O desenvolvimento humano, iniciado há cerca de 300 mil anos, sempre ocorreu em paralelo às variações naturais do clima. No entanto, desde a Revolução Industrial, a ação antrópica intensificou o efeito estufa, elevando a temperatura média global e alterando os padrões climáticos, resultando em impactos severos, como o aumento das temperaturas, alterações nos padrões de precipitação e aumento na frequência de eventos severos de tempo, como tempestades, tornados e furacões. Este artigo explora as principais mudanças climáticas atuais e como elas são monitoradas por meio da análise de dados históricos. Além disso, apresenta projeções de modelos climáticos que permitem antecipar cenários futuros, incluindo o aumento das temperaturas e mudanças nos padrões de precipitação, especialmente na América do Sul. Por fim, o texto destaca a importância de ações concretas para mitigar as emissões de gases de efeito estufa, responsáveis pelas mudanças climáticas atuais, utilizando tecnologias já disponíveis. Concluímos que, para enfrentar a emergência climática, é fundamental integrar os recursos humanos e naturais do Brasil, aliados ao conhecimento científico, a fim de implementar soluções eficazes para reduzir os impactos e proteger as populações mais vulneráveis.
Klinefelter syndrome (KS) is the most prevalent aneuploidy in males and is characterized by a 47,XXY karyotype. Less frequently, higher grade sex chromosome aneuploidies (HGAs) can also occur. Here, using a paradigmatic cohort of KS and HGA induced pluripotent stem cells (iPSCs) carrying 49,XXXXY, 48,XXXY, and 47,XXY karyotypes, we identified the genes within the pseudoautosomal region 1 (PAR1) as the most susceptible to dosage-dependent transcriptional dysregulation and therefore potentially responsible for the progressively worsening phenotype in higher grade X aneuploidies. By contrast, the biallelically expressed non-PAR escape genes displayed high interclonal and interpatient variability in iPSCs and differentiated derivatives, suggesting that these genes could be associated with variable KS traits. By interrogating KS and HGA iPSCs at the single-cell resolution we showed that PAR1 and non-PAR escape genes are not only resilient to the X-inactive specific transcript (XIST)-mediated inactivation but also that their transcriptional regulation is disjointed from the absolute XIST expression level. Finally, we explored the transcriptional effects of X chromosome overdosage on autosomes and identified the nuclear respiratory factor 1 (NRF1) as a key regulator of the zinc finger protein X-linked (ZFX). Our study provides the first evidence of an X-dosage-sensitive autosomal transcription factor regulating an X-linked gene in low- and high-grade X aneuploidies.
V. Astro, G. Ramírez-Calderón, Roberta Pennucci
et al.
Summary The histone demethylase KDM1A is a multi-faceted regulator of vital developmental processes, including mesodermal and cardiac tube formation during gastrulation. However, it is unknown whether the fine-tuning of KDM1A splicing isoforms, already shown to regulate neuronal maturation, is crucial for the specification and maintenance of cell identity during cardiogenesis. Here, we discovered a temporal modulation of ubKDM1A and KDM1A+2a during human and mice fetal cardiac development and evaluated their impact on the regulation of cardiac differentiation. We revealed a severely impaired cardiac differentiation in KDM1A−/− hESCs that can be rescued by re-expressing ubKDM1A or catalytically impaired ubKDM1A-K661A, but not by KDM1A+2a or KDM1A+2a-K661A. Conversely, KDM1A+2a−/− hESCs give rise to functional cardiac cells, displaying increased beating amplitude and frequency and enhanced expression of critical cardiogenic markers. Our findings prove the existence of a divergent scaffolding role of KDM1A splice variants, independent of their enzymatic activity, during hESC differentiation into cardiac cells.
