gebhart/patrepeval huggingface dataset:
Prasugrel (CS-747, LY640315) Hydrochloride, a Novel Thienopyridine Prodrug, Shows Potent Antiplatelet and Antithrombotic Effects with Rapid Onset of Action in Rats. (2005)

Abstract The thienopyridine antiplatelet prodrug clopidogrel bisulfate (C) is widely used for atherothrombotic diseases. However, several reports have described a limitation of C, namely, poor platelet inhibition in many patients following oral dosing. Prasugrel (hydrochloride), currently under investigation in a Phase 3 trial in acute coronary syndrome patients undergoing percutaneous coronary intervention, is a novel thienopyridine antiplatelet prodrug. In recent clinical studies, prasugrel has shown more consistent platelet inhibition than C. To date, several preclinical studies have demonstrated that the prasugrel base formulation has more potent antiplatelet and antithrombotic effects than C. The effects of prasugrel hydrochloride (P), which has a higher solubility than the base formulation, have not been reported. The present studies examined the effects of P on platelet aggregation, arterial thrombosis, and bleeding time in rats. Single oral administration of P (0.3 to 3 mg/kg) resulted in inhibition of platelet aggregation (IPA) induced by ADP in a dose- and time-related manner with an ED50 value of 1.1 mg/kg at 4 hr postdose. After dosing of 3 and 10 mg/kg P, statistically significant IPA was observed at 30 and 15 min, and the time required to achieve 50% IPA was approximately 50 and 23 min, respectively (Figure). These results indicate that P has potent antiplatelet effects with an extremely fast onset of action. Multiple P dosing also resulted in potent IPA, with an ED50 value of 0.45 mg/kg/day (p.o.) at 4 hr after the last dose. Our previous report indicated an ED50 value of C at 4 hr after single oral dosing of 16 mg/kg (Br. J. Pharmacol. 129, 1439, 2000), demonstrating about 10-times greater potency of P compared to C. Potent dose-related antithrombotic effects of P were further confirmed in an arterial thrombosis model in rats. P (0.1–1 mg/kg, p.o.) inhibited thrombus formation in the arterial thrombosis induced by extravascular application of FeCl3 solution. All these results taken together indicate that prasugrel hydrochloride is a novel, potent and fast acting thienopyridine prodrug, potentially providing superior efficacy in the treatment of atherothrombotic disorders. Figure Figure
Multiresistant Gram-negative bacteria: the role of high-risk clones in the dissemination of antibiotic resistance (2011)

Multilocus sequence typing reveals that many bacterial species have a clonal structure and that some clones are widespread. This underlying phylogeny was not revealed by pulsed-field gel electrophoresis, a method better suited to short-term outbreak investigation. Some global clones are multiresistant and it is easy to assume that these have disseminated from single foci. Such conclusions need caution, however, unless there is a clear epidemiological trail, as with KPC carbapenemase-positive Klebsiella pneumoniae ST258 from Greece to northwest Europe. Elsewhere, established clones may have repeatedly and independently acquired resistance. Thus, the global ST131 Escherichia coli clone most often has CTX-M-15 extended-spectrum β-lactamase (ESBL), but also occurs without ESBLs and as a host of many other ESBL types. We explore this interaction of clone and resistance for E. coli, K. pneumoniae, Acinetobacter baumannii- a species where three global lineages dominate--and Pseudomonas aeruginosa, which shows clonal diversity, but includes the relatively 'tight' serotype O12/Burst Group 4 cluster that has proved adept at acquiring resistances--from PSE-1 to VIM-1 β-lactamases--for over 20 years. In summary, 'high-risk clones' play a major role in the spread of resistance, with the risk lying in their tenacity--deriving from poorly understood survival traits--and a flexible ability to accumulate and switch resistance, rather than to constant resistance batteries.
The Spatial Organization of Lipid Synthesis in the Yeast Saccharomyces cerevisiae Derived from Large Scale Green Fluorescent Protein Tagging and High Resolution Microscopy (2005)

