Macroscopic elastic anisotropy in tough ceramics from the single crystal elastic behaviour

The modern techniques for engineering analysis are based on a deep understanding of the proportional relationship between stress and strain and the description in terms of isotropic elastic constants, in many cases, is enough. In anisotropic materials the knowledge of the elastic constants is important for the manufacturing process and for micro mechanical modelling behaviour of the material to develop the new composite materials. Theoretical calculations of elastics constants and anisotropies are applied to tough ceramics ZrO2, HfO2 and in rutile TiO2 and SnO2. Their dependence of the residual hydrostatic stress in the crystal are given. The microscopic elastic anisotropy determined in this work, could be applied in the macro scale in the case the constituent grains have a preferred orientation in the crystal lattice or the grains shape is not spherical (faceted) and it is aligned to a common crystal axis. To cover the case where the grains are distributed at randomly, the Voigt-Reuss-Hill polycrystalline approach is applied to obtain the average values of Young, bulk, shear modules, Poisson coefficient and sound velocity in the transversal and longitudinal modes. These theoretical results, could be useful in the interpretation of experimental results obtained with the method known as diffraction elastic constant (DEC).Fil: Caravaca, Maria de Los Angeles Dominga. Universidad Nacional del Nordeste. Facultad de Ingeniería; ArgentinaFil: Casali, Ricardo Antonio. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Física; ArgentinaFil: Ponce Altamirano, Claudio Ariel. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Nicotinic Acid Adenine Dinucleotide Phosphate Induces Intracellular Ca2+ Signalling and Stimulates Proliferation in Human Cardiac Mesenchymal Stromal Cells

Nicotinic acid adenine dinucleotide phosphate (NAADP) is a newly discovered second messenger that gates two pore channels 1 (TPC1) and 2 (TPC2) to elicit endo-lysosomal (EL) Ca2+ release. NAADP-induced lysosomal Ca2+ release may be amplified by the endoplasmic reticulum (ER) through the Ca2+-induced Ca2+ release (CICR) mechanism. NAADP-induced intracellular Ca2+ signals were shown to modulate a growing number of functions in the cardiovascular system, but their occurrence and role in cardiac mesenchymal stromal cells (C-MSCs) is still unknown. Herein, we found that exogenous delivery of NAADP-AM induced a robust Ca2+ signal that was abolished by disrupting the lysosomal Ca2+ store with Gly-Phe β-naphthylamide, nigericin, and bafilomycin A1, and blocking TPC1 and TPC2, that are both expressed at protein level in C-MSCs. Furthermore, NAADP-induced EL Ca2+ release resulted in the Ca2+-dependent recruitment of ER-embedded InsP3Rs and SOCE activation. Transmission electron microscopy revealed clearly visible membrane contact sites between lysosome and ER membranes, which are predicted to provide the sub-cellular framework for lysosomal Ca2+ to recruit ER-embedded InsP3Rs through CICR. NAADP-induced EL Ca2+ mobilization via EL TPC was found to trigger the intracellular Ca2+ signals whereby Fetal Bovine Serum (FBS) induces C-MSC proliferation. Furthermore, NAADP-evoked Ca2+ release was required to mediate FBS-induced extracellular signal-regulated kinase (ERK), but not Akt, phosphorylation in C-MSCs. These finding support the notion that NAADP-induced TPC activation could be targeted to boost proliferation in C-MSCs and pave the way for future studies assessing whether aberrant NAADP signaling in C-MSCs could be involved in cardiac disorders

Path analysis under multicollinearity in green pepper

Os objetivos deste trabalho foram: a) desdobrar correlações genotípicas em efeitos diretos e indiretos de componentes primários e secundários sobre a produção de frutos, em genótipos de pimentão (Capsicum annuum L.), por meio de análises de trilha; b) comparar métodos alternativos de estimação dos coeficientes de trilha para contornar os efeitos adversos da multicolinearidade. Com base nas magnitudes dos efeitos diretos e indiretos, nenhum dos componentes primários ou secundários mostrou ser importante na seleção dos genótipos mais produtivos. Em populações segregantes, o caráter altura da planta poderá ser útil em resposta correlacionada, por meio de seleção indireta. Na ocorrência de multicolinearidade de moderada a severa entre os caracteres, a eliminação de variáveis do modelo de regressão e a análise de trilha em crista mostraram-se eficientes para reduzir as altas variâncias dos coeficientes de trilha encontradas. Contudo, quando várias variáveis necessitam ser eliminadas, o processo de descarte torna-se difícil e muitas análises podem ser necessárias. A análise de trilha em crista, por sua vez, deve contornar os efeitos adversos da multicolinearidade, sem que haja grande redução nos valores dos coeficientes de determinação dos modelos de regressão.The main goals of this work were: a) to display genotype correlations in direct and indirect effects of primary and secondary components on the production of fruits, in green pepper (Capsicum annuum L.) genotypes, by mean of path analysis; b) to compare alternative methods of estimation of the path coefficients to avoid the adverse effects of multicollinearity. Based on the magnitude of direct and indirect effects, none of the primary or secondary components showed to be more important in the selection of more productive genotypes. In segregating populations, the character height of the plant might be useful in correlated response, by means of indirect selection. In the occurrence of moderate to severe multicollinearity between the characters, the elimination of variables from the regression model and the ridge path analysis showed to be efficient in reducing the high variances of the path coefficients found. However, when several variables need to be eliminated, the disposal process becomes difficult and many analysis might be necessary. Ridge path analysis, although, should by-pass the adverse effects of multicollinearity, without having great reduction on the coefficient determination values of the regression models

