gebhart/patrepeval huggingface dataset:
Recombinant immunotoxins containing anti-Tac(Fv) and derivatives of Pseudomonas exotoxin produce complete regression in mice of an interleukin-2 receptor-expressing human carcinoma (1994)

Anti-Tac(Fv)-PE40 is a recombinant single-chain immunotoxin composed of the variable domains of the monoclonal antibody anti-Tac, which binds to the p55 subunit of the interleukin-2 receptor (IL-2R), and a truncated form of Pseudomonas exotoxin (PE), which does not bind to the PE receptor (Chaudhary et al, Nature 339:394, 1989). Whereas its cytotoxic activity toward autoimmune and malignant target cells has been established, its efficacy in vivo remains unknown. To establish an animal model, we produced ATAC-4 cells by transfecting the gene encoding the low-affinity IL-2R (p55) into A431 epidermoid carcinoma cells. ATAC-4 cells contained low-affinity IL-2Rs (2 x 10(5)/cell) and formed tumors in nude mice. In tissue culture, protein synthesis in ATAC-4 cells was inhibited 50% (IC50) at 0.06 ng/mL (0.9 pmol/L) of anti-Tac(Fv)-PE40. IC50s for the derivatives anti-Tac(Fv)-PE38, which is missing PE amino acids 365-380, and anti-Tac(Fv)-PE38KDEL, which contains the same deletion plus the KDEL carboxyl terminus, were 0.04 and 0.025 ng/mL, respectively. All the agents produced complete tumor regressions in ATAC-4 tumor-bearing mice and anti-Tac(Fv)-PE38KDEL had significant antitumor activity at 1% of the LD50. The dose limiting toxicity of anti-Tac(Fv)-PE38KDEL was from hemorrhagic liver necrosis, which was observed at approximately 55% of the LD50.
Phase I trial of murine monoclonal antibody L6 in breast, colon, ovarian, and lung cancer. (1990)

Murine monoclonal antibody (MAb) L6 binds to an antigen expressed on the surface of breast, colon, ovary, and nonsmall-cell lung cancer. This antibody effects antibody-dependent cellular cytotoxicity (ADCC) with human mononuclear cells and complement-dependent cytotoxicity (CDC) with human complement. Because of these activities, we conducted a phase I trial of MAb L6 in patients with advanced cancer. Nineteen patients whose tumors highly expressed antigen were selected for this trial. Eighteen were evaluable. MAb L6 was administered at dose levels ranging from 5 mg/m2/d to 400 mg/m2/d for 7 days and was well tolerated. The only side effects detected were fever and headaches at the highest dose levels. The serum half-life of L6 was directly related to dose and ranged from a mean of 7.7 hours at 5 mg/m2/d to 29.1 hours at 400 mg/m2/d. Peak serum concentrations ranged from 0.22 micrograms/mL to 362 micrograms/mL. Biopsies at the end of treatment showed L6 to localize well to tumor cells with apparent in vivo saturation occurring at dose levels above 100 mg/m2/d. Thirteen patients formed human antimouse antibodies (HAMA), some as early as day 13. One patient with recurrent breast cancer on the chest wall achieved a complete remission. The response was first noted at 5 weeks and a pathologic complete remission occurred at 14 weeks. Because of its favorable binding properties and the encouraging clinical effect observed, future evaluation of this MAb appears warranted.
Structural, signalling and regulatory properties of the group I metabotropic glutamate receptors: prototypic family C G-protein-coupled receptors (2001)

In 1991 a new type of G-protein-coupled receptor (GPCR) was cloned, the type 1a metabotropic glutamate (mGlu) receptor, which, despite possessing the defining seven-transmembrane topology of the GPCR superfamily, bore little resemblance to the growing number of other cloned GPCRs. Subsequent studies have shown that there are eight mammalian mGlu receptors that, together with the calcium-sensing receptor, the GABAB receptor (where GABA is γ-aminobutyric acid) and a subset of pheromone, olfactory and taste receptors, make up GPCR family C. Currently available data suggest that family C GPCRs share a number of structural, biochemical and regulatory characteristics, which differ markedly from those of the other GPCR families, most notably the rhodopsin/family A GPCRs that have been most widely studied to date. This review will focus on the group I mGlu receptors (mGlu1 and mGlu5). This subgroup of receptors is widely and differentially expressed in neuronal and glial cells within the brain, and receptor activation has been implicated in the control of an array of key signalling events, including roles in the adaptative changes needed for long-term depression or potentiation of neuronal synaptic connectivity. In addition to playing critical physiological roles within the brain, the mGlu receptors are also currently the focus of considerable attention because of their potential as drug targets for the treatment of a variety of neurological and psychiatric disorders.
A recombinant Bacillus anthracis strain producing the Clostridium perfringens Ib component induces protection against iota toxins (1997)

