that accumulation of any one of the six B-type cyclin proteins could account for the precocious replication of cdc16 and cdc23 mutants.
O,O'-Diphenyldithiophosphatotetracarbonylmanganese(I) and Related Compounds (1966)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTO,O'-Diphenyldithiophosphatotetracarbonylmanganese(I) and Related CompoundsR. L. Lambert and T. A. ManuelCite this: Inorg. Chem. 1966, 5, 7, 1287–1289Publication Date (Print):July 1, 1966Publication History Published online1 May 2002Published inissue 1 July 1966https://doi.org/10.1021/ic50041a051RIGHTS & PERMISSIONSArticle Views28Altmetric-Citations14LEARN 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 (396 KB) Get e-Alerts Get e-Alerts