gebhart/patrepeval huggingface dataset:
Targeted Inactivation of the Coagulation Factor IX Gene Causes Hemophilia B in Mice (1998)

Hemophilia B is a leading target for gene therapy because current therapy is not optimal. Hence, a murine model of factor IX (F. IX) deficiency was generated to develop gene therapy strategies for hemophilia B. A targeting vector was created by replacing a 3.2-kb segment of the gene encompassing the catalytic domain with a phosphoglycerokinase promoter-driven neomycin resistant (neor) gene cassette. The transfected embryonic stem cell clones generated chimeric male mice, and germ line transmission of the inactivated F. IX gene was observed in their offsprings. Southern analysis confirmed the mutant genotype in hemizygous male and carrier female mice. F. IX transcripts were not detected in liver RNA isolated from hemizygous mice, and lower levels of F. IX mRNA were noted in carrier female mice when compared with those of normal litter mates. As expected, the mean F. IX coagulant titer of affected male mice was 2.8 U/dL (n = 10), while the mean F. IX titer of carrier female mice was 35 U/dL (n = 14), compared with 69 U/dL (n = 9) for the normal female mice and 92 U/dL (n = 22) for normal male and female litter mates. Further, the tail bleeding time of hemizygous mice was markedly prolonged (>3 hours) compared with those of normal and carrier female litter mates (15 to 20 minutes). Seven of 19 affected male mice died of exsanguination after tail snipping, and two affected mice died of umbilical cord bleeding. Currently, there are 10 affected mice surviving at 4 months of age. Aside from the factor IX defect, the carrier female and hemizygous male mice had no liver pathology by histologic examination, were fertile, and transmitted the F. IX gene mutation in the expected Mendelian frequency. Taken together, we have generated a F. IX knockout mouse for evaluation of novel gene therapy strategies for hemophilia B.
Integration of accessible secondary metal sites into MOFs for H2S removal (2014)

2,2′-Bipyridine-5,5′-dicarboxylic acid (H<sub>2</sub>bipy) was utilized for the synthesis of a zirconium based MOF isoreticular to UiO-67. The chelating bipyridine moiety was used for postsynthetic functionalization of the MOF with different metal salts giving materials with good performance in capture of toxic H<sub>2</sub>S.
Cell Surface-localized Nucleolin Is a Eukaryotic Receptor for the Adhesin Intimin-γ of Enterohemorrhagic Escherichia coliO157:H7 (2002)

Intimin-gamma is an outer membrane protein of enterohemorrhagic Escherichia coli (EHEC) O157:H7 that is required for the organism to adhere tightly to HEp-2 cells and to colonize experimental animals. Another EHEC O157:H7 protein, the Transferred intimin receptor (Tir), is considered the primary receptor for intimin-gamma. Nevertheless, Tir-independent binding of intimin-gamma to HEp-2 cells has been reported. This observation suggests the existence of a eukaryotic receptor(s) for intimin-gamma. In this study, we sought to identify that receptor(s). First, we determined by equilibrium binding titration that the association of purified intimin-gamma with HEp-2 cells was specific and consistent with a single host cell receptor. Second, we isolated a protein from lysates of HEp-2 cells that bound intimin-gamma and subsequently identified this molecule as nucleolin, a protein involved in cell growth regulation that can be cell surface-expressed. Third, we established that purified intimin-gamma and nucleolin were co-localized on the surface of HEp-2 cells and that the site of EHEC O157:H7 attachment was associated with regions of nucleolin expression. Finally, we demonstrated that mouse anti-nucleolin sera significantly decreased the adherence of EHEC O157:H7 to HEp-2 cells. From this, we conclude that nucleolin is the HEp-2 cell receptor for intimin-gamma expressed by EHEC O157:H7.
Effects of dietary supplementation with cod-liver oil on endothelium-dependent responses in porcine coronary arteries. (1987)

