gebhart/patrepeval huggingface dataset:
Recent progress in the development of coumarin derivatives as potent anti‐HIV agents (2003)

Numerous plant-derived compounds have been evaluated for inhibitory effects against HIV replication, and some coumarins have been found to inhibit different stages in the HIV replication cycle. This review article describes recent progress in the discovery, structure modification, and structure-activity relationship studies of potent anti-HIV coumarin derivatives. A dicamphanoyl-khellactone (DCK) analog, which was discovered and developed in our laboratory, and calanolide A are currently in preclinical studies and clinical trials, respectively.
DNA Arrays Reveal Cancer in Its Many Forms (2000)

The use of microarrays--slides or chips systematically dotted with DNA from thousands of genes--to determine gene expression patterns is providing a wealth of new information that should aid in cancer diagnosis and ultimately in therapy. In the past several months, researchers in several labs have used microarray technology to identify specific subtypes of a variety of cancers, including leukemias and lymphomas, the dangerous skin cancer melanoma, and breast cancer. In some cases, they can determine which cancers are likely to respond to current therapies and which aren't. In addition, the studies are giving researchers a fix on which genes are important for the development, maintenance, and spread of the various cancers, and are thus possible drug targets.
Chromosome position effects on gene expression in Escherichia coli K-12 (2014)

In eukaryotes, the location of a gene on the chromosome is known to affect its expression, but such position effects are poorly understood in bacteria. Here, using Escherichia coli K-12, we demonstrate that expression of a reporter gene cassette, comprised of the model E. coli lac promoter driving expression of gfp, varies by ∼300-fold depending on its precise position on the chromosome. At some positions, expression was more than 3-fold higher than at the natural lac promoter locus, whereas at several other locations, the reporter cassette was completely silenced: effectively overriding local lac promoter control. These effects were not due to differences in gene copy number, caused by partially replicated genomes. Rather, the differences in gene expression occur predominantly at the level of transcription and are mediated by several different features that are involved in chromosome organization. Taken together, our findings identify a tier of gene regulation above local promoter control and highlight the importance of chromosome position effects on gene expression profiles in bacteria.
Overexpression of [delta]-Pyrroline-5-Carboxylate Synthetase Increases Proline Production and Confers Osmotolerance in Transgenic Plants (1995)

Proline (Pro) accumulation has been correlated with tolerance to drought and salinity stresses in plants. Therefore, overproduction of Pro in plants may lead to increased tolerance against these abiotic stresses. To test this possibility, we overexpressed in tobacco the mothbean [delta]-pyrroline-5-carboxylate synthetase, a bifunctional enzyme able to catalyze the conversion of glutamate to [delta]-pyrroline-5-carboxylate, which is then reduced to Pro. The transgenic plants produced a high level of the enzyme and synthesized 10- to 18-fold more Pro than control plants. These results suggest that activity of the first enzyme of the pathway is the rate-limiting factor in Pro synthesis. Exogenous supply of nitrogen further enhanced Pro production. The osmotic potentials of leaf sap from transgenic plants were less decreased under water-stress conditions compared to those of control plants. Overproduction of Pro also enhanced root biomass and flower development in transgenic plants under drought-stress conditions. These data demonstrated that Pro acts as an osmoprotectant and that overproduction of Pro results in the increased tolerance to osmotic stress in plants.
Light modulation of Rubisco in Arabidopsis requires a capacity for redox regulation of the larger Rubisco activase isoform (2002)

The light activation of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) in vivo requires the presence of Rubisco activase, a nuclear-encoded chloroplast protein that consists of two isoforms arising from alternative splicing in most plants. We examined the function of each isoform by characterizing Rubisco activation in transgenic Arabidopsis plants that express only one or both isoforms, as compared with the wild type. In plants expressing only the shorter isoform, Rubisco activity was as high as in the wild type under saturating light, but the activity was not down-regulated at intensities limiting for photosynthesis. In contrast, in plants expressing only the longer isoform, Rubisco activity was down-regulated at limiting light, but the activity was slightly lower and increased much more slowly at saturating light intensities as compared with the wild type. Light regulation of Rubisco similar to that in the wild-type plants was observed in the progeny of a genetic cross of these two transformants in which both isoforms were again present. When the capacity to redox regulate the activity of the larger activase isoform was eliminated by replacement of the critical cysteine residues in the carboxyl-terminal extension unique to this isoform, Rubisco activity in saturating light was similar to the wild type, but the ability of the larger isoform to down-regulate Rubisco activity at limiting light intensities in transgenic plants was almost abolished. These results indicate that the light modulation of Rubisco under limiting light is mainly due to the ability to regulate the activity of Rubisco activase by redox changes in the stroma.
Evolutionarily Conserved Function of a Viral MicroRNA (2008)

