gebhart/patrepeval huggingface dataset:
A New Method for Straightening DNA Molecules for Optical Restriction Mapping (1997)

We have developed an improved method of straightening DNA molecules for use in optical restriction mapping. The DNA was straightened on 3-aminopropyltriethoxysilane-coated glass slides using surface tension generated by a moving meniscus. In our method the meniscus motion was controlled mechanically, which provides advantages of speed and uniformity of the straightened molecules. Variation in the affinity of the silanized surfaces for DNA was compensated by precoating the slide with single-stranded non-target blocking DNA. A small amount of MgCl2 added to the DNA suspension increased the DNA-surface affinity and was necessary for efficient restriction enzyme digestion of the straightened surface-bound DNA. By adjusting the amounts of blocking DNA and MgCl2, we prepared slides that contained many straight parallel DNA molecules. Straightened lambda phage DNA (48 kb) bound to a slide surface was digested by EcoRI restriction endonuclease, and the resulting restriction fragments were imaged by fluorescence microscopy using a CCD camera. The observed fragment lengths showed excellent agreement with their predicted lengths.
Gee Fu: a sequence version and web-services database tool for genomic assembly, genome feature and NGS data (2011)

dan.maclean@tsl.ac.uk.
Accurate modeling of trench isolation induced mechanical stress effects on MOSFET electrical performance (2003)

A new approach is presented aimed at modeling mechanical stress effects which impact MOSFET electrical behavior. It is successful in accounting for mobility variations experimentally evidenced on complex MOSFET geometries. The newly developed mobility model proves to be an efficient way to include mechanical stress effects into standard simulation models. We show that stress effects can and should be taken into account in the IC design phase in present and sub 90 nm nodes CMOS generations.
Fatty acyl transfer by human N-myristyl transferase is dependent upon conserved cysteine and histidine residues. (1994)

N-Myristyl transferase (Nmt) catalyzes attachment of myristate onto the N terminus of suitable proteins. In order to identify amino acids important for catalytic functions, human Nmt and mutants representing all six conserved cysteine and histidine residues (Cys-169, Cys-214, His-131, His-171, His-218, and His-293) were expressed in Escherichia coli and analyzed for their ability to bind and transfer myristic acid. N-Terminal histidine-tagged fusion proteins displayed varying abilities to form an association with radiolabeled myristic acid indicative of an acyl-enzyme intermediate. When co-expressed with an acceptor substrate protein, pp60v-src, the mutants showed differential incorporation of radiolabeled myristic acid into v-Src protein. In vitro experiments monitoring transfer of myristyl CoA to a peptide homologous to the N terminus of pp60 v-src gave results similar to those obtained in vivo. Our studies showed that mutation at Cys-169, His-171, and especially His-293 interfered with formation of an acyl-enzyme intermediate, while human Nmts containing mutations at Cys-169, His-218, or His-293 showed greatly attenuated abilities to form acylated product. We propose a model for the Nmt reaction mechanism in which Cys-169 serves as the fatty acid attachment site for a covalent myristyl enzyme intermediate, while His-171 acts as a general acid/base and His-293 as a specific acid/base during acyl-enzyme intermediate formation. His-218 could then act as an acid or base needed to catalyze transfer of the acyl group from the acyl-enzyme intermediate to a polypeptide substrate. This working model will be useful for the design of regulators of Nmt function.
The concentration of the cross-linking agent as a tool for the control of release and swelling properties of gelatin microspheres. (1992)

The effect of the concentration of a cross-linking agent (gelatin hardener) on gelatin microspheres was evaluated. A concentration increase of the gelatin hardener (formaldehyde) produced a decrease of drug loading, swelling degree and drug release rate. The cross-linking agent concentration affected also the kinetics of water absorption and drug release. This paper suggests a decreasing significance of the diffusion-type mechanism of drug release as the concentration of the cross-linking agent increased.
Dynamics of CRISPR-Cas9 genome interrogation in living cells (2015)

