gebhart/patrepeval huggingface dataset:
Recellularization of biological heart valves with human vascular cells: In vitro hemocompatibility assessment (2008)

Coverage of cardiovascular bioprostheses with autologous endothelium is used for the purpose of improving blood compatibility. The aim of our study was to analyze endothelialization potential of glutaraldehyde-fixed heart valves, cellular functions of seeded endothelial cells (EC), and the impact of a two-stage seeding protocol using human vascular fibroblasts (FB) and EC from saphenous veins (HSVEC) on cellular functional properties in vitro. Adherence and morphology of adhered cells were assessed by scanning electronic microscopy and immunohistochemistry. Reproducible, complete surface coverage with EC was established on decellularized and glutaraldehyde-fixed bovine pericardium. Analyzing functional properties of cells directly adhered to biomaterial revealed nonproliferative cells, which were capable of inflammatory stimulation in terms of TNF-induced increase in interleukin-6 secretion and adhesion of inflammatory cells. Furthermore, EC showed sustained antithrombotic properties quantified by platelet adhesion onto EC and prostacyclin secretion by EC. Preseeding with vascular fibroblasts using a two-stage seeding protocol induced EC proliferation and improved inflammatory and anti-thrombotic functions. Cardiovascular biomaterials differ significantly in their potential to allow for adhesion of human EC. Successfully endothelialized biomaterial, however, revealed cellular properties which are likely to be favorable to improving performance of biomaterials. Two-stage seeding adds regenerative potential and improves cell functions of adherent EC.
In vitro inhibition of endothelial cell growth by the antiangiogenic drug AGM-1470 (TNP-470) and the anti-endoglin antibody TEC-11 (1997)

Angiogenesis plays a key role in tumor growth, progression and metastasis. The modulation of angiogenesis represents a potentially useful target for novel forms of anticancer therapy. Two such modulators are AGM-1470 (TNP-470, angioinhibin), which is a synthetic analog of the antibiotic fumagallin, and the monoclonal antibody TEC-11 to endoglin. We investigated the mechanisms of action of these modulators on human microvascular and macrovascular endothelial cells and on the transformed endothelial cell line ECV-304 in vitro. The administration of AGM-1470 or TEC-11 resulted in a significant inhibition of cell proliferation in all cell types used; this effect was reversible upon removal of these compounds from the culture medium. Furthermore, biochemical and morphological analyses showed that neither AGM-1470 or TEC-11 induce apoptosis. Both AGM-1470 and TEC-11 inhibited the production of urokinase-type plasminogen activator (u-PA), an enzyme involved in the early steps of neovascularization. Finally, the incubation of endothelial cells with both AGM-1470 and TEC-11 did not produce an additive effect on growth cell inhibition, apoptosis or u-PA production. Since both AGM 1470 and TEC-11 inhibit crucial events such as endothelial cell growth and protease production, our results provide a basis for their therapeutic use as angiostatic molecules in cancer.
Small Molecule Vascular Disrupting Agents: Potential New Drugs for Cancer Treatment, a 2009 Update (2010)

Vascular disrupting agents (VDAs) are a new class of potential anticancer drugs that selectively destroy tumor vasculature and shutdown blood supply to solid tumors, causing extensive tumor cell necrosis. VDAs target established tumor blood vessels, which are distinct from antiangiogenic agents that prevent the formation of new blood vessels. There are two types of VDAs, small molecules and ligand-directed agents. Most of the small molecule VDAs are tubulin inhibitors, including CA4P, ZD6126, AVE8062, OXi-4503, NPI-2358, MN-029, EPC2407, CYT997, MPC-6827, ABT-751 and TZT-1027. The others are synthetic flavonoids including FAA and DMXAA that induce the production of local cytokines such as TNF-alpha. VDAs have shown good antitumor efficacy in animal models, especially in combination with established anticancer agents. Several VDAs, including CA4P and DMXAA, have demonstrated good safety profile as well as some promising efficacy in phase I and II clinical trials. Currently CA4P, DMXAA and AVE8062 are in phase III clinical trials, NPI-2358, CYT997, MPC-6827 and ABT-751 are in phase II clinical trials, and OXi-4503 and EPC2407 are in phase I clinical trials. This review will focus on recent progress in the discovery and development of small molecule VDAs, including recently published patent applications and issued patents related with small molecule VDAs.
Image enhancement through turbid media under a microscope by use of polarization gating methods (1999)

