gebhart/patrepeval huggingface dataset:
<i>In silico</i> methods for predicting metabolism and mass fragmentation applied to quetiapine in liquid chromatography/time‐of‐flight mass spectrometry urine drug screening (2009)

Current in silico tools were evaluated for their ability to predict metabolism and mass spectral fragmentation in the context of analytical toxicology practice. A metabolite prediction program (Lhasa Meteor), a metabolite detection program (Bruker MetaboliteDetect), and a fragmentation prediction program (ACD/MS Fragmenter) were used to assign phase I metabolites of the antipsychotic drug quetiapine in the liquid chromatography/time-of-flight mass spectrometry (LC/TOFMS) accurate mass data from ten autopsy urine samples. In the literature, the main metabolic routes of quetiapine have been reported to be sulfoxidation, oxidation to the corresponding carboxylic acid, N- and O-dealkylation and hydroxylation. Of the 14 metabolites predicted by Meteor, eight were detected by LC/TOFMS in the urine samples with use of MetaboliteDetect software and manual inspection. An additional five hydroxy derivatives were detected, but not predicted by Meteor. The fragment structures provided by ACD/MS Fragmenter software confirmed the identification of the metabolites. Mean mass accuracy and isotopic pattern match (SigmaFit) values for the fragments were 2.40 ppm (0.62 mDa) and 0.010, respectively. ACD/MS Fragmenter, in particular, allowed metabolites with identical molecular formulae to be differentiated without a need to access the respective reference standards or reference spectra. This was well exemplified with the hydroxy/sulfoxy metabolites of quetiapine and their N- and O-dealkylated forms. The procedure resulted in assigning 13 quetiapine metabolites in urine. The present approach is instrumental in developing an extensive database containing exact monoisotopic masses and verified retention times of drugs and their urinary metabolites for LC/TOFMS drug screening.
TotalCOW (2015)

Modern file systems leverage the Copy-on-Write (COW) technique to efficiently create snapshots. COW can significantly reduce demand on disk space and I/O bandwidth by not duplicating entire files at the time of making the snapshots. However, memory space and I/O requests demanded by applications cannot benefit from this technique. In existing systems, a disk block shared by multiple files due to COW would be read from the disk multiple times. Each block in the reads is treated as an independent one in different files and is cached as a sperate block in memory. This issue is due to the fact that current file access and caching are based on logic file addresses. It poses a significant challenge on the emerging light-weight container virtualization techniques, such as Linux Container and Docker, which rely on COW to quickly spawn a large number of thin-provisioned container instances. We propose a lightweight approach to address this issue by leveraging knowledge about files produced by COW. Experimental results show that a prototyped system using the approach, named TotalCOW, can significantly remove redundant disk reads and caching without compromising efficiency of accessing COW files.
Prevention with clodronate of osteoporosis secondary to inhaled corticosteroid treatment in patients with chronic asthmatic bronchitis. (2000)

Steroid therapy is the third most common cause of osteoporosis, after loss of gonad function and senescence. The aim of the present study was to evaluate the protective action of clodronate on bone mass loss induced by steroid therapy. Sixty patients with bronchial asthma receiving either fluticasone (250 mg x 4/day) or beclomethasone (250 mg x 4/day) inhaled corticosteroid treatment were enrolled. Half the patients received combination treatment with clodronate (100 mg i.m./14 days), for a total period of 12 months. All patients were evaluated at baseline and at the end of treatment for bone mineral density (BMD) and calcium/phosphor metabolism parameters (kalemia, kaluria, phosphoremia, phosphaturia, alkaline phosphatase and hydroxyprolinuria over a 24-h period). The results of this preliminary study confirm the protective influence of clodronate on bone mass loss, as documented by the increment in mean values in BMD reported at the end of treatment compared with baseline values.
Endothelial cell myosin light chain kinase (MLCK) regulates TNF?-induced NF?B activity (2004)

