gebhart/patrepeval huggingface dataset:
C-Reactive Protein and Hypertension: Is there A Causal Relationship? (2007)

There is a large body of evidence indicating that inflammation plays a crucial role in all steps characterizing the atherosclerotic process. C-Reactive Protein is a circulating marker of inflammation which recently emerged as a powerful independent determinant of cardiovascular events. Hypertension is closely linked to inflammation. Experimental data and results from cross-sectional studies in humans indicate a relationship between CRP levels and blood pressure. In particular, CRP seems to be related with markers of arterial stiffness, thus suggesting a specific interaction between CRP and systolic blood pressure. However, such observational studies cannot provide any direct evidence for a cause-effect relation. Prospective studies are likely candidates to better define the putative causal relationship on this association. Available results from longitudinal studies are scanty, and do not allow to draw definitive conclusions. Moreover, prospective, placebo-controlled intervention trials documenting that reduction of CRP levels by pharmacological treatment might lead to a reduced risk to develop hypertension are not yet available. Without such crucial information, at the present time the causal connection between inflammation and blood pressure, although regarded as an intriguing possibility, remains undiscovered.
Enhancement of gilthead seabream (Sparus aurata) larval growth by dietary vitamin E in relation to two different levels of essential fatty acids (2011)

The objective of this study was to determine the effect of dietary vitamin E on gilthead seabream (Sparus aurata) growth and survival, at two different highly unsaturated fatty acids (HUFAs) levels. Eighteen days old gilthead seabream larvae were fed four formulated experimental diets combining two different dietary levels of HUFAs (M: medium 2.5 + 1.5, DHA + EPA, H: high 5 + 2.5 DHA + EPA g per 100 g) with two different levels of vitamin E (M: medium 540 mg kg−1, H: high 2900 mg kg−1): MM, MH, HM, HH (HUFA/vitamin E). After 2-week feeding trial, the average survival rate was 52.6% and there were no significant differences found among treatments. Increase in vitamin E up to high level markedly improved larval growth, particularly when dietary HUFA levels were lower, suggesting a higher protection value when these fatty acids are more limiting. At medium dietary HUFA levels, increase in vitamin E from medium to high level enhanced larval growth performance in terms of total length. Moreover, increase in vit E enhanced HUFAs content in the larval polar lipids denoting the anti-oxidative effect of vitamin E.
Monoclonal antibodies as probes of the alpha-bungarotoxin and cholinergic binding regions of the acetylcholine receptor. (1987)

We have probed the acetylcholine receptor (AcChR) molecule with six anti-AcChR monoclonal antibodies (mAbs) whose binding to the AcChR is inhibited or blocked by alpha-bungarotoxin (alpha BgTx). mAbs bound with a maximum stoichiometry of either one mAb (387D, 247G) or two mAbs (383C, 572C, 370C, 249E) per AcChR monomer, and the extent to which they inhibited alpha BgTx binding directly correlated with their stoichiometry of binding. The effect of mAbs on the alpha BgTx and cholinergic ligand binding properties of the AcChR molecule defined three major categories of mAbs: those that block alpha BgTx and carbamylcholine (agonist) binding, but do not block d-tubocurarine (antagonist) binding (383C, 572C, 370C and 249E); mAb 387D, which blocks agonist binding and partially blocks alpha BgTx and d-tubocurarine binding; and mAb 247G, which does not affect agonist binding, blocks at most 50% of the alpha BgTx binding sites, and decreases the affinity of the high affinity component of d-tubocurarine binding (Mihovilovic, M., and Richman, D. P. (1984) J. Biol. Chem. 259, 15051-15059). Except for mAb 247G, these mAbs strongly competed with each other for binding to the AcChR. In contrast, mAb 247G blocks about 50% of the binding of all the other mAbs. The results demonstrate the ability of mAbs to stabilize different conformational states of the AcChR and to probe cholinergic epitopes of functional importance. They also indicate the nonequivalence of the two alpha-toxin binding regions of the AcChR molecule and suggest that it is possible to identify epitopes within the alpha BgTx binding region that when bound produce differential effects on the binding of the agonist (carbamylcholine) and the antagonist (d-tubocurarine).
Cooperative cobinding of synthetic and natural ligands to the nuclear receptor PPARγ (2018)

