gebhart/patrepeval huggingface dataset:
Understanding the Relative Acyl-Transfer Reactivity of Oxoesters and Thioesters:  Computational Analysis of Transition State Delocalization Effects (2001)

Computational studies were performed in an effort to understand the relative reactivity of oxoesters and thioesters in nucleophilic acyl transfer reactions. Transition state models were developed for the reactions of methyl acetate and methyl thioacetate with hydroxide, ammonia, and methylcyanoacetate carbanion. Quantum mechanical calculations based on these models reproduced experimental observations that oxoesters and thioesters have similar reactivity toward hydroxide while thioesters are about 100-fold and at least 2000-fold more reactive than oxoesters toward amine and carbanion nucleophiles, respectively. NBO analysis was performed to elucidate the role of electron delocalization in reactant and transition state stabilization. These calculations indicate similar losses of delocalization energy for the oxoester and thioester in going from the reactants to the transition state in reaction with hydroxide while the loss of delocalization energy is significantly greater for the oxoester in reactions with the other nucleophiles. Bond rotational analysis of the transition states for the reactions with hydroxide and ammonia provide support for an important role of the p(X) --> sigma(C-Nu) interaction (X = O or S of the oxoester or thioester respectively, Nu = nucleophile) in governing the reactivity of oxoesters and thioesters in nucleophilic acyl substitution.
Combined Transcriptomics, Proteomics and Bioinformatics Identify Drug Targets in Spinal Cord Injury (2018)

Spinal cord injury (SCI) causes irreversible tissue damage and severe loss of neurological function. Currently, there are no approved treatments and very few therapeutic targets are under investigation. Here, we combined 4 high-throughput transcriptomics and proteomics datasets, 7 days and 8 weeks following clinically-relevant rat SCI to identify proteins with persistent differential expression post-injury. Out of thousands of differentially regulated entities our combined analysis identified 40 significantly upregulated versus 48 significantly downregulated molecules, which were persistently altered at the mRNA and protein level, 7 days and 8 weeks post-SCI. Bioinformatics analysis was then utilized to identify currently available drugs with activity against the filtered molecules and to isolate proteins with known or unknown function in SCI. Our findings revealed multiple overlooked therapeutic candidates with important bioactivity and established druggability but with unknown expression and function in SCI including the upregulated purine nucleoside phosphorylase (PNP), cathepsins A, H, Z (CTSA, CTSH, CTSZ) and proteasome protease PSMB10, as well as the downregulated ATP citrate lyase (ACLY), malic enzyme (ME1) and sodium-potassium ATPase (ATP1A3), amongst others. This work reveals previously unappreciated therapeutic candidates for SCI and available drugs, thus providing a valuable resource for further studies and potential repurposing of existing therapeutics for SCI.
Red Cell Filtration and the Pathogenesis of Certain Hemolytic Anemias (1961)

Abstract Studies were made of the filterability of normal and abnormal red cells through an inert membrane-type (Millipore) filter having uniform non-branching capillary pores 5 µ in diameter. With this filter it was possible to remove selectively certain kinds of abnormal red cells from mixed suspensions of normal and abnormal red cells. The red cells of patients with sickle cell anemia were selectively trapped by the filter under low oxygen tensions. Such sickled red cells were unable to pass through the filter even under a pressure differential across the filter (perfusion pressure) of over 120 mm. Hg. Red cells agglutinated by anti-A were completely retained by the filter at perfusing pressures of 4 mm. Hg., but were partially disagglutinated and forced through the filter when the pressure was increased. Red cells coated with an incomplete (Rh) agglutinin and red cells from a patient with acquired hemolytic anemia were retained by the filter only in the presence of rouleaux-producing agents such as P.V.P. or fibrinogen and only at low perfusion pressures. A small fraction of the red cells of patients with hereditary spherocytosis were trapped by a single passage through the filter; the trapped cells were largely derived from the minor population of hyperspheroidal cells. The relevance of these findings to the mechanisms of red cell sequestration in vivo is discussed.
Preoperative Serum Levels of Epidermal Growth Factor Receptor, HER2, and Vascular Endothelial Growth Factor in Malignant and Benign Ovarian Tumors (2008)