The localization pattern of proteins involved in lipid metabolism in the yeast Saccharomyces cerevisiae was determined using C-terminal green fluorescent protein tagging and high resolution confocal laser scanning microscopy. A list of 493 candidate proteins ( approximately 9% of the yeast proteome) was assembled based on proteins of known function in lipid metabolism, their interacting proteins, proteins defined by genetic interactions, and regulatory factors acting on selected genes or proteins. Overall 400 (81%) transformants yielded a positive green fluorescent protein signal, and of these, 248 (62% of the 400) displayed a localization pattern that was not cytosolic. Observations for many proteins with known localization patterns were consistent with published data derived from cell fractionation or large scale localization approaches. However, in many cases, high resolution microscopy provided additional information that indicated that proteins distributed to multiple subcellular locations. The majority of tagged enzymes localized to the endoplasmic reticulum (91), but others localized to mitochondria (27), peroxisomes (17), lipid droplets (23), and vesicles (53). We assembled enzyme localization patterns for phospholipid, sterol, and sphingolipid biosynthetic pathways and propose a model, based on enzyme localization, for concerted regulation of sterol and sphingolipid metabolism that involves shuttling of key enzymes between endoplasmic reticulum, lipid droplets, vesicles, and Golgi.
<title>Optical properties of circulating human blood</title> (1998)

We investigated the optical properties (mu) <SUB>a</SUB>, (mu) <SUB>s</SUB>, and g of human blood under flow conditions using integrating sphere measurements and inverse Monte-Carlo-simulations. The experiments were conducted at 633 nm with regard to the influence of the most important physiological and biochemical blood parameters. In addition, a spectrum of all three parameters was measured in the wavelength range 400 to 2500 nm for oxygenated and deoxygenated blood.
Cell‐Penetrating‐Peptide‐Coated Nanoribbons for Intracellular Nanocarriers (2007)

Wrap it up: Nanoribbons coated with cell-penetrating peptides (CPPs) allowed the encapsulation of hydrophobic guest molecules. The nanoassembly internalized into mammalian cells with high efficiency and showed selective intracellular compartmentalization owing to its sensitivity to the solution environment. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2007/z604576_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Use of OSI IS-IS for routing in TCP/IP and dual environments (1990)

This RFC specifies an integrated routing protocol, based on the OSI Intra-Domain IS-IS Routing Protocol, which may be used as an interior gateway protocol (IGP) to support TCP/IP as well as OSI. This allows a single routing protocol to be used to support pure IP environments, pure OSI environments, and dual environments. This specification was developed by the IS-IS working group of the Internet Engineering Task Force.
Multicentre trial on feeding low birthweight infants: effects of diet on early growth. (1984)

A large multicentre study on the short and long term clinical and developmental outcome of infants randomised to different diets is being undertaken. This report represents an interim analysis of the early postnatal growth performance of an unselected population of 194 preterm infants (gestation, mean (SD) 31 . 0 (2 . 9) weeks; birthweight, mean (SD) 1364 (294) g), both ill and well, examined in two (of four) parallel trials. One trial compared banked breast milk with a new preterm formula (primary trial); the other compared these diets as supplements to maternal milk (supplement trial). A major dietary effect on the number of days taken to regain birthweight and subsequent gains in weight, length, and head circumference was observed in the primary trial. Infants fed banked breast milk and weighing less than 1200 g at birth took a calculated additional three weeks to reach 2000 g compared with those fed on the preterm formula. A significant influence of diet on body proportions was seen in the relation between body weight, head circumference, and length. Similar though smaller differences in growth patterns were seen in the supplement trial. By the time they reach 2000 g, infants of birthweights 1200 to 1849 g fed on banked breast milk and infants below 1200 g fed on either banked breast milk or maternal milk supplemented (as necessary) with banked breast milk, fulfilled stringent criteria for failure to thrive (weight less than 2 SD below the mean for age). Only infants fed the preterm formula as their sole diet had maintained their birth centile by discharge from hospital. The misleading nature of comparisons between extrauterine and intrauterine steady state weight gains is emphasised.
Bacterial peptidoglycan (murein) hydrolases (2008)

