gebhart/patrepeval huggingface dataset:
Effect of the Frequency of Transcutaneous Electrical Nerve Stimulation on the Postoperative Opioid Analgesic Requirement and Recovery Profile (1999)

TENS decreased postoperative opioid analgesic requirements and opioid-related side effects when utilized as an adjunct to PCA after lower abdominal surgery. Use of TENS at mixed (2- and 100-Hz) frequencies of stimulation produced a slightly greater opioid-sparing effect than either low (2-Hz) or high (100 Hz) frequencies alone.
Synthesis of 2-Alkoxy-Substituted Thiophenes, 1,3-Thiazoles, and Related S-Heterocycles via Lawesson's Reagent-Mediated Cyclization under Microwave Irradiation:  Applications for Liquid Crystal Synthesis (2001)

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTSynthesis of 2-Alkoxy-Substituted Thiophenes, 1,3-Thiazoles, and Related S-Heterocycles via Lawesson's Reagent-Mediated Cyclization under Microwave Irradiation: Applications for Liquid Crystal SynthesisAndre A. Kiryanov, Paul Sampson, and Alexander J. SeedView Author Information Department of Chemistry, Kent State University, Kent, Ohio 44242 %[email protected]Cite this: J. Org. Chem. 2001, 66, 23, 7925–7929Publication Date (Web):October 17, 2001Publication History Received28 August 2001Published online17 October 2001Published inissue 1 November 2001https://pubs.acs.org/doi/10.1021/jo016063xhttps://doi.org/10.1021/jo016063xbrief-reportACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views2492Altmetric-Citations127LEARN 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:Cyclization,Irradiation,Liquid crystals,Organic compounds,Reagents Get e-Alerts
Use of psoralen-modified oligonucleotides to trap three-stranded RecA-DNA complexes and repair of these cross-linked complexes by ABC excinuclease. (1988)

A series of site-specifically cross-linked, three-stranded complexes has been prepared using the RecA protein, form I (covalently closed and negatively supercoiled) pUC19 plasmid, and eight psoralen-monoadducted oligonucleotides between 30 and 107 residues in length. Complexes formed much less efficiently if linearized pUC19 was used as the duplex substrate. Quantitative analysis indicates that although RecA is able to utilize a 30-mer in its homologous pairing reaction, incorporation at 50% efficiency requires a single-stranded substrate at least 50 residues long. These three-stranded complexes have been used to study the action mechanism for cross-link repair by ABC excinuclease, and the results are consistent with the recent model of Van Houten, B., Gamper, H., Holbrook, S. R., Hearst, J. E., and Sancar, A. (1986b) Proc. Natl. Acad. Sci. U. S. A. 83, 8077-8081.
The Transcriptional Activity of the CCAAT-binding Factor CBF Is Mediated by Two Distinct Activation Domains, One in the CBF-B Subunit and the Other in the CBF-C Subunit (1996)

CBF-A, CBF-B, and CBF-C together form the heterotrimeric mammalian CCAAT-binding factor, CBF, which binds to DNA to form a CBF-DNA complex. Here we examined the transcription activation function of CBF in an in vitro reconstituted system using the three purified recombinant CBF subunits expressed in Escherichia coli. Two of the subunits, CBF-A and CBF-C, were coexpressed and purified as a CBF-A/CBF-C complex. Addition of the three wild-type recombinant CBF subunits to EL4 cell nuclear extracts depleted of CBF stimulated transcription 5-20-fold from proalpha2(1) collagen promoters and 10-fold from the Rous sarcoma virus long terminal repeat. Two CBF deletion mutants, one containing full-length CBF-A and CBF-C and a CBF-B lacking the NH2-terminal residues 1-224, and the other containing full- length CBF-A and CBF-B and a CBF-C lacking the COOH-terminal residues 114-309, also stimulated transcription from these promoters, but the level of activation was reduced to half that obtained with the full-length CBF subunits. In contrast, a CBF deletion mutant protein containing full-length CBF-A and deleted forms of both CBF-B and CBF-C showed very little transcription activation from these promoters. Hence, this study demonstrates that the heterotrimeric CBF protein consists of two transcription activation domains, one present in CBF-B and the other in CBF-C, and that the two domains act additively in the in vitro assay. The activation domains of both CBF-B and CBF-C, which are rich in glutamine and hydrophobic residues, showed amino acid sequence similarities with each other and with the glutamine-rich activation domain of transcription factor Sp1.
Evidence for gut factor in K+ homeostasis (2007)

