gebhart/patrepeval huggingface dataset:
Redefinition of the human kappa opioid receptor gene (OPRK1) structure and association of haplotypes with opiate addiction (2004)

The kappa opioid receptor (KOR) plays a role in stress responsivity, opiate withdrawal and responses to cocaine. KOR activation by its endogenous ligand dynorphin A(1-17) decreases basal and drug-induced striatal levels of dopamine. The complete structure of the human KOR gene (hOPRK1) has not been previously determined. This study: (i) characterized the genomic structure of the hOPRK1 gene; (ii) identified single nucleotide polymorphisms (SNPs) in the hOPRK1 gene; and (iii) investigated possible associations of these variants with vulnerability to develop heroin addiction. Analysis of 5'-RACE cDNA clones revealed the presence of a novel exon 1 ranging in length from 167 to 251 nucleotides in the 5' 5'-untranslated region of the hOPRK1 mRNA. We found that the hOPRK1 gene has four major exons and three introns, similar to rodent OPRK1 genes. Direct sequencing of amplified DNA containing all four exons and intron 1 of the hOPRK1 gene were evaluated for polymorphisms in 291 subjects (145 former heroin addicts and 146 controls). Twelve SNPs were identified, nine novel variants and three previously reported SNPs. Using logistic regression with opioid dependence as the dependent variable, the 36G>T SNP exhibited a point-wise significant association (P = 0.016) with disease status. The number of haplotypes seen in the three ethnic groups were nine, six and five for African-Americans, Caucasians, and Hispanics, respectively, with corresponding significance levels for differences in haplotype frequencies between cases and controls of P = 0.0742, 0.1015 and 0.0041. Combining ethnicities by Fisher's method yields an empirical significance level of P = 0.0020.
An implantable mixed analog/digital neural stimulator circuit (2003)

This paper describes a chip for a multichannel neural stimulator for functional electrical stimulation. The chip performs all the signal processing required in an implanted neural stimulator. The power and signal transmission to the stimulator is carried out via an inductive link. From the signals transmitted to the stimulator, the chip is able to generate charge-balanced current pulses with a controllable length and amplitude for stimulation of nerve fibres. The chip has 4 output channels so that it can be employed in a cuff electrode with multiple connections to a nerve. The purpose of the functional electrical stimulation is to restore various bodily functions (e.g. motor functions) in patients who have lost them due to injury or disease.
Deep learning to generate in silico chemical property libraries and candidate molecules for small molecule identification in complex samples (2019)

Comprehensive and unambiguous identification of small molecules in complex samples will revolutionize our understanding of the role of metabolites in biological systems. Existing and emerging technologies have enabled measurement of chemical properties of molecules in complex mixtures and, in concert, are sensitive enough to resolve even stereoisomers. Despite these experimental advances, small molecule identification is inhibited by (i) chemical reference libraries (e.g. mass spectra, collision cross section, and other measurable property libraries) representing <1% of known molecules, limiting the number of possible identifications, and (ii) the lack of a method to generate candidate matches directly from experimental features (i.e. without a library). To this end, we developed a variational autoencoder (VAE) to learn a continuous numerical, or latent, representation of molecular structure to expand reference libraries for small molecule identification. We extended the VAE to include a chemical property decoder, trained as a multitask network, in order to shape the latent representation such that it assembles according to desired chemical properties. The approach is unique in its application to metabolomics and small molecule identification, with its focus on properties that can be obtained from experimental measurements (m/z, CCS) paired with its training paradigm, which involved a cascade of transfer learning iterations. First, molecular representation is learned from a large dataset of structures with m/z labels. Next, in silico property values are used to continue training, as experimental property data is limited. Finally, the network is further refined by being trained with the experimental data. This allows the network to learn as much as possible at each stage, enabling success with progressively smaller datasets without overfitting. Once trained, the network can be used to predict chemical properties directly from structure, as well as generate candidate structures with desired chemical properties. Our approach is orders of magnitude faster than first-principles simulation for CCS property prediction. Additionally, the ability to generate novel molecules along manifolds, defined by chemical property analogues, positions DarkChem as highly useful in a number of application areas, including metabolomics and small molecule identification, drug discovery and design, chemical forensics, and beyond.
1.1 W continuous-wave, narrow spectral width (&lt;1 Å) emission from broad-stripe, distributed-feedback diode lasers (λ=0.893 μm) (1998)