Tumor necrosis factor (TNFalpha-) generates both apoptotic and survival signals with endothelial cell (EC) survival dependent on nuclear factor kappa-B (NFkappaB) activation, a regulator of anti-apoptotic genes. We previously demonstrated that increased EC contractility, rearrangement of the actin cytoskeleton, and increased myosin light chain (MLC) phosphorylation occurs as a consequence of TNFalpha-induced activation of EC MLC kinase (EC MLCK) and is required for bovine lung EC apoptosis. As the association between MLCK and pro-survival signals such as NFkappaB activation is unknown, we studied the role of MLCK in the regulation of NFkappaB-dependent transactivation in bovine pulmonary artery EC. Both TNFalpha-induced increase in NFkappaB dependent transactivation measured by NFkappaB luciferase reporter assay (approximately fivefold) and nuclear translocation of NFkappaB were significantly inhibited by MLCK-selective inhibitors, KT5926 (60% inhibition of luciferase activity) and ML7 (50% decrease). Furthermore, our data revealed that inhibition of MLCK attenuated the TNFalpha-induced IkappaB phosphorylation, translocation of p65, NFkappaB-DNA binding, and NFkappaB transcriptional activity. Molecular approaches to either reduce EC MLCK expression (AdV EC MLCK antisense construct) or to reduce kinase activity (kinase-dead EC MLCK ATPdel mutant) produced similar attenuation of the TNFalpha-induced NFkappaB response. In contrast, a constitutively active MLCK mutant (EC MLCK1745) enhanced TNFalpha-induced luciferase activity. Together, these novel observations indicate that TNFalpha-induced cytoskeletal rearrangement driven by MLCK activity is necessary for TNFalpha-dependent NFkappaB activation and amplification of pro-survival signals.
Web Accessibility by Morse Code Modulated Haptics for Deaf-Blind (2014)

Providing information using a modality that is both non-visual and non-auditory such as haptic feedback, may be a viable approach regarding web accessibility for deaf-blind. Haptic navigation systems have been shown to be easy to learn (Venesvirta 2008), and modulating navigation related information as patterns of vibrations has been shown to be perceived as natural and non-intrusive (Szymzcak, Magnusson and Rassmus-Grohn 2012). To minimise the bandwidth needed, a varying length encoding scheme such as Morse code may be considered. A prototype Morse code vibration modulated system for web page navigation was developed, using a standard game controller as a means of output. Results show that simulated deaf-blind test subjects using the system were able to navigate a web site successfully in three cases out of four, and that in some situations a version of the system with a higher degree of manual interaction performed better.
NMDA Receptor GluN2B (GluRε2/NR2B) Subunit Is Crucial for Channel Function, Postsynaptic Macromolecular Organization, and Actin Cytoskeleton at Hippocampal CA3 Synapses (2009)

GluN2B (GluRepsilon2/NR2B) subunit is involved in synapse development, synaptic plasticity, and cognitive function. However, its roles in synaptic expression and function of NMDA receptors (NMDARs) in the brain remain mostly unknown because of the neonatal lethality of global knock-out mice. To address this, we generated conditional knock-out mice, in which GluN2B was ablated exclusively in hippocampal CA3 pyramidal cells. By immunohistochemistry, GluN2B disappeared and GluN1 (GluRzeta1/NR1) was moderately reduced, whereas GluN2A (GluRepsilon1/NR2A) and postsynaptic density-95 (PSD-95) were unaltered in the mutant CA3. This was consistent with protein contents in the CA3 crude fraction: 9.6% of control level for GluN2B, 47.7% for GluN1, 90.6% for GluN2A, and 98.0% for PSD-95. Despite the remaining NMDARs, NMDAR-mediated currents and long-term potentiation were virtually lost at various CA3 synapses. Then, we compared synaptic NMDARs by postembedding immunogold electron microscopy and immunoblot using the PSD fraction. In the mutant CA3, GluN1 was severely reduced in both immunogold (20.6-23.6%) and immunoblot (24.6%), whereas GluN2A and PSD-95 were unchanged in immunogold but markedly reduced in the PSD fraction (51.4 and 36.5%, respectively), indicating increased detergent solubility of PSD molecules. No such increased solubility was observed for GluN2B in the CA3 of GluN2A-knock-out mice. Furthermore, significant decreases were found in the ratio of filamentous to globular actin (49.5%) and in the density of dendritic spines (76.2%). These findings suggest that GluN2B is critically involved in NMDAR channel function, organization of postsynaptic macromolecular complexes, formation or maintenance of dendritic spines, and regulation of the actin cytoskeleton.
Temporal modulation sensitivity and pulse-detection thresholds for chromatic and luminance perturbations: errata (1988)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text William H. Swanson, Takehiro Ueno, Vivianne C. Smith, and Joel Pokorny, "Temporal modulation sensitivity and pulse-detection thresholds for chromatic and luminance perturbations: errata," J. Opt. Soc. Am. A 5, 1525-1525 (1988) Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Development of novel biosensor enzyme electrodes: Glucose oxidase multilayer arrays immobilized onto self‐assembled monolayers on electrodes (1993)

