Adhesion and detachment fluxes of micro-particles from a permeable wall under turbulent flow conditions

We report a numerical investigation of the deposition and re-entrainment of Brownian particles from a permeable plane wall. The tangential flow was turbulent. The suspension dynamics were obtained through direct numerical simulation of the Navier–Stokes equations coupled to the Lagrangian tracking of individual particles. Physical phenomena acting on the particles such as flow transport, adhesion, detachment and re-entrainment were considered. Brownian diffusion was accounted for in the trajectory computations by a stochastic model specifically adapted for use in the vicinity of the wall. Interactions between the particles and the wall such as adhesion forces and detachment were modeled. Validations of analytical solutions for simplified cases and comparisons with theoretical predictions are presented as well. Results are discussed focusing on the interplay between the distinct mechanisms occurring in the fouling of filtration devices. Particulate fluxes towards and away from the permeable wall are analyzed under different adhesion strengths

Modeling and simulation of inertial drop break-up in a turbulent pipe flow downstream of a restriction.

This work deals with the modeling of drop break-up in an inhomogeneous turbulent flow that develops downstream of a concentric restriction in a pipe. The proposed approach consists in coupling Euler–Lagrange simulations of the drop motion to an interface deformation model. First the turbulent flow downstream of the restriction is solved by means of direct numerical simulation. Single drop trajectories are then calculated from the instantaneous force balance acting on the drop within the turbulent field (one-way coupling). Concurrently, the interface deformation is computed assuming the drop to behave as a Rayleigh–Lamb type oscillator forced by the turbulent stress along its trajectory. Criterion for break-up is based upon a critical value of drop eformation. This model has been tested against experimental data. The flow conditions and fluids properties have been chosen to match those experimental investigations. Both turbulent flow statistics and break-up probability calculations are in good agreement with experimental data, strengthening the relevance of this approach for modeling break-up in complex unsteady flow

A functional study on novel genes involved in regulating aldosterone secretion in normal human zona glomerulosa and in aldosterone-producing adenomas

Primary aldosteronism is the most common secondary cause of hypertension with a prevalence of about 10%. About half of PA cases are caused by aldosterone-producing adenomas (APA). Two APA subtypes, ZG-like and ZF-like APAs, have been described, according to the histological resemblance to normal zona glomerulosa (ZG) and zona fasciculata (ZF), underlying somatic mutations (KCNJ5 commonly found in ZF-like, CACN1AD, ATP1A1, ATP2B3, CTNNB1 in ZG-like APAs), and transcriptome profile. It is unknown if the process of tumorigenesis differs between ZG- and ZF-like APAs. In order to define ZG specific genes, we have compared the transcriptome of APAs and their adjacent adrenal glands by microarray assay. RNA was isolated by laser capture microdissection (LCM) from adjacent ZG, ZF and APAs from 14 patients with Conn’s and 7 patients with phaeocromocytoma. Two top hit genes from the comparison of ZG vs ZF were functionally studied, ANO4 and NEFM. NEFM, encoding neurofilament medium, was the fourth most up-regulated gene in ZG vs ZF, showing 14.8-fold-fold higher expression levels (p=9.16-12) in ZG than ZF. NEFM was also one of the most down-regulated genes in ZF-like vs ZG-like APAs. Immunohistochemistry (IHC) confirmed selective high expression of NEFM in ZG and ZG-like APAs. Silencing NEFM in H295R cells increased aldosterone secretion and cell proliferation. In addition, it increased stimulation and inhibition, respectively, of aldosterone secretion from H295R cells by the dopamine receptor D1R agonist fenoldopam and antagonist SCH23390. IHC showed predominantly intracellular staining for D1R in NEFM-rich ZG-like APAs, but membranous staining in NEFM-poor ZF-like APAs. Aldosterone secretion in response to fenoldopam in primary cells from ZG-like APAs was lower than in cells from ZF-like APAs. NEFM expression levels directly correlate with KCNJ5 phenotype: KCNJ5 mutations down-regulate NEFM mRNA and protein levels in H295R cells and in primary cells from ZG-like APAs. ANO4,encoding a Ca2+-activated chloride channel family member, was the third most upregulated gene, showing 19.9-fold higher expression levels (p=6.6x10-24) in ZG than ZF. IHC confirmed ZG selectivity of ANO4 protein in the adrenal cortex. The staining was mainly cytoplasmic. Unlike NEFM, there was no difference in expression of ANO4 between ZG- and ZF-like APAs, the levels being mid-way between those of ZF and ZG. Overexpression of ANO4 in H295R cells caused an increase in CYP11B2 and NR4A2 gene expression levels but basal aldosterone secretion was unchanged. In the presence of calcium agonists, ANO4 reduced aldosterone secretion. ANO4 subcellular localisation was confirmed as cytoplasmic by immunofluorescence microscopy of transfected cells. When exposed to calcium ionophores, ANO4 generated small chloride currents as detected by YFP assay. In summary, the comparison of transcriptome of ZG with paired ZF found unexpected up-regulated genes. Most of the highly up regulated genes in human ZG, including NEFM and ANO4, inhibit either basal or stimulated aldosterone secretion, and this may reflect an adaptive response to high salt intake. No clear-cut correspondence was found between transcriptome of APAs and their resembling zone of adrenal cortex. The down-regulation of NEFM following transfection of mutant KCNJ5 suggests that ZF-like properties may be a consequence of mutation, rather than tissue of origin.British Heart Foundatio

