gebhart/patrepeval huggingface dataset:
Chemical and Biological Assessment of Angelicae Sinensis Radix after Processing with Wine: An Orthogonal Array Design To Reveal the Optimized Conditions (2011)

The roots of Angelica sinensis [Angelica Sinensis Radix (ASR)] have been used as a common health food supplement for women's care for thousands of years in China. According to Asian tradition, ASR could be processed with the treatment of wine, which subsequently promoted the biological functions of ASR. By chemical and biological assessments, an orthogonal array design was employed here to determine the roles of three variable parameters in the processing of ASR, including oven temperature, baking time, and flipping frequency. The results suggested that oven temperature and baking time were two significant factors, while flipping frequency was a subordinate factor. The optimized condition of processing with wine therefore was considered to be heating in an oven at 80 °C for 90 min with flipping twice per hour. Under the optimized processing conditions, the solubilities of ferulic acid and Z-ligustilide from ASR were markedly increased and decreased, respectively. In parallel, the biological functions of processed ASR were enhanced in both anti-platelet aggregation and estrogenic activation; these increased functions could be a result of the altered levels of ferulic acid and Z-ligustilide in wine-processed ASR. Thus, the chemical and biological assessment of the processed ASR was in full accordance with the Chinese old tradition.
Electrochemical oxygen reduction catalysed by Ni3(hexaiminotriphenylene)2 (2016)

Control over the architectural and electronic properties of heterogeneous catalysts poses a major obstacle in the targeted design of active and stable non-platinum group metal electrocatalysts for the oxygen reduction reaction. Here we introduce Ni3(HITP)2 (HITP=2, 3, 6, 7, 10, 11-hexaiminotriphenylene) as an intrinsically conductive metal-organic framework which functions as a well-defined, tunable oxygen reduction electrocatalyst in alkaline solution. Ni3(HITP)2 exhibits oxygen reduction activity competitive with the most active non-platinum group metal electrocatalysts and stability during extended polarization. The square planar Ni-N4 sites are structurally reminiscent of the highly active and widely studied non-platinum group metal electrocatalysts containing M-N4 units. Ni3(HITP)2 and analogues thereof combine the high crystallinity of metal-organic frameworks, the physical durability and electrical conductivity of graphitic materials, and the diverse yet well-controlled synthetic accessibility of molecular species. Such properties may enable the targeted synthesis and systematic optimization of oxygen reduction electrocatalysts as components of fuel cells and electrolysers for renewable energy applications.
Multi-drug resistant typhoid: a global problem (1996)

Microbiology Society journals contain high-quality research papers and topical review articles. We are a not-for-profit publisher and we support and invest in the microbiology community, to the benefit of everyone. This supports our principal goal to develop, expand and strengthen the networks available to our members so that they can generate new knowledge about microbes and ensure that it is shared with other communities.
Strain balanced InAs/InAsSb superlattice structures with optical emission to 10 μm (2009)

We report the growth and optical characterization of InAsSb/InAs strain balanced superlattice structures on GaSb substrates for potential application in midinfrared photodetectors. Photoluminescence (PL) emission was observed in the range 5 μm≤λ≤10 μm at 4 K for Sb compositions 0.14≤xSb≤0.27. The PL energy was found to depend approximately linearly on antimony, consistent with a type II band lineup. The dependence of the emission energies on the Sb mole fraction is in agreement with trends predicted by various theoretical works. The data suggest that this transition reaches zero energy for a composition of xSb=0.37.
Heavy trypan blue staining of epiretinal membranes: an alternative to infracyanine green (2007)

Heavy TB can be delivered efficiently to the retinal surface without an AFX. Staining was sufficient to allow a safe and efficient peeling of ERM. Repeat applications were easily performed. Its use was associated with vision improvement and decreased in foveal thickness, and the absence of adverse events in this small case series.
Effect of Nɛ-carboxymethyllysine on oxidative stress and the glutathione system in beta cells (2014)

