gebhart/patrepeval huggingface dataset:
Control of steroid, heme, and carcinogen metabolism by nuclear pregnane X receptor and constitutive androstane receptor (2003)

Through a multiplex promoter spanning 218 kb, the phase II UDP-glucuronosyltransferase 1A (UGT1) gene encodes at least eight differently regulated mRNAs whose protein products function as the principal means to eliminate a vast array of steroids, heme metabolites, environmental toxins, and drugs. The orphan nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) were originally identified as sensors able to respond to numerous environmentally derived foreign compounds (xenobiotics) to promote detoxification by phase I cytochrome P450 genes. In this report, we show that both receptors can induce specific UGT1A isoforms including those involved in estrogen, thyroxin, bilirubin, and carcinogen metabolism. Transgenic mice expressing a constitutively active form of human PXR show markedly increased UGT activity toward steroid, heme, and carcinogens, enhanced bilirubin clearance, as well as massively increased steroid clearance. The ability of PXR and constitutive androstane receptor and their ligands to transduce both the phase I and phase II adaptive hepatic response defines a unique transcriptional interface that bridges the ingestion and metabolism of environmental compounds to body physiology.
6H-Pyrazolo[4,5,1-de]acridin-6-ones as a Novel Class of Antitumor Agents.Synthesis and Biological Activity (1994)

The 7-substituted 6H-pyrazolo[4,5,1-de]acridin-6-ones with (aminoalkyl)amino and/or (hydroxyalkyl)amino groups in the side chains were synthesized by bromination using N-bromosuccinimide and the subsequent reaction with amines from the 7-substituted 5-bromo-2-methyl-6H-pyrazolo-[4,5,1-de]acridin-6-one. The substitution reaction of the amines with alkyl bromide (the C2 position) and aryl bromide (the C5 position) was accomplished by choosing the proper reaction conditions. These compounds show DNA intercalating ability in ethidium fluorescence assay and antiproliferative activity against Hela S3 cells. Impressive antitumor activity in vivo against murine P388 leukemia and murine sarcoma 180 solid tumor in mice was demonstrated for the 7-hydroxy analogs. In addition, some of these showed excellent antitumor activity against adriamycin-resistant murine P388 leukemia (P388/ADM) in mice.
Complex Inheritance of the 5-Lipoxygenase Locus Influencing Atherosclerosis in Mice (2006)

We previously mapped a locus on chromosome 6 with a large effect (LOD > 6) on aortic lesion size in a (C57BL/6J x CAST/Ei) F(2) cross and identified arachidonate 5-lipoxygenase (5LO) as a candidate gene in this region. Subsequent studies with the 5LO knockout model showed effects on atherosclerosis and aortic aneurysms. We now report detailed genetic analysis of the chromosome 6 locus. We created a panel of overlapping and reciprocal subcongenic lines from the B6.CAST Ldlr(-/-) chromosome 6 congenic strain (CON6.Ldlr(-/-)) and analyzed aortic lesion size in different subcongenic lines. Our results revealed that there are at least two subregions, designated as Ath37 and Ath38 that affect the size of aortic lesions independently of 5LO. We also showed that homozygote 5LO null mice develop smaller atherosclerotic lesions. We conclude that the relation between the mouse chromosome 6 locus and atherosclerosis is complex and is due to at least two genes with large effects within this region. This complexity should be considered when interpreting results of knockout studies.
A novel compound, 12,13,17‐trihydroxy‐9(<i>Z</i>)‐Octadecenoic acid, from linoleic acid by a new microbial isolate<i>Clavibacter</i> sp. ALA2 (1996)

Abstract A novel compound, 12,13,17‐trihydroxy‐9( Z )‐octadecenoic acid (THOA), was produced from linoleic acid by microbial transformation at 25% yield. The newly isolated microbial strain that catalyzed this transformation was identified as Clavibacter sp. ALA2. The product was purified by high‐pressure liquid chromatography, and its structure was determined by 1 H and 13 C nuclear magnetic resonance, Fourier transform infrared, and mass spectroscopy. Maximum production of THOA was reached after 85 h of reaction. THOA was not further metabolized by strain ALA2. This is the first report on 12,13,17‐trihydroxy unsaturated fatty acid and its production by microbial transformation.
Cystatin C deficiency in human atherosclerosis and aortic aneurysms (1999)

