gebhart/patrepeval huggingface dataset:
Differential effects of angiostatic steroids and dexamethasone on angiogenesis and cytokine levels in rat sponge implants (1996)

. Subcutaneous implantation of sterile polyether sponges elicited a reproducible neovascular response in rats, as determined by blood flow measurement with a 133 Xe clearance technique and confirmed histologically. This model was used to monitor the levels of two cytokines during angiogenesis and to compare the activities of angiostatic steroids and anti‐inflammatory steroids. . Initial experiments followed the neovascular development over a 20‐day period. Daily local injection of hydrocortisone caused a dose‐dependent (0.5, 5 and 50 μg per sponge) inhibition of the basal sponge‐induced angiogenesis. However, daily systemic treatment of hydrocortisone (2, 10 and 50 mg kg −1 , s.c.) was less effective at inhibiting angiogenesis, and this inhibition was not sustained by day 20 after sponge implantation. . To investigate the involvement of cytokines during the course of angiogenesis, we measured the endogenous levels of tumour necrosis factor‐α (TNF‐α) and interleukin 6 (IL‐6) in sponge implants. Levels of IL‐6 and TNF‐α peaked at day 7 and day 11 after implantation, respectively. These cytokine levels subsided through the completion of angiogenesis by day 20. . Subsequent experiments were carried out over a 14‐day period. Among the three angiostatic steroids tested, U‐24067 (6α‐fluoro‐17,21‐dihydroxy‐16α‐methylpregna‐4,9(11)‐diene‐3,20‐dione‐21‐acetate) showed a dose‐dependent inhibition (0.5, 5 and 50 μg per sponge per day) of sponge‐induced angiogenesis. Tetrahydro‐S was also effective at 5 μg doses, but medroxyprogesterone failed to affect the angiogenic response. None of these steroids caused atrophies of the spleen and thymus. . Daily local injection of dexamethasone (0.5 μg per sponge) inhibited the basal sponge‐induced angiogenesis almost completely. Although higher doses of dexamethasone (5 and 50 μg per sponge) did not produce further inhibition of angiogenesis, they caused severe spleen and thymus weight losses, indicative of immunosuppression. . At the daily dose of 5 μg per sponge, dexamethasone inhibited angiogenesis and produced a marked reduction in the levels of TNF‐α and IL‐6 at day 14. In contrast, hydrocortisone, U‐24067 and tetrahydro‐S did not influence the levels of TNF‐α and IL‐6. . We concluded that the anti‐angiogenic activity of angiostatic steroids and anti‐inflammatory steroids in the rat sponge model is independent of their ability to reduce the production of TNF‐α and IL‐6. The differential effects of angiostatic and anti‐inflammatory steroids suggest that U‐24067 and its derivatives may have therapeutic potential in the management of angiogenic diseases such as rheumatoid arthritis.
AUTOMATED REQUIREMENTS ELICITATION: COMBINING A MODEL-DRIVEN APPROACH WITH CONCEPT REUSE (2003)

Extracting pertinent and useful information from customers has long plagued the process of requirements elicitation. This paper presents a new approach to support the elicitation process. This approach combines various techniques for requirements elicitation which include model-based concept acquisition, goal-driven structured interview and concept reuse. Compared with the available approaches for requirements elicitation, the most significant feature of our approach is that it supports both the automation of interaction with customers by using domain terminology, not software terminology and the automated construction of application requirements models using model-based concept elicitation and concept reuse. The capacity of this approach comes from its rich knowledge which is clustered into several abstract levels.
Synergism of energy starvation and dextran-conjugated doxorubicin in the killing of multidrug-resistant KB carcinoma cells (1999)

Here we report that 2-deoxyglucose/Na azide treatment and free/conjugated doxorubicin are synergistic in cell killing. As demonstrated by fluorescence confocal microscopy, KB-V1 cells retained more conjugated doxorubicin than free doxorubicin. Verapamil or 2-deoxyglucose/Na azide enhanced only the retention of the free drug and the small (<70 kDa) conjugates, indicating that P-glycoprotein (P-gp) is not effective against large conjugates. Conjugated doxorubicin was excluded from nuclei. Initially both free and conjugated doxorubicin accumulated in cytoplasmic organelles. Upon 2-deoxyglucose/Na azide treatment, fluorescence labeling of organelles dissipated. Prolonged (24 h) incubation of conjugate-preloaded cells resulted in redistribution of some of the organelle-associated fluorescence to nuclei, suggesting decoupling. The appearance of free doxorubicin was confirmed by capillary electrophoresis. 2-Deoxyglucose/Na azide treatment also retarded decoupling. Our results suggest that energy starvation, in addition to increasing cellular retention of P-gp substrates, may affect cellular fate of conjugated drugs with a possible enhancing effect in cancer cell killing.
Cross-Laboratory Experimental Study of Non-Noble-Metal Electrocatalysts for the Oxygen Reduction Reaction (2009)

