gebhart/patrepeval huggingface dataset:
Synthesis of a tight-binding, multisubstrate analog inhibitor of gentamicin acetyltransferase I. (1979)

Gentamicin acetyltransferase I will catalyze acyl transfer from chloroacetylcoenzyme A to form 3-N-chloroacetylgentamicin. This product can be linked to coenzyme A to form a multisubstrate analog by nucleophilic displacement of the chlorine by the sulfur of coenzyme A. The analog can be purified by selective binding to cationic and anionic ion exchange resins. Kinetic analysis of a time-dependent onset and reversal of inhibition of gentamicin acetyltransferase I by the purified multisubstrate analog yields an inhibition constant of 5 approximately 20 x 10(-10) M. The inhibitor does not potentiate antibiotic activity against resistant Escherichia coli. Nevertheless, the effectiveness of the tight-binding between the enzyme and the multisubstrate analog demonstrates that inhibitors of resistance can be designed and prepared by specific enzymatic synthesis.
TiO2 Nanotube Arrays of 1000 μm Length by Anodization of Titanium Foil:  Phenol Red Diffusion (2007)

We report for the first time fabrication of self-aligned hexagonally closed-packed titania nanotube arrays of over 1000 μm in length and aspect ratio ≈10 000 by potentiostatic anodization of titanium. We describe a process by which such thick nanotube array films can be transformed into self-standing, flat or cylindrical, mechanically robust, polycrystalline TiO2 membranes of precisely controlled nanoscale porosity. The self-standing membranes are characterized using Brunauer−Emmett−Teller surface area measurements, glancing angle X-ray diffraction, and transmission electron microscopy. In initial application, such membranes are used to control the diffusion of phenol red.
Chronic daily headache (2002)

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Rational design of highly potent broad-spectrum enterovirus inhibitors targeting the nonstructural protein 2C (2020)

There is a great need for antiviral drugs to treat enterovirus (EV) and rhinovirus (RV) infections, which can be severe and occasionally life-threatening. The conserved nonstructural protein 2C, which is an AAA+ ATPase, is a promising target for drug development. Here, we present a structure-activity relationship study of a previously identified compound that targets the 2C protein of EV-A71 and several EV-B species members, but not poliovirus (PV) (EV-C species). This compound is structurally related to the Food and Drug Administration (FDA)-approved drug fluoxetine-which also targets 2C-but has favorable chemical properties. We identified several compounds with increased antiviral potency and broadened activity. Four compounds showed broad-spectrum EV and RV activity and inhibited contemporary strains of emerging EVs of public health concern, including EV-A71, coxsackievirus (CV)-A24v, and EV-D68. Importantly, unlike (S)-fluoxetine, these compounds are no longer neuroactive. By raising resistant EV-A71, CV-B3, and EV-D68 variants against one of these inhibitors, we identified novel 2C resistance mutations. Reverse engineering of these mutations revealed a conserved mechanism of resistance development. Resistant viruses first acquired a mutation in, or adjacent to, the α2 helix of 2C. This mutation disrupted compound binding and provided drug resistance, but this was at the cost of viral fitness. Additional mutations at distantly localized 2C residues were then acquired to increase resistance and/or to compensate for the loss of fitness. Using computational methods to identify solvent accessible tunnels near the α2 helix in the EV-A71 and PV 2C crystal structures, a conserved binding pocket of the inhibitors is proposed.
MinK-Related Peptide 1 (2001)

The HCN family of ion channel subunits underlies the currents I(f) in heart and I(h) and I(q) in the nervous system. In the present study, we demonstrate that minK-related peptide 1 (MiRP1) is a beta subunit for the HCN family. As such, it enhances protein and current expression as well as accelerating the kinetics of activation. Because MiRP1 also functions as a beta subunit for the cardiac delayed rectifier I(Kr), these results suggest that this peptide may have the unique role of regulating both the inward and outward channels that underlie cardiac pacemaker activity. The full text of this article is available at http://www.circresaha.org.
Trachyspic Acid, a New Metabolite Produced by Talaromyces trachyspermus, that Inhibits Tumor Cell Heparanase: Taxonomy of the Producing Strain, Fermentation, Isolation, Structural Elucidation, and Biological Activity. (1995)

