gebhart/patrepeval huggingface dataset:
Characteristic impedance of multilevel, multiconductor hybrid mode microstrip (1989)

Two definitions of modal characteristic impedance for multiconductor, hybrid-mode microstrip are compared. The sensitivity of each to numerical inaccuracies is discussed. The plausibility of negative values of modal characteristic impedance is shown for two-mode (three-line) asymmetric geometries, and numerical results are presented for dual-plane, asymmetric, coupled microstrip.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Preclinical Development of an AAV8-hUGT1A1 Vector for the Treatment of Crigler-Najjar Syndrome (2018)

Adeno-associated viruses (AAVs) are among the most efficient vectors for liver gene therapy. Results obtained in the first hemophilia clinical trials demonstrated the long-term efficacy of this approach in humans, showing efficient targeting of hepatocytes with both self-complementary (sc) and single-stranded (ss) AAV vectors. However, to support clinical development of AAV-based gene therapies, efficient and scalable production processes are needed. In an effort to translate to the clinic an approach of AAV-mediated liver gene transfer to treat Crigler-Najjar (CN) syndrome, we developed an (ss)AAV8 vector carrying the human UDP-glucuronosyltransferase family 1-member A1 (hUGT1A1) transgene under the control of a liver-specific promoter. We compared our construct with similar (sc)AAV8 vectors expressing hUGT1A1, showing comparable potency <i>in vitro</i> and <i>in vivo</i>. Conversely, (ss)AAV8-hUGT1A1 vectors showed superior yields and product homogeneity compared with their (sc) counterpart. We then focused our efforts in the scale-up of a manufacturing process of the clinical product (ss)AAV8-hUGT1A1 based on the triple transfection of HEK293 cells grown in suspension. Large-scale production of this vector had characteristics identical to those of small-scale vectors produced in adherent cells. Preclinical studies in animal models of the disease and a good laboratory practice (GLP) toxicology-biodistribution study were also conducted using large-scale preparations of vectors. These studies demonstrated long-term safety and efficacy of gene transfer with (ss)AAV8-hUGT1A1 in relevant animal models of the disease, thus supporting the clinical translation of this gene therapy approach for the treatment of CN syndrome.
Wirkung neuer Pyridiniumverbindungen gegen ausgewählte Bakterien‐ und Pilzstämme, 6. Mitt.<sup>1</sup>) Synthese von 3,5‐Dimethyl‐, 3‐Brom‐ und 3‐Chlor‐1‐(n‐alkylthiomethyl)pyridiniumchloriden (1983)

Abstract Es wird die Synthese und die antibakterielle Wirkung der Pyridinium‐Verbindungen 1, 2 und 3 beschrieben. Die quartären Pyridiniumchloride wurden durch Reaktion von Chlormethyl‐n‐alkylsulfid mit 3,5‐Dimethyl‐, 3‐Brom‐ und 3‐Chlorpyridin synthetisiert. Die Verbindungen mit dem Dodecylrest wirken auf die Mikroben am besten.
Bradykinin antagonist dimer, CU201, inhibits the growth of human lung cancer cell lines in vitro and in vivo and produces synergistic growth inhibition in combination with other antitumor agents. (2002)

Small cell lung cancers (SCLCs), many non-SCLCs, and other cancers have neuroendocrine features, including paracrineand autocrine growth stimulation by various neuropeptides. Interference with this pathway is an attractive target for novel therapies. We developed a novel bradykinin antagonist dimer, CU201 (B9870), that acts as a "biased agonist" for neuropeptides by blocking G(alphaq) signaling and activating G(alpha12,13) signaling. CU201 induced apoptosis and complete growth inhibition in various lung cancer and other cancer cell lines. CU201 was 10-fold more potent than substance P derivatives and was stable in serum for >7 days. In this study, we evaluated the ability of CU201 to produce additive or synergistic growth inhibition in combination with various antitumor agents used in lung cancer therapy. We found that CU201 produced additive or synergistic growth inhibition when combined with doxorubicin, etoposide, cisplatin, vinorelbine, and paclitaxel for SCLC lines and with paclitaxel and ZD1839, an epidermal growth factor receptor tyrosine kinase inhibitor, for non-SCLC cell lines. Pharmacokinetic parameters associated with the i.v. administration of CU201 were evaluated in normal mice, and the effects of CU201 on the growth of human lung cancer xenografts were evaluated in athymic nude mice. In CD2F1 mice given an i.v. bolus infusion of 5 mg/kg, the c(max) was 5773 ng/ml (5 microM), and the decay was biexponential. When fitted to a two-compartment model, the t(1/2alpha) was 14.4 min, and the t(1/2beta) was 44.3 h, indicating a long terminal half-life consistent with the prolonged in vitro effects. CU201 inhibited the growth of human lung cancers in athymic nude mice by the intratumoral, s.c., and i.p. routes at a dose of 5 mg/kg/day. This dose is >10-fold less than the dose of substance P derivatives used to inhibit SCLC xenografts in nude mice. We conclude that CU201 should undergo further preclinical toxicology studies in its development as a novel targeted therapy for the treatment of lung cancers with neuroendocrine features. These studies are in progress through the NCI RAID mechanism.
Prescribing preferences of U.S. oncologists for patients (Pts) with metastatic urothelial carcinoma (mUC) at first recurrence: Impact of novel agents. (2017)

