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Abstract The principles of ergodicity and thermalization constitute the foundation of statistical mechanics, positing that a many-body system progressively loses its local information as it evolves. Nevertheless, these principles can be disrupted when thermalization dynamics lead to the conservation of local information, as observed in the phenomenon known as many-body localization. Quantum spin chains provide a fundamental platform for exploring the dynamics of closed interacting quantum many-body systems. This study explores the dynamics of a spin chain with $$S\ge 1/2$$ S ≥ 1 / 2 within the $$J_1-J_2,$$ incorporating a non-uniform magnetic field and single-ion anisotropy. Through the use of exact numerical diagonalization, we unveil that a nearly constant-gradient magnetic field suppresses thermalization, a phenomenon termed Stark many-body localization (SMBL), previously observed in $$S=1/2$$ S = 1 / 2 chains. Furthermore, our findings reveal that the sole presence of single-ion anisotropy is sufficient to prevent thermalization in the system. Interestingly, when the magnitudes of the magnetic field and anisotropy are comparable, they compete, favoring delocalization. Despite the potential hindrance of SMBL by single-ion anisotropy in this scenario, it introduces an alternative mechanism for localization. Our interpretation, considering local energetic constraints and resonances between degenerate eigenstates, not only provides insights into SMBL but also opens avenues for future experimental investigations into the enriched phenomenology of disordered free localized $$S\ge 1/2$$ S ≥ 1 / 2 systems.

Abstract Within the thymus, thymic epithelial cells (TECs) create dedicated microenvironments for T cell development and selection. Considering that TECs are sensitive to distinct pathophysiological conditions, uncovering the molecular elements that coordinate their thymopoietic role has important fundamental and clinical implications. Particularly, medullary thymic epithelial cells (mTECs) play a crucial role in central tolerance. Our previous studies, along with others, suggest that mTECs depend on molecular factors linked to genome-protecting pathways, but the precise mechanisms underlying their function remain unknown. These observations led us to examine the role of Foxo3, as it is expressed in TECs and involved in DNA damage response. Our findings show that mice with TEC-specific deletion of Foxo3 (Foxo3cKO) displayed a disrupted mTEC compartment, with a more profound impact on the numbers of CCL21+ and thymic tuft mTEClo subsets. At the molecular level, Foxo3 controls distinct functional modules in the transcriptome of cTECs and mTECs under normal conditions, which includes the regulation of ribosomal biogenesis and DNA damage response, respectively. These changes in the TEC compartment resulted in a reduced total thymocyte cellularity and specific changes in regulatory T cell and iNKT cell development in the Foxo3cKO thymus. Lastly, the thymic defects observed in adulthood correlated with mild signs of altered peripheral immunotolerance in aged Foxo3cKO mice. Moreover, the deficiency in Foxo3 moderately aggravated the autoimmune predisposition observed in Aire-deficient mice. Our findings highlight the importance of Foxo3 in preserving the homeostasis of TECs and in supporting their role in T cell development and tolerance.

ABSTRACT Dengue virus (DENV) infection is known to affect host cell metabolism, but the molecular players involved are still poorly known. Using a proteomics approach, we identified six DENV proteins associated with mitochondria isolated from infected hepatocytes, and most of the peptides identified were from NS3. We also found an at least twofold decrease of several electron transport system (ETS) host proteins. Thus, we investigated whether NS3 could modulate the ETS function by incubating recombinant DENV NS3 constructs in mitochondria isolated from mouse liver. We found that NS3pro (NS3 protease domain), but not the correspondent catalytically inactive mutant (NS3proS135A), impairs complex I (CI)-dependent NADH:ubiquinone oxidoreductase activity, but not the activities of complexes II, III, IV, or V. Accordingly, using high-resolution respirometry, we found that both NS3pro and full-length NS3 decrease the respiratory rates associated with malate/pyruvate oxidation in mitochondria. The NS3-induced impairment in mitochondrial respiration occurs without altering either leak respiration or mitochondria’s capacity to maintain membrane potential, suggesting that NS3 does not deeply affect mitochondrial integrity. Remarkably, CI activity is also inhibited in DENV-infected cells, supporting that the NS3 effects observed in isolated mitochondria may be relevant in the context of the infection. Finally, in silico analyses revealed the presence of potential NS3 cleavage sites in 17 subunits of mouse CI and 16 subunits of human CI, most of them located on the CI surface, suggesting that CI is prone to undergo proteolysis by NS3. Our findings suggest that DENV NS3 can modulate mitochondrial bioenergetics by directly affecting CI function.IMPORTANCEDengue virus (DENV) infection is a major public health problem worldwide, affecting about 400 million people yearly. Despite its importance, many molecular aspects of dengue pathogenesis remain poorly known. For several years, our group has been investigating DENV-induced metabolic alterations in the host cells, focusing on the bioenergetics of mitochondrial respiration. The results of the present study reveal that the DENV non-structural protein 3 (NS3) is found in the mitochondria of infected cells, impairing mitochondrial respiration by directly targeting one of the components of the electron transport system, the respiratory complex I (CI). NS3 acts as the viral protease during the DENV replication cycle, and its proteolytic activity seems necessary for inhibiting CI function. Our findings uncover new nuances of DENV-induced metabolic alterations, highlighting NS3 as an important player in the modulation of mitochondria function during infection.