Amperometric biosensors under development are based on electron transfer communication between enzyme redox sites and electrodes. These require well‐organized networks of enzymes exhibiting long‐range electron transfer properties. An enzyme electrode is described that consists of glucose oxidase networks organized on a self‐assembled monolayer of functionalized thiols on gold electrodes. The protein array supports electrical communication with the electrode, and the resulting assembly can be used as a glucose biosensor.
Involvement of xeroderma pigmentosum group A (XPA) in progeria arising from defective maturation of prelamin A (2007)

Cellular accumulation of DNA damage has been widely implicated in cellular senescence, aging, and premature aging. In Hutchinson-Gilford progeria syndrome (HGPS) and restrictive dermopathy (RD), premature aging is linked to accumulation of DNA double-strand breaks (DSBs), which results in genome instability. However, how DSBs accumulate in cells despite the presence of intact DNA repair proteins remains unknown. Here we report that the recruitment of DSB repair factors Rad50 and Rad51 to the DSB sites, as marked by gamma-H2AX, was impaired in human HGPS and Zmpste24-deficient cells. Consistently, the progeria-associated DSBs appeared to be unrepairable although DSBs induced by camptothecin were efficiently removed in the progeroid cells. We also found that these progeroid cells exhibited nuclear foci of xeroderma pigmentosum group A (XPA), a unique nucleotide excision repair protein. Strikingly, these XPA foci colocalized with the DSB sites in the progeroid cells. This XPA-DSB association was further confirmed and found to be mediated by DNA, using a modified chromatin immunoprecipitation assay and coimmunoprecipitation. RNA interference (RNAi) knockdown of XPA in HGPS cells partially restored DSB repair as evidenced by Western blot analysis, immunofluorescence and comet assays. We propose that the uncharacteristic localization of XPA to or near DSBs inhibits DSB repair, thereby contributing to the premature aging phenotypes observed in progeria arising from genetic defects in prelamin A maturation.
Electrostatic Steering Enables Flow-Activated Von Willebrand Factor to Bind Platelet Glycoprotein, Revealed by Single-Molecule Stretching and Imaging (2019)

Von Willebrand factor (VWF), a large multimeric blood protein, senses changes in shear stress during bleeding and responds by binding platelets to plug ruptures in the vessel wall. Molecular mechanisms underlying this dynamic process are difficult to uncover using standard approaches due to the challenge of applying mechanical forces while monitoring structure and activity. By combining single-molecule fluorescence imaging with high-pressure, rapidly switching microfluidics, we reveal the key role of electrostatic steering in accelerating the binding between flow-activated VWF and GPIbα, and in rapidly immobilizing platelets under flow. We measure the elongation and tension-dependent activation of individual VWF multimers under a range of ionic strengths and pH levels, and find that the association rate is enhanced by 4 orders of magnitude by electrostatic steering. Under supraphysiologic salt concentrations, strong electrostatic screening dramatically decreases platelet binding to VWF in flow, revealing the critical role of electrostatic attraction in VWF-platelet binding during bleeding.
Blockade of LH Release and Ovulation in the Rabbit with Inhibitory Analogues of Luteinizing Hormone Releasing Hormone<sup>1</sup> (1977)

