gebhart/patrepeval huggingface dataset:
Emerging cardiovascular actions of the incretin hormone glucagon‐like peptide‐1: potential therapeutic benefits beyond glycaemic control? (2009)

Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted by the small intestine in response to nutrient ingestion. It has wide-ranging effects on glucose metabolism, including stimulation of insulin release, inhibition of glucagon secretion, reduction of gastric emptying and augmentation of satiety. Importantly, the insulinotropic actions of GLP-1 are uniquely dependent on ambient glucose concentrations, and it is this particular characteristic which has led to its recent emergence as a treatment for type 2 diabetes. Although the major physiological function of GLP-1 appears to be in relation to glycaemic control, there is growing evidence to suggest that it may also play an important role in the cardiovascular system. GLP-1 receptors (GLP-1Rs) are expressed in the heart and vasculature of both rodents and humans, and recent studies have demonstrated that GLP-1R agonists have wide-ranging cardiovascular actions, such as modulation of heart rate, blood pressure, vascular tone and myocardial contractility. Importantly, it appears that these agents may also have beneficial effects in the setting of cardiovascular disease (CVD). For example, GLP-1 has been found to exert cardioprotective actions in experimental models of dilated cardiomyopathy, hypertensive heart failure and myocardial infarction (MI). Preliminary clinical studies also indicate that GLP-1 infusion may improve cardiac contractile function in chronic heart failure patients with and without diabetes, and in MI patients after successful angioplasty. This review will discuss the current understanding of GLP-1 biology, examine its emerging cardiovascular actions in both health and disease and explore the potential use of GLP-1 as a novel treatment for CVD.
Antifungal Activities of Antineoplastic Agents:Saccharomyces cerevisiaeas a Model System To Study Drug Action (1999)

Recent evolutionary studies reveal that microorganisms including yeasts and fungi are more closely related to mammals than was previously appreciated. Possibly as a consequence, many natural-product toxins that have antimicrobial activity are also toxic to mammalian cells. While this makes it difficult to discover antifungal agents without toxic side effects, it also has enabled detailed studies of drug action in simple genetic model systems. We review here studies on the antifungal actions of antineoplasmic agents. Topics covered include the mechanisms of action of inhibitors of topoisomerases I and II; the immunosuppressants rapamycin, cyclosporin A, and FK506; the phosphatidylinositol 3-kinase inhibitor wortmannin; the angiogenesis inhibitors fumagillin and ovalicin; the HSP90 inhibitor geldanamycin; and agents that inhibit sphingolipid metabolism. In general, these natural products inhibit target proteins conserved from microorganisms to humans. These studies highlight the potential of microorganisms as screening tools to elucidate the mechanisms of action of novel pharmacological agents with unique effects against specific mammalian cell types, including neoplastic cells. In addition, this analysis suggests that antineoplastic agents and derivatives might find novel indications in the treatment of fungal infections, for which few agents are presently available, toxicity remains a serious concern, and drug resistance is emerging.
Virus resistance induced by NB–LRR proteins involves Argonaute4‐dependent translational control (2009)

Active resistance to viruses is afforded by plant disease resistance (R) genes, which encode proteins with nucleotide-binding (NB) and leucine-rich repeat (LRR) domains. Upon recognition of pathogen-derived elicitors, these NB-LRR proteins are thought to initiate a number of signaling pathways that lead to pathogen restriction. However, little is known about the molecular mechanisms that ultimately curtail virus accumulation. Here, we show that the co-expression of a plant NB-LRR protein with its cognate elicitor results in an antiviral response that inhibits the translation of virus-encoded proteins in Nicotiana benthamiana. This antiviral response is dependent on viral cis elements, and, upon activation of the NB-LRR protein, viral transcripts accumulate but do not associate with ribosomes. The induced inhibition of viral transcript translation and NB-LRR-mediated virus resistance were compromised by the downregulation of Argonaute4-like genes. Argonaute proteins have been implicated in small RNA-mediated RNA degradation, and in degradation-independent translational control. Our results suggest that the engagement of Argonaute proteins in the specific translational control of viral transcripts is a key factor in virus resistance mediated by NB-LRR proteins.
Synthesis, Structure, and CO2 Reactivity of a Two-Coordinate (Carbene)copper(I) Methyl Complex (2004)

