gebhart/patrepeval huggingface dataset:
Natural IgM Blockade Limits Infarct Expansion and Left Ventricular Dysfunction in a Swine Myocardial Infarct Model (2015)

Treatment with m21G6 significantly reduced infarct size and troponin-T release, and led to marked preservation of cardiac function in our study. Overall, these findings suggest that pathogenic IgM blockade represents a valid therapeutic strategy in mitigating myocardial ischemia-reperfusion injury.
The challenges and promises of new therapies for cystic fibrosis (2012)

Therapeutic intervention in cystic fibrosis (CF) remains a challenge, partly because of the number of organs and tissues affected by the lack of a functional cystic fibrosis transmembrane conductance regulator (CFTR) protein. CF was originally regarded primarily as a gastrointestinal (GI) disease because of the failure to thrive and early death from malnutrition in infants with CF. However, successful interventions for the GI manifestations of CF have left chronic lung infections as the primary cause of morbidity and mortality. Despite a complex microbiology within the CF lung, one pathogen, Pseudomonas aeruginosa, remains the critical determinant of pulmonary pathology. Treatment and management of this infection and its associated symptoms are the major targets of extant and developing CF therapies. Understanding the multitude of effects of CFTR on mucosal physiology and susceptibility and progression of chronic lung disease, and how host immune responses fail to adequately control lung infection, will be essential for the development of improved therapies for CF.
Evaluation of the in vitro Activity of Cefprozil Relative to Other Oral Antimicrobial Agents Against Bacteria in Clinical Specimens from Patients in São Paulo With Respiratory Tract Infections. (1998)

Cefprozil is a new oral second generation cephalosporin. Its in vitro antimicrobial activity was evaluated against 371 recent clinical isolates from patients with respiratory infections. We tested the susceptibility of 244 streptococci (96 Streptococcus pneumoniae, 105 group viridans streptococci, 32 Streptococcus agalactiae, and 11 group A beta-hemolitic streptococci) 107 Haemophilus influenzae, and 20 oxacillin-susceptible S.aureus (OSSA). The isolates were susceptibility tested against cefprozil, cefaclor and amoxicillin/clavulanic acid by the E-test method; and against cefadroxil, cefuroxime, cefetamet, erythromycin, and azythromycin by disk diffusion. The methods and the susceptibility categorization followed the National Committee for Clinical Laboratory Standards (NCCLS) procedures. Amoxicillin/clavulanic acid was slightly more active againstH.influenzae (MICs(90) 0.5µg/mL) than cefprozil or cefaclor (MICs(90) 4 and 2µg/mL respectively). Cefprozil demonstrated potent activity against streptococci. Against S.pneumoniae, cefprozil was 2-4 fold more active than cefaclor (MICs(90)0.125 and 0.38µg/mL, respectively). S. pneumoniae susceptibility was 84% to penicillin, 95% to erythromycin and 97% to azithromycin by disk diffusion. Viridans streptococci showed higher MICs for cefprozil and cefaclor (MICs(90) 4µg/mL and 8µg/mL, respectively) and only 50% susceptibility to the macrolides. Cefprozil was four times more active than cefaclor and as active as amoxieillin/clavulanic acid against group A beta-hemolytic streptococci and S.agalactiae. These three compounds showed similar activity against OSSA. In conclusion, cefprozil demonstrated excellent in vitro activity against bacterial species responsible for respiratory infections in São Paulo.
[Effect of piracetam and lithonite on the course of experimental myocardial infarction]. (1994)

The effect of lithonite and piracetam on the cardiac rhythm, dynamics of infarction, metabolism, and immunological reactivity of the animals' organism was studied in dogs with experimental myocardial infarction. The pharmacotherapeutic activity of lithonite was found to be higher than that of piracetam.
Post-traumatic arthritis: overview on pathogenic mechanisms and role of inflammation (2016)

