gebhart/patrepeval huggingface dataset:
At least five related, but distinct, hepatitis C viral genotypes exist. (1992)

Hepatitis C virus, the major causative agent of blood-borne non-A, non-B hepatitis in the world, has been the subject of considerable nucleic acid sequence analysis. Although all reported hepatitis C sequences from the United States have been represented by the prototype hepatitis C virus type 1 sequence, two groups of variant sequences have been reported in Japan. However, we have noted five distinct, but related, genotypes (I-V) throughout the world, based on detailed sequence determination and analysis of the first 1700 nucleotides and part of the nonstructural region 5 at the C terminus of the open reading frame. The nucleotide sequence for a large number of hepatitis C virus isolates spanning six continents was obtained by direct sequence analysis of PCR products after reverse transcription. Genotype was classified by using several distinct sequence motifs. We observed that most genotypes coexist in several geographic regions, including the United States, Japan, Germany, and Italy. So far, genotype V has been found only in South Africa. Interestingly, each distinct genotype seems to be maintained throughout the genome in the segments studied. These genotype distinctions should be considered when designing specific diagnostic tests, developing potential vaccines, and studying viral transmission.
Distinctive expression of STAT3 in papillary thyroid carcinomas and a subset of follicular adenomas. (2003)

Hepatocyte growth factor (HGF), HGF receptor (c-met) and the interleukin 6 (IL-6) are expressed in thyroid nodules. In extra-thyroidal tissues, the HGF/c-met and IL-6/IL-6 receptor (IL-6R) systems activate STAT3, a member of the signal transducers and activators of transcription (STATs) family. To evaluate whether either system utilizes STAT3 in thyroid nodules, we examined the immunohistochemical expression of HGF, c-met, IL-6, IL-6R, STAT3 in 6 normal thyroids and in 68 thyroid nodules. STAT3 expression was observed in 12/12 (100%) papillary thyroid carcinomas (PTC) but in none of the follicular tumors. Among benign thyroid nodules, only 2/10 (20%) follicular adenomas (FA) were STAT3+. All these 14 STAT3+ cases expressed both HGF and c-met, but only 5 PTC co-expressed IL-6 and IL-6R and the 2 FA were IL-6+ but IL-6R-. The remaining 8 FA were all HGF/c-met-, but IL-6+; of these 8, only 2 were also IL-6R+. In conclusion, in thyroid nodules STAT3 is expressed only in PTC and a number of FA. Since these cases are consistently HGF+/c-met+ and only one-third of them co-express IL-6/IL-6R, STAT3 expression correlates with the HGF/c-met expression, not with the IL-6/IL-6R expression. The 100% rate of expression of the HGF/c-met/STAT3 signaling in PTC could be relevant for the establishment of the papillary phenotype. Because of the communeness of a HGF/c-met/STAT3 pattern between all PTC and a subset of FA, we speculate that a fraction of FA may progress to PTC.
Fibronectin deposition in delayed-type hypersensitivity. Reactions of normals and a patient with afibrinogenemia. (1984)

During development of delayed hypersensitivity (DH) skin reactions, fibronectin accumulates in two distinct sites: (a) the dermal interstitium in a pattern similar to fibrin and with a time course similar to that of fibrin deposition and mononuclear cell infiltration, and (b) blood vessel walls in a pattern suggestive of basement membrane staining and with a time course similar to that of endothelial cell proliferation. In vitro fibronectin can bind to monocytes or endothelial cells and simultaneously bind to fibrin or collagen matrices; by such interaction in vivo it may affect cell migration or proliferation. Thus, fibronectin deposition in DH reactions may facilitate cell-matrix interactions; however, the possibility exists that extravascular fibronectin accumulation may be only secondary to interstitial fibrin clot formation, and that blood vessel-associated fibronectin may be only a function of adsorption onto basement membrane (type IV) collagen. To address these possibilities, we investigated the association of fibronectin with fibrin, type IV collagen, and mononuclear cell infiltrates in DH reactions. Skin sites of DH reactions in normal volunteers were biopsied at 24, 48, and 72 h after intradermal challenge and examined by immunofluorescence technique. At all time points most of the interstitial fibronectin coincided with fibrin; however, some interstitial fibronectin was coincident with mononuclear cells positive for HLA-DR or monocyte-specific antigen. The coincidence of fibronectin with mononuclear cells was more apparent in a 48-h DH reaction from a patient with congenital afibrinogenemia. Vessel wall fibronectin was increased by 48 h after challenge and appeared as a fine linear band on the luminal side of a much thicker band of type IV collagen. Thus, the coincidence of extravascular fibronectin with mononuclear cells, its appearance without fibrin in the site from a patient with afibrinogenemia, and incomplete correspondence of vessel wall fibronectin with type IV collagen suggest that fibronectin localization in DH reactions involves endothelial cell and mononuclear cell binding as well as adsorption to fibrin and/or type IV collagen.
Immobilized pH gradient two‐dimensional gel electrophoresis and mass spectrometric identification of cytokine‐regulated proteins in ME‐180 cervical carcinoma cells (1997)