The pathogenesis of atherosclerosis and abdominal aortic aneurysm involves breakdown of the elastic laminae. Elastolytic cysteine proteases, including cathepsins S and K, are overexpressed at sites of arterial elastin damage, but whether endogenous local inhibitors counterbalance these proteases is unknown. We show here that, whereas cystatin C is normally expressed in vascular wall smooth muscle cells (SMCs), this cysteine protease inhibitor is severely reduced in both atherosclerotic and aneurysmal aortic lesions. Furthermore, increased abdominal aortic diameter among 122 patients screened by ultrasonography correlated inversely with serum cystatin C levels. In vitro, cytokine-stimulated vascular SMCs secrete cathepsins, whose elastolytic activity could be blocked when cystatin C secretion was induced by treatment with TGF-beta(1). The findings highlight a potentially important role for imbalance between cysteine proteases and cystatin C in arterial wall remodeling and establish that cystatin C deficiency occurs in vascular disease.
Polysaccharide-Coated Thermosets for Orthopedic Applications: From Material Characterization to In Vivo Tests (2012)

The long-term stability and success of orthopedic implants depend on the osseointegration process, which is strongly influenced by the biomaterial surface. A promising approach to enhance implant integration involves the modification of the surface of the implant by means of polymers that mimic the natural components of the extracellular matrix, for example, polysaccharides. In this study, methacrylate thermosets (bisphenol A glycidylmethacrylate/triethyleneglycol dimethacrylate), a widely used composition for orthopedic and dental applications, have been coated by electrostatic deposition of a bioactive chitosan-derivative. This polysaccharide was shown to induce osteoblasts aggregation in vitro, to stimulate cell proliferation and to enhance alkaline phosphatase activity. The coating deposition was studied by analyzing the effect of pH and ionic strength on the grafting of the polysaccharide. Contact angle studies show that the functionalized material displays a higher hydrophilic character owing to the increase of surface polar groups. The mechanical properties of the coating were evaluated by nanoindentation studies which point to higher values of indentation hardness and modulus (E) of the polysaccharide surface layer, while the influence of cyclic stress on the construct was assessed by fatigue tests. Finally, in vivo tests in minipigs showed that the polysaccharide-based implant showed a good biocompatibility and an ability for osseointegration at least similar to that of the titanium Ti6Al4V alloy with roughened surface.
Proteomic‐based prediction of clinical behavior in adult acute lymphoblastic leukemia (2006)

Peripheral blood plasma is adequate to predict clinical behavior in ALL patients irrespective of the percentage of bone marrow blasts. Proteomic analysis of plasma offers a useful approach for profiling patients with ALL.
Line-Based Laser Induced Plasma Micro-Machining (L-LIPMM) (2013)

Recently, the technique of Spot-based Laser Induced Plasma Micro-Machining (Spot-LIPMM) has been developed to address the limitations of conventional ultrashort pulse laser micro-machining. Its main advantages are adaptability to a wide range of materials and superior wall geometries. We propose a variation of the Spot-LIPMM process by creating line plasma instead of spot plasma, with the use of suitable optics. This paper describes the experimental setup used to create line plasma and the process used for micro-machining with L-LIPMM. Optics simulations are developed as a means of guiding the choice of optics to be used for line plasma generation and estimating the energy and shape of the plasma created. It is shown that this Line-based LIPMM (L-LIPMM) process is capable of micromachining channels at a much higher speed than conventional Spot-based laser ablation or spot-based LIPMM. Additionally, the effects of process parameters on machined geometry using L-LIPMM are discussed.
New expression vectors for the fission yeast <i>Schizosaccharomyces pombe</i> (1989)