Abstract Excessive salts in irrigation water and water stress have a negative impact on the productive yield of agricultural crops. In this regard, the objective was to evaluate the effect of combined saline and water stress on the agronomic performance of the beet crop. The experiment was conducted in a greenhouse located at the Universidade da Integração Internacional da Lusofonia Afro-Brasileira, in Redenção, Ceará. The experimental design used was completely randomized with split-plots arrangement. The main plots were formed by the electrical conductivities of the irrigation water (0.8, 1.5, 3.0, 4.5, and 6.0 dS m-1), while the irrigation depths of 50 and 100% of the crop evapotranspiration (ETc) were the subplots, with 6 replications. Saline stress negatively affected growth, biomass, tuber root length, and productivity, while increasing the soluble solids of the beet crop. Excessive salts in the irrigation water caused reductions in physiological indices of the beet crop, although with less severity under the 100% ETc.

Background: In 2004, the International Pharmaceutical Federation (FIP) adopted a Statement of Professional Standard on the supply of medicines affecting driving performance, transformed to FIP guidelines in 2014. In 2011, the final report from the European initiative on Driving Under the Influence of Drugs, Alcohol and Medicines (DRUID) was published. Both documents provided recommendations for improving dispensing guidelines for driving-impairing medicines for patients who use psychoactive medicines. Objective: This study investigated the extent that European professional organizations of pharmacists (POPs) implemented existing guidelines and DRUID results. Methods: An online questionnaire survey was conducted in April–May 2022. Questionnaires were sent by e-mail to POPs in 46 European countries. The questionnaire addressed the following topics: awareness of FIP guidelines and DRUID outcomes (a), development of dispensing guidelines (b), target groups for information materials (c), evaluations of dispensing practices (d), examples of projects on medicines affecting driving fitness (e), development of ICT (Information and Communication Technology) -support (f), collaboration with organizations of physicians (g), and patients (h). The data were analyzed by indicating implementation initiatives in different countries. Open-ended questions were assessed qualitatively. Results: POPs in 23 European countries responded to the invitation (response rate: 50%). Guidelines for improving dispensing practices were available in 5 countries targeted at professionals, patients, and the general population. Patient and physician organizations were involved in 4 and 3 countries, respectively. Implementation was supported by computerized dispensing systems (5 countries) and public campaigns (5 countries). Conclusions: Twenty years after the introduction of FIP guidelines and ten years after the DRUID outcomes, only 5 European POPs have implemented this knowledge. Different activities were performed to support implementation, resulting in examples of successful use of recommendations for driving-impairing medicines in pharmacy practice. Implementation needs further attention. The successful practices that have been developed are an example for dissemination to other countries.

Neutral sodium (Na i ) is an alkali metal with a favorable absorption cross section such that tenuous gases are easily illuminated at select transiting exoplanet systems. We examine both the time-averaged and time-series alkali spectral flux individually, over 4 nights at a hot Saturn system on a ∼2.8 day orbit about a Sun-like star WASP-49 A. Very Large Telescope/ESPRESSO observations are analyzed, providing new constraints. We recover the previously confirmed residual sodium flux uniquely when averaged, whereas night-to-night Na i varies by more than an order of magnitude. On HARPS/3.6 m Epoch II, we report a Doppler redshift at v _Γ,NaD = + 9.7 ± 1.6 km s ^−1 with respect to the planet’s rest frame. Upon examining the lightcurves, we confirm night-to-night variability, on the order of ∼1%–4% in NaD, rarely coinciding with exoplanet transit, not readily explained by stellar activity, starspots, tellurics, or the interstellar medium. Coincident with the ∼+10 km s ^−1 Doppler redshift, we detect a transient sodium absorption event dF _NaD / F _⋆ = 3.6% ± 1% at a relative difference of Δ F _NaD ( t ) ∼ 4.4% ± 1%, lasting Δ t _NaD ≳ 40 minutes. Since exoplanetary alkali signatures are blueshifted due to the natural vector of radiation pressure, estimated here at roughly ∼−5.7 km s ^−1 , the radial velocity is rather at +15.4 km s ^−1 , far larger than any known exoplanet system. Given that the redshift magnitude v _Γ is in between the Roche limit and dynamically stable satellite orbits, the transient sodium may be a putative indication of a natural satellite orbiting WASP-49 A b.

Abstract Uncaria tomentosa is a plant native to the Amazon that has immunomodulatory and antitumor properties due to the alkaloids found in the plant, being able to modify the immune response by potentiating or suspending the action of cytokines secreted by macrophages that induce the immune response, either by the classical route (M1) or through the alternative route (M2). Macrophages activated by M1 convert L-arginine into L-citrulline and nitric oxide (NO), whereas macrophages activated by the M2 pathway use the enzymatic activity of arginase to convert the same substrate into L-ornithine and urea. The aim of this work was to evaluate the immunostimulating activity of the crude hydroalcoholic extract from the bark of the U. tomentosa stem in RAW 264.7 macrophages. Concentrations of 0.2, 0.1 and 0.05 mg/mL of U. tomentosa extract associated with LPS, INF-γ and IL-4 inducers were tested by determining NO production and arginase enzyme activity. Nitric oxide production was enhanced by the extract when associated with LPS and LPS + INF-γ inducers. In the activity of the arginase enzyme, the extract decreased the stimulation of IL-4 on the enzyme, mainly at 0.2 mg/mL concentration. Therefore, it is concluded that the crude hydroalcoholic extract of the stem bark of U. tomentosa in RAW 264.7 cells, at a concentration of 0.2 mg/mL, showed considerable pro-inflammatory activity.