MicroRNAs (miRNAs) are potent RNA regulators of gene expression. Some viruses encode miRNAs, most of unknown function. The majority of viral miRNAs are not conserved, and whether any have conserved functions remains unclear. Here, we report that two human polyomaviruses associated with serious disease in immunocompromised individuals, JC virus and BK virus, encode miRNAs with the same function as that of the monkey polyomavirus simian virus 40 miRNAs. These miRNAs are expressed late during infection to autoregulate early gene expression. We show that the miRNAs generated from both arms of the pre-miRNA hairpin are active at directing the cleavage of the early mRNAs. This finding suggests that despite multiple differences in the miRNA seed regions, the primary target (the early mRNAs) and function (the downregulation of early gene expression) are evolutionarily conserved among the primate polyomavirus-encoded miRNAs. Furthermore, we show that these miRNAs are expressed in individuals diagnosed with polyomavirus-associated disease, suggesting their potential as targets for therapeutic intervention.
PAR1 Thrombin Receptor-G Protein Interactions (2000)

Signal transfer between the protease-activated PAR1 thrombin receptor and membrane-associated heterotrimeric G proteins is mediated by protein-protein interactions. We constructed a yeast signaling system that resolves domain-specific functions of binding from coupling in the Galpha subunit. The endogenous yeast Galpha subunit, Gpa1, does not bind to PAR1 and served as a null structural template. N- and C-terminal portions of mammalian G(i2) and G(16) were substituted back into the Gpa1 template and gain-of-function assessed. The C-terminal third of G(16), but not of G(i2), provides sufficient interactions for coupling to occur with PAR1. The N-terminal two-thirds of G(i2) also contains sufficient determinants to bind and couple to PAR1 and overcome the otherwise negative or missing interactions supplied by the C-terminal third of Gpa1. Replacement of the N-terminal alpha-helix of G(i2), residues 1-34, with those of Gpa1 abolishes coupling but not binding to PAR1 or to betagamma subunits. These data support a model that the N-terminal alphaN helix of the Galpha subunit is physically interposed between PAR1 and the Gbeta subunit and directly assists in transferring the signal between agonist-activated receptor and G protein.
PEA I and PEA II based implantable haemodynamic monitor: pre clinical studies in sheep (2002)

The simultaneous recording of PEA I and PEA II with an implantable system offers a new chance to monitor indexes of LV systolic and diastolic function.
Prospective comparison of the immune response of infants to three Haemophilus influenzae type b vaccines (1991)

The antibody response to three Haemophilus influenzae type b vaccines was examined in 134 infants 17 to 22 months of age. Sera were collected from each subject before and 1 month after vaccination with either purified H. influenzae type b capsular polysaccharide (polyribosyl-ribitol phosphate (PRP] or one of two protein-conjugated vaccines (PRP-D or HbOC). Comparison of the two conjugate vaccines revealed that HbOC produced an antibody response greater than or equal to 1.0 micrograms/ml in 96% compared with 72% who were vaccinated with PRP-D (P less than 0.05). The isotype distribution of the antibodies produced by the two vaccines was similar. While all of the vaccines resulted in higher concentrations of anticapsular IgG1 than IgG2, the IgG1:IgG2 ratio was significantly higher in subjects immunized with HbOC. The IgG1:IgG2 ratio was similar in subjects immunized with PRP or PRP-D. The clinical significance of these observations remains to be determined.
cDNA Library Preparation (2013)