Epidermal growth factor receptors ([EGFRs]; EGFR/HER1 and ErbB2/HER2) and vascular endothelial growth factor (VEGF) are essential to tumor growth and angiogenesis. The aim of the present study was to investigate the serum levels of these potential biomarkers in benign, borderline, and malignant ovarian tumors. Serum from 233 patients (75 serous ovarian/tubal/peritoneal cancers, 24 borderline tumors, 110 benign ovarian tumors, and 24 with normal ovaries) were analyzed for EGFR, HER2, and VEGF using commercially available enzyme-linked immunosorbent assays (ELISA). The median EGFR serum level in patients with ovarian cancer was 51 ng/mL, and this was significantly lower than the median serum levels in borderline tumors (P = .0054) and benign ovarian tumors (P < .000001) as well as in patients with normal ovaries (P = .00028). The HER2 median serum level in patients with ovarian cancer was 10.2 ng/mL and not significantly different from any of the other patient groups. The median VEGF serum level in patients with ovarian cancer was 449 pg/mL and significantly higher than the levels found in borderline tumors (P = .021) and benign tumors (P = .0087) as well as in patients with normal ovaries (P = .00024). Significantly lower serum EGFR levels and higher VEGF levels were noted in patients with ovarian cancer compared with the levels in benign tumors and normal ovaries. Vascular endothelial growth factor and EGFR could have clinical importance as serum biomarkers but need further investigation.
Dimensional effects on current and field properties in NbN films (1981)

We have investigated dimensional effects, i.e., variations in thickness, width, grain size, and separation between grains, on the current and field properties of NbN films. The films, all of which had T <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">c</inf> 's of ∼ 16K were prepared by reactive sputtering, Self-field current densities measured at 4.2K ranged from <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\sim 5 \times 10^{5}</tex> to > 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">7</sup> Amps/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . Measured upper critical fields at 4.2K varied from < 100 kG to > 220 kG. Extrapolated H <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">c2</inf> 's of over 500 kG were calculated from data taken near T <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">c</inf> . All of these results are correlated with transmission electron microscopy studies. The very highest upper critical fields are attributed to an H <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">c3</inf> arising from a column-void microstructure. In general, we conclude that dimensional effects are a dominant factor in achieving the very high current and field values observed in these films.
Mural repair following obliteration of aneurysms: Production of experimental aneurysms (1987)

One hundred thirty-two experimental rat carotid artery aneurysms were produced using a variety of methods, in order to determine which of these approaches should be employed in the development of a satisfactory laboratory model. The gross appearance and pathomorphology of aneurysms created by vein pouch and partial arteriotomy methods most closely resembled those features reported in clinical intracranial aneurysms.
A Developer's Guide to Amazon SimpleDB (2010)

The Complete Guide to Building Cloud Computing Solutions with Amazon SimpleDB Using SimpleDB, any organization can leverage Amazon Web Services (AWS), Amazons powerful cloud-based computing platformand dramatically reduce the cost and resources associated with application infrastructure. Now, for the first time, theres a complete developers guide to building production solutions with Amazon SimpleDB. Pioneering SimpleDB developer Mocky Habeeb brings together all the hard-to-find information you need to succeed. Mocky tours the SimpleDB platform and APIs, explains their essential characteristics and tradeoffs, and helps you determine whether your applications are appropriate for SimpleDB. Next, he walks you through all aspects of writing, deploying, querying, optimizing, and securing Amazon SimpleDB applicationsfrom the basics through advanced techniques. Throughout, Mocky draws on his unsurpassed experience supporting developers on SimpleDBs official Web forums. He offers practical tips and answers that cant be found anywhere else, and presents extensive working sample codefrom snippets to complete applications. With A Developers Guide to Amazon SimpleDB you will be able to Evaluate whether a project is suited for Amazon SimpleDB Write SimpleDB applications that take full advantage of SimpleDBs availability, scalability, and flexibility Effectively manage the entire SimpleDB application lifecycle Deploy cloud computing applications faster and more easily Work with SELECT and bulk data operations Fine tune queries to optimize performance Integrate SimpleDB security into existing organizational security plans Write and enhance runtime SimpleDB clients Build complete applications using AJAX and SimpleDB Understand low-level issues involved in writing clients and frameworks Solve common SimpleDB usage problems and avoid hidden pitfalls This book will be an indispensable resource for every IT professional evaluating or using SimpleDB to build cloud-computing applications, clients, or frameworks.
Underwater laser imaging system (UWLIS) (1995)

