Enhanced optical gain clamping for upstream packet based traffic on hybrid WDM/TDM-PON using fiber bragg grating

In this paper, we propose a method to mitigate the temporal power transients arising from Erbium doped fiber amplifiers (EDFAs) on packeted/bursty scenario. The technique, applicable on hybrid WDM/TDM-PON for extended reach, is based on a low power clamping provided by a distributed feedback (DFB) laser and a fiber Bragg grating (FBG). An mprovement in the data signal Q factor was achieved keeping the clamping control signal with a low power, accompanied by a maximum reduction in the gain excursion of 1.12 d

Neuropatia óptica isquêmica anterior não arterítica bilateral após crise de fechamento angular num paciente com iridosquise: relato de caso

A 55-year-old woman was referred to our clinic because of a one-week history of visual loss and raised intraocular pressure in the left eye followed 4 days later by visual loss in the right eye. Slit-lamp examination showed bilateral conjunctival hyperemia, slight diffuse corneal edema, shallow anterior chamber and fixed and dilated pupil in both eyes. Splitting of the anterior layers of the iris with fibrillar degeneration extending for approximately one quadrant inferiorly was presented in each eye. Fundus examination showed opitc disc edema with no vascular tortuosity and no cup in both eyes. The condition was treated as bilateral acute angle-closure glaucoma in a patient with irisdoschisis. After medical treatment and improvement of visual acuity, perimetry revealed a significant visual field defect especially in left eye; this case represents a rare concurrence of acute angle-closure glaucoma and bilateral nonarteritic ischemic optic neuropathy. Although most cases of elevated intraocular pressure, including acute angle-closure glaucoma, do not result in optic disc edema and irreversible vision loss, variations in the vascular supply of the nerve optic head along with others ocular systemic risk factors, may predispose certain individuals to nonarteritic ischemic optic neuropathy during periods of elevated intraocular pressure.Paciente de 55 anos, sexo feminino, encaminhada para nosso serviço com história de perda de visão e aumento da pressão intraocular no olho esquerdo há uma semana seguida quatro dias após de perda visual no olho direito. À biomicroscopia hiperemia conjuntival bilateral, edema difuso da córnea, câmara anterior rasa e pupilas fixas e dilatadas em ambos os olhos. Separação do folheto anterior da íris no quadrante inferior estava presente em ambos os olhos. O exame do fundo do olho mostrava edema de disco sem tortuosidade vascular e sem escavação em ambos os olhos. O quadro clínico foi tratado como crise de fechamento angular bilateral num paciente com iridosquise. Após tratamento clínico e iridotomia bilateral com melhora da acuidade visual, a perimetria computadorizada revelou grave perda de campo visual, especialmente no olho esquerdo; este caso representa a rara ocorrência simultânea de crise de fechamento angular e neuropatia óptica isquêmica anterior não-arterítica bilateral. Embora a maioria dos casos com pressão intraocular elevada, incluindo crise de fechamento angular, não resulta em edema de disco e perda visual irreverssível, variações no suprimento vascular da cabeça do nervo óptico associados com outros fatores de risco sistêmicos, podem predispor certos indivíduos à neuropatia óptica isquêmica anterior durante períodos de elevação da pressão intraocular

AKT can modulate the in vitro response of HNSCC cells to irreversible EGFR inhibitors

Epidermal growth factor receptor (EGFR) is overexpressed in up to 90% of head and neck squamous cell carcinoma (HNSCC) tumors. Cetuximab is the first targeted (anti-EGFR) therapy approved for the treatment of HNSCC patients. However, its efficacy is limited due to primary and secondary resistance, and there is no predict biomarkers of response. New generation of EGFR inhibitors with pan HER targeting and irreversible action, such as afatinib and allitinib, represents a significant therapeutic promise. In this study, we intend to compare the potential cytotoxicity of two anti-EGFR inhibitors (afatinib and allitinib) with cetuximab and to identify potential predictive biomarkers of response in a panel of HNSCC cell lines. The mutational analysis in the eight HNSCC cell lines revealed an EGFR mutation (p.H773Y) and gene amplification in the HN13 cells. According to the growth inhibition score (GI), allitinib was the most cytotoxic drug, followed by afatinib and finally cetuximab. The higher AKT phosphorylation level was associated with resistance to anti-EGFR agents. Therefore, we further performed drug combinations with anti-AKT agent (MK2206) and AKT1 gene editing, which demonstrated afatinib and allitinib sensitivity restored. Additionally, in silico analysis of TCGA database showed that AKT1 overexpression was present in 14.7% (41/279) of HNSCC cases, and was associated with perineural invasion in advanced stage. In conclusion, allitinib presented a greater cytotoxic profile when compared to afatinib and cetuximab. AKT pathway constitutes a predictive marker of allitinib response and combination with AKT inhibitors could restore response and increase treatment success.FINEP (MCTI/FINEP/MS/SCTIE/DECIT-01/2013 - FPXII-BIOPLAT) and the Assistance Program and Incentive Research (PAIP), Barretos Cancer Hospital São Paulo, Brazil. The authors would like to acknowledge the technical support of Gabriela Lamberti in the clonogenic assays. A.L.C and R.M.R are recipients of a National Counsel of Technological and Scientific Development (CNPq) scholarship and O.C.M is recipient of a Portuguese Foundation for Science and Technology (FCT) scholarship (SFRH/BPD/108351/2015)info:eu-repo/semantics/publishedVersio