A general expression vector (pMB332) for the fission yeast Schizosaccharomyces pombe was constructed. The heterologous gene expression is driven by the S. pombe alcohol dehydrogenase (adh) promoter. Transcription termination signals were isolated from the S. pombe actin gene. The vectors carry the Saccharomyces cerevisiae Ura3 gene, which complements the S. pombe ura4 mutation. The plasmid stability is conferred by the S. pombe ars and stb elements isolated from pFL120 [(1983) Cell 32, 371-377]. An 'ATG' vector (pMB340) was created, which allows the expression of protein fragments fused to a translational start codon downstream of the adh promoter. The function of this vector system is shown by the production of the human blood coagulation protein factor XIIIa.
Peer Reviewed: Measuring DNA Synthesis Rates with Stable Isotopes. (2003)

ADVERTISEMENT RETURN TO ISSUEPREVFeaturesNEXTPeer Reviewed: Measuring DNA Synthesis Rates with Stable Isotopes.Although stable isotopes are not hazardous in vitro or in vivo, using them to measure DNA synthesis rates has not been attempted until recently.Gavin E. Black Fred P. AbramsonCite this: Anal. Chem. 2003, 75, 3, 56 A–63 APublication Date (Web):February 1, 2003Publication History Published online1 February 2003Published inissue 1 February 2003https://pubs.acs.org/doi/10.1021/ac031229ahttps://doi.org/10.1021/ac031229anewsACS Publications. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views423Altmetric-Citations6LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (221 KB) Get e-Alertsclose SUBJECTS:Genetics,Stable isotopes Get e-Alerts
Controlled crack propagation for atomic precision handling of wafer-scale two-dimensional materials (2018)

Although flakes of two-dimensional (2D) heterostructures at the micrometer scale can be formed with adhesive-tape exfoliation methods, isolation of 2D flakes into monolayers is extremely time consuming because it is a trial-and-error process. Controlling the number of 2D layers through direct growth also presents difficulty because of the high nucleation barrier on 2D materials. We demonstrate a layer-resolved 2D material splitting technique that permits high-throughput production of multiple monolayers of wafer-scale (5-centimeter diameter) 2D materials by splitting single stacks of thick 2D materials grown on a single wafer. Wafer-scale uniformity of hexagonal boron nitride, tungsten disulfide, tungsten diselenide, molybdenum disulfide, and molybdenum diselenide monolayers was verified by photoluminescence response and by substantial retention of electronic conductivity. We fabricated wafer-scale van der Waals heterostructures, including field-effect transistors, with single-atom thickness resolution.
Sensorimotor control: computing the immediate future from the delayed present (2016)

Three claims with varying degrees of experimental support are proposed in this paper. Firstly, the brain or any sensorimotor system has time-delay estimation circuits for the various sensorimotor control systems. Secondly, the brain continuously estimates current/future sensory states from the previously sensed states. Thirdly, the brain uses predicted sensory states to perform optimal motor control.
Algae Extract-Mediated Stimulation and Protection of Proteasome Activity Within Human Keratinocytes Exposed to UVA and UVB Irradiation (2006)

Sun exposure is the major environmental influence for epidermal cells; the harmful effect of UV radiation on skin is related to the generation of reactive oxygen species that alter cellular components including proteins. It is now well established that the proteasome is responsible for the degradation of most of oxidized proteins and that impairment of proteasome function is a hallmark of cellular aging. In a previous study, we investigated the effects of UV irradiation on proteasomes in human keratinocyte cultures and showed that all three peptidase activities were decreased 24 h after irradiation of the cells. Increased levels of oxidatively modified proteins were observed in irradiated cells and were found to act as endogenous inhibitors of the proteasome. We report here on the stimulating and protective effects of an algae extract, prepared from Phaeodactylum tricornutum, on proteasome peptidase activities of human keratinocytes exposed to UVA and UVB irradiation. In addition, preserving proteasome function resulted in lowering the extent of the irradiation-induced protein oxidative damage, opening up new strategies for protection of epidermal cells against the detrimental effects of UV irradiation.
RTSP: An Accurate and Energy-Efficient Protocol for Clock Synchronization in WSNs (2013)

