gebhart/patrepeval huggingface dataset:
Crystal structures of human glutaminyl cyclase, an enzyme responsible for protein N-terminal pyroglutamate formation (2005)

N-terminal pyroglutamate (pGlu) formation from its glutaminyl (or glutamyl) precursor is required in the maturation of numerous bioactive peptides. The aberrant formation of pGlu may be related to several pathological processes, such as osteoporosis and amyloidotic diseases. This N-terminal cyclization reaction, once thought to proceed spontaneously, is greatly facilitated by the enzyme glutaminyl cyclase (QC). To probe this important but poorly understood modification, we present here the structure of human QC in free form and bound to a substrate and three imidazole-derived inhibitors. The structure reveals an alpha/beta scaffold akin to that of two-zinc exopeptidases but with several insertions and deletions, particularly in the active-site region. The relatively closed active site displays alternate conformations due to the different indole orientations of Trp-207, resulting in two substrate (glutamine t-butyl ester)-binding modes. The single zinc ion in the active site is coordinated to three conserved residues and one water molecule, which is replaced by an imidazole nitrogen upon binding of the inhibitors. Together with structural and kinetic analyses of several active-site-mutant enzymes, a catalysis mechanism of the formation of protein N-terminal pGlu is proposed. Our results provide a structural basis for the rational design of inhibitors against QC-associated disorders.
Site-specific cleavage at a DNA bulge by neocarzinostatin chromophore via a novel mechanism (1993)

The chromophore of the anticancer drug neocarzinostatin (NCS-Chrom) oxidatively cleaves single-stranded or duplex DNA site-specifically in the absence of activating thiol provided that the DNA contains a bulged structure. Point mutations, deletions, and insertions in the DNA analogue and its complement of the 3'-terminus of yeast tRNA(Phe) show that for a single-stranded DNA to be cleaved by NCS-Chrom the DNA must generate a hairpin structure with an apical loop and at least a two-base-pair stem hinged to a region of duplex structure via a bulge containing a target nucleotide at its 3' side. The size of the loop is not critical so long as it contains at least three nucleotides; the bulge requires a minimum of two nucleotides but must have fewer than five. With a notable exception involving base-pair changes immediately 3' to the bulge, base changes in the bulge and base-pair changes immediately 5' to the bulge retain substrate activity for NCS-Chrom. Maintenance of the bulged structure requires stable duplex regions on each side of the bulge. A similar bulged structure, but lacking a loop, formed by the annealing of a linear 8-mer and a 6-mer is an excellent target for cleavage in the thiol-independent reaction. Drugs such as netropsin, which sequester the DNA into nonbulge containing structures inhibit the reaction. In the absence of O2 strand cleavage is blocked and quantitatively replaced by a presumed drug-DNA covalent adduct.(ABSTRACT TRUNCATED AT 250 WORDS)
Electro-optical response of a single-crystal diamond ultraviolet photoconductor in transverse configuration (2005)

Diamond has been identified as a very promising material for X and ultraviolet sensing. In this Letter, a photoconductive device based on a freestanding homoepitaxial chemically vapor deposition (CVD) single-crystal diamond 500μm thick has been tested. Photoconductive measurements in coplanar and transverse configurations have been performed to characterize the device sensitivity in the 140–250 nm spectral range. Very high sensitivity values were achieved in both configurations. The sensitivity in the transverse configuration is at least 300 times higher than in the coplanar configuration.
Culturable Surface and Endophytic Bacterial Flora of the Maturing Seeds of Rice Plants (Oryza sativa) Cultivated in a Paddy Field (2006)

The endophytic bacteria in the seeds of rice plants (Oryza sativa, cultivar Kinuhikari) cultivated on an experimental plot adjacent to a paddy field were studied as the seeds matured by comparing them with the bacteria on the surface of the seeds. Endophytic and surface bacteria were isolated using a nutrient broth and a diluted nutrient broth agar medium. The isolates were identified based on 16S rRNA gene sequences. Three genera (Paenibacillus, Acidovorax and Pantoea) and 2 genera (Stenotrophomonas and Rhizobium) were specific to the inside and to the surface of the seeds, respectively. Six genera (Bacillus, Curtobacterium, Methylobacterium, Sphingomonas, Xanthomonas and Micrococcus) were common to both the inside and the surface. As the seed matured, the flora of culturable endophytic bacteria changed in a different manner from that of culturable surface bacteria. More isolates tolerant of high osmotic pressure were found among the endophytes than among the surface bacteria, especially at the later stages of the maturation process. An increasing number of endophytic isolates exhibited amylase activity at the later stages.
Least squares conformal maps for automatic texture atlas generation (2002)