365 Background: In May 2016 atezolizumab (A) was approved for the treatment of pts with locally advanced or mUC who have disease progression during or following platinum-containing chemotherapy (PCCT), or within 12 months (mos) of neoadjuvant or adjuvant treatment with PCCT. We evaluated prescribing preferences (PPrefs) of 248 U.S-based oncologists for 1 st recurrence treatment across a range of clinical scenarios prior to and following A approval. Methods: PPrefs were assessed through a validated, case-based market research tool (Challenging Cases). Assessment dates were 3/5 and 4/30 (PRE-) and 8/6 (POST-approval). Data were acquired using blinded, audience-response technology. A core scenario (CS) and 5 variant scenarios (V1, 2, 3, 4, 5) were utilized. CS: 69-year-old pt with muscle invasive bladder cancer, with a CrCl 62 ml/min, Hgb 12.5, and PS 1, recurs in the liver and bone 18 months after receiving neoadjuvant gemcitabine/cisplatin and a radical cystectomy. V1: Same as CS but with reduced CrCl 48 ml/min. V2: Same as CS but recurrence at 6 months. V3: Same as V2 but multiple comorbidities and PS 2. V4: Same as CS but age 79. V5: Same as V4 but multiple comorbidities. The same query was posed in each setting: What therapy would you choose? Results: See Table. Conclusions: Following the approval of A, overall PPref of most regimens offered decreased across nearly all 1 st recurrence scenarios in favor of A. This is particularly stark in platinum unfit (older, comorbid, poor PS) pts. This highlights the previously unmet medical need in the PCCT pre-treated mUC pts. [Table: see text]
Change in compositional fluctuation in Pb(Zr<sub>x</sub>Ti<sub>1</sub>−x)O<sub>3</sub>solid solution during spark plasma sintering (2005)

Changes in compositional fluctuation during sintering of PZT ceramics were studied both for ordinary sintering and for the spark plasma sintering (SPS) method. Generally, sintering is established by diffusion at high temperatures. In ordinary sintering, compositional fluctuation decreased with increasing bulk density. In contrast, compositional fluctuation changed little with increasing bulk density during SPS.
Activated Internal Gettering (1985)

Lifetimes of minority carriers in silicon webs improved by annealing. Heat treatment of silicon web ribbons considerably improves efficiency of solar cells.
Design of minimum visual modulation halftone patterns (1991)

The visibility of binary image noise at low-to-medium dot densities of current binary printers, i.e 300-400 dots/in, is not subthreshold. Standard halftoning algorithms such as clustered-dot or dispersed-dot dither produce periodic patterns at these dot densities that are easily visible at normal viewing distances in uniform areas. A novel method of halftoning computer-generated uniform areas that reduces noise visibility by using a database of minimum visual modulation bit patterns is introduced. Applications include all paint-by-numbers prints such as those that offer tint-fill or object highlighting.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Compression of spectral meteorological imagery (1993)