The construction of full-length cDNA libraries allows researchers to study gene expression and protein interactions and undertake gene discovery. Recent improvements allow the construction of high-quality cDNA libraries, with small amounts of mRNA. In parallel, these improvements allow for the incorporation of adapters into the cDNA, both at the 5' and 3' end of the cDNA. The 3' adapter is attached to the oligo-dT primer that is used by the reverse transcriptase, whereas the 5' adapter is incorporated by the template switching properties of the MMLV reverse transcriptase. This allows directional cloning and eliminates inefficient steps like adapter ligation, phosphorylation, and methylation. Another important step in the construction of high-quality cDNA libraries is the normalization. The difference in the levels of expression between genes might be several orders of magnitude. Therefore, it is essential that the cDNA library is normalized. With a recently discovered enzyme, duplex-specific nuclease, it is possible to normalize the cDNA library, based on the fact that more abundant molecules are more likely to reanneal after denaturation compared to rare molecules.
Role of NO in Flow-Induced Remodeling of the Rabbit Common Carotid Artery (1996)

Flow-induced changes in vessel caliber tend to restore baseline wall shear stress (WSS) and have been reported to be endothelium-dependent. To investigate the role of endothelium-derived nitric oxide (NO) in the adaptive increase in artery diameter in response to a chronic increase in blood flow, an arteriovenous fistula was constructed between the left common carotid artery (CCA) and the external jugular vein in 22 New Zealand White rabbits, and NO synthesis was inhibited in 14 animals by long-term administration of NG-nitro-L-arginine-methyl ester (L-NAME) in drinking water given for 4 weeks. The remaining 8 animals served as controls. Mean arterial blood pressure was not significantly altered by L-NAME treatment (91 +/- 2 in control versus 98 +/- 3 mm Hg in L-NAME-treated rabbits). Blood flow significantly increased in the left CCA in both groups but was lower in L-NAME-treated than control animals (106.1 +/- 10.7 versus 196.2 +/- 32.3 mL/min, P < .003). The diameter of the flow-loaded left CCA also increased significantly in both groups compared with the right CCA (2.15 +/- 0.12 and 2.54 +/- 0.1 mm, respectively, P < .02), but the increase was less in the L-NAME-treated than the control group (3.24 +/- 0.09 and 4.64 +/- 0.17 mm, respectively, P < .0001). The diameter of the anastomosed veins was also increased but to a much lesser degree in L-NAME-treated animals than in controls (4.14 +/- 0.29 versus 7.94 +/- 0.51 mm, P < .0001). As a result of artery enlargement, WSS was normalized in the flow-loaded left CCA of the control group (8.87 +/- 0.77 dynes/cm2) regardless of blood flow values. In L-NAME-treated animals, however, WSS was only partially regulated, the mean value being significantly increased (18.7 +/- 2.2 dynes/cm2, P < .006). Moreover, a highly significant positive correlation between WSS and blood flow was obtained in L-NAME-treated animals (r = .84, P < .0001). We also found remodeling of the artery wall, with a larger increase in the medial cross-sectional area associated with an increased number of smooth muscle cells, in the control group compared with the L-NAME-treated group (0.75 +/- 0.09 versus 0.49 +/- 0.04 mm2 and 4504 +/- 722 versus 2717 +/- 282 cells/mm2, P < .03). We conclude that NO plays a role in the increase of vessel caliber in response to chronic increase in blood flow. As yet unidentified additional metabolic processes appear to be necessary for a complete regulatory response.
Antenna system for multi-band satellite communications (2002)

Multi-band satellite communications antennas have applications in the commercial, defense, and civilian federal marketplace. All defence agencies have requirements for transportable multi-band systems. There are many civilian federal organizations requiring multi-band capabilities, and the commercial market uses C- and Ku-band systems, with future requirements for Ka-band coverage. The latest Intelsat satellites carry both C- and Ku-band transponders, therefore, many of the world's earth stations are, or will be, operating in both bands. The use of an antenna permitting operation of the earth terminal in all three bands without requiring the replacement of the feed is a highly desirable capability. This paper describes the design, development, and testing of an antenna system that permits operation in the three main frequency bands, (C, X, and Ku), including simultaneous operation in multiple bands. This antenna system operates in all three bands without the need to replace any components. The paper also discusses the possibilities of extending the frequency coverage of the antenna system into the Ka-band. The multi-band antenna system can increase the capabilities and operational flexibility of existing earth stations as well as new systems.
유산염과 pH가 사람의 복막 증피 세포 기능에 미치는영향 (2000)