Two-dimensional (2-D) polyacrylamide gel electrophoresis combined with mass spectrometry is a powerful combination of technologies that allows high resolution separation of proteins and their rapid identification. Immobilized pH gradient (IPG) first-dimensional gels have several advantages over carrier ampholyte isoelectric focusing, including a high degree of reproducibility, good protein spot resolution, and a selection of pH range. Here we demonstrate the utility and efficacy of combining IPG 2-D gel electrophoresis with mass spectrometry to identify interferon-gamma- (IFN) and tumor necrosis factor (TNF)-regulated proteins in ME-180 cervical carcinoma cells. Three cytokine-regulated proteins have been identified, using imidazole-zinc-stained preparative IPG 2-D gels and in-gel tryptic digestion followed by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry for determination of peptide masses and sequences: 1) triosephosphate isomerase, a glycolytic pathway enzyme, 2) proteasome subunit C3, which is important in protein degradation, and 3) Ran, a GTP-binding protein important in cell cycle regulation, protein import into the nucleus, and RNA export from the nucleus.
On Monolayer Formation of Pyrenebutyric Acid on Graphene (2017)

As a two-dimensional material with high charge carrier mobility, graphene may offer ultrahigh sensitivity in biosensing. To realize this, the first step is to functionalize the graphene. This is commonly done by using 1-pyrenebutyric acid (PBA) as a linker for biomolecules. However, the adsorption of PBA on graphene remains poorly understood despite reports of successful biosensors functionalized via this route. Here, the PBA adsorption on graphene is characterized through a combination of Raman spectroscopy, ab initio calculations, and spectroscopic ellipsometry. The PBA molecules are found to form a self-assembled monolayer on graphene, the formation of which is self-limiting and Langmuirian. Intriguingly, in concentrated solutions, the PBA molecules are found to stand up and stack horizontally with their edges contacting the graphene surface. This morphology could facilitate a surface densely populated with carboxylic functional groups. Spectroscopic analyses show that the monolayer saturates at 5.3 PBA molecules per nm<sup>2</sup> and measures ∼0.7 nm in thickness. The morphology study of this PBA monolayer sheds light on the π-π stacking of small-molecule systems on graphene and provides an excellent base for optimizing functionalization procedures.
Identification and functional characterization of a dual GABA/taurine transporter in the bullfrog retinal pigment epithelium. (1995)