The rational search for selective anticancer derivatives of the peptide Trichogin GA IV: a multi-technique biophysical approach

Peptaibols are peculiar peptides produced by fungi as weapons against other microorganisms. Previous studies showed that peptaibols are promising peptide-based drugs because they act against cell membranes rather than a specific target, thus lowering the possibility of the onset of multi-drug resistance, and they possess non-coded alpha-amino acid residues that confer proteolytic resistance. Trichogin GA IV (TG) is a short peptaibol displaying antimicrobial and cytotoxic activity. In the present work, we studied thirteen TG analogues, adopting a multidisciplinary approach. We showed that the cytotoxicity is tuneable by single amino-acids substitutions. Many analogues maintain the same level of non-selective cytotoxicity of TG and three analogues are completely non-toxic. Two promising lead compounds, characterized by the introduction of a positively charged unnatural amino-acid in the hydrophobic face of the helix, selectively kill T67 cancer cells without affecting healthy cells. To explain the determinants of the cytotoxicity, we investigated the structural parameters of the peptides, their cell-binding properties, cell localization, and dynamics in the membrane, as well as the cell membrane composition. We show that, while cytotoxicity is governed by the fine balance between the amphipathicity and hydrophobicity, the selectivity depends also on the expression of negatively charged phospholipids on the cell surface

Le reti territoriali per l’orientamento nelle scuole del Veneto: governo e gestione

The research has its starting point in the tenyear experience of youth guidance networks in Regione Veneto, where school’s actors and extra-school actors which collaborate to organize multiple initiatives for student guidance. The main problem which motivated the present work is the presence of heterogeneous elements in the network types, distributed in a bipolar continuum from “networks of information and collaboration”, to “cooperative networks”, with a high degree of coordination. Empirical research has focused on seven “cooperative networks”, through a series of semi-structured interviews with coordinators of the seven networks. Interviews with network coordinators allowed to reconstruct the historical background of the networks, the characteristics of their governance, coordination and communication and the role played by the coordinators themselves, identifying some success factors.La ricerca si colloca nell’esperienza decennale delle reti territoriali di orientamento per i giovani della Regione del Veneto, in cui attori scolastici ed extra-scolastici collaborano nella realizzazione di una ampia gamma di azioni di orientamento rivolte agli studenti. Il problema dal quale il lavoro ha presoavvio è la presenza di eterogeneità nelle tipologie di reti, distribuite in un continuum bipolare da “reti di informazione e collaborazione”, a “reti cooperative” che presentano un alto grado di coordinamento. La ricerca empirica si è focalizzata sull’indagine approfondita di sette “reti di tipo cooperativo” attraverso interviste semi-strutturate ai coordinatori delle sette reti. Le interviste hanno permesso di esplicitare la storia delle reti, le caratteristiche del sistema di governance e di coordinamento, di comunicazione ed il ruolo svolto dal coordinatore, individuando alcuni fattori di successo di tale esperienza

Photocatalytic Degradation Of Ofloxacin And Evaluation Of The Residual Antimicrobial Activity.