We tested the hypothesis that K(+) intake is sensed by putative K(+) sensors in the splanchnic areas, and renal K(+) handling is regulated by this signal. K(+) was infused for 2 h into overnight-fasted rats via the jugular vein (systemic infusion), hepatic portal vein (intraportal infusion), or stomach (intragastric infusion) (n = 5 each), and plasma K(+) concentration ([K(+)]) and renal K(+) excretion were measured during the 2-h preinfusion, 2-h K(+) infusion, and 3-h washout periods. During systemic K(+) infusion, plasma [K(+)] increased by approximately 1.3 mM (P < 0.05), and, on cessation of the K(+) infusion, plasma [K(+)] fell to the preinfusion level within 1-2 h. Renal K(+) excretion changed in proportion to the changes in plasma [K(+)]. During intraportal or intragastric K(+) infusion, plasma [K(+)] and renal K(+) excretion profiles were similar to those with systemic infusion. The effects of K(+) infusions via the different routes (n = 5 or 6 each) were also studied during simultaneous feeding of overnight-fasted rats with a K(+)-deficient diet. During the meal, intraportal infusion resulted in increases in plasma [K(+)] similar to those with the systemic K(+) infusion, while intragastric K(+) infusion did not significantly increase plasma [K(+)]. Thus, when the intragastric K(+) infusion was combined with a meal, there was marked enhancement of clearance of the K(+) infused, which was associated with an apparent increase in renal efficiency of K(+) excretion. These data suggest that there may be a gut factor that enhances renal efficiency of K(+) excretion during meal (or dietary K(+)) intake.
Urine RAS components in mice and people with type 1 diabetes and chronic kidney disease (2017)

The pathways implicated in diabetic kidney disease (DKD) are largely derived from animal models. To examine if alterations in renin-angiotensin system (RAS) in humans are concordant with those in rodent models, we measured concentration of angiotensinogen (AOG), cathepsin D (CTSD), angiotensin-converting enzyme (ACE), and ACE2 and enzymatic activities of ACE, ACE2, and aminopeptidase-A in FVB mice 13-20 wk after treatment with streptozotocin (<i>n</i> = 9) or vehicle (<i>n</i> = 15) and people with long-standing type 1 diabetes, with (<i>n</i> = 37) or without (<i>n</i> = 81) DKD. In streptozotocin-treated mice, urine AOG and CTSD were 10.4- and 3.0-fold higher than in controls, respectively (<i>P</i> < 0.001). Enzymatic activities of ACE, ACE2, and APA were 6.2-, 3.2-, and 18.8-fold higher, respectively, in diabetic animals (<i>P</i> < 0.001). Angiotensin II was 2.4-fold higher in diabetic animals (<i>P =</i> 0.017). Compared with people without DKD, those with DKD had higher urine AOG (170 vs. 15 μg/g) and CTSD (147 vs. 31 μg/g). In people with DKD, urine ACE concentration was 1.8-fold higher (1.4 vs. 0.8 μg/g in those without DKD), while its enzymatic activity was 0.6-fold lower (1.0 vs. 1.6 × 10<sup>9</sup> RFU/g in those without DKD). Lower ACE activity, but not ACE protein concentration, was associated with ACE inhibitor (ACEI) treatment. After adjustment for clinical covariates, AOG, CTSD, ACE concentration, and ACE activity remained associated with DKD. In conclusion, in mice with streptozotocin-induced diabetes and in humans with DKD, urine concentrations and enzymatic activities of several RAS components are concordantly increased, consistent with enhanced RAS activity and greater angiotensin II formation. ACEI use was associated with a specific reduction in urine ACE activity, not ACE protein concentration, suggesting that it may be a marker of exposure to this widely-used therapy.
Progress in the discovery of Factor Xa inhibitors (2006)

Factor Xa is a serine protease that has a critical role in the blood coagulation cascade by ultimately regulating the production of thrombin. There is now ample evidence for the role of Factor Xa inhibitors as anticoagulants and they represent potential new therapeutic agents for the treatment and prevention of arterial and venous thrombosis. During the past five years, research in the field of Factor Xa inhibitors has been marked with enormous efforts to identify highly potent, selective and orally-active agents. This research has led to the discovery of a number of clinical candidates that are currently progressing at different stages of drug development. This review examines the patent and scientific literature during the period 2000 – 2005.
Evaluation of nucleic acid-based test (PACE 2C) for simultaneous detection of Chlamydia trachomatis and Neisseria gonorrhoeae in endocervical specimens (1995)

