gebhart/patrepeval huggingface dataset:
Angiogenic Pathways in Diabetic Retinopathy (2005)

Visual loss is often considered the most feared complication of human disease, other than death. In 2002, 124 million people worldwide had poor vision and 37 million were blind.1 In developed countries, the primary causes of visual loss are age-related macular degeneration, in the elderly, and diabetic retinopathy, in working-age persons. It is estimated that diabetes mellitus affects 4 percent of the world's population, almost half of whom have some degree of diabetic retinopathy at any given time. Visual loss primarily occurs from either proliferation of new retinal vessels (proliferative diabetic retinopathy) or increased permeability of retinal vessels (diabetic macular . . .
Activation of Rac1, RhoA, and Mitogen-Activated Protein Kinases Is Required for Ras Transformation (1995)

Although substantial evidence supports a critical role for the activation of Raf-1 and mitogen-activated protein kinases (MAPKs) in oncogenic Ras-mediated transformation, recent evidence suggests that Ras may activate a second signaling pathway which involves the Ras-related proteins Rac1 and RhoA. Consequently, we used three complementary approaches to determine the contribution of Rac1 and RhoA function to oncogenic Ras-mediated transformation. First, whereas constitutively activated mutants of Rac1 and RhoA showed very weak transforming activity when transfected alone, their coexpression with a weakly transforming Raf-1 mutant caused a greater than 35-fold enhancement of transforming activity. Second, we observed that coexpression of dominant negative mutants of Rac1 and RhoA reduced oncogenic Ras transforming activity. Third, activated Rac1 and RhoA further enhanced oncogenic Ras-triggered morphologic transformation, as well as growth in soft agar and cell motility. Finally, we also observed that kinase-deficient MAPKs inhibited Ras transformation. Taken together, these data support the possibility that oncogenic Ras activation of Rac1 and RhoA, coupled with activation of the Raf/MAPK pathway, is required to trigger the full morphogenic and mitogenic consequences of oncogenic Ras transformation.
Cytokine-induced Acute Inflammation in the Brain and Spinal Cord (1999)

Different compartments in the central nervous system mount distinct inflammatory responses. The meninges and choroid plexus respond to pro-inflammatory stimuli in a manner reminiscent of a peripheral inflammatory response, whereas the brain parenchyma is refractory. Trauma-induced lesions in brain and in spinal cord are associated with leukocyte infiltration, blood-brain barrier (BBB) breakdown, and secondary tissue destruction. Unexpectedly, these phenomena are generally more pronounced in the parenchyma of the spinal cord than in the parenchyma of the brain. To investigate whether these differences between brain and spinal cord can be attributed, at least in part, to differing sensitivities to proinflammatory cytokines, we stereotactically injected recombinant rat (rr) TNFalpha or rrIL-1beta into the striatum or the spinal cord of Wistar rats. In the brain, the injection of rrTNFalpha failed to evoke BBB breakdown or leukocyte recruitment, whereas in the spinal cord injection of TNFalpha resulted in marked BBB breakdown and leukocyte recruitment. Similarly, the injection of rrIL-1beta into the brain parenchyma failed to induce BBB breakdown and gave rise to only minimal neutrophil recruitment, whereas the injection of rrIL-1beta into the spinal cord induced significant BBB breakdown and recruitment of neutrophils and lymphocytes. Thus, using a minimally invasive injection technique, equivalent in both circumstances, we have shown that there are marked differences in the inflammatory response between the brain parenchyma and spinal cord parenchyma. This observation has important implications for the treatment of spinal cord injuries.
Transmission line design of clock trees (2002)

We investigate appropriate regimes for transmission line propagation of signals on digital integrated circuits. We start from exact solutions to the transmission line equations proposed by Davis and Meindl (IEEE Trans. Electron. Dev., vol. 47, no. 11, pp. 2068-2087, 2000.). We make appropriate modifications due to finite rise time. They affect the delay calculation and hypothesis pertaining to the constancy of the electromagnetic parameters. We study these effects in detail. To find the domain of physical variables where transmission line behavior is feasible, we pose the problem as a nonlinear minimization problem in a space spanned by two continuous variables, with four parameters. From the resulting solutions and employing monotonicity properties of the functional we extract regimes of validity. These regimes of validity happen to be commensurate with what is reachable and doable with current leading technologies. We complete this study with a qualitative analysis of driver insertion in the presence of transmission lines. The resulting configurations are suitable for the development of an improved clock design discipline.
51.4: Color‐Sequential LCoS Projector with a Rotating Drum (2002)

