Optimal Single-Choice Prophet Inequalities from Samples

We study the single-choice Prophet Inequality problem when the gambler is given access to samples. We show that the optimal competitive ratio of $1/2$ can be achieved with a single sample from each distribution. When the distributions are identical, we show that for any constant $\varepsilon > 0$, $O(n)$ samples from the distribution suffice to achieve the optimal competitive ratio ($\approx 0.745$) within $(1+\varepsilon)$, resolving an open problem of Correa, D\"utting, Fischer, and Schewior.Comment: Appears in Innovations in Theoretical Computer Science (ITCS) 202

Variance Reduction Techniques in Monte Carlo Methods

Monte Carlo methods are simulation algorithms to estimate a numerical quantity in a statistical model of a real system. These algorithms are executed by computer programs. Variance reduction techniques (VRT) are needed, even though computer speed has been increasing dramatically, ever since the introduction of computers. This increased computer power has stimulated simulation analysts to develop ever more realistic models, so that the net result has not been faster execution of simulation experiments; e.g., some modern simulation models need hours or days for a single ’run’ (one replication of one scenario or combination of simulation input values). Moreover there are some simulation models that represent rare events which have extremely small probabilities of occurrence), so even modern computer would take ’for ever’ (centuries) to execute a single run - were it not that special VRT can reduce theses excessively long runtimes to practical magnitudes.common random numbers;antithetic random numbers;importance sampling;control variates;conditioning;stratied sampling;splitting;quasi Monte Carlo

Exploiting Machine Learning to Subvert Your Spam Filter

Using statistical machine learning for making security decisions introduces new vulnerabilities in large scale systems. This paper shows how an adversary can exploit statistical machine learning, as used in the SpamBayes spam filter, to render it useless—even if the adversary’s access is limited to only 1 % of the training messages. We further demonstrate a new class of focused attacks that successfully prevent victims from receiving specific email messages. Finally, we introduce two new types of defenses against these attacks.

DRD4 genotype predicts longevity in mouse and human

Longevity is influenced by genetic and environmental factors. The brain's dopamine system may be particularly relevant, since it modulates traits (e.g., sensitivity to reward, incentive motivation, sustained effort) that impact behavioral responses to the environment. In particular, the dopamine D4 receptor (DRD4) has been shown to moderate the impact of environments on behavior and health. We tested the hypothesis that the DRD4 gene influences longevity and that its impact is mediated through environmental effects. Surviving participants of a 30-year-old population-based health survey (N = 310; age range, 90-109 years; the 90+ Study) were genotyped/resequenced at the DRD4 gene and compared with a European ancestry-matched younger population (N = 2902; age range, 7-45 years). We found that the oldest-old population had a 66% increase in individuals carrying the DRD4 7R allele relative to the younger sample (p = 3.5 × 10(-9)), and that this genotype was strongly correlated with increased levels of physical activity. Consistent with these results, DRD4 knock-out mice, when compared with wild-type and heterozygous mice, displayed a 7-9.7% decrease in lifespan, reduced spontaneous locomotor activity, and no lifespan increase when reared in an enriched environment. These results support the hypothesis that DRD4 gene variants contribute to longevity in humans and in mice, and suggest that this effect is mediated by shaping behavioral responses to the environment.Fil: Grady, Deborah L.. University of California. College of Medicine. Department of Biological Chemistry; Estados UnidosFil: Thanos, Panayotis K.. National Institute on Alcohol Abuse and Alcoholism. Laboratory of Neuroimaging; Estados Unidos. Brookhaven National Laboratory. Medical Department. Behavioral Neuropharmocology and Neuroimaging Laboratory; Estados Unidos. Stony Brook University. Department of Psychology; Estados UnidosFil: Corrada, Maria M.. University of California. Department of Neurology; Estados UnidosFil: Barnett Jr., Jeffrey C.. Brookhaven National Laboratory. Medical Department. Behavioral Neuropharmocology and Neuroimaging Laboratory; Estados UnidosFil: Ciobanu, Valentina. University of California. College of Medicine. Department of Biological Chemistry; Estados UnidosFil: Shustarovich, Diana. Brookhaven National Laboratory. Medical Department. Behavioral Neuropharmocology and Neuroimaging Laboratory; Estados UnidosFil: Napoli, Anthony. Brookhaven National Laboratory. Medical Department. Behavioral Neuropharmocology and Neuroimaging Laboratory; Estados UnidosFil: Moyzis, Alexandra G.. University of California. College of Medicine. Department of Biological Chemistry; Estados UnidosFil: Grandy, David. Oregon Health Sciences University. Physiology and Pharmacology; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; ArgentinaFil: Wang, Gene-Jack. Brookhaven National Laboratory. Medical Department. Behavioral Neuropharmocology and Neuroimaging Laboratory; Estados UnidosFil: Kawas, Claudia H.. University of California. Department of Neurology; Estados UnidosFil: Chen, Chuansheng. University of California. Department of Psychology and Social Behavior; Estados UnidosFil: Dong, Qi. Beijing Normal University. National Key Laboratory of Cognitive Neuroscience and Learning; ChinaFil: Wang, Eric. University of California. College of Medicine. Department of Biological Chemistry; Estados Unidos. Aria Diagnostics Inc.; Estados Unidos. University of California. Institute of Genomics and Bioinformatics; Estados UnidosFil: Volkow, Nora D.. National Institute on Alcohol Abuse and Alcoholism. Laboratory of Neuroimaging; Estados Unidos. Brookhaven National Laboratory. Medical Department. Behavioral Neuropharmocology and Neuroimaging Laboratory; Estados Unidos. National Institute on Drug Abuse; Estados UnidosFil: Moyzis, Robert K.. University of California. College of Medicine. Department of Biological Chemistry; Estados Unidos. Beijing Normal University. National Key Laboratory of Cognitive Neuroscience and Learning; China. University of California. Institute of Genomics and Bioinformatics; Estados Unido

