gebhart/patrepeval huggingface dataset:
Nucleotide sequence of the simian virus 40 small-t gene (1978)

The nucleotide sequence of the segment of simian virus 40 DNA between standard map positions 0.53 and 0.65, i.e., approximately half of the restriction fragment Hind A, is reported. This segment is located near the beginning of the early region and is transcribed counterclockwise. There is a potential initiating ATG signal at 13 nucleotides from the Hind C-Hind A junction in the strand with the same polarity as the early mRNA. From this signal on, an open reading frame is present which would allow the synthesis of a polypeptide of 174 amino acids until a TAA termination codon is reached at nucleotide 602 (map position 0.547). This polypeptide, revealed by the DNA sequence, corresponds almost certainly to small-t antigen. Correlation of the deduced amino acid sequence with the NH(2)-terminal sequences of small-t and large-T (tumor) antigens of simian virus 40, as established by Paucha et al. [Paucha, E., Mellor, A., Harvey, R., Smith, A. E., Hewick, R. M. & Waterfield, M. D. (1978) [Proc. Natl. Acad. Sci. USA 75, 2165-2169], strongly argues that both proteins are indeed initiated at the ATG triplet. Because the DNA region between 0.547 and 0.534 is blocked for translation in all three reading frames by multiple termination condons, we conclude that the large-T antigen must be coded for by two noncontiguous DNA segments: the segment from 0.65 to around 0.60, which small-t and large-T antigens share, and another segment starting at some point after position 0.534 and continuing counterclockwise until it terminates at map position 0.174. Small-t antigen is methionine-rich and has a remarkably high number of cysteine residues clustered mainly in its COOH-terminal half. It is rich in both basic and acidic residues, the former being slightly in excess.
Theileria annulatain CD5+Macrophages and B1 B Cells (1999)

Theileria parasites infect and transform bovine leukocytes. We have analyzed laboratory-established Theileria sp.-infected leukocyte lines and observed that transformed macrophages express CD5. Low-level expression of CD5 by macrophages was further confirmed on three independent Theileria annulata clinical isolates from Tunisia. Interestingly, the fourth CD5(+) clinical isolate (MB2) was morphologically different, expressed surface immunoglobulin M (IgM) and BoLA class II, and had rearranged Ig light-chain genes. To demonstrate that MB2 did indeed contain CD5(+) B cells, individual clonal lines were obtained by limiting dilution, and CD5 expression and Ig gene rearrangement were confirmed. This suggests that in natural infections T. annulata can invade and transform CD5(+) B cells.
Low Complexity Transmitter-side Compensation for Optical Device Nonlinearities in 100Gb/s Transmission over 500m SMF (2013)

The device nonlinearity by laser diode and photo detector is identified as one of the major distortions in a 100Gb/s-class transmission over 500m SMF using discrete multi-tone technology. A novel transmitter-side DSP algorithm is proposed and 20% capacity improvement is achieved by a simple structure without usage of any feedback iterations.
Pulsed infrared laser induced visible luminescence (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPulsed infrared laser induced visible luminescenceG. E. Hardy, B. P. Chandra, Jeffrey I. Zink, Arthur W. Adamson, Robert C. Fukuda, and R. T. WaltersCite this: J. Am. Chem. Soc. 1979, 101, 10, 2787–2788Publication Date (Print):May 1, 1979Publication History Published online1 May 2002Published inissue 1 May 1979https://pubs.acs.org/doi/10.1021/ja00504a076https://doi.org/10.1021/ja00504a076research-articleACS PublicationsRequest reuse permissionsArticle Views102Altmetric-Citations28LEARN 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
Abstract 4421: SY-5609, an orally available selective CDK7 inhibitor demonstrates broad anti-tumor activityin vivo (2019)