Preservation of peritoneal membrane function is important in the success of long-term peritoneal dialysis (PD). During PD, human peritoneal mesothelial cells (HPMC) are continuously exposed to unphysiological peritoneal dialysis solution(PDS) charaterized by high glucose and lactate concentrations, low pH, and hyperosmolality. Since few studies have examined the effects of lactate and pH on HPMC biology, the present study investigated the effects of lactate and pH on the viability and proliferation of cultured HPMC and on the production of TGF-β1, a fibrogenic cytokine, and fibronectin by cultured HPMC. HPMC were obtained from the omental tissue of pregnant women who were undergoing Cesarean section. Cells at confluence were utilized to determine the viability(LDH release), proliferation([³H]-thymidine incorporation), and the production of fibronectin and TGF-β1(ELISA) after synchronizing the cell growth by incubating with serum free media for 24 hours. After exposure to the media containing lactate and pH, LDH release increased in dose- and time-dependent manner. Both 1.5% and 4.25% commercial PD solutions were cytotoxic and induced more than 80% LDH release within 24 hours. LDH release decreased with increasing dilution of commercial peritoneal dialysate, but there was no significant difference in LDH release between 1.5% and 4.25% PDS. LDH release increased in response to pH 5.5. Thymidine incorporation assay revealed that lactate and low pH significantly inhibited proliferation of HPMC. ELISA revealed that exposure of HPMC to lactate and low pH decreased fibronectin protein synthesis, when compared to cell exposed to bicarbonate containing M199 media. Our results clearly show that lactate and low pH lead to dose- and time-dependent cell death and reduce proliferation of cultured HPMC. Lactate and low pH per se appear to decrease fibronectin production by HPMC but may set a stage for other factors to promote progressive fibrosis during the healing stage in long-term PD.
Online measurements of crystallinity using Raman spectroscopy during blown film extrusion of a linear low‐density polyethylene (2004)

Abstract Real‐time, Raman spectroscopic measurements of crystallinity during the blown film extrusion of a linear low‐density polyethylene (LLDPE) are reported. The take‐up ratio (TUR), inflation air pressure, and cooling conditions were varied, and their effect on the development of crystallinity was studied. The results indicate that the crystallization process starts at the freeze line, increases along the film line, and finally plateaus. It was observed that with changing processing conditions, the differences in the profiles for crystallinity were evident when plotted as a function of time rather than distance along the machine direction. The influence of take‐up ratio and bubble inflation air pressure on the development of crystallinity clearly established the role of flow‐induced crystallization during film extrusion. Polym. Eng. Sci. 44:1484–1490, 2004. © 2004 Society of Plastics Engineers.
Nitroxyl (HNO): A Novel Redox Signaling Molecule (2011)

Nitroxyl (HNO), the one electron reduced and protonated congener of nitric oxide, is emerging as a novel nitrogen oxide with distinct chemistry and biological actions as compared with its redox sibling. The "thiophilic" nature of HNO underlies many of its unique properties, and attention has been focused on its regulation of cellular function and therapeutic potential, particularly in the treatment of cardiovascular disease. The present Forum issue summarizes the intriguing chemistry and biology of HNO and highlights its impact in the cardiovascular and central nervous systems. Recent advances in the development of new HNO donors and their potential use as tools to study HNO signaling and therapeutic agents are discussed. Evidence is also provided for a role of HNO as a putative, endogenous regulator of vascular function. However, as highlighted in this Forum issue, the development of sensitive methods for HNO detection in a biological system is needed to conclusively prove its in vivo generation. As research expands in this area, it is likely that new targets and pharmacological applications of HNO will be discovered.
Effects of a single bolus of urokinase in patients with life-threatening pulmonary emboli: a descriptive trial. (1984)