Abstract Recent studies have shown that the addition of non-viable microbial biomass or their components (postbiotics) to fish feed can modulate the gut microbiome and positively influence fish health in aquaculture systems. However, no information was hitherto available on the use of non-viable microbial biomass to manipulate aquaculture bacterioplankton communities. To fill this gap, here we used an in vitro model to assess the effects of heat-killed biomasses of an antagonistic strain Pseudoalteromonas rubra SubTr2 and a non-antagonist strain Escherichia coli DH5α on bacterioplankton communities of a recirculating aquaculture system (RAS). Our results showed that these biomasses can have generalist and species-specific effects on aquaculture bacterioplankton structure and function. In addition, they enriched the abundance of bacterial predators, reduced bacterial load and potentially influenced nutrient cycling and pathogen development in aquaculture water. Despite its preliminary nature, for the first time, this study showed that heat-killed microbial biomass has potential application as an in situ modulator of bacterioplankton in aquaculture systems.

The effect of thermal pasteurization (TP, 62.5 °C/30 min—conditions similar to those used in milk banks/hospitals, known as Holder pasteurization) and high-pressure pasteurization (HPP: 400–625 MPa/2.5–30 min) was studied on immunoglobulin (IgG, IgM and IgA) content, lysozyme activity and microbial load of donkey colostrum (in this case, after 40 days at 4 °C). IgG level remained unchanged with HPP at 400 MPa, increased up to 4-fold at 625 MPa/10 min and decreased 90% with TP, while IgM decreased progressively with pressure treatment intensity increment to below the detection limit at 625 MPa and decreased 20% with TP. IgA decreased to below the detection limit after TP and all HPP treatments. Lysozyme activity presented overall a higher decrease after TP (37%) compared to HPP (decreasing from 20% at 400 MPa to about 40% at 600 MPa/10 and 30 min). Furthermore, both total aerobic mesophiles and Enterobacteriaceae remained below detection limits after 40 days of refrigerated storage for both TP and HPP. So, HPP can be considered a potential alternative to the conventional TP to preserve donkey colostrum, with overall equal to better retention, particularly for IgG and lysozyme activity. As far as the authors are aware, this is the first study evaluating the effects of HPP on donkey colostrum, and research in this field should be pursued.

The recent discoveries of Neptune-sized ultra-short-period planets (USPs) challenge existing planet formation theories. It is unclear whether these residents of the Hot Neptune Desert have similar origins to smaller, rocky USPs, or if this discrete population is evidence of a different formation pathway altogether. We report the discovery of TOI-3261b, an ultrahot Neptune with an orbital period P = 0.88 day. The host star is a V = 13.2 mag, slightly supersolar metallicity ([Fe/H] ≃0.15), inactive K1.5 main-sequence star at d = 300 pc. Using data from the Transiting Exoplanet Survey Satellite and the Las Cumbres Observatory Global Telescope, we find that TOI-3261b has a radius of ${3.82}_{-0.35}^{+0.42}$ R _⊕ . Moreover, radial velocities from ESPRESSO and HARPS reveal a mass of ${30.3}_{-2.4}^{+2.2}$ M _⊕ , more than twice the median mass of Neptune-sized planets on longer orbits. We investigate multiple mechanisms of mass loss that can reproduce the current-day properties of TOI-3261b, simulating the evolution of the planet via tidal stripping and photoevaporation. Thermal evolution models suggest that TOI-3261b should retain an envelope potentially enriched with volatiles constituting ∼5% of its total mass. This is the second highest envelope mass fraction among ultrahot Neptunes discovered to date, making TOI-3261b an ideal candidate for atmospheric follow-up observations.

Abstract The Covid-19 pandemic, caused by SARS-CoV-2, has resulted in over 6 million reported deaths worldwide being one of the biggest challenges the world faces today. Here we present optimizations of all steps of an enzyme-linked immunosorbent assay (ELISA)-based test to detect IgG, IgA and IgM against the trimeric spike (S) protein, receptor binding domain (RBD), and N terminal domain of the nucleocapsid (N-NTD) protein of SARS-CoV-2. We discuss how to determine specific thresholds for antibody positivity and its limitations according to the antigen used. We applied the assay to a cohort of 126 individuals from Rio de Janeiro, Brazil, consisting of 23 PCR-positive individuals and 103 individuals without a confirmed diagnosis for SARS-CoV-2 infection. To illustrate the differences in serological responses to vaccinal immunization, we applied the test in 18 individuals from our cohort before and after receiving ChAdOx-1 nCoV-19 or CoronaVac vaccines. Taken together, our results show that the test can be customized at different stages depending on its application, enabling the user to analyze different cohorts, saving time, reagents, or samples. It is also a valuable tool for elucidating the immunological consequences of new viral strains and monitoring vaccination coverage and duration of response to different immunization regimens.