To study the effect of dietary supplementation with fish oil on endothelium-dependent responses, Yorkshire pigs were maintained on a normal diet or on a low (0.6 ml/kg/day) or a high (1.0 ml/kg/day) dose of cod-liver oil for 4 weeks. Endothelium-dependent responses were examined in vitro in rings of proximal left anterior descending coronary arteries taken from control and treated animals studied in parallel. Endothelium-dependent relaxations in response to bradykinin, serotonin, adenosine diphosphate, and thrombin were facilitated in arteries from treated but not in those from control animals, whereas the relaxations in response to A23187 were unaltered. The facilitated relaxations were not altered by indomethacin but significantly inhibited by methylene blue. Aggregating platelets from control and treated pigs induced comparable, facilitated endothelium-dependent relaxations in rings taken from treated pigs. The platelet-induced contractions were significantly reduced in rings with endothelium taken from treated pigs, and they were comparable in rings without endothelium in both groups. Aggregating platelets from control and treated pigs released comparable amounts of serotonin and thromboxane A2. Endothelium-dependent relaxations induced by arachidonic acid and eicosapentaenoic acid were unaltered, whereas transient endothelium-dependent contractions induced by arachidonic acid were significantly reduced by the treatment with cod-liver oil. Relaxations to sodium nitroprusside or isoproterenol,and contractions to potassium chloride or serotonin were not different in rings without endothelium from control or treated pigs. These results indicate that dietary supplementation with cod-liver oil facilitates endothelium-dependent relaxations and inhibits endothelium-dependent contractions in porcine coronary arteries.
Magnetic Nanoparticles and Their Applications in Medicine (2006)

Magnetic nanoparticles have attracted attention in modern medicine and pharmacology owing to their potential usefulness as contrast agents for MRI, as colloidal mediators for cancer magnetic hyperthermia or as active constituents of drug-delivery platforms. This review examines these in vivo applications through an understanding of the involved problems and the current and future possibilities for resolving them. A special emphasis is placed upon magnetic nanoparticle requirements from a physical viewpoint (e.g., relaxivity for MRI, specific absorption rate for hyperthermia and magnetic guidance), the factors affecting their biodistribution after intravenous injection (e.g., size and surface hydrophobic/hydrophilic balance) and the solutions envisaged for enhancing their half-life in the blood compartment and in targeting tumor cells.
Involvement of cysteine 289 in the catalytic activity of an NADP+-specific fatty aldehyde dehydrogenase from Vibrio harveyi (1995)

Fatty aldehyde dehydrogenase (Vh.ALDH) from the luminescent bacterium, Vibrio harveyi, may be implicated in controlling luminescence as it catalyzes the oxidation of the fatty aldehyde substrate for the light-emitting reaction. On the basis of the amino-terminal sequence of Vh.ALDH, a degenerate probe was used to screen a genomic library of V harveyi in pBR322, a positive clone was selected containing the Vh.ALDH gene and expressed in Escherichia coli, and the enzyme was purified to homogeneity. Although the sequence of the V. harveyi ALDH significantly diverged from other aldehyde dehydrogenases, mutation of a conserved cysteine implicated in catalysis completely inactivated the enzyme without loss of its ability to bind nucleotides, consistent with a catalytic role for this residue. Using absorption and fluorescence assays for NAD(P)H, it was shown that NAD+ and NADP+ bound to the same site and that saturation of Vh.ALDH with NADP+ occurred with a Michaelis constant (Km = 1.4 microM) over 40 times lower than that reported for other aldehyde dehydrogenases. Although V. harveyi aldehyde dehydrogenase is unique in terms of its high specificity for NADP+, the identification of a catalytic conserved cysteine in Vh.ALDH clearly indicates that a highly related mechanism and structure have been retained among even the most diverged aldehyde dehydrogenases.
A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction (2006)

IC and EC injection of MSCs post-MI resulted in increased engraftment within infarcted tissue when compared with IV infusion, and IC was more efficient than EC. However, IC delivery was also associated with a higher incidence of decreased coronary blood flow. EC delivery into acutely infarcted myocardial tissue was safe and well tolerated and was associated with decreased remote organ engraftment with compared with IC and IV deliveries.
The Chemistry of Perfluoroisobutene (1984)

The literature data on the methods of synthesis and reactions of the highly electrophilic perfluoroisobutene with nucleophiles as well as electrophiles are surveyed. The possibilities of employing this fluoro-olefin in organofluorine synthesis are discussed. The advances in the study of the perfluoro-t-butyl anion, generated from perfluoroisobutene and the fluoride anion, are considered in a special section. The bibliography includes 199 references.
Introduction of Functional Groups into Peptides via N-Alkylation (2008)

