Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Optimized Control for Water Utilities

AbstractThe rising demand for water and the need for more electricity to transport it, from remote sources to consumers, are pushing hu- manity to find ways to save water as well as energy. Thus, this paper presents a novel technique to optimize the control operations in water utilities, where the water distribution system is modeled as a Markov Decision Process to produce a control policy to minimize the energy expenses. We report experiments in a water utility that provided reduction of 39.3% in energy expenses. Moreover, it was possible to increase soundness of the system operation in order to avoid water outages

Qualidade para processamento de clones de batata cultivados durante a primavera e outono no Rio Grande do Sul Processing quality of potato clones during spring and autumn grown conditions of Rio Grande do Sul

A industrialização da batata (Solanum tuberosum L.) tem sido limitada no Brasil, quase que exclusivamente, pela falta de matéria-prima adequada. Alta qualidade do produto processado é dependente de altos teores de matéria seca, que reduz a absorção de óleo durante a fritura e confere crocância, e baixos teores de açúcares redutores, que mantêm a coloração clara das fritas. O objetivo deste trabalho foi identificar clones de batata de alta qualidade para processamento a partir da avaliação de tubérculos produzidos durante os cultivos de primavera de 2003 e outono de 2004 em Santa Maria, RS. O experimento foi conduzido em um fatorial (15 clones e duas épocas de cultivo) no delineamento de blocos ao acaso, com quatro repetições. Foram avaliados os clones Dakota Rose, SMINIAIporã, SMIJ461-1, SMIJ319-1, SMIJ456-4Y, SMID040-4RY, SMIE040-6RY, SMIC148-A, SMIF165-6RY, SMIH095-1, SMINIA90244-1, SMINIA793101-3, SMINIA95043-11, Macaca e Asterix nos cultivos de primavera de 2003 e outono de 2004 em Santa Maria, RS. As condições ambientais, durante o período de produção, influenciaram a qualidade pós-colheita dos tubérculos. Os clones SMIJ461-1, SMIJ319-1, SMIJ456-4Y, SMIC148-A, SMIDO40-4RY e SMIH095-1 foram os que apresentaram o melhor desempenho nas características desejáveis para processamento, sendo superiores a Asterix, cultivada para consumo de mesa ou para processamento na forma de chips nas diferentes regiões produtoras de batata. Dentre esses clones, SMIDO40-4RY e SMIH095-1 foram os menos influenciados pelas diferenças de temperatura e insolação típicas das épocas de cultivo de outono e primavera no RS. Os clones SMIJ461-1 e SMIJ456-4Y apresentaram maior teor de matéria seca e coloração mais clara do chips no cultivo da primavera.<br>The development of the potato (Solanum tuberosum L.) processing industry has been limited in Brazil, because of the low availability of tubers with adequate quality. High dry matter, responsible for chips with low oil content and crispy consistency, and low reduced sugars, keep chips with light color, are necessary for high quality processing products. The objective was to identify potato clones with high processing quality based upon the evaluation of tubers produced under spring 2003 and autumn 2004 grown seasons at Santa Maria, RS, Brazil. The experiment was conducted in a factorial (15 clones and two grown seasons) in a complete random design with four replications. The clones Dakota Rose, SMINIAIporã, SMIJ461-1, SMIJ319-1, SMIJ456-4Y, SMID040-4RY, SMIE040-6RY, SMIC148-A, SMIF165-6RY, SMIH095-1, SMINIA90244-1, SMINIA793101-3, SMINIA95043-11, Macaca and Asterix were evaluated in Santa Maria, Rio Grande do Sul (RS) State, during spring 2003 and autumn 2004 grown seasons. The environmental conditions during grown season affected the postharvest quality of tubers. The clones SMIJ461-1, SMIJ319-1, SMIJ456-4Y, SMIC148-A, SMIDO40-4RY and SMIH095-1 had the highest processing quality, even better than Asterix cultivated for tablestock or chip processing in different potato production regions. Different environmental conditions of temperature and sunshine, common between spring and autumn grown seasons of RS, had little effect in the processing quality performance of SMIDO40-4RY and SMIH095-1 clones. The clones SMIJ461-1 and SMIJ456-4Y had the highest dry matter content and the lightest chip color during the spring grown conditions

A Quarter of Century in Artificial Intelligence and Law: Projects, Personal Trajectories, a Subjective PerspectiveLanguage, Culture, Computation. Computing of the Humanities, Law, and Narratives

This article describes projects in the domain of artificial intelligence and law, which resulted from the research of the five authors listed, when they formed teams (of the first author named and each one of the other authors). Therefore, the present paper offers a subjective perspective, from the viewpoint of personal trajectories within AI & Law. Several, though not all, of the projects concerned dealt with facets of legal evidence. These projects include: ALIBI (an AI planner generating exonerating accounts); a representation of Italy’s regional constitutions in a nested-relation representation (a precursor of XML); the application of kappa calculus and a probabilistic interpretation to a Scandinavian approach to evidential strength; the application of Petri Nets for representing temporal relations in mutual wills; Daedalus (Judge Asaro’s software assisting Italy’s examining magistrates with inquiries, and then when they turn prosecutors); a study in occurrences in court of allegations echoing the pretext archetype “The dog ate my homework” (even when the claim was not pretextuous); an application of Wigmore Charts to an analysis of both the argumentation and the rhetoric of an Italian arringa (final submissions to the court) from a real court case; editorial projects which promoted the emergence of evidence as a conspicuous field within AI & Law (thus overturning previous neglect); and a magnum opus (Nissan 2012a) which presents the state of the art of computational applications to legal evidence, police inquiries, or argumentation