The Bacillus anthracis toxinogenic Sterne strain is currently used as a live veterinary vaccine against anthrax. The capacity of a toxin-deficient derivative strain to produce a heterologous antigen by using the strong inducible promoter of the B. anthracis pag gene was investigated. The expression of the foreign gene ibp, encoding the Ib component of iota toxin from Clostridium perfringens, was analyzed. A pag-ibp fusion was introduced by allelic exchange into a toxin-deficient Sterne strain, thereby replacing the wild-type pag gene. This recombinant strain, called BAIB, was stable and secreted large quantities of Ib protein in induced culture conditions. Mice given injections of live BAIB spores developed an antibody response specific to the Ib protein. The pag-ibp fusion was therefore functional both in vitro and in vivo. Moreover, the immunized animals were protected against a challenge with C. perfringens iota toxin or with the homologous Clostridium spiroforme toxin. The protective immunity was mediated by neutralizing antibodies. In conclusion, B. anthracis is promising for the development of live veterinary vaccines.
Regulation of p53 by macrophage migration inhibitory factor in inflammatory arthritis (2003)

These results indicate a role for MIF in the regulation of p53 expression and p53-mediated events in the inflamed synovium and support the hypothesis that MIF is of critical importance in the pathogenesis of RA.
CDDO induces granulocytic differentiation of myeloid leukemic blasts through translational up-regulation of p42 CCAAT enhancer–binding protein alpha (2007)

2-Cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) induces differentiation and apoptosis of tumor cells in vitro and in vivo. Here we assessed the effects of CDDO on CCAAT enhancer-binding protein alpha (CEBPA), a transcription factor critical for granulocytic differentiation. In HL60 acute myeloid leukemia (AML) cells, CDDO (0.01 to 2 muM) induces apoptosis in a dose-dependent manner. Conversely, subapoptotic doses of CDDO promote phagocytic activity and granulocytic-monocytic differentiation of HL60 cells through increased de novo synthesis of p42 CEBPA protein. CEBPA translational up-regulation is required for CDDO-induced granulocytic differentiation and depends on the integrity of the CEBPA upstream open reading frame (uORF). Moreover, CDDO increases the ratio of transcriptionally active p42 and the inactive p30 CEBPA isoform, which, in turn, leads to transcriptional activation of CEBPA-regulated genes (eg, GSCFR) and is associated with dephosphorylation of eIF2alpha and phosphorylation of eIF4E. In concordance with these results, CDDO induces a CEBPA ratio change and differentiation of primary blasts from patients with acute myeloid leukemia (AML). Because AML is characterized by arrested differentiation, our data suggest the inclusion of CDDO in the therapy of AML characterized by dysfunctional CEBPA expression.
Factor VIIa's First Epidermal Growth Factor-like Domain's Role in Catalytic Activity† (1998)

Factor VIIa-tissue factor complex formation initiates the extrinsic blood coagulation pathway. We investigated factor VIIa's first epidermal growth factor-like (egf1) domain's role in the catalytic activity increase caused when factor VIIa binds tissue factor. Starting with a factor VIIa with factor IX's egf1 domain (factor VII(IXegf1)a), we made 4 proteins with egf1 residues changed to those in factor VIIa, including E51A, D64Q, FG74-75PA, and K79R. We measured each enzyme's affinity for tissue factor and determined the enzymes' kinetic constants with and without tissue factor. The Kd for factor VII(IXegf1)a binding to tissue factor was 60-200-fold higher than that of factor VIIa depending on the assay employed. Only factor VII(IXegf1)a with the K79R (K79Ra) mutation, among all the mutants, had an effect on binding with a Kd 3-8-fold lower than that of factor VII(IXegf1)a. In kinetic analyses with a small peptide substrate, in the absence of tissue factor, factor VIIa, factor VII(IXegf1)a, and K79Ra had similar kcat's and Km's. With tissue factor, due to a kcat decrease, factor VII(IXegf1)a's catalytic efficiency (kcat/Km) was 2-fold lower than factor VIIa's. K79Ra's catalytic efficiency was intermediate between those of factor VIIa and factor VII(IXegf1)a. With factor X as substrate, in the absence of tissue factor, K79Ra and factor VII(IXegf1)a had catalytic efficiencies 1.5-fold and 2-fold lower than that of factor VIIa. In contrast, with tissue factor and with factor X as substrate, due to higher Km's, factor VII(IXegf1)a and K79Ra had only 9% and 33% of factor VIIa's catalytic efficiency. Our results suggest the egf1 domain's role in tissue factor binding involves critical alignment of tissue factor with factor VIIa's catalytic domain. Proper alignment in turn promotes optimal catalytic activities.
Studies on the reaction between silane and hydrogen peroxide vapour; surface formation of planarized silica layers (1997)