An optimized protocol for the mild and selective Fukuyama-Mitsunobu reaction was used for mono- and di- N-alkylation on solid support. Thereby, nonfunctionalized aliphatic and aromatic residues are quickly introduced into transiently protected, primary amines of a linear peptide. N-Alkylation can also be used to implement alkyl chains carrying (protected) functionalities suited for subsequent modification. Applicability of this method is demonstrated by various N-alkylated analogues of a cyclic CXCR4 receptor antagonist originally developed by Fujii et. al.
Analysis of nucleic acids by on‐line liquid chromatography–Mass spectrometry (2001)

The numerous problems posed by modern biochemistry, biology, and medicine, as well as the growing significance of genetic engineering require the application of fast and reliable methods of utmost sensitivity and selectivity for the analysis of nucleic acids. High-performance liquid chromatography (HPLC) and mass spectrometry (MS) represent established analytical techniques for the characterization and structural elucidation of single- and double-stranded nucleic acids, ranging in size from a few nucleotides to several thousand base pairs. Although both techniques are independently applicable for nucleic acid analysis, the on-line hyphenation significantly enhances their potential for the robust and fully automable routine analysis of minute amounts of biological samples. Among the various chromatographic and mass spectrometric modes available in principle, ion-pair reversed-phase HPLC and electrospray ionization mass spectrometry (ESI-MS) have been shown to be the most suitable for the direct interfacing of liquid chromatography (LC) and MS. Instrumental setup, as well as chromatographic and mass spectrometric experimental conditions, need to be carefully selected in order to maximize the performance of the hyphenated analytical system. Applications of HPLC-ESI-MS include the characterization of oligodeoxynucleotides synthesized by solid-phase synthesis, the analysis of antisense oligodeoxynucleotides, oligonucleotide metabolites, and DNA adducts, the analysis of genomic segments specifically amplified by the polymerase chain reaction (PCR), the characterization of ribonucleic acids, the sizing of double-stranded DNA restriction fragments, the genotyping of short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs), the detection of mutations in nucleic acid sequences, and the sequencing of nucleic acids.
Derivatives of Imidazo [2, 1-b] benzothiazole (Studies on Heterocyclic Compounds. VII) (1970)

Condensation reaction of 2-aminobenzothiazole and bromoacetone under the condition of boiling alcohol afforded a molecular compound of equimolecular of 2-amino-benzothiazole and 2-methylimidazo [2, 1-b] benzothiazole. When the reaction condition under standing at room temperature was adopted, 2-imino-3-acetonyl-2, 3-dihydrobenzothiazole was obtained. 3-Phenylimidazo [2, 1-b] benzothiazole was prepared from 1- (m-chlorophenyl) -2-mercapto-4-phenylimidazole and potassium amide in liquid ammonia. Imidazo [2, 1-b] benzothiazole was also prepared from 1- (m-chlorophenyl) -2-mercaptoimidazole.
Comparison of Three Tests for Confirmation of the Diagnosis of Heparin Induced Thrombocytopenia. (2004)

Abstract In a recent two year period only 14% of platelet aggregation tests performed on 230 patients suspected of having heparin induced thrombocytopenia (HIT) were positive. The test (control platelet-rich plasma 0.14 mL, fresh heated patient serum 0.22 mL plus heparin 0.04 mL (1 Unit/mL final concentration) was performed using suitable controls on a commercial 4 channel aggregometer. 20% or greater increase in light transmission was a positive result. We then started a prospective study in which three different tests were done on the serum of each of 96 consecutive Hines Veterans Affairs Hospital patients who were clinically suspected of having HIT. The three tests were: platelet aggregation (PA) (same method as in the earlier study), C14 serotonin release (standard washed platelet method-SRA) and ELISA (GTI-PF4, Waukeshaw, Wisconsin), all performed on the same serum sample. The SRA and ELISA tests were performed on serum stored at −70°C. Blinded to the test results, a clinical score was determined from the record as HIGH (30% or greater fall in platelet count with recovery within 15 days off heparin), MEDIUM (same criteria but other cause present, or failure to recover platelet counts on continued heparin therapy) or LOW probability (failure to fall at least 30% or to recover from 30% or greater fall within 15 days observation). Results of the clinical scoring and laboratory tests were as follows: Clinical Probabilities: High (n=23), Medium (N=33), Low (n=40). Of the 56 who were High or Medium probability, 41% were High and 59% were Medium probability. Analysis of the results of the laboratory tests for sensitivity and specificity for each category revealed the following: Clinical Probability PA SRA ELISA Sensitivity Specificity Sensitivity Specificity Sensitivity Specificity High and Medium (n=56) 19.6% 97.5% 10.7% 97.5% 10.7% 90% High (n=23) 30.4% 93.1% 17.4% 95.9% 8.7% 89% Conclusions: Sensitivity of the PA test was greater than either of the other two tests, with specificities for the PA and SRA being nearly equal. The ELISA test was relatively insensitive and less specific than then other two.
Pulmonary emboli from pulse-spray and mechanical thrombolysis: evaluation with an animal dialysis-graft model. (1996)

