gebhart/patrepeval huggingface dataset:
Metabolism of retinol and retinoic acid in N-methyl-N-nitrosourea-induced mammary carcinomas in rats. (1989)

This study was conducted to examine the in vivo uptake and metabolism of natural retinoids by N-methyl-N-nitrosourea-induced mammary carcinomas. In this study, endogenous retinol and retinyl esters were present in normal mammary epithelial cells, but were undetectable in N-methyl-N-nitrosourea-induced mammary carcinomas in rats as determined by high-pressure liquid chromatography. No differences were found in plasma levels of retinol, in liver retinyl esters, or total content of vitamin A between tumor-bearing and control animals. Administered labeled retinol was taken up and esterified by normal mammary epithelial cells. Tumor-bearing rats were given injections i.p. of either [3H]retinol or [3H]retinoic acid. Radioactivity increased progressively with time in liver and other tissues except in breast tumor, where the uptake fluctuated over the 8 days after the injection of [3H]retinol; in mammary tumors practically no metabolism of [3H]retinol occurred, while in other tissues extensive esterification was detectable. In contrast, in animals given injections of [3H]retinoic acid, the uptake and metabolism of the label in the breast tumors paralleled with those found in other tissues. Neither the activity of acyl coenzyme A:retinol acyl transferase nor the activity of retinyl ester hydrolase was altered in the mammary tumor compared to the normal mammary gland. On the other hand, a significant decrease in the retinal oxidase activity was found in tumor tissue compared to normal mammary tissue. Since no esterification of [3H]retinol occurred in vivo despite the presence of acyl coenzyme A:retinol acyl transferase activity, it is possible that a specific defect in the cellular uptake of retinol may exist in N-methyl-N-nitrosourea-induced mammary carcinomas.
Effects of Soy Isoflavones and Conjugated Equine Estrogens on Inflammatory Markers in Atherosclerotic, Ovariectomized Monkeys (2005)

The effects of dietary soy isoflavones (IF) and conjugated equine estrogens (CEE) on circulating inflammatory markers were determined at the end of a 3-yr study of ovariectomized monkeys consuming a moderately atherogenic diet. Treatments were: 1) control, receiving alcohol-extracted soy-protein-based diet with low IF content (comparable to approximately 5 mg/d); 2) CEE, added to the control diet at a dose comparable to 0.625 mg/d; and 3) IF, consumed as a part of unextracted soy protein isolate at a dose comparable to 129 mg/d. Serum soluble vascular cell adhesion molecule-1 (sVCAM-1) was reduced by both IF (P < 0.006) and CEE (P < 0.0001) relative to controls. Serum monocyte chemoattractant protein (MCP)-1 was reduced by CEE (P < 0.0001) but not by IF (P = 1.00). Treatments did not affect serum IL-6 (P = 0.40), soluble E-selectin (P = 0.17), or C-reactive protein (P = 0.15). Serum MCP-1 and, to a lesser extent, IL-6 significantly correlated with atherosclerosis (plaque area) in the iliac and carotid arteries (all P < 0.05). Serum MCP-1 was also strongly associated with coronary artery atherosclerosis and with indices of plaque inflammation and matrix remodeling (matrix metalloproteinase-9) in the coronary artery intima (all P < 0.01). We conclude that, in this well-established nonhuman primate model of atherosclerosis, this dose of soy IF provided an antiinflammatory effect specific for sVCAM-1, whereas the effects of CEE extended to both sVCAM-1 and MCP1. It is possible that the atheroprotective effects of IF and CEE are mediated, at least in part, by effects on VCAM-1. The sites of IF inhibitory effects on sVCAM-1 production are not known, but likely candidates include the liver and/or the cardiovascular system.
Tetraspanins and malignancy (2001)

Tetraspanins, also called tetraspans or the transmembrane 4 superfamily (TM4SF), are cell-surface proteins that span the membrane four times and are found on many different cell types in many organisms. They display numerous properties that indicate their physiological importance in cell adhesion, motility, activation and proliferation, as well as their contribution to pathological conditions such as metastasis or viral infection. A major characteristic of tetraspanins is their ability to form cell-surface complexes with other molecules participating in cell adhesion, either to the extracellular matrix (ECM) or to other cells, and with molecules required for signalling. It is not yet known how the structure of the complexes might affect the functions of other molecules or what basic biochemical mechanisms allow their formation and regulation. Nevertheless, an intriguing association between tetraspanin expression and metastatic potential indicates that these molecules may provide novel insights into tumour progression.
Human Metapneumovirus Elicits Weak IFN-γ Memory Responses Compared with Respiratory Syncytial Virus (2006)

