754 research outputs found

    Pluripotential Theory and Convex Bodies: A Siciak-Zaharjuta theorem

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    We work in the setting of weighted pluripotential theory arising from polynomials associated to a convex body PP in (R+)d({\bf R}^+)^d. We define the {\it logarithmic indicator function} on Cd{\bf C}^d: HP(z):=supJPlogzJ:=supJPlog[z1j1zdjd]H_P(z):=\sup_{ J\in P} \log |z^{ J}|:=\sup_{ J\in P} \log[|z_1|^{ j_1}\cdots |z_d|^{ j_d}] and an associated class of plurisubharmonic (psh) functions: LP:={uPSH(Cd):u(z)HP(z)=0(1), z}.L_P:=\{u\in PSH({\bf C}^d): u(z)- H_P(z) =0(1), \ |z| \to \infty \}. We first show that LPL_P is not closed under standard smoothing operations. However, utilizing a continuous regularization due to Ferrier which preserves LPL_P, we prove a general Siciak-Zaharjuta type-result in our PP-setting: the weighted PP-extremal function VP,K,Q(z):=sup{u(z):uLP, uQ on K}V_{P,K,Q}(z):=\sup \{u(z):u\in L_P, \ u\leq Q \ \hbox{on} \ K\} associated to a compact set KK and an admissible weight QQ on KK can be obtained using the subclass of LPL_P arising from functions of the form 1degP(p)logp\frac{1}{deg_P(p)}\log |p| (appropriately normalized)

    Dual Suppressive Effect of miR-34a on the FOXM1/eEF2-Kinase Axis Regulates Triple-Negative Breast Cancer Growth and Invasion

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    Purpose: Recent studies indicated that dysregulation of noncoding KNAs (ncRNA) such as miRNAs is involved in pathogenesis of various human cancers. However, the molecular mechanisms underlying miR-34a are not fully understood in triple-negative breast cancer (TNBC). Experimental Design: We performed in vitro functional assays on TNBC cell lines to investigate the role of mi R-34a in FOLM1/eEF2K signaling axis. TNBC tumor xenograft models were used for in vivo therapeutic delivery of miR-34a. Results: In this study, we investigated the role of p53-driven ncRNA miR-34a and found that miR-34a is associated with significantly longer patient survival in TNBC and inversely correlated with levels of proto-oncogenic eEF2K, which was associated with significantly shorter overall patient survival, We showed that miR-34a directly binds to the 3'-untranslated region of eEF2K and FOXM1 mRNAs and suppresses their expression, leading to inhibition of TNBC cell proliferation, motility, and invasion. Notably, restoring miR-34a expression recapitulated the effects of inhibition of eEF2K and FOXM1, the transcription factor for eEF2K and the direct target of p53, in TNBC cell lines, whereas overexpression of eEF2K and FOXM1 rescued the effects and signaling pathways mediated by miR-34a. Moreover, in vivo therapeutic delivery of miR-34a nanopartides by systemic intravenous administration delayed tumor growth of two different orthotopic TNBC tumor xenograft models by inhibiting eEF2K and FOXM1, intratumoral proliferation and angiogenesis, and inducing apoptosis. Conclusions: Overall, our findings provide new insights into the tumor suppressor role of miR-34a by dual-targeting of FOXM1/eEF2K signaling axis and suggest that miR-34a-based gene therapy may be a potential therapeutic strategy in TNBC. (C)2018 AACR.NIH/NCIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R21CA199050, P30CA016672]; noncoding RNA center; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30CA016672] Funding Source: NIH RePORTERThis work was supported in part by grants from the NIH/NCI (R21CA199050 and P30CA016672) and the funding from noncoding RNA center and used the Functional Proteomics RPPA Core Facility

    Comparative assessment of the laboratory selected and active dried Saccharomyces cerevisiae yeast culture in biotechnology of the brandy production

