SEARCH FOR THE STANDARD MODEL HIGGS BOSON PRODUCED IN ASSOCIATION WITH TOP QUARK PAIRS IN MULTI-LEPTONIC FINAL STATES WITH THE ATLAS DETECTOR AT THE LHC

The search for the Standard Model (SM) Higgs boson produced in asso- ciation with top quarks - known as ttH production - plays a crucial role in the Large Hadron Collider (LHC) physics programme, as it allows a direct measurement of the Higgs field Yukawa coupling to the heaviest fermion and can constrain effects of new physics beyond the Standard Model in the top coupling sector. This thesis presents a search for the ttH production in an inclusive mul- tileptonic final state, with a proton-proton collision dataset corresponding to an integrated luminosity of Int( L dt ) = 36.1 fb 121, collected by the ATLAS experiment at the LHC in 2015 and 2016 at a centre-of-mass energy 1as=13TeV. The final state is characterised by high jet multiplicity, and the presence of several electrons and muons, as well as hadronically decaying tau leptons. The multiplicity of these physics objects allows the definition of several categories to enhance the sensitivity of the analysis. The particular focus of my work lies on the final state where exactly two light leptons with the same electric charge and no hadronic taus are found - indicated as 2l SS 0\u3c4had - for which I developed a novel technique to estimate the reducible background of non-prompt (fake) electrons and muons. Boosted decision tree algorithms are trained to discriminate the ttH signal events from the two major background processes in this channel: ttV (V=W,Z) and events with fake leptons. A fit of our model to the observed data is performed, and the results are interpreted using a frequentist approach. A best-fit value for the strength of the ttH production cross section with respect to the Standard Model expectation of \u3bc = 1.5+0.7 is observed. The observed sensitivity of this search corresponds to a 2.7\u3c3 excess of events above the SM background-only hypothesis, with an expected median sensitivity of 1.9\u3c3 for a model where the SM ttH production is assumed. Combination with the other categories of the ttH to multi-leptons analysis eventually leads to a signal strength of \u3bc = 1.6+0.5, with an observed (expected) sensitivity of 4.1\u3c3 (2.8\u3c3) above the SM background-only hypothesis. This indicates the strongest evidence to date for the ttH production mode. Furthermore, I present a study on improvements to the ATLAS track re- construction algorithm to enhance its performance in environments with high density of tracks, such as the core of boosted hadronic jets and hadronically decaying tau leptons

Estilos de desarrollo, ideología e Intervención antrópica en Misiones (Argentina): Un análisis multidimensional y comparativo. 16H201

Esta es una continuación del Programa ECIS (Estudio Comparativo de los Impactos Sociales de los Grandes Proyectos de Desarrollo), constituído a partir del 2005 en el Programa de Ecología Humana (PEH). Los ejes convocantes para esta nueva etapa, son, en primer lugar, la compleción del análisis del Proyecto Yacyretá, que en el período anterior concretó la publicación de un volumen. Una segunda vertiente remite a la ideología de los movimientos sociales opuestos a la construcción de represas y a la concepción de desarrollo explícitas o implícitas en sus propuestos y su comparación con otros movimientos ecologistas (Córdoba). Asimismo, nos proponemos realizar estudios de campo de las prácticas agrícolas de los colonos asentados en áreas de la provincia incluidas en el proyecto de "corredor verde", con el objeto de analizar su compatibilidad o no con los modelos de "explotación sustentable" que se vienen manejando, así como analizar otros desarrollos recientes en el agro misionero. Finalmente, se contemplan estudios comparativos sobre desarrollo socioeconómico de minorías en la Patagonia argentina

Formative Assessment and Professional Training: Reflections from a Mathematics course in Bioengineering

