gebhart/patrepeval huggingface dataset:
Construction of intertypic chimeric dengue viruses exhibiting type 3 antigenicity and neurovirulence for mice (1995)

There are four dengue virus serotypes (DEN1 to -4), each of which causes major epidemics in tropical or subtropical areas. The current strategy for dengue virus immunization favors the use of a tetravalent vaccine preparation. We have previously employed full-length DEN4 cDNA to construct a viable intertypic dengue virus type 1 or type 2 chimera that contained the C-PreM-E or only the PreM-E genes of DEN1 or DEN2 substituting for the corresponding genes of DEN4. This success implied that it might be possible to create mutants of all four dengue virus serotypes for evaluation as candidate vaccines. In this study, we constructed DEN3-DEN4 chimeras that contained DEN3 C-PreM-E genes and expressed DEN3 antigenic specificity. Unlike our previous successes in cloning DEN1 or DEN2 chimeric cDNA, we were not able to clone the DEN3 C-PreM-E genes directly in the 5' intermediate vector or in the full-length chimeric DEN3-DEN4 plasmid in Escherichia coli. Nevertheless, a full-length DNA template of DEN3-DEN4 that could be used for transcription of infections RNAs was prepared by in vitro ligation. Progeny virus recovered from RNA-transfected C6/36 mosquito cells exhibited DEN3 antigenic specificity as determined by a reaction with monoclonal antibodies. Gel electrophoresis of virus-infected cell lysates yielded the predicted viral protein pattern, i.e., DEN3 C, PreM, and E and DEN4 nonstructural proteins. Two amino acid substitutions, Thr-435-->Leu and Glu-406-->Lys, which are analogous to mutations that, respectively, confer mouse neurovirulence on DEN4 and DEN2, were introduced into DEN3 E. A mutant chimera containing the Thr-435-->Leu substitution, which ablates the potential glycosylation site sequence, produced an E protein identical in size to that of wild-type DEN3 E, indicating that the glycosylation site is normally not used. Intracerebral inoculation of suckling mice revealed that the mutant chimera containing the Glu-406-->Lys substitution was neurovirulent, whereas its wild-type counterpart or parent DEN3 was not.
Antidiabetic plants improving insulin sensitivity (2014)

The different metabolic and cellular effects of the antidiabetic plants improving insulin sensitivity are reported indicating the important role of medicinal plants as potential alternative or complementary use in controlling insulin resistance associated with diabetes mellitus.
Zero-Knowledge against Quantum Attacks (2009)

This paper proves that several interactive proof systems are zero-knowledge against general quantum attacks. This includes the well-known Goldreich–Micali–Wigderson classical zero-knowledge protocols for graph isomorphism and graph 3-coloring (assuming the existence of quantum computationally concealing commitment schemes in the second case). Also included is a quantum interactive proof system for a complete problem for the complexity class of problems having honest verifier quantum statistical zero-knowledge proofs, which therefore establishes that honest verifier and general quantum statistical zero-knowledge are equal: $\mathrm{QSZK}= \mathrm{QSZK}_{\mathrm{HV}}$. Previously no nontrivial interactive proof systems were known to be zero-knowledge against quantum attacks, except in restricted settings such as the honest verifier and common reference string models. This paper therefore establishes for the first time that true zero-knowledge is indeed possible in the presence of quantum information and computation.
Translocation of DNA across bacterial membranes (1994)

DNA translocation across bacterial membranes occurs during the biological processes of infection by bacteriophages, conjugative DNA transfer of plasmids, T-DNA transfer, and genetic transformation. The mechanism of DNA translocation in these systems is not fully understood, but during the last few years extensive data about genes and gene products involved in the translocation processes have accumulated. One reason for the increasing interest in this topic is the discussion about horizontal gene transfer and transkingdom sex. Analyses of genes and gene products involved in DNA transfer suggest that DNA is transferred through a protein channel spanning the bacterial envelope. No common model exists for DNA translocation during phage infection. Perhaps various mechanisms are necessary as a result of the different morphologies of bacteriophages. The DNA translocation processes during conjugation, T-DNA transfer, and transformation are more consistent and may even be compared to the excretion of some proteins. On the basis of analogies and homologies between the proteins involved in DNA translocation and protein secretion, a common basic model for these processes is presented.
Human Type I Interferons Differ Greatly in Their Effects on the Proliferation of Primary B Cells (1999)