Crystal structures of peroxisome proliferator-activated receptor gamma (PPARγ) have revealed overlapping binding modes for synthetic and natural/endogenous ligands, indicating competition for the orthosteric pocket. Here we show that cobinding of a synthetic ligand to the orthosteric pocket can push natural and endogenous PPARγ ligands (fatty acids) out of the orthosteric pocket towards an alternate ligand-binding site near the functionally important omega (Ω)-loop. X-ray crystallography, NMR spectroscopy, all-atom molecular dynamics simulations, and mutagenesis coupled to quantitative biochemical functional and cellular assays reveal that synthetic ligand and fatty acid cobinding can form a ‘ligand link’ to the Ω-loop and synergistically affect the structure and function of PPARγ. These findings contribute to a growing body of evidence indicating ligand binding to nuclear receptors can be more complex than the classical one-for-one orthosteric exchange of a natural or endogenous ligand with a synthetic ligand.
Risk-free simultaneous prenatal identification of fetal Rhesus D status and sex by multiplex real-time PCR using cell free fetal DNA in maternal plasma (2001)

By developing a novel multiplex real-time PCR assay we present the first report describing the determination of multiple fetal loci from cell free DNA in maternal plasma by these means. As this assay is suitable for automation, our data, therefore, suggest that such assays provide a good basis for the clinical examination of multiple fetal loci, in particular Rhesus D status or fetal sex, and can be performed effectively using real-time multiplex PCR assays.
Characterization of Cells with a High Aldehyde Dehydrogenase Activity from Cord Blood and Acute Myeloid Leukemia Samples (2005)

Aldehyde dehydrogenase (ALDH) is a cytosolic enzyme that is responsible for the oxidation of intracellular aldehydes. Elevated levels of ALDH have been demonstrated in murine and human progenitor cells compared with other hematopoietic cells, and this is thought to be important in chemoresistance. A method for the assessment of ALDH activity in viable cells recently has been developed and made commercially available in a kit format. In this study, we confirmed the use of the ALDH substrate kit to identify cord blood stem/progenitor cells. Via multicolor flow cytometry of cord blood ALDH+ cells, we have expanded on their phenotypic analysis. We then assessed the incidence, morphology, phenotype, and nonobese diabetic/ severe combined immunodeficiency engraftment ability of ALDH+ cells from acute myeloid leukemia (AML) samples. AML samples had no ALDH+ cells at all, an extremely rare nonmalignant stem/progenitor cell population, or a less rare, leukemic stem cell population. Hence, in addition to identifying nonmalignant stem cells within some AML samples, a high ALDH activity also identifies some patients' CD34+/ CD38- leukemic stem cells. The incidence of normal or leukemic stem cells with an extremely high ALDH activity may have important implications for resistance to chemotherapy. Identification and isolation of leukemic cells on the basis of ALDH activity provides a tool for their isolation and further analysis.
Signaling Compression (SigComp) Requirements & Assumptions (2003)

The purpose of this document is to outline requirements and motivations for the development of a scheme for compression and decompression of messages from signaling protocols. In wireless environments and especially in cellular systems, e.g., GSM (Global System for Mobile communications) and UMTS (Universal Mobile Telecommunications System), there is a need to maximize the transport efficiency for data over the radio interface. With the introduction of SIP/SDP (Session Initiation Protocol/Session Description Protocol) to cellular devices, compression of the signaling messages should be considered in order to improve both service availability and quality, mainly by reducing the user idle time, e.g., at call setup.
Protection from Fas-Mediated Apoptosis by a Soluble Form of the Fas Molecule (1994)

Fas is an apoptosis-signaling receptor molecule on the surface of a number of cell types. Molecular cloning and nucleotide sequence analysis revealed a human Fas messenger RNA variant capable of encoding a soluble Fas molecule lacking the transmembrane domain because of the deletion of an exon encoding this region. The expression of soluble Fas was confirmed by flow cytometry and immunocytochemical analysis. Supernatants from cells transfected with the variant messenger RNA blocked apoptosis induced by the antibody to Fas. Levels of soluble Fas were elevated in patients with systemic lupus erythematosus, and mice injected with soluble Fas displayed autoimmune features.
Human kallikrein 5: a potential novel serum biomarker for breast and ovarian cancer. (2003)