Bioengineering is currently considered an interdisciplinary professional field which provides solutions to different problems arising in the area of health care. Its strategic importance is widely acknowledged since its developments and proposals could help diminish the level of technological dependence in the sector. The fast pace of innovation in the area of biomedical technology gives rise to permanent reflection on the learning goals and teaching strategies proposed by educators in the different training stages of a bioengineer. In this context, learning assessment appears as a controversial issue which needs to be debated and rethought. This paper describes the reflections of teachers of a Mathematics course within a Bioengineering program around the question, What approach to assessment favors the student's participation, autonomy and training as a future bioengineer? The investigation was carried out in the framework of a Participatory Research Action project and helped us to redesign assessment activities from a different perspective.Fil: Carrere, C.. Universidad Nacional de Entre Ríos. Facultad de Ingeniería; ArgentinaFil: Milesi, S.. Universidad Nacional de Entre Ríos. Facultad de Ingeniería; ArgentinaFil: Lapyckyj, I.. Universidad Nacional de Entre Ríos. Facultad de Ingeniería; ArgentinaFil: Ravera, Emiliano Pablo. Universidad Nacional de Entre Ríos. Facultad de Ingeniería; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Escher, L.. Universidad Nacional de Entre Ríos. Facultad de Ingeniería; ArgentinaFil: Miyara, A.. Universidad Nacional de Rosario; Argentina. Universidad Nacional de Entre Ríos. Facultad de Ingeniería; ArgentinaFil: Pita, G.. Universidad Nacional de Entre Ríos. Facultad de Ingeniería; ArgentinaFil: Añino, M.. Universidad Nacional de Entre Ríos. Facultad de Ingeniería; Argentin

Genomic data provide new insights on the demographic history and the extent of recent material transfers in Norway spruce

Primeval forests are today exceedingly rare in Europe, and transfer of forest reproductive material for afforestation and improvement has been very common, especially over the last two centuries. This can be a serious impediment when inferring past population movements in response to past climate changes such as the last glacial maximum (LGM), some 18,000 years ago. In the present study, we genotyped 1,672 individuals from three Picea species (P. abies, P. obovata, and P. omorika) at 400K SNPs using exome capture to infer the past demographic history of Norway spruce (P. abies) and estimate the amount of recent introduction used to establish the Norway spruce breeding program in southern Sweden. Most of these trees belong to P. abies and originate from the base populations of the Swedish breeding program. Others originate from populations across the natural ranges of the three species. Of the 1,499 individuals stemming from the breeding program, a large proportion corresponds to recent introductions from mainland Europe. The split of P. omorika occurred 23 million years ago (mya), while the divergence between P. obovata and P. abies began 17.6 mya. Demographic inferences retrieved the same main clusters within P. abies than previous studies, that is, a vast northern domain ranging from Norway to central Russia, where the species is progressively replaced by Siberian spruce (P. obovata) and two smaller domains, an Alpine domain and a Carpathian one, but also revealed further subdivision and gene flow among clusters. The three main domains divergence was ancient (15 mya), and all three went through a bottleneck corresponding to the LGM. Approximately 17% of P. abies Nordic domain migrated from P. obovata ~103K years ago, when both species had much larger effective population sizes. Our analysis of genomewide polymorphism data thus revealed the complex demographic history of Picea genus in Western Europe and highlighted the importance of material transfer in Swedish breeding program

Activation of human smooth muscle BK channels by hydrochlorothiazide requires cell integrity and the presence of BK β1 subunit

Thiazide-like diuretics are the most commonly used drugs to treat arterial hypertension, with their efficacy being linked to their chronic vasodilatory effect. Previous studies suggest that activation of the large conductance voltage- and Ca2+-dependent K+ (BK) channel (Slo 1, MaxiK channel) is responsible for the thiazide-induced vasodilatory effect. But the direct electrophysiological evidence supporting this claim is lacking. BK channels can be associated with one small accessory β-subunit (β1–β4) that confers specific biophysical and pharmacological characteristics to the current phenotype. The β1-subunit is primarily expressed in smooth muscle cells (SMCs). In this study we investigated the effect of hydrochlorothiazide (HCTZ) on BK channel activity in native SMCs from human umbilical artery (HUASMCs) and HEK293T cells expressing the BK channel (with and without the β1-subunit). Bath application of HCTZ (10 µmol/L) significantly augmented the BK current in HUASMCs when recorded using the whole-cell configurations, but it did not affect the unitary conductance and open probability of the BK channel in HUASMCs evaluated in the inside-out configuration, suggesting an indirect mechanism requiring cell integrity. In HEK293T cells expressing BK channels, HCTZ-augmented BK channel activity was only observed when the β1-subunit was co-expressed, being concentration-dependent with an EC50 of 28.4 µmol/L, whereas membrane potential did not influence the concentration relationship. Moreover, HCTZ did not affect the BK channel current in HEK293T cells evaluated in the inside-out configuration, but significantly increases the open probability in the cell-attached configuration. Our data demonstrate that a β1-subunit-dependent mechanism that requires SMC integrity leads to HCTZ-induced BK channel activation.Instituto de Estudios Inmunológicos y Fisiopatológico

Comparison of Protein- or Amino Acid-Based Supplements in the Rehabilitation of Men with Severe Obesity: A Randomized Controlled Pilot Study