Abstract Solar activity (SA) dynamics increases mankind’s evolutionary adaptability to pandemics. Flu pandemics from 1880 to 2020 took place during maximum or minimum of solar cycles. The article discusses several factors that modulated the development of the COVID-19 pandemic: SA dynamic, genetic population features, environment temperature, the effect of lockdowns, and vaccination in various countries. The population genetic composition turned out to be the most significant factor for coronavirus mortalities during a SA global minimum 2019-2020. COVID-19 pandemic is most severe in countries with a dominant haplogroup R1b (the relative number of deaths per million is more than 12-25). Local COVID-19 epidemics were more easily in countries with a dominant haplogroup N (relative number of deaths less than 3). The incidence per million people in haplogroups R1b: R1a: N has a ratio of about 7: 2: 1. This ratio does not depend on the pandemic waves and the population vaccinated rate. Vaccination effectiveness may depend on the population’s genetic characteristics too. It is expected to maintain extremely low solar activity during the 30 years. Under these conditions, a twofold increase in the number of pandemics (every 5-6 years instead of 10-11 years) can be expected with pronounced genogeographic differences.
Astronomical images captured using optical telescopes usually suffer from severe noise effects which makes the denoising step inevitable for image analysis. This paper proposes a denoising framework for astronomical images based on Convolutional Neural Network (Astro U-net). The modified Astro U-net model has been learned in four ways, the first method is using astronomical images from the Hubble Space Telescope data set with three types of noise (dark noise, read- out noise, shot noise) added, the second method is learned using the same data set with the dark noise (dn) added only, the third method is using the same data set with the read-out noise (ron) overlaid, the fourth method is using the same data set with the shot noise (sn) added. The proposed framework for denoising the astronomical images is based on a fusion of the image that was improved by the model learned in the first method with the image that was improved by the three models that were learned by the second, third and fourth methods sequentially. Experimentally, the proposed framework shows a significant improvement in both the peak signal-to-noise ratio (PSNR) and the structural similarity index (SSIM) as compared to the Astro U-net model on different exposure time ratios.
Background and Purpose The use of external beam accelerated partial breast irradiation (APBI) using a twice-per-day regimen has raised concerns about increase rates of late toxicities. We compared toxicity outcomes of external beam APBI using a once-per-day regimen and accelerated hypofractionated whole breast irradiation (AWBI) in patients with early-stage breast cancer. Materials and Methods This was a single-institution, retrospective cohort study. Patients aged ≥50 years with pTisN0 or pT1N0 breast cancer who underwent breast-conserving surgery and adjuvant radiotherapy were included. APBI was delivered at 38.5 Gy in 10 fractions once daily using magnetic resonance imaging (MRI)-guided radiotherapy only to patients who were strictly “suitable”, according to the ASTRO-APBI guidelines. AWBI was delivered at 40.5–43.2 Gy in 15 or 16 fractions with or without a boost. Results Between October 2015 and December 2018, 173 and 300 patients underwent APBI and AWBI, respectively. At a median follow-up of 34.9 months (range 7.1 to 55.4 months), the 3-year recurrence-free survival rates of the APBI and AWBI groups were both 99.2% (p=0.63). Acute toxicities were less frequent in the APBI than AWBI group (grade 1: 95 [54.9%] vs. 233 [77.7%] patients; grade 2: 7 [4.0%] vs. 44 [14.7%] patients; no grade ≥3 toxicities were observed in either group, p<0.001). Late toxicities were less common in the APBI than AWBI group (grade 1: 112 [64.7%] vs. 197 [65.7%] patients; grade 2: 9 [5.2%] vs. 64 [21.3%] patients; grade 3: 0 vs. 5 [1.7%] patients, p<0.001). Multivariate analysis showed that APBI was significantly associated with fewer late toxicities of grade ≥2 compared with AWBI (odds ratio 4.17, p=0.006). Conclusion Once-per-day APBI afforded excellent locoregional control and fewer toxicities compared with AWBI. This scheme could be an attractive alternative to AWBI in patients who meet the ASTRO-APBI guidelines.
Discute-se de que forma se dava o entendimento da atração gravitacional na teoria de Newton e até o advento da relatividade geral de Einstein. Explica-se como o surgimento do eletromagnetismo levantou questões à física newtoniana e conduziu até a relatividade especial. Também se discute as dificuldades de se adequar a gravitação de Newton a uma formulação relativística e as diversas teorias gravitacionais que surgiram antes de Einstein apresentar sua ideia de interpretar a gravitação como um fenômeno geométrico.