A Texture Atlas is an efficient color representation for 3D Paint Systems. The model to be textured is decomposed into charts homeomorphic to discs, each chart is parameterized, and the unfolded charts are packed in texture space. Existing texture atlas methods for triangulated surfaces suffer from several limitations, requiring them to generate a large number of small charts with simple borders. The discontinuities between the charts cause artifacts, and make it difficult to paint large areas with regular patterns.In this paper, our main contribution is a new quasi-conformal parameterization method, based on a least-squares approximation of the Cauchy-Riemann equations. The so-defined objective function minimizes angle deformations, and we prove the following properties: the minimum is unique, independent of a similarity in texture space, independent of the resolution of the mesh and cannot generate triangle flips. The function is numerically well behaved and can therefore be very efficiently minimized. Our approach is robust, and can parameterize large charts with complex borders.We also introduce segmentation methods to decompose the model into charts with natural shapes, and a new packing algorithm to gather them in texture space. We demonstrate our approach applied to paint both scanned and modeled data sets.
The Design of Chelating Agents for the Treatment of Iron Overload (1980)

The starting point for the development of iron chelating drugs is the identification of ligands which have a high and preferential affinity for iron(III). Affinity in vivo may be defined in terms of an effective stability constant, Keff, which can be estimated from the stability constant (β) of the iron(III) complex measured under optimum in vitro conditions by correcting for the physiological pH and competing endogenous metals and ligands. 6Two analogs of HBED that failed to show significant activity in transfused mouse screen Other factors which influence in vivo efficacy are the chelate effect, iron solubilizing ability, kinetic and steric effects, bioavailability and stability, and the chemical state and location of the iron which is to be removed. Using these criteria, the chelating agents with the highest affinity and specificity for iron(III) in vivo should be polydentate and relatively acidic oxy-donors, e.g., derivatives of phenol, catechol, 8-hydroxyquinoline, hydroxamic acid, tropolone, and carboxylic acids such as salicylic acid and glycine. The results of screening such compounds using animal models of iron overload are discussed with the above principles in mind.
Rapid Antimicrobial Susceptibility Testing Using Forward Laser Light Scatter Technology (2016)

The delayed reporting of antimicrobial susceptibility testing remains a limiting factor in clinical decision-making in the treatment of bacterial infection. This study evaluates the use of forward laser light scatter (FLLS) to measure bacterial growth for the early determination of antimicrobial susceptibility. Three isolates each (two clinical isolates and one reference strain) of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa were tested in triplicate using two commercial antimicrobial testing systems, the Vitek2 and the MicroScan MIC panel, to challenge the BacterioScan FLLS. The BacterioScan FLLS showed a high degree of categorical concordance with the commercial methods. Pairwise comparison with each commercial system serving as a reference standard showed 88.9% agreement with MicroScan (two minor errors) and 72.2% agreement with Vitek (five minor errors). FLLS using the BacterioScan system shows promise as a novel method for the rapid and accurate determination of antimicrobial susceptibility.
The zebrafish gene cloche acts upstream of a flk-1 homologue to regulate endothelial cell differentiation (1997)