Inhalation therapy in the next decade : Determinants of adherence to treatment in asthma and COPD

Peer reviewedPublisher PD

Modulation of Nerve Growth Factor receptors in human monocytes and their influence in pulmonary inflammatory diseases

Neurotrophins (NTs) are a family of growth/survival factors with well-established functions in the nervous system. In the last decade, novel biological actions, from oncogenicity to inflammation, have been attributed to these factors. In particular, Nerve Growth Factor (NGF) acts through two different classes of receptors: the high affinity transducing TrKA receptor, associated to proliferation/survival, and the low affinity p75 receptor that, depending on its cross talk with TrKA, induces either apoptosis or survival. Recently, NGF and its receptors have been detected in healthy pulmonary tissues and seem to be involved in pulmonary inflammatory diseases. Since the expression of these NGF receptors in circulating monocytes is controversial, our initial aim was to investigate the role of these receptors both in pulmonary tissues and in peripheral blood monocytes of patients with Chronic Obstructive Pulmonary Disease (COPD). We therefore analyzed 38 healthy control subjects divided in two groups based on their smoking status. Serendipitously, the data obtained in these two control groups may have a value of their own, with potential implications in preventive medicine. We show here that in healthy subjects, smoking induces an early increase in p75 expression in monocytes, while TrKA seems unaffected. Furthermore, our control subjects could be divided in three subsets according to the constitutive TrKA expression in monocytes: TrKA-negatives, -intermediates (up to 50%) or -high (> 50%), independently on their smoking status. Since TrKA activation promotes inflammation, we hypothesize that subjects with high-TrKA monocytes could be more prone to pulmonary inflammatory diseases, such as COPD. In fact, all 28 COPD patients in our series belonged to the high-TrKA subset, while all long term heavy smokers with no evidence of pneumologic diseases belonged to TrKA-negative subset. In conclusion, our data support the hypothesis that, since TrKA expression promotes survival, elevated levels of TrKA-positive monocytes may render subjects more prone to long term inflammatory diseases (e.g., COPD). Moreover, in patients constitutively expressing high levels of TrKA in monocytes, the smoking-dependent increase in p75 may in turn further extend monocytes survival, contributing to a chronic inflammation. Furthermore, the early increase in p75 expression in monocytes following smoking may support the hypothesis that p75 determination might represent a novel marker for passive smoking. Acknowledgments. This study was totally supported by Fondazione Cassa di Risparmio di Tern

ATM Polymorphisms and their Relationship to Radiation Toxicity in Breast Cancer Patients / Polimorfismos ATM e sua relação com a toxicidade por radiação em pacientes com câncer de mama

