Inter-core crosstalk in weakly coupled MCFs with arbitrary core layout and the effect of bending and twisting on the coupling coefficient

We investigate the bending and twisting-induced longitudinal variation of the inter-core coupling coefficient (ICCC) and its effect on inter-core crosstalk (ICXT) in weakly coupled multi-core fibers (MCFs) with an arbitrary core layout. An analytical discrete changes model (DCM) for ICXT field propagation under those conditions is proposed for the first time, providing very fast and rather accurate mean ICXT power estimates. The analytical mean ICXT power estimates are validated through numerical simulation. It is predicted that the mean ICXT power between adjacent cores of the outer ring of the 19-core MCF can be more than 10 dB higher than the one between adjacent cores of the inner ring. It is also predicted that the difference between the mean ICXT power of cores in the inner and outer rings can be much smaller by decreasing the core pitch and increasing the bending radius. This behavior is attributed to the ICXT dependence on the bending and twisting-induced longitudinal variation of the ICCCs. In particular, larger bending and twisting-induced fluctuations of the ICCCs along the longitudinal coordinate are observed in the cores of the outer ring, but the fluctuations become smaller for smaller core pitches and larger bending radii. Furthermore, it is shown that, if the ICCCs’ longitudinal variation is neglected, the mean ICXT power estimates between two adjacent cores are very similar despite the location of those cores. This means that neglecting the longitudinal variation of the ICCCs can lead to misleading estimates of the mean ICXT power, with an error exceeding 15 dB.info:eu-repo/semantics/publishedVersio

Dual polarization discrete changes model of inter-core crosstalk in multi-core fibers

The discrete changes model (DCM) of inter-core crosstalk (ICXT) in weakly-coupled homogeneous multi-core fibers (MCFs) is generalized to a dual polarization (DP) scheme. This model provides theoretical expressions for the two polarization fields of the ICXT at the MCF output. Therefore, it may be of particular interest in the design of direct-detection MCF systems, where the photodetected ICXT results mainly from the beating between the ICXT field at the MCF output and the carrier of the interfered core. The DP-DCM is validated by comparison of the mean ICXT power and ICXT field amplitude estimates with the ones obtained with a rigorous, yet much more computationally demanding, model based on the coupled local mode theory (CLMT). Good agreement between the mean ICXT power estimates obtained with the DP-DCM and CLMT is observed when the inter-core coupling coefficient variation along the MCF is small. Good agreement is also observed when comparing the probability density functions of the ICXT field amplitude

Glomerular filtration rate change during chronic hepatitis C treatment with Sofosbuvir/Ledipasvir in HCV/HIV Coinfected patients treated with Tenofovir and a boosted protease inhibitor: an observational prospective study

INTRODUCTION: Concomitant use of ledipasvir and boosted protease inhibitors (PIs) may increase the risk of tenofovir (TDF) nephrotoxicity, since both these drugs increase TDF levels. Our aim was to evaluate glomerular filtration rate (eGFR) evolution during HCV treatment with sofosbuvir/ledipasvir (SOF/LDV) in HCV/HIV coinfected patients, according to their antiretroviral treatment (ARV). METHODS: Observational prospective study of HCV/HIV coinfected patients treated with SOF/LDV. eGFR evolution was evaluated during and 12 weeks after HCV treatment. Patients were categorized in three groups based on ARV regimen: non TDF, non-boosted TDF and TDF + boosted PI. RESULTS: We included 273 patients: 145 were receiving a non-TDF regimen, 78 a non-boosted TDF scheme and 50 were receiving TDF + boosted PI. We observed a statistically significant decrease in eGFR during treatment in all groups (non TDF p = 0.03, 95%CI [0.23-3.86], non-boosted TDF p < 0.01, 95%CI [3.36-7.44], TDF + PI p = 0.01, 95%CI [1.09-7.53]). The decrease was more pronounced in those receiving unboosted TDF (- 5.40 ml/min/1.73m2), but differences in eGFR decrease between the three groups were small and not statistically different (p = 0.06). eGFR decrease was greater in patients treated for 24 weeks (p = 0.009) and in cirrhotic patients (p = 0.036). At the end of follow up a recovery of eGFR was observed in all groups. CONCLUSION: We observed a significant decrease in eGFR during treatment in all study groups, that was small and reversible after SOF/LDV discontinuation. TDF was not associated with an increase in renal toxicity.info:eu-repo/semantics/publishedVersio

Drug screening using shape-based virtual screening and in vitro experimental models of cutaneous Leishmaniasis