Most bacteria have multiple peptidoglycan hydrolases capable of cleaving covalent bonds in peptidoglycan sacculi or its fragments. An overview of the different classes of peptidoglycan hydrolases and their cleavage sites is provided. The physiological functions of these enzymes include the regulation of cell wall growth, the turnover of peptidoglycan during growth, the separation of daughter cells during cell division and autolysis. Specialized hydrolases enlarge the pores in the peptidoglycan for the assembly of large trans-envelope complexes (pili, flagella, secretion systems), or they specifically cleave peptidoglycan during sporulation or spore germination. Moreover, peptidoglycan hydrolases are involved in lysis phenomena such as fratricide or developmental lysis occurring in bacterial populations. We will also review the current view on the regulation of autolysins and on the role of cytoplasm hydrolases in peptidoglycan recycling and induction of beta-lactamase.
Cooperative Effect of Two Surface Amino Acid Mutations (Q252L and E170K) in Glucose Dehydrogenase from Bacillus megaterium IWG3 on Stabilization of Its Oligomeric State (2005)

A thermostable glucose dehydrogenase (GlcDH) mutant of Bacillus megaterium IWG3 harboring the Q252L substitution (Y. Makino, S. Negoro, I. Urabe, and H. Okada, J. Biol. Chem. 264:6381-6385, 1989) is stable at pH values above 9, but only in the presence of 2 M NaCl. Another GlcDH mutant exhibiting increased stability at an alkaline pH in the absence of NaCl has been isolated previously (S.-H. Baik, T. Ide, H. Yoshida, O. Kagami, and S. Harayama, Appl. Microbiol. Biotechnol. 61:329-335, 2003). This mutant had two amino acid substitutions, Q252L and E170K. In the present study, we characterized three GlcDH mutants harboring the substitutions Q252L, E170K, and Q252L/E170K under low-salt conditions. The GlcDH mutant harboring two substitutions, Q252L/E170K, was stable, but mutants harboring a single substitution, either Q252L or E170K, were unstable at an alkaline pH. Gel filtration chromatography analyses demonstrated that the oligomeric state of the Q252/E170K enzyme was stable, while the tetramers of the enzymes harboring a single substitution (Q252L or E170K) dissociated into dimers at an alkaline pH. These results indicated that the Q252L and E170K substitutions synergistically strengthened the interaction at the dimer-dimer interface. The crystal structure of the E170K/Q252L mutant, determined at 2.0-angstroms resolution, showed that residues 170 and 252 are located in a hydrophobic cavity at the subunit-subunit interface. We concluded that these residues in the wild-type enzyme have thermodynamically unfavorable effects, while the Q252L and E170K substitutions increase the subunit-subunit interactions by stabilizing the hydrophobic cavity.
Real-time sign language recognition based on neural network architecture (2011)

In real-time, it is highly essential to have an autonomous translator that can process the images and recognize the signs very fast at the speed of streaming images. In this paper, architecture is being proposed using the neural networks identification and tracking to translate the sign language to a voice/text format. Introduction of Point of Interest (POI) and track point provides novelty and reduces the storage memory requirement.
Prospective Study on the Incidence of Chronic Ear Complaints Related to Gastroesophageal Reflux and on the Outcome of Antireflux Therapy (2002)

Over a 2-year period (1997 to 1999), 5 consecutive adult patients with chronic refractory secretory otitis media (CSOM) and 16 with a chronic refractory feeling of pressure in the ear(s) (CRFP) thought to be related to concomitant eustachian tube dysfunction were prospectively studied for coexisting gastroesophageal reflux (GER). All patients underwent an extensive standardized otorhinolaryngological examination, ambulatory 24-hour dual-probe esophageal pH monitoring with a distal pH probe 5 cm and a proximal probe 20 cm above the lower esophageal sphincter, and upper gastrointestinal endoscopy. Most of them also underwent esophageal manometry. All patients with CSOM and 12 of the 16 patients with CRFP had evidence of GER. Only 5 patients experienced heartburn or regurgitation. All patients responded very well to antireflux therapy with omeprazole 20 mg twice per day (40 mg twice per day in 2 patients) accompanied by conservative antireflux measures, ie, complete cessation of their middle ear complaints. This study demonstrates the role of GER in the pathogenesis of refractory CSOM and CRFP and the effectiveness of sustained antireflux therapy.
The Role of Thionins in Plant Protection (1994)