Intracellular microelectrodes, fluorescence imaging, and radiotracer flux techniques were used to investigate the physiological response of the retinal pigment epithelium (RPE) to the major retinal inhibitory neurotransmitter, gamma-aminobutyric acid (GABA). GABA is released tonically in the dark by amphibian horizontal cells, but is not taken up by the nearby Müller cells. Addition of GABA to the apical bath produced voltage responses in the bullfrog RPE that were not blocked nor mimicked by any of the major GABA-receptor antagonists or agonists. Nipecotic acid, a substrate for GABA transport, inhibited the voltage effects of GABA. GABA and nipecotic acid also inhibited the voltage effects of taurine, suggesting that the previously characterized beta-alanine sensitive taurine carrier also takes up GABA. The voltage responses of GABA, taurine, nipecotic acid, and beta-alanine all showed first-order saturable kinetics with the following Km's: GABA (Km = 160 microM), beta-alanine (Km = 250 microM), nipecotic acid (Km = 420 microM), and taurine (Km = 850 microM). This low affinity GABA transporter is dependent on external Na, partially dependent on external Cl, and is stimulated in low [K]o, which approximates subretinal space [K]o during light onset. Apical GABA also produced a significant conductance increase at the basolateral membrane. These GABA-induced conductance changes were blocked by basal Ba2+, suggesting that GABA decreased basolateral membrane K conductance. In addition, the apical membrane Na/K ATPase was stimulated in the presence of GABA. A model for the interaction between the GABA transporter, the Na/K ATPase, and the basolateral membrane K conductance accounts for the electrical effects of GABA. Net apical-to-basal flux of [3H]-GABA was also observed in radioactive flux experiments. The present study shows that a high capacity GABA uptake mechanism with unique pharmacological properties is located at the RPE apical membrane and could play an important role in the removal of GABA from the subretinal space (SRS). This transporter could also coordinate the activities of GABA and taurine in the SRS after transitions between light and dark.
Cisplatin, vinblastine, and mitoguazone chemotherapy for epidermoid and adenocarcinoma of the esophagus. (1987)

Thirty-six patients with adenocarcinoma or epidermoid carcinoma of the esophagus were entered into a phase II trial evaluating the combination of cisplatin 100 mg/m2 intravenously (IV) day 2, vinblastine 1.6 mg/m2 IV days 1 to 4, and mitoguazone (MGBG) 500 mg/m2 IV days 1 and 8. Twenty-nine patients (group A) were newly diagnosed with local-regional disease only and were candidates for transhiatal esophagectomy (THE). These patients received two courses of chemotherapy at 3-week intervals prior to surgery. Response was assessed by measuring changes in the primary tumor length and depth on serial biphasic contrast esophagrams and comparing this result with tumor measurements obtained from the surgical specimen. Complete (CR) and partial responders (PR) received three additional postoperative cycles. Seven patients had recurrent or metastatic disease (group B) and were treated every 4 weeks until disease progression. Of 34 patients evaluable for response, there was one pathologically confirmed CR and 15 PRs (47%). This consisted of 12 of 27 (44%) group A patients (seven of 11 epidermoid, five of 16 adenocarcinoma) and four of seven (57%) group B patients (two of four epidermoid, two of three adenocarcinoma). Toxicity included leukopenia in one third of treatment courses and thrombocytopenia in 21%. Nausea and vomiting occurred in 60% of patients, diarrhea in 18%, transient nephrotoxicity in 18%, peripheral neuropathy in 12%, and ototoxicity in 3%. Twenty-five group A patients underwent resection. Four chemotherapy nonresponders (NR) and one PR had known disease left at surgery; all others (80%) had gross total removal of their disease. The median survival time (MST) of the 29 group A patients was 14 months, with 21% alive at 36 months. The MST of group A chemotherapy responders was 15 months compared with 9 months for NRs (P = .032). Initial sites of recurrence in 14 patients were local-regional in six, distant only in six, both local-regional and distant in two. This regimen, administered in maximally tolerated doses, was active in epidermoid and adenocarcinoma histologies, recurrent disease and newly diagnosed patients. However, nearly all responses were PRs and the MST of resected patients was similar to a prior series of patients treated with esophagectomy alone. Observations from this pilot trial and those of others have led to a follow-up study, in progress, evaluating intensive preoperative chemotherapy and concurrent radiation therapy (RT).
Engineered chloroplast dsRNA silences cytochrome p450 monooxygenase, V‐ATPase and chitin synthase genes in the insect gut and disrupts Helicoverpa armigera larval development and pupation (2015)