The RNA-guided CRISPR-associated protein Cas9 is used for genome editing, transcriptional modulation, and live-cell imaging. Cas9-guide RNA complexes recognize and cleave double-stranded DNA sequences on the basis of 20-nucleotide RNA-DNA complementarity, but the mechanism of target searching in mammalian cells is unknown. Here, we use single-particle tracking to visualize diffusion and chromatin binding of Cas9 in living cells. We show that three-dimensional diffusion dominates Cas9 searching in vivo, and off-target binding events are, on average, short-lived (<1 second). Searching is dependent on the local chromatin environment, with less sampling and slower movement within heterochromatin. These results reveal how the bacterial Cas9 protein interrogates mammalian genomes and navigates eukaryotic chromatin structure.
Rat Brain p64H1, Expression of a New Member of the p64 Chloride Channel Protein Family in Endoplasmic Reticulum (1997)

Many plasma membrane Cl- channels have been cloned, including the cystic fibrosis transmembrane conductance regulator and several members of the voltage-gated ClC family. In contrast, very little is known about the molecular identity of intracellular Cl- channels. We used a polymerase chain reaction-based approach to identify candidate genes in mammalian brain and cloned the cDNA corresponding to rat brain p64H1. This encoded a microsomal membrane protein of predicted Mr 28,635 homologous to the putative intracellular bovine kidney Cl- channel p64. In situ mRNA hybridization histochemistry showed marked expression in hippocampus and cerebellum, and in vitro expression revealed a large cytoplasmic domain, one membrane-spanning segment, and a small nonglycosylated N-terminal luminal domain. The predicted protein contained consensus phosphorylation sites for protein kinase C and protein kinase A, and protein kinase C-mediated phosphorylation increased the Mr of p64H1 to approximately 43,000, characteristic of the native protein in Western blots. Recombinant p64H1 was immunolocalized to the endoplasmic reticulum of human embryonic kidney 293 and HT-4 cells, and incorporation of human embryonic kidney 293 endoplasmic reticulum vesicles into planar lipid bilayers gave rise to intermediate conductance, outwardly rectifying anion channels. Although p64H1 is the first intracellular Cl- channel component or regulator to be identified in brain, Northern blotting revealed transcripts in many other rat tissues. This suggests that p64H1 may contribute widely to intracellular Cl- transport.
DC-biased electrostrictive materials and transducers for medical imaging (2002)

The field-induced electromechanical properties of several electrostrictive materials have been studied for ultrasonic transducer applications. This paper reviews the most important material properties and summarizes the advantages of using electrostrictive materials in medical imaging applications. By controlling electrostrictive material properties, transducers can be operated over a broad temperature range with minimum variation of sensitivity (within 3dB over the operating temperature range). Electrostrictive transducers with either 2 or 4 elevation aperture groups have been built and the results demonstrate the benefits of using electrostrictive tuning capability to achieve elevation aperture control and apodization. A novel type of f/sub 0//2f/sub 0/ switchable transducer in which the operating frequency can be switched between two separated frequency bands expands the usable frequency range to over 100% -6dB bandwidth.
Green Electroluminescent Emission from Substituted Polyacetylenes (1996)

Electroluminescent (EL) cells fabricated utilizing monophenyl and diphenyl substituted polyacetylenes, i.e. poly(phenylacetylene) (PPA) and poly(diphenylacetylene) (PDPA) derivatives, as emitters are reported on. Green light emission from these polymers which are sandwiched between an ITO (indium-tin oxide) coated glass substrate and a Mg/Al cathode has been observed at a 6 V ITO forward bias. Among these polymers, poly[1-( p - n -butylphenyl)-2-phenylacetylene] (PDPA- n Bu) shows the highest efficiency for green light emission. The EL efficiency was improved by doping an electron transporting material, 2-(4-biphenylyl)-5-(4- t -butylphenyl)-1,3,4-oxadiazole (PBD), in these polymers, and a fivefold increase in EL efficiency was achieved.
Discharge current steering for battery lifetime optimization (2003)

Portable and wearable computers can be powered by different combinations of two or more battery packs to give the user the possibility of choosing an optimal compromise between lifetime and weight/size. Recent work on battery-driven power management has demonstrated that sequential discharge is suboptimal in multibattery systems and lifetime can be maximized by distributing (steering) the current load on the available batteries, thereby discharging them in a partially concurrent fashion. Based on these observations, we formulate multibattery lifetime maximization as a continuous, constrained optimization problem, which can be efficiently solved by nonlinear optimizers. We show that significant lifetime extensions can be obtained with respect to standard sequential discharge (up to 160 percent), as well to previously proposed battery scheduling algorithms (up to 12 percent).
Deep Sequencing of the Human TCRγ and TCRβ Repertoires Suggests that TCRβ Rearranges After αβ and γδ T Cell Commitment (2011)