Nine non-noble-metal catalysts (NNMCs) from five different laboratories were investigated for the catalysis of O(2) electroreduction in an acidic medium. The catalyst precursors were synthesized by wet impregnation, planetary ball milling, a foaming-agent technique, or a templating method. All catalyst precursors were subjected to one or more heat treatments at 700-1050 degrees C in an inert or reactive atmosphere. These catalysts underwent an identical set of electrochemical characterizations, including rotating-disk-electrode and polymer-electrolyte membrane fuel cell (PEMFC) tests and voltammetry under N(2). Ex situ characterization was comprised of X-ray photoelectron spectroscopy, neutron activation analysis, scanning electron microscopy, and N(2) adsorption and its analysis with an advanced model for carbonaceous powders. In PEMFC, several NNMCs display mass activities of 10-20 A g(-1) at 0.8 V versus a reversible hydrogen electrode, and one shows 80 A g(-1). The latter value corresponds to a volumetric activity of 19 A cm(-3) under reference conditions and represents one-seventh of the target defined by the U.S. Department of Energy for 2010 (130 A cm(-3)). The activity of all NNMCs is mainly governed by the microporous surface area, and active sites seem to be hosted in pore sizes of 5-15 A. The nitrogen and metal (iron or cobalt) seem to be present in sufficient amounts in the NNMCs and do not limit activity. The paper discusses probable directions for synthesizing more active NNMCs. This could be achieved through multiple pyrolysis steps, ball-milling steps, and control of the powder morphology by the addition of foaming agents and/or sulfur.
Synthesis of a Series of Potent and Orally Bioavailable Thrombin Inhibitors That Utilize 3,3-Disubstituted Propionic Acid Derivatives in the P3 Position (1997)

As part of an effort to prepare efficacious and orally bioavailable analogs of the previously reported thrombin inhibitors 1a, b, we have synthesized a series of compounds that utilize 3,3-disubstituted propionic acid derivatives as P3 ligands. By removing the N-terminal amino group, the general oral bioavailability of this class of compounds was enhanced without excessively increasing the lipophilicity of the compounds. The overall properties of the molecules could be drastically altered depending on the nature of the groups substituted onto the 3-position of the P3 propionic acid moiety. A number of the compounds exhibited good oral bioavailability in rats and dogs, and numerous compounds were efficacious in a rat FeCl3-induced model of arterial thrombosis. Compound 7, the 3,3-diphenylpropionic acid derivative, showed the best overall profile of in vivo and in vitro activity. Molecular modeling studies suggest that these compounds bind in the thrombin active site in a manner essentially identical to that previously reported for compound 1a.
Proteome-wide analysis of mutant p53 targets in breast cancer identifies new levels of gain-of-function that influence PARP, PCNA, and MCM4 (2015)

The gain-of-function mutant p53 (mtp53) transcriptome has been studied, but, to date, no detailed analysis of the mtp53-associated proteome has been described. We coupled cell fractionation with stable isotope labeling with amino acids in cell culture (SILAC) and inducible knockdown of endogenous mtp53 to determine the mtp53-driven proteome. Our fractionation data highlight the underappreciated biology that missense mtp53 proteins R273H, R280K, and L194F are tightly associated with chromatin. Using SILAC coupled to tandem MS, we identified that R273H mtp53 expression in MDA-MB-468 breast cancer cells up- and down-regulated multiple proteins and metabolic pathways. Here we provide the data set obtained from sequencing 73,154 peptide pairs that then corresponded to 3,010 proteins detected under reciprocal labeling conditions. Importantly, the high impact regulated targets included the previously identified transcriptionally regulated mevalonate pathway proteins but also identified two new levels of mtp53 protein regulation for nontranscriptional targets. Interestingly, mtp53 depletion profoundly influenced poly(ADP ribose) polymerase 1 (PARP1) localization, with increased cytoplasmic and decreased chromatin-associated protein. An enzymatic PARP shift occurred with high mtp53 expression, resulting in increased poly-ADP-ribosylated proteins in the nucleus. Mtp53 increased the level of proliferating cell nuclear antigen (PCNA) and minichromosome maintenance 4 (MCM4) proteins without changing the amount of pcna and mcm4 transcripts. Pathway enrichment analysis ranked the DNA replication pathway above the cholesterol biosynthesis pathway as a R273H mtp53 activated proteomic target. Knowledge of the proteome diversity driven by mtp53 suggests that DNA replication and repair pathways are major targets of mtp53 and highlights consideration of combination chemotherapeutic strategies targeting cholesterol biosynthesis and PARP inhibition.
T Cell Recognition Patterns of Immunodominant Cytomegalovirus Antigens in Primary and Persistent Infection (2007)