Abstract Thionins are a group of small (5000 Da), sulfur-rich plant proteins found mainly in cereals and mistletoes. Their three-dimensional structures are very compact and amphipathic, stabilized by three or four disulfide bridges. Thionins are usually basic and exert toxicity in various biological systems by destroying membranes. Thionins are synthesized as preproproteins and secreted into vacuoles, protein bodies, and the cell wall. Their antibacterial and antifungal activities point to a role as plant defense proteins. Support for this possible function comes particularly from work on the leaf thionins of barley, showing that these proteins can be induced by several stress factors. Infection of barley with mildew, one of its most devastating pathogens, leads to an incorporation of leaf thionins into papillae in incompatible interactions. The possible role of thionins to enhance the resistance of crop plants by genetic engineering is discussed.
Phase II Study of the Oral MEK Inhibitor Selumetinib in Advanced Acute Myelogenous Leukemia: A University of Chicago Phase II Consortium Trial (2013)

Selumetinib is associated with modest single-agent antileukemic activity in advanced AML. However, given its favorable toxicity profile, combination with drugs that target other signaling pathways in AML should be considered. The potential association of SNP rs3733542 in exon 18 of the KIT gene with antileukemic activity of selumetinib is intriguing, but will require validation in larger trials.
Classification of Agents-based Mobile Assistants (2004)

In this paper, we argue that agent-based approaches oﬀer &#13;\npromising techniques for dealing with the challenges of service delivery &#13;\nto mobile users. In particular, we present a classiﬁcation of the types &#13;\nof services agents can oﬀer as mobile assistants. This serves both as &#13;\na guide for analysing existing systems, and as a means for identifying &#13;\nnew opportunities. We review a number of existing attempts to build &#13;\nagent-based mobile assistants applications and we place these within our &#13;\nclassiﬁcation. &#13;\n
Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 2: Smoke chemistry and in vitro toxicological evaluation using smoking regimens reflecting human puffing behavior (2012)

Chemical analysis of up to 49 harmful and potentially harmful constituents (HPHC) in mainstream smoke, in vitro cytotoxicity of the particulate and gas/vapor phase of mainstream smoke determined in the Neutral Red Uptake assay, and in vitro bacterial mutagenicity of the particulate phase determined in the Salmonella typhimurium Reverse Mutation (Ames) assay are reported for three Electrically Heated Cigarette Smoking System (EHCSS) series-K cigarettes, the University of Kentucky Reference Cigarette 2R4F, and a number of comparator commercial conventional lit-end cigarettes (CC) under ISO machine-smoking conditions and a total of 25 additional smoking regimens reflecting 'human puffing behavior' (HPB). The smoking machines were set to deliver nicotine yields for the EHCSS and comparator CC derived from the 10th percentile to the 90th percentile of nicotine uptake distributions in smokers determined in two clinical studies. Duplication of the smoking intensity 'per cigarette' on a smoking machine may provide an insight into product performance that is directly relevant to obtaining scientific evidence for reduced exposure substantiation based on mainstream cigarette smoke HPHC-to-nicotine regressions. The reported data support an overall evaluation of reduced exposure to HPHC and biological activity.
β-Turns and their distortions: a proposed new nomenclature (1990)