T lymphocytes respond to a broad array of pathogens with the combinatorial diversity of the T cell receptor (TCR). This adaptive response is possible because of the unique structure of the TCR, which is composed of two chains, either αβ or γδ, that undergo genetic rearrangement in the thymus. αβ and γδ T cells are functionally distinct within the host but are derived from a common multipotent precursor. The canonical model for T cell lineage commitment assumes that the γ, δ, and β chains rearrange before αβ or γδ T cell commitment. To test the standard model in humans, we used high-throughput sequencing to catalog millions of TCRγ and TCRβ chains from peripheral blood αβ and γδ T cells from three unrelated individuals. Almost all sampled αβ and γδ T cells had rearranged TCRγ sequences. Although sampled αβ T cells had a diverse repertoire of rearranged TCRβ chains, less than 4% of γδ T cells in peripheral blood had a rearranged TCRβ chain. Our data suggest that TCRγ rearranges in all T lymphocytes, consistent with TCRγ rearranging before T cell lineage commitment. However, rearrangement of the TCRβ locus appears to be restricted after T cell precursors commit to the αβ T cell lineage. Indeed, in T cell leukemias and lymphomas, TCRγ is almost always rearranged and TCRβ is only rearranged in a subset of cancers. Because high-throughput sequencing of TCRs is translated into the clinic for monitoring minimal residual for leukemia/lymphoma, our data suggest the sequencing target should be TCRγ.
Sphingosine 1-Phosphate Protects Human Umbilical Vein Endothelial Cells from Serum-deprived Apoptosis by Nitric Oxide Production (2001)

Sphingosine 1-phosphate (S1P) can prevent endothelial cell apoptosis. We investigated the molecular mechanisms and signaling pathways by which S1P protects endothelial cells from serum deprivation-induced apoptosis. We show here that human umbilical vein endothelial cells (HUVECs) undergo apoptosis associated with increased DEVDase activity, caspase-3 activation, cytochrome c release, and DNA fragmentation after 24 h of serum deprivation. These apoptotic markers were suppressed by the addition of S1P, the NO donor S-nitroso-N-acetylpenicillamine (100 micrometer), or caspase-3 inhibitor z-VAD-fmk. The protective effects of S1P were reversed by the nitric-oxide synthase (NOS) inhibitor N-monomethyl-l-arginine, but not by the soluble guanylyl cyclase inhibitor 1H-(1,2,4)oxadiazolo[4,3-a]-quanoxaline-1-one, suggesting that NO, but not cGMP, is responsible for S1P protection from apoptosis. Furthermore, S1P increased NO production by enhancing Ca(2+)-sensitive NOS activity without changes in the eNOS protein level. S1P-mediated cell survival and NO production were suppressed significantly by pretreatment with antisense oligonucleotide of EDG-1 and partially by EDG-3 antisense. S1P-mediated NO production was suppressed by the addition of pertussis toxin, an inhibitor of G(i) proteins, the specific inhibitor of phospholipase C (PLC), and the Ca(2+) chelator BAPTA-AM. These findings indicate that S1P protects HUVECs from apoptosis through the activation of eNOS activity mainly through an EDG-1 and -3/G(i)/PLC/Ca(2+) signaling pathway.
Effect of Different Doses of Galcanezumab vs Placebo for Episodic Migraine Prevention (2017)

clinicaltrials.gov Identifier: NCT02163993.
Characterization of a Novel Methanol Dehydrogenase in Representatives of Burkholderiales : Implications for Environmental Detection of Methylotrophy and Evidence for Convergent Evolution (2008)

