gebhart/patrepeval huggingface dataset:
Lixisenatide, a novel GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus. (2009)

Lixisenatide, under development by sanofi-aventis, is a novel human glucagon-like peptide-1 receptor (GLP-1R) agonist for the treatment of type 2 diabetes mellitus (T2DM; non-insulin dependent diabetes). The structure of lixisenatide, based on exendin-4(1-39) modified C-terminally with six Lys residues, is able to withstand physiological degradation by dipeptidyl peptidase IV. In vitro, lixisenatide bound to human GLP-1R with a greater affinity than native human GLP-1 (7-36 amide). In various in vitro and in vivo models of T2DM, lixisenatide improved glycemic measures and demonstrated promising pancreatic beta-cell-preserving actions. In patients with T2DM, subcutaneously administered lixisenatide displayed linear pharmacokinetics. In two phase II clinical trials, lixisenatide improved glucose tolerance, resulted in weight loss and lowered HbA1C, thereby causing significantly more patients to achieve target HbA1C levels compared with placebo. Lixisenatide exhibited well-established GLP-1-related gastrointestinal side effects, with mild nausea occurring most frequently; a low frequency of hypoglycemia was also reported. The results of phase III trials are awaited for confirmation of the anticipated effects of lixisenatide on glycemic measures and weight; favorable results would place lixisenatide for consideration among other GLP-1R agonists in the treatment armamentarium for T2DM.
Gene expression of human DNA polymerase alpha during cell proliferation and the cell cycle. (1988)

We studied the expression of the human DNA polymerase alpha gene during cell proliferation, during cell progression through the cell cycle, and in transformed cells compared with normal cells. During the activation of quiescent cells (G0 phase) to proliferate (G1/S phases), the steady-state mRNA levels, rate of synthesis of nascent polymerase protein, and enzymatic activity in vitro exhibited a substantial and concordant increase prior to the peak of in vivo DNA synthesis. In transformed cells, the respective values were amplified greater than 10-fold. In actively growing cells separated into discrete stages of the cell cycle by counterflow elutriation or by mitotic shakeoff, levels of steady-state transcripts, translation rates, and enzymatic activities of polymerase alpha were constitutively and concordantly expressed at all stages of the cell cycle, with only a moderate elevation prior to the S phase and a slight decline in the G2 phase. These findings support the conclusion that the regulation of human DNA polymerase alpha gene expression is at the transcriptional level and strongly suggest that the regulatory mechanisms that are operative during the entrance of a cell into the mitotic cycle are fundamentally different from those that modulate polymerase alpha expression in continuously cycling cells.
Development of an Infectious HCV Cell Culture System (2006)

Hepatitis C virus (HCV) infection causes chronic liver diseases and is a health problem worldwide. Despite the increasing demand for knowledge on viral replication and pathogenesis, detailed examinations of the viral life cycle have been hampered by the lack of efficient viral culture systems, owing in part to its narrow host range. We isolated full-length HCV clone, JFH-1strain, from a fulminant hepatitis C patient. The JFH-1strain fit into the cluster of genotype 2a with notable deviations in the 5′-untranslated region (5′UTR), core, NS3 and NS5A regions, and monoclonality of the hyper-variable region sequence. The JFH-1 subgenomic replicon replicated efficiently in a variety of cell lines without acquiring adaptive mutations in its genome. Transfection of in vitro transcribed full-length RNA into Huh7 cells, efficient replication of JFH-1 RNA and secretion of recombinant viral particles into culture medium. Importantly, secreted viral particles were infectious for both cultured cells and a chimpanzee. Furthermore, infectivity for cultured cells was improved by using permissive cell lines. This infectious HCV system provides for the first time a powerful tool to study the full viral life cycle, to construct antiviral strategies and to develop effective vaccines.
Peptoids—A New Approach to the Development of Pharmaceuticals (1993)