The kallikrein family is a group of 15 serine protease genes clustered on chromosome 19q13.4. Human kallikrein (hK) gene 5 (KLK5) is a member of this family and encodes for a secreted serine protease (hK5). KLK5 was shown to be differentially expressed at the mRNA level in breast and ovarian cancer. Until now, detection of hK5 protein in either biological fluids or tissues has not been described due to lack of suitable reagents and methods. The aim of this study was to develop immunological reagents and a sensitive and specific fluorometric immunoassay (ELISA) for hK5, to examine the presence of hK5 in human tissues and biological fluids, and to study the possible clinical utility of hK5 as a biomarker for endocrine-related malignancies. Recombinant hK5 protein was produced and purified using a Pichia pastoris yeast expression system. The protein was used as an immunogen to generate mouse and rabbit polyclonal anti-hK5 antibodies. A sandwich-type microplate immunoassay (ELISA) was developed using these antibodies, coupled with a time-resolved fluorometric detection technique. The ELISA assay was then used to measure hK5 in various biological fluids, tissue extracts, and serum samples from normal individuals and patients with various malignancies. The hK5 ELISA immunoassay has a lower detection limit of 0.1 micro g/liter, is specific for hK5, and has no cross-reactivity with other homologous kallikreins. The dynamic range is 0.1-25 micro g/liter, and within-run and between-run coefficients of variation within this range are <10%. hK5 is found in many tissues, with the highest expression levels seen in the skin, breast, salivary gland, and esophagus. hK5 is present at relatively high levels in milk of lactating women. Whereas the levels of hK5 are almost undetectable in serum of normal individuals (male and female) and patients with diverse malignancies, higher concentrations were found in a proportion of patients with ovarian (69%) and breast (49%) cancer. High levels were also detected in ascites fluid from metastatic ovarian cancer patients and in ovarian cancer tissue extracts. In conclusion, we report development of the first immunofluorometric assay for hK5 and describe the distribution of hK5 in biological fluids and tissue extracts. Our preliminary data indicate that hK5 is a potential biomarker in patients with ovarian and breast cancer.
Alu sequences (1997)

Alu sequences are frequently encountered during study of human genomic nucleic acid and form a major component of repetitive DNA. This review describes the origin of Alu sequences and their subsequent amplification and evolution into distinct subfamilies. In recent years a number of different functional roles for Alu sequences have been described. The multiple influences of Alu sequences on RNA polymerase II-mediated gene expression and the presence of Alu sequences in RNA polymerase III-generated transcripts are discussed.
SiO2-Supported CeCl3·7H2O−NaI Lewis Acid Promoter:  Investigation into the Garcia Gonzalez Reaction in Solvent-Free Conditions⊥ (2007)

The Knoevenagel condensation of aldose sugars with beta-dicarbonyl compounds produces furan derivatives having polyhydroxyalkylated alkyl side chains; this reaction is known as the Garcia Gonzalez reaction. Despite the fact that these polyhydroxyalkyl furans are interesting scaffolds for synthetic chemists to utilize in the synthesis of a variety of biologically interesting molecules, the reported approach suffers from harsh conditions. The development of a general and more efficient protocol is of considerable importance, and in this manuscript, we wish to explore the role of the NaI in enhancing the activity of CeCl3.7H2O as a useful water-tolerant Lewis acid promoter for the Garcia Gonzalez reaction. The procedure proceeds with good yields at 50 degrees C using our system supported on SiO2 in solvent-free conditions and represents a simple and convenient methodology for the preparation of densely functionalized molecules. Furthermore, the first qualitative results obtained on mechanistic investigation on the role of iodide on this our heterogeneous reaction may be of value for optimization of existing organic transformations and for the development of new ones.
Evidence of insulin-stimulated phosphorylation and activation of the mammalian target of rapamycin mediated by a protein kinase B signaling pathway (1998)