Data compression is essential to current low-earth-orbit spectral sensors with global coverage, e.g., meteorological sensors. Such sensors routinely produce in excess of 30 Gb of data per orbit (over 4 Mb/s for about 110 min) while typically limited to less than 10 Gb of downlink capacity per orbit (15 minutes at 10 Mb/s). Astro-Space Division develops spaceborne compression systems for compression ratios from as little as three to as much as twenty-to-one for high-fidelity reconstructions. Current hardware production and development at Astro-Space Division focuses on discrete cosine transform (DCT) systems implemented with the GE PFFT chip, a 32x32 2D-DCT engine. Spectral relations in the data are exploited through block mean extraction followed by orthonormal transformation. The transformation produces blocks with spatial correlation that are suitable for further compression with any block-oriented spatial compression system, e.g., Astro-Space Division's Laplacian modeler and analytic encoder of DCT coefficients.
Tetra- and Pentacyclic Triterpene Acids from the Ancient Anti-inflammatory Remedy Frankincense as Inhibitors of Microsomal Prostaglandin E<sub>2</sub>Synthase-1 (2014)

The microsomal prostaglandin E2 synthase (mPGES)-1 is the terminal enzyme in the biosynthesis of prostaglandin (PG)E2 from cyclooxygenase (COX)-derived PGH2. We previously found that mPGES-1 is inhibited by boswellic acids (IC50 = 3-30 μM), which are bioactive triterpene acids present in the anti-inflammatory remedy frankincense. Here we show that besides boswellic acids, additional known triterpene acids (i.e., tircuallic, lupeolic, and roburic acids) isolated from frankincense suppress mPGES-1 with increased potencies. In particular, 3α-acetoxy-8,24-dienetirucallic acid (6) and 3α-acetoxy-7,24-dienetirucallic acid (10) inhibited mPGES-1 activity in a cell-free assay with IC50 = 0.4 μM, each. Structure-activity relationship studies and docking simulations revealed concrete structure-related interactions with mPGES-1 and its cosubstrate glutathione. COX-1 and -2 were hardly affected by the triterpene acids (IC50 > 10 μM). Given the crucial role of mPGES-1 in inflammation and the abundance of highly active triterpene acids in frankincence extracts, our findings provide further evidence of the anti-inflammatory potential of frankincense preparations and reveal novel, potent bioactivities of tirucallic acids, roburic acids, and lupeolic acids.
ENU Mutagenesis Screen Identifies a Novel Regulator of Platelet Production. (2004)

Abstract The genes that regulate variation in steady-state platelet count are largely unknown. We have attempted to identify novel genes that regulate platelet production by creating heritable models of thrombocytosis in mice by randomly inducing point mutations in the genome with chemical mutagenesis. Mice with a high platelet count were identified in the third generation of an ENU mutagenesis screen and several different lines of thrombocytotic mice have been established. Subsequent breeding of one line has demonstrated that this mutation, called Plt2, is inherited in an autosomal recessive manner. Automated platelet counts for Plt2 homozygote mice were 1997±642x109/L (mean±2SD; n=51), 140% of those observed for wild-type mice (1487±372; n=56) and Plt2 heterozygote mice (1402±554; n=76). Analysis of Plt2 animals has shown increased numbers of megakaryocyte precursors (as measured by meg-CFC/5x105 cells to maximal cytokine stimulation) in the bone marrow (Plt2 40±20 compared to wild-type (WT) animals 28±8; n=7) and spleen (Plt2 16±6 compared to WT 8±3; n=7, p=0.01). Mature megakaryocytes were increased in frequency in bone marrow sections (Plt2 86.8±28.4 compared to WT 56.8±18.5) and demonstrate a similar maturation profile to control animals when their nuclear ploidy is measured by flow cytometry. Reciprocal bone marrow transplantation experiments demonstrate that the thrombocytotic phenotype was observed in Plt2 homozygous recipients of either wild type or Plt2 homozygous bone marrow, but not observed in wild type recipients of Plt2 homozygous bone marrow. This data indicates that the Plt2 mutation is acting extrinsically on the haemopoietic system. Despite having an elevated platelet count, Plt2 mutant mice have inappropriately elevated serum thrombopoietin levels (Plt2 5420±2842; n=15) compared to controls (2947 ±2310; n=13; p&lt;0.0001). Mapping experiments have excluded both thrombopoietin and the thrombopoietin receptor, c-mpl, as the mutated gene. Further experiments will aim to map this mutation, which may be a novel regulator of thrombopoietin.
Cigarette smoke modulates the oral epithelial cell innate immunity (2013)

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The effects of shadow‐fading on QoS‐aware routing and admission control protocols designed for multi‐hop MANETs (2010)