Proposta metodológica para o Ensino de ferramentas computacionais aplicadas ao planejamento de fármacos

As competências do profissional farmacêutico que envolvem a pesquisa de novos medicamentos têm tomado lugar de destaque. Uma técnica amplamente empregada para reduzir custos e potencializar a chance de sucesso nesse processo consiste na modelagem molecular computacional (in sílico). Dada a importância dessas ferramentas na formação do farmacêutico, o presente trabalho objetivou relatar a aplicação de uma metodologia didática de aulas práticas que ilustram sua aplicação no contexto de um componente curricular do curso de Farmácia. Em sala, equipes de 3 a 4 alunos foram formadas e foi solicitado a cada equipe a seleção de um alvo farmacológico. As coordenadas atômicas do alvo em complexo com um inibidor foram obtidas pelos discentes a partir do Protein Data Bank, que procederam com a submissão do complexo cristalográfico ao servidor PDB2PQR para adição de átomos de hidrogênio à estrutura do alvo. As coordenadas do inibidor co-cristalizado foram utilizadas para a delimitação do espaço para um acoplamento molecular, executado pelo programa on-line Dockthor. A avaliação da performance do Dockthor foi realizada através do redocking (re-acoplamento) e investigação da sua capacidade em discriminar ligantes ativos de não ativos. Por fim, os estudantes propuseram novas moléculas candidatas a fármacos e avaliaram sua afinidade frente ao alvo, através do protocolo discutido, comparando os resultados com o ligante cristalizado ao alvo. Concluiu-se que a metodologia se mostrou útil para ilustrar a aplicação de ferramentas in silico no ensino de competências referentes a Pesquisa e Desenvolvimento de Fármacos para o Curso de Farmácia

Agronomic biofortification with selenium impacts storage proteins in grains of upland rice

© 2019 Society of Chemical Industry BACKGROUND: Selenium (Se) is an essential element for humans and animals. Rice is one of the most commonly consumed cereals in the world, so the agronomic biofortification of cereals with Se may be a good strategy to increase the levels of daily intake of Se by the population. This study evaluated the agronomic biofortification of rice genotypes with Se and its effects on grain nutritional quality. Five rates of Se (0, 10, 25, 50, and 100 g ha−1) were applied as selenate via the soil to three rice genotypes under field conditions. RESULTS: Selenium concentrations in the leaves and polished grains increased linearly in response to Se application rates. A highly significant correlation was observed between the Se rates and the Se concentration in the leaves and grains, indicating high translocation of Se. The application of Se also increased the concentration of albumin, globulin, prolamin, and glutelin in polished grains. CONCLUSION: Biofortifying rice genotypes using 25 g Se ha−1 could increase the average daily Se intake from 4.64 to 66 μg day−1. Considering that the recommended daily intake of Se by adults is 55 μg day−1, this agronomic strategy could contribute to alleviating widespread Se malnutrition. © 2019 Society of Chemical Industry

The use of cecal samples from Wistar rats in in vitro fermentation to determine the effect of Fish and Pomegranate oil in gut microbiota alterations induced by a Western diet

The influence of gut microbiota in the onset and development of several metabolic diseases, such as obesity and diabetes, has gained attention over the last few years. Indeed, diet plays an essential role in gut microbiota modulation. Western diet (WD), characterized by high-sugar and high-fat consumption, alters gut microbiome composition, diversity index, microbial relative levels, and functional pathways. Several polyunsaturated fatty acids have been showing promising health effects, but their impact on gut microbiota is still overlooked. The effect of Fish oil (omega-3 source - EPA and DHA) and Pomegranate oil (punicic acid source), and a mixture of both oils in gut microbiota was determined by subjecting the oil samples to in vitro fecal fermentations using as fecal inoculum cecal samples from rats from two different dietary groups: control diet (CD) and high-fat high-sugar diet (WD). 16S amplicon metagenomics sequencing showed that Fish oil+Pomegranate oil from the WD group increased α-diversity. This sample can also increase the relative abundance of the Firmicutes and Bacteroidetes phylum as well as Akkermansia and Blautia, which were affected by the WD consumption. All samples were able to increase butyrate and acetate concentration in the WD group. Amino acids are precursors of important neuroactive molecules. Tyrosine concentrations, a precursor for dopamine and norepinephrine, increased in the Fish oil+Pomegranate oil WD sample. GABA, an important neurotransmitter, was also increased in WD samples. These results suggest a positive impact of these oils’ mixture on gut-brain axis modulation. It was demonstrated, for the first time, the great potential of using a mixture of both Fish and Pomegranate oil to restore the gut microbiota changes associated with WD consumption.info:eu-repo/semantics/publishedVersio