Previously, we reported on a series of highly potent, selective, and non-covalent CDK7 inhibitors that demonstrated antiproliferative activity against triple-negative breast cancer (TNBC) and ovarian cancer (OVA) cell lines and tumor growth inhibition in cell line-derived (CDX) and patient-derived (PDX) mouse xenograft models. Here, we report on the in vitro and in vivo profile of our development candidate, SY-5609. Methods: Kinase inhibition assays at both Km and 2 mM [ATP] were used to assess inhibition of CDK2, CDK7, CDK9, and CDK12. SPR was used to determine the Kd, kon, and koff binding characteristics of SY-5609 to immobilized CDK7/Cyclin H dimer. CDK7 compound occupancy was determined using a biotinylated small molecule probe to pull down free CDK7 following incubating of HL60 cells with SY-5609. Inhibition of tumor cell line growth was assessed following 72 hrs of incubation with SY-5609. Flow cytometry was used to assess apoptosis and cell cycle modulation after 48 hrs of treatment. Effects on DNA damage and repair were assessed by immunofluorescence staining for γH2AX and RAD51 proteins. To assess in vivo effects, mice were implanted subcutaneously and randomized for treatment when tumors reached 150-200 mm3 and dosed orally for 3 weeks by both QD and BID dosing regimens. Collected tumor tissue samples were analyzed for protein levels of MCL1, pCDK2, MYC, and RNA Pol II CTD pSer5 by western blot. Results: SY-5609 bound CDK7/Cyclin H with a Kd of 0.059 nM and occupied CDK7 in HL60 cells with an EC50 of 33 nM. Cell growth inhibition EC50 values were 6-17 nM in a panel of solid tumor cell lines. Selectivity of SY-5609 over CDK12, CDK9, and CDK2 was 2492-, 2508-, and 8068-fold, respectively. SY-5609 led to induction of apoptosis, cell cycle arrest, and inhibition of DNA damage repair in tumor cell lines. Dose-dependent tumor growth inhibition was observed in a panel of CDX and PDX solid tumor models with both QD and BID dosing of SY-5609 with resulting decreases in direct (pCDK2, RNA Pol II CTD pSer5) and indirect (MCL1, MYC) protein biomarkers. In summary, we describe SY-5609, an orally available, potent, and selective CDK7 inhibitor that drives strong responses in CDX and PDX tumor models. These data support the rationale for advancing SY-5609 into IND-enabling studies.Citation Format: Shanhu Hu, Jason Marineau, Kristin Hamman, Michael Bradley, Anneli Savinainen, Sydney Alnemy, Nisha Rajagopal, David Orlando, Claudio Chuaqui, Eric Olson. SY-5609, an orally available selective CDK7 inhibitor demonstrates broad anti-tumor activity in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4421.
Review of Best Practice Methods for Determining an Electrode Material's Performance for Ultracapacitors (2010)

Ultracapacitors are rapidly being adopted for use for a wide range of electrical energy storage applications. While ultracapacitors are able to deliver high rates of charge and discharge, they are limited in the amount of energy stored. The capacity of ultracapacitors is largely determined by the electrode material and as a result, research to improve the performance of electrode materials has dramatically increased. While test methods for packaged ultracapacitors are well developed, it is often not feasible for the materials scientist to assemble full sized, packaged cells to test electrode materials. Methodology to reliably measure a material's performance for ultracapacitor electrode use is not well standardized with the different techniques currently being used yielding widely varying results. In this manuscript, we review the best practice test methods that accurately predict a materials performance, yet are flexible and quick enough to accommodate a wide range of material sample types and amounts.
High-speed microparticle isolation unlimited by Poisson statistics (2019)

High-speed isolation of microparticles (e.g., microplastics, heavy metal particles, microbes, cells) from heterogeneous populations is the key element of high-throughput sorting instruments for chemical, biological, industrial and medical applications. Unfortunately, the performance of continuous microparticle isolation or so-called sorting is fundamentally limited by the trade-off between throughput, purity, and yield. For example, at a given throughput, high-purity sorting needs to sacrifice yield, or vice versa. This is due to Poisson statistics of events (i.e., microparticles, microparticle clusters, microparticle debris) in which the interval between successive events is stochastic and can be very short. Here we demonstrate an on-chip microparticle sorter with an ultrashort switching window in both time (10 μs) and space (10 μm) at a high flow speed of 1 m s<sup>-1</sup>, thereby overcoming the Poisson trade-off. This is made possible by using femtosecond laser pulses that can produce highly localized transient cavitation bubbles in a microchannel to kick target microparticles from an acoustically focused, densely aligned, bumper-to-bumper stream of microparticles. Our method is important for rare-microparticle sorting applications where both high purity and high yield are required to avoid missing rare microparticles.
Membrane-Permeable Octanoyloxybenzyl-Masked cNMPs As Novel Tools for Non-Invasive Cell Assays (2018)