N-substituted oligoglycines, “peptoids”, can be prepared in good yields and high purity without protected monomer building blocks and without deprotection according to Equation (a). This class of compounds should be of great utility in screening for new pharmaceutical lead structures.
Catalytic reduction of CO2 by H2 for synthesis of CO, methanol and hydrocarbons: challenges and opportunities (2015)

Controlling the catalytic reduction of CO<sub>2</sub> by H<sub>2</sub> to produce CO, methanol or hydrocarbons requires stabilization of key reaction intermediates.
Role of mitochondrial re-energization and Ca influx in reperfusion injury of metabolically inhibited cardiac myocytes (2005)

Reperfusion-induced hypercontracture, and loss of Ca2+ homeostasis and contractile function are initiated following mitochondrial re-energization. The hypercontracture requires the production of oxidative ATP but not Ca2+ influx during reperfusion. Loss of Ca2+ homeostasis and contractile function are linked to Ca2+ influx during reperfusion, probably via opening of mitochondrial permeability transition pores.
Role of c-kit ligand in the expansion of human hematopoietic progenitor cells (1992)

To test the hypothesis that the c-kit ligand plays an important role in the regulation of early events occurring during human hematopoiesis, we determined the effect of a recombinant form of c-kit ligand, termed mast cell growth factor (MGF), on the high-proliferative potential colony-forming cell (HPP-CFC) and the cell responsible for initiating long-term hematopoiesis in vitro (LTBMIC). MGF alone did not promote HPP-CFC colony formation by CD34+ DR- CD15- marrow cells, but synergistically augmented the ability of a combination of granulocyte- monocyte colony-stimulating factor (GM-CSF) interleukin (IL)-3 and a recombinant GM-CSF/IL-3 fusion protein (FP) to promote the formation of HPP-CFC-derived colonies. MGF had a similarly profound effect on in vitro long-term hematopoiesis. Repeated additions of IL-3, GM-CSF, or FP alone to CD34+ DR- CD15- marrow cells in a stromal cell-free culture system increased cell numbers 10(3)-fold by day 56 of long-term bone marrow culture (LTBMC), while combinations of MGF with IL-3 or FP yielded 10(4)- and 10(5)-fold expansion of cell numbers. Expansion of the number of assayable colony-forming unit-granulocyte-monocyte (CFU- GM) generated during LTBMC was also markedly enhanced when MGF was added in combination with IL-3 or FP. In addition, MGF, IL-3, and FP individually led to a twofold to threefold increase in HPP-CFC numbers after 14 to 21 days of LTBMC. Furthermore, the effects of these cytokines on HPP-CFC expansion during LTBMC were additive. Throughout the LTBMC, cells receiving MGF possessed a higher cloning efficiency than those receiving IL-3, GM-CSF, or FP alone. These data indicate that the c-kit ligand synergistically interacts with a number of cytokines to directly augment the proliferative capacity of primitive human hematopoietic progenitor cells.
A fast and simple method to fabricate circular microchannels in polydimethylsiloxane (PDMS) (2010)

A simple method to fabricate circular microchannels in polydimethylsiloxane (PDMS) is presented. A coating of liquid PDMS is applied on the walls of rectangular microchannels, fabricated using standard soft-lithography, by introducing a pressurized air stream inside the PDMS filled microchannels. Surface tension of the liquid PDMS forces the coating to take a circular cross-section which is preserved by baking the device to cure the coated layer. Diameters ranging from a few micrometres to a few hundreds of micrometres were achieved. The method was verified to work on microchannel networks as well as in straight channels. Different coating conditions were systematically tested. Design curves are reported for one to choose appropriate coating conditions for obtaining a desired diameter. A comparison between the performance of square and circular microchannels in trapping SiHa cells (cervical cancer cell line) is shown.
beta-Glucosidase: an elicitor of herbivore-induced plant odor that attracts host-searching parasitic wasps. (1995)

