244 research outputs found

    Black Hole Entropy, Topological Entropy and the Baum-Connes Conjecture in K-Theory

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    We shall try to exhibit a relation between black hole entropy and topological entropy using the famous Baum-Connes conjecture for foliated manifolds which are particular examples of noncommutative spaces. Our argument is qualitative and it is based on the microscopic origin of the Beckenstein-Hawking area-entropy formula for black holes, provided by superstring theory, in the more general noncommutative geometric context of M-Theory following the Connes- Douglas-Schwarz article.Comment: 17 pages, Latex, contains an important paragraph in section 2 which gives a better understandin

    Carbon Nanodot:Supramolecular electron donor-acceptor hybrids featuring Perylenediimides

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    We describe the formation of charge-transfer complexes that feature electron-donating carbon nanodots (CND) and electron-accepting perylenediimides (PDI). The functionalities of PDIs have been selected to complement those of CNDs in terms of electrostatic and \u3c0-stacking interactions based on oppositely charged ionic head groups and extended \u3c0-systems, respectively. Importantly, the contributions from electrostatic interactions were confirmed in reference experiments, in which stronger interactions were found for PDIs that feature positively rather than negatively charged head groups. The electronic interactions between the components in the ground and excited state were characterized in complementary absorption and fluorescence titration assays that suggest charge-transfer interactions in both states with binding constants on the order of 8 7104\u2009M 121 (25\u2005L\u2009g 121). Selective excitation of the two components in ultrafast pump probe experiments gave a 210\u2005ps lived charge-separated state

    Quantum Metrology: Towards an alternative definition for the meter

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    The motivation for this article came from an attempt to give an alternative definition for the meter, the SI unit for measuring length. As a starting point towards this goal, in this piece of work we present the underlying theory behind our approach which uses ideas from quantum field theory and noncommutative geometry, in particular the notion of an odd K-cycle which is based on the Dirac operator (and its inverse, the Dirac propagator). Using (the perhaps more familiar) physics terminology, the key point in our strategy is this: instead of measuring length directly in space-time we measure the "algebraic (spectral) length" in the space of the corresponding quantum states of some particle (fermion) acted upon by the Dirac propagator. This approach shares the spirit of the unanimus vote of the 24th General Conference of Standards and Measures (21st October 2011) in Serves, France for the redefinition of the fundamental units using Planck's constant.Comment: Extended version of an invited talk during the 4th Tactical Conference on Metrology, 3-4 February 2012, National Technical University of Athens, Athens Greec

    An Examination of Gender Differences in the Construct Validity of the Silencing the Self Scale

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    Jack’s (1991) theory of self-silencing was originally designed to explain higher rates of depression in women in comparison to men. However, research finding that men score equal or even higher than women on measures of self-silencing has led theorists to speculate that self-silencing tendencies may be driven by different motivations and have different consequences for women versus men (Jack & Ali, 2010). Using a sample of 247 college students, we examined gender differences in the construct validity of the Silencing the Self Scale (STSS; Jack & Dill, 1992). We hypothesized that women would score higher on the Externalized Self-Perception subscale, but not in the other three subscales. Gender differences in the relationship between the STSS subscales and theoretically relevant constructs were also explored. The results indicated that women on average scored higher than men on the Externalized Self-Perception subscale, whereas men scored higher on the Care as Self-Sacrifice subscale. Further, there was a significant Gender × Care as Self-Sacrifice subscale interaction in the prediction of depression, such that this subscale was negatively correlated to depression in men and uncorrelated in women. These results clarify how self-silencing might translate into different mental health outcomes for women and men. Highlights: As hypothesized, women scored higher on the Externalized Self-Perception subscale of the STSS. * We examined Gender × Subscale interactions in prediction of theoretically-relevant constructs. * The Gender × Care as Self-Sacrifice subscale interaction significantly predicted depression

    Disruption of hypoxia-inducible fatty acid binding protein 7 induces beige fat-like differentiation and thermogenesis in breast cancer cells