Two-coordinate copper(I) acetate and copper(I) methyl complexes, bearing an N-heterocyclic carbene (NHC) supporting ligand, have been synthesized and structurally characterized, and the stability of the monodentate acetate has been examined by DFT calculations. The methyl complex readily inserts carbon dioxide at ambient temperature and pressure, regenerating the acetate in near-quantitative yield.
Determination of the apparent thermodynamic activities of saturated protein solutions. (1979)

Although the solubility of a protein is a particularly informative solution parameter, little is known about the thermodynamics of protein solubilization. In these experiments, polyethylene glycol (PEG) is used to decrease the solubility of a number of proteins in a quantifiable manner. Simple thermodynamic considerations show that if the chemical potential of the PEG-induced solid phase is constant and plots of log protein solubility versus PEG concentration are linear, a valid extrapolation of the apparent solubility to zero PEG content can be made. Given the validity of these assumptions, extrapolated values should represent the activity of the protein in saturated solution. Evidence for the validity of this extrapolation includes (a) the experimentally observed linearity of log solubility versus PEG concentration plots, (b) the extrapolation of such plots to correct activities in the situation where protein activities can be experimentally determined, and (c) the independence of the extrapolated activities on protein concentration over a wide range. The utility of the PEG-determined activities, when applied in a comparative manner, is illustrated by application to various hemoglobin solutions. It is found that saturated solutions of the various hemoglobin forms, with the exception of deoxyhemoglobin S, manifest similar activities. In addition, all of the solutions demonstrate an apparent, surprising thermodynamic ideality.
The basic helix-loop-helix transcription factor DEC2 inhibits TGF-β-induced tumor progression in human pancreatic cancer BxPC-3 cells (2012)

The basic helix loop helix (bHLH) transcription factor DEC2 is associated with the regulation of apoptosis, circadian rhythm and the response to hypoxia. However, the significance of DEC2 in pancreatic cancer remains unknown. Here, we showed for the first time that DEC2 inhibits the progression of human pancreatic cancer. Human pancreatic cancer BxPC-3 cells were treated with or without transforming growth factor-β (TGF-β), siRNA against DEC2, or a combination of TGF-β and DEC2 siRNA or DEC2 overexpression. The cells were analyzed by RT-PCR, real-time PCR, western blotting, immunofluorescent staining and ChIP assay. We also performed immunohistochemical analyses of DEC2 expression in surgically-resected pancreatic cancers. The expression of DEC2 was increased in TGF-β-treated BxPC-3 cells. In the presence of TGF-β, DEC2 overexpression decreased the migration and invasion of BxPC-3 cells. Knockdown of DEC2 by siRNA in the presence of TGF-β significantly increased the expression and nuclear concentration of slug. We also showed that DEC2 siRNA decreased the binding of DEC2 to the E-box of the slug promoter. Immunohistochemically, little DEC2 was detected in pancreatic cancer tissues, whereas significant amounts were detected in the adjacent non-cancerous pancreatic tissues. These results indicate that DEC2 has inhibitory effects against human pancreatic cancer that involve TGF-β and slug.
Effect of pH on solubility and ionic state of lipopolysaccharide obtained from the deep rough mutant of Escherichia coli (1993)

The dissociation of the highly aggregated form of lipopolysaccharide (LPS) from Gram-negative bacteria to the monomeric (or soluble) form is though to be the initial step in the activation of responding cells (macrophages, B-cells, neutrophils, monocytes, and endothelial cells) by LPS. This process is presently not adequately understood. Using the equilibrium dialysis apparatus and a highly purified and well-characterized radiolabeled deep rough chemotype LPS ([14C]ReLPS) from Escherichia coli D31m4, we have examined the effect of pH on its solubility (CT) and ionic states in aqueous media. The solubility range of [14C]ReLPS suspended in 50 mM Tris-HCl-100 mM KCl buffer (or 50 mM MES-100 mM KCl buffer at pH 6.5) was determined to be from (2.91 +/- 0.01) x 10(-8) to (4.55 +/- 0.07) x 10(-8) M over a pH range of 6.50-8.20, respectively. These experimental data satisfactorily fitted the curve generated by the solubility equation CT = S0(1 + K5/[H+])/([H+]/K4' + 1), where S0 is the concentration of the tetraanionic ReLPS, K5 is the dissociation constant of the tetraanionic ReLPS in solution, and K4' is the dissociation constant of the trianionic ReLPS at the surface of the solid particles in suspension. The increase in solubility of ReLPS with increase in pH from 7.00 to 8.20 is primarily caused by the formation of the pentaanionic form from the tetraanions. The pK5 (primarily the second dissociation of the 1-phosphate) of ReLPS was determined to be 8.58 from experimental data.(ABSTRACT TRUNCATED AT 250 WORDS)
Risk, Firm Heterogeneity, and Dynamics of FDI Entry (2009)

