66- #1165 MODELOS DE PROGRAMACIÓN LINEAL 71 ENTERA MIXTA PARA EL PROBLEMA DE REPOSICIONAMIENTO DE BICICLETAS

Los sistemas de bicicletas compartidas (BSS, por sussiglas en inglés) representan una estrategia paramitigar efectos adversos propios del proceso deurbanización en las ciudades. Los BSSs permiten a sususuarios usar un conjunto de bicicletas como mediopara transportarse entre dos puntos diferentes(estaciones de origen y de destino) de una zonaurbana. Para el eficiente funcionamiento de un BSS esindispensable tener un número adecuado de bicicletasy espacios de parqueo disponibles de acuerdo a lademanda de cada uno de ellos. Para tal fin, esnecesario que un vehículo entregue o recoja bicicletaspara redistribuirlas en las estaciones si es necesario.Este proceso se conoce como reposicionamiento ydesde la perspectiva de la optimización, puedemodelarse como un problema de ruteo de vehículoscon operaciones de recolección y entrega (PDVRP, porsus siglas en inglés). En este trabajo, se modela elproblema de reposicionamiento a través deformulaciones de programación lineal entera mixta.Siendo la capacidad del vehículo una restricción aconsiderar, se describen características adicionalestales como entregas parciales (split delivery) einventario temporal de bicicletas en las estaciones. Lascaracterísticas anteriores implican que algunasestaciones pueden ser visitadas múltiples vecesdurante la operación de reposicionamiento. Comoestrategia de solución, usamos un optimizadorcomercial para resolver instancias conocidas de laliteratura. Finalmente, analizamos cuales son losbeneficios de permitir múltiples visitas a una estaciónrealizando entregas parciales o almacenando temporalmente unidades que posteriormente sontransportadas a otra estación

How to measure student's performance in PBL?

[EN] In this paper, we present an analysis of metrics for teamwork efficiency in University degrees, by considering Project Based Learning as a teaching methodology. We defined indicators to evaluate the ability to prioritize tasks, the group communication and the produced value. Such parameters were designed to provide objective information about teamwork efficiency. To test the effectiveness of the proposed indicators, an experiment based on a classic team-building game was performed in the context of the Interactive Technologies Degree at Universitat Politècnica de València. Students were divided into two groups (one from the first course and another the fourth course) and were asked to solve a problem in a limited amount of time. Our hypothesis was that the group corresponding to the fourth course would achieve higher teamwork efficiency because of their experience with the Project Based Learning methodology. After measuring the proposed indicators and other state-of-the-art parameters, we assessed the evolution and improvement of teamwork efficiency by comparing the results of both sets of metrics. Finally, we concluded that the presented metrics can be useful for teamwork efficiency evaluation, but also for students to manage their work.This work has been partially financed by UPV-Innovation Project PIME-I 1776 (2022-2024).Pérez Pascual, MA.; Alberola Oltra, JM.; Marín-Roig Ramón, J.; Toledo Alarcón, JF.; Palacio Samitier, D.; Giménez López, JL.; Heras, S.... (2023). How to measure student's performance in PBL?. IATED. 1-9. https://doi.org/10.21125/inted.2023.08461

ADGRL3 (LPHN3) variants predict substance use disorder

Genetic factors are strongly implicated in the susceptibility to develop externalizing syndromes such as attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder, conduct disorder, and substance use disorder (SUD). Variants in the ADGRL3 (LPHN3) gene predispose to ADHD and predict ADHD severity, disruptive behaviors comorbidity, long-term outcome, and response to treatment. In this study, we investigated whether variants within ADGRL3 are associated with SUD, a disorder that is frequently co-morbid with ADHD. Using family-based, case-control, and longitudinal samples from disparate regions of the world (n = 2698), recruited either for clinical, genetic epidemiological or pharmacogenomic studies of ADHD, we assembled recursive-partitioning frameworks (classification tree analyses) with clinical, demographic, and ADGRL3 genetic information to predict SUD susceptibility. Our results indicate that SUD can be efficiently and robustly predicted in ADHD participants. The genetic models used remained highly efficient in predicting SUD in a large sample of individuals with severe SUD from a psychiatric institution that were not ascertained on the basis of ADHD diagnosis, thus identifying ADGRL3 as a risk gene for SUD. Recursive-partitioning analyses revealed that rs4860437 was the predominant predictive variant. This new methodological approach offers novel insights into higher order predictive interactions and offers a unique opportunity for translational application in the clinical assessment of patients at high risk for SUD

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

Mutations in sphingolipid metabolism genes are associated with ADHD.