Adenine nucleotide (AN) 2nd messengers, such as 3',5'-cyclic adenosine monophosphate (cAMP), are central elements of intracellular signaling, but many details of their underlying processes remain elusive. Like all nucleotides, cyclic nucleotide monophosphates (cNMPs) are net-negatively charged at physiologic pH which limits their applicability in cell-based settings. Thus, many cellular assays rely on sophisticated techniques like microinjection or electroporation. This setup is not feasible for medium- to high-throughput formats, and the mechanic stress that cells are exposed to raises the probability of interfering artefacts or false-positives. Here, we present a short and flexible chemical route yielding membrane-permeable, bio-reversibly masked cNMPs for which we employed the octanoyloxybenzyl (OB) group. We further show hydrolysis studies on chemical stability and enzymatic activation, and present results of real-time assays, where we used cAMP and Ca<sup>2+</sup> live cell imaging to demonstrate high permeability and prompt intracellular conversion of some selected masked cNMPs. Based on these results, our novel OB-masked cNMPs constitute valuable precursor-tools for non-invasive studies on intracellular signaling.
GH action influences adipogenesis of mouse adipose tissue-derived mesenchymal stem cells (2015)

GH influences adipocyte differentiation, but both stimulatory and inhibitory effects have been described. Adipose tissue-derived mesenchymal stem cells (AT-MSCs) are multipotent and are able to differentiate into adipocytes, among other cells. Canonical Wnt/β-catenin signaling activation impairs adipogenesis. The aim of the present study was to elucidate the role of GH on AT-MSC adipogenesis using cells isolated from male GH receptor knockout (GHRKO), bovine GH transgenic (bGH) mice, and wild-type littermate control (WT) mice. AT-MSCs from subcutaneous (sc), epididiymal (epi), and mesenteric (mes) AT depots were identified and isolated by flow cytometry (Pdgfrα+ Sca1+ Cd45- Ter119- cells). Their in vitro adipogenic differentiation capacity was determined by cell morphology and real-time RT-PCR. Using identical in vitro conditions, adipogenic differentiation of AT-MSCs was only achieved in the sc depot, and not in epi and mes depots. Notably, we observed an increased differentiation in cells isolated from sc-GHRKO and an impaired differentiation of sc-bGH cells as compared to sc-WT cells. Axin2, a marker of Wnt/β-catenin activation, was increased in mature sc-bGH adipocytes, which suggests that activation of this pathway may be responsible for the decreased adipogenesis. Thus, the present study demonstrates that (i) adipose tissue in mice has a well-defined population of Pdgfrα+ Sca1+ MSCs; (ii) the differentiation capacity of AT-MSCs varies from depot to depot regardless of GH genotype; (iii) the lack of GH action increases adipogenesis in the sc depot; and iv) activation of the Wnt/β-catenin pathway might mediate the GH effect on AT-MSCs. Taken together, the present results suggest that GH diminishes fat mass in part by altering adipogenesis of MSCs.
Quantum dots on vertically aligned gold nanorod monolayer: plasmon enhanced fluorescence (2014)

CTAB-coated Au nanorods were directly self-assembled into a vertically aligned monolayer with highly uniform hot spots through a simple but robust approach. By coupling with CdSe/ZnS quantum dots, a maximum enhancement of 10.4 is achieved due to: increased excitation transition rate, radiative rate, and coupling efficiency of emission to the far field.
Identification of a Novel Non-desmoglein Autoantigen in Pemphigus Vulgaris (2019)

