Vintage Capital and the Dynamics of the AK Model

This paper analyzes the equilibrium dynamics of an AK-type endogenous growth model with vintage capital. The inclusion of vintage capital leads to oscillatory dynamics governed by replacement echoes, which additionally influence the intercept of the balanced growth path. These features, which are in sharp contrast to those from the standard AK model, can contribute to explaining the short-run deviations observed between investment and growth rates time series. To characterize the convergence properties and the dynamics of the model we develop analytical and numerical methods that should be of interest for the general resolution of endogenous growth models with vintage capital.

Enhanced expression of the voltage-dependent anion channel 1 (VDAC1) in Alzheimer's disease transgenic mice: an insight into the pathogenic effects of amyloid-β

The mitochondrial voltage-dependent anion channel 1 (VDAC1) is involved in the release of apoptotic proteins with possible relevance in Alzheimer's disease (AD) neuropathology. Through proteomic analysis followed by Western blotting and immunohistochemical techniques, we have found that VDAC1 is overexpressed in the hippocampus from amyloidogenic AD transgenic mice models. VDAC1 was also overexpressed in postmortem brain tissue from AD patients at an advanced stage of the disease. Interestingly, amyloid-β (Aβ) soluble oligomers were able to induce upregulation of VDAC1 in a human neuroblastoma cell line, further supporting a correlation between Aβ levels and VDAC1 expression. In hippocampal extracts from transgenic mice, a significant increase was observed in the levels of VDAC1 phosphorylated at an epitope that is susceptible to phosphorylation by glycogen synthase kinase-3β, whose activity was also increased. The levels of hexokinase I (HXKI), which interacts with VDAC1 and affects its function, were decreased in mitochondrial samples from AD models. Since phospho-VDAC and reduced HXKI levels favors a VDAC1 conformational state more prone to the release proapoptotic factors, regulation of the function of this channel may be a promising therapeutic approach to combat AD

Computer simulation study of the nematic–vapour interface in the Gay–Berne model

We present computer simulations of the vapour–nematic interface of the Gay–Berne model. We considered situations which correspond to either prolate or oblate molecules. We determine the anchoring of the nematic phase and correlate it with the intermolecular potential parameters. On the other hand, we evaluate the surface tension associated to this interface. We find a corresponding states law for the surface tension dependence on the temperature, valid for both prolate and oblate molecules.Fundación Portuguesa para la Ciencia y la Tecnología EXCL / FIS-NAN / 0083/2012Ministerio de Economía y Competitividad FIS2012-32455Junta de Andalucía P09-FQM-493

Initiatives and facilities for E&T in the nuclear science and technology master at UPM

The present Master/Doctorate in Nuclear Science and Technology programme implemented in the Department of Nuclear Engineering of the Universidad Politécnica de Madrid (NED-UPM) has the excellence qualification by the Spanish Ministry of Education. One of the main of this programme is the training for the development of methodologies of simulation, design and advanced analysis, including experimental tools, necessary in research and in professional work in the nuclear field

Nature-based strategies to regenerate the functioning and biodiversity of vineyards

