11 research outputs found

    A longitudinal analysis of the hot hand and gambler’s fallacy biases

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    Researchers have found evidence of both hot hand and gambler’s fallacy biases in lottery number selection. Which of the two opposite effects is observed is often dependent upon the nature of the lottery game, the particular sample, the local culture of the participants, or the time transpired since the seed event. By observing hundreds of millions of lottery entries over 118 consecutive semiweekly drawings, we present evidence of both effects and their longitudinal properties. With respect to the selection of individual numbers, lottery participants tend to avoid recently selected winning numbers. This gambler’s fallacy effect diminishes and the number becomes increasingly ‘hot’ until it is selected again. With respect to winning number combinations, we found strong evidence of a small but persistent hot hand bias. This bias gradually diminishes over time, but remains detectable and highly consistent for a number of years

    Lysine 53 Acetylation of Cytochrome c in Prostate Cancer: Warburg Metabolism and Evasion of Apoptosis

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    Prostate cancer is the second leading cause of cancer-related death in men. Two classic cancer hallmarks are a metabolic switch from oxidative phosphorylation (OxPhos) to glycolysis, known as the Warburg effect, and resistance to cell death. Cytochrome c (Cytc) is at the intersection of both pathways, as it is essential for electron transport in mitochondrial respiration and a trigger of intrinsic apoptosis when released from the mitochondria. However, its functional role in cancer has never been studied. Our data show that Cytc is acetylated on lysine 53 in both androgen hormone-resistant and -sensitive human prostate cancer xenografts. To characterize the functional effects of K53 modification in vitro, K53 was mutated to acetylmimetic glutamine (K53Q), and to arginine (K53R) and isoleucine (K53I) as controls. Cytochrome c oxidase (COX) activity analyzed with purified Cytc variants showed reduced oxygen consumption with acetylmimetic Cytc compared to the non-acetylated Cytc (WT), supporting the Warburg effect. In contrast to WT, K53Q Cytc had significantly lower caspase-3 activity, suggesting that modification of Cytc K53 helps cancer cells evade apoptosis. Cardiolipin peroxidase activity, which is another proapoptotic function of the protein, was lower in acetylmimetic Cytc. Acetylmimetic Cytc also had a higher capacity to scavenge reactive oxygen species (ROS), another pro-survival feature. We discuss our experimental results in light of structural features of K53Q Cytc, which we crystallized at a resolution of 1.31 AÌŠ, together with molecular dynamics simulations. In conclusion, we propose that K53 acetylation of Cytc affects two hallmarks of cancer by regulating respiration and apoptosis in prostate cancer xenografts

    Lysine 53 Acetylation of Cytochrome c in Prostate Cancer: Warburg Metabolism and Evasion of Apoptosis

    No full text
    Prostate cancer is the second leading cause of cancer-related death in men. Two classic cancer hallmarks are a metabolic switch from oxidative phosphorylation (OxPhos) to glycolysis, known as the Warburg effect, and resistance to cell death. Cytochrome c (Cytc) is at the intersection of both pathways, as it is essential for electron transport in mitochondrial respiration and a trigger of intrinsic apoptosis when released from the mitochondria. However, its functional role in cancer has never been studied. Our data show that Cytc is acetylated on lysine 53 in both androgen hormone-resistant and -sensitive human prostate cancer xenografts. To characterize the functional effects of K53 modification in vitro, K53 was mutated to acetylmimetic glutamine (K53Q), and to arginine (K53R) and isoleucine (K53I) as controls. Cytochrome c oxidase (COX) activity analyzed with purified Cytc variants showed reduced oxygen consumption with acetylmimetic Cytc compared to the non-acetylated Cytc (WT), supporting the Warburg effect. In contrast to WT, K53Q Cytc had significantly lower caspase-3 activity, suggesting that modification of Cytc K53 helps cancer cells evade apoptosis. Cardiolipin peroxidase activity, which is another proapoptotic function of the protein, was lower in acetylmimetic Cytc. Acetylmimetic Cytc also had a higher capacity to scavenge reactive oxygen species (ROS), another pro-survival feature. We discuss our experimental results in light of structural features of K53Q Cytc, which we crystallized at a resolution of 1.31 Ã…, together with molecular dynamics simulations. In conclusion, we propose that K53 acetylation of Cytc affects two hallmarks of cancer by regulating respiration and apoptosis in prostate cancer xenografts

    Probing the Fundamental Nature of Dark Matter with the Large Synoptic Survey Telescope

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    94 pages, 22 figures, 1 tableAstrophysical and cosmological observations currently provide the only robust, empirical measurements of dark matter. Future observations with Large Synoptic Survey Telescope (LSST) will provide necessary guidance for the experimental dark matter program. This white paper represents a community effort to summarize the science case for studying the fundamental physics of dark matter with LSST. We discuss how LSST will inform our understanding of the fundamental properties of dark matter, such as particle mass, self-interaction strength, non-gravitational couplings to the Standard Model, and compact object abundances. Additionally, we discuss the ways that LSST will complement other experiments to strengthen our understanding of the fundamental characteristics of dark matter. More information on the LSST dark matter effort can be found at https://lsstdarkmatter.github.io/

    Dark Matter Science in the Era of LSST

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    Astrophysical observations currently provide the only robust, empirical measurements of dark matter. In the coming decade, astrophysical observations will guide other experimental efforts, while simultaneously probing unique regions of dark matter parameter space. This white paper summarizes astrophysical observations that can constrain the fundamental physics of dark matter in the era of LSST. We describe how astrophysical observations will inform our understanding of the fundamental properties of dark matter, such as particle mass, self-interaction strength, non-gravitational interactions with the Standard Model, and compact object abundances. Additionally, we highlight theoretical work and experimental/observational facilities that will complement LSST to strengthen our understanding of the fundamental characteristics of dark matter
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