Falha de resposta à glibenclamida em criança brasileira com diabetes melito neonatal permanente e síndrome DEND devido a mutação C166Y no gene KCNJ11 (Kir6.2)

Heterozygous activating mutations of KCNJ11 (Kir6.2) are the most common cause of permanent neonatal diabetes mellitus (PNDM) and several cases have been successfully treated with oral sulfonylureas. We report on the attempted transfer of insulin therapy to glibenclamide in a 4-year old child with PNDM and DEND syndrome, bearing a C166Y mutation in KCNJ11. An inpatient transition from subcutaneous NPH insulin (0.2 units/kg/d) to oral glibenclamide (1 mg/kg/d and 1.5 mg/kg/d) was performed. Glucose and C-peptide responses stimulated by oral glucose tolerance test (OGTT), hemoglobin A1c levels, the 8-point self-measured blood glucose (SMBG) profile and the frequency of hypoglycemia episodes were analyzed, before and during treatment with glibenclamide. Neither diabetes control nor neurological improvements were observed. We concluded that C166Y mutation was associated with a form of PNDM insensitive to glibenclamide.As mutações ativadoras, heterozigóticas do gene KCNJ11 (Kir6.2) são a causa mais freqüente de diabetes melito neonatal permanente (DMNP) e a terapêutica oral com sulfoniluréias tem sido bem sucedida em muitos destes casos. Relatamos o processo de substituição da insulinoterapia convencional para o tratamento oral com glibenclamida em uma paciente de 4 anos, portadora de DMNP e síndrome DEND devido a uma mutação C166Y no gene KCNJ11. A insulina NPH (0,2 U/kg/dia) foi substituída pela glibenclamida (1 mg/kg/dia e 1,5 mg/kg/dia) durante internação hospitalar. As respostas de glicose e peptídeo-C no teste de tolerância oral à glicose (OGTT), os níveis de hemoglobina glicada, o perfil de glicemias capilares de 8 pontos e a freqüência de hipoglicemias foram comparados antes e durante o tratamento com glibenclamida. Não houve melhora no controle glicêmico, nem no quadro neurológico. Concluímos que a mutação C166Y associa-se a uma forma de DMNP insensível à glibenclamida

Expression of tumor suppressors miR-195 and let-7a as potential biomarkers of invasive breast cancer

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the posttranscriptional level. Some miRNAs, including let-7a and miR-195, have been described as tumor suppressors. However, the roles of these microRNAs in breast cancer progression remain controversial. The aim of this study is to evaluate miR-195 and let-7a expression as potential biomarkers of invasive breast cancer.The authors acknowledge the Avon Institute for sponsoring this study. The authors would like to thank the Barretos Cancer Hospital's Research Support Nucleus for patient identification, sample selection, and biostatistics support, as well as Barretos Cancer Hospital's Tumor Bank for sample provision and RNA extraction.info:eu-repo/semantics/publishedVersio

Genetically engineered silk-based composite biomaterials functionalized with fibronectin type-II that promote cell adhesion

[Excerpt] Recombinant protein-based polymers (rPBPs) are an emerging class of biopolymers inspired by Nature and produced by synthetic protein biotechnology approaches. Due to their exceptional physical-chemical and biological characteristics, as well as their ability to be customized for specific applications, rPBPs have been explored for the development of advanced biomaterials [1]. Within rPBPs, silk-like polymers (SLP) are being utilized in a range of studies in materials science [2]. [...]This work was supported by FCT Funded Project “Chimera” (PTDC/EBB-EBI/109093/2008), by FCT/MEC through Portuguese funds (PIDDAC) – PEst-OE/BIA/UI4050/2014, by the strategic programme UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569) funded by national funds through the FCT I.P. and by the ERDF through COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI). TC is thankful to the FCT for its support through Investigador FCT 2015. ARibeiro thanks FCT for the SFRH/BPD/98388/2013 grant. RMachado and AdaCosta acknowledge FCT for SFRH-BPD/86470/2012 and SFRH/BD/75882/2011 grants, respectively