Cutaneous leishmaniasis (CL) is one of the most disregarded tropical neglected disease with the occurrence of self-limiting ulcers and triggering mucosal damage and stigmatizing scars, leading to huge public health problems and social negative impacts. Pentavalent antimonials are the first-line drug for CL treatment for over 70 years and present several drawbacks in terms of safety and efficacy. Thus, there is an urgent need to search for non-invasive, non-toxic and potent drug candidates for CL. In this sense, we have implemented a shape-based virtual screening approach and identified a set of 32 hit compounds. In vitro phenotypic screenings were conducted using these hit compounds to check their potential leishmanicidal effect towards Leishmania amazonensis (L. amazonensis). Two (Cp1 and Cp2) out of the 32 compounds revealed promising antiparasitic activities, exhibiting considerable potency against intracellular amastigotes present in peritoneal macrophages (IC₅₀ values of 9.35 and 7.25 μm, respectively). Also, a sterile cidality profile was reached at 20 μm after 48 h of incubation, besides a reasonable selectivity (≈8), quite similarly to pentamidine, a diamidine still in use clinically for leishmaniasis. Cp1 with an oxazolo[4,5-b]pyridine scaffold and Cp2 with benzimidazole scaffold could be developed by lead optimization studies to enhance their leishmanicidal potency

Saccharomyces cerevisiae as a toxicological model to study synthetic cannabinoids and its pyrolysis products

Poster presented at the 7th European Academy of Forensic Science Conference. Prague, 6-11 September 2015"Synthetic cannabinoids are among the major psychoactive drugs widespread as safe and legal alternatives to cannabis. They are commercially available as herbal incense products intended for smoke. This has led most of developed countries to concentrate efforts in order to ban the so called “legal highs”. Despite of their increasing use, there is still a lack of information on both synthetic and natural ingredients, pharmacokinetic properties and toxic effects. In fact some of the substances seem to have stronger toxicological effects when compared to their legal counterpart. Toxicological assays are paramount to know how harmful these new substances are, helping increase public awareness since several hospitalization cases have been reported due to consumption. To tackle the new challenges posed by novel drugs worldwide, we developed an approach using Saccharomyces cerevisiae as a model to investigate the toxicity of pyrolysis products of synthetic cannabinoids. S. cerevisiae.

BAY 41-2272, a soluble guanylate cyclase agonist, activates human mononuclear phagocytes

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOPhagocyte function is critical for host defense against infections. Defects in phagocytic function lead to several primary immunodeficiencies characterized by early onset of recurrent and severe infections. In this work, we further investigated the effects of BAY 41-2272, a soluble guanylate cyclase (sGC) agonist, on the activation of human peripheral blood monocytes (PBM) and THP-1 cells. EXPERIMENTAL APPROACH THP-1 cells and PBM viability was evaluated by methylthiazoletetrazolium assay; reactive oxygen species production by lucigenin chemiluminescence; gene and protein expression of NAPDH oxidase components by qRT-PCR and Western blot analysis, respectively; phagocytosis and microbicidal activity by co-incubation, respectively, with zymosan and Escherichia coli; and cytokine release by elisa. KEY RESULTS BAY 41-2272, compared with the untreated group, increased spreading of monocytes by at least 35%, superoxide production by at least 50%, and gp91PHOX and p67PHOX gene expression 20 to 40 times, in both PBM and THP-1 cells. BAY 41-2272 also augmented phagocytosis of zymosan particles threefold compared with control, doubled microbicidal activity against E. coli and enhanced the release of TNF-a and IL-12p70 by both PBM and THP-1 cells. Finally, by inhibiting sGC with ODQ, we showed that BAY 41-2272-induced superoxide production and phagocytosis is not dependent exclusively on sGC activation. CONCLUSIONS AND IMPLICATIONS In addition to its ability to induce vasorelaxation and its potential application for therapy of vascular diseases, BAY 41-2272 was shown to activate human mononuclear phagocytes. Hence, it is a novel pro-inflammatory drug that may be useful for controlling infections in the immunocompromised host166516171630FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO06/51004-2; 06/52483-1470978/2008-

Novel amidines and analogues as promising agents against intracellular parasites: a systematic review