The percutaneous thrombolytic device is effective for declotting dialysis grafts in dogs and results in statistically significantly fewer pulmonary emboli compared with PSPMT.
The Genetic Approach in Pulmonary Fibrosis: Can It Provide Clues to This Complex Disease? (2006)

Multiple investigators have undertaken genetic studies in idiopathic pulmonary fibrosis populations in attempts to define genetic links to disease in hopes that this would improve understanding of disease pathogenesis and target pathways for therapy. Multiple genes have been evaluated using a candidate gene approach with limited success, with results suggesting a disease modifier effect rather than a disease causing effect. Using this approach, associations have been observed between idiopathic pulmonary fibrosis and specific polymorphisms in genes encoding interleukin-1 receptor antagonist, tumor necrosis factor-alpha, and complement receptor 1. Recently investigators have used familial pulmonary fibrosis cohorts to evaluate for genetic mutations associated with idiopathic pulmonary fibrosis. Using one pulmonary fibrosis kindred, a mutation in the gene encoding surfactant protein C was identified as the cause of pulmonary fibrosis in this family. Subsequently, another individual with idiopathic pulmonary fibrosis was identified with a different mutation in surfactant protein C. Though rarely found in patients with idiopathic pulmonary fibrosis, these surfactant protein C mutations highlight the importance of the alveolar epithelium in disease pathogenesis. A recent collaboration between investigators at three major centers has resulted in the largest collection of families with pulmonary fibrosis to date, with hopes that this effort will identify genetic mutations associated with idiopathic pulmonary fibrosis. If genetic links to idiopathic pulmonary fibrosis are defined in this study, then the pathways involved with these genes and gene products can be targeted by investigators to help identify potential treatment options for this disease.
Calcitonin-Gene-Related Peptide: A Possible Role in Human Penile Erection and its Therapeutic Application in Impotent Patients (1991)

A functional study was done to examine a possible role of calcitonin-gene-related peptide in human penile erection and its possible therapeutic applications for patients with erectile dysfunction. In the determination of an effective dosage, 5 ng. (2 patients), 50 ng. (2 patients), 500 ng. (4 patients), 5 micrograms (4 patients) and 25 micrograms (7 patients) were injected intracavernously, and pulse and blood pressure were monitored. Arterial inflow was measured by Doppler sonography, smooth muscle relaxation was determined by the analysis of cavernous electrical activity and cavernous outflow occlusion was recorded by cavernosometry. In 12 patients the erectile response of prostaglandin E1 was compared to the response of an equal (6 patients) or decreased dose of prostaglandin E1 combined with an equal weight of calcitonin-gene-related peptide. In 14 patients the erectile response to the combination of calcitonin-gene-related peptide and prostaglandin E1 was compared to the response of prostaglandin E1 alone, and with a combination of 15 mg./ml. papaverine and 0.5 mg./ml. phentolamine. Calcitonin-gene-related peptide induced an increase in the penile arterial inflow, cavernous smooth muscle relaxation and cavernous outflow occlusion. Histochemical results indicated nerve fibers positive for calcitonin-gene-related peptide within the cavernous bodies. A dose-dependent erectile response to calcitonin-gene-related peptide was observed at doses of 500 ng. to 25 micrograms. Systemic side effects were first observed at a dose of 25 micrograms in 2 of 7 patients. The combination of calcitonin-gene-related peptide and prostaglandin E1 was more effective in inducing a full erection than either prostaglandin E1 alone or the combination of papaverine and phentolamine. Pain was reported in 4% of the patients who received the combination of calcitonin-gene-related peptide and prostaglandin E1, whereas 42% of those who received prostaglandin E1 alone reported pain. Our results suggest that calcitonin-gene-related peptide may be a possible neurotransmitter for penile erection. A combination of calcitonin-gene-related peptide and prostaglandin E1 seems to be an effective alternative combination in the treatment of impotence.
Immunoelectrophoretic analysis, toxicity, and kinetics of in vitro production of the protective antigen and lethal factor components of Bacillus anthracis toxin (1984)