Replication of human cytomegalovirus is controlled by a vigorous CD8 T cell response. The persistent nature of infection is believed to periodically stimulate T cell responses resulting in considerable expansions of virus-specific CD8 T cells over time. In this study, we describe the magnitude and breadth of CD8 T cell responses against the immunodominant viral Ags, IE-1 and pp65, in acute and long-term infection using the IFN-gamma ELISPOT assay. Simultaneously, we have identified several novel MHC class I restricted CD8 T cell epitopes. Acute phase responses in immunocompetent donors appear to be extremely focused as early as 1 week post diagnosis with dominant peptide-specific responses observed against both proteins. These dominant responses remain detectable at all later time points over a 4-year follow-up. Interestingly the IE-1 responses show an increase over time whereas the pp65 responses do not, which contrasts with data showing that responses against both Ags are elevated in elderly individuals. We also observe the rapid emergence of an effector memory phenotype for virus-specific CD8 T cells as observed in persistent infection. Over time the revertant CD45RA(pos) effector cell population is also expanded, and this is more evident in the preferentially expanded IE-1 responses. We postulate that periodic low-level virus reactivation after the acute infection phase preferentially stimulates these responses whereas pp65-specific T cell expansions probably occur during the infrequent episodes of lytic viral replication or secondary infection.
Genetic Mapping of the Bovine Genome Using Deoxyribonucleic Acid-Level Markers to Identify Loci Affecting Quantitative Traits of Economic Importance (1990)

The first experiment designed to map loci affecting quantitative traits through linkage to Mendelian marker loci was carried out in 1923. In the past, application of these procedures was limited by lack of suitable genetic markers. The advent of immunological, biochemical, and, more recently, of DNA-level markers, has virtually removed this limitation, making possible an attempt to map most of the quantitative trait loci affecting traits of economic importance in dairy cattle. Theoretical studies show that experiments based on crosses will be most effective for mapping quantitative trait loci affecting traits whose value differs markedly between populations (e.g., populations differing in resistance or susceptibility to particular diseases). Experiments based on analyses of progeny groups withinsires will be most effective for mapping quantitative trait loci affecting traits showing considerable within-population genetic variation (e.g., growth-rate or milk production and composition). Analyses of progeny-tested sons of elite dairy sires can be an efficient means of mapping quantitative trait loci within dairy cattle populations.
Epac Activation Regulates Human Mesenchymal Stem Cells Migration and Adhesion (2016)

How to enhance the homing of human mesenchymal stem cells (hMSCs) to the target tissues remains a clinical challenge nowadays. To overcome this barrier, the mechanism responsible for the hMSCs migration and engraftment has to be defined. Currently, the exact mechanism involved in migration and adhesion of hMSCs remains unknown. Exchange protein directly activated by cAMP (Epac), a novel protein discovered in cAMP signaling pathway, may have a potential role in regulating cells adhesion and migration by triggering the downstream Rap family signaling cascades. However, the exact role of Epac in cells homing is elusive. Our study evaluated the role of Epac in the homing of hMSCs. We confirmed that hMSCs expressed functional Epac and its activation enhanced the migration and adhesion of hMSCs significantly. The Epac activation was further found to be contributed directly to the chemotactic responses induced by stromal cell derived factor-1 (SDF-1) which is a known chemokine in regulating hMSCs homing. These findings suggested Epac is connected to the SDF-1 signaling cascades. In conclusion, our study revealed that Epac plays a role in hMSCs homing by promoting adhesion and migration. Appropriate manipulation of Epac may enhance the homing of hMSCs and facilitate their future clinical applications.
Peptide assembly in the absence of base via Fmoc amino acid fluorides (1995)