By etching a distributed-feedback grating directly into the Al-free optical confinement region of a 100 μm stripe InGaAs/InGaP/GaAs diode laser, 1.1 W cw front-facet output power has been obtained at 0.893 μm with a spectral full width at half maximum of 0.9 Å. These devices have 1 mm long cavities and shallow gratings with a coupling coefficient, κ∼7 cm−1. The combination of long device length and low grating coupling results in both efficient operation as well as a longitudinally uniform field profile. As a result, all excited lateral modes oscillate at the same longitudinal cavity resonance to high power levels. Using shallow gratings etched in an InGaP upper confinement layer permits the growth of a high-quality cladding layer over the grating surface yielding excellent device performance. Facet-coated (5%/95%) devices demonstrate external differential quantum efficiencies of 51% and peak wallplug efficiencies of 32% at 1.1 W cw output power.
A Learning Optimizer for a Federated Database Management System. (2005)

Anfrageoptimierer in modernen Datenbanksystemen (DBS) verwenden ein Kostenmodell, um fur eine Anfrage einen effizienten Zugriffsplan aus der Menge aller moglichen Zugriffsplane auszuwahlen. Die Genauigkeit, mit der diese Kosten geschatzt werden, hangt stark davon ab, wie genau Statistiken uber die Datenverteilung die ihnen zugrunde liegenden Daten modellieren. Veraltete Statistiken, oder ungultige Annahmen im statistischen Modell, fuhren haufig zur Auswahl suboptimaler Zugriffsplane und dadurch zu Defiziten bei der Ausfuhrungsgeschwindigkeit von Datenbankanfragen. Foderierte Systeme mussen auf dem koordinierenden DBS Statistiken uber verteilte Daten unterhalten, um effiziente Zugriffsplane zu entwickeln, wenn Daten aus verschiedenen Datenquellen zusammengefuhrt werden. Fehlerhafte Statistiken verursachen in diesem Fall schlechte Lastenverteilung sowie zusatzlichen Kommunikationsaufwand und Netzlast. Die Synchronisation dieser zusatzlichen Statistiken mit den Statistiken der entfernten Datenquellen ist problematisch, da Datenquellen vollig unabhangig voneinander sind und ihre Statistiken eventuell nicht externalisieren oder inkompatible bzw. andere statistische Modelle verwenden als das koordinierende DBS. Im folgenden zeigen wir eine Erweiterung der Feedback-Schleife von DB2s lernendem Optimierer (LEO) auf foderierte Architekturen, die es LEO ermoglicht, automatisch Statistiken uber Daten auf entfernten Datenquellen zu lernen und zu verwalten. Wir diskutieren mehrere Moglichkeiten, Feedback fur foderierte Anfragen zu erhalten und stellen einen Losung vor, die lokales Feedback verwendet, und einen Stichprobenprozess (statistical sampling) zu steuren, der die benotigten entfernten Daten basierend auf dem Feedback effizient ermittelt. Mittels einer detaillierten Leistungsanalyse der vorgestellten Moglichkeiten im Rahmen einer Fallstudie belegen wir, dass der potenzielle Geschwindigkeitszuwachs fur Datenbankanfragen sehr hoch ist, wahrend die Zusatzbelastung durch LEO in moderaten Grenzen liegt.
Isosorbide-based Polymethacrylates (2015)