Wireless sensor networks need accurate time synchronization for data consistency and coordination. Although the existing algorithms for time synchronization offer very good accuracy, their energy consumption is high, and distant nodes are poorly synchronized. We propose a Recursive Time Synchronization Protocol (RTSP) which accurately synchronizes all the nodes in a network to a global clock using multi-hop architecture in an energy-efficient way. It achieves better performance due to the MAC-layer time-stamping based on Start of Frame Delimiter byte, infrequent broadcasts by a dynamically elected reference node, compensation of the propagation delay and adjustment of the timestamps at each hop, estimation of the relative skew and offset using least square linear regression on two data points (2LR), adaptive re-synchronization interval, aggregation of the synchronization requests, and energy awareness. A detailed analysis of the sources of errors is also provided. Simulation results show that the RTSP can achieve an average accuracy of 0.3 microseconds in a large multi-hop flat network while using five-times lesser energy than that of FTSP in the long run and performs even better in a clustered network where it can achieve an average accuracy of 0.23 microseconds while using seven-times lesser energy.
A nuclear protein essential for binding of rat 1,25-dihydroxyvitamin D3 receptor to its response elements. (1992)

Recombinant 1,25-dihydroxyvitamin D3 receptor from a baculovirus expression system requires a mammalian-derived nuclear accessory protein for binding to a vitamin D response element (DRE). This was established by electrophoretic mobility shift analyses using radiolabeled DNA probes consisting of DREs from two vitamin D-responsive genes. Mammalian nuclear extract was also required for the binding of wild-type porcine vitamin D receptor to a DRE. Surprisingly, the accessory factor-dependent formation of receptor-DRE complex was independent of exogenous 1,25-dihydroxyvitamin D3. A 59- to 64-kDa accessory protein from porcine intestinal nuclear extract was identified by size-exclusion chromatography. Nuclear extracts from rat liver and kidney contained accessory factor, whereas smaller amounts were detected in heart muscle. Spleen and skeletal muscle contained no detectable accessory factor.
New phase-change rewritable optical recording film having well suppressed material flow for repeated rewriting (1995)

Characteristics of a phase-change optical disk using a (Ge–Sb–Te)-(Cr–Te) recording film containing a high-melting-point component Cr–Te are studied. The high-melting-point component Cr–Te precipitates in the recording film, and prevents a material flow of the recording film during repeated rewrites in which the recording film is melted. There is no drawback such as noise increase by the addition of Cr–Te. Thus the phase-change optical disk using this recording film shows very small distortion in the reproduced signal wave form even after 2×104 rewrites of high-density recording signals that are liable to cause the material flow by forming long and short recording marks on the disk. With a phase-change optical disk, it is easy to overwrite (rewrite without prior erasure) information, which makes it highly suitable for digital recording of motion pictures and sound. They are expected to be used as rewritable compact disks, rewritable CD-ROM disks, rewritable video disks, and small recording media for personal computers.
A randomised controlled trial of bumetanide in the treatment of autism in children (2012)

Gamma aminobutyric acid (GABA)-mediated synapses and the oscillations they orchestrate are altered in autism. GABA-acting benzodiazepines exert in some patients with autism paradoxical effects, raising the possibility that like in epilepsies, GABA excites neurons because of elevated intracellular concentrations of chloride. Following a successful pilot study,(1) we have now performed a double-blind clinical trial using the diuretic, chloride-importer antagonist bumetanide that reduces intracellular chloride reinforcing GABAergic inhibition. Sixty children with autism or Asperger syndrome (3-11 years old) received for 3 months placebo or bumetanide (1 mg daily), followed by 1-month wash out. Determination of the severity of autism was made with video films at day 0 (D0) and D90 by blind, independent evaluators. Bumetanide reduced significantly the Childhood Autism Rating Scale (CARS) (D90-D0; P<0.004 treated vs placebo), Clinical Global Impressions (P<0.017 treated vs placebo) and Autism Diagnostic Observation Schedule values when the most severe cases (CARS values above the mean ± s.d.; n=9) were removed (Wilcoxon test: P-value=0.031; Student's t-test: P-value=0.017). Side effects were restricted to an occasional mild hypokalaemia (3.0-3.5 mM l(-1) K(+)) that was treated with supplemental potassium. In a companion study, chronic bumetanide treatment significantly improved accuracy in facial emotional labelling, and increased brain activation in areas involved in social and emotional perception (Hadjikhani et al., submitted). Therefore, bumetanide is a promising novel therapeutic agent to treat autism. Larger trials are warranted to better determine the population best suited for this treatment.
Efficacious Vaccine against Heroin Contaminated with Fentanyl (2018)