One of the pathways involved in the pathogenesis of diabetic complications is the formation of excessive levels of advanced glycation end (AGE) products. N<sup>ɛ</sup>-carboxymethyllysine (CML) is one of the best-characterized AGEs. Because little is known about the effects of AGEs on pancreatic beta cells, we investigated the effect of CML on human pancreatic cells and determined the activity and gene expression of glutathione system components. CML at a concentration of 0.5 mM induced cell death in human pancreatic beta cells, which was accompanied by increased intracellular oxidative stress. No changes in the gene expression of the receptor for AGEs (RAGE) were found, although an increase in the level of a target cytokine of RAGE after CML exposure was observed. Additionally we found that CML lowered the levels of GSH and affected the activity and expression of other components of the glutathione system. These changes indicate that the cells are even more vulnerable for oxidative stress after exposure to CML. Since beta cells are low in antioxidant enzymes and repair for oxidized DNA, CML, but most likely also other AGEs, accelerates beta cell dysfunction and increases beta cell death during chronic hyperglycemia.
Total Synthesis and Structural Revision of Callipeltoside C (2008)

Look again: Highlights of the 20-step synthesis of callipeltoside C include the proline-catalyzed direct aldol reaction, enantioselective α-oxyamination reaction, and rapid access to the carbohydrate framework using a de novo synthesis protocol. Based on this work the previously assigned absolute configuration of the pendent 2-O-methylevalose unit has been revised.
Hypoxia-Inducible Factor-1 Target Genes as Indicators of Tumor Vessel Response to Vascular Endothelial Growth Factor Inhibition (2008)

Antiangiogenic therapy improves survival in patients with advanced stage cancers. Currently, there are no reliable predictors or markers for tumor vessel response to antiangiogenic therapy. To model effective antiangiogenic therapy, we disrupted the VEGF gene in three representative cancer cell lines. HCT116 xenografts had low proportions of endothelial tubes covered by pericytes that stained with alpha-smooth muscle actin (SMA) antibody. Upon disruption of VEGF, HCT116(VEGF-/-) xenografts had significantly decreased tumor microvessel perfusion compared with their parental counterparts. Furthermore, HCT116(VEGF-/-) xenografts mounted a tumor-reactive response to hypoxia, characterized by the induction of hypoxia-inducible factor-1 (HIF-1) target genes. One highly induced protein was DPP4, a measurable serum protein that has well-described roles in cancer progression. In contrast, LS174T and MKN45 tumor xenografts had high proportion of endothelial tubes that were covered by SMA+ pericytes. Upon disruption of VEGF, LS174T(VEGF-/-) and MKN45(VEGF-/-) xenografts maintained tumor microvessel perfusion. As such, there were no changes in intratumoral hypoxia or HIF-1 alpha induction. Together, these data show that the extent of tumor vessel response to angiogenic inhibition could be correlated with (a) the preexisting coverage of tumor endothelial tubes with SMA+ pericytes and (b) differential tumor induction of HIF-1 target genes. The data further show that DPP4 is a novel marker of HIF-1 induction. Altogether, these preclinical findings suggest novel clinical trials for predicting and monitoring tumor vessel responses to antiangiogenic therapy.
A Semisynthetic Kanglemycin Shows In Vivo Efficacy against High-Burden Rifampicin Resistant Pathogens (2020)

Semisynthetic rifamycin derivatives such as rifampicin (Rif) are first line treatments for tuberculosis and other bacterial infections. Historically, synthetic modifications made to the C-3/C-4 region of the rifamycin naphthalene core, like those seen in Rif, have yielded the biggest improvements in pharmacological properties. However, modifications found in natural product rifamycin congeners occur at other positions in the structure. The kanglemycins (Kangs) are a family of rifamycin congeners with a unique collection of natural modifications including a dimethylsuccinic acid appended to their polyketide backbone. These modifications confer activity against the single most common clinically relevant Rif resistance (Rif<sup>R</sup>) mutation in the antibiotic's target, the bacterial RNA polymerase (RNAP). Here we evaluate the in vivo efficacy of Kang A, the parent compound in the Kang family, in a murine model of bacterial peritonitis/sepsis. We then set out to improve its potency by combining its natural tailoring modifications with semisynthetic derivatizations at either its acid moiety or in the C-3/C-4 region. A collection of C-3/C-4 benzoxazino Kang derivatives exhibit improved activity against wild-type bacteria, and acquire activity against the second most common clinically relevant Rif<sup>R</sup> mutation. The semisynthetic analogue 3'-hydroxy-5'-[4-isobutyl-1-piperazinyl] benzoxazino Kang A (Kang KZ) protected mice against infection with either Rif sensitive MRSA or a highly virulent Rif<sup>R</sup><i>Staphylococcus aureus</i> strain in a neutropenic peritonitis/sepsis model and led to reduced bacterial burdens. The compounds generated in this study may represent promising candidates for treating Rif<sup>R</sup> infections.
Discovery of Insect Anti-Juvenile Hormones in Plants (1976)