Cabbage plants respond to caterpillar (Pieris brassicae) herbivory by releasing a mixture of volatiles that makes them highly attractive to parasitic wasps (Cotesia glomerata) that attack the herbivores. Cabbage leaves that are artificially damaged and subsequently treated with gut regurgitant of P. brassicae caterpillars release a volatile blend similar to that of herbivore-damaged plants. We demonstrate the presence of beta-glucosidase in P. brassicae regurgitant. Leaves treated with commercial beta-glucosidase (from almonds) release a volatile blend similar to that of leaves treated with P. brassicae regurgitant. In a flight bioassay, leaves treated with almond beta-glucosidase are highly attractive to the parasitic wasp C. glomerata. Furthermore, the wasps do not discriminate between cabbage leaves treated with almond beta-glucosidase and leaves treated with larval regurgitant. beta-Glucosidase was also recorded in cabbage leaf extract, but this is not as effective as caterpillar beta-glucosidase in eliciting the volatile production. Caterpillars that feed on a beta-glucosidase-free diet secrete the enzyme, and their regurgitant is an effective elicitor of the plant response. These findings show that beta-glucosidase is a P. brassicae-secreted elicitor of the defense response of cabbage plants to herbivore injury, inducing the emission of volatiles that are used by parasitoids of the herbivore to locate their victims.
Unanticipated differences between α- and γ-diaminobutyric acid-linked hairpin polyamide-alkylator conjugates (2006)

Hairpin polyamide-chlorambucil conjugates containing an alpha-diaminobutyric acid (alpha-DABA) turn moiety are compared to their constitutional isomers containing the well-characterized gamma-DABA turn. Although the DNA-binding properties of unconjugated polyamides are similar, the alpha-DABA conjugates display increased alkylation specificity and decreased rate of reaction. Treatment of a human colon carcinoma cell line with alpha-DABA versus gamma-DABA hairpin conjugates shows only slight differences in toxicities while producing similar effects on cell morphology and G2/M stage cell cycle arrest. However, striking differences in animal toxicity between the two classes are observed. Although mice treated with an alpha-DABA hairpin polyamide do not differ significantly from control mice, the analogous gamma-DABA hairpin is lethal. This dramatic difference from a subtle structural change would not have been predicted.
Isolation and Characterization of Allergens from Ragweed Pollen. II* (1964)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIsolation and Characterization of Allergens from Ragweed Pollen. II*T. P. King, P. S. Norman, and J. T. ConnellCite this: Biochemistry 1964, 3, 3, 458–468Publication Date (Print):March 1, 1964Publication History Published online1 May 2002Published inissue 1 March 1964https://pubs.acs.org/doi/10.1021/bi00891a026https://doi.org/10.1021/bi00891a026research-articleACS PublicationsRequest reuse permissionsArticle Views219Altmetric-Citations166LEARN 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 optionsGet e-Alertsclose Get e-Alerts
Most compact hairpin-turn structure exerted by a short DNA fragment, d(GCGAAGC) in solution: an extraordinarily stable structure resistant to nucleases and heat (1994)

The three-dimensional structure of a short DNA fragment, d(GCGAAGC) exhibiting an extraordinarily stable hairpin structure was determined by nuclear magnetic resonance spectroscopy. Two possible models were obtained by molecular modelling using distance and torsion constraints. Only one of these two models is the correct structure, which can clearly explain all the 1H chemical shifts. d(GCGAAGC) is folded back on itself between A4 and A5, and all the sugars in the fragment adopt the C2'-endo conformation. This compact molecule is stabilized by regular extensive base-stacking interaction within each B-form helical strand of G1C2G3A4 and A5G6C7, and by two G-C and one G3-A5 base pairs. The molecule is hard to differentiate into stem and loop regions, so that we classify it as a turn (hairpin-turn) structure experted by a single-stranded DNA. This highly stacked structure shows high thermostability and strong resistance against nucleases contained in E. coli extracts and in human serum.
Discrete Cerebral Hypothermia in the Management of Severe Traumatic Brain Injury (2008)