Practical limitations of underwater imaging systems are reached when the noise in the back scattered radiation generated in the water between the imaging system and the target obscures the spatial contrast and the resolution necessary for target discovery and identification. The advent of high power lasers operating in the oceanic transmission window of the visible spectrum (blue-green portion) has led to improved experimental illumination systems for underwater imaging The properties of laser bearm in range-gated and synchronously scanned devices take advantage of the unique temporal and spatial coherence effect of common volume back scatter to reduce or eliminate noise, increase signal to noise levels. Synchronously scanned systems rely on the highly collimated nature of the laser beam for spatial rejection of common volume back scatter. A synchronous, raster-scanning underwater laser imaging system (UWLIS) has been developed at Lawrence liver-more National Laboratory. The present UWLIS system differs from earlier synchronous scanners in its ability to scan in two dimensions at conventional video frame rate (30 Hz). The imaging performance of the present UWLIS was measured at distances of up to 6.3 AL (at a physical distance of 15.2 meters) during an in-water tank test and 4.5 to 5.0 AL (at a physical distance of 30 meters) during open water oceanic testing. The test results indicate that the UWLIS system is already capable of extending the underwater imaging range beyond that of conventional floodlight illuminated SIT cameras. The real or near real time frame rates of the UWLIS make possible operations in a mode in which the platform speed is randomly varied. This is typical of the operational environment in which the platform is often maneuvered above and around rugged seafloor terrain`s and obstacles.
<I>Aedes aegypti</I> (Diptera: Culicidae) Biting Deterrence: Structure-Activity Relationship of Saturated and Unsaturated Fatty Acids (2012)

In this study we evaluated the biting deterrent effects of a series of saturated and unsaturated fatty acids against Aedes aegypti (L), yellow fever mosquito (Diptera: Culicidae) using the K & Dbioassay module system. Saturated (C6:0 to C16:0 and C18:0) and unsaturated fatty acids (C11:1 to C14:1, C16:1, C18:1, and C18:2) showed biting deterrence index (BDI) values significantly greater than ethanol, the negative control. Among the saturated fatty acids, mid chain length acids (C10:0 to C13:0) showed higher biting deterrence than short (C6:0 to C9:0) and long chain length acids (C14:0 to C18:0), except for C8:0 and C16:0 that were more active than the other short and long chain acids. The BDI values of mid chain length acids (C10:0 to C13:0) were not significantly less than N, N-diethyl-meta-toluamide (DEET), the positive control. Among the unsaturated fatty acids, C11:1 showed the highest activity (BDI = 1.05) and C18:2 had the lowest activity (BDI = 0.7). In C11:1, C12:1, and C14:1 BDI values were not significantly less than DEET. After the preliminary observations, residual activity bioassays were performed on C11:0, C12:0, C11:1, and C12:1 over a 24-h period. All the fatty acids (C11:0, C12:0, C11:1, and C12:1) and DEET showed significantly higher activity at all test intervals than the solvent control. At treatment and 1-h posttreatment, all fatty acids showed proportion not biting (PNB) values not significantly less than DEET. At 3-, 6-, and 12-h posttreatment, all fatty acids showed PNB values significantly greater than DEET. At 24-h posttreatment, only the PNB value for C12:0 was significantly higher than DEET. The dose-responses of C12:0 and DEET were determined at concentrations of 5-25 nmol/cm2. As in the residual activity bioassays, the PNB values for C12:0 and DEET at 25 nmol/cm(2) were not significantly different. However, at lower concentrations, the PNB values for C12:0 were significantly greater than DEET. These results clearly indicate that mid chain length fatty acids not only have levels of biting deterrence similar to DEET at 25 nmnol/cm(2) in our test system, but also appeared to be more persistent than DEET. In contrast, in vivo cloth patch assay system showed that the mid-chain length fatty acids, C11:0, C11:1, C12:0, and C12:1 had minimum effective dose (MED) values greater than DEET against Ae. aegypti and their relative repellency varied according to species tested. The MED values of 120 (C11:0), 145 (C12:0) and 116 (C11:1) nmol/cm(2) against Anopheles quadrimaculatus Say, indicated that these acids were not as potent as DEET with a MED of 54 nmol/cm(2). The MED ratio of the C11:0 and C11:1 for all three mosquito species indicated the C11 saturated and unsaturated acids as more repellent than their corresponding C12:0 and C12:1 homologues.
Role of calcium in the secretion of leptin from white adipocytes (2004)