A nucleic acid-based test (Gen-Probe PACE 2C System) was evaluated for the ability to detect Chlamydia trachomatis and Neisseria gonorrhoeae from endocervical specimens in a single assay. Three swab samples, randomized for collection order, were obtained from each patient and tested by N. gonorrhoeae and C. trachomatis culture and by the PACE 2C probe assay. Fifty of 395 specimens were culture positive for N. gonorrhoeae (17 specimens), C. trachomatis (26 specimens), or both (7 specimens), of which PACE 2C testing detected 48 specimens. The PACE 2C assay was positive for 56 specimens, including 8 specimens not positive by culture. Of the total of 10 discrepancies between culture and PACE 2C results, resolution testing yielded four false-negative culture, four false-positive PACE 2C, and two false-negative PACE 2C results. The sensitivity, specificity, and positive and negative predictive values for PACE 2C after reevaluation were 96.3, 98.8, 92.9 and 99.4%, respectively. The overall sensitivities for C. trachomatis and N. gonorrhoeae culture were 89.2 and 88.9%, respectively. The prevalence rate for C. trachomatis was 9.4%, and that for N. gonorrhoeae was 6.8%. The Gen-Probe PACE 2C System is a reliable alternative for screening endocervical specimens for both C. trachomatis and N. gonorrhoeae in a single assay.
Structure of human IFIT1 with capped RNA reveals adaptable mRNA binding and mechanisms for sensing N1 and N2 ribose 2′-O methylations (2017)

IFIT1 (IFN-induced protein with tetratricopeptide repeats-1) is an effector of the host innate immune antiviral response that prevents propagation of virus infection by selectively inhibiting translation of viral mRNA. It relies on its ability to compete with the translation initiation factor eIF4F to specifically recognize foreign capped mRNAs, while remaining inactive against host mRNAs marked by ribose 2'-O methylation at the first cap-proximal nucleotide (N1). We report here several crystal structures of RNA-bound human IFIT1, including a 1.6-Å complex with capped RNA. IFIT1 forms a water-filled, positively charged RNA-binding tunnel with a separate hydrophobic extension that unexpectedly engages the cap in multiple conformations (<i>syn</i> and <i>anti</i>) giving rise to a relatively plastic and nonspecific mode of binding, in stark contrast to eIF4E. Cap-proximal nucleotides encircled by the tunnel provide affinity to compete with eIF4F while allowing IFIT1 to select against N1 methylated mRNA. Gel-shift binding assays confirm that N1 methylation interferes with IFIT1 binding, but in an RNA-dependent manner, whereas translation assays reveal that N1 methylation alone is not sufficient to prevent mRNA recognition at high IFIT1 concentrations. Structural and functional analysis show that 2'-O methylation at N2, another abundant mRNA modification, is also detrimental for RNA binding, thus revealing a potentially synergistic role for it in self- versus nonself-mRNA discernment. Finally, structure-guided mutational analysis confirms the importance of RNA binding for IFIT1 restriction of a human coronavirus mutant lacking viral N1 methylation. Our structural and biochemical analysis sheds new light on the molecular basis for IFIT1 translational inhibition of capped viral RNA.
Inhibition of tyrosine sulfation in the trans-Golgi retards the transport of a constitutively secreted protein to the cell surface. (1988)