In the past two decades, chloroplast genetic engineering has been advanced to achieve high-level protein accumulation but not for down-regulation of targeted genes. Therefore, in this report, lepidopteran chitin synthase (Chi), cytochrome P450 monooxygenase (P450) and V-ATPase dsRNAs were expressed via the chloroplast genome to study RNA interference (RNAi) of target genes in intended hosts. PCR and Southern blot analysis confirmed homoplasmy and site-specific integration of transgene cassettes into the chloroplast genomes. Northern blots and real-time qRT-PCR confirmed abundant processed and unprocessed dsRNA transcripts (up to 3.45 million copies of P450 dsRNAs/μg total RNA); the abundance of cleaved dsRNA was greater than the endogenous psbA transcript. Feeding of leaves expressing P450, Chi and V-ATPase dsRNA decreased transcription of the targeted gene to almost undetectable levels in the insect midgut, likely after further processing of dsRNA in their gut. Consequently, the net weight of larvae, growth and pupation rates were significantly reduced by chloroplast-derived dsRNAs. Taken together, successful expression of dsRNAs via the chloroplast genome for the first time opens the door to study RNA interference/processing within plastids. Most importantly, dsRNA expressed in chloroplasts can be utilized for gene inactivation to confer desired agronomic traits or for various biomedical applications, including down-regulation of dysfunctional genes in cancer or autoimmune disorders, after oral delivery of dsRNA bioencapsulated within plant cells.
Identification and quantitation of the impurities in sodium pyruvate (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIdentification and quantitation of the impurities in sodium pyruvateS. A. Margolis and Bruce. CoxonCite this: Anal. Chem. 1986, 58, 12, 2504–2510Publication Date (Print):October 1, 1986Publication History Published online1 May 2002Published inissue 1 October 1986https://pubs.acs.org/doi/10.1021/ac00125a033https://doi.org/10.1021/ac00125a033research-articleACS PublicationsRequest reuse permissionsArticle Views888Altmetric-Citations43LEARN 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
Insulin Administered Intranasally as an Insulin-Bile Salt Aerosol: Effectiveness and Reproducibility in Normal and Diabetic Subjects (1983)

Efficacy and reproducibility of insulin administered intranasally as an insulin-deoxycholate 1% (w/v) aerosol to normal and diabetic subjects were assessed by measurements of blood glucose and serum insulin levels. Following administration of 0.5 U insulin/kg with the unconjugated bile salt to fasting volunteers (N = 29), peak serum insulin levels of 103 +/- 49 microU/ml above baseline were observed at 10 min. Blood glucose concentration began to fall by 10 min, reaching 54 +/- 14% of control levels by 30 min, and returning to baseline by 60-80 min. Blood glucose response and peak serum insulin levels were reproducible when the same aerosol dose was repeatedly administered to the same subjects; however, intersubject variations were noted. By comparing serum insulin levels after i.v. and nasal routes of administration, nasal insulin absorption was approximately 10% as efficient as intravenous insulin. Dose response studies revealed that peak serum insulin concentrations were a linear function of the administered dose. In subjects with type I and type II diabetes mellitus, serum insulin levels increased in a manner similar to controls, and resulted in a prompt reduction of blood glucose concentration. However, in contrast to normal subjects, the duration of the glucose response was more prolonged, lasting as long as 5 h. Nasal administration of insulin as an aerosol with bile salts or bile salt analogs should be further evaluated as a possible nonparenteral approach to insulin therapy.
Factorial Design of Experiments to Optimize Multiple Protein Delivery for Cardiac Repair (2016)

Myocardial infarction (MI) is a major cardiovascular disease responsible for millions of deaths annually. Protein therapies can potentially repair and regenerate the infarcted myocardium. However, because of the short half-lives of proteins in vivo, their low retention at the target tissue, and the lack of spatiotemporal cues upon injection, the efficacy of protein therapy can be limited. This efficacy can be improved by utilizing controlled release systems to overcome shortcomings associated with a direct bolus injection. Equally important is the determination of an optimal combination of different proteins having distinct roles in cardiac function and repairs to prevent or reverse the multiple pathologies that develop after infarction. In this work, we used a rat MI model to test a combination of potentially complementary proteins: tissue inhibitor of metalloproteinases 3 (TIMP-3), interleukin-10 (IL-10), basic fibroblast growth factor (FGF-2), and stromal cell-derived factor 1 alpha (SDF-1α). To achieve controlled and timed release of the proteins per their physiologic cues during proper tissue repair, we used a fibrin gel-coacervate composite. TIMP-3 and IL-10 were encapsulated in fibrin gel to offer early release, while FGF-2 and SDF-1α were encapsulated in heparin-based coacervates and distributed in the same fibrin gel to offer sustained release. We utilized a powerful statistical tool, factorial design of experiments (DOE), to refine this protein combination based on its improvement of ejection fraction 4 weeks after MI. We found that TIMP-3, FGF-2, and SDF-1α demonstrated significant contributions toward improving the ejection fraction, while the IL-10's effect was insignificant. The results also suggested that the higher doses tested for TIMP-3, FGF-2, and SDF-1α had greater benefit on function than lower doses and that there existed slight antagonism between TIMP-3 and FGF-2. Taken together, we conclude that factorial DOE can guide the evolution of multiple protein therapies in a small number of runs, saving time, money, and resources for finding the optimal dose and composition.
Induction of Apoptosis by X-linked Ectodermal Dysplasia Receptor via a Caspase 8-dependent Mechanism (2004)

