gebhart/patrepeval huggingface dataset:
[Changes of retinal neurons and Muller glial cells in patients with type II diabetes in treatment of diabetic retinopathy with angiotensin-converting enzyme inhibitor]. (2013)

Flicker-ERG (FERG) amplitude and glial indices Cg were measured to estimate angiotensin- converting enzyme (ACE) inhibitor Perindopril effect on retinal glial-neuronal interactions in patients with type II diabetes and diabetic retinopathy (DR). Intake of 5 mg Perindopril daily during 2 months improved photoreceptor and bipolar cells function in all stages of DR with the most significant effect in preproliferative DR (PPDR). After treatment course initially supernormal FERG scotopic glial indices reduced by 8,3-12 Hz (25-33%) in nonproliferative DR and PPDR and by 10% in proliferative DR. In photopic conditions moderate decrease of index was revealed in FERG by 30Hz only in PPDR. Obtained results show Perindopril to cause significant improvement of retinal glial-neuronal interactions in dark adaptation and poor positive dynamics in photopic conditions.
A novel form of complete IL-12/IL-23 receptor 1 deficiency with cell surface-expressed nonfunctional receptors (2004)

Complete interleukin-12/interleukin-23 receptor beta1 (IL-12Rbeta1) deficiency is the most frequent known genetic etiology of the syndrome of Mendelian susceptibility to mycobacterial disease. The patients described to date lack IL-12Rbeta1 at the surface of their natural killer (NK) and T cells due to IL12RB1 mutations, which either interrupt the open reading frame or disrupt protein folding. We describe a patient with a large in-frame deletion of 12165 nucleotides (nt) in IL12RB1, encompassing exons 8 to 13 and resulting in the surface expression of nonfunctional IL-12Rbeta1. These 6 exons encode the proximal NH2-terminal half of the extracellular domain downstream from the cytokine-binding domain. Five of 6 monoclonal anti-IL-12Rbeta1 antibodies tested recognized the internally truncated chain on the cell surface. However, IL-12 and IL-23 did not bind normally to the patient's IL-12Rbeta1-containing respective heterodimeric receptors. As a result, signal transducer and activator of transcription-4 (STAT4) was not phosphorylated and interferon-gamma (IFN-gamma) production was not induced in the patient's cells upon stimulation with even high doses of IL-12 or IL-23. The functional defect was completely rescued by retrovirus-mediated IL-12Rbeta1 gene transfer. Thus, the detection of IL-12Rbeta1 on the cell surface does not exclude the possibility of complete IL-12Rbeta1 deficiency in patients with mycobacteriosis or salmonellosis. Paradoxically, the largest IL12RB1 mutation detected is associated with the cell surface expression of nonfunctional IL-12Rbeta1, defining a novel genetic form of IL-12Rbeta1 deficiency.
Effects of thymoquinone (volatile oil of black cumin) on rheumatoid arthritis in rat models (2007)

Many studies have been carried out in recent years on the pharmacological effects of Nigella sativa seeds that have uncovered their antiinflammatory and immunological effects. The objective of this study was to explore the antiinflammatory effects of thymoquinone on arthritis in rat models. Rats with arthritis induced by Freund's incomplete adjuvant were assigned to five groups: group 1: controls 0.9% NaCl (n = 7); group 2: 2.5 mg/kg thymoquinone (n = 7); group 3: 5 mg/kg thymoquinone (n = 7); group 4: Bacilli Chalmette Guerin (BCG) 6 x 105 CFU (n = 7); group 5: methotrexate 0.3 mg/kg (n = 7). Signs of inflammation on the claw and radiological signs were searched for and TNF-alpha and IL-1beta were measured. The results of the control and other groups were compared. As a result, thymoquinone, confirmed clinically and radiologically, suppressed adjuvant-induced arthritis in rats.
Function Assignment to Conserved Residues in Mammalian Alkaline Phosphatases (2002)