Abstract Providing quality‐of‐service (QoS) assurances in a mobile ad hoc network (MANET) is difficult due to node mobility, contention for channel access, a lack of centralised coordination, and the unreliable nature of the wireless channel. QoS‐aware routing (QAR) and admission control (AC) protocols comprise two of the most important components of a system attempting to provide QoS guarantees in the face of the above‐mentioned difficulties. This paper presents a comparative study, utilising a realistic shadow fading channel, of the performance of several state‐of‐the‐art amalgamated QAR‐AC protocols, which are designed for providing throughput guarantees to applications. The advantages and drawbacks of their particular features are highlighted. For an environment where link quality varies rapidly, the results of the study highlight the ineffectiveness of previously‐proposed methods of relying merely on the success of route discovery to perform AC, of relying on the exceeding of the MAC layer retransmission count for link failure detection, of existing congestion detection schemes and of careful re‐admission of data sessions rather than fast re‐routing after shadowing‐induced link failures. Based on the lessons learnt, design guidelines for future QAR and AC protocols operating in a mobile shadow‐fading‐afflicted environment are presented. Copyright © 2010 John Wiley & Sons, Ltd.
A total synthesis of magnoline (1969)

A total synthesis of magnoline (I) has been achieved by the Ullmann reaction between (+)-L-7-benzyloxy-1-(4-benzyloxy-3-bromobenzyl)-6-methoxy-2-methyl- and (–)-D-7-benzyloxy-1-(4-hydroxybenzyl)-6-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline. Spectroscopic comparisons between magnoline and its antipode or diastereoisomer are also described.
Role of interleukin‐4 in down‐regulation of contact sensitivity by γδ T cells from tolerized T‐cell receptor α<sup>−/−</sup> mice (1999)

Contact sensitivity (CS) is a classical example of an in vivo T-cell-mediated immune response that is under regulation. Such down-regulation can be mediated by alphabeta T cells in mice that are tolerized by prior exposure to high doses of antigen. In contrast, we demonstrated previously that such high-dose antigen tolerance in T-cell receptor (TCR) alpha-/- H-2d mice induced antigen-specific, apparently major histocompatibility complex-unrestricted, CD4- CD8- gammadelta T cells, that also could down-regulate CS responses antigen-specifically in vivo, and also inhibited in vitro production of IFN-gamma. In the present experiments we employed H-2b-deficient TCRalpha-/- and TCRbeta-/- mice, owing to different molecular constructs than were used previously, and confirmed that tolerized gammadelta T cells in these different H-2b alphabeta TCR-/- mice down-regulated CS. Thus, gammadelta T-cell suppressor function was not limited to mice bearing a special transgenic TCRalpha-/- DNA construct. Furthermore, employing monoclonal antibody and complement depletion in vitro and adoptive transfer in vivo, characterized the phenotype of these gammadelta down-regulatory T cells as: CD3+, CD28+, CD40-ligand+, Fas+, FcgammaR+ and NK1.1-. Also, in vitro antigen desensitization of these trinitrophenyl (TNP)-specific TCRgammadelta+ down-regulatory cells was achieved with soluble TNP-bovine serum albumin (BSA), but not with oxazolone-BSA, showing that these suppressive gammadelta T cells have antigen-specific receptors. Moreover, employing monoclonal antibody blocking of gammadelta suppressors in vitro, and of recipients in vivo, we showed that interleukin-4 (IL-4) was involved in this down-regulation of CS by gammadelta T cells, while IL-10 and transforming growth factor-beta2 were not. In summary, generation of antigen-specific, double-negative, gammadelta suppressor cells, by tolerance of high antigen doses in TCRalpha-/- mice, appears to be a general phenomenon, and IL-4 production is involved in their down-regulation of the T helper type 1 cells that mediate CS.
Long Palindromic Sequences Induce Double-Strand Breaks during Meiosis in Yeast (2000)