Image enhancement through a turbid medium by use of polarization gating methods in a microscopic imaging system is studied both theoretically and experimentally. A Monte Carlo simulation model based on Mie theory and geometric optics is adopted to calculate, for use with polarization gating and pinhole gating methods, image resolution of a sharp edge embedded in a turbid medium consisting of polystyrene beads. Both theoretical and experimental results show that polarization gating methods, particularly the differential polarization gating method, can be efficient in suppressing scattered photons, thus leading to image enhancement. In addition, a theoretical comparison of polarization gating and pinhole gating methods, based on the trade-off between resolution and signal strength, reveals that polarization gating methods are superior to the pinhole gating method when signal strength is weak.
Two FAD3 Desaturase Genes Control the Level of Linolenic Acid in Flax Seed (2005)

Industrial oil flax (Linum usitatissimum) and edible oil or solin flax differ markedly in seed linolenic acid levels. Despite the economic importance of low-linolenic-acid or solin flax, the molecular mechanism underlying this trait has not been established. Two independently inherited genes control the low-linolenic-acid trait in flax. Here, we identified two genes, LuFAD3A and LuFAD3B that encode microsomal desaturases capable of desaturating linoleic acid. The deduced proteins encoded by these genes shared 95.4% identity. In the low-linolenic-acid line solin 593-708, both LuFAD3A and LuFAD3B carry point mutations that produce premature stop codons. Expression of these genes in yeast (Saccharomyces cerevisiae) demonstrated that, while the wild-type proteins were capable of desaturating linoleic acid, the truncated proteins were inactive. Furthermore, the low-linolenic-acid phenotype in flax was complemented by transformation with a wild-type gene. Codominant DNA markers were developed to distinguish between null and wild-type alleles of both genes, and linolenic acid levels cosegregated with genotypes, providing further proof that LuFAD3A and LuFAD3B are the major genes controlling linolenic acid levels in flax. The level of LuFAD3 transcripts in seeds peaked at about 20 d after flowering, and transcripts were not detectable in leaf, root, or stem tissue. A dramatic reduction in transcript levels of both genes occurred in the low-linolenic-acid solin line, which was likely due to nonsense-mediated decay.
Inhibition of glioma cell growth by a truncated platelet-derived growth factor-beta receptor. (1994)

Abnormal expression of platelet-derived growth factor (PDGF) receptors has been observed in malignant glioma and other tumors such as osteosarcomas and malignant melanomas. However, their role in the development and maintenance of the tumors is not understood. Signaling through the PDGF receptors is activated by ligand-induced dimerization. Thus, introduction of mutant receptors that are kinase deficient but still dimerization competent is one strategy to study the importance of PDGF receptors in glioma cell growth. A truncated PDGF-beta receptor was introduced into C6 rat glioma cells and the PDGF-mediated signaling and subsequent cell growth studied. In clones expressing the mutant receptor, PDGF-BB-induced tyrosine phosphorylation of the endogenous receptor was significantly reduced. In addition, these cells grew to lower density in culture and formed smaller colonies in soft agar than the C6 parental cells. Furthermore, the ability of cells expressing the truncated receptor to grow as xenografts in nude mice was significantly impaired. These results support the important role for the PDGF-beta receptor in C6 glioma cell growth. They also demonstrate the usefulness of dominant-negative mutants of the PDGF receptor for the evaluation of the role of the receptor in tumorigenesis.
Evidence of increased angiogenesis in patients with acute myeloid leukemia (2000)