We have probed the structural/functional relationship of key residues in human placental alkaline phosphatase (PLAP) and compared their properties with those of the corresponding residues in Escherichia coli alkaline phosphatase (ECAP). Mutations were introduced in wild-type PLAP, i.e. [E429]PLAP, and in some instances also in [G429]PLAP, which displays properties characteristic of the human germ cell alkaline phosphatase isozyme. All active site metal ligands, as well as residues in their vicinity, were substituted to alanines or to the homologous residues present in ECAP. We found that mutations at Zn2 or Mg sites had similar effects in PLAP and ECAP but that the environment of the Zn1 ion in PLAP is less affected by substitutions than that in ECAP. Substitutions of the Mg and Zn1 neighboring residues His-317 and His-153 increased k(cat) and increased K(m) when compared with wild-type PLAP, contrary to what was predicted by the reciprocal substitutions in ECAP. All mammalian alkaline phosphatases (APs) have five cysteine residues (Cys-101, Cys-121, Cys-183, Cys-467, and Cys-474) per subunit, not homologous to any of the four cysteines in ECAP. By substituting each PLAP Cys by Ser, we found that disrupting the disulfide bond between Cys-121 and Cys-183 completely prevents the formation of the active enzyme, whereas the carboxyl-terminally located Cys-467-Cys-474 bond plays a lesser structural role. The substitution of the free Cys-101 did not significantly affect the properties of the enzyme. A distinguishing feature found in all mammalian APs, but not in ECAP, is the Tyr-367 residue involved in subunit contact and located close to the active site of the opposite subunit. We studied the A367 and F367 mutants of PLAP, as well as the corresponding double mutants containing G429. The mutations led to a 2-fold decrease in k(cat), a significant decrease in heat stability, and a significant disruption of inhibition by the uncompetitive inhibitors l-Phe and l-Leu. Our mutagenesis data, computer modeling, and docking predictions indicate that this residue contributes to the formation of the hydrophobic pocket that accommodates and stabilizes the side chain of the inhibitor during uncompetitive inhibition of mammalian APs.
Effect of Sand Content on the Filter Cake Properties and Removal During Drilling Maximum Reservoir Contact Wells in Sandstone Reservoir (2015)

The drilling mud program contains many tests such as filtration rate and filter cake properties to select the proper drilling fluid additives that yield the standard ranges of the viscosity, filtration rate, etc. However, the physical and chemical changes in the mud composition during the mud circulating will cause changes to the filter cake properties. The changes in the filter cake properties should be considered in the mud design program to prevent the problems associated with the change in the drilling fluid properties. For long horizontal wellbores penetrating plastic formations, the two sources of solids in filter cake are drilling chemical additives and formation cuttings (sand particles in the case of sandstone reservoir). This study focuses on the effect of introducing sand particles from the drilled—formations on the filter cake properties. Real drilling fluid samples from the field were collected at different location during drilling a 3600 ft of the horizontal section of a sandstone formation. Calcium Carbonate (CaCO3) was used as weighting material in this filed. The drilling fluid samples were collected at two different points: the flow line coming from the well after shale shaker and the flow line going to the well to verify the effect of separation stages on filter cake properties. The primary drilling fluid properties of the collected samples were measured such as density and rheological parameters. High pressure high temperature (HPHT) filter press was used to perform the filtration and filter cake experiments at 300 psi differential pressure and room temperature (25 °C). The mineralogy of the external filter cake formed by fluid loss cell is determined using SEM (scanning electron microscopy) and XRD (X-ray diffraction). Finally, solubility test was conducted to evaluate the effect of sand particles on filter cake removal (containing Calcium Carbonate as weighting material) using chelating agent: glutamic diacetic acid (GLDA) at pH 4. The results showed that for long horizontal sections, the effect of introducing sand particles to the composition of the filter cake can cause significant change to the properties of filter cake such as mineralogy, thickness, porosity, and permeability. For instant the thickness of filter cake increased about 40% of its original thickness when drilling sandstone formation in horizontal well due to fine sand particle settling. The filter cake porosity and permeability increment in the first 2000 ft part of the horizontal section was observed clearly due to the irregular shape of the drilling particles. However for the points after the first 2000 ft of horizontal lateral, the porosity and permeability almost remained constant. Increasing the sand content up to 20% degrade the dissolution rate of calcium carbonate in the GLDA (pH = 3.8) to 80% instead of 100%.
Microbubble oscillation in tubes with diameters of 12, 25, and 195 microns (2006)

Ultrasound contrast agents are often used to measure flow rate in the microvasculature; however, the oscillation of these agents in capillary-sized tubes has not been directly observed. Here, oscillations of microbubbles are examined in microvessel phantoms with diameters similar to those of capillaries. High-speed camera images demonstrate the effects of ultrasonic pressure and tube diameter and length on microbubble expansion and fragmentation occurrence. Microbubble displacement due to radiation force is also demonstrated in a phantom microvessel.
Exosomes from Drug-Resistant Breast Cancer Cells Transmit Chemoresistance by a Horizontal Transfer of MicroRNAs (2014)