Fmoc amino acid fluorides are highly efficient reagents for peptide assembly in the absence of tertiary bases, the presence of which may cause a variety of side reactions.
The gastrointestinal tract as a barrier in sepsis (1999)

The gastrointestinal tract is an organ of digestion and absorption which is metabolically active and has specific nutrient requirements. In health, it has an additional function as a major barrier, protecting the body from harmful intraluminal pathogens and large antigenic molecules. In disease states, such as sepsis when the mucosal barrier is compromised, micro-organisms and their toxic products gain access to the portal and systemic circulations producing deleterious effects. Under these circumstances, systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) develop leading to deterioration and death of the patient in the intensive care unit. Therapeutic strategies for such patients in the intensive care unit aim to support general immune function and maintain the structure and function of the gastrointestinal tract. For these therapies to be successful, the underlying septic or necrotic focus must be ablated using appropriate surgical or other invasive techniques.
Testing Interestingness Measures in Practice: A Large-Scale Analysis of Buying Patterns (2016)

Understanding customer buying patterns is of great interest to the retail industry. Association rule mining is a common technique for extracting correlations such as people in the South of France buy rosé wine or customers who buy paté also buy salted butter and sour bread. Unfortunately, sifting through a high number of buying patterns is not useful in practice, because of the predominance of popular products in the top rules. As a result, a number of "interestingness" measures (over 30) have been proposed to rank rules. However, there is no agreement on which measures are more appropriate for retail data. Moreover, since pattern mining algorithms output thousands of association rules for each product, the ability for an analyst to rely on ranking measures to identify the most interesting ones is crucial. In this paper, we develop CAPA (Comparative Analysis of PAtterns), a framework that provides analysts with the ability to compare different rule rankings. We report on how we used C A PA to compare 34 interestingness measures applied to patterns extracted from customer receipts of more than 1,800 stores for a period of one year.
Short-chain fatty acids induce γ-globin gene expression by displacement of a HDAC3-NCoR repressor complex (2006)

High-level induction of fetal (gamma) globin gene expression for therapy of beta-hemoglobinopathies likely requires local chromatin modification and dissociation of repressor complexes for gamma-globin promoter activation. A novel gamma-globin-inducing short-chain fatty acid derivative (SCFAD), RB7, which was identified through computational modeling, produced a 6-fold induction in a reporter assay that detects only strong inducers of the gamma-globin gene promoter and in cultured human erythroid progenitors. To elucidate the molecular mechanisms used by high-potency SCFADs, chromatin immunoprecipitation (ChIP) assays performed at the human gamma- and beta-globin gene promoters in GM979 cells and in erythroid progenitors demonstrate that RB7 and butyrate induce dissociation of HDAC3 (but not HDAC1 or HDAC2) and its adaptor protein NCoR, specifically from the gamma-globin gene promoter. A coincident and proportional recruitment of RNA polymerase II to the gamma-globin gene promoter was observed with exposure to these gamma-globin inducers. Knockdown of HDAC3 by siRNA induced transcription of the gamma-globin gene promoter, demonstrating that displacement of HDAC3 from the gamma-globin gene promoter by the SCFAD is sufficient to induce gamma-globin gene expression. These studies demonstrate new dynamic alterations in transcriptional regulatory complexes associated with SCFAD-induced activation of the gamma-globin gene and provide a specific molecular target for potential therapeutic intervention.
Local electronic properties of single-wall nanotube circuits measured by conducting-tip AFM (2000)

We use conducting-tip atomic force microscopy (AFM) to measure local electronic properties of single-wall carbon nanotube (SWNT) circuits on insulating substrates. When a voltage is applied to the tip and AFM feedback is used to position the tip, images formed from the tip-sample tunnel current have single tube resolution (near 1 nm diameter), more than an order of magnitude better than simultaneously acquired topographic AFM images. By finding points where the tip-sample current is zero, it is possible to measure the electrochemical potential within the circuit, again with nanometer resolution. Such measurements provide compelling evidence that nanotubes within a bundle have only weak electronic coupling. Finally, the AFM tip is used as a local electrostatic gate, and the gating action can be correlated with the structure of the SWNT bundle sample. This technique should be useful for a broad range of circuits containing SWNT's and other molecules.
Concanavalin a injection activates intrahepatic innate immune cells to provoke an antitumor effect in murine liver (2004)