Angiogenesis plays a key role in solid tumor growth. The purpose of this work was to study angiogenesis in acute myeloid leukemia (AML). We stained bone marrow samples from 20 adult patients with untreated AML and 20 normal controls using endothelial cell markers (ULEX-E and von Willebrand factor [vWF]). The number of vessels per millimeter length of bone marrow core biopsy specimen was scored by light microscopy. Using ULEX-E staining, AML marrows had (average +/- SEM) 8.3 +/- 3.6 vessels/mm (range, 3.7-19.3), whereas normal marrows had 4.3 +/- 1.8 vessels/mm (range, 1.6-7.9). A similar difference was noted using vWF staining (8.6 +/- 3.0 vessels/mm vs 4. 9 +/- 2.2 vessels/mm in AML vs normal bone marrows, respectively). The differences between the numbers of vessels/mm in AML and normal marrows were highly significant (P <.0001 for both ULEX-E and vWF staining). When analyzed by FAB category, there was no difference in the average number of vessels/mm among the different subgroups of AML. Using reverse transcriptase polymerase chain reaction, we observed that the HL-60 and U937 human AML cell lines and 4 of 4 freshly isolated AML cells from untreated patients expressed mRNA for vascular endothelial growth factor (VEGF). Both cell lines as well as all fresh AML isolates tested expressed VEGF protein. Basic fibroblast growth factor was expressed only in HL-60 cells and in only 3 of 4 fresh AML samples. These observations suggest that angiogenesis may play a role in the pathogenesis of AML. Inhibition of angiogenesis could constitute a novel strategy for the treatment of AML. (Blood. 2000;95:309-313).
Proteome-Wide Reactivity Profiling Identifies Diverse Carbamate Chemotypes Tuned for Serine Hydrolase Inhibition (2013)

Serine hydrolases are one of the largest and most diverse enzyme classes in Nature. Inhibitors of serine hydrolases are used to treat many diseases, including obesity, diabetes, cognitive dementia, and bacterial and viral infections. Nonetheless, the majority of the 200+ serine hydrolases in mammals still lack selective inhibitors for their functional characterization. We and others have shown that activated carbamates, through covalent reaction with the conserved serine nucleophile of serine hydrolases, can serve as useful inhibitors for members of this enzyme family. The extent to which carbamates, however, cross-react with other protein classes remains mostly unexplored. Here, we address this problem by investigating the proteome-wide reactivity of a diverse set of activated carbamates in vitro and in vivo, using a combination of competitive and click chemistry (CC)-activity-based protein profiling (ABPP). We identify multiple classes of carbamates, including O-aryl, O-hexafluoroisopropyl (HFIP), and O-N-hydroxysuccinimidyl (NHS) carbamates that react selectively with serine hydrolases across entire mouse tissue proteomes in vivo. We exploit the proteome-wide specificity of HFIP carbamates to create in situ imaging probes for the endocannabinoid hydrolases monoacylglycerol lipase (MAGL) and α-β hydrolase-6 (ABHD6). These findings, taken together, designate the carbamate as a privileged reactive group for serine hydrolases that can accommodate diverse structural modifications to produce inhibitors that display exceptional potency and selectivity across the mammalian proteome.
Rate control for videophone using local perceptual cues (2005)

We present a method for extracting local visual perceptual cues and its application for rate control of videophone, in order to ensure the scarce bits to be assigned for maximum perceptual coding quality. The optimum quantization step is determined with the rate-distortion model considering the local perceptual cues in the visual signal. For extraction of the perceptual cues, luminance adaptation and texture masking are used as the stimulus-driven factors, while skin color serves as the cognition-driven factor in the current implementation. Both objective and subjective quality evaluations are given by evaluating the proposed perceptual rate control (PRC) scheme in the H.263 platform, and the evaluations show that the proposed PRC scheme achieves significant quality improvement in block-based coding for bandwidth-hungry applications.
Prevalence and Diagnosis of Legionella Pneumonia: A 3-Year Prospective Study with Emphasis on Application of Urinary Antigen Detection (1990)

During a 3-year period the frequency of legionellosis in hospitalized patients with community-acquired and nosocomial pneumonias was 3.4% (23/684 cases) and 5.9% (33/559), respectively. Of the diagnostic tests evaluated, detection of Legionella pneumophila serogroup 1 antigen in urine had the highest sensitivity, with 86% of culture-proven cases being positive. Sensitivities of serologic tests and examination of respiratory secretions (culture and direct immunofluorescence) were 36% and 26%, respectively. The diagnostic value of serology and of examination of respiratory secretions can be low when specimens are obtained and processed under the typical conditions of hospitalization. Urinary antigen detection represents an important diagnostic addition, and examination of postmortem lung tissue from fatal cases with pneumonia is an important adjunct for estimating the prevalence of legionellosis and for assessing the effectiveness of premortem diagnostic tests.
A Projection Pursuit Algorithm for Exploratory Data Analysis (1974)