ABSTRACT: Few studies have been published on the body growth of replacement dairy heifers from Jersey (JER) and Holstein × Gyr (H × G) breeds, as most of them have focused on Holstein (HOL) heifers. In addition, HOL genetics vary significantly across countries. Our goal was to study the body growth curves of 3 distinct genetic groups of heifers (HOL, H × G, and JER) using data from Brazilian commercial dairy herds. Heart girth [to estimate body weight (BW)], hip height (HH), and withers height (WH) were measured. Weights (heifers and cows) and heights (only heifers) were collected from animals in several herds for each genetic group to model and describe the growth rates, mature body weight (MBW), weights, and heights for the recommended age at first breeding (RAFB) and first calving (RAFC). The RAFB values for HOL, H × G, and JER cattle were 15, 18, and 13 mo, respectively. The RAFC values for HOL, H × G, and JER cattle were 24, 27, and 22 mo, respectively. Data were obtained from 18 dairy farms located in 4 Brazilian states and analyzed using nonlinear modeling. Data were collected from 2,266 animals: 878 HOL, 610 H × G, and 778 JER cattle. We observed different body growth patterns in each genetic group. Jersey cattle matured earlier than HOL and H × G, especially for BW and HH. Mature BW of the HOL, H × G, and JER cattle was 681, 607, and 440 kg, respectively. All genetic groups reached the recommended BW at RAFB. However, the genetic groups did not reach the recommended BW at RAFC. Average daily weight gain from weaning to RAFB was 0.84, 0.53, and 0.54 kg/d for HOL, H × G, and JER cattle, respectively. Average daily gain from RAFB to RAFC was 0.53, 0.42, and 0.48 kg/d for HOL, H × G, and JER cattle, respectively. The HH at RAFB and RAFC were 130 and 139 cm for HOL, 130 and 137 cm for H × G, and 114 and 124 cm for JER. Withers height at RAFB and RAFC were 125 and 134 cm, 125 and 134 cm, and 110 and 121 cm for HOL, H × G, and JER cattle, respectively. In general, the rearing practices were adequate to reach the recommended BW at RAFB but below the recommended BW at RAFC for all genetic groups. In addition, each genetic group demonstrated different body growth patterns, especially for BW.

Background: Myxomatous mitral valve degeneration (MMVD) is the most common heart disease affecting small dogs, it reduces cardiac output resulting in compensatory adaptation of the autonomic nervous system. Chronically it leads to reduced heart rate variability (HRV) which is an accurate marker for autonomic balance. More than two decades ago in human medicine an indicator of autonomic balance that happens after a premature ventricular beat, it was described as heart rate turbulence (HRT). In humans with ischaemic heart disease the absence of HRT has proven to be a more accurate and an independent indicator of mortality than known HRV parameters. Currently there are very few studies of HRT in dogs and it is still not tested in small dogs within different stages of myxomatous mitral valve disease. Aim: The aim of this study was to assess the HRT indicators, onset and slope, in small dogs with myxomatous mitral valve disease and to statistically test it. Methods: Dogs under 25 kg had electrocardiogram and echocardiography performed and, in some patients, holter monitoring was carried out. Data was divided into groups B1, B2, C and D for mean comparison with ANOVA and Tukey test. In addition, Receiver Operating Characteristic (ROC) curve for differentiating among symptomatic and asymptomatic dogs and for differentiating between remodeled and non-remodeled hearts. The Pearson was executed after correlations of TO and TS with commonly used echocardiographic parameters. Results: Variance analyses held significant differences in TO and TS between stages B1 from stages C and D, while B2 held similarity to the other groups. In the Receiver Operating Curve(ROC) was found a very good AUC for differentiating among symptomatic and asymptomatic dogs and remodeled and non-remodeled dogs. Few echocardiography parameters held weak correlation with TO while others held weak to moderate correlation with TS. Conclusion: In dogs with MMVD and without other diseases, heart rate turbulence is a feasible indicator for autonomic balance. Our result suggests HRT changes as the MMVD progresses and CHF is present. More studies with HRT are needed. The number of VPCs may be the strongest limitation for the technique.

A fast Monte Carlo technique to simulate equatorial ionospheric scintillation on global navigation satellite system signals is proposed. The algorithm uses a single-layer phase-screen model of the ionosphere and the scintillation is expressed as a Huygens-Fresnel integral (HFI). By assuming a specially-tailored random phase screen, the HFI can be expressed in closed form as a combination of Fresnel integrals. We statistically characterize the amplitude and phase computed by the HFI for different values of the scintillation index S4. Results for the L1, L2, and L5 bands were obtained and compared with real data, showing good agreement. Some of the advantages of the proposed technique are: (a) the amplitude and phase of the scintillation process are simultaneously obtained; (b) arbitrarily long ionospheric scintillation time series with pre-defined stationary characteristics are synthesized; and (c) several scintillation time series corresponding to different carrier frequencies are generated using a common phase-screen model.