Using the new version of a Protein Structural Database, BIPED, beta-turns have been extracted from 58 non-identical proteins (resolution less than or equal to 2 A) using the standard criteria that the distance between C alpha i and C alpha i + 3 is less than 7 A and that the central residues are not helical. It has been shown that 42% of these do not fit into the eight conventional turn types (I, I', II, II', VIa, VIb and VIII) as defined by phi, psi limits for residues i + 1 and i + 2. Most of the unclassified turns are 'distortions' of the standard turn types, lying just outside the specified limits. Eleven per cent of the turns are not related to the standard types, and have completely different phi, psi combinations. Therefore, the conformational space available to a trans tetrapeptide has been explored to find all two-residue phi, psi combinations which satisfy the criteria for beta-turn formation. The conformations generated by the search are the conformations observed in the data. On the basis of these observations a new nomenclature is suggested for beta-turns based on a shorthand descriptor of populated regions of the phi, psi plot. For example, it is proposed that a type I turn should now be described as an alpha alpha turn, the descriptor indicating the phi, psi regions of the i + 1 and i + 2 positions of the turn. The use of descriptors, which convey information about the turn type conformation, should aid protein structural workers in turn classification and visualization. The sequence preferences for the alpha beta turn have been elucidated: Pro, Asp and Ser at i + 1; Asn and His at i + 2; Pro at i + 3. These preferences have been explained in terms of specific interactions involving the side-chains. The beta-turn prediction program, BTURN 1.0, has been further developed by alterations to the calculation of parameters, the removal of incompatible multiple turn predictions and the inclusion of the distorted types alpha alpha and beta p gamma data in the respective sets of parameters, to yield BTURN 2.0. A variation of this beta-turn prediction program, called GORBTURN 1.0, has been developed, which uses the directional parameters produced from work by Garrett et al., to eliminate potential helix and strand-forming residues from the beta-turn prediction.(ABSTRACT TRUNCATED AT 400 WORDS)
SYNbiotics Easing Renal failure by improving Gut microbiologY (SYNERGY): a protocol of placebo-controlled randomised cross-over trial (2014)

Universal Trial Number: U1111-1142-4363. Australian New Zealand Clinical Trials Registry Number: ACTRN12613000493741, date registered: 2nd May 2013.
Structure of a promoter for T7 RNA polymerase. (1977)

We have determined the nucleotide sequence of a Hpa II restriction fragment of the phage T7 DNA containing a promoter for the phage-specified RNA polymerase. (Hpa II is a restriction endonuclease from Haemophilus parainfluenzae.) Mapping of the Hpa II restriction fragments on the T7 genome shows this promoter to be the second of tandem promoters separated by approximately 170 base pairs that begin transcription by the T7 RNA polymerase at approximately 15% of the genome. Features of the sequence involved in recognition by the T7 RNA polymerase are discussed and include the following region of hyphenated 2-fold symmetry (boxed regions are related through a 2-fold axis of symmetry at the center of the sequence shown). (See article). This sequence includes the initiation site, since the message transcribed from this fragment begins pppG-G-G-A. Combination of our results with work of others has permitted this fragment to be mapped at the junction of T7 genes 1 and 1.1. The RNA transcribed from this fragment begins within gene 1 and contains the RNase III cleavage site that lies between genes 1 and 1.1. This sequence is compared to other processing sites in T7 early message.
Fixation strength of a biodegradable interference screw and a press‐fit technique in anterior cruciate ligament reconstruction with a BPTB graft (1997)

The objective of this study was to evaluate the fixation strength of a biodegradable interference screw (Arthrex, Naples, FL) compared with press fit fixation and a titanium interference screw in anterior cruciate ligament (ACL) reconstruction using a bone-patellar tendon-bone (BPTB) graft. Porcine lower limbs were used. Ultimate failure loads of the biodegradable screw (805.2 N; range 680 to 995 N) did not differ significantly from ultimate failure loads of titanium interference screws (768.6 N; range 544 to 1094 N). Press fit fixation provided significant (P < .01) lower fixation strength (462.5 N; range 80 to 825 N). These results support the conclusion that biodegradable interference screws are a reasonable alternative in terms of primary fixation strength.
ASAView: Database and tool for solvent accessibility representation in proteins (2004)

These graphical plots of solvent accessibility are likely to provide a quick view of the overall topological distribution of residues in proteins. Chain-wise computation of solvent accessibility is also provided.
Increased Sympathetic and Decreased Parasympathetic Activity Rather Than Changes in Hypothalamic-Pituitary-Adrenal Axis Activity Is Associated with Metabolic Abnormalities (2010)

Our findings suggest that increased sympathetic and decreased parasympathetic nervous system activity is associated with metabolic syndrome, whereas HPA axis activity is not.