16 páginas.- 2 figuras.- 1 Box.- 138 referenciasGrapevine is one of the most important perennial fruit crops worldwide. Historically, vineyards were compatible with soil conservation practices and multitrophic biodiversity, but vineyards are now generally eroded and biologically impoverished, making them more susceptible to pests and diseases. However, the idiosyncrasy of the wine sector places wine growers in a unique position to lead the adoption of a range of sustainable management strategies and, thus, to pioneer a wider transformation of the agricultural sector. In this article, we provide an overview of nature-based management strategies that may be used for the regeneration of the functioning and biodiversity of vineyards and that may also lead to improved plant nutrition, grape berry quality and the suppression of pathogens and pests. These strategies include the use of microbial and nonmicrobial biostimulants, fertilization with organic amendments as well as foliar fertilization with nature-based products, the use of cover crops and the reintegration of livestock in vineyards, especially sheep. We will also pay special attention to the implementation of circular economy in the vineyard in relation to the previously mentioned management strategies and will also discuss the importance of considering all these aspects from a holistic and integrative perspective, rather than taking them into account as single factors. Assuming the integral role of soils in the functioning of agroecosystems, soils will be considered transversally across all sections. Finally, we will argue that the time is now ripe for innovation from the public and private sectors to contribute to the sustainable management of vineyards while maintaining, or even improving, the profit margin for farmers and winemakers.This review article is, in part, the result of a workshop (I Jornadas ‘Suelos Vivos’ para la regeneración de la vida en suelos de viñedos gaditanos; https://suelosvivos.es/i-jornadas-suelos-vivos/) carried out within the context of the ‘Suelos Vivos’ Regional Operational Group of the EIP-Agri, which was celebrated between 23 and 24 March 2023 in Puerto Real, Cádiz. Raúl Ochoa-Hueso was supported by the Ramón y Cajal programme from the MICINN (RYC-2017 22032), by the Spanish Ministry of Science and Innovation for the I + D + i project PID2019-106004RA-I00 funded by MCIN/AEI/10.13039/501100011033, by the Fondo Europeo de Desarrollo Regional (FEDER) y la Consejería de Transformación Económica, Industria, Conocimiento y Universidades of the Junta de Andalucía (FEDER Andalucía 2014-2020 Objetivo temático ‘01 - Refuerzo de la investigación, el desarrollo tecnológico y la innovación’): P20_00323 (FUTUREVINES), and by the Fondo Europeo Agrícola de Desarrollo Rural (FEADER) through the ‘Ayudas a Grupos operativos de la Asociación Europea de Innovación (AEI) en materia de productividad y sostenibilidad agrícolas’, Referencia: GOPC-CA-20-0001. Manuel Delgado-Baquerizo acknowledges support from TED2021-130908B-C41/AEI/10.13039/501100011033/Unión Europea NextGenerationEU/PRTR and from the Spanish Ministry of Science and Innovation for the I + D + i project PID2020-115813RA-I00 funded by MCIN/AEI/10.13039/501100011033. Cristina Lazcano acknowledges support from the California Department of Food and Agriculture (21-0433-021-SF) and the Foundation for Food and Agriculture Research (FFAR, CA21-SS-0000000193). Lilia Serrano-Grijalva thanks the European Union's Horizon 2020 research and innovation programme who funded her work under the Marie Skłodowska-Curie Grant Agreement No. 890874Peer reviewe

Variable frequency of LRRK2 variants in the Latin American research consortium on the genetics of Parkinson's disease (LARGE-PD), a case of ancestry

ABSTARCT: Mutations in Leucine-Rich Repeat Kinase 2 (LRRK2), primarily located in codons G2019 and R1441, represent the most common genetic cause of Parkinson's disease in European-derived populations. However, little is known about the frequency of these mutations in Latin American populations. In addition, a prior study suggested that a LRRK2 polymorphism (p.Q1111H) specific to Latino and Amerindian populations might be a risk factor for Parkinson's disease, but this finding requires replication. We screened 1734 Parkinson's disease patients and 1097 controls enrolled in the Latin American Research Consortium on the Genetics of Parkinson's disease (LARGE-PD), which includes sites in Argentina, Brazil, Colombia, Ecuador, Peru, and Uruguay. Genotypes were determined by TaqMan assay (p.G2019S and p.Q1111H) or by sequencing of exon 31 (p.R1441C/G/H/S). Admixture proportion was determined using a panel of 29 ancestry informative markers. We identified a total of 29 Parkinson's disease patients (1.7%) who carried p.G2019S and the frequency ranged from 0.2% in Peru to 4.2% in Uruguay. Only two Parkinson's disease patients carried p.R1441G and one patient carried p.R1441C. There was no significant difference in the frequency of p.Q1111H in patients (3.8%) compared to controls (3.1%; OR 1.02, p = 0.873). The frequency of LRRK2-p.G2019S varied greatly between different Latin American countries and was directly correlated with the amount of European ancestry observed. p.R1441G is rare in Latin America despite the large genetic contribution made by settlers from Spain, where the mutation is relatively common