We study the dynamics of FDI entry under a setting with firm heterogeneity and FDI uncertainty. The risk of FDI failure depends positively on the complexity of production technology, negatively on the quality of infrastructure in the host country, and evolves over time with the extent of knowledge diffusion. The incorporation of FDI uncertainty leads to a non-monotonic relationship between technology complexity and the timing of FDI entry: firms with intermediate technology levels lead the first wave of FDI, which helps lower the investment uncertainty facing subsequent investors and induces a wider range of FDI entry in the second period. We prove the existence of a stable steady state for this self-reinforcing process and identify how the extensive margin of FDI at the steady state varies with the host and home country characteristics. Supporting empirical observations are also provided.
A Microassembled Low-Profile Three-Dimensional Microelectrode Array for Neural Prosthesis Applications (2007)

This paper describes the design and micro- assembly process of a low-profile 3-D microelectrode array for mapping the functional organization of targeted areas of the central nervous system and for possible application in neural prostheses. The array consists of multiple planar complimentary metal-oxide-semiconductor stimulating probes and 3-D assembly components. Parylene-encapsulated gold beams supported by etch-stopped silicon braces allow the backends of the probes to be folded over to reduce the height of the array above the cortical surface. A process permitting parylene to be used at wafer level with bulk-silicon wet release has been reported. Spacers are used to fix the microassembled probes in position and are equipped with interlocking structures to facilitate the assembly process and increase yield. Four-probe 256-site 3-D arrays operate from plusmn5 V with an average per-channel power dissipation of 97 muW at full range stimulation with pulse widths of 100 mus at 500-Hz frequency. Thirty-two sites can be stimulated simultaneously with maximum currents of plusmn127 muA and a current resolution of plusmn1 muA. The microassembly techniques allow a variety of 3-D microstructures to be created from planar components.
LIGR, a protease‐activated receptor‐2‐derived peptide, enhances skin pigmentation without inducing inflammatory processes (2008)

The protease-activated receptor-2 (PAR-2) is a seven transmembrane G-protein-coupled receptor that could be activated by serine protease cleavage or by synthetic peptide agonists. We showed earlier that activation of PAR-2 with Ser-Leu-Ile-Gly-Arg-Leu-NH(2) (SLIGRL), a known PAR-2 activating peptide, induces keratinocyte phagocytosis and increases skin pigmentation, indicating that PAR-2 regulates pigmentation by controlling phagocytosis of melanosomes. Here, we show that Leu-Ile-Gly-Arg-NH(2) (LIGR) can also induce skin pigmentation. Both SLIGRL and LIGR increased melanin deposition in vitro and in vivo, and visibly darkened human skins grafted onto severe combined immuno-deficient (SCID) mice. Both SLIGRL and LIGR stimulated Rho-GTP activation resulting in keratinocyte phagocytosis. Interestingly, LIGR activates only a subset of the PAR-2 signaling pathways, and unlike SLIGRL, it does not induce inflammatory processes. LIGR did not affect many PAR-2 signaling pathways, including [Ca(2+)] mobilization, cAMP induction, the induction of cyclooxgenase-2 (COX-2) expression and the secretion of prostaglandin E2, interleukin-6 and -8. PAR-2 siRNA inhibited LIGR-induced phagocytosis, indicating that LIGR signals via PAR-2. Our data suggest that LIGR is a more specific regulator of PAR-2-induced pigmentation relative to SLIGRL. Therefore, enhancing skin pigmentation by topical applications of LIGR may result in a desired tanned-like skin color, without enhancing inflammatory processes, and without the need of UV exposure.
Large-scale holographic switch with a ferroelectric liquid-crystal spatial light modulator (1998)