Ofloxacin is an antimicrobial agent frequently found in significant concentrations in wastewater and surface water. Its continuous introduction into the environment is a potential risk to non-target organisms or to human health. In this study, ofloxacin degradation by UV/TiO2 and UV/TiO2/H2O2, antimicrobial activity (E. coli) of samples subjected to these processes, and by-products formed were evaluated. For UV/TiO2, the degradation efficiency was 89.3% in 60 min of reaction when 128 mg L(-1) TiO2 were used. The addition of 1.68 mmol L(-1) hydrogen peroxide increased degradation to 97.8%. For UV/TiO2, increasing the catalyst concentration from 4 to 128 mg L(-1) led to an increase in degradation efficiency. For both processes, the antimicrobial activity was considerably reduced throughout the reaction time. The structures of two by-products are presented: m/z 291 (9-fluoro-3-methyl-10-(methyleneamino)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid) and m/z 157 ((Z)-2-formyl-3-((2-oxoethyl)imino)propanoic acid).14556-6

Dadoxylon whitei sp.n.

In the present paper the A. describes Dadoxylon Whitei n. sp. based on a fossil wood collected in Assistência, municipal district of Rio Claro, State of São Paulo. The fossil in question occurs in beds of the Irati formation of the permian age.The A. also discusses the characters which distinguish the above-mentiened species from other Dadoxylon of south Brazil studied up to this dat

MicroRNA e il recettore adenosinico A3 come biomarcatori del mesotelioma maligno della pleura

Background: Malignant pleural mesothelioma (MPM) is an aggressive asbestosrelated cancer that develops via mesothelial cell transformation. At present there are no effective therapies for MPM. Great efforts have been made in finding specific markers/mechanisms for MPM onset, including studies into microRNAs and adenosine receptors (ARs). Recent studies have shown the differential expression of mature microRNAs in several human cancers, suggesting their potential role as oncogenes or tumor suppressor genes, and the involvement of ARs in the regulation of cell death and proliferation. Methods: In this study, we investigated miRNAs profile and the expression of A3ARs in MPM. MiRNAs profile was investigated in 5 HMCs (human normal pleural mesothelial short term cell cultures) and 5 MPMs, with microarray approach. These results were confirmed by Real Time quantitative RT-PCR and western blotting. ARs were analyzed by using RT-PCR, western blotting and saturation binding assays. HMC were treated with crocidolite asbestos which is the principal risk factor of MM. The role of A3ARs on these cellular models, evaluating cAMP production, Akt phosphorylation and NF-kB activation was investigated. The dual effect of A3AR stimulation on healthy and cancer cell growth was studied by means of proliferation, apoptosis and cytotoxicity assays. Results: A comparative analysis of miRNA expression in MPM and HMCs was carried out. Microarray profiling showed different miRNA expression between MPM and HMCs. Specifically, 13 miRNAs (17-5p, 18a, 19b, 20a, 20b, 25, 92, 106a, 106b), members of the oncomiRNA miR 17-92 and its paralogs were markedly dysregulated. Besides, in our investigation, additional miRNAs, such as miR-7, miR-182, miR-214 and miR-497 were found to be dysregulated in MPM. A3AR was up-regulated by 2.5 fold (P<0.01) in MMP when compared with HMP. Stimulation of A3ARs decreases proliferation and exerts cytotoxic and proapoptotic effect on MMC and on HMC exposed to asbestos and TNF-�, but not in HMC with an involvement of the de-regulation of Akt/NF-kB cell survival pathway. Conclusion: These data are in agreement with results which have previously been reported on dysregulated miRNAs for other solid human tumors. Moreover, in our investigation, additional miRNAs were found to be dysregulated in MPM. Interestingly, gene products which regulate the cell cycle are targets and predicted targets for these miRNAs. Our data suggest that specific miRNAs and A3ARs could be key players in MPM development/progression. In addition, some of these miRNAs may represent MPM markers and potential targets for new therapeutic approaches. Besides, our data suggest that A3AR could represent a pharmacological target to prevent tumor development after asbestos exposure and to treat full blown MPM

O Programa Farmácia Popular contribui para redução nas internações pediátricas por asma no Brasil?