A new monomer, acetylated methacrylic isosorbide (AMI), was synthesized in two steps employing scandium(III) triflate as a remarkably efficacious catalyst for the tandem esterification of isosorbide with acetic anhydride and methacrylic anhydride. Analysis of the crude product mixture after acetylation indicated that functionalization occurred preferentially at the endo hydroxyl group of isosorbide (endo-acetate:exo-acetate = 4.2:1). Reaction of this mixture with methacrylic anhydride gave the corresponding isomeric mixture of AMI monomers. Poly(AMI) [PAMI] prepared by radical polymerization of the mixture of AMI regioisomers was found to have a high glass transition temperature (Tg ≈ 130 °C) and good thermal stability (Td, 5% weight loss; N2 = 251 °C, air = 217 °C). Reversible addition–fragmentation chain transfer (RAFT) polymerization of AMI using a new chain transfer agent, hydroxyethyl 4-cyano-4-(phenylcarbonothioylthio)pentanoate (HO-CPAD), yielded PAMI-CTA samples with controlled molar masses and narrow molar mass distributions (Đ ≤ 1.09). Subsequent chain extension of PAMI-CTA with n-butyl acrylate gave a series of PAMI-b-PnBA block copolymers ranging from 17–36 wt % PAMI. All samples of PAMI-b-PnBA exhibited two well-separated Tg values at approximately −45 and +120 °C, indicative of microphase separation.
Noise quenching in lasers and masers by strong coherent pumping (1991)

An intense single-mode correlated-spontaneous-emission laser or maser can be realized by driving the active atoms coherently with an injected external field. The scheme involves single-photon transitions unlike the two-photon or quantum-beat correlated-emission lasers that utilize correlations between successive photon-cascade emissions or between simultaneous emissions into modes of the field. Quenching of both the amplitude and phase noise and, in certain cases, squeezing of the amplitude fluctuations are found.
Air Cooling Concepts for Li-Ion Battery Pack in Cell Level (2017)

Computational Fluid Dynamics (CFD) modeling is used to study different cooling architectures for the next generation (Gen-2) EREV Li-Ion battery package. There might be advantages of air cooled batteries with respect to complexity, cost and reliability compared to liquid cooled systems like the EREV (Extended Range Electric Vehicle) GEN1 battery. Therefore, the feasibility of air cooling architectures is investigated first and later liquid cooling strategies. In this study, the thermal performance and pressure drop of the cell level for two of the core product designs are reported. The parameters considered in this study include two different heat generations (heat sources) by the battery pack and three cooling flow rates. The heat generations used are 500 W and 1500 W representing the normal driving and peak load conditions, respectively. The cooling flow rates are 100, 200 and 600 m3/h. The battery cell temperatures, both in terms of absolute value and the variation within the cell, and the pressure drop which is related to the required pumping power, are evaluated and presented.
Halloysite clay nanotubes as a ceramic “skeleton” for functional biopolymer composites with sustained drug release (2013)

Halloysite, naturally occurring clay nanotubes, is described as an additive for functional polymer composites. Due to the empty tubular lumen capable of being loaded with chemically active agents, halloysite provides additional functions (drug delivery, antibiotic, flame-retardant, anticorrosion, and crack self-healing) to polymeric composites synergistically combined with enhanced tensile, impact and adhesive strength. Doping loaded clay nanotubes into a polymeric matrix provides a kind of ceramic "skeleton", and these "skeleton bones" are loaded with functional chemicals like real bones loaded with marrow. Tunable controlled release of active agents through synthesis of artificial nano-caps at the tube endings and halloysite lumen enlargement by selective etching allowed for tubular nanocontainers with chemicals release time from 10 to 200 h and a loading capacity of ca. 30 wt%. Halloysite is well mixable with polymers of high and medium polarities without any surface modification.
Immunization Against Feline Calicivirus Infection (1976)

Forty-three cats (experiments 1 and 2) were vaccinated (2 doses, 27 and 30 days between doses) with the F-9 strain of feline calicivirus by the intramuscular route. There was no untoward response in any of the cats to the administration of the vaccinal virus nor was there spread of the virus from 20 vaccinated cats to nonvaccinated cats held in contact during the next 6 months (experiment 2). The vaccinated cats developed serum-neutralizing antibodies that were increased further after the 2nd vaccination. The level of serum-neutralizing antibodies was related to the quantity of vaccinal virus administered. Twenty-three cats vaccinated with the F-9 strain were protected to a significant degree when challenge exposed to virulent calicivirus strain FPV-255 (experiment 1).
Initial Characterization of a Rat Model of Diabetic Nephropathy (2004)