The chemistry of the reaction of gaseous silane with hydrogen peroxide vapour at low pressure, which yields commercially valuable planarized silica layers on line-etched silicon wafers, has been studied for the first time. Monitoring the mixed vapours by line-of-sight mass spectrometry and by low temperature infrared spectroscopy together with deuteriation and quantification studies indicates the reaction occurs only on surfaces, probably by a free radical mechanism. The conditions which allow the formation of self-planarizing, ‘flowy' silica films are consistent with a sol–gel process. It was found that hydroxyl radicals, formed in this work by microwave dissociation of water vapour, react in the gas phase with silane to give silica films which do not form planar layers on line-etched wafers.
Application of Wittig Reaction to Adenosine Derivatives (1990)

2′,3′-O-Ethoxymethyleneadenosine 5′-aldehyde (3)was reacted with Wittig reagents 4 and 5 to give the corresponding α,β- unsaturated adenosine esters 6 and 7. The dehydrated compounds 9 and 10 were separated from this reaction and inversion of configuration at C-3′ in ribofuranoside was observed.
GLP-1 (9–36) Amide Metabolite Suppression of Glucose Production in Isolated Mouse Hepatocytes (2010)

The glucoincretin hormone glucagon-like peptide-1 (GLP-1) augments glucose-stimulated insulin secretion and is in use as an effective treatment for diabetes. However, after its secretion from the intestine, the insulinotropic GLP-1 (7-36) amide hormone is rapidly inactivated by enzymatic cleavage by the diaminopeptidyl peptidase-4 giving rise to GLP-1 (9-36) amide. Inasmuch as most of the circulating GLP-1 is in the form of the metabolite GLP-1 (9-36) amide it has been suggested that it has insulin-like actions on peripheral insulin-sensitive tissues. In earlier studies, infusions of GLP-1 (9-36) amide in obese insulin-resistant subjects showed a marked suppression of hepatic glucose production. However, it remained uncertain whether the effects on glucose production were due to direct effects on hepatocytes, involved central or portal vein-mediated actions, or were mediated by insulin secretion. Here we show that GLP-1 (9-36) amide directly suppresses glucose production in isolated mouse hepatocytes ex vivo independent of the GLP-1 receptor. These findings support direct insulinomimetic actions of the GLP-1 metabolite on gluconeogenesis in hepatocytes that are independent of insulin action and the GLP-1 receptor, and suggest that GLP-1 (9-36) amide-based peptides might present a novel therapy for the treatment of excessive hepatic glucose production in individuals with insulin-resistant diabetes.
Elevated Superoxide Dismutase in Black Alcoholics (1980)

Superoxide dismutase concentrations in lysates of erythrocytes from black alcoholics were higher than those of white alcoholics and of nonalcoholics of both races. Higher concentrations of enzyme protein, as determined by competition radioimmunoassay, correspond to proportionately higher enzyme activity. Elevated superoxide dismutase levels were not related to any other clinical, historical, or demographic variables. Increased superoxide dismutase levels may delay or prevent some of the pathological sequelae of alcoholism and may be a useful biological marker for alcohol abuse.
Development of latent Interferon alpha 2b as a safe therapeutic for treatment of Hepatitis C virus infection (2019)