Abstract We have proposed a holographic switch with a ferroelectric liquid-crystal spatial light modulator for a large-scale switch. 4 × 1204 switching was demonstrated to show that the proposed switch structure is suitable for a large-scale switch. The average losses of the four inputs were 28, 33, 35, and 36 dB. The average crosstalk-to-signal ratio of one of the inputs was-16 dB.
Prostate-specific membrane antigen as a marker of pancreatic cancer cells (2014)

The aim of this study was to identify the expression of prostate-specific membrane antigen (PSMA) and analyze the correlation between PSMA with clinical characteristics in patients with pancreatic cancer. The expression of PSMA protein and mRNA was detected by immunohistochemistry and real-time quantitative poly- merase chain reaction in pancreatic cancer tissues, pancre- atic intraepithelial neoplasia or normal pancreatic tissues, respectively. And clinical characteristics and prognosis of patients were investigated. PSMA was expressed in pan- creatic cancer cells, both in protein and mRNA levels. Moreover, the PSMA levels were associated with the prognosis of patients with pancreatic ductal adenocarci- noma. The overall survival time of pancreatic cancer patients with high expression of PSMA was significantly shorter than that of the low ones. Moreover, the PSMA levels were correlated with clinicopathological features including the histological grade and pathological tumor- node-metastasis stage. PSMA is involved in the carcino- genesis of pancreatic cancer, and it might serve as a potential therapeutic target for pancreatic cancer.
Composites of poly(vinyl chloride) and wood fibers. Part II: Effect of chemical treatment (1990)

Abstract This study examines the influence of different cellulose treatments, including coating by latex or by grafting with polymer/vinyl monomers, as well as with various additive dispersants (e.g., stearic acid or anhydrides) and coupling agents (e.g., maleic anhydride, abietic acid, and linoleic acid). The mechanical properties are examined for poly(vinyl chloride) treated hardwood (chemithermomechanical pulp and sawdust). In most cases, properties are improved compared with untreated composites. Among all methods, grafting was found to be the most effective. Coupling agents show better performance compared with dispersants. Linoleic acid is believed to be the best coupling agent.
A constitutively active epidermal growth factor receptor cooperates with disruption of G1 cell-cycle arrest pathways to induce glioma-like lesions in mice (1998)

The epidermal growth factor receptor (EGFR) gene is amplified or mutated in 30%-50% of human gliobastoma multiforme (GBM). These mutations are associated usually with deletions of the INK4a-ARF locus, which encodes two gene products (p16(INK4a) and p19(ARF)) involved in cell-cycle arrest and apoptosis. We have investigated the role of EGFR mutation in gliomagenesis, using avian retroviral vectors to transfer a mutant EGFR gene to glial precursors and astrocytes in transgenic mice expressing tv-a, a gene encoding the retrovirus receptor. TVA, under control of brain cell type-specific promoters. We demonstrate that expression of a constitutively active, mutant form of EGFR in cells in the glial lineage can induce lesions with many similarities to human gliomas. These lesions occur more frequently with gene transfer to mice expressing tv-a from the progenitor-specific nestin promoter than to mice expressing tv-a from the astrocyte-specific glial fibrillary acidic protein (GFAP) promoter, suggesting that tumors arise more efficiently from immature cells in the glial lineage. Furthermore, EGFR-induced gliomagenesis appears to require additional mutations in genes encoding proteins involved in cell-cycle arrest pathways. We have produced these combinations by simultaneously infecting tv-a transgenic mice with vectors carrying cdk4 and EGFR or by infecting tv-a transgenic mice bearing a disrupted INK4a-ARF locus with the EGFR-carrying vector alone. Moreover, EGFR-induced gliomagenesis does not occur in conjunction with p53 deficiency, unless the mice are also infected with a vector carrying cdk4. The gliomagenic combinations of genetic lesions required in mice are similar to those found in human gliomas.
Treatment of Human Colon Cancer Xenografts with TRA-8 Anti-death Receptor 5 Antibody Alone or in Combination with CPT-11 (2008)