The mechanism by which calcium regulates leptin secretion was studied in adipocytes isolated from rat white adipose tissue. Incubation of adipocytes in a medium containing glucose, but no calcium, markedly inhibited insulin-stimulated leptin secretion (ISLS) and synthesis, without affecting basal leptin secretion or lipolysis. However, when pyruvate was used as a substrate, ISLS was insensitive to the absence of calcium. Likewise, the stimulatory effects of insulin were completely prevented by phloretin, cytochalasin B, and W-13 (3 agents that interfere with early steps of glucose metabolism) in the presence of glucose, but not in the presence of pyruvate. Thus calcium appears to be specifically required for glucose utilization. On the other hand, (45)Ca uptake and leptin secretion were not affected by insulin or by inhibitors of L-type calcium channels. However, agents increasing plasma membrane permeability to calcium (high calcium concentrations, A-23187, and ATP) increased (45)Ca uptake and concomitantly inhibited ISLS. Similarly, release of endogenous calcium stores by thapsigargin inhibited ISLS in a dose-dependent manner. ATP, A-23187, calcium, and thapsigargin inhibited ISLS, even in the presence of pyruvate. These results show that 1) extracellular calcium is necessary for ISLS, mainly by affecting glucose uptake, 2) insulin does not affect extracellular calcium uptake, and 3) increasing cytosolic calcium by stimulating its uptake or its release from endogenous stores inhibits ISLS at a level independent of glucose metabolism. Thus calcium regulates leptin secretion from adipocytes in a manner that is markedly different from its role in the exocytosis of many other polypeptidic hormones.
Programmatic risk analysis (2015)

AccessScience is an authoritative and dynamic online resource that contains incisively written, high-quality educational material covering all major scientific disciplines. An acclaimed gateway to scientific knowledge, AccessScience is continually expanding the ways it can demonstrate and explain core, trustworthy scientific information that inspires and guides users to deeper knowledge.
The absorption, metabolism and excretion of flavan-3-ols and procyanidins following the ingestion of a grape seed extract by rats (2005)

Rats were fed a grape seed extract (GSE) containing (+)-catechin, (-)-epicatechin and dimers, trimers, tetramers and polymeric procyanidins. Liver, kidney, brain and gastrointestinal (GI) tract together with plasma, urine and faeces were collected over a 24 h period and their flavan-3-ol content was analysed by HPLC with tandem mass spectrometry and diode array detection. Small amounts of the GSE flavan-3-ols moved out of the stomach and into the duodenum/jejunum, and to a greater extent the ileum 1 h after ingestion, and into the caecum after 2 h with relatively small amounts being detected in the colon after 3 h. The GI tract contained the parent GSE flavan-3-ols and procyanidins with only trace amounts of metabolites and there were no indications that proanthocyanidins were depolymerised in the GI tract releasing monomeric flavan-3-ols. Plasma contained exclusively catechin glucuronides and methylated glucuronide metabolites which were also detected in the liver and kidneys. These metabolites were also present in urine together with sulphated metabolites and low amounts of the procyanidin dimers B1, B2, B3 and B4 as well as the trimer C2 and an unknown GSE trimer. The amounts of (+)-catechin and (-)-epicatechin metabolites excreted in urine relative to the quantity of the monomers ingested were 27 and 36 %, respectively, after 24 h. This is similar to the levels of urinary excretion reported to occur by other investigators after feeding (-)-epicatechin to rats and provides further, albeit indirect, evidence that the procyanidin oligomers in the GSE were not depolymerised to monomers to any extent after ingestion. No convincing analytical data were obtained for the presence of flavan-3-ol metabolites in the brain.
Nanostructured fiber optic sensors for detection of volatile organic compounds in breath (2006)