Human metapneumovirus (MPV) is a recently discovered pathogen that causes repeated lower respiratory tract infections beginning in infancy. The prevalence, nature and control of human regulatory responses to MPV are unknown. In this study, we develop and optimize systems to evaluate MPV-driven cytokine responses. Using primary culture of human PBMC from previously exposed adults, MPV-stimulated responses were directly compared with those elicited by genetically and clinically similar respiratory syncytial virus (RSV). Intense IL-6 production was evident following culture with infectious or inactivated RSV. MPV elicited IL-6 responses averaging 3.5-fold more intense (p < 0.001). Virus-dependent expression of IL-11, IL-12, IFN-alpha, and other innate immunity cytokines differed little between MPV and RSV. When examining adaptive immunity, RSV infection elicited strong IFN-gamma responses by all 60 adults. In marked contrast, MPV elicited IFN-gamma in a lower frequency of adults (p < 0.002) and at levels averaging 6-fold weaker (p < 0.001). These Th1-dominated responses were CD4, CD8, CD86 dependent, and were closely paralleled by strong virus-driven IL-10 and CCL5 production. For MPV and RSV, Th2 (IL-5, IL-13) responses were sporadic, occurring in 10-40% of the population. Thus, MPV and RSV, although both ubiquitous and leading to very high levels of infection, seroconversion, and clinically similar presentation in the population, evoke distinct innate and adaptive T cell-dependent cytokine responses. Although both viruses yield Th1-dominated responses with strong IL-10 and CCL5 production, MPV restimulation results in markedly more robust IL-6 and significantly weaker adaptive cytokine responses, in both prevalence and intensity, than does RSV.
Critical Point and the Nature of the Pseudogap of Single-Layered Copper-OxideBi2Sr2−xLaxCuO6+δSuperconductors (2005)

We apply strong magnetic fields of H=28.5 to 43 T to suppress superconductivity (SC) in the cuprates Bi2Sr2-xLaxCuO6+delta (x=0.65, 0.40, 0.25, 0.15, and 0), and investigate the low temperature (T) normal state by 63Cu nuclear spin-lattice relaxation rate (1/T1) measurements. We find that the pseudogap (PG) phase persists deep inside the overdoped region but terminates at x approximately 0.05, which corresponds to the hole doping concentration of approximately 0.21. Beyond this critical point, the normal state is a Fermi liquid that persists as the ground state when superconductivity is removed by the magnetic field. A comparison of the superconducting state with the H-induced normal state in the x=0.40 (Tc=32 K) sample indicates that there remains substantial part of the Fermi surface even in the fully developed PG state, which suggests that the PG and SC are coexisting matters.
Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models (2010)

To examine the role of breast cancer stem cells (BCSCs) in metastasis, we generated human-in-mouse breast cancer orthotopic models using patient tumor specimens, labeled with optical reporter fusion genes. These models recapitulate human cancer features not captured with previous models, including spontaneous metastasis in particular, and provide a useful platform for studies of breast tumor initiation and progression. With noninvasive imaging approaches, as few as 10 cells of stably labeled BCSCs could be tracked in vivo, enabling studies of early tumor growth and spontaneous metastasis. These advances in BCSC imaging revealed that CD44(+) cells from both primary tumors and lung metastases are highly enriched for tumor-initiating cells. Our metastatic cancer models, combined with noninvasive imaging techniques, constitute an integrated approach that could be applied to dissect the molecular mechanisms underlying the dissemination of metastatic CSCs (MCSCs) and to explore therapeutic strategies targeting MCSCs in general or to evaluate individual patient tumor cells and predict response to therapy.
Sympathetic activation of lipid synthesis in brown adipose tissue in the rat. (1988)