In vitro and in vivo effects of TRA-8 anti-DR5 monoclonal antibody on four different colon cancer cell lines and xenografts were quite variable. The HT-29 cell line had low surface DR5 expression and was resistant to TRA-8 both in vitro and in vivo. Three cell lines (COLO 205, SW948, and HCT116) exhibited moderate to high sensitivity to TRA-8-mediated cytotoxicity which was further enhanced by the addition of SN-38, the active metabolite of CPT-11. In vivo, the combination of TRA-8 and CPT-11 treatment produced the highest antitumor efficacy against xenografts established from the three TRA-8-sensitive tumor cell lines. All four colon cancer xenografts had comparable localization of (99m)Tc-TRA-8. These studies support the strategy of TRA-8/CPT-11 combined treatment in human colon cancer clinical trials.
Vaccine‐Preventable Disease (2001)

Active immunisation is based on adaptive mechanisms that involve B and T lymphocytes. Attenuated live vaccines induce humoral and cell-mediated responses, and inactivated vaccines induce a humoral response requiring often several doses of vaccine. Passive immunisation consists of the administration of preformed polyclonal antibodies; protection is afforded within hours but lasts for only a few weeks and this method of immunisation is used under specific circumstances only. The general principles of vaccines are reviewed including combination vaccines, adjuvants, storage of vaccines, routes of administration, safety and adverse events and contraindications to vaccination. The following vaccines are considered with emphasis on the use of vaccines in travellers: anthrax, cholera, diphtheria, Haemophilus influenzae, hepatitis A (including combined hepatitis A and B, and hepatitis A and typhoid vaccines), hepatitis B, influenza, Japanese encephalitis, Lyme disease, meningoccocal meningitis A and C, MMR, pertussis, plague, pneumococcal, poliomyelitis, rabies, rubella, tetanus, tick-borne encephalitis, BCG, typhoid, varicella and yellow fever. Passive immunisation with immunoglobulin and hyperimmune immunoglobulin is also reviewed.
Human herpesvirus 6 major immediate early promoter has strong activity in T cells and is useful for heterologous gene expression (2011)

These data suggest that HHV-6 MIEp functions more strongly than CMV MIEp in various T-cell lines.
Six monoclonal antibodies to human pancreatic cancer antigens. (1987)

Murine monoclonal antibodies were generated against FG, a human pancreatic carcinoma (HPC) cell line. Of the six monoclonal antibodies, five (S3-15, S3-23, S3-41, S3-60, and S3-110) reacted by indirect immunoperoxidase assays with HPC of the ductal type, and another (S3-53) reacted with both ductal and acinar HPC. Strong reactivity was also found with tumors of the stomach, colon, mouth, lung, and cervix, while a large panel of normal human tissues displayed little reactivity. Indirect immunofluorescence staining revealed that, except for S3-23, the antigens recognized by these antibodies are expressed at the cell surface. Immunoprecipitation of metabolically radiolabeled FG cells indicated that the epitopes recognized by these antibodies are carried by distinct proteins or glycoproteins, differentiated on the basis of the apparent molecular weight and/or subunit composition as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This panel of antibodies will be useful to study antigenic variations associated with malignant cell transformation in HPC as well as other tumors.
Sickle cell anemia: a potential nutritional approach for a molecular disease (2000)

A certain population of red blood cells in patients with sickle cell anemia has an elevated density and possesses an abnormal membrane. These "dense cells" have a tendency to adhere to neutrophils, platelets, and vascular endothelial cells, and, thus, they could trigger vasoocclusion and the subsequent painful crisis from which these patients suffer. We developed a laboratory method of preparing such dense cells and found that nutritional antioxidant supplements, hydroxyl radical scavengers, and iron-binding agents could inhibit the formation of dense cells in vitro. The concentrations at which effective nutritional supplements could inhibit dense cell formation by 50% were 4.0 mg/mL for aged garlic extract, 0.38 mg/mL for black tea extract, 0.13 mg/mL for green tea extract, 0.07 mg/mL for Pycnogenol, 930 microM for alpha-lipoic acid, 270 microM for vitamin E, 45 microM for coenzyme Q(10), and 32 microM for beta-carotene. Both an ex vivo study and a pilot clinical trial demonstrated that a cocktail consisting of daily doses of 6 g of aged garlic extract, 4-6 g of vitamin C, and 800 to 1200 IU of vitamin E may indeed be beneficial to the patients.