Adriamycin and docetaxel are two agents commonly used in treatment of breast cancer, but their efficacy is often limited by the emergence of chemoresistance. Recent studies indicate that exosomes act as vehicles for exchange of genetic cargo between heterogeneous populations of tumor cells, engendering a transmitted drug resistance for cancer development and progression. However, the specific contribution of breast cancer-derived exosomes is poorly understood. Here we reinforced other's report that human breast cancer cell line MCF-7/S could acquire increased survival potential from its resistant variants MCF-7/Adr and MCF-7/Doc. Additionally, exosomes of the latter, A/exo and D/exo, significantly modulated the cell cycle distribution and drug-induced apoptosis with respect to S/exo. Exosomes pre-treated with RNase were unable to regulate cell cycle and apoptosis resistance, suggesting an RNA-dependent manner. Microarray and polymerase chain reaction for the miRNA expression profiles of A/exo, D/exo, and S/exo demonstrated that they loaded selective miRNA patterns. Following A/exo and D/exo transfer to recipient MCF-7/S, the same miRNAs were significantly increased in acquired cells. Target gene prediction and pathway analysis showed the involvement of miR-100, miR-222, and miR-30a in pathways implicated in cancer pathogenesis, membrane vesiculation and therapy failure. Furthermore, D/exo co-culture assays and miRNA mimics transfection experiments indicated that miR-222-rich D/exo could alter target gene expression in MCF-7/S. Our results suggest that drug-resistant breast cancer cells may spread resistance capacity to sensitive ones by releasing exosomes and that such effects could be partly attributed to the intercellular transfer of specific miRNAs.
Synthesis of Chiral 1-(2‘-Amino-2‘-carboxyethyl)-1,4-dihydro-6,7-quinoxaline-2,3-diones:  α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate Receptor Agonists and Antagonists (1996)

Recently discovered 6,7-disubstituted quinoxaline-2,3-diones, 1, have been found to antagonize specific binding and functional responses to both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and kainic acid. Although a variety of studies have analyzed the activity of quinoxaline-2,3-diones with various substitutions at positions 6 and 7, there is little information regarding the effects of N-substitution. A racemic mixture of 1-(2'-amino-2'-carboxyethyl)-1,4-dihydroquinoxaline-2, 3-dione (QXAA, 2, R1 = R2 = H) has been synthesized from 1 (R1 = R2 = H). This compound inhibited specific [3H]AMPA binding but not [3H]kainate binding. IC50 values for QXAA, AMPA, and DNQX were 0.69, 0.012, and 0.74 microM, respectively. The R- and S-enantiomers were prepared by asymmetric synthesis. The S-isomer (2b) was 160-fold more potent in binding assays than the R-isomer (2d), with IC50 values of 0.23 and 38 microM, respectively. Both enantiomers were agonists in a functional assay, with the S-isomer having an EC50 value of 3 microM while that for the R-isomer was greater than 1 mM. Methyl substitutions at positions 6 and 7 (2a and 2c) resulted in antagonist compounds characterized by the S- and R-isomers being nearly equipotent, with IC50 values of 51 and 22 microM in the binding assay and EC50 values of 290 and 300 microM in the functional assay. AMPA had an EC50 value of 11 microM and DNQX an EC50 value of 30 microM in the functional assay. Analogs of quinoxalinediones with side chains other than an amino acid moiety on the nitrogen did not show good binding activities.
Mechanism of translation of monocistronic and multicistronic human immunodeficiency virus type 1 mRNAs. (1992)

We have used a panel of cDNA clones expressing wild-type and mutant human immunodeficiency virus type 1 (HIV-1) mRNAs to study translation of these mRNAs in eucaryotic cells. The tat open reading frame (ORF) has a strong signal for translation initiation, while rev and vpu ORFs have weaker signals. The expression of downstream ORFs is inhibited in mRNAs that contain the tat ORF as the first ORF. In contrast, downstream ORFs are expressed efficiently from mRNAs that have rev or vpu as the first ORF. All env mRNAs contain the upstream vpu ORF. Expression of HIV-1 Env protein requires a weak vpu AUG, which allows leaky scanning to occur, thereby allowing ribosomes access to the downstream env ORF. We concluded that HIV-1 mRNAs are translated by the scanning mechanism and that expression of more than one protein from each mRNA was caused by leaky scanning at the first AUG of the mRNA.
A Synthesis ofN-Substituted β-Alanines: Michael Addition of Amines to Trimethylsilyl Acrylate (1989)