Post-traumatic arthritis (PTA) develops after an acute direct trauma to the joints. PTA causes about 12% of all osteoarthritis cases, and a history of physical trauma may also be found in patients with chronic inflammatory arthritis. Symptoms include swelling, synovial effusion, pain and sometimes intra-articular bleeding. Usually, PTA recoveries spontaneously, but the persistence of symptoms after 6 months may be considered pathological and so-called chronic PTA. A variety of molecular, mechanobiological and cellular events involved in the pathogenesis and the progression of PTA have been identified. The activation of inflammatory mechanisms during the PTA acute phase appears to play a critical role in the chronic disease onset. Human studies and experimental models have revealed that a series of inflammatory mediators are released in synovial fluid immediately after the joint trauma. These molecules have been proposed as markers of disease and as a potential target for the development of specific and preventative interventions. Currently, chronic PTA cannot be prevented, although a large number of agents have been tested in preclinical studies. Given the relevance of inflammatory reaction, anticytokines therapy, in particular the inhibition of interleukin 1 (IL-1), seems to be the most promising strategy. At the present time, intra-articular injection of IL-1 receptor antagonist is the only anticytokine approach that has been used in a human study of PTA. Despite the fact that knowledge in this area has increased in the past years, the identification of more specific disease markers and new therapeutic opportunities are needed.
PDL1 is expressed in the islets of people with type 1 diabetes and is up-regulated by interferons-α and-γ via IRF1 induction (2018)

These findings indicate that PDL1 is expressed in beta cells from people with T1D, possibly to attenuate the autoimmune assault, and that it is induced by both type I and II interferons via IRF1.
100 mW spectrally-uniform broadband ASE source forspectrum-slicedWDM systems (1994)

A &gt; 100 mW source of broadband ASE with exceptionally flat spectral density and 22 nm bandwidth is presented. The source is ideally suited for spectrum-sliced WDM systems. Data transmission at 622 Mbit/s using a spectrally-sliced channel tuned over a 15 nm range is demonstrated.
Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced DNA adduct formation and tumorigenicity in the lung of F344 rats by dietary phenethyl isothiocyanate. (1989)

F344 rats fed diets containing phenethyl isothiocyanate (PEITC, 3 mumol/g diet), a cruciferous vegetable component, before and during treatment with the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), developed about 50% fewer lung tumors than NNK-treated rats fed control diets. NNK-induced liver and nasal cavity tumors in rats were, however, not affected by this dietary treatment. The effects of PEITC diets on the formation of DNA adducts by NNK were also investigated in these target tissues. DNA methylation and pyridyloxobutylation by NNK were both decreased by 50% in lung of rats fed PEITC diets compared to that of rats fed control diets, but the levels of DNA methylation were not affected in liver and nasal mucosa. These results correlated with those from the carcinogenicity bioassay, suggesting that DNA alkylations could be used as indicators for screening inhibitors of NNK tumorigenesis. A slight increase in the number of tumors of the exocrine pancreas was observed in PEITC-fed rats with or without NNK treatments. However, these incidences were not statistically significant when compared to the control groups. The potential toxicity of PEITC at concentrations ranging from 0.75 mumol to 6 mumol/g diet was evaluated in a 13-week study. The only toxicity caused by this treatment was minimal fatty metamorphosis in the liver. Considering the widespread human exposure to NNK through tobacco use, it is of practical importance to demonstrate inhibition of lung tumors induced by this carcinogen. These results provide a basis for studies designed to discover agents of better efficacy for the prevention of NNK-induced tumorigenesis.
A v-sis oncogene protein produced in bacteria competes for platelet-derived growth factor binding to its receptor. (1984)

The oncogene of simian sarcoma virus, v-sis, encodes a protein which is homologous to human platelet-derived growth factor (PDGF). This v-sis-encoded protein was expressed in bacteria using an inducible promotor of lambda phage. Soluble extracts from these bacteria contained a substance which competed with 125I-PDGF for PDGF receptor sites in fibroblast membranes. The receptor competition activity was correlated with the presence of the v-sis-encoded protein as assessed by genetic and immunochemical criteria. These results directly demonstrate that the v-sis oncogene product is functionally related to PDGF.
A novel p53 mutation hotspot at codon 132 (AAG‐‐‐‐> AGG) in human renal cancer (1998)