1. The roles of the sympathetic nerves in regulating lipid synthesis in brown adipose tissue (BAT) were studied by measuring incorporation of 3H from 3H2O into glyceride glycerol and glyceride fatty acids in the interscapular BAT in anaesthetized rats. 2. When noradrenaline was infused intravenously at a total dose of 1-8 micrograms/100 g body weight over 30 min, 3H incorporation into glyceride glycerol increased whereas 3H incorporation into fatty acids did not change. Similar responses were found when the sympathetic nerves entering the interscapular BAT were stimulated continuously at 10 Hz. However, when electrical stimuli consisting of a much shorter train (2 s) were applied to the nerves at 3 min intervals at 10 Hz (stimulation in bursts). 3H incorporation into both glyceride glycerol and fatty acids was enhanced. Stimulation in bursts elicited more pronounced lipogenic responses than other patterns that were employed, and involved the delivery of precisely the same number of impulses over the whole period of stimulation. The lipogenic responses to nerve stimulation in bursts were increased by increasing the stimulus frequency over the range 4-40 Hz. 3. Simultaneous administration of propranolol and phenoxybenzamine had little effect on either the fatty acid or the glyceride glycerol response to nerve stimulation. In contrast, these blocking agents almost completely eliminated the responses to noradrenaline infusion. 4. Pre-treatment with guanethidine effectively abolished the lipogenic response to nerve stimulation but potentiated the response to noradrenaline infusion. 5. It is concluded that lipid synthesis in BAT is enhanced by direct electrical stimulation of the sympathetic nerves only when they are stimulated in bursts. Sympathetic activation of lipogenesis in BAT is not solely attributable to the action of noradrenaline but involves some non-adrenergic mechanism.
Stereocontrolled Total Synthesis of (−)-Vincamajinine and (−)-11-Methoxy-17-epivincamajine (2004)

The first total syntheses of (-)-vincamajinine (5) (from Na-methyl-d-tryptophan methyl ester) and (-)-11-methoxy-17-epivincamajine (6) (from Na-methyl-6-methoxy-d-tryptophan ethyl ester) are described. The syntheses have been completed in a highly stereocontrolled manner (>98% ee). Key steps included the asymmetric Pictet-Spengler reaction, enolate-mediated palladium cross-coupling reaction, and acid-catalyzed formation of the C(7)-C(17) bond. In addition, the triethylsilane/TFA-mediated incorporation of the 2alpha-H (11 to 12) and the borohydride generation of the C(17) hydroxyl function (R) were also stereospecific. The unique highly conjested carbon skeletons of the two alkaloids were completed in a concise manner and in regiospecific fashion.
Identification of RNA sequences and structures involved in site-specific cleavage of IGF-II mRNAs (1998)

Insulin-like growth factor-II (IGF-II) mRNAs are subject to site-specific endonucleolytic cleavage in the 3' untranslated region (UTR), rendering an unstable 5' cleavage product containing the coding region and a very stable 3' cleavage product of 1.8 kb consisting of the 3'-UTR sequence and the poly(A) tail. Previously, it was established that two widely separated elements in the 3'-UTR (elements I and II), that can form a duplex structure, are necessary and sufficient for cleavage. To further investigate the sequence and secondary structure requirements for cleavage, we have introduced a number of mutations around the cleavage site and assayed their effects on cleavage. Several recognition determinants involved in the endonucleolytic cleavage of IGF-II mRNAs were identified. Mutational analysis around the cleavage site revealed that cleavage is sequence specific and that the cleavage site must be in a single-stranded conformation to allow efficient cleavage. In addition, we have identified an accessory protein that specifically interacts with a stem-loop structure located 133 to 73 nt upstream of the cleavage site.
Pre-validation and inference in microarrays (2002)

In microarray studies, an important problem is to compare a predictor of disease outcome derived from gene expression levels to standard clinical predictors. Comparing them on the same dataset that was used to derive the microarray predictor can lead to results strongly biased in favor of the microarray predictor. We propose a new technique called "pre-validation'' for making a fairer comparison between the two sets of predictors. We study the method analytically and explore its application in a recent study on breast cancer.
[Vascular endothelial growth factor. From basic research to clinical application]. (1999)