DHODH modulates transcriptional elongation in the neural crest and melanoma

Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma1. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation

Implementation Science to Accelerate Clean Cooking for Public Health

Clean cooking has emerged as a major concern for global health and development because of the enormous burden of disease caused by traditional cookstoves and fires. The World Health Organization has developed new indoor air quality guidelines that few homes will be able to achieve without replacing traditional methods with modern clean cooking technologies, including fuels and stoves. However, decades of experience with improved stove programs indicate that the challenge of modernizing cooking in impoverished communities includes a complex, multi-sectoral set of problems that require implementation research. The National Institutes of Health, in partnership with several government agencies and the Global Alliance for Clean Cookstoves, has launched the Clean Cooking Implementation Science Network that aims to address this issue. In this article, our focus is on building a knowledge base to accelerate scale-up and sustained use of the cleanest technologies in low- and middle-income countries. Implementation science provides a variety of analytical and planning tools to enhance effectiveness of clinical and public health interventions. These tools are being integrated with a growing body of knowledge and new research projects to yield new methods, consensus tools, and an evidence base to accelerate improvements in health promised by the renewed agenda of clean cooking.Fil: Rosenthal, Joshua. National Institutes Of Health. Fogarty International Center; Estados UnidosFil: Balakrishnan, Kalpana. Sri Ramachandra University; IndiaFil: Bruce, Nigel. University of Liverpool; Reino UnidoFil: Chambers, David. National Institutes of Health. National Cancer Institute; Estados UnidosFil: Graham, Jay. The George Washington University; Estados UnidosFil: Jack, Darby. Columbia University; Estados UnidosFil: Kline, Lydia. National Institutes Of Health. Fogarty International Center; Estados UnidosFil: Masera, Omar Raul. Universidad Nacional Autónoma de México; MéxicoFil: Mehta, Sumi. Global Alliance for Clean Cookstoves; Estados UnidosFil: Mercado, Ilse Ruiz. Universidad Nacional Autónoma de México; MéxicoFil: Neta, Gila. National Institutes of Health. National Cancer Institute; Estados UnidosFil: Pattanayak, Subhrendu. University of Duke; Estados UnidosFil: Puzzolo, Elisa. Global LPG Partnership; Estados UnidosFil: Petach, Helen. U.S. Agency for International Development; Estados UnidosFil: Punturieri, Antonello. National Heart, Lung, and Blood Institute; Estados UnidosFil: Rubinstein, Adolfo Luis. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sage, Michael. Centers for Disease Control and Prevention; Estados UnidosFil: Sturke, Rachel. National Institutes Of Health. Fogarty International Center; Estados UnidosFil: Shankar, Anita. University Johns Hopkins; Estados UnidosFil: Sherr, Kenny. University of Washington; Estados UnidosFil: Smith, Kirk. University of California at Berkeley; Estados UnidosFil: Yadama, Gautam. Washington University in St. Louis; Estados Unido

Repurposing Probenecid for the Treatment of Heart Failure (Re-Prosper-Hf): A Study Protocol for a Randomized Placebo-Controlled Clinical Trial

BACKGROUND: Improving contractility in heart failure with reduced ejection fraction (HFrEF) has resurfaced as a potential treatment goal. Inotropic therapy is now better understood through its underlying mechanism as opposed to the observed effect of increasing contractility. Calcitropes are a subgroup of inotropes that largely depend on the stimulation of adenylyl cyclase to transform ATP into cyclic adenosine monophosphate (cAMP). At least two clinically relevant calcitropes-istaroxime and probenecid-improve contractility through an increase in systolic intracellular calcium without activating cAMP production. Probenecid, which has been safely used clinically for decades in non-cardiac conditions, has recently been identified as an agonist of the transient receptor potential vanilloid 2 channel. Translational studies have shown that it improves calcium cycling and contractility without activating noxious pathways associated with cAMP-dependent calcitropes and can improve cardiac function in patients with HFrEF. METHODS: The Re-Prosper-HF study (Repurposing Probenecid for the Treatment of Heart Failure with Reduced Ejection Fraction) is a three-site double-blinded randomized-controlled trial that will test the hypothesis that probenecid can improve cardiac function in patients with HFrEF. Up to 120 patients will be randomized in this double-blind, placebo-controlled study that will assess whether oral probenecid administered at 1 g orally twice per day for 180 days in patients with NYHA II-III HFrEF improves systolic function (aim 1), functional status (aim 2), and self-reported health status (aim 3). DISCUSSION: Findings from this study will provide data informing its use for improving symptomatology in patients with HFrEF as well as exploratory data for outcomes such as hospital admission rates. TRIAL TEGISTRATION: The Re-Prosper HF Study (Re-Prosper HF) is registered on ClinicalTrials.gov with the identifier as NCT04551222. Registered on 9 September 2020