Concanavalin A (ConA), directly injected into mice, induces T cell-mediated liver injury. However, it remains unclear whether ConA injection can activate innate immune cells, including natural killer (NK) cells and natural killer T (NKT) cells, both of which exist abundantly in the liver. Here we report that ConA injection stimulated interferon (IFN)-gamma production from liver NKT cells as early as 2 hours after injection and augmented YAC-1 cytotoxicity of liver NK cells. ConA-induced NK cell activation required other types of immune cells and critically depended on IFN-gamma. Because a nonhepatotoxic low dose of ConA was capable of fully activating both NKT cells and NK cells, we next addressed the possibility of ConA injection displaying an antitumor effect in the liver without liver injury. A nonhepatotoxic low-dose ConA injection augmented the cytotoxicity of liver NK cells against Colon-26 colon cancer cells and suppressed hepatic metastasis of Colon-26 cells in a NK cell- and IFN-gamma-dependent manner. In conclusion, a nonhepatotoxic low dose of ConA might serve as an immunomodulator that can preferentially activate the innate immune cells to induce an antitumor effect against metastatic liver tumor.
Measurement of growth hormone-releasing hormone and somatostatin in hypothalamic-portal plasma of unanesthetized sheep. Spontaneous secretion and response to insulin-induced hypoglycemia. (1990)

To elucidate the role of growth hormone (GH)-releasing hormone (GRH) and somatostatin (SRIH) in the regulation of the growth hormone (GH) secretory pattern, we collected portal blood from five unanesthetized ovariectomized ewes for repeated measurements of GRH and SRIH simultaneous with those of peripheral GH. Hormones were measured at 10-min intervals for 5.5 h and their interrelationships analyzed. Mean portal GRH was 20.4 +/- 6.7 (SD) pg/ml and the estimated overall secretion rate was 13 pg/min. GRH secretion was pulsatile with peaks of 25-40 pg/ml and a mean pulse interval of 71 min. Mean portal SRIH was 72 +/- 33 pg/ml and the estimated overall secretion rate was 32 pg/min. SRIH secretion was also pulsatile with peaks of 65-160 pg/ml and a mean pulse interval of 54 min. The GH pulse interval was 62 min. A significant association was present between GRH and GH secretory peaks though not between GRH and SRIH or SRIH and GH. Insulin hypoglycemia resulted in a rapid and brief stimulation of SRIH secretion followed by a decline in GH levels. No effect was observed on GRH secretion until 90 min, when a slight increase occurred. The results suggest (a) the presence of an independent neural rhythmicity of GRH and SRIH secretion with a primary role of GRH in determining pulsatile GRH secretion, and (b) that the inhibitory effects of insulin hypoglycemia on GH in this species are attributable to a combination of enhanced SRIH secretion and possibly other factors, though without significant inhibition of GRH.
The Escherichia coli polB Locus Is Identical to dinA, the Structural Gene for DNA Polymerase II (1997)

Escherichia coli DNA polymerase II (Pol II) is a member of the group B, "alpha-like" family of DNA polymerases. Pol II is encoded by the damage-inducible dinA gene and exhibits SOS induction under the control of Lex A repressor. The polB gene was originally designated as the structural gene for Pol II based on the absence of detectable Pol II activity in cell lysates prepared from a strain containing the mutant polB100 allele. Because polB and dinA mapped at different chromosomal locations, it remained an open question whether polB, in addition to lexA, might be involved in regulating the expression of Pol II. We have cloned and sequenced the polB100 mutant allele, including adjacent surrounding sequences, and have expressed the mutant dinA gene from Pol B100 on a high copy number plasmid. Our sequence data reveal that polB and dinA represent the same gene and that the original transduction mapping of polB was inaccurate. We purified the mutant Pol B100 polymerase and show that it retains 5 to 10% of the wild-type level of polymerase activity. The Pol B100 mutation, Gly401 --> Asp401, is not located within any of the five conserved domains that define group B polymerases. Pol B100 retains a wild-type level of 3' --> 5' exonuclease activity. We suggest that the normal level of exonucleolytic proofreading associated with the mutant Pol B100 enzyme may explain the repeated failures, over the past two decades, to detect phenotypes in polB mutant strains.