Pemphigus vulgaris (PV) is an autoimmune bullous disease of the skin and mucous membranes characterized by the presence of circulating and tissue-bound autoantibodies against keratinocyte cell surface antigens, specifically desmoglein (Dsg) 1 and 3. The pathogenic role of anti-Dsg antibodies is well-established, while the mechanism of blister formation is only partly defined. We have applied a previously developed method for the efficient immortalization of IgG+ memory B cells to identify novel target antigens in PV. A human monoclonal antibody reactive with a hitherto unreported non-Dsg antigen was isolated. Immunoprecipitation and immunoblotting studies with keratinocyte extracts indicated α-catenin as the putative antigen, then confirmed by immunoblotting on the recombinant protein. Four of ten PV sera reacted with recombinant α-catenin. Although the isolated human monoclonal antibody was <i>per se</i> unable to dissociate keratinocyte monolayers and also to synergize with a pathogenic antibody <i>in vitro</i>, further studies are warranted to assess its possible <i>in vivo</i> contribution in the multifactorial pathogenesis and heterogeneous manifestations of PV disease.
Differential Poisoning of Topoisomerases by Menogaril and Nogalamycin Dictated by the Minor Groove-Binding Nogalose Sugar (1997)

The effect of DNA binding on poisoning of human DNA TOP1 has been studied using a pair of related anthracyclines which differ only by a nogalose sugar ring. We show that the nogalose sugar ring of nogalamycin, which binds to the minor groove of DNA, plays an important role in affecting topoisomerase-specific poisoning. Using purified mammalian topoisomerases, menogaril is shown to poison topoisomerase II but not topoisomerase I. By contrast, nogalamycin poisons topoisomerase I but not topoisomerase II. Consistent with the biochemical studies, CEM/VM-1 cells which express drug-resistant TOP2alpha are cross-resistant to menogaril but not nogalamycin. The mechanism by which nogalamycin poisons topoisomerase I has been studied by analyzing a major topoisomerase I-mediated DNA cleavage site induced by nogalamycin. This site is mapped to a sequence embedded in an AT-rich region with four scattered GC base pairs (bps) (at -10, -6, +2, and +12 positions). GC bps embedded in AT-rich regions are known to be essential for nogalamycin binding. Surprisingly, DNase I footprinting analysis of nogalamycin-DNA complexes has revealed a drug-free region from -2 to +9 encompassing the major cleavage site. Our results suggest that nogalamycin, in contrast to camptothecin, may stimulate TOP1 cleavage by binding to a site(s) distal to the site of cleavage.
A Genome-Wide Association Study Identifies Susceptibility Variants for Type 2 Diabetes in Han Chinese (2010)

To investigate the underlying mechanisms of T2D pathogenesis, we looked for diabetes susceptibility genes that increase the risk of type 2 diabetes (T2D) in a Han Chinese population. A two-stage genome-wide association (GWA) study was conducted, in which 995 patients and 894 controls were genotyped using the Illumina HumanHap550-Duo BeadChip for the first genome scan stage. This was further replicated in 1,803 patients and 1,473 controls in stage 2. We found two loci not previously associated with diabetes susceptibility in and around the genes protein tyrosine phosphatase receptor type D (PTPRD) (P = 8.54x10(-10); odds ratio [OR] = 1.57; 95% confidence interval [CI] = 1.36-1.82), and serine racemase (SRR) (P = 3.06x10(-9); OR = 1.28; 95% CI = 1.18-1.39). We also confirmed that variants in KCNQ1 were associated with T2D risk, with the strongest signal at rs2237895 (P = 9.65x10(-10); OR = 1.29, 95% CI = 1.19-1.40). By identifying two novel genetic susceptibility loci in a Han Chinese population and confirming the involvement of KCNQ1, which was previously reported to be associated with T2D in Japanese and European descent populations, our results may lead to a better understanding of differences in the molecular pathogenesis of T2D among various populations.
Impact of Crosslinking on the Dielectric Loss and Temperature Coefficient of Capacitance of Polyethylene (2018)