The lack of an appropriate animal model that spontaneously develops diabetic nephropathy has been a significant limitation in the search for genetic factors underlying this disease and the development of new therapeutic strategies to prevent progressive renal disease in diabetes. We introgressed the mitochondria and some passenger loci from the FHH/EurMcwi rat into the genetic background of diabetic GK rats, creating a new rat strain, T2DN (T2DN/Mcwi). Despite the high degree of genetic similarity between T2DN and GK rats (97% at 681 loci), diabetes ensues earlier and progresses more severely in T2DN rats. T2DN rats exhibit proteinuria by 6 months of age, accompanied by renal histologic abnormalities such as focal glomerulosclerosis, mesangial matrix expansion, and thickening of basement membranes. These characteristics progress over time, and nearly all T2DN rats exhibit diffuse global glomerulosclerosis with nodule formation and arteriolar hyalinosis by 18 months of age. The histologic changes in the kidney of T2DN rats closely mimic the changes seen in the kidney of patients with diabetes. These results indicate that the T2DN rat is a suitable model for investigating diabetic nephropathy. Here we report the initial genetic and physiological characterization of this new rat model of diabetic nephropathy.
DBXplorer: a system for keyword-based search over relational databases (2003)

Internet search engines have popularized the keyword-based search paradigm. While traditional database management systems offer powerful query languages, they do not allow keyword-based search. In this paper, we discuss DBXplorer, a system that enables keyword-based searches in relational databases. DBXplorer has been implemented using a commercial relational database and Web server and allows users to interact via a browser front-end. We outline the challenges and discuss the implementation of our system, including results of extensive experimental evaluation.
Genetic and Molecular Analysis of High Gamma‐Tocopherol Content in Sunflower (2006)

Sunflower ( Helianthus annuus L.) seeds contain alpha‐tocopherol as the major tocopherol derivative, which accounts for more than 900 g kg −1 total tocopherols. However, four sources of high gamma‐tocopherol content (>850 g kg −1 ) have been developed. First studies on the lines LG‐17 and T2100 concluded that the trait in both lines was determined by recessive alleles at the Tph2 locus. The objectives of the present research were (i) to conduct an allelic study on the other two lines, IAST‐1 and IAST‐540, (ii) to identify markers linked to the Tph2 gene, and (iii) to map this gene. Plants of T2100 were crossed with plants of the other three lines, which resulted in F 1 and F 2 populations with uniformly high gamma‐tocopherol content in the seeds, indicating the presence of tph 2 alleles in the four lines. Genetic mapping of the Tph2 gene was conducted with an F 2 population from the cross between CAS‐12, with standard tocopherol profile, and IAST‐540. F 2 seeds segregated following a 3 low to 1 high gamma‐tocopherol ratio. Bulked segregant analysis identified two simple sequence repeats (SSR) markers on linkage group (LG) 8 linked to Tph2. A large linkage group was constructed by genotyping additional markers. Tph2 mapped between markers ORS312 (3.6 cM proximal) and ORS599 (1.9 cM distal). The availability of closely linked PCR‐based markers and the location of the Tph2 gene on the sunflower genetic map will be useful for marker‐assisted selection and further characterization of tocopherol biosynthesis in sunflower seeds.
Quasi-distributed fibre optics polarimetric chemical sensor (2005)

A quasi-distributed fibre optics polarimetric sensor has been studied both theoretically and experimentally. Theoretical results demonstrate the feasibility of such a sensor when a polarization-maintaining optical fibre has been properly designed. Two designs are proposed. Distributed detection of water has been demonstrated with a standard polarization-maintaining fibre whose cladding was locally removed by chemical etching.
The Relationship between Ligand Aggregation and G-Quadruplex DNA Selectivity in a Series of 3,4,9,10-Perylenetetracarboxylic Acid Diimides (2002)