Mutations of p53 tumor suppressor gene are the most common genetic alterations in a variety of human carcinomas. The sites of p53 mutations, however, vary in different cancers. The present study was designed to characterize p53 mutations in 40 primary human renal cancer specimens using hot-start-PCR-single-strand conformation polymorphism (SSCP) analysis, sequencing of PCR product and immunohistochemistry. DNA extracted from microdissected paraffin-embedded sections was amplified by hot-start-PCR using oligonucleotide primers specific for exons 4-9 of p53. The mutations were analyzed by PCR-SSCP technique and the generated fragments were denatured and analyzed by 6% polyacrylamide gel electrophoresis. The samples showing a band shift were denatured and sequenced using the Sequenase Version 2.0 DNA Sequencing Kit (US Biochemical, Cleveland, Ohio). Genomic DNA from control samples containing wild-type p53 alleles was sequenced in parallel for confirming mutations in samples that were positive for p53 in the PCR-SSCP analysis. The results of these experiments demonstrate that: (1) there were mutations in p53 exon 5 and 8 in 35% (14 out of 40 samples) of human renal cancer tissues as revealed by PCR-SSCP analysis; (2) DNA sequencing of samples showing frame-shift have hot spot of p53 mutation on exon 8 at codon 244 (GGC-->TGC) and exon 5 at codon 132 [AAG (Lys)-->AGG (Arg)]. This mutation in p53 exon 5 at codon 132 is novel and has not yet been reported; (3) immunohistochemical staining of p53 in renal cancer tissue using mouse anti-human p53 monoclonal antibody, clone PAb 1801, correlated with the p53 mutation assessed by PCR-SSCP. No correlation was found between p53 mutations and tumor stage and grade of renal cancer.
Search for Life in the Universe with terrestrial microbes which Thrive under Extreme Conditions (1997)

Abstract It is reasonable to believe that life exists in many places throughout the Universe. Among the many billions of heavenly bodies, there are galaxies with millions of stars that may harbor lower or even higher forms of living organisms («life» in the meaning as we know it, e.g., carbon chemistry, liquid water etc.). This article lists Extremophiles and their various terrestrial enigmatic environments. We discuss the possibilities of Martian life and the origin and evolution of the eukaryotic cell and present some early protists and the Acidothermophilic algae. Among several microbes which can «fit» for extraterrestrial life, one eukaryotic algal group (Cyanidiophyceae) is treated here. The hot spring Cyanidium caldarium members (there are three genera and several species in this family) thrive in excessive growth conditions like in acidic medium (close to IN H 2 SO 4 ), under pure CO 2 atmosphere, in elevated temperature and auto or heterotrophic conditions. These hot spring unicellular algae do not require oxygen for such conditions of growth. Studies have shown that they present one of the earliest and simplest eukaryotic algae. Also, these microbes may be candidates for existing on planets with similar ecological conditions which might support life forms.
Induction of humoral and cellular immune responses by vaccination with M. tuberculosis antigen 85 DNA. (1997)

DNA vaccines have been demonstrated to be effective in inducing protective cell-mediated immune responses in animal models of infectious disease. In order to investigate this approach for potential use as a vaccine for tuberculosis, DNA constructs encoding Mycobacterium tuberculosis antigen 85A (Ag85A) were prepared. Expression of Ag85A in mammalian cells was demonstrated by transient transfection of cells in vitro. Intramuscular injection of Ag85A DNA vaccines resulted in the generation of anti-Ag85A antibodies and robust cell-mediated immune responses, as measured by lymphoproliferation of spleen cells in vitro upon specific antigen restimulation, leading to protection in animal challenge models. Therefore, the technique of DNA vaccination is effective in inducing relevant immune responses for protection against tuberculosis and may be used to identify the protective antigens of M. tuberculosis.
Phase I study of intra-pleural administration of GL-ONC1, an oncolytic vaccinia virus, in patients with malignant pleural effusion. (2015)

