MAGIC eyes to the extreme: testing the blazar emission models on EHBLs

Extreme high-energy peaked BL Lac objects (EHBLs) are blazars whose synchrotron emission peaks at exceptionally high energies, above few keV, in the hard X-ray regime. So far, only a handful of those objects has been detected at very high energy (VHE, E > 100 GeV) gamma rays by Imaging Atmospheric Cherenkov Telescopes. Very remarkably, VHE observations of some of these blazars (like 1ES 0229+200) have provided evidence of a VHE gamma-ray emission extending to several TeV, which is difficult to explain with standard, one-zone synchrotron self-Compton models usually applied to BL Lac objects. The MAGIC collaboration coordinated a multi-year, multi-wavelength observational campaign on ten targets. The MAGIC telescopes detected VHE gamma rays from four EHBLs. In this paper we focus on the source 1ES 1426+426 and its X-ray and VHE gamma-ray properties. The results of different models (synchrotron self-Compton, spine-layer, hadronic) reproducing the broadband spectral energy distribution are also presented.Comment: Proceedings of the 36th International Cosmic Ray Conference (ICRC2019), July 24th-August 1st, 2019. Madison, WI, U.S.

Ambiência nas instalações para produção de leite.

Este capítulo tem por finalidade apresentar as principais instalações de um sistema de produção de leite destinado a animais em pastagem com suplementos alimentícios e uso de inseminação artificial. Não serão apresentados detalhes estruturais das instalações, já que o planejamento de construções rurais deve ser feito por técnicos especializados com base nas características da propriedade e dos objetivos do produtor. No entanto, serão listadas as principais instalações para um sistema de produção de leite e serão propostas algumas estratégias para adequar a ambiência dessas instalações, considerando o clima tropical úmido, que é predominante na Região Amazônica brasileira.bitstream/item/217361/1/cpafro-18462.pd

Nonalcoholic Fatty Liver Disease Is Associated With Higher 1-year All-Cause Rehospitalization Rates in Patients Admitted for Acute Heart Failure

Repeat hospitalization due to acute heart failure (HF) is a global public health problem that markedly impacts on health resource use. Identifying novel predictors of rehospitalization would help physicians to determine the optimal postdischarge plan for preventing HF rehospitalization. Nonalcoholic fatty liver disease (NAFLD) is an emerging risk factor for many heart diseases, including HF. We assessed whether NAFLD at hospital admission predicts 1-year all-cause rehospitalization in patients with acute HF.We enrolled all patients consecutively admitted for acute HF to our General Medicine Division, from January 2013 to April 2014, after excluding patients with acute myocardial infarction, severe heart valve diseases, malignancy, known liver diseases, and those with volume overload related to extracardiac causes. NAFLD was diagnosed by ultrasonography and exclusion of competing etiologies. The primary outcome of the study was the 1-year all-cause rehospitalization rate.Among the 107 patients enrolled in the study, the cumulative rehospitalization rate was 12.1% at 1 month, 25.2% at 3 months, 29.9% at 6 months, and 38.3% at 1 year. Patients with NAFLD had markedly higher 1-year rehospitalization rates than those without NAFLD (58% vs 21% at 1 y; P\u200a<\u200a0.001 by the log-rank test). Cox regression analysis revealed that NAFLD was associated with a 5.5-fold increased risk of rehospitalization (adjusted hazard ratio 5.56, 95% confidence interval 2.46-12.1, P\u200a<\u200a0.001) after adjustment for multiple HF risk factors and potential confounders.In conclusion, NAFLD was independently associated with higher 1-year rehospitalization in patients hospitalized for acute HF

The quassinoid derivative NBT-272 targets both the AKT and ERK signaling pathways in embryonal tumors

The quassinoid analogue NBT-272 has been reported to inhibit MYC, thus warranting a further effort to better understand its preclinical properties in models of embryonal tumors (ET), a family of childhood malignancies sharing relevant biological and genetic features such as deregulated expression of MYC oncogenes. In our study, NBT-272 displayed a strong anti-proliferative activity in vitro that resulted from the combination of diverse biological effects, ranging from G1/S arrest of the cell cycle to apoptosis and autophagy. The compound prevented the full activation of both the eukaryotic initiation factor 4E (eIF4E) and its binding protein 4EBP-1, regulating cap-dependent protein translation. Interestingly, all responses induced by NBT-272 in ET could be attributed to interference with two main pro-proliferative signaling pathways, i.e. the AKT and the MEK/extracellular signal-regulated kinase (ERK) pathways. These findings also suggested that the depleting effect of NBT-272 on MYC protein expression occurred via indirect mechanisms, rather than selective inhibition. Finally, the ability of NBT-272 to arrest tumor growth in a xenograft model of neuroblastoma plays a role in the strong anti-tumor activity of this compound, both in vitro and in vivo, with its potential to target cell-survival pathways that are relevant for the development and progression of ET

Republication: Targeting PI3KC2β Impairs Proliferation and Survival in Acute Leukemia, Brain Tumours and Neuroendocrine Tumours

BACKGROUND Eight human catalytic phosphoinositide 3-kinase (PI3K) isoforms exist which are subdivided into three classes. While class I isoforms have been well-studied in cancer, little is known about the functions of class II PI3Ks. MATERIALS AND METHODS The expression pattern and functions of the class II PI3KC2β isoform were investigated in a panel of tumour samples and cell lines. RESULTS Overexpression of PI3KC2β was found in subsets of tumours and cell lines from acute myeloid leukemia (AML), glioblastoma multiforme (GBM), medulloblastoma (MB), neuroblastoma (NB), and small cell lung cancer (SCLC). Specific pharmacological inhibitors of PI3KC2β or RNA interference impaired proliferation of a panel of human cancer cell lines and primary cultures. Inhibition of PI3KC2β also induced apoptosis and sensitised the cancer cells to chemotherapeutic agents. CONCLUSION Together, these data show that PI3KC2β contributes to proliferation and survival in AML, brain tumours and neuroendocrine tumours, and may represent a novel target in these malignancies