The Michael addition of primary and secondary amines 2 to tromethylsilyl acrylate (1) afforded ß-(alkylamino)- and ß-(dialkylamino)-propionic acids 4, respectively, in good yield.
Biochemical and behavioural characterization of EMPA, a novel high‐affinity, selective antagonist for the OX2 receptor (2009)

EMPA is a high-affinity, reversible and selective OX(2) receptor antagonist, active in vivo, which should prove useful for analysis of OX(2) receptor function.
A Human Mitochondrial Transcription Factor Is Related to RNA Adenine Methyltransferases and Binds S-Adenosylmethionine (2002)

A critical step toward understanding mitochondrial genetics and its impact on human disease is to identify and characterize the full complement of nucleus-encoded factors required for mitochondrial gene expression and mitochondrial DNA (mtDNA) replication. Two factors required for transcription initiation from a human mitochondrial promoter are h-mtRNA polymerase and the DNA binding transcription factor, h-mtTFA. However, based on studies in model systems, the existence of a second human mitochondrial transcription factor has been postulated. Here we report the isolation of a cDNA encoding h-mtTFB, the human homolog of Saccharomyces cerevisiae mitochondrial transcription factor B (sc-mtTFB) and the first metazoan member of this class of transcription factors to which a gene has been assigned. Recombinant h-mtTFB is capable of binding mtDNA in a non-sequence-specific fashion and activates transcription from the human mitochondrial light-strand promoter in the presence of h-mtTFA in vitro. Remarkably, h-mtTFB and its fungal homologs are related in primary sequence to a superfamily of N6 adenine RNA methyltransferases. This observation, coupled with the ability of recombinant h-mtTFB to bind S-adenosylmethionine in vitro, suggests that a structural, and perhaps functional, relationship exists between this class of transcription factors and this family of RNA modification enzymes and that h-mtTFB may perform dual functions during mitochondrial gene expression.
The ε Isoform of 14-3-3 Protein Is a Component of the Prion Protein Amyloid Deposits of Gerstmann-Sträussler-Scheinker Disease (2007)

The 14-3-3 proteins are highly conserved, ubiquitous molecules involved in a variety of biologic events, such as transduction pathway modulation, cell cycle control, and apoptosis. Seven isoforms have been identified that are abundant in the brain, preferentially localized in neurons. Remarkable increases in 14-3-3 are seen in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease (CJD), and it has been found in pathologic inclusions of several neurodegenerative diseases. Moreover, the zeta isoform has been detected in prion protein (PrP) amyloid deposits of CJD patients. To further investigate the cerebral distribution of 14-3-3 in prion-related encephalopathies, we carried out an immunohistochemical and biochemical analysis of brain tissue from patients with Gerstmann-Sträussler-Scheinker disease (GSS) and sporadic, familial and acquired forms of CJD, using specific antibodies against the seven 14-3-3 isoforms. The study showed a strong immunoreactivity of PrP amyloid plaques of GSS patients for the 14-3-3 epsilon isoform, but not for the other isoforms. The epsilon isoform of 14-3-3 was not found in PrP deposits of CJD. These results indicate that the epsilon isoform of 14-3-3 is a component of PrP amyloid deposits of GSS and suggest that this is the sole 14-3-3 isoform specifically involved in the neuropathologic changes associated with this disorder.
INX-08189, a Phosphoramidate Prodrug of 6-O-Methyl-2′-C-Methyl Guanosine, Is a Potent Inhibitor of Hepatitis C Virus Replication with Excellent Pharmacokinetic and Pharmacodynamic Properties (2011)