Trachyspic acid, a new metabolite that inhibited heparanase, was isolated from the culture broth of Talaromyces trachyspermus SANK 12191. Its structure was deduced from NMR spectral analyses and chemical reactions as a tricarboxylic acid derivative containing a spiroketal. The IC50 value of trachyspic acid against heparanase was 36 microM.
A time-of-flight mass spectrometer for static SIMS applications (1985)

A high performance time-of-flight secondary-ion mass spectrometer equipped with a mass selected pulsed primary ion source, an angle and energy focusing time-of-flight analyzer, and a high efficiency single-ion counting detector is described. The instrument can be applied for trace analysis of organic as well as inorganic material for the detection, identification, and structural analysis of large organic molecules in the pico- and femtomol range, as well as for the undisturbed SIMS investigation of surface structures very sensitive to ion bombardment. Spectra of Teflon, a fully protected tetranucleotide and a nonapeptide are reported.
Stability of Cyclic β-Hairpins:  Asymmetric Contributions from Side Chains of a Hydrogen-Bonded Cross-Strand Residue Pair (2002)

Amino acid structural propensities measured in "host-guest" model studies are often used in protein structure prediction or to choose appropriate residues in de novo protein design. While this concept has proven useful for helical structures, it is more difficult to apply successfully to beta-sheets. We have developed a cyclic beta-hairpin scaffold as a host for measurement of individual residue contributions to hairpin structural stability. Previously, we have characterized substitutions in non-backbone-hydrogen-bonded strand sites; relative stability differences measured in the cyclic host are highly predictive of changes in folding free energy for linear beta-hairpin peptides. Here, we examine the hydrogen-bonded strand positions of our host. Surprisingly, we find a large favorable contribution to stability from a valine (or isoleucine) substitution immediately preceding the C-terminal cysteine of the host peptide, but not at the cross-strand position of the host or in either strand of a folded linear beta-hairpin (trpzip peptide). Further substitutions in the peptides and NMR structural analysis indicate that the stabilizing effect of valine is general for CX(8)C cyclic hairpins and cannot be explained by particular side-chain-side-chain interactions. Instead, a localized decrease in twist of the peptide backbone on the N-terminal side of the cysteine allows the valine side chain to adopt a unique conformation that decreases the solvent accessibility of the peptide backbone. The conformation differs from the highly twisted (coiled) conformation of the trpzip hairpins and is more typical of conformations present in multistranded beta-sheets. This unexpected structural fine-tuning may explain why cyclic hairpins selected from phage-displayed libraries often have valine in the same position, preceding the C-terminal cysteine. It also emphasizes the diversity of structures accessible to beta-strands and the importance of considering not only "beta-propensity", but also hydrogen-bonding pattern and strand twist, when designing beta structures. Finally, we observe correlated, cooperative stabilization from side-chain substitutions on opposite faces of the hairpin. This suggests that cooperative folding in beta-hairpins and other small beta-structures is driven by cooperative strand-strand association.
Identification of underexpressed genes in early- and late-stage primary ovarian tumors by suppression subtraction hybridization. (2002)

