gebhart/patrepeval huggingface dataset:
Dexamethasone Is a Novel Potent Inducer of Connective Tissue Growth Factor Expression (1998)

Due to its potent effect on fibroblast proliferation and extracellular matrix deposition, connective tissue growth factor (CTGF) seems to play an important role in the pathogenesis of fibrotic disease. Since glucocorticoids are frequently used for the therapy of these disorders, we determined a potential effect of these steroids on CTGF expression. In cultured fibroblasts, a striking induction of CTGF expression was observed after dexamethasone treatment and occurred in a time- and dose-dependent manner. This effect was obviously not mediated by the CTGF inducer transforming growth factor-beta1, since expression of this factor was down-regulated by the glucocorticoid. Most importantly, CTGF expression levels also increased substantially in various tissues and organs by systemic glucocorticoid treatment of mice. After cutaneous injury, a strong induction of CTGF expression was seen in the wounds of nontreated mice. However, no further increase in the levels of CTGF mRNA occurred in wounded skin compared with unwounded skin of glucocorticoid-treated animals, suggesting the presence of other factors in the wound that might compensate for the effect of the steroids. Tumor necrosis factor-alpha was identified as a possible mediator of this effect because this factor suppressed CTGF expression in cultured fibroblasts and also blocked the glucocorticoid-induced CTGF production by these cells. These findings indicate that glucocorticoids stimulate CTGF expression in normal tissues and organs but not in highly inflamed areas.
Arylsulphatase from Alteromonas carrageenovora (1995)

Arylsulphatase activity was identified in cultures of the marine bacterium Alteromonas carrageenovora, using methylumbelliferyl sulphate as substrate. In contrast with most other microbial arylsulphatases, arylsulphatase production in A. carrageenovora was not repressed by sulphate. The structural gene of arylsulphatase (atsA) was cloned and sequenced. An ORF of 984 bp was found, specifying a primary translation product of 328 amino acids with a molecular mass of 35797 Da. Arylsulphatase was partially purified from cell extracts of both A. carrageenovora and recombinant Escherichia coli. Both the recombinant and native enzymes exhibited a pI of 5.5, a Michaelis constant for methylumbelliferyl sulphate of 68 microM, and a molecular mass of approximately 35,000 Da in SDS-PAGE analysis. Secondary structure comparisons using hydrophobic cluster analysis suggest functional analogies between the arylsulphatase of A. carrageenovora, that of Mycobacterium leprae and a 33.5 kDa protein from Porphyromonas gingivalis. It is speculated that these proteins are all glycosulphohydrolases, involved with desulphatation of sulphated polysaccharides.
The Synergistic Effects of His-D-Trp-Ala-Trp-D-Phe- Lys-NH2on Growth Hormone (GH)-Releasing Factor- Stimulated GH Release and Intracellular Adenosine 3',5'-Monophosphate Accumulation in Rat Primary Pituitary Cell Culture (1989)

His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6) stimulated GH release from rat primary pituitary cells in a time- and dose-dependent manner. Stimulation was observed after a 15-min, but not a 4-h, incubation. The concentrations of GHRP-6 required for half-maximal and maximal stimulation were 7 x 10(-9) and 10(-7) M, respectively. GH release induced by GHRP-6 was not affected by the addition of either naloxone or the GRF antagonist [N-Ac-Tyr1,D-Arg2]GRF-(1-29)-NH2. The latter inhibited GRF-stimulated GH release by shifting the dose-response curve to the right. His-D-Trp-D-Lys-Trp-D-Phe-Lys-NH2, an analog of GHRP-6, inhibited GH release stimulated by GHRP-6 without affecting that induced by GRF. When present together at maximal concentrations, GHRP-6 and GRF produced a synergistic effect on GH release. GHRP-6 had no effect on intracellular cAMP levels, whereas GRF increased intracellular cAMP concentrations by 3-fold. Combined treatment of pituitary cells with GRF and GHRP-6 resulted in a potentiation of the GRF-induced increase in cAMP levels. Basal GH release was reduced by 30% after pretreatment with GHRP-6 (10(-7) M) for 1 h. Pretreatment with GHRP-6 also decreased the subsequent response to GHRP-6, but not GRF. In contrast, pretreatment with GRF for 1 h had no effect on the subsequent action of GHRP-6 or GRF on GH release. The desensitization induced by GHRP-6 was completely reversed within 1 h after removal of the peptide. Results from this study indicate that GHRP-6 and GRF stimulated GH release from somatotrophs via different receptors and through discrete mechanisms.
Design of satellite terminal for Ballistic Missile Defense Organization (BMDO) lasercom technology demonstration (1995)