The kinetics of Bacillus anthracis toxin production in culture and its lethal activity in rats, mice, and guinea pigs were investigated. Lethal toxin activity was produced in vitro throughout exponential growth at essentially identical rates in both encapsulated virulent and nonencapsulated avirulent strains. The two toxin proteins which produce lethality when in combination, lethal factor (LF) and protective antigen (PA), could be quantitated directly from culture fluids by rocket immunoelectrophoresis. Using purified preparations of these proteins, we determined that a combination of 8 micrograms of LF and 40 micrograms of PA was required for a maximal rate of killing (39 to 40 min) in Fischer 344 rats (250 to 300 g). Conversely, a minimum of 0.6 microgram of LF and 3 micrograms of PA was required for lethality. The 50% lethal dose for Hartley guinea pigs was 50 micrograms of LF and 250 micrograms of PA, and for Swiss mice it was 2.5 micrograms of LF and 12.5 micrograms of PA. Analyses classically reserved for enzyme kinetic studies were used to study the kinetics of lethal activity in the rat model after intravenous injection of LF-PA mixtures. The amounts of LF and PA which were required to give half the rate of killing (i.e., double the minimum time to death) were 1.2 and 5.8 micrograms, respectively. A theoretical minimum time to death was determined to be 38 min. A third anthrax toxin component, edema factor, was shown to inhibit lethal toxin activity. Edema factor could not be quantitated by rocket immunoelectrophoresis because the protein did not form distinct precipitin bands with available antisera.
Competitive Inhibition of Rat Brain Hexokinase by 2‐Deoxyglucose, Glucosamine, and Metrizamide (1981)

The effects of metrizamide on the kinetics of rat brain hexokinase were compared in vitro with those of 2-deoxyglucose and glucosamine. Although metrizamide, 2-deoxyglucose, and glucosamine are known to be competitive inhibitors of approximately equal potency for glucose of yeast hexokinase (Ki approximately 0.7 mM for all three), metrizamide is a much weaker competitive inhibitor (Ki about 20 mM) of rat brain hexokinase than either 2-deoxyglucose or glucosamine (Ki about 0.3 mM for both). This indicates a greater active site specificity of rat brain hexokinase than of yeast hexokinase. Rat brain hexokinase activity is enhanced approximately threefold in the presence of 0.05, 0.2, and 0.8 mg/ml bovine serum albumin, while yeast hexokinase is only enhanced by 50% under these conditions. Despite the high Ki value for metrizamide, interference with glucose metabolism may occur whenever metrizamide is present in much higher concentrations than glucose. Myelography in humans is one such situation.
A Multiscale Study of High Performance Double-Walled Nanotube−Polymer Fibers (2010)

The superior mechanical behavior of carbon nanotubes (CNT) and their electrical and thermal functionalities has motivated researchers to exploit them as building blocks to develop advanced materials. Here, we demonstrate high performance double-walled nanotube (DWNT)-polymer composite yarns formed by twisting and stretching of ribbons of randomly oriented bundles of DWNTs thinly coated with polymeric organic compounds. A multiscale in situ scanning electron microscopy experimental approach was implemented to investigate the mechanical performance of yarns and isolated DWNT bundles with and without polymer coatings. DWNT-polymer yarns exhibited significant ductility of ∼20%, with energy-to-failure of as high as ∼100 J g(-1), superior to previously reported CNT-based yarns. The enhanced ductility is not at the expense of strength, as yarns exhibited strength as high as ∼1.4 GPa. In addition, the significance of twisting on the densification of yarns and corresponding enhancement in the lateral interactions between bundles is identified. Experiments at nanometer and macroscopic length scales on DWNT-polymer yarns and bundles further enabled quantification of energy dissipation/storage mechanisms in the yarns during axial deformations. We demonstrate that while isolated DWNT bundles are capable of storing/dissipating up to ∼500 J g(-1) at failure, unoptimal load transfer between individual bundles prevents the stress build up in the yarns required for considerable energy storage at the bundle level. By contrast, through polymer lateral interactions, a much better performance is obtained with the majority of energy dissipated at failure being contributed by the interactions between the polymer coating and the DWNTs as compared to the direct van der Waals interactions between bundles.