The effects of insulin on the mammalian target of rapamycin, mTOR, were investigated in 3T3-L1 adipocytes. mTOR protein kinase activity was measured in immune complex assays with recombinant PHAS-I as substrate. Insulin-stimulated kinase activity was clearly observed when immunoprecipitations were conducted with the mTOR antibody, mTAb2. Insulin also increased by severalfold the 32P content of mTOR that was determined after purifying the protein from 32P-labeled adipocytes with rapamycin.FKBP12 agarose beads. Insulin affected neither the amount of mTOR immunoprecipitated nor the amount of mTOR detected by immunoblotting with mTAb2. However, the hormone markedly decreased the reactivity of mTOR with mTAb1, an antibody that activates the mTOR protein kinase. The effects of insulin on increasing mTOR protein kinase activity and on decreasing mTAb1 reactivity were abolished by incubating mTOR with protein phosphatase 1. Interestingly, the epitope for mTAb1 is located near the COOH terminus of mTOR in a 20-amino acid region that includes consensus sites for phosphorylation by protein kinase B (PKB). Experiments were performed in MER-Akt cells to investigate the role of PKB in controlling mTOR. These cells express a PKB-mutant estrogen receptor fusion protein that is activated when the cells are exposed to 4-hydroxytamoxifen. Activating PKB with 4-hydroxytamoxifen mimicked insulin by decreasing mTOR reactivity with mTAb1 and by increasing the PHAS-I kinase activity of mTOR. Our findings support the conclusion that insulin activates mTOR by promoting phosphorylation of the protein via a signaling pathway that contains PKB.
Phase 1 of Integrated EMDR An Abortive Treatment for Migraine Headaches (2008)

Forty-three individuals diagnosed with classic or common migraine headache were randomly assigned to either phase 1 of integrated eye movement desensitization reprocessing (EMDR) treatment or a standard care medication treatment. Integrated EMDR combines diaphragmatic breathing, cranial compression, and EMDR for abortive migraine treatment. The comparison standard care medication group received various abortive medications, including Demerol, DHE, oral triptans, Excedrin, Fiorinal, Percocet, Toradol, and Vicodin. Participants were treated during mid- to late-stage acute migraine and assessed by an independent evaluator at pretreatment, posttreatment, 24 hours, 48 hours, and 7 days for migraine pain level. Both standard care medication and integrated EMDR treatment groups demonstrated reduced migraine pain levels immediately at posttreatment, 24 hours, 48 hours, and 7 days. However, integrated EMDR treatment reduced or eliminated migraine pain with greater rapidity and showed significantly greater improvement compared to standard care medication immediately posttreatment.
Evaluating risk: IBM's Country Financial Risk and Treasury Risk Scorecards (2014)

IBM is a global enterprise operating in more than 160 countries and therefore needs to constantly monitor the risks that could affect its business. Changes in a country's regulatory, macroeconomic, and socioeconomic environments are all factors that could affect business opportunities. It is important to have an aggregated view of these indicators and be able to combine this data with internal, company-specific data. To accomplish this, IBM has deployed methodologies and tools to identify, assess, and monitor risks in the context of business operations. At the core of these efforts are two tools: the Country Financial Risk Scorecard (CFRS) and the Treasury Risk Scorecard (TRS). CFRS combines IBM's country-level financial information with each country's external macroeconomic profile. CFRS aggregates data from 18 data sources, providing a single financial risk reporting environment for country finance leaders. CFRS allows for risk comparison across countries by assigning a computed risk score based on each country's internal and external data. In addition, the TRS is built on the same aggregated data as CFRS while allowing user inputs in order to gather qualitative data not systematically available. Online Analytical Processing (OLAP) technologies and weighted-scoring rules provide analytical capabilities for risk categories applicable to treasury operations.
Novel Phospholipase-Resistant Lipid/Peptide Synthetic Lung Surfactants (2007)