Human telomeres are comprised of d(TTAGGG) repeats that are capable of forming G-quadruplex DNA structures. Ligands that bind to and stabilize these G-quadruplex DNA structures are potential inhibitors of the cancer cell-associated enzyme telomerase. Other potential biological uses of G-quadruplex targeting ligands have been proposed. One particularly challenging aspect of the contemplated uses of G-quadruplex targeting ligands is their selectivity for G-quadruplex DNA versus double-stranded DNA structures. We have previously reported the observation that two structurally related 3,4,9,10-perylenetetracarboxylic acid diimide-based G-quadruplex DNA ligands, PIPER [N,N'-bis(2-(1-piperidino)ethyl)-3,4,9,10-perylenetetracarboxylic acid diimide] and Tel01 [N,N'-bis(3-(4-morpholino)propyl)-3,4,9,10-perylenetetracarboxylic acid diimide], have different levels of G-quadruplex DNA binding selectivity at pH 7 as determined by absorbance changes in the presence of different DNA structures [Kerwin, S. M., Chen, G., Kern, J. T., and Thomas, P. W. (2002) Bioorg. Med. Chem. Lett. 12, 447-450]. Here we report that the less G-quadruplex DNA selective ligand PIPER can unwind double-stranded, closed circular plasmid DNA, as determined by a topoisomerase I assay. A model for the interaction of Tel01 with the G-quadruplex DNA structure formed by d(TAGGGTTA) was determined from NMR experiments. This model is similar to the previously published model for PIPER bound to the same G-quadruplex DNA and failed to provide a structural basis for the observed increased selectivity of Tel01 interaction with G-quadruplex DNA. In contrast, investigation into the aggregation state of Tel01 and PIPER as well as other 3,4,9,10-perylenetetracarboxylic acid diimide analogues bearing basic side chains demonstrates that ligand aggregation is correlated with G-quadruplex DNA binding selectivity. For all six analogues examined, those ligands that were aggregated at pH 7 in 70 mM potassium phosphate, 100 mM KCl, 1 mM EDTA buffer also demonstrated G-quadruplex DNA binding selectivity under these buffer conditions. Ligands that were not aggregated under these conditions display much lower levels of G-quadruplex DNA selectivity. The aggregation state of these ligands is extremely sensitive to the buffer pH. Tel01, which is aggregated at pH 7, is not aggregated at pH 6.4, where it demonstrates only modest G-quadruplex DNA binding selectivity, and PIPER in pH 8.5 buffer is both aggregated and highly G-quadruplex DNA-selective. To our knowledge, these studies demonstrate the first DNA structure selectivity as achieved through pH-mediated ligand aggregation. The potential impact of these findings on the selectivity of other classes of G-quadruplex DNA ligands is discussed.
Heterocyclic Amine Precursors to Sulfonylurea Herbicides (1991)

Numerous substituted pyrimidine and triazine amines have found utility as precursors to highly active and crop selective sulfonylurea herbicides. In the process of optimizing herbicidal efficacy and crop safety within this class, a variety of structurally diverse heterocyclic amines have been synthesized and evaluated. This paper reviews the methods of preparation that have been developed for some of the different structural types used as intermediates to active sulfonylurea herbicides. These methods include cyclizations, rearrangements, and side-chain metalations that have led to furo[2,3-d]pyrimidines, pyrazinones, and selectively functionalized pyrimidines, triazines, triazoles, and pyridines.
A suppressor to prevent direct wave-induced cavitation in shock wave therapy devices (2005)

Cavitation plays a varied but important role in lithotripsy. Cavitation facilitates stone comminution, but can also form an acoustic barrier that may shield stones from subsequent shock waves. In addition, cavitation damages tissue. Spark-gap lithotripters generate cavitation with both a direct and a focused wave. The direct wave propagates as a spherically diverging wave, arriving at the focus ahead of the focused shock wave. It can be modeled with the same waveform (but lower amplitude) as the focused wave. We show with both simulations and experiments that bubbles are forced to grow in response to the direct wave, and that these bubbles can still be large when the focused shock wave arrives. A baffle or "suppressor" that blocks the propagation of the direct wave is shown to significantly reduce the direct wave pressure amplitude, as well as direct wave-induced bubble growth. These results are applicable to spark-gap lithotripters and extracorporeal shock wave therapy devices, where cavitation from the direct wave may interfere with treatment. A simple direct-wave suppressor might therefore be used to improve the therapeutic efficacy of these devices.
Concepts and Nonmedical Applications of NMR Imaging (1984)

Nuclear Magnetic Resonance Imaging (NMRI) is based on a fundamental relationship in NMR: where ω is the resonant frequency (in radian/sec), ɣ is the gyromagnetic ratio, and H is the magnetic field strength. Application of a linear field gradient across a sample, therefore, gives rise to a spatially dependent distribution of NMR frequencies.