Interferon therapy for the treatment of hepatitis C virus infection has very limited clinical application due to short serum half-life and side effects of therapy in systemic route of administration. In the present study, we have focused to improve the interferon therapy by overcoming the limitation of side effects. We hypothesized that latent interferon alpha 2b (IFNα2b) produced by fusion of Latency associated protein (LAP) domain of TGFβ and IFNα2b having HCV NS3 protease cleavage site as linker that will be activated only at target site (liver) by viral protease (HCV NS3 protease) present on the surface of infected cells. The fusion proteins were expressed in pichia pastoris as homodimer and cleaved by recombinant HCV NS3 protease in vitro into two fragments corresponding to the IFNα-2b and LAP respectively. The latency of chimeric proteins and biological activity after treatment with HCV NS3 protease was assessed by cytopathic effect inhibition assay in A594 cells infected with encephalomyocarditis virus (EMCV) and reduction in HCV viral load in Huh7 cells. The HCV NS3 protease was present on the surface of HCV replicating Huh7 cells in amount that activated half of the effective concentration (EC<sub>50</sub>) of latent IFNα2b fusion protein. As free circulating HCV NS3 protease was not detected in sera from chronic HCV patients and in vitro cleavage of intact latent IFNα2b fusion protein was not observed with peripheral blood mononuclear cells (PBMCs) isolated from chronic HCV patients, thus there are less likely chances of activation and off target binding of latent IFNα2b to show side effects during systemic route of administration. Therefore, most of the side effects of interferon can be overwhelmed at the cost of 50% reduced biological activity. Thus, the use of latent IFNα2b can be considered again as an option for treatment of HCV infection in combination with direct acting antivirals rather than alone with improved safety profile.
Surface and Catalytic Properties of Iron‐Platinum/Carbon Electrocatalysts for Cathodic Oxygen Reduction in PAFC (1993)

A Fe-Pt bimetallic catalyst was prepared by impregnating iron nitrate solution into a carbon-supported platinum catalyst. The catalyst was heat treated in flowing Ar (nontreated) at 450-degrees-C (denoted as PF450), 750-degrees-C (PF750), and 900-degrees-C (PF900), or this process was followed by an acid-treatment in 1M H2SO4 solution to leach out surface-enriched iron (acid-treated). The surface and catalytic properties of these catalysts were studied using H2-O2 titration, XRD and TEM measurements, and oxygen reduction tests in PAFC. With increased heat-treatment temperature, the Pt surface area measured by hydrogen chemisorption (S(CHEM)) decreases rapidly owing to particle sintering, alloying effect, and enrichment of iron on the surface. The mass activity (mA/g Pt) of the alloyed catalyst is about the same as that of pure Pt catalyst due to the particle sintering in the alloyed catalyst. However, the specific activity (mA/m2 Pt, based on S(CHEM)) of the alloyed catalyst is estimated at twice that of pure Pt catalyst. The acid-treatment leads to dissolution of surface-enriched iron and results in an increase of the Pt surface area due to surface roughening. Except for PF450, the specific activities of both nontreated and acid-treated catalysts are the same, indicating that S(CHEM) is a good measure of active site for the reaction. After acid treatment of the partially alloyed PF750, a two-fold increase in the Pt surface area (therefore, twice the increase in the MA) was observed when compared with the nontreated Pt-Fe alloy catalyst.
Quickly Finding Orthologs as Reciprocal Best Hits with BLAT, LAST, and UBLAST: How Much Do We Miss? (2014)

Reciprocal Best Hits (RBH) are a common proxy for orthology in comparative genomics. Essentially, a RBH is found when the proteins encoded by two genes, each in a different genome, find each other as the best scoring match in the other genome. NCBI's BLAST is the software most usually used for the sequence comparisons necessary to finding RBHs. Since sequence comparison can be time consuming, we decided to compare the number and quality of RBHs detected using algorithms that run in a fraction of the time as BLAST. We tested BLAT, LAST and UBLAST. All three programs ran in a hundredth to a 25th of the time required to run BLAST. A reduction in the number of homologs and RBHs found by the faster algorithms compared to BLAST becomes apparent as the genomes compared become more dissimilar, with BLAT, a program optimized for quickly finding very similar sequences, missing both the most homologs and the most RBHs. Though LAST produced the closest number of homologs and RBH to those produced with BLAST, UBLAST was very close, with either program producing between 0.6 and 0.8 of the RBHs as BLAST between dissimilar genomes, while in more similar genomes the differences were barely apparent. UBLAST ran faster than LAST, making it the best option among the programs tested.
Dynamics of the chemisorption of O2 on Pt(111): Dissociation via direct population of a molecularly chemisorbed precursor at high incidence kinetic energy (1991)