Luigi Coviello, F. Cavallo, Raffaele Limosani
et al.
In the near future robots will permeate our daily life empowering human beings in several activities of daily living. Particular, service robots could actively support indoor mobility tasks thus to enhance the independent living of citizens. They should be able to provide tailored services to citizens to achieve higher physical human-robot interaction. Too often service robots were designed without taking into account end-users functional requirements, which can change with age and geriatric syndromes. In this paper, we present a robot smart control based on machine learning strategies and adaptable to different handgrip strengths. The smart control was implemented on ASTRO robot conceived to be a companion and to support indoor mobility, among other activities. Particularly, three smart controller strategies were implemented and tested with end users from technical and user point of view. The results show promising results that underline the proposed approach was suitable for the proposed application.
We evaluated the proportion of patients eligible for alternatives to standard whole breast irradiation (WBI) following breast‐conserving surgery using the National Cancer Database (NCDB). Using the 2016 dataset, Stage I‐III patients were identified. Eligibility for hypofractionated WBI (HFRT), accelerated partial breast irradiation (APBI) and endocrine therapy (ET‐alone) was defined using eligibility from large clinical trials as well as consensus guidelines. For patients with pN0 breast cancer, 20.6% and 37.0% were eligible for ET‐alone based on the CALGB 9343/PRIME‐II trials, respectively. In terms of HFRT, 72.5% and 50.4% were eligible based on IMPORT LOW/ASTRO HFRT guidelines, respectively. Based on IMPORT LOW/GEC‐ESTRO trial/ASTRO guidelines/ABS guidelines/GEC‐ESTRO guidelines, 72.5%, 86.1%, 39.0%, 72.5%, 45.7%, respectively, were eligible for APBI. Of those who qualify for HFRT per ASTRO guidelines, approximately 90% were eligible for APBI and 50% for ET‐alone. This analysis shows that a large proportion of patients with node‐negative breast cancer are eligible for HFRT, APBI and/or ET‐alone after breast‐conserving surgery.
The GRAINE project (Gamma-Ray Astro-Imager with Nuclear Emulsion) has been developed for the observation of cosmic γ -rays in the energy range 10 MeV–100 GeV with a precise (0.08 ◦ at 1–2 GeV), polarization-sensitive, large-aperture-area ( ∼ 10 m 2 ) emulsion telescope by repeated long-duration balloon flights. In 2011, the first balloon-borne experiment was successfully performed with a 12 . 5 × 10 cm 2 aperture area and 4.6 hour flight duration for a feasibility and performance test. Systematic detection, energy reconstruction, and timestamping of γ -ray events were performed across the whole area of the emulsion film, up to 45 ◦ incident zenith angle, down to 50 MeV γ -ray energy, with 97% detection reliability, 0.2 sec timestamp accuracy, and 98% timestamp reliability. A γ -ray data checking and calibration method was created using the γ -rays produced in the converter. We measured the atmospheric γ -ray flux in the energy range 50–300 MeV and obtained a first understanding of the cosmic γ -ray background. By combining the attitude data, we established a procedure for determining the γ -ray arrival direction in celestial coordinates. The first flight of the balloon-borne emulsion telescope confirmed its potential as a high-performance cosmic γ -ray detector.
Abstract The physical nature of the presently dominating enigmatic dark energy in the expanding universe is demonstrated to be explainable as an excess of the kinetic energy with respect to its potential energy. According to traditional Friedman cosmology, any non-zero value of the total energy integral is ascribed to the space curvature. However, as we show, in the flat universe the total energy also can be different from zero. Initially, a very small excess of kinetic energy originates from the early universe. The present observational data show that our universe has probably a flat space with an excess of kinetic energy. The evolutionary scenario shows that the universe presently is in the transitional stage where its radial coordinate expansion approaches the velocity of light. A possibility of the closed Bubble universe with the local Big Bang and everlasting expansion is demonstrated. Dark matter can be essentially contributed by the non-relativistic massive neutrinos, which have cooled to very low temperatures and velocities thus favoring the formation of the observed broad equipotential wells in galaxies.