Plasma LH levels and ovulation were studied in female rabbits following administration of several inhibitory analogues of luteinizing hormone-releasing hormone (LHRH) before and after mating with experienced males. Administration of (D-Phe2, D-Leu6)-LHRH (1.5 mg/kg sc) to does 30 min before mating did not prevent either LH release or ovulation. However, a single sc injection of (D-Phe2, L-Phe3, D-Phe6y-LHRH (6 mg/kg) given 30 min before mating in 4 rabbits resulted in a 30-60 min delay in the coitus-induced release of LH when compared with post-coital changes in the same animals injected with vehicle; however, all of the does ovulated. When multiple dosages of 4 mg/kg (D-Phe2, L-Phe3, D-Phe6)-LHRH were administered 3-5 times at half-hourly intervals beginning 30 min prior to mating there was a considerable reduction in plasma LH elevations at 0.5, 1.0, 2.0 and 4.0 h after mating and 3/5 treated rabbits showed partial or complete blockade of ovulation. Quite similar results were obtained with the same dosage of (D-Phe2, D-Trp3, D-Phe6)-LHRH. An early sharp peak in LH release and full ovulation were stimulated in 6 out of 6 does by a single iv injection of synthetic LHRH (500 ng/kg). However, in another experiment, three half-hourly sc injections (4 mg/kg) of (D-Phe2, L-Phe3, D-Phe6)-LHRH beginning 30 min before administering LHRH markedly reduced the rise in plasma LH (P less than 0.01) and completely blocked ovulation in all of the same 6 animals. An unsuccessful attempt was made to provide a test animal for LHRH analogue investigations by implanting 4 cm of silastic tubing filled with crystalline estradiol (E2) sc in ovariectomized (OVX) AND INTACT DOES. In OVX does the silastic E2 implants resulted in a progressive decline in the ability to release LH in response to mating at 6 and at 20 days after implantation. With ovaries present, the E2 implant permitted post-coital LH release and ovulation at 4 d but not at 30 d post-implantation. At 30 d after removal of the E2 implant three out of four does had fully recovered the ability to release LH and ovulate post-coitally. Collectively, these results indicate that inhibitory analogues of LHRH can effectively block the ovulatory response to exogenous LHRH in rabbits, but that coitally-induced LH release and ovulation are less susceptible to blockade by the analogues. Silastic E2 implants, however, progressively and reversibly reduce the capacity of does to release LH after mating.
Laboratory Evolution of Toluene Dioxygenase To Accept 4-Picoline as a Substrate (2001)

We are using directed evolution to extend the range of dioxygenase-catalyzed biotransformations to include substrates that are either poorly accepted or not accepted at all by the naturally occurring enzymes. Here we report on the oxidation of a heterocyclic substrate, 4-picoline, by toluene dioxygenase (TDO) and improvement of the enzyme's activity by laboratory evolution. The biotransformation of 4-picoline proceeds at only approximately 4.5% of the rate of the natural reaction on toluene. Random mutagenesis, saturation mutagenesis, and screening directly for product formation using a modified Gibbs assay generated mutant TDO 3-B38, in which the wild-type stop codon was replaced with a codon encoding threonine. Escherichia coli-expressed TDO 3-B38 exhibited 5.6 times higher activity toward 4-picoline and approximately 20% more activity towards toluene than wild-type TDO. The product of the biotransformation of 4-picoline is 3-hydroxy-4-picoline; no cis-diols of 4-picoline were observed.
Hermes: On collaboration across heterogeneous collaborative editing services in the cloud (2014)