An algorithm for the analysis of multivariate data is presented and is discussed in terms of specific examples. The algorithm seeks to find one-and two-dimensional linear projections of multivariate data that are relatively highly revealing.
WHAT CAN WE DO WITH CO? (2007)

RETURN TO ISSUEPREVNewsNEXTWHAT CAN WE DO WITH CO?ACS MEETING NEWS: Scientists are trying to find ways to convert the plentiful greenhouse gas into fuels and other value-added productsSTEPHEN K. RITTERView Author Information C&EN WASHINGTONCite this: Chem. Eng. News 2007, 85, 18, 11–17Publication Date (Print):April 30, 2007Publication History Published online14 November 2010Published inissue 30 April 2007https://pubs.acs.org/doi/10.1021/cen-v085n018.p011https://doi.org/10.1021/cen-v085n018.p011newsACS PublicationsCopyright © 2007 American Chemical SocietyArticle Views27Altmetric-Citations27LEARN 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 SUBJECTS:Climate change,Fossil fuels,Inorganic carbon compounds,Molecules,Oxides Get e-Alerts
Acidosis Activation of the Proton-Sensing GPR4 Receptor Stimulates Vascular Endothelial Cell Inflammatory Responses Revealed by Transcriptome Analysis (2013)

Acidic tissue microenvironment commonly exists in inflammatory diseases, tumors, ischemic organs, sickle cell disease, and many other pathological conditions due to hypoxia, glycolytic cell metabolism and deficient blood perfusion. However, the molecular mechanisms by which cells sense and respond to the acidic microenvironment are not well understood. GPR4 is a proton-sensing receptor expressed in endothelial cells and other cell types. The receptor is fully activated by acidic extracellular pH but exhibits lesser activity at the physiological pH 7.4 and minimal activity at more alkaline pH. To delineate the function and signaling pathways of GPR4 activation by acidosis in endothelial cells, we compared the global gene expression of the acidosis response in primary human umbilical vein endothelial cells (HUVEC) with varying level of GPR4. The results demonstrated that acidosis activation of GPR4 in HUVEC substantially increased the expression of a number of inflammatory genes such as chemokines, cytokines, adhesion molecules, NF-κB pathway genes, and prostaglandin-endoperoxidase synthase 2 (PTGS2 or COX-2) and stress response genes such as ATF3 and DDIT3 (CHOP). Similar GPR4-mediated acidosis induction of the inflammatory genes was also noted in other types of endothelial cells including human lung microvascular endothelial cells and pulmonary artery endothelial cells. Further analyses indicated that the NF-κB pathway was important for the acidosis/GPR4-induced inflammatory gene expression. Moreover, acidosis activation of GPR4 increased the adhesion of HUVEC to U937 monocytic cells under a flow condition. Importantly, treatment with a recently identified GPR4 antagonist significantly reduced the acidosis/GPR4-mediated endothelial cell inflammatory response. Taken together, these results show that activation of GPR4 by acidosis stimulates the expression of a wide range of inflammatory genes in endothelial cells. Such inflammatory response can be suppressed by GPR4 small molecule inhibitors and hold potential therapeutic value.
ATR signaling can drive cells into senescence in the absence of DNA breaks (2008)

The ATR kinase is a key transducer of "replicative stress," the type of genomic damage that has been postulated to be induced by oncogenes. Here we describe a cellular system in which we can unleash ATR activity at will, in the absence of any actual damage or additional signaling pathways triggered by DNA breaks. We demonstrate that activating ATR is sufficient to promote cell cycle arrest and, if persistent, triggers p53-dependent but Ink4a/ARF-independent senescence. Moreover, we show that an ectopic activation of ATR leads to a G1/S arrest in ATM-/- cells, providing the first evidence of functional complementation of ATM deficiency by ATR. Our system provides a novel platform for the study of the specific functions of ATR signaling and adds evidence for the tumor-suppressive potential of the DNA damage response.
Calcium Antagonists and Atherosclerosis Protection in Hypertension (2003)