Background: Vaccination against COVID-19 was implemented very quickly, but the emergence of new variants that can evade the previous acquired immunological protection highlights the importance of understanding the mechanisms involved in the immune response generated after SARS-CoV-2 infection or vaccination. Objectives: Since most of our knowledge on the humoral immunity generated against SARS-CoV-2 has been obtained from studies with infected patients before vaccination, our goal here was to evaluate seroconversion and its correlation with the titers of neutralizing antibodies (NAbs) in individuals who received the complete initial recommended vaccination schedule with three different vaccines. Study design: We analyzed serum IgG, IgA and total NAbs against the trimeric SARS-CoV-2 Spike (S) protein or its receptor binding domain (RBD) in blood samples collected from 118 healthy individuals without known previous infection, before and after receiving the first and the second dose of CoronaVac (n = 18), ChAdOx-1 (n = 68) or BNT162b2 (n = 32) vaccines. Results: We found that although IgG titers were high in all sera collected after the two doses of these vaccines, NAbs amounts varies among the groups. In contrast, serum NAbs concentrations were much more comparable to the IgA levels, indicating that these antibodies would have a major neutralizing capacity against SARS-CoV-2. Conclusions: Altogether our data suggest that quantification of serum anti-S or anti-RBD IgA, rather than IgG, may be a valuable tool to screen NAbs and may be considered for surveillance of vaccine coverage.

Objetivou-se avaliar a inclusão de ureia na dieta de cabritos sobre o desempenho e características de carcaça. Foram utilizados 18 cabritos (150 dias de idade e 21 Kg de peso) distribuídos em dois grupos com dietas isoproteicas. Os animais do grupo controle (GC) foram alimentados com ração sem ureia na sua composição, enquanto os animais do outro grupo (GU) foram alimentados com ração com 1% da MS de ureia na base da matéria seca. Avaliou-se o ganho de peso médio (g/dia), biometrias corporais, assim como o peso e rendimento de carcaça nos animais. Não houve diferenças significativas em nenhuma das variáveis estudadas (p>0,05), como: ganho de peso (g/dia) (GU: 122,1 ± 11,89 vs GC: 132,9 ± 4,97), perímetro torácico (cm) (GU: 73,0 ± 1,2 vs GC: 74,5 ± 0,57), comprimento corporal (cm) (GU: 74,0 ± 1,42 vs GC: 73,67 ± 0,70), peso ao abate (kg) (GU: 34,39 ± 1,76 vs GC: 36,56 ± 0,96), rendimentos de carcaça quente (%) (GU: 47,37 ± 0,82 vs GC: 47,23 ± 0,72) e fria (GU: 45,64 ± 0,60 vs GC: 45,84 ± 0,70). Conclui-se que o uso de 1% de ureia na MS da dieta de caprinos machos jovem não afeta o desempenho dos animais e as características de carcaça.

The design and synthesis of artificial receptors based on molecular imprinting (MI) technology for the development of a new MIP-based biosensor for detection of the stress biomarker α-amylase in human saliva in point-of-care (PoC) applications is described in this work. The portable electrochemical devices for monitoring α-amylase consists of cost-effective and disposable gold screen-printed electrodes (AuSPEs). To build the electrochemical device, the template biomolecule was firstly immobilized directly over the working area of the gold chip previously activated with a self-assembled monolayer (SAM) of cysteamine (CA). Then, pyrrole (Py) monomer was selected as building block of a polymeric network prepared by CV electropolymerization. After the electropolymerization process, the enzyme was removed from the polymer film in order to build the specific recognition sites for the target enzyme. The MIP biosensor showed a very wide linear concentration range (between 3.0 × 10−4 to 0.60 mg mL−1 in buffer solution and between 3.0 × 10−4 to 3.0 × 10−2 mg mL−1 in human saliva) and low detection levels were achieved (LOD < 3.0 × 10−4 mg mL−1) using square wave voltammetry (SWV) as the electroanalytical technique.

ABSTRACT: Electrocardiographic markers have been used in people to classify arrhythmogenic risk. The aims of this study were to investigate electrocardiographic markers of conduction and repolarization in Boxers and non-Boxer dogs, and compare such findings between groups. Ten-lead standard electrocardiograms of Boxer dogs and non-Boxers recorded from 2015 to 2018 were retrospectively reviewed. Dogs ≥4 years of age and weighing >20kg were included. Animals with valvular insufficiencies, congenital cardiopathies, cardiac dilation, suspected systolic dysfunction, biphasic T-wave, bundle branch blocks, and those receiving antiarrhythmics were excluded. Electrocardiographic markers of conduction, QRS duration (QRSd) and dispersion (QRSD), and repolarization (corrected QT interval, Tpeak-Tend, JT and JTpeak), as well as derived indices, were measured. Two hundred dogs met the inclusion/exclusion requirements, including 97 Boxers (8.1±2.5 years old; 30±7kg) and 103 non-Boxer (8.8±2.5 years old, 30±8kg). QRSd and QRSD, and repolarization markers in lead II and left precordial lead V4 were considered similar between groups. Dispersion of late repolarization on lead rV2, Tpeak-Tend interval, was considered longer in Boxers (45±8ms vs 38±10ms, P=0.01). The Tpeak-Tend/JTpeak and the JTpeak/JT also differed between groups. Our results indicate that the dispersion of myocardial late repolarization in lead rV2 is slower in Boxers than other dog breeds.