Two simple chromenes with anti-JH activity have been isolated and identified from the bedding plant Ageratum houstoianum. By contact and fumigation these compounds induce precocious metamorphosis and sterilization in several hemipteran species of insects. Certain holometabolous species are sterilized, forced into diapause, or both. Each of these biological actions is equivalent to removal of the corpora allata, which produce the JH's, and is reversible by treatment with exogenous JH. Thus, the action of these compounds is to stop the production or depress the titer of the JH's. To our knowledge, this is the first discovery of anti-JH, and we hope it will guide the way to the emergence of a fourth generation of safe and insect-specific pesticides.
From the Biopolymer PHB to Biological Investigations of Unnatural β- and γ-Peptides (2001)

An overview is given of the past and present activities of our group in the field of chemical biology. Thus, the polymer of 3-hydroxybutanoic acid (PHS), which is omnipresent in living organisms, triggered our search for a better analytical method for detecting PHB and our syntheses of oligomers of 3-hydroxyalkanoic acids (OHSs). Also, the regulation of DNA replication by poly(β-malic acid) (PMA) in certain eukaryotes inspired synthetic work on the corresponding cyclic and open-chain oligomers. With these oligomers we not only tested the mechanisms of depolymerases, but were able to study the properties and activities of well-characterized compounds (also with isotope and fluorescence labeling). The role of PHS as component of ion transport systems through phospholipid bilayers was unambiguously established, and models for the channel structure were proposed. Replacement of amino acids by 3-hydroxybutanoic acid residues in peptides and replacement of the chain-bound oxygens in OHB by NH paved our way into the world of β- and γ-peptides, the synthesis and physiological and pharmacological properties of which are being investigated. β-Peptides are stable to peptidases, have a long lifetime in mammalian serum and are rather resistant to environmental microbial degradation. The peptides consisting of homologated (β) or doubly homologated (γ) amino acids form stable secondary structures in solution (helices, turns, sheets) which can be used as scaffolds for peptide mimics, such as a β-tetrapeptide with affinity to a somatostatin receptor or a β-nonapeptide that inhibits intestinal lipid-transport protein (SR-BI) in Caco-2 cells. Certain β-peptides have antibacterial, antiproliferative and haemolytic properties. The lessons from studies of β- and γ-peptides teach us about the central role of natural α-peptidic proteins.
Therapeutic Potential of VIVIT, a Selective Peptide Inhibitor of Nuclear Factor of Activated T cells, in Cardiovascular Disorders (2007)

Cardiovascular disease is the major cause of death in industrialized nations. Targeted intervention in calcineurin, a calmodulin-dependent, calcium-activated phosphatase and its substrate, nuclear factor of activated T cells (NFAT), was demonstrated to be effective in the treatment of cardiovascular diseases. Although effective in the disruption of calcineurin phosphatase activity, cyclosporin A (CsA) and FK506 also resulted in undesired side effects and toxicity, prompting the discovery of VIVIT, a novel peptide inhibitor. VIVIT selectively and potently inhibits calcineurin/NFAT interaction, but does not compromise calcineurin phosphatase activity and non-NFAT-mediated signaling. VIVIT displays a favorable therapeutic profile as a potential drug candidate and constitutes a useful tool in exploring calcineurin-NFAT functionality. This review describes the development of VIVIT peptide as a selective NFAT inhibitor and its application as a therapeutic agent in cardiovascular disorders including cardiac hypertrophy, restenosis, atherosclerosis, and angiogenesis.
Type II regulatory subunit (RII) of the cAMP-dependent protein kinase interaction with A-kinase anchor proteins requires isoleucines 3 and 5. (1994)