Aims: The breast cancer is one of the most common types and it treatment brings complications such as skin, dermis and subcutaneous toxicity. Studies about genetic variations of patients are those that enable the identification of prognostic factors for treatment, generally based on greater risk of injury to healthy tissue. Study design: This study examined the association between single nucleotide polymorphisms (SNPs) of ATM gene in patients with breast cancer with adverse reactions presented in normal tissues as result of radiotherapy. Place and Duration of Study: The study was conduct at Pontifícia Universidade Católica de Goiás, and the patients were recruited at Hospital Araújo Jorge, Associação de Combate ao Câncer em Goiás, Radiotherapy Service. Methodology: We evaluated 76 patients, through a retrospective study, based on data contained in records and teletherapy records of patients with this cancer who underwent radiotherapy for at least 5 years. Polymorphisms of the ATM gene were analyzed by microarray technique. Results: The mean age of patients was 50 years and the total dose of radiation was an average of 50,21 Gy ranging from 45Gy to 50.4Gy. Regarding the late toxicities, patients analyzed showed a higher frequency of low-grade morbidities when compared to high grade. Nineteen patients interrupted the radiation therapy for any reason. Patients who have studied polymorphisms have no increased risk of developing acute toxicity changes of the skin. (P>.05). Patients presenting polymorphisms AX-8315255 (TTT insertion) (RR=11.0, 1.08 - 111.97, p=0.045) and rs56128736 (RR=11.0, 1.08 - 111.97, p=0.045) had an increased risk for developing late skin toxicity, but not at subcutaneous tract. Conclusion: ATM is a large gene with many variants documented. Association studies of these SNPs will be needed in larger sample groups to establish whether the single base variants or haplotypes of this gene may indeed contribute to the toxicity of normal tissue. Thus, the personalized treatment with ionizing radiation can be prescribed for patients decreasing complications and improving the effectiveness of treatment and quality of life of patients

ExoClock project: an open platform for monitoring the ephemerides of Ariel targets with contributions from the public

The Ariel mission will observe spectroscopically around 1000 exoplanets to further characterise their atmospheres. For the mission to be as efficient as possible, a good knowledge of the planets’ ephemerides is needed before its launch in 2028. While ephemerides for some planets are being refined on a per-case basis, an organised effort to collectively verify or update them when necessary does not exist. In this study, we introduce the ExoClock project, an open, integrated and interactive platform with the purpose of producing a confirmed list of ephemerides for the planets that will be observed by Ariel. The project has been developed in a manner to make the best use of all available resources: observations reported in the literature, observations from space instruments and, mainly, observations from ground-based telescopes, including both professional and amateur observatories. To facilitate inexperienced observers and at the same time achieve homogeneity in the results, we created data collection and validation protocols, educational material and easy to use interfaces, open to everyone. ExoClock was launched in September 2019 and now counts over 140 participants from more than 15 countries around the world. In this release, we report the results of observations obtained until the 15h of April 2020 for 120 Ariel candidate targets. In total, 632 observations were used to either verify or update the ephemerides of 84 planets. Additionally, we developed the Exoplanet Characterisation Catalogue (ECC), a catalogue built in a consistent way to assist the ephemeris refinement process. So far, the collaborative open framework of the ExoClock project has proven to be highly efficient in coordinating scientific efforts involving diverse audiences. Therefore, we believe that it is a paradigm that can be applied in the future for other research purposes, too

Next Generation Molecular Diagnosis of Hereditary Spastic Paraplegias: An Italian Cross-Sectional Study

Hereditary spastic paraplegia (HSP) refers to a group of genetically heterogeneous neurodegenerative motor neuron disorders characterized by progressive age-dependent loss of corticospinal motor tract function, lower limb spasticity, and weakness. Recent clinical use of next generation sequencing (NGS) methodologies suggests that they facilitate the diagnostic approach to HSP, but the power of NGS as a first-tier diagnostic procedure is unclear. The larger-than-expected genetic heterogeneity-there are over 80 potential disease-associated genes-and frequent overlap with other clinical conditions affecting the motor system make a molecular diagnosis in HSP cumbersome and time consuming. In a single-center, cross-sectional study, spanning 4 years, 239 subjects with a clinical diagnosis of HSP underwent molecular screening of a large set of genes, using two different customized NGS panels. The latest version of our targeted sequencing panel (SpastiSure3.0) comprises 118 genes known to be associated with HSP. Using an in-house validated bioinformatics pipeline and several in silico tools to predict mutation pathogenicity, we obtained a positive diagnostic yield of 29% (70/239), whereas variants of unknown significance (VUS) were found in 86 patients (36%), and 83 cases remained unsolved. This study is among the largest screenings of consecutive HSP index cases enrolled in real-life clinical-diagnostic settings. Its results corroborate NGS as a modern, first-step procedure for molecular diagnosis of HSP. It also disclosed a significant number of new mutations in ultra-rare genes, expanding the clinical spectrum, and genetic landscape of HSP, at least in Italy

Guidelines for the management of neuroendocrine tumours by the Brazilian gastrointestinal tumour group