Background: Weight loss is associated with a reduction in all body compartments, including muscle mass (MM), and this effect produces a decrease in function and muscle strength. Our objective was to assess the impact of protein or amino acid supplements on MM loss in middle-aged men (age 35 kg/m2) during weight loss. Materials and Methods: We conducted a single-site randomized controlled trial (Clinicaltrials.gov NCT05143398) with 40 in-patient male subjects with severe obesity. Participants underwent an intervention program consisting of a low-calorie balanced diet and structured physical activity. They were randomly assigned to 4-week treatment groups: (1) control (CTR, N = 10), (2) protein (P, N = 10), (3) branched-chain amino acid (BCAA, N = 10), and (4) essential amino acid mixture with tricarboxylic acid cycle intermediates (PD-E07, N = 10) supplementation. Results: Following 4 weeks of intervention, all groups showed similar reductions in body weight compared to baseline. When examining the delta values, a notable increase in muscle mass (MM) was observed in the PD-E07 intervention group [MM (kg): 2.84 ± 3.57; MM (%): 3.63 ± 3.14], in contrast to the CTR group [MM (kg): −2.46 ± 3.04; MM (%): −0.47 ± 2.28], with a statistical significance of p = 0.045 and p = 0.023, respectively. However, the MM values for the P group [MM (kg): −2.75 ± 5.98, p = 0.734; MM (%): −0.44 ± 4.02, p = 0.990] and the BCAA group [MM (kg): −1 ± 3.3, p = 0.734; MM (%): 0.34 ± 2.85, p = 0.956] did not exhibit a statistically significant difference when compared to the CTR group. Conclusions: Amino acid-based supplements may effectively mitigate the loss of MM typically observed during weight reduction. Further validation through large-scale studies is necessary

FIRST LINE AVELUMAB IN PD-L1+VE METASTATIC OR LOCALLY ADVANCED UROTHELIAL CANCER (AUC) PATIENTS UNFIT FOR CISPLATIN (CIS): THE ARIES TRIAL

Background: Avelumab (ave) was approved as maintenance therapy after platinum-based first line (1L) therapy for patients (pts) with aUC based on ph. 3 Javelin Bladder 100 study (NCT02603432), showing significant overall survival (OS) improvement. Here we tested the activity of ave as 1L of therapy in pts with aUC and PD-L1+ve expression. Methods: ARIES is a single-arm, multi-site, open-label phase II trial. Enrolled pts had aUC, were cis-unfit (at least one of: ECOG-PS=2, CrCl <60 mL/min, grade ⩾2 peripheral neuropathy/hearing loss, progression within 6-mos before the end of neo/adj chemo), had not previously received chemo for aUC and PD-L1⩾5% (SP263) centrally assessed. Pts received ave 10 mg/Kg IV Q2W until progression, unacceptable toxicity and withdrawal, whichever occurred first. The primary endpoint was the 1-year OS. Key secondary endpoints were median-OS, -PFS, ORR, DOR and safety. The outcome based on PDL1 expression >10 has also been investigated. Results: A total of 198 eligible cis-unfit pts have been tested for PD-L1 and 71 (35.6%) have been found positive. Among enrolled patients (N=71), median age was 75 y, 35 (49.3%) had visceral disease, and 22 (31.0%) had ECOG-PS=2; 50 (70.4%) had CrCl <60 mL/min and 9 (12.7%) progressed within 6-mos from the end of neo/adj chemo. At the cut-off data (Feb 2, 2022), median follow up was 10.0 mos and 14 patients are still on treatment. The median OS was 10.0 mos (95% CI, 5.5-14.5), and 43.0% of patients were alive at 1-year. The ORR for all patients was 24.0%; complete response, 8.5% (n=6); partial response, 15.5% (n=11). Clinical benefit was 43.6% (n=31). Median PFS was 2.0 mos (95% CI, 1.7-2.3). Among the 17 pts who had tumour response 13 had DOR > 1y and 5 > 2y. A total of 67 patients have been evaluated for CPS and among these 56 (83.6%) have been classified as high expression. The median OS was 11.0 mos (95%CI, 0.1 – 22.9) for those with high CPS and 7.0 mos (95%CI 2.8 – 11.2) for low CPS (p=0.13). The median PFS was 2.0 mos for both high and low CPS (p=0.34). Five (7.0%) grade 3 ave-related adverse events, and no treatment-related death were reported. Conclusions: Ave is active and safe in pts with cis-unfit, PD-L1+ve aUC and poor baseline characteristics