INTRODUCTION: Hypothermia has been extensively utilized and evaluated in the management of traumatic brain injury (TBI). To date, no consensus as to its effectiveness has been reached. Hypotheses include a possible confounding effect of the neuroprotective benefits by the negative systemic effects. To minimize these potential confounders of systemic hypothermia, we evaluated the utility of a selective cerebral cooling system in the management of TBI using the CoolSystem Discrete Cerebral Hypothermia System (CSHS). METHODS: This was a randomized clinical control trial conducted from July 2006 to July 2007 at Grady Memorial Hospital (GMH). Patients admitted with a diagnosis of severe TBI (GCS < 8) were eligible. Twenty-five patients comprised the cohort (12 treatments, 13 controls). Treatment patients received the CSHS; controls did not receive the CSHS. Patients were treated with hypothermia for 24 hours, and then rewarmed over a period of 24 hours. The patients' intracranial and bladder temperatures, cranial-bladder temperature gradient, Glasgow Outcome Score (GOS), Functional Independence Measure (FIM), and mortality rates were evaluated. The primary outcome was to establish a cranial-bladder temperature gradient. The secondary outcomes were mortality and morbidity (FIM and GOS) in this population. RESULTS: The CSHS was not effective in establishing a cranial-bladder temperature gradient for either the treatment (P = 0.67) or control (P = 0.07) groups. There was no significant difference in mortality between the treatment and control groups (P = 0.64). There was no observed difference in morbidity as assessed by the median change in GOS (P = 0.5) and FIM (pfeed = 1.0, plocomotion = 0.64, pmotor = 0.64) between the cohorts. CONCLUSION: No significant benefit in morbidity (GOS or FIM) or mortality was achieved with the CSHS. The CSHS was also not effective in establishing the target intracranial-core temperature gradient. Further studies will be needed in order to better refine the available equipment in the delivery of selective cerebral cooling before any definite conclusions can be reached.
Triple-Helix Propensity of Hydroxyproline and Fluoroproline:  Comparison of Host−Guest and Repeating Tripeptide Collagen Models (2003)

Peptide models have proved important in defining the structural features of the collagen triple-helix. Some models are based on multiple repeats of a given tripeptide unit, while a host-guest design includes an individual tripeptide unit substituted within a constant repeating Pro-Hyp-Gly framework. In the present study, proline, hydroxyproline, and fluoroproline residues are incorporated in X- or Y-positions of a guest triplet in the host-guest peptide design. All host-guest peptides, including Hyp-Pro-Gly, formed stable triple-helices, even though a triple-helix cannot be formed by (Hyp-Pro-Gly)10. The order of stability Pro-Hyp-Gly > Pro-Pro-Gly > Hyp-Pro-Gly remains the same in all models, while the Pro-Flp-Gly is very stabilizing in a repeating context but destabilizing in a host-guest context. The range of thermal stabilities and calorimetric enthalpies is very small among the five host-guest peptides, consistent with the concept that the effect of one Xaa-Yaa-Gly tripeptide unit in the host-guest system would be less than the much larger variations when there are 10 repeating units. However, a simple additive model based on host-guest peptides predicts a greater stability than experimentally observed. The difference in stability contributions of the same tripeptide unit in host-guest versus repeating tripeptide systems illustrates the impact of sequence environment on stability, and factors that play a role include ring puckering as a consequence of electron inductive effects, residual monomer structure, and native state hydration networks.
Defeating Memory Corruption Attacks via Pointer Taintedness Detection (2005)

Most malicious attacks compromise system security through memory corruption exploits. Recently proposed techniques attempt to defeat these attacks by protecting program control data. We have constructed a new class of attacks that can compromise network applications without tampering with any control data. These non-control data attacks represent a new challenge to system security. In this paper, we propose an architectural technique to defeat both control data and non-control data attacks based on the notion of pointer taintedness. A pointer is said to be tainted if user input can be used as the pointer value. A security attack is detected whenever a tainted value is dereferenced during program execution. The proposed architecture is implemented on the SimpleScalar processor simulator and is evaluated using synthetic programs as well as real-world network applications. Our technique can effectively detect both control data and non-control data attacks, and it offers better security coverage than current methods. The proposed architecture is transparent to existing programs.
Amelioration of Light-Induced Retinal Degeneration by a Calcium Overload Blocker (1991)

