gebhart/patrepeval huggingface dataset:
Pharmacology of the short QT syndrome N588K‐hERG K<sup>+</sup> channel mutation: differential impact on selected class I and class III antiarrhythmic drugs (2008)

The degree of drug inhibition of hERG channels may vary based on the level of channel inactivation. Drugs previously identified as useful for treating SQT1 have the least dependence on hERG inactivation. In addition, our findings indicate that amiodarone may warrant further investigation as a potential treatment for SQT1.
Unconventional therapies for cancer: 3. Iscador (1998)

This article, on Iscador, is third in the series that reviews the evidence for the safety and effectiveness of 6 unconventional therapies commonly used by Canadian cancer patients. The purpose and methodology of the review of these therapies appear in part 1 (CMAJ 1998[7]:897-902). Annotated bibliographies providing more detailed references are available in print from the Canadian Breast Cancer Research Initiative (CBCRI; address appears at end of article). The reference lists and the lay summaries of the findings (published in 1997) can be found on the CBCRI’s Web site (www.breast.cancer.ca). The following article adapts the lay summary of information on Iscador for clinicians and provides references for the key findings. [Copies of this and other articles in the series can be found on CMAJ’s Web site (www.cma.ca/cmaj/series/therapy.htm).]
Interaction between path and type constraints (1999)

XML [7], which is emerging as an important standard for data exchange on the World-Wide Web, highlights the importance of semistructured data. Although the XML standard itself does not require any schema or type system, a number of proposals [6, 17, 19] have been developed that roughly correspond to data definition languages. These allow one to constrain the structure of XML data by imposing a schema on it. These and other proposals also advocate the need for integrity constraints, another form of constraints that should, for example, be capable of expressing inclusion constraints and inverse relationships. The latter have recently been studied as path constraints in the context of semistructured data [4, 9]. It is likely that future XML proposals will involve both forms of constraints, and it is therefore appropriate to understand the interaction between them.<br/><br/>This paper investigates that interaction. In particular it studies constraint implication problems, which are important both in understanding the semantics of type/constraint systems and in query optimization. A number of results on path constraint implication are established in the presence and absence of type systems. These results demonstrate that adding a type system may in some cases simplify reasoning about path constraints and in other cases make it harder. For example, it is shown that there is a path constraint implication problem that is decidable in PTIME in the untyped context, but that becomes undecidable when a type system is added. On the other hand, there is an implication problem that is undecidable in the untyped context, but becomes not only decidable in cubic time but also finitely axiomatizable when a type system is imposed.
The Cloud: Requirements for a Better Service (2012)

Cloud computing has rapidly made it to the top of the list of considerations for IT strategies in various organizations. However, there are many unanswered requirements delaying the complete adoption of this paradigm. As a result, it is essential to identify the organizations' wish-list for Cloud services. In this paper, we define a set of requirements for Cloud computing. Then we highlight the level of importance of each one for government organizations' applications, large-scale computations, financial services, healthcare applications, and the online entertainment.
Consistent Individualized Feature Attribution for Tree Ensembles (2018)

Interpreting predictions from tree ensemble methods such as gradient boosting machines and random forests is important, yet feature attribution for trees is often heuristic and not individualized for each prediction. Here we show that popular feature attribution methods are inconsistent, meaning they can lower a feature's assigned importance when the true impact of that feature actually increases. This is a fundamental problem that casts doubt on any comparison between features. To address it we turn to recent applications of game theory and develop fast exact tree solutions for SHAP (SHapley Additive exPlanation) values, which are the unique consistent and locally accurate attribution values. We then extend SHAP values to interaction effects and define SHAP interaction values. We propose a rich visualization of individualized feature attributions that improves over classic attribution summaries and partial dependence plots, and a unique "supervised" clustering (clustering based on feature attributions). We demonstrate better agreement with human intuition through a user study, exponential improvements in run time, improved clustering performance, and better identification of influential features. An implementation of our algorithm has also been merged into XGBoost and LightGBM, see http://github.com/slundberg/shap for details.
Modified Heat-Stable Toxins (hSTa) of Enterotoxigenic Escherichia coli Lose Toxicity but Display Antigenicity after Being Genetically Fused to Heat-Labile Toxoid LT(R192G) (2011)

Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of diarrhea in humans and animals. Heat-stable (STa) and heat-labile (LT) enterotoxins produced by ETEC disrupt fluid homeostasis in host small intestinal epithelial cells and cause fluid and electrolyte hyper-secretion that leads to diarrhea. ETEC strains producing STa or LT are sufficiently virulent to cause diarrhea, therefore STa and LT antigens must be included in ETEC vaccines. However, potent toxicity and poor immunogenicity (of STa) prevent them from being directly applied as vaccine components. While LT toxoids, especially LT(R192G), being used in vaccine development, STa toxoids have not been included. A recent study (IAI, 78:316-325) demonstrated porcine-type STa toxoids [pSTa(P12F) and pSTa(A13Q)] elicited protective anti-STa antibodies after being fused to a porcine-type LT toxoid [pLT(R192G)]. In this study, we substituted the 8th, 9th, 16th, or the 17th amino acid of a human-type STa (hSTa) and generated 28 modified STa peptides. We tested each STa peptide for toxicity and structure integrity, and found nearly all modified STa proteins showed structure alteration and toxicity reduction. Based on structure similarity and toxic activity, three modified STa peptides: STa(E8A), STa(T16Q) and STa(G17S), were selected to construct LT(192)-STa(-toxoid) fusions. Constructed fusions were used to immunize mice, and immunized mice developed anti-STa antibodies. Results from this study provide useful information in developing toxoid vaccines against ETEC diarrhea.
Towards self-replicating materials of DNA-functionalized colloids (2009)

We report the first results of ongoing research that involves the creation of a new class of non-biological materials designed to self-replicate and, as a result, to grow exponentially. We propose a system design that exploits the strong specificity and thermal reversibility of the interactions between colloidal particles functionalized with complementary single-stranded DNA ‘sticky ends’. Here, we experimentally test the fundamentals of the different steps that constitute the self-replication scheme. First of all, we quantitatively study the equilibrium and kinetic aspects of the aggregation–dissociation behavior of the particles. We find that the dissociation transition is very sharp (∼1 °C) and that it occurs at unexpectedly low temperatures, with the dissociation temperature shifting further down when the fraction of sticky ends becomes smaller. The sharpness of the transition and its sensitivity to the sticky end fraction are important control parameters in our self-replication scheme. We further find that for our present purposes it is best to use a DNA construct with a double-stranded backbone, as this largely prevents unwanted hybridization events, such as secondary structure formation. The latter is seen to lead to peculiar aggregation kinetics, due to a competition between inter- and intra-particle hybridization. Finally, we show how one can obtain dual recognition at different temperatures by functionalizing a single particle species with two distinct DNA sequences and we demonstrate the formation of permanent bonds, using the chemical intercalator psoralen and long-wavelength UV exposure.
Position-aware ad hoc wireless networks for inter-vehicle communications (2001)

The Fleetnet project aims at the development of a wireless ad hoc network for inter-vehicle communications. We present the rationale behind the choice of an appropriate radio hardware and the use of a position-based routing approach and outline applications to exploit the Fleetnet platform. In addition, we discuss simulation of vehicle movements as a basis for protocol evaluation as well as aspects of Internet integration of Fleetnet. We state the basic problems together with the intended approach of tackling these challenges, thereby providing an overview of the Fleetnet project
High-intensity terahertz radiation from a microstructured large-area photoconductor (2005)

We present a planar large-area photoconducting emitter for impulsive generation of terahertz (THz) radiation. The device consists of an interdigitated electrode metal-semiconductor-metal (MSM) structure which is masked by a second metallization layer isolated from the MSM electrodes. The second layer blocks optical excitation in every second period of the MSM finger structure. Hence charge carriers are excited only in those periods of the MSM structure which exhibit a unidirectional electric field. Constructive interference of the THz emission from accelerated carriers leads to THz electric field amplitudes up to 85V∕cm when excited with fs optical pulses from a Ti:sapphire oscillator with an average power of 100mW at a bias voltage of 65V applied to the MSM structure. The proposed device structure has a large potential for large-area high-power THz emitters.
Evaluation of strain in AlN thin films grown on sapphire and 6H‐SiC by metalorganic chemical vapor deposition (2006)