The zebrafish cloche mutation affects both the endothelial and hematopoietic lineages at a very early stage (Stainier, D. Y. R., Weinstein, B. M., Detrich, H. W., Zon, L. I. and Fishman, M. C. (1995). Development 121, 3141-3150). The most striking vascular phenotype is the absence of endocardial cells from the heart. Microscopic examination of mutant embryos reveals the presence of endothelial-like cells in the lower trunk and tail regions while head vessels appear to be missing, indicating a molecular diversification of the endothelial lineage. Cell transplantation experiments show that cloche acts cell-autonomously within the endothelial lineage. To analyze further the role of cloche in regulating endothelial cell differentiation, we have examined the expression of flk-1 and tie, two receptor tyrosine kinase genes expressed early and sequentially in the endothelial lineage. In wild-type fish, flk-1-positive cells are found throughout the embryo and differentiate to form the nascent vasculature. In cloche mutants, flk-1-positive cells are found only in the lower trunk and tail regions, and this expression is delayed as compared to wild-type. Unlike the flk-1-positive cells in wild-type embryos, those in cloche mutants do not go on to express tie, suggesting that their differentiation is halted at an early stage. We also find that the cloche mutation is not linked to flk-1. These data indicate that cloche affects the differentiation of all endothelial cells and that it acts at a very early stage, either by directly regulating flk-1 expression or by controlling the differentiation of cells that normally develop to express flk-1. cloche mutants also have a blood deficit and their hematopoietic tissues show no expression of the hematopoietic transcription factor genes GATA-1 or GATA-2 at early stages. Because the appearance of distinct levels of flk-1 expression is delayed in cloche mutants, we examined GATA-1 expression at late embryonic stages and found some blood cell differentiation that appears to be limited to the region lined by the flk-1-expressing cells. The spatial restriction of blood in the ventroposterior-most region of cloche mutant embryos may be indicative of a ventral source of signal(s) controlling hematopoietic differentiation. In addition, the restricted colocalization of blood and endothelium in cloche mutants suggests that important interactions occur between these two lineages during normal development.
Self-Assembly Combining Two Bioactive Peptide-Amphiphile Molecules into Nanofibers by Electrostatic Attraction (2003)

We describe a new approach to peptide-amphiphile (PA) nanofiber preparation that allows PAs with different bioactive amino acid sequences to be combined into a single fiber. Oppositely charged PAs are synthesized separately and then mixed to produce gels of nanofiber networks at physiological pH. Transmission electron microscopy reveals the formation of fibers approximately 7 nm in diameter and several micrometers long in these dimeric systems. On the basis of NMR and microscopy, we suggest that these nanofibers are cylindrical micelles of mixed composition, formed due to electrostatic attraction between the oppositely charged PAs. This strategy for self-assembly may be useful in cell therapies that can be implemented without invasive surgery or in in vitro tissue engineering.
Prevention of Apoptosis as a Possible Mechanism behind Improved Cryoprotection of Hematopoietic Cells by Catalase and Trehalose (2005)

We conclude that inclusion of a combination of trehalose and catalase in conventional freezing medium leads to enhanced engraftment potential of cryopreserved mouse bone marrow cells probably by preventing apoptotic cell death. Our observation using animal model may have significant clinical implications.
Scrapie and Cellular Prion Proteins Share Polypeptide Epitopes (1986)

Purified preparations of scrapie prions contain one major protein, PrP 27-30, and aggregates of rod-shaped structures. On the basis of the NH2-terminal amino acid sequence of PrP 27-30, a synthetic peptide (PrP-P1) was constructed. Monospecific rabbit antisera to PrP-P1 were found by immunoblotting to react with PrP 27-30 and its precursor (PrP 33-35Sc), as well as with a related protease-sensitive cellular homologue (PrP 33-35C). An enzyme-linked immunosorbent assay showed that rabbit antiserum to PrP 27-30 was more reactive with PrP 27-30 than with PrP-P1; conversely, antiserum to PrP-P1 was more reactive with the peptide than with the prion proteins. In addition, antibodies to PrP-P1 decorate purified prion rods and stain amyloid plaques in scrapie-infected hamster brain. The peptide epitopes shared by PrP 27-30, PrP 33-35Sc, and PrP 33-35C clearly establish a relationship among these three proteins.
Method for the Accelerated Measurement of Electroosmosis in Chemically Modified Tubes for Capillary Electrophoresis (1996)