Crosslinked polyethylene is a common material for power cable insulation due to its low cost, mechanical stability, and insulating nature. However, the crosslinking process leaves behind byproducts that may compromise its utility. Here, the impact of crosslinking on the capacitance and dielectric loss of polyethylene samples is examined. Crosslinked and noncrosslinked samples exhibit similar dielectric loss values at room temperature. However, crosslinked samples are more insulating at 90 °C. We observe that the amount of peroxide added was not directly related to the electrical properties, but that crosslinking temperature and time are. These results imply that the morphology changes upon crosslinking are as important in controlling the conductivity and loss as any residual byproducts. It is also observed that the degassing at elevated temperatures in vacuum that is normally done to remove byproducts also benefited non-crosslinked films, supporting the argument that morphology changes due to the elevated temperatures used in degassing can cause a reduction of dielectric loss. Analysis of mechanical properties through the use of temperature coefficient of capacitance, used to approximate the linear thermal expansion coefficient, allowed for further analysis of the morphology. Crosslinked films expand more than non-crosslinked films, and their expansion is reduced with degassing. Both ambient and vacuum degassing aid in this, implying that recrystallization and byproduct removal combined lead to reductions in dielectric loss and thermal expansion in crosslinked polyethylene.
Immunohistological localization of three basement membrane components in various forms of epidermolysis bullosa (1982)

The skin biopsies of eight epidermolysis bullosa (EB) patients, representing epidermolytic, junctional and dermolytic forms of the disease were studied immunohistochemically using antibodies against collagen Types IV and V, and a proteoglycan. All these molecules are either basement membrane components or closely associated substances. In two types of EB simplex (subtype of the epidermolytic form) the splicing took place above the basement membrane, whereas the staining with all three antibodies remained localized to the floor of the blister. The herpetiform variant of EB simplex proved to be junctional, i.e. the separation occurred within the lamina lucida. One patient clinically classified as belonging to the junctional EB group, was found to have the epidermolytic form of the disease. In this case all antibodies were localized only on the floor of the blister. In the patients with the dermolytic form of EB, all the antibodies stained the roof of the blister. The immunofluorescence techniques are rapid and easy to perform and are therefore proposed as useful for routine clinical diagnosis.
Clinical application of an angiotensin II analogue (III) (1976)

Blockade of angiotensin II has been attempted by in vivo administration of angiotensin II antagonistic analogue in order to investigate the role of renin-angiotensin-aldosterone system in the maintenance of blood pressure. Preliminary studies showed that blood pressure changes were not uniform, which conceivably depends not only on the antagonistic activity but also on body fluid status, vascular reactivity, autonomic nervous system as well as the agonistic (pressor) activity of the compound per se.Herein, 1-sarcosine, 8-isoleucine angiotensin II was infused intravenously for 30 minutes at a rate of 200ng/kg/min in 45 subjects with a variety of hypertensive as well as body fluid and electrolyte disorders and changes of blood pressure (BP), plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were studied before and after the infusion. Neither of BP, PRA or PAC changes appeared uniform on the whole. Most of low-renin hyper-tensive subjects (low renin essential hypertension and primary aldosteronism) showed elevation of BP and while PRA remained unchanged. Four out of 10 high-renin hypertensive subjects showed reduction of BP and PRA and the rest showed only elevation of BP. Changes of BP and PRA of normal-renin hypertensives were quite variable. Many normotensive subjects showed elevation of PRA and more or less reduction of BP. Subjects with Bartter's syndrome and renal tubular acidosis whose vascular volume was conceivably reduced, showed the largest reduction of BP and elevation of PRA. A curvilinear relation was observed between pre-infusion PRA and percent changes of PAC.It was concluded that BP is maintained by augmented secretion of renin in disorders associated with contracted vascular volume and that, in cases of low-renin hypertensives, 1-sarcosine, 8-isoleucine angiotensin II has an agonistic effect on the adrenal cortex as well.
Microreactor-based reaction optimization in organic chemistry—glycosylation as a challenge (2004)

Glycosylation reactions are performed rapidly over a wide range of conditions as an example of microreactor-based method optimization and process development in organic chemistry.
LTE-advanced pro: part 1 [Guest Editorial] (2016)

Long Term Evolution (LTE) has become the most successful mobile wireless broadband technology, serving over one billion users as of the beginning of 2016. However, looking at the penetration rate, LTE serves only 14.5 percent of the current 7.3 billion mobile subscriptions. Consequently, there is still significant room for LTE to grow as a mobile technology; it will be serving users for a long time to come.