We have used the thermal desorption spectroscopy of the O/O2+CO→CO2 system to probe the chemical nature of oxygen that remains on a Pt(111) surface following exposure to a supersonic O2 beam under various conditions. We find that for a surface temperature of 90 K, the resulting CO2 formation thermal desorption spectrum is the same for all beam kinetic energies employed up to 1.1 eV at normal incidence, in all cases resembling that assigned to the O2+CO co-adsorbate system. This spectrum is clearly distinct from the O+CO case, where atomically chemisorbed oxygen is obtained either by thermal dissociation of O2 on the surface or by exposing the 90 K surface to a beam containing O atoms. These results imply that the dissociative chemisorption of O2 on Pt(111) proceeds by way of a molecular precursor even at relatively high incidence kinetic energies, at least as high as 1.1 eV. This interpretation readily accounts for the strong surface temperature dependence associated with dissociation under these conditions but contrasts with previous assignment of a direct (or quasidirect) dissociation process at high energies. We have also reexamined a number of previous observations in terms of this new picture, including the initial decline in dissociation probability with increasing kinetic energy. This falloff is attributed to a decrease in the trapping probability into a physisorption state, as recently suggested by Luntz et al. Considering the present results in the light of other recent studies, it now seems clear that the physisorption state is then a precursor to the molecular chemisorption state which can also be accessed directly at high kinetic energy. In this picture the molecular chemisorption state is then a precursor to dissociation even at high kinetic energy, and the dissociation probability depends on the (temperature-dependent) branching ratio between the dissociation and ultimate desorption of these species.
Characterization of Progressive Motor Deficits in Mice Transgenic for the Human Huntington’s Disease Mutation (1999)

Transgenic mice expressing exon 1 of the human Huntington’s disease (HD) gene carrying a 141–157 CAG repeat (line R6/2) develop a progressive neurological phenotype with motor symptoms resembling those seen in HD. We have characterized the motor deficits in R6/2 mice using a battery of behavioral tests selected to measure motor aspects of swimming, fore- and hindlimb coordination, balance, and sensorimotor gating [swimming tank, rotarod, raised beam, fore- and hindpaw footprinting, and acoustic startle/prepulse inhibition (PPI)]. Behavioral testing was performed on female hemizygotic R6/2 transgenic mice ( n = 9) and female wild-type littermates ( n = 22) between 5 and 14 weeks of age. Transgenic mice did not show an overt behavioral phenotype until around 8 weeks of age. However, as early as 5–6 weeks of age they had significant difficulty swimming, traversing the narrowest square (5 mm) raised beam, and maintaining balance on the rotarod at rotation speeds of 33–44 rpm. Furthermore, they showed significant impairment in prepulse inhibition (an impairment also seen in patients with HD). Between 8 and 15 weeks, R6/2 transgenic mice showed a progressive deterioration in performance on all of the motor tests. Thus R6/2 mice show measurable deficits in motor behavior that begin subtly and increase progressively until death. Our data support the use of R6/2 mice as a model of HD and indicate that they may be useful for evaluating therapeutic strategies for HD, particularly those aimed at reducing the severity of motor symptoms or slowing the course of the disease.
Modulation of Autoimmune T-Cell Memory by Stem Cell Educator Therapy: Phase 1/2 Clinical Trial (2015)

Obra Social "La Caixa", Instituto de Salud Carlos III, Red de Investigación Renal, European Union FEDER Funds, Principado de Asturias, FICYT, and Hackensack University Medical Center Foundation.
Propane‐1,2‐diols from Dilactides, Oligolactides, or Poly‐L‐lactic Acid (PLLA): From Plastic Waste to Chiral Bulk Chemicals (2014)

The preparation of racemic or enantioenriched propane-1,2-diol from dilactides, oligolactides, or poly-L-lactic acid (PLLA) is described. The transformation is carried out as tandem reactions in MeOH, covering hydrolysis and subsequent hydrogenation by using copper chromite as a catalyst. The starting material present undesired side products of the PLLA synthesis or PLLA waste.
Plasminogen activator (urokinase) causes vascularization of the cornea. (1982)

The presence of a peripheral zone of (presumed intracellular) plasminogen activator in the normal rabbit cornea has suggested that activator, once released, might regulate the permeability of limbal vessels and angiogenesis, by plasmin-dependent pathways. Plasminogen activator (urokinase [UK]) in rabbit serum albumin (RSA) was injected once (20 microliter, 3.7 CTA U) into the corneal stroma, 2 mm from the limbus. Sprouts arose from the engorged circumlimbal vessels (16 of 20 corneas) beginning on the third day and grew into the cornea over the next several days. Histologically, PMNs were observed in association with growing vessels. Contralateral corneas injected with UK (in RSA) previously inactivated by 99.7% with the specific active site inhibitor, Phe-Ala-Arg-chloromethyl ketone showed minimal vessel engorgement or stromal edema and no vascularization (0 to 20 corneas). Injuries to the so-called (plasminogen activator-containing)"critical zone" of the cornea which elicit neovascularization possibly do so by causing extracellular release of endogenous plasminogen activator. Thus, in addition to initiating the destructive events of ulceration, activator might initiate increases in vessel permeability and also neovascularization, which would result in the eventual arrest of ulceration.