Compartmentalization of the type II cAMP-dependent protein kinase is maintained by association of the regulatory subunit (RII) with A-Kinase Anchor Proteins (AKAPs). In previous studies (Scott, J. D., Stofko, R. E., McDonald, J. R., Comer, J. D., Vitalis, E. A., and Mangili J. (1990) J. Biol. Chem. 265, 21561-21566) we have shown that dimerization of RII alpha was required for interaction with the cytoskeletal component microtubule-associated protein 2. In this report we show that the localization and dimerization domains of RII alpha are contained within the first thirty residues of each RII protomer. RII des-5 (an amino-terminal deletion mutant lacking residues 1-5) was unable to bind AKAPs but retained the ability to dimerize. RII alpha I3A,I5A (a mutant where isoleucines 3 and 5 were replaced with alanine) was unable to bind a variety of AKAPs. Mutation of both isoleucines decreased AKAP binding without affecting dimerization, cAMP binding, or the overall secondary structure of the protein. Measurement of RII alpha I3A,I5A interaction with the human thyroid AKAP, Ht 31, by two independent methods suggests that mutation of isoleucines 3 and 5 decreases affinity by at least 6-fold. Therefore, we propose that two isoleucine side chains on each RII protomer are principle sites of contact with the conserved amphipathic helix binding domain on AKAPs.
Inhibition of glutamine synthetase reduces ammonia-induced astrocyte swelling in rat (1996)

Astrocyte hypertrophy and swelling occur in a variety of pathophysiological conditions, including diseases associated with hyperammonemia. Ammonia is rapidly incorporated into glutamine by glutamine synthetase localized in astrocytes. We tested the hypotheses that (1) 6 h of hyperammonemia (500-600 microM) is adequate for producing astrocyte enlargement, and (2) astrocyte enlargement is attenuated by inhibition of glutamine synthetase with methionine sulfoximine. Pentobarbital-anesthetized rats received an intravenous infusion of either sodium or ammonium acetate after intraperitoneal pretreatment with vehicle, methionine sulfoximine (0.8 mmol/kg) or buthionine sulfoximine (4 mmol/kg), an analogue that does not inhibit glutamine synthetase. Hyperammonemia produced enlarged cortical astrocytes characterized by (1) decreased electron density of cytoplasmic matrix in perikaryon, processes and perivascular endfeet, (2) increased circumference of nuclear membrane, (3) increased numbers of mitochondria and rough and smooth endoplasmic reticulum in perikarya and large processes, and (4) less compact bundles of intermediate filaments. Pretreatment with methionine sulfoximine, but not buthionine sulfoximine, attenuated the decrease in cytoplasmic density and the increase in nuclear circumference; most perivascular endfeet remained as dense as occurred with sodium acetate infusion. However, increased numbers of organelles in expanded perikarya and large processes occurred after methionine sulfoximine treatment with and without ammonium acetate infusion. In separate groups of rats, hyperammonemia produced an increase in cortical tissue water content which was inhibited by methionine sulfoximine, but not buthionine sulfoximine. We conclude that clinically-relevant levels of hyperammonemia can cause astrocyte enlargement within 6 h in vivo characterized by both watery cytoplasm and increased organelles indicative of a cellular metabolic stress and altered astrocyte function. The watery cytoplasm component of astrocyte enlargement depends on glutamine synthesis rather than on ammonium ions per se, and is possibly caused by the osmotic effect accumulated glutamine.
Papillomavirus genome structure, expression, and post-transcriptional regulation (2006)

Papillomaviruses are a group of small non-enveloped DNA tumor viruses whose infection usually causes benign epithelial lesions (warts). Certain types of HPVs, such as HPV-16, HPV-18, and HPV-31, have been recognized as causative agents of cervical cancer and anal cancer and their infections, which arise via sexual transmission, are associated with more than 95% of cervical cancer. Papillomaviruses infect keratinocytes in the basal layer of stratified squamous epithelia and replicate in the nucleus of infected keratinocytes in a differentiation-dependent manner. Viral gene expression in infected cells depends on cell differentiation and is tightly regulated at the transcriptional and post-transcriptional levels. A noteworthy feature of all papillomavirus transcripts is that they are transcribed as a bicistronic or polycistronic form containing two or more ORFs and are polyadenylated at either an early or late poly(A) site. In the past ten years, remarkable progress has been made in understanding how this complex viral gene expression is regulated at the level of transcription (such as via DNA methylation) and particularly post-transcription (including RNA splicing, polyadenylation, and translation). Current knowledge of papillomavirus mRNA structure and RNA processing has provided some clues on how to control viral oncogene expression. However, we still have little knowledge about which mRNAs are used to translate each viral protein. Continuing research on post-transcriptional regulation of papillomavirus infection will remain as a future focus to provide more insights into papillomavirus-host interactions, the virus life-cycle, and viral oncogenesis.
Fatty acid synthesis: a potential selective target for antineoplastic therapy. (1994)