Prevalence of abnormal Alzheimer’s disease biomarkers in patients with subjective cognitive decline: cross-sectional comparison of three European memory clinic samples

Introduction: Subjective cognitive decline (SCD) in cognitively unimpaired older individuals has been recognized as an early clinical at-risk state for Alzheimer's disease (AD) dementia and as a target population for future dementia prevention trials. Currently, however, SCD is heterogeneously defined across studies, potentially leading to variations in the prevalence of AD pathology. Here, we compared the prevalence and identified common determinants of abnormal AD biomarkers in SCD across three European memory clinics participating in the European initiative on harmonization of SCD in preclinical AD (Euro-SCD). Methods: We included three memory clinic SCD samples with available cerebrospinal fluid (CSF) biomaterial (IDIBAPS, Barcelona, Spain, n = 44; Amsterdam Dementia Cohort (ADC), The Netherlands, n = 50; DELCODE multicenter study, Germany, n = 42). CSF biomarkers (amyloid beta (Aβ)42, tau, and phosphorylated tau (ptau181)) were centrally analyzed in Amsterdam using prespecified cutoffs to define prevalence of pathological biomarker concentrations. We used logistic regression analysis in the combined sample across the three centers to investigate center effects with regard to likelihood of biomarker abnormality while taking potential common predictors (e.g., age, sex, apolipoprotein E (APOE) status, subtle cognitive deficits, depressive symptoms) into account. Results: The prevalence of abnormal Aβ42, but not tau or ptau181, levels was different across centers (64% DELCODE, 57% IDIBAPS, 22% ADC; p < 0.001). Logistic regression analysis revealed that the likelihood of abnormal Aβ42 (and also abnormal tau or ptau181) levels was predicted by age and APOE status. For Aβ42 abnormality, we additionally observed a center effect, indicating between-center heterogeneity not explained by age, APOE, or the other included covariates. Conclusions: While heterogeneous frequency of abnormal Aβ42 was partly explained by between-sample differences in age range and APOE status, the additional observation of center effects indicates between-center heterogeneity that may be attributed to different recruitment procedures. These findings highlight the need for the development of harmonized recruitment protocols for SCD case definition in multinational studies to achieve similar enrichment rates of preclinical AD

Combined impact of healthy lifestyle factors on risk of asthma, rhinoconjunctivitis and eczema in school children: ISAAC phase III

Background Asthma is not the key focus of prevention strategies. A Healthy Lifestyle Index (HLI) was developed to examine the combined effect of modifiable lifestyle factors on asthma, rhinoconjunctivitis and eczema using data from the International Study of Asthma and Allergies in Childhood (ISAAC) phase III. Methods Information on symptoms of asthma, rhinoconjunctivitis, eczema and several lifestyle factors was obtained from children aged 6-7 years through written questionnaires. The HLI combined five lifestyle factors: no parental smoking, child's adherence to Mediterranean diet, child's healthy body mass index, high physical activity and non-sedentary behaviour. The association between the HLI and risk of asthma, rhinoconjunctivitis and eczema was evaluated using multilevel mixed-effects logistic regression models. Findings Data of 70 795 children from 37 centres in 19 countries were analysed. Each additional healthy lifestyle factor was associated with a reduced risk of current wheeze (OR 0.87, 95% CI 0.84 to 0.89), asthma ever (OR 0.89, 95% CI 0.87 to 0.92), current symptoms of rhinoconjunctivitis (OR 0.95, 95% CI 0.92 to 0.97) and current symptoms of eczema (OR 0.92, 95% CI 0.92 to 0.98). Theoretically, if associations were causal, a combination of four or five healthy lifestyle factors would result into a reduction up to 16% of asthma cases (ranging from 2.7% to 26.3 % according to region of the world). Conclusions These findings should be interpreted with caution given the limitations to infer causality from cross-sectional observational data. Efficacy of interventions to improve multiple modifiable lifestyle factors to reduce the burden asthma and allergy in childhood should be assessed