X-linked ectodermal dysplasia receptor (XEDAR) is a recently isolated member of the tumor necrosis factor receptor family that is highly expressed during embryonic development and binds to ectodysplasin-A2 (EDA-A2). In this report, we demonstrate that although XEDAR lacks a death domain, it nevertheless induces apoptosis in an EDA-A2-dependent fashion. The apoptosis-inducing ability of XEDAR is dependent on the activation of caspase 8 and can be blocked by its genetic and pharmacological inhibitors. Although XEDAR-induced apoptosis can be blocked by dominant-negative Fas-associated death domain (FADD) protein and FADD small interfering RNA, XEDAR does not directly bind to FADD, tumor necrosis factor receptor-associated death domain (TRADD) protein, or RIP1. Instead, XEDAR signaling leads to the formation of a secondary complex containing FADD, caspase 8, and caspase 10, which results in caspase activation. Thus, XEDAR belongs to a novel class of death receptors that lack a discernible death domain but are capable of activating apoptosis in a caspase 8- and FADD-dependent fashion. XEDAR may represent an early stage in the evolution of death receptors prior to the emergence of the death domain and may play a role in the induction of apoptosis during embryonic development and adult life.
Iron Chelation Improves Endothelial Function in Patients With Coronary Artery Disease (2001)

Deferoxamine improved nitric oxide-mediated, endothelium-dependent vasodilation in patients with coronary artery disease. These results suggest that iron availability contributes to impaired nitric oxide action in atherosclerosis.
An Autocrine Loop of HIV Type-1 Tat Protein Responsible for the Improved Survival/Proliferation Capacity of Permanently Tat-Transfected Cells and Required for Optimal HIV-1 LTR Transactivating Activity (1995)

Human immunodeficiency virus type 1 (HIV-1) transactivating Tat protein is pivotal to virus replication. Tat's potential effects on HIV-1 pathogenesis, however, go well beyond its role in the virus's life cycle. Current data indicate that biologically active Tat is released from HIV-1-infected cells and readily endocytosed and targeted to the nucleus of nearby, or perhaps distant, cells, where it may exert a series of pleiotropic effects. This paracrine action has been extensively investigated, and depending on the amounts of exogenously added Tat, its effects may extend from the suppression of immunocompetent cells to transactivation of heterologous genes to the promotion of growth of Kaposi's sarcoma spindle cells. We have already observed that various cell lines, either permanently transfected with an expressive HIV-1 tat gene construct or cultured in the presence of exogenously added Tat protein, are protected from programmed cell death after serum withdrawal or other apoptotic stimuli. The present article shows that various types (lymphoblastoid, epithelial, neuronal) of permanently tat-transfected cell lines actively release fully bioactive Tat protein. The addition of anti-Tat antibody to the culture medium completely abolishes their increased survival/proliferation capacity in serum-free culture. In these conditions, therefore, the enhanced survival/proliferation potential of permanently tat-transfected cells seems entirely dependent on a Tat-protein autocrine loop. The finding that anti-Tat antibody, added to culture medium, exerts a negative influence on the expression of a Tat-responsive HIV-1 long terminal repeat chloramphenicol-acetyltransferase construct, transiently transfected into permanently tat-transfected cells, suggests that the Tat autocrine loop may also be required for optimal HIV-1 long terminal repeat transactivation.