7559 Background: GL-ONC1 is an attenuated vaccinia virus genetically engineered with the insertion of RUC (luciferase)-GFP, LacZ (beta-galactosidase), and gusA (beta-glucuronidase) genes. We investigated the feasibility, safety, and recommended dose of GL-ONC1 when administered intrapleurally. Methods: Pts with pleural effusion from malignant pleural mesothelioma (MPM), NSCLC, breast cancer, or other solid tumor, and a free pleural space were eligible. Single doses of 1x107, 1x108, 1x109, or 3x109 plaque forming units were administered, and escalation used a 3+3 design. Virus was infused with 500cc Ringer’s Lactate over 1hr through a pleural catheter. Fluorescent-imaging guided, thoracoscopic pleural biopsies were performed 2-9 days later. Blood, sputum, urine, and pleural fluid were analyzed for viral shedding by viral plaque assays (VPA). No chemotherapy or radiation was administered during the course of the study (-14 days to 60 days). Results: 14 pts have been treated: MPM (11), NSCLC (2), breast (1). Among 13 evaluable pts (1pt with NSCLC was not evaluable due to the rapid development of brain metastases) no dose limiting toxicities occurred. The most common toxicities were fever (7 pts), chills (6), and flu-like symptoms (5), all grade 1/2 occurring mostly in the 24hr after infusion. One patient at dose level 4 had transient grade 3 AST/ALT elevation. 1/28 urine and 5/28 pleural fluid post-treatment samples had +VPA. Positive GL-ONC1 infection of tumor specimens was identified in 6 of 8 pts with epithelioid MPM based on VPA, IHC and GFP imaging. 5 of the 9 pts with epithelioid MPM had time to progression ≥ 9 mo (18 mo in one pt). Pts with NSCLC and breast cancer progressed quickly at metastatic sites. Conclusions: Single dose, intrapleural administration of GL-ONC1 is safe, but is best suited for patients with MPM whose disease is limited to the pleura. We are now exploring multi-day treatment, and also treatment in conjunction with pleurectomy for pts with MPM. Supported by Genelux Corporation (NCT01766739). Clinical trial information: NCT01766739.
Mutational analysis of the human immunodeficiency virus type 2 (HIV-2) genome in relation to HIV-1 and simian immunodeficiency virus SIV (AGM) (1990)

We constructed an infectious molecular clone of the human immunodeficiency virus type 2 (HIV-2) and generated nine frameshift mutants corresponding to nine open reading frames identified so far. Three structural (gag, pol, env) and two regulative (tat, rev) gene mutants were not infectious, whereas vif, vpx, vpr, and nef genes were dispensable for infectivity. All of the mutants except env and rev were cytopathic in CD4+ human leukemia cells. In transfection assays, the expression of HIV-2 long terminal repeat was activated by infectious clones of HIV-1, HIV-2, and simian immunodeficiency virus from African green monkey but not by the tat mutants. However, an HIV-2 tat mutant could produce small amounts of virus proteins and particles in contrast to a rev mutant, which directed no detectable synthesis of virus proteins and virions.
Glucagon-Like Peptide-1 Regulates the Beta Cell Transcription Factor, PDX-1, in Insulinoma Cells (1999)

Glucagon-like peptide-1 (GLP-1) enhances insulin biosynthesis and secretion as well as transcription of the insulin, GLUT2 and glucokinase genes. The latter are also regulated by the PDX-1 homeoprotein. We investigated the possibility that GLP-1 may be having its long-term pleiotropic effects through a hitherto unknown regulation of PDX-1. We found that PDX-1 mRNA level was significantly increased (p<0.01) after 2 hours and insulin mRNA level was subsequently increased (p<0.01) after 3 hours of treatment with GLP-1 (10 nM) in RIN 1046-38 insulinoma cells. Under these experimental conditions, there was also a 1.6-fold increase in the expression of PDX-1 protein in whole cell and nuclear extracts. Overexpression of PDX-1 in these cells confirmed the finding of the wild type cells such that GLP-1 induced a 2-fold increase in whole cell extracts and a 3-fold increase in nuclear extracts of PDX-1 protein levels. The results of electrophoretic mobility shift experiments showed that PDX-1 protein binding to the Al element of the rat insulin II promoter was also increased 2 h post treatment with GLP-1. In summary, we have uncovered a previously unknown aspect to the regulation of PDX-1 in beta cells. This has important implications in the physiology of adult beta cells and the treatment of type 2 diabetes mellitus with GLP-1 or its analogs.
Photothermal Imaging of Nanometer-Sized Metal Particles Among Scatterers (2002)