We examined the effects of eight subtypes of human interferon-alpha (IFN-alpha) and human IFN-beta on primary human B cells. In costimulation with antibodies to IgM (but not to CD40), some of these induced the cells to proliferate (but not to differentiate). Individual IFN differed greatly in their relative proliferative effects. IFN-alpha8 at 0.1-0.5 ng/ml induced proliferation, whereas most other subtypes were active only at concentrations >5 ng/ml, and IFN-alpha1 was inactive. These marked differences were not due to a selective overall increase in B cell response only to some IFN subtypes, as all those tested similarly induced the IFN-inducible genes 6-16 and HLA class I. Our results show that human B cells must respond to type I IFN via two distinct pathways. One is specific for IFN-alpha8 but can be activated by other IFN at relatively high concentrations. The other responds to them all and causes activation of IFN-inducible genes.
Is REDD1 a Metabolic Éminence Grise ? (2016)

Regulated in development and DNA damage response 1 (REDD1) has been functionally linked to the control of diverse cellular processes due, at least in part, to its ability to repress mammalian or mechanistic Target of Rapamycin (mTOR) Complex-1 (mTORC1), a key protein complex controlled by hormonal and nutrient cues. Notably, emerging evidence suggests that REDD1 also regulates several pathways involved in modulating energy balance and metabolism. Herein, we discuss evidence implicating REDD1 as a key modulator of insulin action and metabolic function, including its potential contribution to mitochondrial biology and pancreatic islet function. Collectively, the available evidence suggests that REDD1 has a more prominent role in energy homeostasis than was previously thought, and implicates REDD1 as a potential therapeutic target for treatment of metabolic disorders.
Controlled Trial of Megestrol Acetate for the Treatment of Cancer Anorexia and Cachexia (1990)

Preliminary information has suggested that megestrol acetate leads to appetite stimulation and nonfluid weight gain in patients with breast cancer, other cancers, and AIDS. Pursuant to this, we developed a randomized, double-blind, placebo-controlled trial of megestrol acetate in patients with cancer-associated anorexia and cachexia. We randomly assigned 133 eligible patients to receive 800 mg of megestrol acetate per day or a placebo. Patients assigned to megestrol acetate more frequently reported improved appetite (P = .003) and food intake (P = .009) when compared with patients receiving the placebo. A weight gain of 15 lb or more over baseline was seen in 11 of 67 (16%) patients receiving megestrol acetate compared with one of 66 (2%) given the placebo (P = .003). Patients receiving megestrol acetate reported significantly less nausea (13% vs. 38%; P = .001) and emesis (8% vs. 25%, P = .009). No clinically or statistically significant toxic reactions were ascribed to megestrol acetate, with the exception of mild edema. This study convincingly demonstrated that megestrol acetate can stimulate appetite and food intake in patients with anorexia and cachexia associated with cancer, leading to significant weight gain in a proportion of such patients.
Glutamate Receptors as Therapeutic Targets for Parkinsons Disease (2009)

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor symptoms including tremor and bradykinesia. The primary pathophysiology underlying PD is the degeneration of dopaminergic neurons of the substantia nigra pars compacta. Loss of these neurons causes pathological changes in neurotransmission in the basal ganglia motor circuit. The ability of ionotropic and metabotropic glutamate receptors to modulate neurotransmission throughout the basal ganglia suggests that these receptors may be targets for reversing the effects of altered neurotransmission in PD. Studies in animal models suggest that modulating the activity of these receptors may alleviate the primary motor symptoms of PD as well as side effects induced by dopamine replacement therapy. Moreover, glutamate receptor ligands may slow disease progression by delaying progressive dopamine neuron degeneration. Antagonists of NMDA receptors have shown promise in reversing motor symptoms, levodopa-induced dyskinesias, and neurodegeneration in preclinical PD models. The effects of drugs targeting AMPA receptors are more complex; while antagonists of these receptors exhibit utility in the treatment of levodopa-induced dyskinesias, AMPA receptor potentiators show promise for neuroprotection. Pharmacological modulation of metabotropic glutamate receptors (mGluRs) may hold even more promise for PD treatment due to the ability of mGluRs to fine-tune neurotransmission. Antagonists of mGluR5, as well as activators of group II mGluRs and mGluR4, have shown promise in several animal models of PD. These drugs reverse motor deficits in addition to providing protection against neurodegeneration. Glutamate receptors therefore represent exciting targets for the development of novel pharmacological therapies for PD.
A Highly Stereoselective Synthesis of Epothilone B (1999)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTA Highly Stereoselective Synthesis of Epothilone BJames D. White, Rich G. Carter, and Kurt F. SundermannView Author Information Department of Chemistry, Oregon State University, Corvallis, Oregon 97331-4003 Cite this: J. Org. Chem. 1999, 64, 3, 684–685Publication Date (Web):February 5, 1999Publication History Received20 October 1998Published online5 February 1999Published inissue 1 February 1999https://pubs.acs.org/doi/10.1021/jo982108rhttps://doi.org/10.1021/jo982108rrapid-communicationACS PublicationsCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views1521Altmetric-Citations62LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information SUBJECTS:Aldehydes,Anions,Ethers,Hydrocarbons,Molecular structure Get e-Alerts
Oxyntomodulin (2006)

