A homogenizing process of selection has maintained an \u27ultra-slow\u27 acetylation NAT2 variant in humans

N-acetyltransferase 2 (NAT2) is an important enzyme involved in the metabolism of a wide spectrum of naturally occurring xenobiotics, including therapeutic drugs and common environmental carcinogens. Extensive polymorphism in NAT2 gives rise to a wide interindividual variation in acetylation capacity which influences individual susceptibility to various drug-induced adverse reactions and cancers. Striking patterns of geographic differentiation have been described for the main slow acetylation variants of the NAT2 gene, suggesting the action of natural selection at this locus. In the present study, we took advantage of the whole-genome sequence data available from the 1000 Genomes project to investigate the global patterns of population genetic differentiation at NAT2 and determine whether they are atypical compared to the remaining variation of the genome. The non-synonymous substitution c.590G\u3eA (rs1799930) defining the slow NAT2*6 haplotype cluster exhibited an unusually low FST value when compared to the genome average (FST = 0.006, P-value = 0.016). It was pointed out as the most likely target of a homogenizing process of selection promoting the same allelic variant in globally distributed populations. The rs1799930 A allele has been associated with the slowest acetylation capacity in vivo and its substantial correlation with the subsistence strategy adopted by past human populations suggests that it may have conferred a selective advantage in populations shifting from foraging to agricultural and pastoral activities in the Neolithic period. Results of neutrality tests further supported an adaptive evolution of the NAT2 gene through either balancing selection or directional selection acting on multiple standing slow-causing variants

Automatic detection of relationships between banking operations using machine learning

In their daily business, bank branches should register their operations with several systems in order to share information with other branches and to have a central repository of records. In this way, information can be analysed and processed according to different requisites: fraud detection, accounting or legal requirements. Within this context, there is increasing use of big data and artificial intelligence techniques to improve customer experience. Our research focuses on detecting matches between bank operation records by means of applied intelligence techniques in a big data environment and business intelligence analytics. The business analytics function allows relationships to be established and comparisons to be made between variables from the bank's daily business. Finally, the results obtained show that the framework is able to detect relationships between banking operation records, starting from not homogeneous information and taking into account the large volume of data involved in the process. (C) 2019 Elsevier Inc. All rights reserved.This work was supported by the Research Program of the Ministry of Economy and Competitiveness - Government of Spain, (DeepEMR project TIN2017-87548-C2-1-R)

A black-Box adversarial attack for poisoning clustering

Clustering algorithms play a fundamental role as tools in decision-making and sensible automation pro-cesses. Due to the widespread use of these applications, a robustness analysis of this family of algorithms against adversarial noise has become imperative. To the best of our knowledge, however, only a few works have currently addressed this problem. In an attempt to fill this gap, in this work, we propose a black-box adversarial attack for crafting adversarial samples to test the robustness of clustering algo-rithms. We formulate the problem as a constrained minimization program, general in its structure and customizable by the attacker according to her capability constraints. We do not assume any information about the internal structure of the victim clustering algorithm, and we allow the attacker to query it as a service only. In the absence of any derivative information, we perform the optimization with a custom approach inspired by the Abstract Genetic Algorithm (AGA). In the experimental part, we demonstrate the sensibility of different single and ensemble clustering algorithms against our crafted adversarial samples on different scenarios. Furthermore, we perform a comparison of our algorithm with a state-of-the-art approach showing that we are able to reach or even outperform its performance. Finally, to highlight the general nature of the generated noise, we show that our attacks are transferable even against supervised algorithms such as SVMs, random forests and neural networks. (c) 2021 Elsevier Ltd. All rights reserved

The new philanthropy : private power in international development policy?