Abstract LCoS microdisplays provide poor efficiency when used with a conventional color wheel in projection systems. This paper will present a new design that replaces the color wheel with a rotating color drum. Throughput of the color drum projector is compared to a system using 3 scanning prisms and to a 3 panel system. System colorimetry and white point correction will be discussed.
A Specificity-Enhancing Factor for the ClpXP Degradation Machine (2000)

Events that stall bacterial protein synthesis activate the ssrA-tagging machinery, resulting in resumption of translation and addition of an 11-residue peptide to the carboxyl terminus of the nascent chain. This ssrA-encoded peptide tag marks the incomplete protein for degradation by the energy-dependent ClpXP protease. Here, a ribosome-associated protein, SspB, was found to bind specifically to ssrA-tagged proteins and to enhance recognition of these proteins by ClpXP. Cells with an sspB mutation are defective in degrading ssrA-tagged proteins, demonstrating that SspB is a specificity-enhancing factor for ClpXP that controls substrate choice.
New Strategies in Prostate Cancer: Translating Genomics into the Clinic (2012)

With the rapidly developing use of next-generation sequencing technologies, there has been a surge in our knowledge of the genomic landscape of prostate cancer and a movement toward developing a molecular subclassification system for the disease. With this new understanding comes great clinical potential, both for the development of biomarkers as well as new therapeutic targets. Herein, we highlight the potential clinical use of recent discoveries and how they fit into our current paradigm. We describe the challenges that lie ahead as we move from genomic sequencing toward routine clinical practice and adopt precision cancer care for patients with prostate cancer.
Novel high performance SPDT power switches using multi-gate FET's (2002)

The development of a 16-watt single-pole double throw (SPDT) MESFET based switch is presented. The switch is unique in its use of a multi-gate FET device which can be fabricated on a standard production switch process. The power handling is nine times that of a single FET while occupying only 30% more die area. The device's bandwidth is comparable to that of a single FET while insertion loss is minimized using a novel N-plus (N+) intergate layer. A switch using the multi-gate device has achieved 0.4 dB insertion loss and 40 dB of isolation at L-band.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
ChemInform Abstract: A New Method for the Synthesis of N3‐Alkylated Analogues of 5‐Fluorouracil. (1999)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Approaches to Antiviral Chemotherapy for Acute Respiratory Infections (1998)

The causative agents of acute respiratory infections (ARI) in infants and children are mostly thought to be viruses. Some ARI in adult patients may be caused by bacteria but most often the causes are virus infections. When ARI affect immunocompromised patients or the elderly the mortality rates are significantly higher than in immunocompetent individuals. Many types of viruses cause ARI. Among them, influenza viruses A and B and respiratory syncytial virus (RSV) are thought to be the most important because of the severity of illness after infection and their high communicability in the human population. Recently, several novel antiviral drugs against ARI have been developed and some are proceeding in clinical trials. This review covers current investigations into antiviral compounds targeted at several points in the virus life-cycle. This includes PM-523, which broadly inhibits ortho- and paramyxo-viruses, two neuraminidase inhibitors for influenza virus, neutralizing antibody to RSV and chimeric soluble ICAM-1-IgA molecules targeted against rhinoviruses.
Antitumor efficacy of wild-type p53-specific CD4(+) T-helper cells. (2002)