Attention deficit hyperactivity disorder (ADHD) is the most prevalent neurodevelopmental disorder in children, with genetic factors accounting for 75-80% of the phenotypic variance. Recent studies have suggested that ADHD patients might present with atypical central myelination that can persist into adulthood. Given the essential role of sphingolipids in myelin formation and maintenance, we explored genetic variation in sphingolipid metabolism genes for association with ADHD risk. Whole-exome genotyping was performed in three independent cohorts from disparate regions of the world, for a total of 1520 genotyped subjects. Cohort 1 (MTA (Multimodal Treatment study of children with ADHD) sample, 371 subjects) was analyzed as the discovery cohort, while cohorts 2 (Paisa sample, 298 subjects) and 3 (US sample, 851 subjects) were used for replication. A set of 58 genes was manually curated based on their roles in sphingolipid metabolism. A targeted exploration for association between ADHD and 137 markers encoding for common and rare potentially functional allelic variants in this set of genes was performed in the screening cohort. Single- and multi-locus additive, dominant and recessive linear mixed-effect models were used. During discovery, we found statistically significant associations between ADHD and variants in eight genes (GALC, CERS6, SMPD1, SMPDL3B, CERS2, FADS3, ELOVL5, and CERK). Successful local replication for associations with variants in GALC, SMPD1, and CERS6 was demonstrated in both replication cohorts. Variants rs35785620, rs143078230, rs398607, and rs1805078, associated with ADHD in the discovery or replication cohorts, correspond to missense mutations with predicted deleterious effects. Expression quantitative trait loci analysis revealed an association between rs398607 and increased GALC expression in the cerebellum

The genomic landscape of molecular responses to natural drought stress in Panicum hallii

Drought is a major factor limiting crop productivity. Here, via eQTL analysis and comparative genomics, the authors show compensatory evolution between trans-regulatory loci and transcription factor binding sites that shape the drought response networks in the model C4 grass Panicum hallii

The genomic landscape of molecular responses to natural drought stress in \u3cem\u3ePanicum hallii\u3c/em\u3e.

Environmental stress is a major driver of ecological community dynamics and agricultural productivity. This is especially true for soil water availability, because drought is the greatest abiotic inhibitor of worldwide crop yields. Here, we test the genetic basis of drought responses in the genetic model for C4 perennial grasses, Panicum hallii, through population genomics, field-scale gene-expression (eQTL) analysis, and comparison of two complete genomes. While gene expression networks are dominated by local cis-regulatory elements, we observe three genomic hotspots of unlinked trans-regulatory loci. These regulatory hubs are four times more drought responsive than the genome-wide average. Additionally, cis- and trans-regulatory networks are more likely to have opposing effects than expected under neutral evolution, supporting a strong influence of compensatory evolution and stabilizing selection. These results implicate trans-regulatory evolution as a driver of drought responses and demonstrate the potential for crop improvement in drought-prone regions through modification of gene regulatory networks

Potential cognitive endophenotypes in multigenerational families: segregating ADHD from a genetic isolate

Endophenotypes are neurobiological markers cosegregating and associated with illness. These biomarkers represent a promising strategy to dissect ADHD biological causes. This study was aimed at contrasting the genetics of neuropsychological tasks for intelligence, attention, memory, visual-motor skills, and executive function in children from multigenerational and extended pedigrees that cluster ADHD in a genetic isolate. In a sample of 288 children and adolescents, 194 (67.4%) ADHD affected and 94 (32.6%) unaffected, a battery of neuropsychological tests was utilized to assess the association between genetic transmission and the ADHD phenotype. We found significant differences between affected and unaffected children in the WISC block design, PIQ and FSIQ, continuous vigilance, and visual-motor skills, and these variables exhibited a significant heritability. Given the association between these neuropsychological variables and ADHD, and also the high genetic component underlying their transmission in the studied pedigrees, we suggest that these variables be considered as potential cognitive endophenotypes suitable as quantitative trait loci (QTLs) in future studies of linkage and association