This paper describes the Eulerian urban dispersion model EPISODE. EPISODE was developed to address a need for an urban air quality model in support of policy, planning, and air quality management in the Nordic, specifically Norwegian, setting. It can be used for the calculation of a variety of airborne pollutant concentrations, but we focus here on the implementation and application of the model for NO2 pollution. EPISODE consists of an Eulerian 3D grid model with embedded sub-grid dispersion models (e.g. a Gaussian plume model) for dispersion of pollution from line (i.e. roads) and point sources (e.g. chimney stacks). It considers the atmospheric processes advection, diffusion, and an NO2 photochemistry represented using the photostationary steady-state approximation for NO2. EPISODE calculates hourly air concentrations representative of the grids and at receptor points. The latter allow EPISODE to estimate concentrations representative of the levels experienced by the population and to estimate their exposure. This methodological framework makes it suitable for simulating NO2 concentrations at fine-scale resolution ( m) in Nordic environments. The model can be run in an offline nested mode using output concentrations from a global or regional chemical transport model and forced by meteorology from an external numerical weather prediction model; it also can be driven by meteorological observations. We give a full description of the overall model function and its individual components. We then present a case study for six Norwegian cities whereby we simulate NO2 pollution for the entire year of 2015. The model is evaluated against in situ observations for the entire year and for specific episodes of enhanced pollution during winter. We evaluate the model performance using the FAIRMODE DELTA Tool that utilises traditional statistical metrics, e.g. root mean square error (RMSE), Pearson correlation R, and bias, along with some specialised tests for air quality model evaluation. We find that EPISODE attains the DELTA Tool model quality objective in all of the stations we evaluate against. Further, the other statistical evaluations show adequate model performance but that the model scores greatly improved correlations during winter and autumn compared to the summer. We attribute this to the use of the photostationary steady-state scheme for NO2, which should perform best in the absence of local ozone photochemical production. Oslo does not comply with the NO2 annual limit set in the 2008/50/EC directive (AQD). NO2 pollution episodes with the highest NO2 concentrations, which lead to the occurrence of exceedances of the AQD hourly limit for NO2, occur primarily in the winter and autumn in Oslo, so this strongly supports the use of EPISODE for application to these wintertime events. Overall, we conclude that the model is suitable for an assessment of annual mean NO2 concentrations and also for the study of hourly NO2 concentrations in the Nordic winter and autumn environment. Further, in this work we conclude that it is suitable for a range of policy applications specific to NO2 that include pollution episode analysis, evaluation of seasonal statistics, policy and planning support, and air quality management. Lastly, we identify a series of model developments specifically designed to address the limitations of the current model assumptions. Part 2 of this two-part paper discusses the CityChem extension to EPISODE, which includes a number of implementations such as a more comprehensive photochemical scheme suitable for describing more chemical species and a more diverse range of photochemical environments, as well as a more advanced treatment of the sub-grid dispersion.

Upper Svaneti (Georgia) is a territory in almost permanent isolation amid the Caucasus mountain range. This strategic position, along with the military nature of its settlements made its defence so effective that Svaneti served as Georgia`s safehouse, protecting its chief historical and religious relics in times of crisis. This isolation also ensured the preservation of archaic cultural traditions and ancient rituals, such as animal sacrifices, ritual shaving and blood feuds, establishing what is known as popular religion. Some of these rituals, mainly those performed by women, take place in the domestic space. This paper, developed under the scope of the 3DPast project, aims to interpret the symbolic use of space in vernacular houses of Upper Svaneti. The methodological strategy combines architectonic survey with documental analysis and brings forward an interpretation of this vernacular house from a space anthropology perspective. The traditional svanetian house (machubi), is composed of a single volume, of rough quadrangular plan. The ground floor (machub) houses, during winter, the family and the cattle, while the upper floor (darbazi) was mostly used as the family residence during warmer periods. This analysis will focus specifically on the machub, where there are traces of the symbolic use of domestic space. The machub is composed of a single space with a central fireplace. This element is the axis of segmentation of female and male spaces inside the house. The present paper will address this gender-differentiated symbolic use of the domestic space through the scope of anthropology and of the Svanetian history.

The World Heritage Committee lists every year, several cultural sites as World Heritage properties. Some of these properties balance the notion of a landscape that bears combined works between nature and men, on which vernacular architecture is part of a local tradition of interaction with nature. The 3dPast research project is a European project, coordinated by Escola Superior Gallaecia and co-funded by the European Union, under the Creative Europe programme. The project studies and values vernacular knowledge of these unique places. In Portugal, the Pico landscape was listed as a World Heritage property due to the 500 years of history of local inhabitants adapting farming practices to produce wine, in a challenge environment and in a remote place in the middle of the Atlantic. This article aims to study, the history and the development of the island's architecture and urbanism, based on an ancestral way of life that is still alive nowadays. The scarcity of natural resources and the difficulties to travel between villages and islands emphasised the effects of insularity. However, the continuity of local culture, passed down through generations, created a strong identity, which is source of pride. The cultural landscape classified area includes about 987 hectares, from the parish of Criação Velha, on the south coast, to Santa Luzia, on the north side, covering part of two municipalities of Pico. The article first presents a brief historical background of the island. Following, it focuses on the evolution of human occupation, through the reading of population indicators and traditional architecture and urbanism, recognizing the unique cultural and landscape values within the property. Finally, it discusses the current regulatory framework on territorial planning, and the architectural and urban regulations in planning framework, with particular emphasis on processes and practices at different scales.