Overexpression of p53 is found in approximately 50% of human cancers, making it an attractive target antigen for immunotherapy of cancer. Research in this area has thus far primarily focused on p53-specific CTLs. Although these CTLs were shown to be highly effective against p53-overexpressing tumors in vivo, immunological tolerance seems to strongly restrict the spectrum of the p53-specific CTL repertoire in p53(+/+) subjects. In view of the emerging role of CD4(+) Th (Th) cells in the antitumor response, we investigated the specificity and antitumor efficacy of the p53-specific Th response in mice. Our data show that high affinity Th cells against the naturally processed epitope p53(108-122) can be elicited in both p53(-/-) and p53(+/+) mice, indicating that the p53-specific T-cell response is not affected by tolerance at the Th level. Furthermore, p53(108-122)-specific Th cells were effective in enabling p53-specific CTLs to control the growth of p53-overexpressing tumors in vivo. Therefore, exploitation of the p53-specific Th response appears to be a highly useful aspect of immunotherapeutic strategies against cancers.
Optimization of Shear Driven Droplet Generation in a Microfluidic Device (2003)

Hydrophilic and lipophilic interfaces of fluids play an important role in the formation of droplets. A large collection of droplets constitutes emulsions of water dispersive phase into oil continuous phase. Since droplet generation forms the basis of the manufacturing of emulsion, great efforts have been made to understand the science, technological and industrial problems associated with the generation of droplets. This paper presents the optimization of a novel method of droplet generation [1] in a microchannel resulting from the laminar co-flow of water and oil in a T type channel. Water in oil droplets are formed with olive oil (interfacial tension 28mN/m, viscosity 84mPa/s, density 918Kg/m3). At the T-junction, the water stream sent through the middle channel is sheared and cut by the oil stream sent through the outer channel. Competition between interfacial tension and the Laplace pressure at the oil/water interface results in droplets of finite diameter. Fluid properties such as density, viscosity and surface tension and the flow parameters such as pressure, mass flow rate and velocity are varied at the inlets and outlets to optimize size, frequency and periodicity of droplets using CFD-ACE+, a multiphysics modeling tool (CFDRC, Huntsville, AL).
Identification and Characterization of the First Class of Potent Bacterial Acetyl-CoA Carboxylase Inhibitors with Antibacterial Activity (2004)

The multisubunit acetyl-CoA carboxylase, which catalyzes the first committed step in fatty acid biosynthesis, is broadly conserved among bacteria. Its rate-limiting role in formation of fatty acids makes this enzyme an attractive target for the design of novel broad-spectrum antibacterials. However, no potent inhibitors have been discovered so far. This report describes the identification and characterization of highly potent bacterial acetyl-CoA carboxylase inhibitors with antibacterial activity for the first time. We demonstrate that pseudopeptide pyrrolidine dione antibiotics such as moiramide B inhibit the Escherichia coli enzyme at nanomolar concentrations. Moiramide B targets the carboxyltransferase reaction of this enzyme with a competitive inhibition pattern versus malonyl-CoA (K(i) value = 5 nm). Inhibition at nanomolar concentrations of the pyrrolidine diones is also demonstrated using recombinantly expressed carboxyltransferases from other bacterial species (Staphylococcus aureus, Streptococcus pneumoniae, and Pseudomonas aeruginosa). We isolated pyrrolidine dione-resistant strains of E. coli, S. aureus, and Bacillus subtilis, which contain mutations within the carboxyltransferase subunits AccA or AccD. We demonstrate that such mutations confer resistance to pyrrolidine diones. Inhibition values (IC(50)) of >100 microm regarding an eukaryotic acetyl-CoA carboxylase from rat liver indicate high selectivity of pyrrolidine diones for the bacterial multisubunit enzyme. The natural product moiramide B and synthetic analogues show broad-spectrum antibacterial activity. The knowledge of the target and the availability of facile assays using carboxyltransferases from different pathogens will enable evaluation of the antibacterial potential of the pyrrolidine diones as a promising antibacterial compound class acting via a novel mode of action.
Formation of dispersions using “flow focusing” in microchannels (2003)

A flow-focusing geometry is integrated into a microfluidic device and used to study drop formation in liquid–liquid systems. A phase diagram illustrating the drop size as a function of flow rates and flow rate ratios of the two liquids includes one regime where drop size is comparable to orifice width and a second regime where drop size is dictated by the diameter of a thin “focused” thread, so drops much smaller than the orifice are formed. Both monodisperse and polydisperse emulsions can be produced.
Decentralized active robotic exploration and mapping for probabilistic field classification in environmental sensing (2012)