Laser communications offers the potential for transferring information at data rates higher than 1 Gigabit per second (Gb/s) between satellites, aircraft, and ground sites using terminals with weights between 15 and 30 pounds, and volumes less than 1 cubic foot. The Ballistic Missile Defense Organization (BMDO), contracting through the U.S. Army Space and Strategic Command, has been funding the development of laser communications technology and demonstration hardware. Applications of near term interest include inter-satellite crosslinks, Low Earth Orbit satellite downlinks to the ground, and Aircraft-to-Aircraft crosslinks. To demonstrate the capability and readiness of laser communications for these applications, we are building a space capable laser communications terminal to be flown on BMDO's STRV-2 experiment with a projected launch date in 1997. The design of that terminal is based on direct modulation of semiconductor lasers, direct detection using avalanche photodiodes, separate acquisition/tracking and communications wavelengths, separate transmit and receive apertures, and a simple optical transceiver package mounted on a hemispherical field of regard gimbal.
Effects of docosahexaenoic acid on retinal development: Cellular and molecular aspects (2001)

We have recently shown that docosahexaenoic acid (DHA) is necessary for survival and differentiation of rat retinal photoreceptors during development in vitro. In cultures lacking DHA, retinal neurons developed normally for 4 d; then photoreceptors selectively started an apoptotic pathway leading to extensive degeneration of these cells by day 11. DHA protected photoreceptors by delaying the onset of apoptosis; in addition, it advanced photoreceptor differentiation, promoting opsin expression and inducing apical differentiation in these neurons. DHA was the only fatty acid having these effects. Mitochondrial damage accompanied photoreceptor apoptosis and was markedly reduced upon DHA supplementation. This suggests that a possible mechanism of DHA-mediated photoreceptor protection might be the preservation of mitochondrial activity; a critical amount of DHA in mitochondrial phospholipids might be required for proper functioning of these organelles, which in turn might be essential to avoid cell death. Müller cells in culture appeared to be involved in DHA processing: they took up DHA, incorporated it into glial phospholipids, and channeled it to photoreceptors in coculture. Both Müller cells, when cocultured with neuronal cells, and the glial-derived neurotrophic factor (GDNF) protected photoreceptors from cell death. These results suggest that glial cells may play a central role in regulating photoreceptor survival during development through the provision of trophic factors. The multiple effects of DHA on photoreceptors suggest that, in addition to its structural role, DHA might be one of the trophic factors required by these cells.
Nanopore-Based Single-Molecule DNA Analysis (2007)

Nanopore-based DNA analysis is a single-molecule technique with revolutionary potential. It promises to carry out a range of analyses, orders of magnitude faster than current methods, including length measurement, specific sequence detection, single-molecule dynamics and even de novo sequencing. The concept involves using an applied voltage to drive DNA molecules through a narrow pore that separates chambers of electrolyte solution. This voltage also drives a flow of electrolyte ions through the pore, measured as an electric current. When molecules pass through the pore, they block the flow of ions and, thus, their structure and length can be determined based on the degree and duration of the resulting current reductions. In this review, I explain the nanopore-based DNA analysis concept and briefly explore its historical foundations, before discussing and summarizing all experimental results reported to date. I conclude with a summary of the obstacles that must be overcome for it to realize its promised potential.
Biogeographic and Phylogenetic Diversity of Thermoacidophilic Cyanidiales in Yellowstone National Park, Japan, and New Zealand (2008)