Neuroendocrine tumours are a heterogeneous group of diseases with a significant variety of diagnostic tests and treatment modalities. Guidelines were developed by North American and European groups to recommend their best management. However, local particularities and relativisms found worldwide led us to create Brazilian guidelines. Our consensus considered the best feasible strategies in an environment involving more limited resources. We believe that our recommendations may be extended to other countries with similar economic standards.Univ Sao Paulo, Inst Canc Estado Sao Paulo, BR-01246000 Sao Paulo, BrazilUniv Sao Paulo, Fac Med, Dept Radiol & Oncol, BR-01246903 Sao Paulo, BrazilHosp Sirio Libanes, BR-01308050 Sao Paulo, BrazilHosp Moinhos de Vento Porto Alegre, BR-90035000 Porto Alegre, RS, BrazilOncoctr, BR-30360680 Belo Horizonte, MG, BrazilUniv Fed Rio Grande do Sul, Dept Cirurgia, BR-90040060 Porto Alegre, RS, BrazilHosp Clin Porto Alegre, BR-90035903 Porto Alegre, RS, BrazilUniv Fed Ceara, Fac Med, Dept Fisiol & Farmacol, BR-60020180 Fortaleza, Ceara, BrazilHosp Univ Walter Cantidio, BR-60430370 Fortaleza, Ceara, BrazilInst Nacl Canc, BR-20230240 Rio De Janeiro, BrazilUniv Sao Paulo, Fac Med, Disciplina Endocrinol & Metabol, BR-01246903 Sao Paulo, BrazilAC Camargo Canc Ctr, Dept Surg, BR-01509010 Sao Paulo, BrazilUniv Sao Paulo, Fac Med, Dept Gastroenterol, Sao Paulo, BrazilUniv Fed Ciencias Saude Porto Alegre, BR-90050170 Porto Alegre, RS, BrazilHosp Albert Einstein, BR-05652900 Sao Paulo, BrazilHosp Base, Fac Med Sao Jose do Rio Preto, BR-15090000 Sao Paulo, BrazilSanta Casa Sao Jose do Rio Preto, BR-15025500 Sao Jose Do Rio Preto, BrazilPontificia Univ Catolica Parana, Hosp Erasto Gaertner, BR-81520060 Curitiba, Parana, BrazilUniv Fed Rio Grande do Norte, BR-59300000 Natal, RN, BrazilUniv Sao Paulo, Inst Coracao, BR-05403900 Sao Paulo, BrazilAC Camargo Canc Ctr, Med Oncol, BR-01509010 Sao Paulo, BrazilUniv Fed Sao Paulo, Disciplina Gastroenterol, BR-04021001 Sao Paulo, BrazilHosp Sao Rafael, BR-41253190 Salvador, BA, BrazilHosp Canc Barretos, Dept Cirurgia Aparelho Digest Alto & Hepatobiliop, BR-14784400 Sao Paulo, BrazilUniv Sao Paulo, Fac Med, Dept Patol, BR-01246903 Sao Paulo, BrazilClin AMO, BR-1950640 Salvador, BA, BrazilHosp Sao Jose, BR-01323001 Sao Paulo, BrazilUniv Nove de Julho, BR-02111030 Sao Paulo, BrazilUniv Fed Sao Paulo, Disciplina Gastroenterol, BR-04021001 Sao Paulo, BrazilWeb of Scienc

Covid-19 and the role of smoking: the protocol of the multicentric prospective study COSMO-IT (COvid19 and SMOking in ITaly).

The emergency caused by Covid-19 pandemic raised interest in studying lifestyles and comorbidities as important determinants of poor Covid-19 prognosis. Data on tobacco smoking, alcohol consumption and obesity are still limited, while no data are available on the role of e-cigarettes and heated tobacco products (HTP). To clarify the role of tobacco smoking and other lifestyle habits on COVID-19 severity and progression, we designed a longitudinal observational study titled COvid19 and SMOking in ITaly (COSMO-IT). About 30 Italian hospitals in North, Centre and South of Italy joined the study. Its main aims are: 1) to quantify the role of tobacco smoking and smoking cessation on the severity and progression of COVID-19 in hospitalized patients; 2) to compare smoking prevalence and severity of the disease in relation to smoking in hospitalized COVID-19 patients versus patients treated at home; 3) to quantify the association between other lifestyle factors, such as e-cigarette and HTP use, alcohol and obesity and the risk of unfavourable COVID-19 outcomes. Socio-demographic, lifestyle and medical history information will be gathered for around 3000 hospitalized and 700-1000 home-isolated, laboratory-confirmed, COVID-19 patients. Given the current absence of a vaccine against SARS-COV-2 and the lack of a specific treatment for -COVID-19, prevention strategies are of extreme importance. This project, designed to highly contribute to the international scientific debate on the role of avoidable lifestyle habits on COVID-19 severity, will provide valuable epidemiological data in order to support important recommendations to prevent COVID-19 incidence, progression and mortality