OA-519 is a prognostic molecule found in tumor cells from breast cancer patients with markedly worsened prognosis. We purified OA-519 from human breast carcinoma cells, obtained its peptide sequence, and unambiguously identified it as fatty acid synthase through sequence homology and enzymology. Tumor fatty acid synthase is an approximately 270-kDa polypeptide which specifically abolished immunostaining of human breast cancers by anti-OA-519 antibodies. Tumor fatty acid synthase oxidized NADPH in a malonyl-CoA-dependent fashion and synthesized fatty acids composed of 80% palmitate, 10% myristate, and 10% stearate from acetyl-CoA, malonyl-CoA, and NADPH with a specific activity of 624 nmol of NADPH oxidized per min per mg. Tumor cell lines with elevated fatty acid synthase showed commensurate increases in incorporation of [U-14C]acetate into acylglycerols demonstrating that fatty acid synthase increases occur in the context of overall increases in endogenous fatty acid synthesis. Cerulenin inhibited acylglycerol synthesis in tumor cells and fibroblast controls in a dose-dependent fashion and also caused a growth inhibition which generally paralleled the level of endogenous fatty acid synthesis. Supraphysiologic levels of palmitate, 14 microM in dimethyl sulfoxide, significantly reversed the growth inhibition caused by cerulenin at concentrations of up to 5 micrograms/ml, indicating that cerulenin-mediated growth inhibition was due to fatty acid synthase inhibition.
A Self-Fulfilling Prophecy (2002)

CRP, at concentrations known to predict adverse vascular events, directly quenches the production of the NO, in part, through posttranscriptional effect on eNOS mRNA stability. Diminished NO bioactivity, in turn, inhibits angiogenesis, an important compensatory mechanism in chronic ischemia. Through decreasing NO synthesis, CRP may facilitate the development of diverse cardiovascular diseases. Risk reduction strategies designed to lower plasma CRP may be effective by improving NO bioavailability.
The carbon brace (2013)

Orthopaedic treatment is still a heavy treatment for teenagers in growth period. This orthosis is designed to partly maintain spine and chest mobility. We hope so to have part in improving life conditions of these teenagers, compared to those treated with rigid braces.
PEPTIDE TOXINS FROM VENOMOUS CONUS SNAILS (1988)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Atherosclerosis: evidence for impairment of resolution of vascular inflammation governed by specific lipid mediators (2008)

Atherosclerosis is now recognized as an inflammatory disease involving the vascular wall. Recent results indicate that acute inflammation does not simply passively resolve as previously assumed but is actively terminated by a homeostatic process that is governed by specific lipid-derived mediators initiated by lipoxygenases. Experiments with animals and humans support a proinflammatory role for the 5-lipoxygenase system. In contrast, results from animal experiments show a range of responses with the 12/15-lipoxygenase pathways in atherosclerosis. To date, the only two clinical epidemiology human studies both support an antiatherogenic role for 12/15-lipoxygenase downstream actions. We tested the hypothesis that atherosclerosis results from a failure in the resolution of local inflammation by analyzing apolipoprotein E-deficient mice with 1) global leukocyte 12/15-lipoxygenase deficiency, 2) normal enzyme expression, or 3) macrophage-specific 12/15-lipoxygenase overexpression. Results from these indicate that 12/15-lipoxygenase expression protects mice against atherosclerosis via its role in the local biosynthesis of lipid mediators, including lipoxin A(4), resolvin D1, and protectin D1. These mediators exert potent agonist actions on macrophages and vascular endothelial cells that can control the magnitude of the local inflammatory response. Taken together, these findings suggest that a failure of local endogenous resolution mechanisms may underlie the unremitting inflammation that fuels atherosclerosis.