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    Samples from different industrial grape cultivars were collected during the vintage season from the vineyard of the winery (the «Shabo» winery Company, located in the Odesa region, Ukraine). The following industrial cultivars of grapes were selected for the research: Chardonnay, Cabernet Sauvignon, Merlot, Sauvignon, Riesling Rhenish, Aligote, Rkatsiteli, Bastardo, Traminer, Telti Kuruk, Grinosh. The grape cultivars were cultivated on the sandy soils in the district located between the Black Sea and the Dnestrovsky estuary. Grape must derived from different grape cultivars was placed into sterile glass flasks to half of the 450ml flask volume. Each flask was carefully closed with a rubber stopper with an injection needle in it. During the fermentation process, it was necessary to remove carbon dioxide, which was present as a result of active anaerobic fermentation processes in the grape must. At the end of grape must fermentation, pure yeast cultures were isolated using traditional microbiological methods by consistent inoculation of a sample into a Petri dish with a few modifications of nutrient selective agar for yeast isolation and cultivation. Primary yeast isolation was carried out using Inhibitory Mold Agar medium (Becton Dickinson Company, USA). The yeast culture morphological properties were analyzed after the primary yeast culture isolation. Yeasts were identified by polymerase chain reaction (PCR) using universal yeast primers. After yeast culture identification, the next step in yeast cultivation was carried out on Wort Agar medium (Becton Dickinson Company, USA). Each isolated, and identified yeast culture was deposited in the Genebank of Japan, MAFF culture Collection, Tsukuba, Ibaraki, Japan and (NCYC) - Yeast Culture Collection (National Collection of Yeast Cultures, Institute of Food Research, Norwich, United Kingdom). Each yeast culture was tested for technological characteristics such as growth resistance to high temperature (+42°C) and low temperature (+6°C), growth at low pH 2.6–3.0 (acid resistance), growth in the presence of 5, 10, and 15% ethanol (ethanol resistance), and growth in the presence of high concentration potassium bisulfite (bisulfite resistance). Hydrosulfide synthesis (H2S gassing production) was studied in addition. Parameters of cellular metabolism in yeast suspension, such as concentration of nitrogen, protein, triglicerides, enzymatic activity and total sugar (which include glucose, fructose, and galactose) were determined. Macro- and micro-element concentrations in fermented grape must, which contained pure yeast culture was determined and included: potassium, sodium, calcium, phosphorus, magnesium, iron, chlorides. In addition to identifying parameters of macro- and micro- element concentration in grape must during and following fermentation based on a principle of photometric analysis, carried out using a biochemical analyser Respons-920 (DiaSys Diagnostic Systems GmbH, Germany). Laboratory selected Saccharomyces cerevisiae wine yeast showed high enzymatic activity with short lag phase. Since of fermentation started on third day concentration of Triglicerides, Protein (total), Potassium and Sodium increased and then level of Protein (total) on the 5th day of fermentation twice decreased. Trigliceride concentration on the 5th day of fermentation continued to increase. Concentration of Iron on the 5th day of fermentation increase in geometrical progression, concentration increase in 4-5 times. Contrary Chloride concentration on the 5th day of fermentation decreased in 3-4 times. Enzymatic activity on 3rd day of fermentation maximal for Lactate Dehydrogenase, Alanine aminotransferase, Aspartate aminotransferase, Phosphatase. Since of 5th day of fermentation Enzymatic activity for Lactate Dehydrogenase, Alanine aminotransferase, Aspartate aminotransferase 3-4 times. Especially level of Phosphatase activity very decreased in 6-7 times. Comparative assessment between our Laboratory selected Saccharomyces cerevisiae yeast culture and Dry active commercial Saccharomyces cerevisiae yeast culture did not showed any difference in enzymatic activity. Both groups showed high enzymatic activity on the third day from the start of fermentation and decreasing on the fifth day since of fermentation started

    Phenological observations belonging to vegetation period of some native and exotic plant species in KTU Kanuni campus

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    It is possible to determine specific periods in plants during the vegetation period making phenological observations. When making phenological observations, one can be collect information about occurrence time of some events, such as sowing, germination and bud bursting. Particularly, this evidence will contribute s to the selection of species in site conditions, when making decisions about the species to be left in the field. Therefore, it is important to know blossoming time and lifespan of flowers during the seasons. If coloration of the plants to be used in the landscape design is known to depend on the season, much better compositions with the plants can be created. The aim of the paper is to reveal the differences in the beginning of vegetation of some native and exotic plant species found in the campus of Karadeniz Technical University. In this study, bud bursting times of 19 species of bud bursting dates, including 10 native trees, 5 exotic trees, 2 native shrubs and 2 exotic shrub species were investigated during the 4 phases. Thus, when observations were made for the times from swelling of the buds to the completion of the bud burst, it appeared that the bursting period for Acer platanoides L. was completed in the longest time and those for Carpinus betulus L. and Liquidambar orientalis Mill. – over the shortest time from the native species. The same period for Wisteria sinensis (Sims) DC. was completed in the longest time, while for Prunus serrulata Lindl. «Kandzan» it was completed in the shortest time for the exotic species

    Data-driven grading of acute graft-versus-host disease

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    : Despite advances in allogeneic hematopoietic cell transplantation, acute graft-versus-host disease (aGVHD) remains its leading complication, yet with heterogeneous outcomes. Here, we analyzed aGVHD phenotypes and clinical classifications in depth in large, multicenter cohorts involving 3019 patients and addressed prevailing gaps by developing data-driven models. We compared, tested and verified these along with all conventional classifications in independent cohorts and found that data-driven grading outperformed conventional grading in Akaike information criterion and concordance index metrics. Data-driven classifications refined aGVHD assessment with up to 12 severity grades, which were associated with distinct nonrelapse mortality (NRM) and confirmed the key role of intestinal aGVHD. We developed an online calculator for physicians to implement principal component-derived grading (PC1). These results provide substantial insight into the evaluation of aGVHD phenotypes and multiorgan involvement, which relegates the exclusive reporting of overall aGVHD severity grades in transplant registries and clinical trials. Data-driven aGVHD grading provides an expandable platform to refine classification and transplant risk assessment
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