Abstract The effect of growth rate on the strain in AlN films grown on sapphire and 6H‐SiC c‐planes at 1150 °C by metalorganic chemical vapor deposition was investigated. The strain was measured by X‐ray diffraction and Raman spectroscopy. It was found that the strain in the films was expressed by the biaxial stress and that it depended on the growth rate of the films and on the surface pre‐treatments. When the growth rate was lower than 2.4 nm/min, the strain was constant, and it was compressive for the films grown on sapphire, and tensile for those on 6H‐SiC. These stresses were produced by the differences of the thermal expansion coefficients between the films and substrates. The low temperature AlN‐buffer layer, which was useful for the high temperature growth of AlN on sapphire, was revealed not to be applicable for 6H‐SiC. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
On Graph Based Cryptocurrency Systems (2019)

Denne oppgaven undersøker og sammenligner trekk ved kryptovaluta basert på blokkjeder med kryptovaluta basert på Rettede Asykliske Grafer (RAG). Blokkjedebasert kryptovaluta møter utfordringer på felt som skalering, desentralisering og ressursutnyttelse. Denne oppgaven undersøker om kryptovaluta som bruker en RAG som sin datastruktur kan løse noen av disse utfordringene. For å besvare dette spørsmålet ble både en teoretisk studie og forskjellige eksperimenter på ulike kryptovalutaer gjennomført. Den teoretiske studien ble gjennomført for å skaffe data på de forskjellige systemene til bruk i sammenligninger mellom dem. Eksperimentene fokuserte på RAG-systemene, siden disse er mye nyere og har mindre forskning enn systemene basert på en blokkjede. \t\n\nResultatene i denne oppgaven viser at RAG systemer generelt sett har bedre løsninger for skalerbarhet. Oppgaven viser også til flere utfordringer disse RAG baserte systemene har, som for eksempel distribuert tjenestenektangrep og en mangel på insentiver i systemene. Oppgaven peker på demonstrert sikkerhet og lang levetid som de største fordelene blokkjedesystemene har over RAG-systemene. Oppgaven legger vekt på valgene som er gjort når man går fra blokkjede til RAG som datalager i en kryptovaluta. Det konkluderes med at RAG-systemer tilbyr bedre skalerbarhet men de har ikke samme tillit blant brukere som blokkjedesystemene.
Inexpensive but accurate driving circuits for quartz crystal microbalances (1999)

The quartz crystal microbalance (QCM) is a common technique which finds a wide variety of applications in many different areas like adsorption, catalysis, analytical chemistry, biochemistry, etc., and more generally as a sensor in the investigation of viscoelastic films. In this article we describe some driving circuits of the quartz which we have realized and tested in our laboratory. These can be assembled with standard components which can be easily found. Their performance, in some cases, is as good as that of the much more expensive frequency modulation technique employed in very precise QCM measurements and which requires high-quality commercial radiofrequency generators and amplifiers.
Tar photoxicity and phototherapy for psoriasis (1975)

The phototoxicity of coal tars was determined by comparing the ultraviolet light (UVL) energy required to produce erythema at tar treated sites (minimal phototoxic dose [MPD]) with the energy required to produce the same degree of erythema at untreated control sites (minimal erythema dose [MED]). The ratio of MED/MPD is the phototoxic index (PI). Tars that were phototoxic had a PI of > 1. Using a UVA (320 to 400 nm) and a UVB (290 to 320 nm) light source, 15 subjects and six tars were tested. All tars were phototoxic to UVA but not to UVB (<i>P</i>< 0.0001). Although tar and UVL is a widely accepted treatment for psoriasis (Goeckerman therapy), the light sources employed at normal exposure times provide insufficient UVA energy to produce a phototoxic reaction to the tars that are used. The therapeutic response seen in psoriatic patients treated with tar and UVL should therefore not be attributed to tar phototoxicity.
Identification of thymidine nucleotidase and deoxyribonucleotidase activities among normal isozymes of 5'-nucleotidase in human erythrocytes. (1984)