Ushguli, located in the Upper Svaneti region (Georgia), represents the highest point of human occupation before the permanent snowed highlands that separate Georgia from Russia. The local inhabitants (Svan) are described as an aggressive community with warrior habits. Their history is one of permanent conflict. Most of the major empires of the ancient world (Persia, Greece, Rome and Byzantium) disputed this territory. In the Middle Ages, when natural conditions secured their isolation, the established feudal system preserved, until recent times, the warrior culture of the Svan through a judicial system based on blood feuds. The necessity to defend their territory from invaders, as well as the violent conflicts between families, influenced their settlement morphology, as well as their vernacular architecture. Four small settlements (Chvibiani, Zhibiani, Chazhashi and Murkmeli) constitute the Ushguli province, inscribed in the UNESCO World Heritage Site list since 1996. This paper aims to study the Ushgulli traditional urban morphology, which does not correspond to any classical urban element. The overlapping between private and public spaces and the inexistence of a standard concept of street or square are some of their peculiar features; some of which have an important influence on the organization of vernacular buildings. These buildings do not present a dominating facade or any other type of hierarchical composition towards the exterior. Under the scope of the Project 3D Past a multidisciplinary approach (Architecture, Urban Morphology and History) is used to better understand the original features of these peculiar settlements.

We report the discovery and characterization of a nearby (∼85 pc), older (27 ± 3 Myr), distributed stellar population near Lower Centaurus Crux (LCC), initially identified by searching for stars comoving with a candidate transiting planet from TESS (HD 109833; TOI 1097). We determine the association membership using Gaia kinematics, color–magnitude information, and rotation periods of candidate members. We measure its age using isochrones, gyrochronology, and Li depletion. While the association is near known populations of LCC, we find that it is older than any previously found LCC subgroup (10–16 Myr), and distinct in both position and velocity. In addition to the candidate planets around HD 109833, the association contains four directly imaged planetary-mass companions around three stars, YSES-1, YSES-2, and HD 95086, all of which were previously assigned membership in the younger LCC. Using the Notch pipeline, we identify a second candidate transiting planet around HD 109833. We use a suite of ground-based follow-up observations to validate the two transit signals as planetary in nature. HD 109833 b and c join the small but growing population of

ABSTRACT: Pulmonary hypertension (PH) in dogs is a syndrome that can occur secondary to several causes, including left heart disease (postcapillary) and chronic respiratory disease (precapillary). This study evaluates morphological and functional consequences in the right ventricle (RV) of dogs with pre- and postcapillary PH through echocardiography, and also considers the severity of PH (mild, moderate or severe). Echocardiography was performed on 66 dogs of various breeds and weights (age >3 years old) which were assigned to three groups: postcapillary PH, which included mitral valve disease/endocardiosis, precapillary PH, which included chronic respiratory diseases (bronchitis, collapse of the trachea and primary lung cancer or metastasis), and finally, a healthy group of controls. The parameters for RV morphology were RV1, RV2, and RV3 for systole and diastole. The following measurements were used to assess RV systolic function: tricuspid annular plane systolic excursion (TAPSE), TAPSE:Ao (aorta), maximum velocity of the tricuspid systolic wave obtained by tissue Doppler (S’), S’:Ao, right ventricle end-diastolic area (RVEDA); RVEDA:BSA (body surface area); flow velocity integral (FVI) and FVI:Ao. The variables were assessed using ANOVA. The results showed that RV3d, RV1s, S’:Ao, S’, and FVI were able to distinguish cases of pre- and postcapillary PH in this study. Remodeling of the RV of dogs with PH was observed, which can be influenced by the pre- or postcapillary origin of the PH, with dilation in dogs with postcapillary PH and severe PH. The results for RV systolic function were similar, with FVI and FVI:Ao showing that RV ejection function is reduced in dogs with postcapillary PH and with severe PH.

ABSTRACT: Boxer dogs with arrhythmogenic right ventricular cardiomyopathy (ARVC) can experience sudden cardiac death regardless of presence/absence of clinical signs. The aims of this retrospective study were two-fold: 1) to investigate the coupling interval (CI) and prematurity index (PI) of ventricular arrhythmias (VA), and the heart rate variability (HRV) in Boxers, and 2) to evaluate their impact on overall survival time. The first 24-hour Holter 36 client-owned Boxer dogs meeting inclusion/exclusion criteria were evaluated for the number, morphology, site of origin, complexity, CI and PI, of ventricular premature complexes (VPCs), and time domain HRV. The effect on survival was assessed, considering the presence/absence of ventricular tachycardia (VT), and syncope. All-cause mortality was considered as the end-point, with median survival times being obtained by Kaplan-Meier analyses and compared by log-rank test. Polymorphic VPCs were more common in symptomatic dogs than asymptomatic. VPCs in dogs with VT were less premature, due to the influence of heart rate on PI despite comparable CI. The PI and mean heart rate (HRme) were significantly different between VT and non-VT dogs but did not discriminate adequately between groups as standalone tests. Median survival time was shorter in Boxer dogs with VT (463 vs 1645 days, HR: 4.31, P=0.03). The HRV parameters, SDNN and SDANN, were both associated with prognosis. The CI and PI were not demonstrated to be prognostic surrogates in Boxer dogs with VA. HRme≥112bpm is 100% sensitive but only 46% specific for detecting VT in Boxers on the 24-hour Holter. Presence of VT, SDNN≤245ms, or SDANN≤134ms at the time of the first 24-hour Holter was associated with a shorter survival.