Members of the rhodophytan order Cyanidiales are unique among phototrophs in their ability to live in extreme environments that combine low pH levels ( approximately 0.2 to 4.0) and moderately high temperatures of 40 to 56 degrees C. These unicellular algae occur in far-flung volcanic areas throughout the earth. Three genera (Cyanidium, Galdieria, and Cyanidioschyzon) are recognized. The phylogenetic diversity of culture isolates of the Cyanidiales from habitats throughout Yellowstone National Park (YNP), three areas in Japan, and seven regions in New Zealand was examined by using the chloroplast RuBisCO large subunit gene (rbcL) and the 18S rRNA gene. Based on the nucleotide sequences of both genes, the YNP isolates fall into two groups, one with high identity to Galdieria sulphuraria (type II) and another that is by far the most common and extensively distributed Yellowstone type (type IA). The latter is a spherical, walled cell that reproduces by internal divisions, with a subsequent release of smaller daughter cells. This type, nevertheless, shows a 99 to 100% identity to Cyanidioschyzon merolae (type IB), which lacks a wall, divides by "fission"-like cytokinesis into two daughter cells, and has less than 5% of the cell volume of type IA. The evolutionary and taxonomic ramifications of this disparity are discussed. Although the 18S rRNA and rbcL genes did not reveal diversity among the numerous isolates of type IA, chloroplast short sequence repeats did show some variation by location within YNP. In contrast, Japanese and New Zealand strains showed considerable diversity when we examined only the sequences of 18S and rbcL genes. Most exhibited identities closer to Galdieria maxima than to other strains, but these identities were commonly as low as 91 to 93%. Some of these Japanese and New Zealand strains probably represent undescribed species that diverged after long-term geographic isolation.
Design of Functionalized Room-Temperature Ionic Liquid-Based Materials for CO2Separations and Selective Blocking of Hazardous Chemical Vapors (2012)

The design and synthesis of several new types of functionalized room-temperature ionic liquids (RTILs), ionic polymers based on RTILs (i.e., poly(RTIL)s), poly(RTIL)-RTIL solid-liquid composites, and gelled RTIL systems for gas separations and reactive vapor transport applications are presented. The design concepts behind these new RTIL materials are discussed in the context of first, CO2 removal from CH4 and N2 for natural gas purification and greenhouse gas reduction, respectively; and second selective blocking or sorption of chemical warfare agent simulant and toxic industrial compound vapors from water vapor for protection applications. The role of the RTIL components and their unique properties in these two separations areas will be highlighted.
In vivo high-frequency ultrasonic characterization of human dermis (1999)

The aim of this study is in vivo skin tissue characterization of young and old human cutaneous tissues by estimating the slope of the attenuation coefficient. The method used is the centroid algorithm with a second-order autoregressive model to perform the spectral analysis. Backscattered signals are acquired with a 40-MHz transducer fixed on a three-dimensional robot. Diffraction phenomena are eliminated via an axial translation of the transducer that allows the acquisition of the signal in the focal zone. The slope of the attenuation coefficient is estimated on phantoms of known attenuation, in order to validate the method. Preliminary measurements of the slope of the attenuation coefficient are subsequently performed in the echographic mode on abdominal human skin samples in vitro at 40 MHz. After assessing the reproducibility of the measurement of the attenuation coefficient slope in human dermis at 40-MHz in vivo, this is carried out on the volar face of the forearm of 150 healthy subjects aged 14-85 yr. The values measured range from 0.7 to 3.6 dB/cm.MHz. The main result of this study is the decrease with advancing age of the attenuation coefficient slope, which may reflect structural modifications of human dermis with age.
Discovery of (S)-6-(3-Cyclopentyl-2-(4-(trifluoromethyl)-1H-imidazol-1-yl)propanamido)nicotinic Acid as a Hepatoselective Glucokinase Activator Clinical Candidate for Treating Type 2 Diabetes Mellitus (2011)