Animal-derived drugs are currently widely-used to treat clinical lung surfactant deficiency, but synthetic surfactants have significant advantages as pharmaceutical agents. This article examines exogenous surfactants containing novel synthetic phospholipase-resistant lipids of extremely high surface activity. Mixtures of these lipid analogs with purified native surfactant apoproteins are detailed as a proof of concept for related fully-synthetic surfactants containing laboratory-produced peptides. The chemistry and biophysics of relevant lipid analogs and peptides are reviewed in the context of developing new synthetic drugs of utility for patients with surfactant deficiency or lung injury-related surfactant dysfunction.
Abstract 191: Desmoplasia in primary tumors and metastatic lesions of pancreatic cancer (2014)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer-related death in the United States. PDAC is characterized by high levels of fibrosis, a feature termed desmoplasia. Desmoplasia is thought to hamper the efficacy of therapeutics treating PDAC. Agents targeting components of the tumor stroma have shown some enhancement of first-line therapeutics targeting tumor cells. As metastatic burden is one of the primary causes for mortality in PDAC, the question remains of whether stromal targeting therapeutics will benefit patients with late stage, metastatic disease. We sought to address this question by assessing the extent of desmoplasia in both primary PDAC tumors and metastatic lesions of pancreatic origin. Patient tissue staining using a pentachrome or standard immunohistochemical technique demonstrates that extracellular matrix components, such as collagen, are found in high levels in both primary tumors and metastatic lesions. The difference in the level of desmoplasia in primary tumors and metastatic lesions was statistically insignificant. We also observed a significant correlation between patient survival and extracellular matrix deposition. Kaplan-meier curves for collagen I showed median survival of 527 days in low collagen patients, and 176.5 in high level patients. Low level hyaluronan patients displayed median survival times of 2107 days as compared to 385 days in high level patients. Our results indicate that both primary tumors and metastases of PDAC have highly fibrotic stroma. Thus, stromal targeting agents may benefit PDAC patients, even those with metastatic disease. Citation Format: Clifford J. Whatcott, Aprill Watanabe, Janine LoBello, Daniel Von Hoff, Haiyong Han. Desmoplasia in primary tumors and metastatic lesions of pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 191. doi:10.1158/1538-7445.AM2014-191
Surface marker for hemopoietic and endothelial cell lineages in quail that is defined by a monoclonal antibody. (1983)

A mouse monoclonal antibody raised in response to quail immunoglobulin mu chain was found to exhibit a broad reactivity towards hemopoietic and endothelial cells in the quail (Coturnix coturnix japonica). Indirect immunofluorescence assays were performed at several stages of embryonic development and until 3 weeks after hatching, on either isolated cells or tissue sections. They revealed that the defined surface marker, referred to as MB1, (i) is expressed early on both intra- and extraembryonic hemopoietic stem cells and is transmitted to the whole progeny of these precursors, with the exception of mature erythrocytes, and (ii) is a constant feature of the endothelial cell surface throughout ontogenesis and adult life. In addition, this epitope is included in several soluble plasma components. MB1 expression was not detected in chicken tissues, and this characteristic was used to confirm its lineage restriction in quail-chicken chimeras. We stress the value of this species- and lineage-specific marker in study of the development of the hemopoietic and endothelial cell families, with special reference to their possible early common embryonic origin.
The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs (2003)

Prostaglandins are involved in a wide variety of physiological and pathophysiological processes, but the mechanism of prostaglandin release from cells is not completely understood. Although poorly membrane permeable, prostaglandins are believed to exit cells by passive diffusion. We have investigated the interaction between prostaglandins and members of the ATP-binding cassette (ABC) transporter ABCC [multidrug resistance protein (MRP)] family of membrane export pumps. In inside-out membrane vesicles derived from insect cells or HEK293 cells, MRP4 catalyzed the time- and ATP-dependent uptake of prostaglandin E1 (PGE1) and PGE2. In contrast, MRP1, MRP2, MRP3, and MRP5 did not transport PGE1 or PGE2. The MRP4-mediated transport of PGE1 and PGE2 displayed saturation kinetics, with Km values of 2.1 and 3.4 microM, respectively. Further studies showed that PGF1alpha, PGF2alpha, PGA1, and thromboxane B2 were high-affinity inhibitors (and therefore presumably substrates) of MRP4. Furthermore, several nonsteroidal antiinflammatory drugs were potent inhibitors of MRP4 at concentrations that did not inhibit MRP1. In cells expressing the prostaglandin transporter PGT, the steady-state accumulation of PGE1 and PGE2 was reduced proportional to MRP4 expression. Inhibition of MRP4 by an MRP4-specific RNA interference construct or by indomethacin reversed this accumulation deficit. Together, these data suggest that MRP4 can release prostaglandins from cells, and that, in addition to inhibiting prostaglandin synthesis, some nonsteroidal antiinflammatory drugs might also act by inhibiting this release.