There is increasing evidence to support the concept that growth and metastasis of solid tumors, including those of gastrointestinal tract, is facilitated by neoangiogenesis. Vascular Endothelial Growth Factor (VEGF) is one of the most powerful known inducer of endothelial cell growth. Therefore, VEGF is likely to contribute to tumor growth by promoting angiogenesis and stroma formation both directly, through its neovascularization inducing activity, and indirectly, by increasing vascular permeability. In addition, VEGF facilitates tumor diffusion favouring metastatic spread of cancer cells. In view of these implications, it is important to understand the physiopathological role played by this factor. In this review the authors present the accumulating body of data on the biological and functional properties of VEGF, paying special reference to new evidence on its contribution in tumor immune escape, through a marked inhibition of differentiation and activity of the professional antigen presenting cells (APC), namely dendritic cells (DC). As the molecular and cellular events that underlie the functional role of VEGF in tumor angiogenesis and immune suppression become better defined, rational pharmacological and/or gene therapies can be derived in order to treat those neoplasms, such as pancreatic adenocarcinoma, not well amenable to chemo- and radiotherapy or immunotherapy.
Characteristic dimensions for heat transfer (2010)

Teniendo en cuenta la necesidad y la importancia de introducir en el currículo de estudio de física e ingeniería los conceptos fundamentales relacionados con la transferencia de calor, en este trabajo, a partir de las soluciones de la ecuación de conducción de calor no estacionaria, discutiremos las escalas espaciales y temporales involucradas en las leyes de ese fenómeno y los límites de validez de su descripción actual, con la esperanza de que esos conceptos puedan ser de utilidad para profesores y estudiantes. Taking into account the actual need and importance of introducing the main concepts of heat transfer in the curriculum of science and engineering studies, and starting from the solutions of the non-stationary heat conduction equation, we discuss the length and time scales involved in the laws of this phenomenon and the limits of validity of its current description, hoping that these concepts can be helpful for teachers and students.
Kinetic Studies of Guinea Pig Liver Transglutaminase Reveal a General-Base-Catalyzed Deacylation Mechanism (2001)

Guinea pig liver transglutaminase (TGase) reacts with 0.1 mM N-Cbz-L-Glu(gamma-p-nitrophenyl ester)Gly (5, prepared herein, K(M) = 0.02 mM) to undergo rapid acylation that can be followed spectrophotometrically at 400 nm (pH 7.0, 25 degrees C). Deacylation of the transiently formed thiolester acyl enzyme intermediate via catalytic aminolysis was studied in the presence of six primary amines of widely varying basicity (pK(NH+) = 5.6-10.5). Steady-state kinetic studies were performed to measure k(cat) and K(M) values for each amine substrate. A Brønsted plot constructed through the correlation of log(k(cat)/K(M)) and pK(NH+) for each amine substrate displays a linear free-energy relationship with a slope beta(nuc) = -0.37 +/- 0.08. The shallow negative slope is consistent with a general-base-catalyzed deacylation mechanism in which a proton is removed from the amine substrate during its rate-limiting nucleophilic attack on the thiolester carbonyl. Kinetic isotope effects were measured for four acceptor substrates (water, kie = 1.1 +/- 0.1; aminoacetonitrile, kie = 5.9 +/- 1.2; glycine methyl ester, kie = 3.4 +/- 0.7; N-Ac-L-lysine methyl ester, kie = 1.1 +/- 0.1) and are consistent with a proton in flight at the rate-limiting transition state. The active site general-base implicated by these kinetic results is believed to be His-334, of the highly conserved TGase Cys-His-Asp catalytic triad.
Phase I study of intravenous Lu-labeled CC49 murine monoclonal antibody in patients with advanced adenocarcinoma. (1995)