The sharp increase in overdose deaths involving illicit opioid use has been declared a national crisis in the United States. This growing number of overdose deaths can in part be attributed to the increased frequency of fentanyl contamination in the United States heroin supply. To combat this growing trend, we designed a vaccine containing a mixture of heroin and fentanyl hapten-conjugates as a proof-of-concept immunotherapy targeting a combination of these drugs. Rodents immunized with the admixture vaccine showed drug retention in serum and reduced distribution in the brain after administration of an intravenous bolus of heroin coadministered with fentanyl (10% w/w). Moreover, the admixture vaccine performed as well as or better than individual immunoconjugate vaccines in antinociception behavioral models and recognized six other fentanyl analogues with nanomolar affinity. Taken together, these data highlight the potential of an admixture vaccine against heroin contaminated with fentanyl.
Ge<i>x</i>Si1−<i>x</i>/Si strained-layer superlattice grown by molecular beam epitaxy (1984)

GexSi1−x films are grown on Si by molecular beam epitaxy and analyzed by Nomarski optical interference microscopy, Rutherford ion backscattering and channeling, x-ray diffraction, and transmission electron microscopy. The full range of alloy compositions will grow smoothly on silicon. GexSi1−x films with x≤0.5 can be grown free of dislocations by means of strained-layer epitaxy where lattice mismatch is accommodated by tetragonal strain. Critical thickness and composition values are tabulated for strained-layer growth. Multiple strained layers are combined to form a GexSi1−x/Si strained-layer superlattice.
Deflation-secure web metering (2007)

As a result of recent changes in the policy governing internet content distribution, such as the institution of per listener royalties for internet radio broadcasters, Content Distributors (CDs) now have an incentive to underreport the size of their audience. Existing metering protocols protect only against the inflation of audience size. We introduce the first protocols for audience metering that protect against deflation attempts by CDs. The protocols trade-off the amount of additional information the CDs must distribute to facilitate metering with the amount of infrastructure required and are applicable to internet radio, web plagiarism, and software licence enforcement.
Comparison of k-shortest paths and maximum flow routing for network facility restoration (1994)

In the development of technologies for span failure restoration, a question arises about the restoration rerouting characteristics to be specified. In theory, maximal rerouting capacity is obtained with a maximum flow (Max Flow) criterion. However, rerouting that realizes the k-successively shortest link disjoint paths (KSP) may be faster, easier, and, in distributed implementation, more robust than a distributed counterpart for Max Flow. The issue is, therefore, what the restoration capacity penalty is if KSP is used instead of Max Flow. To explore this tradeoff, the authors present a comparative study of the effectiveness of KSP versus Max Flow as an alternative rerouting criteria in the context of transport network span restoration. The comparison applies to both centrally controlled and distributed restoration systems. Study methods include exhaustive span failure experiments on a range of network models, and parametric and analytical investigations for insight into the factors resulting in KSP versus Max Flow differences. The main finding is that KSP restoration capacity is more than 99.9% of that from Max Flow in typical network models. The hypothesis is made that a generalized "trap" topology is responsible for all KSP-Max Flow capacity differences. The hypothesis is tested experimentally and used to develop analytical bounds which agree well with observed results. These findings and data are relevant to standards makers and equipment developers in specifying and engineering future restorable networks.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>