Some members of Burkholderiales are able to grow on methanol but lack the genes (mxaFI) responsible for the well-characterized two-subunit pyrroloquinoline quinone-dependent quinoprotein methanol dehydrogenase that is widespread in methylotrophic Proteobacteria. Here, we characterized novel, mono-subunit enzymes responsible for methanol oxidation in four strains, Methyloversatilis universalis FAM5, Methylibium petroleiphilum PM1, and unclassified Burkholderiales strains RZ18-153 and FAM1. The enzyme from M. universalis FAM5 was partially purified and subjected to matrix-assisted laser desorption ionization-time of fight peptide mass fingerprinting. The resulting peptide spectrum was used to identify a gene candidate in the genome of M. petroleiphilum PM1 (mdh2) predicted to encode a type I alcohol dehydrogenase related to the characterized methanol dehydrogenase large subunits but at less than 35% amino acid identity. Homologs of mdh2 were amplified from M. universalis FAM5 and strains RZ18-153 and FAM1, and mutants lacking mdh2 were generated in three of the organisms. These mutants lost their ability to grow on methanol and ethanol, demonstrating that mdh2 is responsible for oxidation of both substrates. Our findings have implications for environmental detection of methylotrophy and indicate that this ability is widespread beyond populations possessing mxaF, the gene traditionally used as a genetic marker for environmental detection of methanol-oxidizing capability. Our findings also have implications for understanding the evolution of methanol oxidation, suggesting a convergence toward the enzymatic function for methanol oxidation in MxaF and Mdh2-type proteins.
Short-Term Hemodynamic Effects of Cardiac Resynchronization Therapy in Patients With Heart Failure, a Narrow QRS Duration, and No Dyssynchrony (2009)

Cardiac resynchronization therapy results in an improvement in short-term hemodynamic variables in patients with a QRS <120 ms related to both contractile improvement and relief of external constraint. These findings provide a potential physiological basis for cardiac resynchronization therapy in this patient population.
Dazoxiben examined for platelet inhibitory effect in an artificial circulation. (1983)

1 Platelet inhibitory therapy may protect patency in prosthetic arterial grafts. 2 The effect of the thromboxane synthetase inhibitor dazoxiben (UK 37248) on 113Indium-labelled platelet deposition on Dacron arterial grafts was examined in an artificial circulation containing human blood which mimics the haemodynamics of femoropopliteal bypass. The influence of this drug on thromboxane production and platelet reactivity was measured during the experiment. The study was controlled and performed in two parts to assess in vitro and ex vivo drug effect. 3 Both in vitro and ex vivo dazoxiben reduced plasma thromboxane by about 80% and in citrated ex vivo blood increased mean (+/- s.e. mean) platelet aggregation threshold to collagen from control values of 4.8 +/- 1.7 mg/ml to 10.6 +/- 3.3 mg/ml (P less than 0.01). Dazoxiben, however, had no effect on platelet deposition on the arterial grafts. 4 Selective thromboxane inhibition failed to exert an antithrombotic effect in this model.
Calpain I activation is specifically related to excitatory amino acid induction of hippocampal damage (1989)

Sustained stimulation of receptors for excitatory amino acids leads to both activation of the calcium-dependent cysteine protease calpain I and to the death of receptive neurons. Here, we have examined the relationship between the calpain I activation and neurodegeneration. Calpain I activation was manifested as increased levels of the major proteolytic fragments of the calpain substrate spectrin, detected and quantified by immunoblotting. Intraventricular administration of the excitatory amino acids kainate or N-methyl-D-aspartate (NMDA) produced calpain I-mediated spectrin degradation and hippocampal neuronal loss. The NMDA antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid selectively blocked NMDA- but not kainate-induced protease activation and hippocampal damage. Temporally, spectrin degradation preceded the onset of pyramidal cell degeneration monitored by silver-impregnation histochemistry. Only those doses of kainate (0.15-1 microgram) or NMDA (40-80 micrograms) sufficient to cause hippocampal damage markedly increased spectrin breakdown. Both the neuronal damage and calpain I activation induced by kainate occurred primarily in area CA3. Degeneration of hippocampal neurons evoked by colchicine was not accompanied by calpain activation, indicating that proteolysis is not stimulated simply as a secondary response to neuronal destruction. Thus, a close correspondence exists between excitatory amino acid induction of neuronal degeneration and of calpain I-mediated spectrin degradation. The results suggest that calpain I may be an intracellular mediator of excitatory amino acid action, and further, they support the hypothesis that calcium influx and calpain I activation are obligatory events in the initiation of excitatory amino acid neurotoxicity.
Genetics of xanthan production in Xanthomonas campestris: the xanA and xanB genes are involved in UDP-glucose and GDP-mannose biosynthesis (1992)