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Ceilândia, Programa de Pós-Graduação em Ciências e Tecnologias em Saúde, 2018.BACKGROUND: Asma é uma inflamação crônica das vias aéreas, que afeta cerca de 235 milhões de pessoas em todo mundo. Crianças com asma têm pior prognóstico de saúde e qualidade de vida quando suas famílias enfrentam dificuldades financeiras para pagar por medicamentos. Esse trabalho teve como objetivo avaliar o impacto da política de copagamento e gratuidade de medicamentos do “Programa Farmácia Popular do Brasil” nas internações por asma na população pediátrica. MÉTODO: foi utilizada a abordagem ecológica longitudinal, comparando o período pré (2007-2009) e pós (2010-2017) fornecimento de medicamentos. A seleção de co-variáveis foi realizada com base em evidências na literatura. Modelos de regressão logística foram utilizados para avaliar a significância das co- variáveis, e aquelas que apresentaram significância foram incluídas no modelo de regressão binomial negativa para avaliar o impacto destas sobre o desfecho (taxa de internação). RESULTADOS: durante todo período de estudo ocorreram 1.097.442 internações de pacientes ente 0 e 19 anos, sendo 80% internações de pacientes de 0 a 9 anos. Nesse período, o programa ATFP expandiu, alcançando uma cobertura de mais de 80% de municípios brasileiros. Houve redução das taxas de internações todas as faixas etárias de 0 a 19 anos, de acordo com os resultados da regressão linear (OR = 0.214, IC (95%) = 0.149 - 0.307). O ATFP e Programa Mais Médicos contribuíram para a redução das internações por asma (OR = 0.993, IC95%: 0.992 - 0.993 e OR =0.909, IC95% = 0.894 - 0.924, respectivamente). CONCLUSÃO: o ATFP contribuiu maneira significante para a redução das internações por asma em pacientes de 0 a 9 anosBACKGROUND: Asthma is a chronic inflammation of the airways, which affects about 235 million people worldwide. Children with asthma have worse prognosis of health and quality of life when their families face financial difficulties to pay for medicines. The objective of this study was to evaluate the impact of the policy of copayment and gratuitousness of medications of the "Brazilian Popular Pharmacy Program" in hospitalizations for asthma in the paediatric population. METHOD: The longitudinal ecological approach was used to evaluate the impact of the “Aqui Tem Farmácia Popular (ATFP) on hospitalizations, comparing the pre (2007-2009) and post (2010-2017) periods of drug supply. The selection of covariates was performed based on evidence in the literature. Logistic regression models were used to evaluate the significance of covariates, and those that presented significance were included in the negative binomial regression model to evaluate their impact on the outcome (hospitalization rate). RESULTS: altogether 1,097,442 hospitalizations were observed of patients between 0 and 19-year-old throughout the study period, out of which 80% are hospitalizations of patients 0 to 9 years old. During this period, the ATFP program expanded, covering more than 80% of Brazilian municipalities. There was a reduction in hospitalization rates for all age groups from 0 to 19 years, according to the results of linear regression (OR = 0.214, CI (95%) = 0.149 - 0.307). The ATFP and Programa Mais Médicos contributed to the reduction of hospitalizations for asthma (OR = 0.993, 95% CI: 0.992 - 0.993 and OR = 0.909, 95% CI = 0.894 - 0.924, respectively). CONCLUSION: ATFP contributed significantly to the reduction of hospitalizations due to asthma in patients aged 0 to 9 year