Calcium antagonists are effective in hypertensive patients of all ethnic groups, irrespective of age, dietary salt intake, salt-sensitivity status or plasma renin activity profile. Some prospective studies show that the calcium antagonists, nifedipine GITS and nitrendipine, reduce cardiovascular morbidity and mortality at least to the same extent as the diuretics. Other prospective studies are in progress to evaluate the effect of calcium antagonists on cardiovascular morbidity and mortality, and the progression of atherosclerosis in hypertensive patients. Calcium antagonists, especially the highly lipophilic amlodipine, lacidipine and nisoldipine, are shown to possess antioxidant properties. These drugs reduce the oxidation of LDL and its influx into the arterial wall, and reduce atherosclerotic lesions in animals. Platelet production of malondialdehyde, a marker of oxygen free radical formation, is suppressed by amlodipine, lacidipine or nifedipine in hypertensive patients. New evidence from long-term clinical trials of calcium antagonists indicates that these drugs can reduce the rate of progression of atherosclerosis in hypertensive and coronary heart disease patients. In the Regression Growth Evaluation Statin Study (REGRESS), co-administration of calcium antagonist, amlodipine or nifedipine with pravasatin caused a significant reduction in the appearance of new angiographic lesions. In the Verapamil in Hypertension and Atherosclerosis Study (VHAS), verapamil was more effective than chlorthalidone in promoting regression of thicker carotid lesions in parallel with a reduction in the incidence of cardiovascular events. In the Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT), amlodipine slowed the progression of early coronary atherosclerosis in patients with coronary artery disease. In a subprotocol of the Intervention as a Goal in the Hypertension Treatment (INSIGHT) study, nifedipine GITS significantly decreased intima-media thickness as compared to co-amilozide (hydrochlorothiazide + amiloride). Preliminary results of the European Lacidipine Study on Atherosclerosis (ELSA) show that lacidipine reduced the intima-media thickness progression rate as compared to atenolol. Thus, selective calcium antagonists are potential antiatherosclerotic agents.
Drug Delivery Systems: Past, Present, and Future (2004)

Drug delivery systems are essential components of drugs controlled release. In the last decades, several drug delivery technologies have emerged including capsules, liposomes, microparticles, nanoparticles, and polymers. These components must be biocompatible, biodegradable, and display a desired biodistribution providing a long-term availability of the therapeutic at specific target over time.
Die Autonomie im System der Minderheitenrechte (2013)

Abstract Autonomy is widely considered one of the most effective ways of protecting minorities. However, problems faced by existing autonomies in some European countries have raised doubts as to whether this holds true. The following article provides – from an exclusively legal perspective – an up-to-date analysis of autonomy as it is practised in different contexts and discusses what can be its contribution to solving minority problems.
Imprinted polymers as tools for the recovery of secondary metabolites produced by fermentation (1999)

Imprinted polymers were synthesized using a mixture of pigments, N-glutamyl-rubropuctamine, and N-glutamyl-monascorubramine (I) as the template, and 2-methacrylamido-6-picoline or 4-aminostyrene as functional monomers, to obtain recognition materials capable of forming hydrogen bonds and charge interactions, respectively, with carboxyl groups of target I in the binding sites. The polymers were prepared thermally at a template loading of 5 mol% using ethylene-glycol dimethacrylate or trimethylolpropane trimethacrylate as crosslinkers and acetonitrile or tetrahydrofuran as porogens. The selective binding of I to both types of polymer was demonstrated, although aminostyrene-based materials showed higher overall adsorption and were studied in more detail. It was shown that the kinetics of binding of I from ethyl-acetate extracts of fermented Monascus sp. was very rapid and virtually all the pigment adsorbed can be released by washing the polymer with ethanol–water mixtures. The feasibility of reusing imprinted polymer in consecutive adsorption/desorption cycles was also demonstrated. © 1999 John Wiley & Sons, Inc. Biotechnol Bioeng 64: 232–239, 1999.