A central problem in environmental sensing and monitoring is to classify/label the hotspots in a large-scale environmental field. This paper presents a novel decentralized active robotic exploration (DARE) strategy for probabilistic classification/labeling of hotspots in a Gaussian process (GP)-based field. In contrast to existing state-of-the-art exploration strategies for learning environmental field maps, the time needed to solve the DARE strategy is independent of the map resolution and the number of robots, thus making it practical for in situ, real-time active sampling. Its exploration behavior exhibits an interesting formal trade-off between that of boundary tracking until the hotspot region boundary can be accurately predicted and wide-area coverage to find new boundaries in sparsely sampled areas to be tracked. We provide a theoretical guarantee on the active exploration performance of the DARE strategy: under reasonable conditional independence assumption, we prove that it can optimally achieve two formal cost-minimizing exploration objectives based on the misclassification and entropy criteria. Importantly, this result implies that the uncertainty of labeling the hotspots in a GP-based field is greatest at or close to the hotspot region boundaries. Empirical evaluation on real-world plankton density and temperature field data shows that, subject to limited observations, DARE strategy can achieve more superior classification of hotspots and time efficiency than state-of-the-art active exploration strategies.
Preparation and Properties of an Aqueous Ferrofluid (1999)

Ferrofluids are colloidal suspensions of surfactant-coated magnetic particles in a liquid medium. This paper describes a simple synthesis of an aqueous-based ferrofluid that may be used in an introductory science or engineering laboratory. Magnetite (Fe3O4) particles are precipitated by combining FeCl3 and FeCl2 in a 2:1 stoichiometric ratio in aqueous ammonia solution. The resulting particles, ~10-20 nm in diameter based on powder X-ray diffraction, are then treated with aqueous tetramethylammonium hydroxide, which acts as a surfactant. When the resulting ferrofluid is placed near a magnet, it forms conical spikes. This paper also describes a method for repelling both oil- and water-based ferrofluid from solid surfaces that would otherwise be stained by the fluid. Finally, a demonstration of the interaction between ferrofluid and magnetic fields, in which ferrofluid is induced to leap upward by a stack of magnets, is described.
Esophageal length in achalasia (1995)

Achalasia is characterized by a primary denervation of the esophagus, which leads to morphological changes in the esophagus depicted radiologically by a dilated tortuous esophagus. To determine whether this decompensation is manifest manometrically by a lengthened esophagus, we compared the manometric length of the esophagus in 190 consecutive achalasic patients to 42 normal controls. The mean esophageal length of the achalasic patients was 25 ± 3.5 cm which was significantly longer than the normal controls of 21 ± 2.5 cm (p < 0.001). There was a progressive and significant increase in esophageal length with increasing age of presentation. Esophageal length is an objective index of esophageal decompensation in achalasic patients.
Polysaccharides for Colon Targeted Drug Delivery (2004)

Colon targeted drug delivery has the potential to deliver bioactive agents for the treatment of a variety of colonic diseases and to deliver proteins and peptides to the colon for their systemic absorption. Various strategies, currently available to target the release of drugs to colon, include formation of prodrug, coating of pH-sensitive polymers, use of colon-specific biodegradable polymers, timed released systems, osmotic systems, and pressure controlled drug delivery systems. Among the different approaches to achieve targeted drug release to the colon, the use of polymers especially biodegradable by colonic bacteria holds great promise. Polysaccharidases are bacterial enzymes that are available in sufficient quantity to be exploited in colon targeting of drugs. Based on this approach, various polysaccharides have been investigated for colon-specific drug release. These polysaccharides include pectin, guar gum, amylose, inulin, dextran, chitosan, and chondroitin sulphate. This family of natural polymers has an appeal to drug delivery as it is comprised of polymers with a large number of derivatizable groups, a wide range of molecular weights, varying chemical compositions, and, for the most part, low toxicity and biodegradability yet high stability. The most favorable property of these materials is their approval as pharmaceutical excipients.
Omeprazole: Pharmacokinetics and Metabolism in Man (1989)