Parasitic protozoa comprise diverse aetiological agents responsible for important diseases in humans and animals including sleeping sickness, Chagas disease, leishmaniasis, malaria, toxoplasmosis and others. They are major causes of mortality and morbidity in tropical and subtropical countries, and are also responsible for important economic losses. However, up to now, for most of these parasitic diseases, effective vaccines are lacking and the approved chemotherapeutic compounds present high toxicity, increasing resistance, limited efficacy and require long periods of treatment. Many of these parasitic illnesses predominantly affect low-income populations of developing countries for which new pharmaceutical alternatives are urgently needed. Thus, very low research funding is available. Amidine-containing compounds such as pentamidine are DNA minor groove binders with a broad spectrum of activities against human and veterinary pathogens. Due to their promising microbicidal activity but their rather poor bioavailability and high toxicity, many analogues and derivatives, including pro-drugs, have been synthesized and screened in vitro and in vivo in order to improve their selectivity and pharmacological properties. This review summarizes the knowledge on amidines and analogues with respect to their synthesis, pharmacological profile, mechanistic and biological effects upon a range of intracellular protozoan parasites. The bulk of these data may contribute to the future design and structure optimization of new aromatic dicationic compounds as novel antiparasitic drug candidate

Multilevel optimization of laminated composite structures

A two-stage optimization method aiming at the optimal design of shells and plates made of laminated composites has been developed. It is based on a mixture of sensitivity analysis, optimality criteria and mathematical programming techniques. The design variables are the optimality criteria and mathematical programming techniques. The design variables are the macro-element thicknesses and the layers' angles. Weight minimization with material efficiency maximization are the objectives with constraints on stresses and displacements. Maximization of the material efficiency is performed at one level using the conjugated method applied to the angles of the macro-element layers keeping the thicknesses constant. The other level is dedicated to weight reduction using optimality criteria and using as variables the macro-element thicknesses with the angles of the macro-element layers constant

Stalking e ciberstalking em estudantes universitários: Uma revisão sistemática

Objetivo: Este artigo tem como objetivo contribuir para o conhecimento dos fenómenos de stalking e ciberstalking  através da identificação e análise dos estudos empíricos referentes à ocorrência daqueles fenómenos em estudantes universitários. Métodos: Para tal adotámos os procedimentos para a realização de uma revisão sistemática sobre a investigação realizada sobre a ocorrência do stalking e do ciberstalking em estudantes do ensino universitário. Resultados: Os resultados mostraram que predominam os estudos quantitativos de natureza transversal, recorrendo a designs exploratórios, descritivos e correlacionais, centrados na vítima. Os instrumentos mais utilizados para avaliar ambos os fenómenos foram diversos, porém todos os estudos recorreram a inventários de autorrelato. Em relação à prevalência dos fenómenos, os valores obtidos nos estudos foram muito diferentes (e.g., de 12% a 96% ao longo da vida). Em ambos os fenómenos, as dinâmicas e os comportamentos revelaram que as vítimas eram maioritariamente do sexo feminino, os ofensores pertenciam maioritariamente ao sexo masculino, decorrendo comumente o fenómeno de uma relação de intimidade ou por pessoas conhecidas (e.g., colega, familiar, vizinho). As áreas mais afetadas, no stalking e no ciberstalking, foram a saúde psicológica e física, com consequências nos estilos de vida e economia dos estudantes universitários. Quanto às respostas à vitimação, as fontes de apoio informal foram as mais ativadas pelas vítimas. Conclusões: Em relação aos fenómenos do stalking ou ciberstalking em estudantes universitários, concluímos que predominam os estudos de prevalência, de natureza transversal e fazendo uso de diferentes tipos de instrumentos. Consideramos que a investigação pode abranger outras amostras, estudos de continuidade, beneficiando com uniformização na escolha de instrumentos para a recolha de dados e no estudo da coocorrência dos fenómenos

Da cozinha ao hospital: Um pré-teste de comportamentos típicos de diferentes grupos profissionais

No presente artigo apresentam-se dois estudos com o objectivo de avaliar descrições de comportamentos típicos de seis grupos profissionais distintos: programador de computadores, trabalhador das obras, cozinheiro, médico, músico e agricultor. De um conjunto inicial de comportamentos gerados para cada grupo profissional por um grupo de 83 participantes, foram seleccionados 420 que foram avaliados por uma nova amostra de 122 participantes divididos em duas sub-amostras. Após a determinação de medidas de tendência central e intervalos de confiança a 95%, os comportamentos foram ordenados de acordo com a sua média de tipicidade. As listas de comportamentos obtidas constituem um recurso para investigação futura em diversas áreas da psicologia nomeadamente nas áreas da cognição situada e corporalizada e da memória de acção