To identify novel tumor suppressor genes involved in ovarian carcinogenesis, we generated four down-regulated suppression subtraction cDNA libraries from two early-stage (stage I/II) and two late-stage (stage III) primary ovarian tumors, each subtracted against cDNAs derived from normal ovarian epithelial cell brushings. Approximately 600-700 distinct clones were sequenced from each library. Comparison of down-regulated clones obtained from early- and late-stage tumors revealed genes that were unique to each library which suggested tumor-specific differences. We found 45 down-regulated genes that were common in all four libraries. We also identified several genes, the role of which in tumor development has yet to be elucidated, in addition to several under expressed genes, the potential role of which in carcinogenesis has been described previously (Bagnoli et al., Oncogene, 19: 4754-4763, 2000; Yu et al., Proc. Natl. Acad. Sci. USA, 96: 214-219, 1999; Mok et al., Oncogene, 12: 1895-1901, 1996). The differential expression of a subset of these genes was confirmed by semiquantitative reverse transcription-PCR using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as control in a panel of 15 stage I and 15 stage III tumors of mixed histological subtypes. Chromosomal sorting of library sequences revealed that several of the genes mapped to known regions of deletion in ovarian cancer. Loss of heterozygosity (LOH) analysis revealed multiple genomic regions with a high frequency of loss in both early- and late-stage tumors. To determine whether loss of expression of some of the genes corresponds to loss of an allele by LOH, we used a microsatellite marker for one of the novel genes on 8q and have shown that loss of expression of this novel gene correlates with loss of an allele by LOH. In conclusion, our analysis has identified down-regulated genes, which map to known as well as novel regions of deletions and may represent potential candidate tumor suppressor genes involved in ovarian cancer.
Near-peer Learning in Clinical Education: A Systematic Review (2010)

Background: Near-peer learning in Clinical Education (CE) has been considered an alternative to faculty led learning in undergraduate health professional curricula due to factors such as staffing shortages, financial pressures, increased student numbers, and emphasis on providing different types of learning for students. Currently at the University of Otago School of Physiotherapy (UOSP), fourth year students provide clinical supervision for second year students. Aims: To review the literature surrounding near-peer learning in health professional undergraduate curricula, identify evidence for the current nearpeer learning model at the UOSP, and suggest directions for further research. Methods: Four assessors reviewed near peer literature for methodological quality, according to Sackett et al. (2000) and Law et al. (1998). Seventeen articles were selected. Articles were tiered according to subject: Non-physiotherapy field, non-clinical setting; Physiotherapy field, non-clinical setting; Nonphysiotherapy field, clinical education; and Physiotherapy field, clinical education. Results: The majority of research analysed perceptions of the effectiveness of near-peer learning programs. Despite several articles having poor methodology and mixed results, the majority were in favour of near-peer learning. No articles fitted into our main area of interest, which was physiotherapy in a clinical setting. Conclusion: Literature in the area of peer learning in undergraduate clinical education is of poor quality. No clear parameters have been identified on a gold standard inter-year peer learning model. Further research with control groups, objective outcome measures and definitive conclusions is warranted in the field of near peer learning in clinical fields.
Carbon monoxide: an endogenous modulator of sinusoidal tone in the perfused rat liver. (1995)

Heme oxygenase is a heme-oxidizing enzyme which generates biliverdin and carbon monoxide (CO). The present study was designed to elucidate whether CO endogenously produced by this enzyme serves as an active vasorelaxant in the hepatic microcirculation. Microvasculature of the isolated perfused rat liver was visualized by dual-color digital microfluorography to alternately monitor sinusoidal lining and fat-storing Ito cells. In the control liver, the CO flux in the venous effluent ranged at 0.7 nmol/min per gram of liver. Administration of a heme oxygenase inhibitor zinc protoporphyrin IX (1 microM) eliminated the baseline CO generation, and the vascular resistance exhibited a 30% elevation concurrent with discrete patterns of constriction in sinusoids and reduction of the sinusoidal perfusion velocity. The major sites of the constriction corresponded to local sinusoidal segments colocalized with Ito cell which were identified by imaging their vitamin A autofluorescence. The increase in the vascular resistance and sinusoidal constriction were attenuated significantly by adding CO (1 microM) or a cGMP analogue 8-bromo-cGMP (1 microM) in the perfusate. From these findings, we propose that CO can function as an endogenous modulator of hepatic sinusoidal perfusion through a relaxing mechanism involving Ito cells.
Professional certification through ICCP (1996)

This article deals with professional and entry-level certification through the examination programs of the Institute for Certification of Computing Professionals (ICCP). The material is organized by frequently-asked questions (FAQs).
EGFR family: Structure physiology signalling and therapeutic targets † (2008)