Glucokinase is a key regulator of glucose homeostasis, and small molecule allosteric activators of this enzyme represent a promising opportunity for the treatment of type 2 diabetes. Systemically acting glucokinase activators (liver and pancreas) have been reported to be efficacious but in many cases present hypoglycaemia risk due to activation of the enzyme at low glucose levels in the pancreas, leading to inappropriately excessive insulin secretion. It was therefore postulated that a liver selective activator may offer effective glycemic control with reduced hypoglycemia risk. Herein, we report structure-activity studies on a carboxylic acid containing series of glucokinase activators with preferential activity in hepatocytes versus pancreatic β-cells. These activators were designed to have low passive permeability thereby minimizing distribution into extrahepatic tissues; concurrently, they were also optimized as substrates for active liver uptake via members of the organic anion transporting polypeptide (OATP) family. These studies lead to the identification of 19 as a potent glucokinase activator with a greater than 50-fold liver-to-pancreas ratio of tissue distribution in rodent and non-rodent species. In preclinical diabetic animals, 19 was found to robustly lower fasting and postprandial glucose with no hypoglycemia, leading to its selection as a clinical development candidate for treating type 2 diabetes.
Extending autocompletion to tolerate errors (2009)

Autocompletion is a useful feature when a user is doing a look up from a table of records. With every letter being typed, autocompletion displays strings that are present in the table containing as their prefix the search string typed so far. Just as there is a need for making the lookup operation tolerant to typing errors, we argue that autocompletion also needs to be error-tolerant. In this paper, we take a first step towards addressing this problem. We capture input typing errors via edit distance. We show that a naive approach of invoking an offline edit distance matching algorithm at each step performs poorly and present more efficient algorithms. Our empirical evaluation demonstrates the effectiveness of our algorithms.
Modular Organization of T4 DNA Polymerase (1995)

We describe the use of a phylogenetic approach to analyze the modular organization of the single-chained (898 amino acids) and multifunctional DNA polymerase of phage T4. We have identified, cloned in expression vectors, and sequenced the DNA polymerase gene (gene 43) of phage RB69, a distant relative of T4. The deduced primary structure of the RB69 protein (RB69 gp43) differs from that of T4 gp43 in discrete clusters of short sequence that are interspersed with clusters of high similarity between the two proteins. Despite these differences, the two enzymes can substitute for each other in phage DNA replication, although T4 gp43 does exhibit preference to its own genome. A 55-amino acid internal gp43 segment of high sequence divergence between T4 and RB69 could be replaced in RB69 gp43 with the corresponding segment from T4 without loss of replication function. The reciprocal chimera and a deletion mutant of the T4 gp43 segment were both inactive for replication and specifically inhibitory ("dominant lethal") to the T4 wild-type allele. The results show that phylogenetic markers can be used to construct chimeric and truncated froms of gp43 that, although inactive for replication, can still exhibit biological specificity.
Identification of Putative c-Myc-Responsive Genes: Characterization of rcl , a Novel Growth-Related Gene† (1997)

The c-Myc protein is a helix-loop-helix leucine zipper oncogenic transcription factor that participates in the regulation of cell proliferation, differentiation, and apoptosis. The biochemical function of c-Myc has been well described, yet the identities of downstream effectors are just beginning to emerge. We describe the identification of a set of c-Myc-responsive genes in the Rat1a fibroblast through the application of cDNA representational difference analysis (RDA) to cDNAs isolated from nonadherent Rat1a and Rat1a-myc cells. In this system, c-Myc overexpression is sufficient to induce the transformed phenotype of anchorage-independent growth. We identified 20 differentially expressed cDNAs, several of which represent novel cDNA sequences. We further characterized one of the novel cDNAs identified in this screen, termed rcl. rcl expression is (i) directly stimulated by c-Myc; (ii) stimulated in the in vivo growth system of regenerating rat liver, as is c-myc; and (iii) elevated in human lymphoid cells that overexpress c-myc. By using an anti-Rcl antibody, immunoblot analysis, and immunofluorescence microscopy, the Rcl protein was found to be a 23-kDa nuclear protein. Ectopic expression of the protein encoded by the rcl cDNA induces anchorage-independent growth in Rat1a fibroblasts, albeit to a diminished extent compared to ectopic c-Myc expression. These data suggest a role for rcl during cellular proliferation and c-Myc-mediated transformation.
Comparison of NEMA and ultra-high slip motors on cyclic loads (1989)