CC49, a murine monoclonal antibody that recognizes the tumor-associated glycoprotein 72, was conjugated to the chemical chelate 1,4,7,10-tetraaza-1-(1-carboxy-3-(4-aminophenyl) propyl)-tris-4,7,10- ((carboxy)methyl)cyclododecane that had been labeled with a beta emitter, Lu. Preclinical studies had shown that Lu-labeled CC49 caused regression of human colon adenocarcinoma xenografts in nude mice. Patients with advanced adenocarcinoma who had failed standard treatment and whose tumors expressed the tumor-associated glycoprotein 72 antigen were eligible for treatment to determine the maximum tolerated dose of Lu-labeled CC49. The starting dose of Lu was 10 mCi/m2 given i.v. with the dose of CC49 held constant at 20 mg. Pharmacokinetic sampling and immunoscintigraphy were performed over the ensuing 3 weeks. The dose of radioactive Lu was escalated by 15 mCi/m2 for each successive dose level. Unexpected bone marrow toxicity developed in patients treated at the second dose level with 25 mCi/m2 Lu; two patients developed grade 4 thrombocytopenia, while the third patient developed grade 3 thrombocytopenia. Pharmacokinetic studies showed that the plasma half-life of the immunoconjugate was 67 h; whole-body retention, however, was prolonged with a biological half-life of 258 h. Serial gamma camera imaging localized known tumor in all patients, and also demonstrated prolonged Lu retention in the reticuloendothelial system (RES). Bone marrow dosimetry estimates ranged from 4 to 5 REMS/mCi Lu based on imaging and biopsy data. Analysis of bone marrow biopsies demonstrated that most of the Lu was localized in the cellular compartment and not in the bone. No antitumor responses were observed. Intravenous administration of 15 mCi/m2 Lu-labeled CC49 to previously treated advanced cancer patients was associated with acceptable hematological toxicity and was the maximum tolerated dose. However, prolonged retention of Lu in the RES, including the bone marrow, was observed and limited the dose of Lu that could be given. Additional studies are indicated to reduce RES uptake and retention of this immunoconjugate.
CD-I full-motion video encoding on a parallel computer (1991)

article Free Access Share on CD-I full-motion video encoding on a parallel computer Authors: Frans Sijstermans Philips Research Labs, Eindhoven, The Netherlands Philips Research Labs, Eindhoven, The NetherlandsView Profile , Jan van der Meer Philips Consumer Electronics, Eindhoven, The Netherlands Philips Consumer Electronics, Eindhoven, The NetherlandsView Profile Authors Info & Claims Communications of the ACMVolume 34Issue 4April 1991pp 81–91https://doi.org/10.1145/103085.103093Published:01 April 1991Publication History 25citation523DownloadsMetricsTotal Citations25Total Downloads523Last 12 Months41Last 6 weeks7 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Evidence for the nature of true Lewis sites in faujasite-type zeolites (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEvidence for the nature of true Lewis sites in faujasite-type zeolitesPeter A. Jacobs and Hermann K. BeyerCite this: J. Phys. Chem. 1979, 83, 9, 1174–1177Publication Date (Print):May 1, 1979Publication History Published online1 May 2002Published inissue 1 May 1979https://pubs.acs.org/doi/10.1021/j100472a013https://doi.org/10.1021/j100472a013research-articleACS PublicationsRequest reuse permissionsArticle Views553Altmetric-Citations177LEARN 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 options Get e-Alerts
Identification and analysis of the gene encoding human PC2, a prohormone convertase expressed in neuroendocrine tissues. (1992)

In recent studies we have identified PC2 and PC3, members of a family of serine proteases that are related structurally to subtilisin, and have provided evidence that these are involved in the tissue-specific processing of prohormones and neuropeptides. PC2 is expressed at high levels in the islets of Langerhans, where it participates in the processing of proinsulin to insulin (S.P.S. and D.F.S., unpublished data). To evaluate the regulated expression of the human PC2 (hPC2) gene we have analyzed its structure and characterized its promoter. A map of the gene was constructed by using 11 clones isolated from two human genomic DNA libraries. The gene spans greater than 130 kilobase pairs and consists of 12 exons. Comparison with the structure of the gene encoding human furin, another member of this superfamily, revealed a high degree of conservation of exon-intron junctions. The hPC2 gene was localized to chromosome 20, band p11.2. The 5' flanking region of the hPC2 gene is very G+C-rich and contains six potential Sp1 binding sites but no TATA or CAAT box. Expression of chloramphenicol acetyltransferase reporter fusions containing the putative promoter region was observed to occur in beta TC-3 mouse insulinoma cells but not in HepG2 human hepatoma cells, consistent with the known tissue-specific pattern of expression of the hPC2 gene. Analysis of the level of chloramphenicol acetyltransferase activity with several deletion mutants identified the region from -1100 to -539 from the translation start site as essential for hPC2 promoter activity.