Omeprazole is acid labile and, therefore, has to be protected from exposure to the acidic gastric juice when given orally. Following a single oral dose of buffered suspension, omeprazole is rapidly absorbed with peak plasma concentrations within 0.5 hours. The volume of distribution is 0.3 litres/kg corresponding to the volume of extracellular water. In contrast to the long duration of antisecretory action, omeprazole is rapidly eliminated from plasma. The half-life is less than 1 hour, and omeprazole is almost entirely cleared from plasma within 3-4 hours. Omeprazole is completely metabolized in the liver. The two major plasma metabolites are the sulphone and hydroxyomeprazole, neither of which contributes to the antisecretory activity. About 80% of a given dose is excreted in the urine, and the remainder via the bile. The absorption of the coated granule formulation dispensed in hard gelatine capsules is slower, with peak concentrations 1-3 hours after dose. Bioavailability after a single dose is 35% and increases during repeated once-daily dosing to 60%. Omeprazole can potentially interact with the hepatic microsomal cytochrome P-450 enzymes. Studies show that the clearance of both diazepam and phenytoin are decreased and their terminal half-lives are increased during concomitant omeprazole treatment, both interactions being attributable to inhibition of hepatic metabolism. No interaction with propranolol or theophylline has been noted.
A novel inhibitor of glucose uptake sensitizes cells to FAS-induced cell death (2008)

Evasion of death receptor ligand-induced apoptosis is an important contributor to cancer development and progression. Therefore, molecules that restore sensitivity to death receptor stimuli would be important tools to better understand this biological pathway and potential leads for therapeutic adjuncts. Previously, the small-molecule N-[4-chloro-3-(trifluoromethyl)phenyl]-3-oxobutanamide (fasentin) was identified as a chemical sensitizer to the death receptor stimuli FAS and tumor necrosis factor apoptosis-inducing ligand, but its mechanism of action was unknown. Here, we determined that fasentin alters expression of genes associated with nutrient and glucose deprivation. Consistent with this finding, culturing cells in low-glucose medium recapitulated the effects of fasentin and sensitized cells to FAS. Moreover, we showed that fasentin inhibited glucose uptake. Using virtual docking studies with a homology model of the glucose transport protein GLUT1, fasentin interacted with a unique site in the intracellular channel of this protein. Additional chemical studies with other GLUT inhibitors and analogues of fasentin supported a role for partial inhibition of glucose transport as a mechanism to sensitize cells to death receptor stimuli. Thus, fasentin is a novel inhibitor of glucose transport that blocks glucose uptake and highlights a new mechanism to sensitize cells to death ligands.
Enhanced increase of omega-3 index in response to long-term n-3 fatty acid supplementation from triacylglycerides versus ethyl esters (2010)

A six-month supplementation of identical doses of EPA+DHA led to a faster and higher increase in the omega-3 index when consumed as triacylglycerides than when consumed as ethyl esters.
Diversity of human colonic butyrate‐producing bacteria revealed by analysis of the butyryl‐CoA:acetate CoA‐transferase gene (2009)

Butyrate-producing bacteria play an important role in the human colon, supplying energy to the gut epithelium and regulating host cell responses. In order to explore the diversity and culturability of this functional group, we designed degenerate primers to amplify butyryl-CoA:acetate CoA-transferase sequences from faecal samples provided by 10 healthy volunteers. Eighty-eight per cent of amplified sequences showed >98% DNA sequence identity to CoA-transferases from cultured butyrate-producing bacteria, and these fell into 12 operational taxonomic units (OTUs). The four most prevalent OTUs corresponded to Eubacterium rectale, Roseburia faecis, Eubacterium hallii and an unnamed cultured species SS2/1. The remaining 12% of sequences, however, belonged to 20 OTUs that are assumed to come from uncultured butyrate-producing strains. Samples taken after ingestion of inulin showed significant (P=0.019) increases in Faecalibacterium prausnitzii. Because several of the dominant butyrate producers differ in their DNA % G+C content, analysis of thermal melt curves obtained for PCR amplicons of the butyryl-CoA:acetate CoA-transferase gene provides a convenient and rapid qualitative assessment of the major butyrate producing groups present in a given sample. This type of analysis therefore provides an excellent source of information on functionally important groups within the colonic microbial community.