Activity of venetoclax in patients with relapsed or refractory chronic lymphocytic leukaemia: analysis of the VENICE-1 multicentre, open-label, single-arm, phase 3b trial

Background: Most patients with chronic lymphocytic leukaemia progress after treatment or retreatment with targeted therapy or chemoimmunotherapy and have limited subsequent treatment options. Response levels to the single-agent venetoclax in the relapsed setting is unknown. We aimed to assess venetoclax activity in patients with or without previous B-cell receptor-associated kinase inhibitor (BCRi) treatment. Methods: This multicentre, open-label, single-arm, phase 3b trial (VENICE-1) assessed activity and safety of venetoclax monotherapy in adults with relapsed or refractory chronic lymphocytic leukaemia, stratified by previous exposure to a BCRi. Eligible participants were aged 18 years or older with previously treated relapsed or refractory chronic lymphocytic leukaemia. Presence of del(17p) or TP53 aberrations and previous BCRi treatment were permitted. Patients received 5-week ramp-up to 400 mg of oral venetoclax once daily and were treated for up to 108 weeks, with 2 years follow-up after discontinuation, or optional extended access. The primary activity endpoint was complete remission rate (complete remission or complete remission with incomplete marrow recovery) in BCRi-naive patients. Analyses used the intent-to-treat (ie, all enrolled patients, which coincided with those who received at least one dose of venetoclax). This study was registered with ClinicalTrials.gov, NCT02756611, and is complete. Findings: Between June 22, 2016, and March 11, 2022, we enrolled 258 patients with relapsed or refractory chronic lymphocytic leukaemia (180 [70%] were male; 252 [98%] were White; 191 were BCRi-naive and 67 were BCRi-pretreated). Median follow-up in the overall cohort was 49·5 months (IQR 47·2–54·1), 49·2 months (47·2–53·2) in the BCRi-naive group, and 49·7 months (47·4–54·3) in the BCRi-pretreated group. Of 191 BCRi-naive patients, 66 (35%; 95% CI 27·8−41·8) had complete remission or complete remission with incomplete marrow recovery. 18 (27%; 95% CI 16·8–39·1) of 67 patients in the BCRi-pretreated group had complete remission or complete remission with incomplete marrow recovery. Grade 3 or worse treatment-emergent adverse events were reported in 203 (79%) and serious adverse events were reported in 136 (53%) of 258 patients in the overall cohort. The most common treatment-emergent adverse event was neutropenia (96 [37%]) and the most common and serious adverse event was pneumonia (21 [8%]). There were 13 (5%) deaths reported due to adverse events; one of these deaths (autoimmune haemolytic anaemia) was possibly related to venetoclax. No new safety signals were identified. Interpretation: These data demonstrate deep and durable responses with venetoclax monotherapy in patients with relapsed or refractory chronic lymphocytic leukaemia, including BCRi-pretreated patients, suggesting that venetoclax monotherapy is an effective strategy for treating BCRi-naive and BCRi-pretreated patients. Funding: AbbVie

Subcellular specificity of cannabinoid effects in striatonigral circuits

Recent advances in neuroscience have positioned brain circuits as key units in controlling behavior, implying that their positive or negative modulation necessarily leads to specific behavioral outcomes. However, emerging evidence suggests that the activation or inhibition of specific brain circuits can actually produce multimodal behavioral outcomes. This study shows that activation of a receptor at different subcellular locations in the same neuronal circuit can determine distinct behaviors. Pharmacological activation of type 1 cannabinoid (CB1) receptors in the striatonigral circuit elicits both antinociception and catalepsy in mice. The decrease in nociception depends on the activation of plasma membrane-residing CB1 receptors (pmCB1), leading to the inhibition of cytosolic PKA activity and substance P release. By contrast, mitochondrial-associated CB1 receptors (mtCB1) located at the same terminals mediate cannabinoid-induced catalepsy through the decrease in intra-mitochondrial PKA-dependent cellular respiration and synaptic transmission. Thus, subcellular-specific CB1 receptor signaling within striatonigral circuits determines multimodal control of behavior