The persistence of normal thymidine nucleotidase (ThyNase) activity in subjects with pyrimidine nucleotidase (PyrNase) deficiency suggested the possible existence of separate isozymes in normal human erythrocytes. This hypothesis was confirmed by studies of PyrNase-deficient individuals from five unrelated families. Erythrocytes deficient in PyrNase retained normal activity of an enzyme system preferentially active at pH 6.2 with a variety of 2'-deoxyribonucleoside 5'-monophosphate substrates, including those of uridine, thymidine, and cytidine. Lesser activities were observed with the corresponding ribonucleotides. Normal control hemolysates were also found capable of effectively dephosphorylating purine nucleotides (dAMP greater than AMP) when pH was lowered sufficiently from the pH 7.4-8.0 region commonly used in conventional assays. Variations in substrate specificity, pH optima, kinetics, and sensitivity to inactivation by Pb2+ indicated the existence of multiple 5'-nucleotidase isozymes in normal erythrocytes: PyrNase and deoxyribonucleotidase(s) that might function physiologically in the conversion of DNA-derived nucleotides to diffusible nucleosides. Evolution of such a unique 5'-nucleotidase suggests that normal erythroblast maturation and nuclear extrusion is accompanied by a degree of karyolysis sufficient to require dephosphorylation and clearance of DNA degradation products.
Enhanced Detection of Benzodiazepines by Immunoassay (1997)

Fraser and Meatherall (1) recently reported their results on the ability of five immunoassay systems to detect alprazolam and triazolam metabolites. One of the methods evaluated in the study was the CEDIA DAU benzodiazepine assay from Boehringer Mannheim Corporation (Concord, CA). Subsequent to this study, this product was replaced worldwide with a new product which has substantially different sensitivity to some benzodiazepine compounds. The crossreactivity to triazolarn was increased from 18 to 198%, and the crossreactivity to ~-OH-triazolam was increased from 12 to 193%.
Partial Purification of Plasma Thromboplastin Antecedent (Factor XI) and its Activation by Trypsin (1973)

A persistent puzzle in our understanding of hemostasis has been the absence of hemorrhagic symptoms in the majority of patients with Hageman trait, the hereditary deficiency of Hageman factor (factor XII). One proposed hypothesis is that alternative mechanisms exist in blood through which plasma thromboplastin antecedent (PTA, factor XI) can become active in the absence of Hageman factor. In order to test this hypothesis, the effect of several proteolytic enzymes, among them thrombin, plasma kallikrein, and trypsin, was tested upon unactivated PTA. PTA was prepared from normal human plasma by Ca(3)(PO(4))(2) adsorption, ammonium sulfate fractionation, and successive chromatography on QAE-Sephadex (twice). Sephadex-G150, and SP-Sephadex. The partially purified PTA was almost all in its native form, with a specific activity of 45-70 U/mg protein; the yield was about 10%. It contained no measurable amounts of other known clotting factors, plasmin, plasminogen, nor IgG. Incubation of PTA with trypsin generated potent clot-promoting activity that corrected the abnormally long clotting time of plasma deficient in Hageman factor or PTA but not in Christmas factor. This clot-promoting agent behaved like activated PTA on gel filtration (apparent molecular weight: 185,000) and was specifically inhibited by an antiserum directed against activated PTA. These data suggested that PTA can be converted into its active form by trypsin. PTA was not activated by thrombin, chymotrypsin, papain, ficin, plasmin, plasma kallikrein, tissue thromboplastin, or C. Trypsin converted PTA to its active form enzymatically. Whether trypsin serves to activate PTA in vivo is not yet clear.
Pd(0)‐catalyzed polyaddition of bifunctional vinyloxiranes with 1,3‐dicarbonyl compounds: The synthesis of polymers containing hydroxy and carbonyl groups (2002)

Abstract The palladium(0)‐catalyzed polyaddition of bifunctional vinyloxiranes [1,4‐bis(2‐vinylepoxyethyl)benzene ( 1a ) and 1,4‐bis(1‐methyl‐2‐vinylepoxyethyl)benzene ( 1b )] with 1,3‐dicarbonyl compounds [methyl acetoacetate ( 4 ), dimethyl malonate ( 6 ), and Meldrum's acid ( 8 )] was investigated under various conditions. The polyaddition of 1 with 4 was carried out in tetrahydrofuran with phosphine ligands such as PPh 3 and 1,2‐bis(diphenylphosphino)ethane (dppe). Polymers having hydroxy, ketone, and ester groups in the side groups ( 5 ) were obtained in good yields despite the kinds of ligands employed. The number‐average molecular weight value of 5b was higher than that of 5a . The polyaddition of 1b and 6 was affected by the kinds of ligands employed. The corresponding polymer 7b was not obtained when PPh 3 and 1,2‐bis(diphenylphosphino)ferrocene were used. The polyaddition was carried out with dppe as the ligand and gave polymer 7b in a good yield. The molecular weight of the polymer obtained from 1b and 8 was much higher than those of polymers 5b and 7b . The polyaddition with Pd 2 (dba) 3 · CHCl 3 /dppe as a catalyst (where dba is dibenzylideneacetone) produced polymer 9b in a 92% yield (number‐average molecular weight = 45,600). The stereochemistries of all the obtained polymers were confirmed as an E configuration by the coupling constant of the vinyl proton. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2487–2494, 2002
H5N2 Avian Influenza Outbreak in Texas in 2004: the First Highly Pathogenic Strain in the United States in 20 Years? (2005)