Purpose of review The prevalence of obesity is increasing rapidly, and the associated morbidity and mortality has led to interest in potential therapeutic targets to reduce appetite and food intake. Gut hormones released after eating and which coordinate digestive activity and promote satiety have potential as obesity treatments. Oxyntomodulin is one such hormone, produced by the L-cells in the small intestine, and with the potential to reduce food intake. It is timely to review some of the original literature on oxyntomodulin, to evaluate what is already known about the peptide, and also to set the recent findings on its effects on food intake and body weight into context. Recent findings Recent studies have shown that chronic peripheral administration of oxyntomodulin to rats reduces both food intake and weight gain. Studies in human subjects have demonstrated that acute administration reduces food intake by 19%. When given preprandially by subcutaneous injection three times a day, oxyntomodulin results in a reduction in food intake and mean weight loss of 2.8 kg over 4 weeks. Oxyntomodulin thus represents a potential therapy for obesity. Current evidence for the mechanism of action of oxyntomodulin suggests that it acts via the glucagon-like peptide-1 receptor. There may be an additional receptor in the gastric mucosa mediating its effects on gastric acid. Although oxyntomodulin probably acts via the glucagon-like peptide-1 receptor, oxyntomodulin and glucagon-like peptide-1 differentially regulate food intake and energy expenditure in the mouse. Summary Oxyntomodulin represents a potential therapy for obesity. Further work is needed to clarify its mechanisms of action.
A novel process of viral vector barcoding and library preparation enables high-diversity library generation and recombination-free paired-end sequencing (2016)

Detailed characterization and mapping of oligonucleotide function in vivo is generally a very time consuming effort that only allows for hypothesis driven subsampling of the full sequence to be analysed. Recent advances in deep sequencing together with highly efficient parallel oligonucleotide synthesis and cloning techniques have, however, opened up for entirely new ways to map genetic function in vivo. Here we present a novel, optimized protocol for the generation of universally applicable, barcode labelled, plasmid libraries. The libraries are designed to enable the production of viral vector preparations assessing coding or non-coding RNA function in vivo. When generating high diversity libraries, it is a challenge to achieve efficient cloning, unambiguous barcoding and detailed characterization using low-cost sequencing technologies. With the presented protocol, diversity of above 3 million uniquely barcoded adeno-associated viral (AAV) plasmids can be achieved in a single reaction through a process achievable in any molecular biology laboratory. This approach opens up for a multitude of in vivo assessments from the evaluation of enhancer and promoter regions to the optimization of genome editing. The generated plasmid libraries are also useful for validation of sequencing clustering algorithms and we here validate the newly presented message passing clustering process named Starcode.
Gelatinases and their inhibitors in tumor metastasis: from biological research to medical applications. (2002)

The involvement of matrix metalloproteinase (MMPs)-2 and -9, also known as gelatinases, in cancer cell migration and invasion has been well documented, although it is not yet clear how they facilitate metastasis formation in the course of malignancies. The idea that gelatinases are responsible for degradation of extracellular matrix (ECM) components and breakdown of basement membrane (BM) tissue boundaries has turned out not to be entirely correct. An action by remodelling the ECM components of the BM exposing new cryptic sites, or releasing growth factors, cytokines, or active ECM proteolysed fragments seems to be nearer to the truth. On the other hand, tissue inhibitors of gelatinase activity (TIMP-2), are involved both in the MMP-2 activation process; in concert with membrane type 1-MMP (MT1-MMP), and in the inhibition of gelatinolytic activity. Therefore proteolysis, the central step for cancer metastasis, should occur as a result of an imbalance between MMP-2 and TIMP-2. Many studies have reported the importance of this balance in patients with different malignancies, and considerable effort is currently being spent on the study of molecules that can shift the balance in favour of inhibition of MMP proteolytic activity. In this review we focus on the role of gelatinase activity in cancer invasion, addressing the following issues: how and where proteolysis occurs in cancer tissues, how it can be regulated, what the clinical implications are of the studies reported in literature so far, and finally what the future developments in this field that could have an impact on the management of patients affected by malignancies may be.
Dietary Fecal Tagging as a Cleansing Method before CT Colonography: Initial Results—Polyp Detection and Patient Acceptance (2002)

FT offers the patient a well-tolerated preparation and improves specificity, with improved differentiation of polyps from residual stool.
Skin conductance; validation of Skicon‐200EX® compared to the original model, Skicon‐100® (2007)