Inverted-repeated or palindromic sequences have been found to occur in both prokaryotic and eukaryotic genomes. Such repeated sequences are usually short and present at several functionally important regions in the genome. However, long palindromic sequences are rare and are a major source of genomic instability. The palindrome-mediated genomic instability is believed to be due to cruciform or hairpin formation and subsequent cleavage of this structure by structure-specific nucleases. Here we present both genetic and physical evidence that long palindromic sequences (>50 bp) generate double-strand breaks (DSBs) at a high frequency during meiosis in the yeast Saccharomyces cerevisiae. The palindrome-mediated DSB formation depends on the primary sequence of the inverted repeat and the location and length of the repeated units. The DSB formation at the palindrome requires all of the gene products that are known to be responsible for DSB formation at the normal meiosis-specific sites. Since DSBs are initiators of nearly all meiotic recombination events, most of the palindrome-induced breaks appear to be repaired by homologous recombination. Our results suggest that short palindromic sequences are highly stable in vivo. In contrast, long palindromic sequences make the genome unstable by inducing DSBs and such sequences are usually removed from the genome by homologous recombination events.
Synthesis, reactions and biological evaluation of some 1,2,4‐triazine derivatives (1988)

Abstract 6‐Substituted benzyl‐4‐phenyl‐3‐thioxo‐2,3,4,5‐tetrahydro‐1,2,4‐triazin‐5‐ones 3a‐d were prepared and converted into their corresponding 3‐methylthio derivatives 4a‐d . Reaction of compounds 4a‐d with hydrazine hydrate gave the corresponding 4‐amino‐3‐anilino‐4,5‐dihydro‐1,2,4‐triazin‐5‐ones 5a‐d . 6‐Substituted benzyl‐4‐phenyl‐2,3,4,5‐tetrahydro‐1,2,4‐triazin‐3,5‐diones 9a‐c were synthesized and allowed to react with hydrazine hydrate to give the corresponding 6‐substituted benzyl‐4‐amino‐2,3,4,5‐tetrahydro‐1,2,4‐triazin‐3,5‐diones 10a‐c . The biological evaluation of some of these triazines is described. All compounds were screened for antiviral, antibacterial, antimycobacterial, antifungal and antiyeast activity. No important biological activity was found.
Specific and selective site reactions of alkanoate derivatives. 2. Isomerization and lactonization of chloroalkanoic acids in strong acid media (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSpecific and selective site reactions of alkanoate derivatives. 2. Isomerization and lactonization of chloroalkanoic acids in strong acid mediaDolores A. Konen, Leonard S. Silbert, and Calvin J. DooleyCite this: J. Org. Chem. 1982, 47, 14, 2779–2782Publication Date (Print):July 1, 1982Publication History Published online1 May 2002Published inissue 1 July 1982https://doi.org/10.1021/jo00135a019RIGHTS & PERMISSIONSArticle Views146Altmetric-Citations2LEARN 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 InReddit PDF (462 KB) Get e-Alertsclose Get e-Alerts
Studies on Coupling Reaction of 1-Naphthol. XI. Effect of Additives on the Dissociation Equilibrium of 4-(4-Nitrophenylazo)-1-naphthol in Pyridine (1988)

Abstract The dissociation of 4-(4-nitrophenylazo)-1-naphthol (azo dye) in pyridine was found to be accelerated by the addition of small amounts of quaternary ammonium compounds, R4N+X−. The apparent equilibrium constant of the azo dye was influenced enormously by the species of X−, but was little affected by the structures of R. The effect increased as the X− became more basic, ClO4−&lt;I−&lt;BF4−&lt;Br−&lt;HSO4&lt;Cl−, in proportion to the ability of X− to bind with protons formed by dissociated azo dye. The basicity of the X−, pKc, was correlated linearly with the variation of the equilibrium constant, owing to the addition of R4N+X−, δpKa. The dissociation of the azo dye in pyridine–water mixtures was also accelerated upon increasing the amount of water (0–10 vol%), correlating with an increase in the basicity of the solution.
Using density functional theory to engineer direct gap germanium-tin alloy (2015)

Germanium is a group IV semiconductor commonly used in Short Wave Infrared (SWIR) optical devices due to its relatively small band gap of 0.66eV. Like silicon in the period above it, the conduction band minimum of germanium does not lie at the same point in k space as the valence band maximum, making it an indirect-gap material and thus reducing its absorption efficiency. Unlike silicon however, the direct-gap of germanium is only slightly larger than its indirect-gap energy, giving it the possibility of possibly transitioning to a direct-gap material with clever band structure engineering. One such method showing promise involves alloying germanium with tin in various ratios. Using density functional theory (DFT), we can calculate the effects the alloy has on the band structure for different percentages of tin and thus predict the percentage needed to transition germanium into a direct-gap material.