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    Background Humans produce heat through non-shivering thermogenesis, a metabolic process that occurs in inducible beige adipocytes expressing uncoupling protein 1 (UCP1). UCP1 dissipates the proton gradient of the mitochondrial inner membrane and converts that energy into heat. It is unclear whether cancer cells can exhibit autonomous thermogenesis. Previously, we found that the knockdown of hypoxia-inducible fatty acid binding protein 7 (FABP7) increased reactive oxygen species (ROS) in breast cancer cells. ROS are known to induce beige adipocyte differentiation. Methods We investigated the association of tumor hypoxia, FABP7, and UCP1 across breast cancer patients using METABRIC and TCGA data sets. Furthermore, using a breast cancer cell line, HCC1806, we tested the effect of FABP7 knockdown on cellular physiology including thermogenesis. Results We found a strong mutual exclusivity of FABP7 and UCP1 expression both in METABRIC and in TCGA, indicating major metabolic phenotypic differences. FABP7 was preferentially distributed in poorly differentiated-, estrogen receptor (ER) negative tumors. In contrast, UCP1 was highly expressed in normal ducts and well-differentiated-, ER positive-, less hypoxic tumors. In the cell line-based experiments, UCP1 and its transcriptional regulators were upregulated upon FABP7 knockdown. UCP1 was induced in about 20% of cancer cells, and the effect was increased further in hypoxia. UCP1 depolarized mitochondrial membranes at the site of expression. UCP1 induction was associated with the increase in proton leak, glycolysis, and maximal respiration, mimicking the typical energy profile of beige adipocytes. Most importantly, UCP1 induction elevated cancer cell temperature associated with increased vulnerability to hypoxia and gamma-irradiation. Conclusions We demonstrated that breast cancer cells can undergo thermogenesis through UCP1 induction. Disrupting FABP7-mediated fatty acid metabolism can unlock UCP1-mediated thermogenesis, potentially making it possible to develop therapies to target thermogenesis. Further study would be warranted to investigate the effect of rise in temperature of cancer cells on patients' outcomes and the relationship to other metabolic pathways

    Glycogen synthase 1 targeting reveals a metabolic vulnerability in triple-negative breast cancer

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    BACKGROUND: Hypoxia-induced glycogen turnover is implicated in cancer proliferation and therapy resistance. Triple-negative breast cancers (TNBCs), characterized by a hypoxic tumor microenvironment, respond poorly to therapy. We studied the expression of glycogen synthase 1 (GYS1), the key regulator of glycogenesis, and other glycogen-related enzymes in primary tumors of patients with breast cancer and evaluated the impact of GYS1 downregulation in preclinical models.METHODS: mRNA expression of GYS1 and other glycogen-related enzymes in primary breast tumors and the correlation with patient survival were studied in the METABRIC dataset (n = 1904). Immunohistochemical staining of GYS1 and glycogen was performed on a tissue microarray of primary breast cancers (n = 337). In four breast cancer cell lines and a mouse xenograft model of triple-negative breast cancer, GYS1 was downregulated using small-interfering or stably expressed short-hairpin RNAs to study the effect of downregulation on breast cancer cell proliferation, glycogen content and sensitivity to various metabolically targeted drugs.RESULTS: High GYS1 mRNA expression was associated with poor patient overall survival (HR 1.20, P = 0.009), especially in the TNBC subgroup (HR 1.52, P = 0.014). Immunohistochemical GYS1 expression in primary breast tumors was highest in TNBCs (median H-score 80, IQR 53-121) and other Ki67-high tumors (median H-score 85, IQR 57-124) (P &lt; 0.0001). Knockdown of GYS1 impaired proliferation of breast cancer cells, depleted glycogen stores and delayed growth of MDA-MB-231 xenografts. Knockdown of GYS1 made breast cancer cells more vulnerable to inhibition of mitochondrial proteostasis.CONCLUSIONS: Our findings highlight GYS1 as potential therapeutic target in breast cancer, especially in TNBC and other highly proliferative subsets.</p
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