The nucleotide sequence of a 3.4-kb EcoRI-PstI DNA fragment of Xanthomonas campestris pv. campestris revealed two open reading frames, which were designated xanA and xanB. The genes xanA and xanB encode proteins of 448 amino acids (molecular weight of 48,919) and 466 amino acids (molecular weight of 50,873), respectively. These genes were identified by analyzing insertion mutants which were known to be involved in xanthan production. Specific tests for the activities of enzymes involved in the biosynthesis of UDP-glucose and GDP-mannose indicated that the xanA gene product was involved in the biosynthesis of both glucose 1-phosphate and mannose 1-phosphate. The deduced amino acid sequence of xanB showed a significant degree of homology (59%) to the phosphomannose isomerase of Pseudomonas aeruginosa, a key enzyme in the biosynthesis of alginate. Moreover, biochemical analysis and complementation experiments with the Escherichia coli manA fragment revealed that xanB encoded a bifunctional enzyme, phosphomannose isomerase-GDP-mannose pyrophosphorylase.
Soluble normal and mutated DNA sequences from single-copy genes in human blood. (1994)

Healthy individuals have soluble (extracellular) DNA in their blood, and increased amounts are present in cancer patients. Here we report the detection of specific sequences of the cystic fibrosis and K-ras genes in plasma DNA from normal donors by amplification with the polymerase chain reaction. In addition, mutated K-ras sequences are identified by polymerase chain reaction utilizing allele-specific primers in the plasma or serum from three patients with pancreatic carcinoma that contain mutated K-ras genes. The mutations are confirmed by direct sequencing. These results indicate that sequences of single-copy genes can be identified in normal plasma and that the sequences of mutated oncogenes can be detected and identified with allele-specific amplification by polymerase chain reaction in plasma or serum from patients with malignant tumors containing identical mutated genes. Mutated oncogenes in plasma and serum may represent tumor markers that could be useful for diagnosis, determining response to treatment, and predicting prognosis.
Cancer risk in patients with inflammatory bowel disease (2001)

There appear to be similar increased risks for developing colon carcinoma and hepatobiliary carcinoma among patients with Crohn disease and UC. There is an increased risk of developing rectal carcinoma in UC patients, an increased risk of developing carcinoma of the small bowel in Crohn disease patients, and an increased risk of developing lymphoma among males with Crohn disease.
A service-oriented monitoring registry (2003)

Web services are software modules that expose their functionality over the Internet via well-defined interfaces. Although Web services are promising technologies in that they facilitate application-to-application communication over the Internet, they still rely on traditional distributed computing communication models such as the remote procedure call, in which a Web service requestor needs to have complete knowledge of a Web service provider interface. If a Web service requestor did not use the latest version of a Web service provider interface to generate a proxy service, then static binding to the Web service provider's services fails. In this paper, we provide functional requirements for a Service-Oriented Monitoring Registry (SOMR) that provides notification to service requestors when a version of an interface changes or a service becomes disabled. In order to present a more complete picture of SOMR we include four architectural views covering (i) the over-all system, (ii) its four tiers and their interconnection, (iii) details of the service tier and (iv) its deployment onto executable environments. SOMR provides public Web service registries that can be used by Web service providers, developers, and consumers to register their profiles so that whenever any change happens to Web service interfaces they are notified about these changes and can respond accordingly. In contrast with current static solutions, the proposed system provide a significant step toward achieving solutions that are consistent with the dynamic nature and evolution of Web services.
ETosis: A Novel Cell Death Pathway (2008)

The formation of extracellular traps (ETs) by neutrophils and mast cells is an important mechanism in the innate immune response. These structures consist of a chromatin-DNA backbone with attached antimicrobial peptides and enzymes that trap and kill microbes. After stimulation of neutrophils and mast cells with phorbol esters, chemoattractant peptides, or chemokines, the generation of reactive oxygen species (ROS), such as hydrogen peroxide, by NAPDH [nicotinamide adenine dinucleotide phosphate (reduced form)] oxidase initiates a signaling cascade that leads to the disintegration of the nuclear and cellular membranes and the formation of ETs. This form of cell death is neither apoptotic nor necrotic, but whether it occurs because of the oxidation of phosphatases and kinases, as in other ROS-mediated signaling cascades, remains to be elucidated. These findings implicate "ETosis" as a novel cell death pathway in leukocytes.