With the prevalence of cloud services, more and more editing tools are moving from client to cloud for collaboration. Google Docs, Microsoft Office Web Apps, Zoho Office Suite are such representative cloud backed co-editing services. People from different organizations may choose different service providers, which implies the needs of cross-cloud document collaboration. However, it is hard to make different collaborative editing services interoperate with each other. On the one hand, it is not realistic to let all service providers comply to a unified standard and provide interoperation interfaces. On the other hand, the challenge of consistency maintenance in real-time document synchronization still exists. These make interoperability one of the most significant collaboration barriers in online collaborative editing. This paper presents a transparent approach called Hermes to interoperating between heterogeneous collaborative editing services in the cloud. Users are allowed to use their familiar services to participate in the cross-cloud document collaboration. Service providers do not need to put any effort to interoperate with other services. Our approach is validated by a system prototype.
Diffusion of low molecular weight fluid in EPDM (2002)

EPDM is widely used in outdoor insulation. It has the ability to maintain its hydrophobic surface in the presence of moisture and pollution even after being in service for many years. The maintenance of the hydrophobicity of the surface is achieved by the diffusion of low molecular weight fluid from the bulk to the surface. This inhibits the spread of water on the insulator surface and thus reduces the formation of leakage current. The generation of the LMW fluid in EPDM was confirmed after heating at different temperatures using a Fourier Transform Infrared spectrometer with an Attenuated Total Reflection attachment. By using gas chromatography (GC-MS) the fluid components were identified.
Pharmacogenomic Biomarkers for Prediction of Severe Adverse Drug Reactions (2008)

The accumulating knowledge of human genomic variation is being used for the development of personalized medicine, with the aims of decreasing the number of adverse drug reactions and increasing the efficacy of drug treatment. Considerable pharmacogenomic research has focused on understanding the molecular mechanisms behind adverse drug reactions and finding biomarkers that identify people at risk.Serious adverse drug reactions have been shown to cause or contribute to 6 to 7% of all hospitalizations, a 2-day increase in the average length of hospitalization, and 100,000 deaths annually in the United States — and may, according to some estimates, cost about . . .
Catalytic Amphiphilic Allylation via Bis-π-allylpalladium Complexes and Its Application to the Synthesis of Medium-Sized Carbocycles (2000)

The reaction of certain activated alkenes 3 with allyltributylstannane (4) and allyl chloride (5a) in the presence of palladium catalyst gave the bis-allylation products, 1,7-octadiene derivatives 6a−k, in good to high yields. The reaction of certain imines 9 with 4 and 5a under similar conditions as above afforded the bis-allylated amines, N-allyl-N-3-butene-1-amine derivatives 10a−f, in good to high yields. The bis-allylation reactions most probably proceed through bis-π-allylpalladium intermediate 2. The above intermolecular bis-allylation was extended to the intramolecular reaction. The reaction of 8-chloro-2,6-octadienyltributylstannane (17a) with activated alkenes 3 gave a mixture of regioisomeric cycloadducts, [8+2] and [4+2] cycloaddition products. The regioisomeric ratio was dependent on solvent and the electron density at the β-position of activated alkenes. In general, the [8+2] cycloadducts 18 were obtained predominantly in CH2Cl2, whereas the [4+2] adducts 24 and 25 were produced predominantly in DMF. The reaction of 7-chloro-2,8-nonadienyltributylstannane (17b) with activated alkenes gave selectively the [9+2] cycloadducts 19 and 22: the regioisomeric [5+2] and [7+2] adducts were not obtained at all. The reaction of 10-chloro-2,8-decadienyltributylstannane (17c) with activated alkene 3a afforded the [10+2] cycloadducts 20 and 23 in low yields. The mechanism on the intramolecular bis-allylation reaction is discussed.
Aluminum oxide assisted stereoselective rearrangement of a cyclopropyl ketone to 4,5-dihydrofuran (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAluminum oxide assisted stereoselective rearrangement of a cyclopropyl ketone to 4,5-dihydrofuranMiguel E. Alonso and Angelina MoralesCite this: J. Org. Chem. 1980, 45, 22, 4530–4532Publication Date (Print):October 1, 1980Publication History Published online1 May 2002Published inissue 1 October 1980https://pubs.acs.org/doi/10.1021/jo01310a062https://doi.org/10.1021/jo01310a062research-articleACS PublicationsRequest reuse permissionsArticle Views224Altmetric-Citations48LEARN 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 Other access optionsGet e-Alertsclose Get e-Alerts