ABSTRACT In early 2004, an H5N2 avian influenza virus (AIV) that met the molecular criteria for classification as a highly pathogenic AIV was isolated from chickens in the state of Texas in the United States. However, clinical manifestations in the affected flock were consistent with avian influenza caused by a low-pathogenicity AIV and the representative virus (A/chicken/Texas/298313/04 [TX/04]) was not virulent for experimentally inoculated chickens. The hemagglutinin (HA) gene of the TX/04 isolate was similar in sequence to A/chicken/Texas/167280-4/02 (TX/02), a low-pathogenicity AIV isolate recovered from chickens in Texas in 2002. However, the TX/04 isolate had one additional basic amino acid at the HA cleavage site, which could be attributed to a single point mutation. The TX/04 isolate was similar in sequence to TX/02 isolate in several internal genes (NP, M, and NS), but some genes (PA, PB1, and PB2) had sequence of a clearly different origin. The TX/04 isolate also had a stalk deletion in the NA gene, characteristic of a chicken-adapted AIV. By analyzing viruses constructed by in vitro mutagenesis followed by reverse genetics, we found that the pathogenicity of the TX/04 virus could be increased in vitro and in vivo by the insertion of an additional basic amino acid at the HA cleavage site and not by the loss of a glycosylation site near the cleavage site. Our study provides the genetic and biologic characteristics of the TX/04 isolate, which highlight the complexity of the polygenic nature of the virulence of influenza viruses.
Spin trapping of superoxide and hydroxyl radicals with substituted pyrroline 1-oxides (1986)

The synthesis of three nitrones, 5-butyl-5-methyl-1-pyrroline 1-oxide (BMPO), 5,5-dipropyl-1-pyrroline 1-oxide (DPPO), and 2-aza-2-cyclopentenespirocyclopentane 2-oxide (CPPO), was conducted with use of the zinc/ammonium chloride reduction of appropriately substituted gamma-nitrocarbonyl compounds. The lipophilicity of these nitrones was estimated by determining their partition coefficients in a 1-octanol/water system. These nitrones were found to possess more lipophilic character than the most frequently used cyclic nitrone, 5,5-dimethyl-1-pyrroline 1-oxide (DMPO), which exhibits a partition coefficient of only 0.02. Hyperfine coupling constants for the spin trapping of superoxide and hydroxyl radical by the various nitrones were determined. The rate of spin trapping of superoxide with each nitrone was conducted by competitive kinetics with superoxide dismutase (SOD). In addition, the ability of DPPO and BMPO to spin trap free radicals generated during the metabolism of menadione by rat enterocyte cells was investigated. From these studies, DPPO and BMPO appear to be more suitable spin traps than DMPO when one is interested in monitoring free radicals generated intracellularly.
Gallium (III) triflate catalyzed efficient Strecker reaction of ketones and their fluorinated analogs (2007)

The synthesis of alpha-aminonitriles and their fluorinated analogs has been carried out in high yield and purity by the Strecker reaction from the corresponding ketones and amines with trimethylsilyl cyanide using gallium triflate in dichloromethane. Monofluoro-, difluro-, or trifluoromethyl groups can be incorporated into the alpha-aminonitrile product by varying the nature of the fluorinated ketones. Study with various fluorinated and nonfluorinated ketones reveals that the choice of proper catalyst and the solvent system (suitable metal triflates as a catalyst and dichloromethane as a solvent) plays the key role in the direct Strecker reactions of ketones.