This chapter examines the role and function of philanthropy in international development policy. Philanthropy has deep roots in international development and its present influence is far from novel. Yet changes in the political economy of development finance, including growing private aid flows and continuing strain on the bilateral and multilateral aid systems, have increased its relative importance. Simultaneously, newly emerging foundations have financed novel institutional mechanisms for aid delivery in global health and transnational policy networks focussed on democratisation. These mechanisms have substantively shaped international development policy in key development sectors with important implications for the aid architecture by bringing in additional resources, ideas and approaches, while concurrently raising concerns, around the legitimacy and accountability of private actors

Realización de un estudio de asociación genómica en el repositorio público ADNI

Los estudios de asociación del genoma completo (GWAS) pertenecen a un campo en desarollo muy explotado en los últimos años. En concreto, este método ha intentado asociar la enfermedad de ALzheimer con su base genética, especialmente con ciertos SNPs, mediante el uso fenotipos cuantitativos como el volumen de estructuras cerebrales (que se sabe disminuyen con el progreso de esta infermedad). Algunas iniciativas como ADNI (Alzheimer’s Disease Neuroimaging Initiative) se establecieron para probar si marcadores anatómicos o biológicos (desde Imágenes de Resonancia Magnética (MRI) hasta Tomografı́as por emisión de positrones (PET)), la información genética, clı́nica o análisis neuropsicológicos se pueden combinar para medir la progresión del Alzheimer. En la última década, la base de datos de ADNI ha aumentado considerablemente, dando lugar a las cohortes ADNI1, ADNIGO y ADNI2. Aunque se han llevado a cabo algunos GWAS con subpoblaciones de ADNI1, que sepamos no se han realizado con todo el proyecto de ADNI1 ni el resto de cohortes. En esta tesis se trata de estudiar qué SNPs están preservados de forma consistente en los diferentes GWAS de las cohortes, de forma que se haga posible la reproducción de los resultados previos del estudio en ADNI Hippocampal Atrophy as a Quantitative Trait in a Genome-Wide Association Study Identifying Novel Susceptibility Genes for Alzheimer’s Disease (Potkin et al. 2009). También tiene por objetivo descubrir nuevos posibles genes que representen factores de riesgo de padecer Alzheimer. Estos objetivos han sido abordados mediante la realización de GWAS para las cohortes ADNI1 y ADNI2 por separado, para la población conjunta de ADNI1 y ADNI2, ası́ como para subpoblaciones randomizadas. Los resultados muestran en varios SNPs una asociación positiva con el volumen de hipocampo en el análisis de ADNI1 y en la población total. Se trata de dos SNPs ya relacionados con ALzheimer: rs429358 del gen APOE y rs2075650 del gen TOMM40. Sin embargo, esta relación no se encontró en ADNI2. Se podrı́a hipotetizar que la razón de este resultado reside en la variabilidad encontrada en la asociación dependiendo del tamaño muestral. Esta hipótesis estarı́a respaldada teniendo en cuenta los resultados que se obtienen para el 50% de la población randomizada (ADNI2 representa aproximadamente el 50% de la población total). Sin embargo, se necesitarı́a profundizar en este aspecto para poder confirmar la hipótesis. Además, en este estudio se encontró una leve asociación en dos SNPs ya relacionados con otros transtornos mentales

Endowment effects at different time scenarios: the role of ownership and possession

The central issue of the wide literature about the endowment effect is the search for an explanation of the fact that the selling price of a good will be higher than that at which a person is willing to buy that same good, once they own it. The experimental evidence is not unanimous in replicating the results found by Kahneman et al. (1990 and 1991). The challenge is that of disentangling the several determinants that may be at work in generating the final effect, as the loss aversion is not considered the only explanation. We dig deeper by examining two of these likely determinants which remain understudied: the first is the impact that the amount of time of ownership can have on the endowment effect. The second is the type of item (non-material good and exchange goods) used to test the effect. Through an online questionnaire we investigate these aspects by using three different goods: a mug, an Amazon Gift Card and a quarterly subscription to Spotify. We also test whether the endowment effect occurs in different time scenarios, that is if participants imagine to own the good for one day, one week or one month. We find that the endowment effect clearly appears for all types of goods while less clear results take shape when considering the duration of the ownership