To evaluate hemodynamic, angiographic, and biological effects of a single bolus of urokinase, an open descriptive trial was conducted in a homogeneous group of 14 patients with acute life-threatening pulmonary emboli and without prior cardiopulmonary disease. For every patient the efficacy of the treatment was evaluated by comparing control and posttherapeutic values after the bolus injection of 15,000 IU/kg body weight urokinase (urinary source) administered in 10 min in the right atrium, followed by continuous intravenous full-dose heparin therapy. In two patients clinical status, hemodynamics, vascular obstruction, and biological (fibrinogen and plasminogen levels) parameters remained unchanged. One of these two patients died, making the mortality rate for the whole group 7%. Twelve of 14 patients showed rapid clinical improvement. Evaluation at 12 hr demonstrated significant decreases in pulmonary vascular obstruction (Miller index, 34%), total pulmonary vascular resistances (37%), and fibrinogen and plasminogen levels (41% and 40%, respectively), without any significant change in cardiac index. The hemodynamic sequential measurements performed (1,3, 6, and 12 hr) in seven of the 12 improved patients showed that the greatest percentage of the total hemodynamic improvement occurred within the first 3 hr after bolus administration of urokinase. No severe hemorrhagic complications were observed. Because of its rapid efficacy and its low cost, the bolus technique appeared particularly useful in the treatment of patients with acute life-threatening pulmonary emboli.
CD28 and T cell antigen receptor signal transduction coordinately regulate interleukin 2 gene expression in response to superantigen stimulation. (1992)

Activation of an immune response requires intercellular contact between T lymphocytes and antigen-presenting cells (APC). Interaction of the T cell antigen receptor (TCR) with antigen in the context of major histocompatibility molecules mediates signal transduction, but T cell activation appears to require the induction of a second costimulatory signal transduction pathway. Recent studies suggest that interaction of CD28 with B7 on APC might deliver such a costimulatory signal. To investigate the role of CD28 signal transduction during APC-dependent T cell activation, we have used Staphylococcal enterotoxins (SEs) presented by a B7-positive APC. We used anti-B7 monoclonal antibodies and a mutant interleukin 2 (IL-2) promoter construct, unresponsive to CD28-generated signals, in transient transfection assays to examine the contribution of the CD28-B7 interaction to IL-2 gene activation. These studies indicate that the CD28-regulated signal transduction pathway is activated during SE stimulation of T cells and plays an important role in SE induction of IL-2 gene expression through its influence upon the CD28-responsive element contained within the IL-2 gene promoter. This effect is particularly profound in the activation of the IL-2 gene in peripheral blood T cells.
Micro-Raman thermometry for measuring the temperature distribution inside the microchannel of a polymerase chain reaction chip (2006)

The temperature distribution inside the microchannel was first measured using a micro-Raman spectroscopy system. Polymerase chain reaction (PCR) inside the microchannel, which is very sensitive to temperature change, was chosen to validate a novel thermometry. The micro PCR chip was fabricated by silicon micromachining. The microchip consisted of a microchannel inside the chip, a Pt film heater and a Pt film sensor on the silicon surface. The O–H stretch vibration mode of water was analyzed using a micro-Raman spectroscopy system. Its spectral changes were calibrated with temperature. The intensity ratio of the hydrogen-bonded (HB) to non-hydrogen-bonded (NHB) O–H stretch vibration modes has a linear relation with temperature. The temperature of the microchannel controlled at 55 °C varied from 53.6 to 54.8 °C depending on the location of the microchannel.
Locked Nucleic Acid Holds Promise in the Treatment of Cancer (2008)

Providing novel treatments to help cancer patients live longer and have better lives remains one of the biggest challenges of the pharmaceutical industry. Today much is known about the molecular and genetic causes of cancers thus facilitating the development of novel targeted cancer drugs with improved risk-benefit ratios compared to contemporary broadly-acting, cytotoxic cancer drugs. Antisense therapy, e.g. the use of single stranded oligonucleotides as therapeutic modalities, provides the means to develop such targeted drugs, and in recent years this concept has enjoyed a major renaissance. Locked Nucleic Acid (LNA) is a novel, third generation RNA analogue that displays most if not all of the characteristics required to make potent and safe antisense drugs. Here we review the key properties of LNA oligonucleotides in the context of their use as safe and effective antisense drugs and provide a status on their therapeutic development in the field of cancer.