Recent progress in nanostructured optical fiber-based sensors for the noninvasive, fast and quantitative measurement of volatile organic compounds (VOC) in human breath is reported. The sensor array, which is constituted with multilayered, interleaved metal nanocluster and polymer thin films on the distal ends of optical fibers, is fabricated by the electrostatic self-assembly (ESA) process. Initial research and early sensor prototype demonstrations indicate that the specific detection of acetone, ethane and other molecular targets in exhaled human breath is achievable. Moreover, the selectivity and sensitivity of the system are significantly improved by incorporating an advanced data analysis model.
Plant polyphenols inhibit VacA, a toxin secreted by the gastric pathogen <i>Helicobacter pylori</i> (2003)

VacA is a major virulence factor of the widespread stomach-dwelling bacterium Helicobacter pylori. It causes cell vacuolation and tissue damage by forming anion-selective, urea-permeable channels in plasma and endosomal membranes. We report that several flavone derivatives and other polyphenols present in vegetables and plants inhibit ion and urea conduction and cell vacuolation by VacA. Red wine and green tea, which contain many of the compounds in question, also potently inhibit the toxin. These observations suggest that polyphenols or polyphenol derivatives may be useful in the prevention or cure of H. pylori-associated gastric diseases.
Settling Properties of Asphaltene Aggregates (2005)

Stokes law is the fundamental equation to describe the settling velocity of a particle for small Reynolds number flow and is applicable when the particle is spherical and impermeable. However, this equation is not suitable to describe the settling of porous aggregates found in many industrial applications, because of the nonsphericity and flow through the pores of the aggregates. Free-settling tests were used in the present work to estimate asphaltene aggregates porosity and effective density. The settling velocities of individual asphaltene aggregates are measured in a quiescent column via a photographic technique. Data analysis was conducted with a video frame grabber and digital imaging software, to determine the particle size, shape, and settling velocity. Results show that the aggregate size (area-equivalent diameter) determined from the video images ranged from 20 μm to 200 μm and the measured settling velocities varied from 100 μm/s to 564 μm/s. Settling velocity measurements indicated an inverse relationship between aggregate size and density. The reduced aggregate density with increasing size was attributed to the entrainment of fluid into the aggregate structure. These porous aggregates further collided with each other to form increasingly more-porous structures. An analysis was performed to understand the importance of aggregate fractal structure and its effective density on the settling velocity. The size-density fractal dimension of the asphaltene aggregates was estimated to be in the range of D3 = 1.3−2.0. These relatively low fractal dimensions suggest that the asphaltene aggregates are highly porous and very tenuous.
1,2,3-Dithiazoles – new reversible melanin synthesis inhibitors: a chemical genomics study (2015)

1,2,3-Dithiazolimines show potent and reversible inhibition of melanin synthesis in<italic>Xenopus laevis</italic>embryos.
Delivery systems for gene therapy (2013)

The structure of DNA was unraveled by Watson and Crick in 1953, and two decades later Arber, Nathans and Smith discovered DNA restriction enzymes, which led to the rapid growth in the field of recombinant DNA technology. From expressing cloned genes in bacteria to expressing foreign DNA in transgenic animals, DNA is now slated to be used as a therapeutic agent to replace defective genes in patients suffering from genetic disorders or to kill tumor cells in cancer patients. Gene therapy provides modern medicine with new perspectives that were unthinkable two decades ago. Progress in molecular biology and especially, molecular medicine is now changing the basics of clinical medicine. A variety of viral and non-viral possibilities are available for basic and clinical research. This review summarizes the delivery routes and methods for gene transfer used in gene therapy.
ChemInform Abstract: A Convenient and One‐Pot Synthesis of Methyl α‐(3,4‐Dihydro‐3‐oxo‐2H‐1,4‐benzoxazin‐,2‐yl)acetates. (1986)

Abstract Während die Reaktion der Aminophenole (III) mit dem Anhydrid (II) die erwarteten Acetate (I) ergibt, erhält man aus (III) und dem Anhydrid (IV) statt der entsprechenden Propionate die Acetate (V) (Untersuchung und Diskussion des Bildungsmechanismus).