INX-08189 is an aryl-phosphoramidate of 6-O-methyl-2'-C-methyl guanosine. INX-08189 was highly potent in replicon assays, with a 50% effective concentration of 10±6 nM against hepatitis C genotype 1b at 72 h. The inhibitory effect on viral replication was rapid, with a 50% effective concentration (EC50) of 35±8 nM at 24 h. An intracellular 2'-C-methyl guanosine triphosphate (2'-C-MeGTP) concentration of 2.43±0.42 pmol/10(6) cells was sufficient to achieve 90% inhibition of viral replication. In vitro resistance studies confirmed that the S282T mutation in the NS5b gene conferred an approximately 10-fold reduction in sensitivity to INX-08189. However, the complete inhibition of S282T mutant replicons still could be achieved with an EC90 of 344±170 nM. Drug combination studies of INX-08189 and ribavirin indicated significant synergy in antiviral potency both in wild-type and S282T-expressing replicons. Genotype 1b replicons could be cleared after 14 days of culture when exposed to as little as 20 nM INX-08189. No evidence of mitochondrial toxicity was observed after 14 days of INX-08189 exposure in both HepG2 and CEM human cell lines. In vivo studies of rats and cynomolgus monkeys demonstrated that 2'-C-MeGTP concentrations in liver equivalent to the EC90 could be attained after a single oral dose of INX-08189. Rat liver 2'-C-MeGTP concentrations were proportional to dose, sustained for greater than 24 h, and correlated with plasma concentrations of the nucleoside metabolite 2'-C-methyl guanosine. The characteristics displayed by INX-08189 support its continued development as a clinical candidate for the treatment of chronic HCV infection.
A pilot study of surfactant inhalation in the treatment of asthmatic attack. (1991)

The pulmonary surfactant is thought to be important in the stability of the small airways. In this study, we conducted a double-blind, placebo-controlled trial to determine whether surfactant inhalation has a therapeutic effect in asthmatic attack. Eleven patients with asthmatic attack whose conditions were stable for at least six hours before the study were randomly assigned to placebo or surfactant inhalation. Respiratory function tests and blood gas analysis were performed before and 20 minutes after the treatment. After placebo administration, no significant change was observed from baseline in pulmonary functions. After surfactant administration (1 ml; 10 mg per milliliter), respiratory functions were markedly improved in all patients. The mean (+/- SE) change in the FVC, FEV1.0, MMF, delta N2 and PaO2 was, respectively, an increase of 11.7 +/- 1.3% (p less than 0.001), an increase of 27.3 +/- 4.4% (p less than 0.05), an increase of 33.3 +/- 4.7% (p less than 0.05), a decrease of 31 +/- 8.4% (p less than 0.05) and an increase of 13.4 +/- 0.8% (p less than 0.05). No difference was detected in PaCO2 after surfactant inhalation. This study indicates that airway surfactant is involved in the pathogenesis of bronchoobstruction of the patients with asthma.
Microbial Signalling and Communication (1999)

Preface 1. Overview P. Williams 2. Intercellular signalling and the multiplication of prokaryotes: bacterial cytokines A. S. Kaprelyants, G. V. Mukamolova, S. S. Kormer, D. H. Weichart, M. Young and D. B. Kell 3. Quorum sensing in gram-negative bacteria: acylhomoserine lactone signalling and cell-cell communication E. P. Greenberg 4. Homoserine-lactones and non Vibrio signalling mechanisms G. S. A. B. Stewart 5. Signalling in Pseudomonas E. C. Pesci and B. H. Iglewski 6. Sex pheromones of Enterococcus faecalis G. M. Dunny 7. Intercellular signalling in the control of of cell density and development of Myxococcus xanthus D. Kaiser 8. Beta-lactam production in response to signalling G. P. C. Salmond 9. Autoregulatory factors and regulation of antibiotic production in Streptomyces Y. Yamada 10. Signalling in pathogenic bacteria G. M. Frankel 11. Communication between Yersinia and host cells G. R. Cornelis 12. Mathematical modelling of signalling in Dictyostelium discoideum J. A. Sherratt, J. C. Dallon, T. Hofer and P. K. Maini 13. Pheromone communication in the fission yeast Schizosaccharomyces pombe J. Davey 14. Zoospoe-Zoospore and Zoospore-plant signalling N. A. R. Gow 15. Signalling in dinoflagellates J. Burkholder 16. Hyphal interactions G. Gooday 17. Index.
Cardiorenal Syndrome Type 4: A Review (2013)

There is a bidirectional and complex relationship between the heart and kidneys. This interaction is physical, chemical as well as biological and is also reflected in a strong connection between renal and cardiovascular diseases. Cardiorenal syndrome type 4 (CRS type 4) is characterized by primary chronic kidney disease (CKD) leading to an impairment of cardiac function, with ventricular hypertrophy, diastolic dysfunction, and/or increased risk of adverse cardiovascular events. The incidence of CKD is increasing, and CRS type 4 is becoming a major public health problem associated with a high morbidity and mortality. In this study, we briefly review the epidemiology and pathophysiology of CRS type 4, the role of biomarkers in its early identification, and its management.