The effect of tyrosine sulfation on the transport of a constitutively secreted protein, yolk protein 2 (YP2) of Drosophila melanogaster, to the cell surface was investigated after expression of YP2 in mouse fibroblasts. Inhibition of YP2 sulfation was achieved by two distinct approaches. First, the single site of sulfation in YP2, tyrosine 172, was changed to phenylalanine by oligonucleotide-directed mutagenesis. Second, L cell clones stably expressing YP2 were treated with chlorate, a reversible inhibitor of sulfation. Pulse-chase experiments with transfected L cell clones showed that the half-time of transport from the rough endoplasmic reticulum to the cell surface of the unsulfated mutant YP2 and the unsulfated wild-type YP2 produced in the presence of chlorate was 15-18 min slower than that of the sulfated wild-type YP2. Control experiments indicated (a) that the tyrosine to phenylalanine change itself did not affect YP2 transport, (b) that the retardation of YP2 transport by chlorate occurred only with sulfatable but not with unsulfatable YP2, (c) that the transport difference between wild-type and mutant YP2 was not due to the level of YP2 expression, and (d) that transport of the endogenous secretory protein fibronectin was the same in L cell clones expressing wild-type and mutant YP2. Since the half-time of transport of wild-type YP2 from the intracellular site of sulfation, the trans-Golgi, to the cell surface was found to be 10 min, the 15-18-min retardation seen upon inhibition of tyrosine sulfation reflected a two- to threefold increase in the half-time of trans-Golgi to cell surface transport, which was most probably caused by an increased residence time of unsulfated YP2 in the trans-Golgi. The results demonstrate a role of tyrosine sulfation in the intracellular transport of a constitutively secreted protein.
Combination Treatment With Remdesivir and Ivermectin Exerts Highly Synergistic and Potent Antiviral Activity Against Murine Coronavirus Infection (2021)

The recent COVID-19 pandemic has highlighted the urgency to develop effective antiviral therapies against the disease. Murine hepatitis virus (MHV) is a coronavirus that infects mice and shares some sequence identity to SARS-CoV-2. Both viruses belong to the <i>Betacoronavirus </i>genus, and MHV thus serves as a useful and safe surrogate model for SARS-CoV-2 infections. Clinical trials have indicated that remdesivir is a potentially promising antiviral drug against COVID-19. Using an <i>in vitro</i> model of MHV infection of RAW264.7 macrophages, the safety and efficacy of monotherapy of remdesivir, chloroquine, ivermectin, and doxycycline were investigated. Of the four drugs tested, remdesivir monotherapy exerted the strongest inhibition of live virus and viral RNA replication of about 2-log<sub>10</sub> and 1-log<sub>10</sub>, respectively (at 6 µM). Ivermectin treatment showed the highest selectivity index. Combination drug therapy was also evaluated using remdesivir (6 µM) together with chloroquine (15 µM), ivermectin (2 µM) or doxycycline (15 µM) - above their IC50 values and at high macrophage cell viability of over 95%. The combination of remdesivir and ivermectin exhibited highly potent synergism by achieving significant reductions of about 7-log<sub>10</sub> of live virus and 2.5-log<sub>10</sub> of viral RNA in infected macrophages. This combination also resulted in the lowest cytokine levels of IL-6, TNF-α, and leukemia inhibitory factor. The next best synergistic combination was remdesivir with doxycycline, which decreased levels of live virus by ~3-log<sub>10</sub> and viral RNA by ~1.5-log<sub>10</sub>. These results warrant further studies to explore the mechanisms of action of the combination therapy, as well as future <i>in vivo</i> experiments and clinical trials for the treatment of SARS-CoV-2 infection.
Repeated Vergence Adaptation Causes the Decline of Visual Functions in Watching Stereoscopic Television (2005)

To evaluate visual fatigue when viewing stereoscopic TV, a technology expected to become the broadcasting display system of the future. Wide public acceptance of stereoscopic TV awaits resolution of many issues, including visual fatigue on viewing TV images. Visual fatigue was induced using a visual function simulator, consisting of prism and lens optical systems, while viewing stereoscopic TV. We assessed subject visual fatigue through subjective reports of symptoms and by the changes in visual functions. These functions included: viewer B [Js fusional break point, recovery point, accommodation step response, and visual evoked cortical potentials (VECP)]. Significant changes of some visual functions were found after watching simulated stereoscopic TV when the vergence load was heavy or when it changed over time; relative vergence limits decreased and the latency of VECP increased after watching, reflecting visual fatigue. After subjects rested, relative vergence limits recovered to pre-viewing levels. Our findings lead us to conclude that, aside from excessive horizontal binocular parallax, discontinuous changes in parallax is also a major factor that contributes to visual fatigue in the viewing of stereoscopic images. It also causes a decreased range of relative vergence, accommodation response, and a delay in the P100 latency of VECP.
Transmitter Optimization and Optimality of Beamforming for Multiple Antenna Systems (2004)