Ambient optical detection of labeled molecules is limited for fluorescent dyes by photobleaching and for semiconducting nanoparticles by "blinking" effects. Because nanometer-sized metal particles do not optically bleach, they may be useful optical labels if suitable detection signals can be found. We demonstrate far-field optical detection of gold colloids down to diameters of 2.5 nanometers with a photothermal method that combines high-frequency modulation and polarization interference contrast. The photothermal image is immune to the effects of scattering background, which limits particle imaging through Rayleigh scattering to diameters larger than 40 nanometers.
Physiological and Proteomic Analysis of Escherichia coli Iron-Limited Chemostat Growth (2014)

Iron bioavailability is a major limiter of bacterial growth in mammalian host tissue and thus represents an important area of study. Escherichia coli K-12 metabolism was studied at four levels of iron limitation in chemostats using physiological and proteomic analyses. The data documented an E. coli acclimation gradient where progressively more severe iron scarcity resulted in a larger percentage of substrate carbon being directed into an overflow metabolism accompanied by a decrease in biomass yield on glucose. Acetate was the primary secreted organic by-product for moderate levels of iron limitation, but as stress increased, the metabolism shifted to secrete primarily lactate (∼70% of catabolized glucose carbon). Proteomic analysis reinforced the physiological data and quantified relative increases in glycolysis enzyme abundance and decreases in tricarboxylic acid (TCA) cycle enzyme abundance with increasing iron limitation stress. The combined data indicated that E. coli responds to limiting iron by investing the scarce resource in essential enzymes, at the cost of catabolic efficiency (i.e., downregulating high-ATP-yielding pathways containing enzymes with large iron requirements, like the TCA cycle). Acclimation to iron-limited growth was contrasted experimentally with acclimation to glucose-limited growth to identify both general and nutrient-specific acclimation strategies. While the iron-limited cultures maximized biomass yields on iron and increased expression of iron acquisition strategies, the glucose-limited cultures maximized biomass yields on glucose and increased expression of carbon acquisition strategies. This study quantified ecologically competitive acclimations to nutrient limitations, yielding knowledge essential for understanding medically relevant bacterial responses to host and to developing intervention strategies.
Microstructural changes in GeSbTe film during repetitious overwriting in phase-change optical recording (1995)

Microstructural changes that occur in a GeSbTe film during repetitious overwriting in phase-change optical recording were investigated. The GeSbTe active layer was melted by a focused laser diode (LD) beam during each overwriting process over amorphous mark formation. The repetitious solidification and liquefaction process in such a short time as 50–200 ns resulted in microstructural changes in the active layer: a segregation, sink, and void formations. The sink was formed in the low-density active layer due to the shrinking of the volume during the resolidification process. Sink formation could be suppressed when a high-density active layer, having more than 80% of the bulk density, was used. Such a high-density GeSbTe film, however, resulted in a void formation of the size of 0.1 μm. The voids were thought to be nucleated by residual vacancies and Ar precipitation, since the active layer contained a high concentration of Ar impurities, due to the atomic peening effect. The subsequent void coalescence and migration processes across the beam scanning direction could result in the formation of thermally discontinuous grooves at the edges of the written marks. The voids could also migrate along the LD beam scanning direction, accompanied by a material flow of the active layer in the opposite direction. These phenomena were also found to depend on the material used to fabricate the protective layers which sandwiched the active layer. A TaOx protective layer enhanced the void migration across the track, resulting in the removal of voids from the center of the track. Use of the ZnS:SiO2 compound protective layer confined voids to the center of the track. The ZnS:SiO2 protective layer also promoted the formation of thermally discontinuous grooves at the edges of amorphous marks. The material flow along the track resulted in a thicker active layer at the start of the consecutive LD irradiation, and also in a high void density region at the final edge of the irradiation having a length on the order of 10 μm. This tendency was found for both the ZnS:SiO2 and TaOx sandwiching media.
A randomized clinical trial to determine the efficacy of manufacturers’ recommended doses of omega-3 fatty acids from different sources in facilitating cardiovascular disease risk reduction (2014)

ClinicalTrials.gov: NCT01960660.