We present here emissions estimated from a newly developed emission model for residential wood combustion (RWC) at high spatial and temporal resolution, which we name the MetVed model. The model estimates hourly emissions resolved on a 250 m grid resolution for several compounds, including particulate matter (PM), black carbon (BC) and polycyclic aromatic hydrocarbons (PAHs) in Norway for a 12-year period. The model uses novel input data and calculation methods that combine databases built with an unprecedented high level of detail and near-national coverage. The model establishes wood burning potential at the grid based on the dependencies between variables that influence emissions: i.e. outdoor temperature, number of and type and size of dwellings, type of available heating technologies, distribution of wood-based heating installations and their associated emission factors. RWC activity with a 1 h temporal profile was produced by combining heating degree day and hourly and weekday activity profiles reported by wood consumers in official statistics. This approach results in an improved characterisation of the spatio-temporal distribution of wood use, and subsequently of emissions, required for urban air quality assessments. Whereas most variables are calculated based on bottom-up approaches on a 250 m spatial grid, the MetVed model is set up to use official wood consumption at the county level and then distributes consumption to individual grids proportional to the physical traits of the residences within it. MetVed combines consumption with official emission factors that makes the emissions also upward scalable from the 250 m grid to the national level. The MetVed spatial distribution obtained was compared at the urban scale to other existing emissions at the same scale. The annual urban emissions, developed according to different spatial proxies, were found to have differences up to an order of magnitude. The MetVed total annual PM2.5 emissions in the urban domains compare well to emissions adjusted based on concentration measurements. In addition, hourly PM2.5 concentrations estimated by an Eulerian dispersion model using MetVed emissions were compared to measurements at air quality stations. Both hourly daily profiles and the seasonality of PM2.5 show a slight overestimation of PM2.5 levels. However, a comparison with black carbon from biomass burning and benzo(a)pyrene measurements indicates higher emissions during winter than that obtained by MetVed. The accuracy of urban emissions from RWC relies on the accuracy of the wood consumption (activity data), emission factors and the spatio-temporal distribution. While there are still knowledge gaps regarding emissions, MetVed represents a vast improvement in the spatial and temporal distribution of RWC.

Summary: CellMinerCDB provides a web-based resource (https://discover.nci.nih.gov/cellminercdb/) for integrating multiple forms of pharmacological and genomic analyses, and unifying the richest cancer cell line datasets (the NCI-60, NCI-SCLC, Sanger/MGH GDSC, and Broad CCLE/CTRP). CellMinerCDB enables data queries for genomics and gene regulatory network analyses, and exploration of pharmacogenomic determinants and drug signatures. It leverages overlaps of cell lines and drugs across databases to examine reproducibility and expand pathway analyses. We illustrate the value of CellMinerCDB for elucidating gene expression determinants, such as DNA methylation and copy number variations, and highlight complexities in assessing mutational burden. We demonstrate the value of CellMinerCDB in selecting drugs with reproducible activity, expand on the dominant role of SLFN11 for drug response, and present novel response determinants and genomic signatures for topoisomerase inhibitors and schweinfurthins. We also introduce LIX1L as a gene associated with mesenchymal signature and regulation of cellular migration and invasiveness. : Genomics; Bioinformatics; Biological Database; Cancer Systems Biology Subject Areas: Genomics, Bioinformatics, Biological Database, Cancer Systems Biology

Abstract Fungi are important in several aspects of human life. In particular, to agriculture, pathogenic fungi are of great importance, as they are responsible for production losses of the most diverse types. Because of this, knowledge about pathogenic fungus is of extreme importance for farmers and professionals working in agricultural areas. Among farmers who use specific agroecological practices, this knowledge is even more valuable, since by not adopting conventional methods of production, they resort to non-invasive alternatives that are less or not harmful at all to the environment in consideration of production management methods. This study aimed to assess farmer perception in the Cerrado biome in the city of Goiás (GO), Brazil, in order to understand their ethnomycological perceptions to verify historical management practices, their knowledge about phytopathogenic fungi, and how these producers perceive fungi. We used the theoretical reference method “From peasant to peasant” formulated by ANPA - National Association of Small Farmers. Some aspects of farmers’ ethnomycological knowledge are discussed. These ease identification the representatives of the Fungi Kingdom is associated with organisms that present easily recognizable characteristics, such as wood-ears or disease-causing fungi. In general, farmers are able to identify representatives of the Fungi Kingdom that are found in their daily lives. The perception of farmers about fungi, a group still much unknown by society, is very relevant for future actions of ethnomycology.