We solve the transmitter optimization problem and determine a necessary and sufficient condition under which beamforming achieves Shannon capacity in a linear narrowband point-to-point communication system employing multiple transmit and receive antennas with additive Gaussian noise. We assume that the receiver has perfect channel knowledge while the transmitter has only knowledge of either the mean or the covariance of the channel coefficients. The channel is modeled at the transmitter as a matrix of complex jointly Gaussian random variables with either a zero mean and a known covariance matrix (covariance information), or a nonzero mean and a white covariance matrix (mean information). For both cases, we develop a necessary and sufficient condition for when the Shannon capacity is achieved through beamforming; i.e., the channel can be treated like a scalar channel and one-dimensional codes can be used to achieve capacity. We also provide a waterpouring interpretation of our results and find that less channel uncertainty not only increases the system capacity but may also allow this higher capacity to be achieved with scalar codes which involves significantly less complexity in practice than vector coding.
Micro Magnetic Separator for Stem Cell Sorting System (2005)

Final goal of the present study is to develop micro immunomagnetic cell sorting (uIMCS) system for ex- tracting stem cells from peripheral blood. In this report, micro magnetic separator is designed to extract target cells bound to magnetic beads with the aid of on-chip micro coil. Channel geometry and coil arrange- ment are determined through a series of numerical simulation of magnetic field and the flow field. Prototype device with embedded coil is microfabricated with the soft lithography technology.
Cell‐Penetrating, Dimeric α‐Helical Peptides: Nanomolar Inhibitors of HIV‐1 Transcription (2014)

We constructed dimeric α-helical peptide bundles based on leucine (L) and lysine (K) residues for both efficient cell penetration and inhibition of the Tat-TAR interaction. The LK dimers can penetrate nearly quantitatively into eukaryotic cells and effectively inhibit the elongation of the TAR transcript at low nanomolar concentrations. The effective inhibition of HIV-1 replication strongly suggests that the LK dimer has strong potential as an anti-HIV-1 drug.
Discovery and Development of Pyrazole-Scaffold Hsp90 Inhibitors (2006)

This review explains why the chaperone Hsp90 is an exciting protein target for the discovery of new drugs to treat cancer in the clinic, and summarises the properties of natural product derived inhibitors before relating the discovery and current state of development of synthetic pyrazole compounds. Blockade of Hsp90 results in reduced cellular levels of several proteins implicated in cancer including CDK4, ERBB2 and C-RAF, and causes simultaneous inhibition of cancer cell proliferation in culture and of tumor xenograft growth in vivo. Hsp90 has an ATPase domain that is necessary for its Hsp chaperone function, and X-ray crystallography has shown that natural product inhibitors (geldanamycin, radicicol) of Hsp90 function bind to this domain. High throughput assays focusing on the ATPase activity of Hsp90 were developed and used to discover novel chemical starting points for cancer drug discovery. The discovery, synthesis and SAR of 3,4-diaryl pyrazoles is described. X-Ray crystallography of protein-inhibitor complexes revealed important interactions involving the resorcinol substituent at C-3, and these X-ray structures strongly influenced subsequent medicinal chemistry research that has resulted in highly potent inhibitors with sub-micromolar activity in cells. SAR and X-ray data are summarised for analogues in which the 4-phenyl substituent is replaced by amides or piperazine derivatives. Prospects for the pyrazoles as they progress towards clinical development are discussed in relation to current Phase I trials with derivatives of geldanamycin.
Higher frequency of alterations in the p16/CDKN2 gene in squamous cell carcinoma cell lines than in primary tumors of the head and neck. (1994)

Sixty-eight primary head and neck squamous cell carcinomas and nine head and neck squamous cell carcinoma cell lines were examined for mutations and homozygous deletions of the p16/CDKN2 gene. Homozygous deletions of the p16/CDKN2 gene were found in three lines, and a mutation was detected in another cell line. In contrast, none of the primary tumors showed homozygous deletions and 11 of 68 tumors had missense or nonsense base changes. Seven tumors contained somatic mutations. Five tumors, including one that also had a somatic mutation, had a probable polymorphism at codon 140 leading to an amino acid change from Ala to Thr. Three of these also contained an apparent polymorphism at codon 98, which did not lead to an amino acid change. The frequency of mutations and deletions detected differs markedly between cell lines (44%) and primary tumors (10%) suggesting that while p16/CDKN2 may play a role in tumorigenesis in some head and neck squamous cell carcinomas, inactivation of p16/CDKN2 probably occurs more frequently in cell lines as a result of adaptation to cell culture.