Although free radical formation and lipid peroxidation have been implicated in photoreceptor degeneration following continuous light exposure, recent evidence led us to hypothesize that excessive stimulation of the photoreceptor cells in prolonged light exposure may cause intracellular calcium overload and consequent photoreceptor cell injury. To test this hypothesis, we studied the effects of flunarizine hydrochloride, a calcium overload blocker that inhibits the inositol 1,4,5-triphosphate-induced release of intracellular stores of calcium, in an established rat model of light-induced retinal degeneration. Light and electron microscopic examination of the flunarizine-treated retinas revealed remarkable preservation of the retinal pigment epithelium, rod inner and outer segments, nuclei, and synapses of the photoreceptor cells at all phases of the recovery period. This observation was further supported by morphometric evaluation of the outer nuclear layer thickness, which revealed a greater preservation of the photoreceptor nuclei in the drug-treated animals at 6 and 14 days after exposure. In addition, the rhodopsin levels in the flunarizine-treated retinas were also significantly higher than in the controls in all phases of recovery. The ability of flunarizine to ameliorate light-induced retinal degeneration in the rat supports our hypothesis that elevated intracellular calcium may indeed play a role in light-induced photoreceptor degeneration.
Transformation-dependent expression of interleukin genes delivered by a recombinant parvovirus (1992)

The prototype strain of minute virus of mice [MVM(p)] is an autonomous parvovirus with a tropism for cells expressing a neoplastically transformed phenotype. To generate gene transfer vectors for tumor-specific gene expression, human interleukin-2 (IL-2) and murine interleukin-4 (IL-4) genes were cloned under the control of the p38 late promoter of MVM(p). Upon transfection into permissive cells, the recombinant MVMIL2 or MVMIL4 DNA was excised, amplified, and, in the presence of a helper plasmid, packaged into recombinant viral particles. The recombinant viruses were able to transfer fully functional IL-2 and IL-4 genes to permissive target cells and retained the oncotropic host range properties of the parental virus. Following infection with MVMIL2, nontransformed fibroblasts of rodent (FR3T3) or human (MRC-5) origin produced minimal IL-2 compared with the high levels of IL-2 production observed in their transformed derivatives (FREJ4 and MRC-5V1).
Disorders of glycoprotein degradation (1990)

The intracellular degradation of glycoproteins occurs predominantly in the lysosomes through the concerted action of proteases and glycosidases. Genetic defects in any of the enzymes cleaving the oligosaccharide side chains lead to specific diseases because of an excessive lysosomal accumulation of partially degraded material, mostly oligosaccharides. This paper presents an overview of the biochemistry and the clinical spectrum of this group of diseases including sialidosis, galactosialidosis, alpha- and beta-mannosidosis, fucosidosis, aspartylglucosaminuria, and alpha-N-acetylgalactosaminidase deficiency (Schindler disease). In addition, the sialic acid storage disorder (Salla disease) which is caused by a defect in the lysosomal transport of this acidic monosaccharide is included because of functional and clinical correlations.
Treatment of recalcitrant verruca vulgaris with Candida antigen in patient with human immunodeficiency virus. (2009)

Verruca vulgaris is often difficult to treat in individuals with human immunodeficiency virus (HIV) infection. We present a case of an HIV positive 44-year-old male with a 3-year history of multiple recalcitrant verruca vulgaris involving his hands and face. He did not respond to cryotherapy, urea 40% cream, imiquimod 5% cream, paring, intralesional bleomycin, salicylic acid 6% gel, and electrodesiccation and curettage. The patient achieved complete clearance of all warts within 1 month following treatment of his hands with intralesional Candida antigen. This case reports a complete response of verruca vulgaris to intralesional Candida antigen in an immunocompromised patient.