A traditional neutral marker approach is combined with fast pressure-driven mobilization to achieve a method that provides accelerated electroosmosis measurements in capillary electrophoresis systems. A marker injection is made prior to and following timed high-voltage application. The marker-sandwiched electrolyte plug is then pressure-driven out of the capillary tube under closely controlled conditions, while the signal is monitored in the usual way. Substantial reduction in measurement time is achieved by allowing the marker to travel only a fraction of the effective length (the injection to detection distance) over a shorter period of time, compared to the traditional method where voltage is applied until the neutral marker shows up at the detector window. One simple equation was derived to express the electroosmotic mobility of the electrolyte (μ(eo)) in terms of common operational variables. The method is particularly useful for low-electroosmosis measurements in wall-modified capillary tubes. The scope and limitations of the method are discussed.
The Relation Between Major Histocompatibility Complex (MHC) Restriction and the Capacity of Ia to Bind Immunogenic Peptides (1987)

The capacity of purified I-Ad, I-Ed, I-Ak, and I-Ek to bind to protein derived peptides that have been previously reported to be T cell immunogens has been examined. For each of the 12 peptides studied strong binding to the relevant Ia restriction element was observed. All the peptides bound more than one Ia molecule; however, for 11 of 12 peptides, the dominant binding was to the restriction element, whereas in one instance the dominant binding was to a nonrestriction element. When the peptides were used to inhibit the presentation of antigen by prefixed accessory cells to T cells, an excellent correlation was found between the capacity of a peptide to inhibit the binding of an antigen to purified Ia and the capacity of the peptide to inhibit accessory cell presentation of the antigen. Thus, the binding of peptide to purified Ia is immunologically relevant, and Ia seems to be the only saturable molecule on the surface of the accessory cell involved in antigen presentation. Inhibition analysis also indicated that all peptides restricted to a particular Ia molecule competitively inhibited one another, suggesting that each Ia restriction element has a single binding site for antigen. Cross-linking of labeled peptides to Ia followed by electrophoretic analysis and autoradiography suggested that this single binding site is made up of portions of both alpha and beta chains of Ia.
Electrical and thermal analyses of catheter-based irreversible electroporation of digestive tract (2019)

<b>Introduction:</b> Irreversible electroporation (IRE) combined with a catheter-based electrode during endoscopy is a potential alternative treatment method for digestive tract tumors. The aim of this study was to investigate the electrical injury (EI) and thermal injury (TI) to the digestive tract via numerical analyses and to evaluate the role and impact of electrode configurations and pulse settings on the efficacy and outcomes of IRE. <b>Materials and methods:</b> A finite element method was used to solve the numerical model. A digestive tract model having 4-mm-thick walls and two catheter-based electrode configuration models were constructed. The distributions of electric fields, temperature, electrical conductivity, tissue injury and limitation on the pulse number required for IRE were calculated and compared. <b>Results:</b> Electrode length is an important geometric parameter for electrodes in the monopolar model (MPM), while electrode spacing affects the outcomes in the bipolar model (BPM). Increasing the pulse voltage reduces the pulse number required for tissue ablation, while increasing the risk of TI. In total, there were 6 NT-IRE protocols, 12 thermal-IRE protocols and 30 TI protocols. All of the NT-IRE protocols were set in BPMs with a voltage of 0.50 kV. With increasing electrode spacing, the minimum pulse number decreased. However, thermal effects were inevitable in the MPM. <b>Conclusions:</b> The electrode configuration and pulse settings are adjusted to achieve NT-IRE synergistically. The BPM is more reliable for achieving NT-IRE in 4-mm-thick digestive wall. Future <i>in vitro</i> and <i>in vivo</i> studies are needed to support and validate this conclusion.
D‐Lactic Acidosis (2005)

D-lactic acidosis, also referred to as D-lactate encephalopathy, is a rare neurologic syndrome that occurs in individuals with short bowel syndrome or following jejuno-ileal bypass surgery. Symptoms typically present after the ingestion of high-carbohydrate feedings. Neurologic symptoms include altered mental status, slurred speech, and ataxia, with patients often appearing drunk. Onset of neurologic symptoms is accompanied by metabolic acidosis and elevation of plasma D-lactate concentration. In these patients, malabsorbed carbohydrate is fermented by an abnormal bacterial flora in the colon, which produces excessive amounts of D-lactate. High amounts of D-lactate are absorbed into the circulation, resulting in an elevated concentration of D-lactate in the blood. Development of neurologic symptoms has been attributed to D-lactate, but it is unclear if this is the cause or whether other factors are responsible. This review examines the pathophysiology of the production and accumulation of D-lactate while exploring the potential factors contributing to the development of neurologic manifestations. Methods of diagnosis and treatment are reviewed. Areas requiring further investigation are identified.
Preparation and properties of poly‐9‐vinyladenine (1970)