There are four members of the EGFR family: EGFR, erbB2, erbB3 and erbB4. These receptors form ligand-activated oligomers which regulate intracellular processes via an oligomeric tyrosine kinase scaffold. The receptors are activated when the extracellular domain undergoes a conformational change which facilitates either homo- or hetero-oligomerization with other family members. The absence of one EGFR family member leads to embryonic or early post-natal death due to implantation, central nervous system or cardiac defects. Many mouse models of defective or deficient EGFR family members are available for studying physiology and/or pathology of EGFR family members. Sophisticated antibody and kinase inhibitors which target different family members have been designed, produced. EGFR and erbB2 are frequently activated, over expressed or mutated in many common cancers and the antagonists and/or inhibitors of EGFR and/or erbB2 signalling have already been shown to have therapeutic benefits for cancer patients.
Coronavirus transcription: subgenomic mouse hepatitis virus replicative intermediates function in RNA synthesis (1990)

Both genomic and subgenomic replicative intermediates (RIs) and replicative-form (RF) structures were found in 17CL1 mouse cells that had been infected with the A59 strain of mouse hepatitis virus (MHV), a prototypic coronavirus. Seven species of RNase-resistant RF RNAs, whose sizes were consistent with the fact that each was derived from an RI that was engaged in the synthesis of one of the seven MHV positive-strand RNAs, were produced by treatment with RNase A. Because the radiolabeling of the seven RF RNAs was proportional to that of the corresponding seven positive-strand RNAs, the relative rate of synthesis of each of the MHV positive-strand RNAs may be controlled by the relative number of each of the size classes of RIs that are produced. In contrast to alphavirus, which produced its subgenome-length RF RNAs from genome-length RIs, MHV RF RNAs were derived from genome- and subgenome-length RIs. Only the three largest MHV RF RNAs (RFI, RFII, and RFIII) were derived from the RIs that migrated slowest on agarose gels. The four smallest RF RNAs (RFIV, RFV, RFVI, and RFVII) were derived from RIs that migrated in a broad region of the gel that extended from the position of 28S rRNA to the position of the viral single-stranded MHV mRNA-3. Because all seven RIs were labeled during very short pulses with [3H]uridine, we concluded that the subgenome-length RIs are transcriptionally active. These findings, with the recent report of the presence of subgenome-length negative-strand RNAs in cells infected with porcine transmissible gastroenteritis virus (P. B. Sethna, S.-L. Hung, and D. A. Brian, Proc. Natl. Acad. Sci. USA 86: 5626-5630, 1989), strongly suggest that coronaviruses utilize a novel replication strategy that employs the synthesis of subgenomic negative strands to produce subgenomic mRNAs.
Next‐generation peptide vaccines for advanced cancer (2012)

Many clinical trials of peptide vaccines have been carried out since the first clinical trial of a melanoma antigen gene-1-derived peptide-based vaccine was reported in 1995. The earlier generations of peptide vaccines were composed of one to several human leukocyte antigen class I-restricted CTL-epitope peptides of a single human leukocyte antigen type. Currently, various types of next-generation peptide vaccines are under development. In this review, we focus on the clinical trials of the following categories of peptide vaccines mainly published from 2008 to 2012: (i) multivalent long peptide vaccines; (ii) multi-peptide vaccines consisting of CTL- and helper-epitopes; (iii) peptide cocktail vaccines; (iv) hybrid peptide vaccines; (v) personalized peptide vaccines; and (vi) peptide-pulsed dendritic cell vaccines.
Palladium-Catalyzed Alkoxyallylation of Activated Olefins (1998)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTPalladium-Catalyzed Alkoxyallylation of Activated OlefinsHiroyuki Nakamura, Masaru Sekido, Masateru Ito, and Yoshinori YamamotoView Author Information Department of Chemistry, Graduate School of Science Tohoku University, Sendai 980-8578, Japan Cite this: J. Am. Chem. Soc. 1998, 120, 27, 6838–6839Publication Date (Web):June 26, 1998Publication History Received23 March 1998Published online26 June 1998Published inissue 13 June 1998https://pubs.acs.org/doi/10.1021/ja980959ahttps://doi.org/10.1021/ja980959arapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views1068Altmetric-Citations51LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Allyl group,Anions,Ethyl groups,Hydrocarbons,Inorganic carbon compounds Get e-Alerts
Approaches for chemically synthesized siRNA and vector‐mediated RNAi (2005)