Cyclic loads, such as eccentric pumping units, cause a varying torque on the driver. Determination of the most efficient induction motor for such a load is discussed. Ultra-high-slip motors as well as NEMA design motors are evaluated. Operating costs and investment are compared. The study indicates that: (1) any type of motor will work on a pumping unit; (2) the motor must be carefully sized to provide minimum operating cost; (3) the least expensive operating cost and the smallest investment are for the motors with the least slip; (4) the lower slip motors cause an increase in peak torque on the unit; and (5) an accurate computer model with an easy-to-use program that allows 'what if' options is highly desirable. >
Identification of Defensin-1, Defensin-2, and CAP37/Azurocidin as T-cell Chemoattractant Proteins Released from Interleukin-8-stimulated Neutrophils (1996)

Reports that interleukin-8 (IL-8) induces the infiltration of neutrophils followed by T-cells into injection sites led us to postulate that by stimulation of neutrophil degranulation IL-8 may cause the release of factors with chemoattractant activity for T-lymphocytes. Extracts of human neutrophil granules were chromatographed to isolate and purify T-lymphocyte chemoattractant factors. Two major peaks of T-cell chemotactic activity were purified by C18 reversed phase high pressure liquid chromatography (HPLC). The first peak was resolved further by C4 reversed phase HPLC and yielded an active fraction shown by NH2-terminal amino acid sequence analysis to contain defensins HNP-1, HNP-2, and HNP-3. Purified defensins HNP-1 and HNP-2 (kindly provided by Dr. R. I. Lehrer, UCLA) were also potent chemoattractants for human T-cells, while HNP-3 was inactive. The second peak of T-cell chemoattractant activity was also further purified to homogeneity by C4 reversed phase HPLC and identified by NH2-terminal sequence analysis as CAP37/azurocidin, a protein with sequence homology to serine proteases. 0.1 100 ng of defensins and 1.0 100 ng/ml CAP37 were able to stimulate in vitro T-cell chemotaxis. Neutrophil activating factors, i.e. IL-8, phorbol 12-myristate 13-acetate/ionomycin, and formylmethionylleucylphenylalanine each induced the release of CAP37 and defensins from neutrophil granules. Subcutaneous administration of defensins or CAP37/azurocidin into BALB/c mice resulted in a moderate neutrophil and mononuclear cell infiltrate by 4 h, which was greater by 24 h at the site of injection. Additionally, subcutaneous injection of defensins into chimeric huPBL-SCID mice resulted in significant infiltration by human CD3+ cells within 4 h. These results identify the antimicrobial proteins, CAP37/azurocidin and defensins HNP-1 and HNP-2, as potent neutrophil-derived chemoattractants for T-cells. These proteins represent primordial antimicrobial peptides which may have evolved into acute inflammatory cell-derived signals that mobilize immunocompetent T-cells and other inflammatory cells.
Evaluation of a new system for ventilatory administration of nitric oxide (1993)

A new system for delivery of nitric oxide (NO) to inspiratory gas consisting of two mass flow regulators and a soda-lime absorber for scavenging of nitrogen dioxide (NO2) is described. The system was evaluated using three different techniques for NO analysis (infrared, chemiluminescence and electro-chemical fuel cell technique). The electro-chemical fuel cell was less sensitive to humidity in the sample and is suitable for clinical routine use. The infrared analyser was very sensitive to humidity and the gas sample must be dried by silica gel, which absorbs NO2 and will cause falsely low NO2 values. NO2 was analysed with ultra-violet methodology. NO2 is highly toxic and the highest recommended occupational health and safety level for inhalation is 5 ppm. The highest values of NO2 in our system were detected before the absorber in the inspiratory limb of the breathing system, being 5 ppm at 100% oxygen and 100 ppm NO using "infant" respiratory settings (3 l/min in ventilation, frequency of 30/min). The corresponding value for "adult" respiratory settings (10 l/min in ventilation, frequency of 15/min) was 3.2 ppm. The absorber reduced these levels to well below 1 ppm. When clinically relevant levels of NO were used (20 ppm), no NO2 could be detected after the absorber, irrespective of oxygen concentration in the breathing gas. It was observed that gas cylinders with NO mixed in nitrogen may initially have a high NO2 concentration (around 12 ppm) and should be flushed thoroughly before use.