Abstract Poly‐9‐vinyladenine was prepared by reaction of poly‐6‐chloro‐9‐vinylpurine with ammonia and poly‐1‐vinyluracil by hydrolysis of poly‐ L ‐vinyl‐2‐ethoxy‐4‐pyrimidinone. In aqueous solutions poly‐9‐vinyladenine shows hypochromism in the ultraviolet spectrum and forms a complex with polyuridylic acid as detected by a further decrease in the ultraviolet absorption. Under the same conditions, poly‐9‐vinyladenine and poly‐ L ‐vinyluracil interact with formation of higher aggregates.
A phase I trial of 5-fluorouracil, leucovorin and interferon-α2b administered by 24 h infusion in metastatic colorectal carcinoma (1996)

A phase I trial of 5-fluorouracil (5-FU), leucovorin (LV) and interferon (IFN) was conducted in 15 advanced colorectal cancer patients refractory to a bolus regimen of 5-FU/LV. Therapy consisted of a weekly i.v. infusion of 5-FU at 2600 mg/m2 administered concomitantly with LV at 500 mg/m2 over a 24 h period. IFN-alpha 2b was administered by 24 h infusion from the second cycle at escalating dose (4.5, 9, 18 and 27 MU/m2). The maximum tolerated dose of IFN was 18 MU/m2. At 27 MU/m2 two patients complained of diarrhea grade 3, so that the escalation of IFN dose was stopped. Two patients achieved a partial response (IFN level dose 9-18 MU/m2). Eight patients had stable disease. Pharmacokinetics of 5-FU were not influenced by IFN at any level dose. Our results show that doses of IFN of 18 MU/m2 given by a 24 h infusion can be administered safely to an established and active schedule of weekly 24 h infusion of 5-FU and LV. A phase II study has been planned to define the level of activity of this regimen.
A drowsy driver detection system for heavy vehicles (2002)

Driver drowsiness/fatigue is an important cause of combination-unit truck crashes. Drowsy driver detection methods can form the basis of a system to potentially reduce accidents related to drowsy driving. We report on efforts performed at the Carnegie Mellon Driving Research Center to develop such in vehicle driver monitoring systems. Commercial motor vehicle truck drivers were studied in actual fleet operations. The drivers operated vehicles that were equipped to measure vehicle performance and driver psychophysiological data. Based on this work, two drowsiness detection methods are being considered. The first is a video-based system that measures PERCLOS, a scientifically supported measure of drowsiness associated with slow eye closure. The second detection method is based on a model to estimate PERCLOS based on vehicle performance data. A non-parametric (neural network) model was used to estimate PERCLOS using measures associated with lane keeping, steering wheel movements and lateral acceleration of the vehicle.
High performance liquid chromatographic determination of phenolic acids in fruits and vegetables. (1993)

A simple isocratic HPLC technique has been developed for the quantitative analysis of phenolic acids (PAs) in fruits and vegetables. Nine benzoic and cinnamic acid derivatives were separated in less than 30 min, and the resolution was all more than 1.23. The ranges of linearity for PAs standards were 0.2-100 ng, even up to 600 ng (r = 0.983-1.000) and the detection limits were 0.02-0.24 mg/kg. Samples of fresh vegetables and fruits were extracted with 80% methanol and ethyl acetate, then purified with C18 Sep-Pak cartridge and determined by HPLC. This method was applied to the determination of PAs in 7 kinds of fruits and vegetables, i.e., apple, pear, Chinese cabbage, cauliflower, turnip, soybean sprout and white grape wine. The content of the 9 PAs varied widely in the 7 kinds of foods studied. The average concentrations of chlorogenic acid in apple (100.2 mg/kg) and pear (30.8 mg/kg) were quite high, and sinapinic acid was remarkable (42.5 mg/kg) in Chinese cabbage, and protocatechuic acid had the highest concentration of all the PAs in white wine.