Successful applications of RNAi in mammalian cells depend upon effective knockdown of targeted transcripts and efficient intracellular delivery of either preformed si/shRNAs or vector expressed si/shRNAs. We have previously demonstrated that 27 base pair double stranded RNAs which are substrates for Dicer can be up to 100 times more potent than 21mer siRNAs. In this mini-review we elaborate upon the rationale and design strategies for creating Dicer substrate RNAs that provide enhanced knockdown of targeted RNAs and minimize the utilization of the sense strand as RNAi effectors. Expression of shRNAs or siRNAs in mammalian cells can be achieved via transcription from either Pol II or Pol III promoters. There are certain constrictions in designing such vectors, and these are described here. Additionally, we review strategies for inducible shRNA expression and the various viral vectors that can be used to transduce shRNA genes into a variety of cells and tissues. The overall goal of this mini-review is to provide an overview of available approaches for optimizing RNAi mediated down regulation of gene expression in mammalian cells via RNA interference. Although the primary focus is the use of RNAi mediated cleavage of targeted transcripts, it is highly probable that some of the approaches described herein will be applicable to RNAi mediated inhibition of translation and transcriptional gene silencing.
Cellulase digestibility of pretreated biomass is limited by cellulose accessibility (2007)

Attempts to correlate the physical and chemical properties of biomass to its susceptibility to enzyme digestion are often inconclusive or contradictory depending on variables such as the type of substrate, the pretreatment conditions and measurement techniques. In this study, we present a direct method for measuring the key factors governing cellulose digestibility in a biomass sample by directly probing cellulase binding and activity using a purified cellobiohydrolase (Cel7A) from Trichoderma reesei. Fluorescence-labeled T. reesei Cel7A was used to assay pretreated corn stover samples and pure cellulosic substrates to identify barriers to accessibility by this important component of cellulase preparations. The results showed cellulose conversion improved when T. reesei Cel7A bound in higher concentrations, indicating that the enzyme had greater access to the substrate. Factors such as the pretreatment severity, drying after pretreatment, and cellulose crystallinity were found to directly impact enzyme accessibility. This study provides direct evidence to support the notion that the best pretreatment schemes for rendering biomass more digestible to cellobiohydrolase enzymes are those that improve access to the cellulose in biomass cell walls, as well as those able to reduce the crystallinity of cell wall cellulose.
Delta-9-Tetrahydrocannabinol: Localization in Body Fat (1973)

[(14)C]Delta(9)-Tetrahydrocannabinol (Delta(9)THC) was injected subcutaneously in rats every day for 1 to 26 days. Concentrations of Delta(9)THC and its metabolites, 11-hydroxytetrahydrocannabinol and 8,11-dihydroxytetrahydrocannabinol, were determined in various tissues. After a single injection, the concentration of Delta(9)THC in fat was ten times greater than in any other tissue examined, and persisted in this tissue for 2 weeks. With repeated injection, Delta(9)THC and its metabolites accumulated in fat and brain.
New Phosphonate Analogues of 3′-Thia-2′,3′-dideoxycytidine(BCH-189) Synthesis and Anti-HIV Evaluation (1993)

Abstract New phosphonate analogues of 3′-thia-2′,3′-dideoxycytidine (BCH-189) were synthesized in 5 steps via cyclocondensation of 2-mercaptoacetaldehyde di[2-methoxyethyl]acetal with 3-diethylphosphonopropionaldehyde as a key step, followed by a Lewis acid catalyst addition of the appropriate nucleic base. Anti-HIV evaluation of these analogues showed that the α-form 3b of 3′-thia-2′,3′-dideoxycytidine-4′-ethylene phosphonic acid was inactive while the β-form 3a was found to be less potent than the parent compound (BCH-189), showing that the replacement of the oxygen in position 5′ by a methylene group in the monophosphorylated intermediate diminishes the antiviral activity.