Background/purpose: Measurement of skin surface and stratum corneum (SC) hydration during experimental trials needs devices with acceptable precision under conditions ranging from decreased, and normal to high hydration. The aim of this study was to validate the recent model of a commonly used device for measurement of skin conductance (Skicon‐200EX ® ) vs. the original model (Skicon‐100 ® ) introduced 20 years ago. Methods: Twenty‐six healthy Danish volunteers (16 women and 10 men, aged between 22 and 67, with a median age of 42 years) were studied using the Skicon‐100 ® and the Skicon‐200EX ® mounted with three different probes. Normal skin of the cheek, forearm, antecubital fossa, palm, lower leg, and popliteal fossa was studied. The sorption–desorption test was performed on the forearm. Result: The two instruments displayed closely correlated conductance levels. However, the Skicon‐200EX ® displayed systematically 1.6‐fold higher values than the Skicon‐100 ® . Different body sites showed different levels depending on anatomical regions. The three probes measured systematically different levels with the original probe measuring lower values. The sorption–desorption test showed high skin conductance values which peaked a few minutes after hydration, in accordance with the original experiments of Tagami. Conclusion: The two Skicon ® instruments evaluated in this study correlated well, however, they displayed different levels depending on instrument main body and probes. Overall, the Skicon‐200EX ® gave 1.6‐fold higher value, and this instrument might be more sensitive than the original device, Skicon‐100 ® . In scientific reports, the type of instrument main body as well as probe shall be clearly specified.
Plasma kallikrein/kinin system: a revised hypothesis for its activation and its physiologic contributions (2000)

Recent studies indicate that assembly of high molecular weight kininogen on its multiprotein receptor allows for prekallikrein activation. On endothelial cells, factor XII activation is secondary to prekallikrein activation and amplifies it. The immediate consequence of plasma prekallikrein activation is the cleavage of high molecular weight kininogen (HK) with liberation of bradykinin. Cleaved high molecular weight kininogen is antiangiogenic. Bradykinin stimulates tPA liberation and nitric oxide formation. In addition, formed plasma kallikrein promotes single-chain urokinase activation and subsequent plasminogen activation. Kininogens and their breakdown products also are antithrombins. The angiotensin converting enzyme breakdown product of bradykinin prevents canine coronary thrombosis. The author presents a new hypothesis for physiologic assembly and activation of the plasma kallikrein/kinin system and discusses its influence on vascular biology.
A novel human cDNA with a predicted protein similar to lysyl oxidase maps to chromosome 15q24-q25. (1993)

A novel human cDNA with a predicted protein homologous to the carboxyl end of lysyl oxidase, an extracellular enzyme involved in the maturation of collagen and elastin, has been isolated. The homology to lysyl oxidase begins exactly at the position of the exon 1/exon 2 boundary in the mouse gene (Contente, S., Csiszar, K., Kenyon, K., and Friedman, R. M. (1993) Genomics 16, 395-400). This lysyl oxidase-like gene, which appears to be no larger than 22.1 kilobases, codes for a single polyadenylated RNA species of 2.48 kilobases and has been mapped to chromosome 15q24-q25.
The domain organization of streptokinase: Nuclear magnetic resonance, circular dichroism, and functional characterization of proteolytic fragments (1996)

Streptococcus equisimilis streptokinase (SK) is a bacterial protein of unknown tertiary structure and domain organization that is used extensively to treat acute myocardial infarction following coronary thrombosis. Six fragments of SK were generated by limited proteolysis with chymotrypsin and purified. NMR and CD experiments have shown that the secondary and tertiary structure present in the native molecule is preserved within all fragments, except the N-terminal fragment SK7. NMR spectra demonstrate the presence in SK of three structurally autonomous domains and a less structured C-terminal "tail." Cleavage within the N-terminal domain generates an N-terminal fragment, SK7, which remains noncovalently associated with the remainder of the molecule; in isolation, SK7 adopts an unfolded conformation. The abilities of these fragments to induce active site formation within human plasminogen upon formation of their heterodimeric complex were assayed. The lowest mass SK fragment exhibiting Plg-dependent activator activity was shown to be SK27 (mass 27,000, residues 147-380), which contains both central and C-terminal domains, although this activity was reduced approximately 6,000-fold relative to that of full-length SK. The activity of a 36,000 mass fragment, SK36 (residues 64-380), which differs from SK27 in possessing a portion of the N-terminal domain, was reduced to 0.1-1.0% of that of SK. Other fragments (masses 7,000, 11,000, 16,000, 17,000, 25,000, and 26,000), representing either single domains or single domains extended by portions of other domains, were inactive. However, SK7 (residues 1-63), at a 100-fold molar excess concentration, greatly potentiated the activities of SK27 and SK36, by up to 50- and > 130-fold, respectively. These findings demonstrate that all of SK's three domains are essential for native-like SK activity. The central and C-terminal domains mediate plasminogen-binding and active site-generating functions, whereas the N-terminal domain mediates an activity-potentiating function.