Sistema de Controlo Remoto de Luzes de Aeródromo

Este relatório apresenta o trabalho realizado no âmbito da unidade curricular de Dissertação do Mestrado em Engenharia Electrotécnica e de Computadores – área de especialização de Automação e Sistemas. O trabalho realizado consiste no desenvolvimento de um Sistema de Controlo Remoto de Luzes de Aeródromo (SCRLA) que pode ser aplicado em paralelo aos comandos locais de controlo das luzes de aproximação, pista ou circulação, entre outras, de uma infra-estrutura aeroportuária. O objectivo fundamental deste sistema consiste em permitir ao piloto de uma aeronave o acendimento das luzes do aeródromo desde a própria aeronave, recorrendo apenas ao equipamento de rádio VHF existente a bordo da mesma e que é normalmente usado para comunicações com os serviços de controlo de tráfego aéreo. Este sistema, em aeródromos com possível operação nocturna (e.g., heliportos de hospitais), permite uma redução dos custos associados a despesas com eventual pessoal técnico ou a redução da carga de trabalho neste, e uma diminuição do consumo de energia eléctrica, uma vez que as luzes apenas são acendidas quando necessário. Este sistema permite também reduzir a poluição luminosa no ambiente e contribui positivamente para a longevidade dos equipamentos luminosos. No desenvolvimento do sistema, foram adquiridos e/ou aplicados conhecimentos nas áreas de navegação aérea, infra-estruturas aeroportuárias, telecomunicações, normalização e estandardização, electrónicas analógica e digital, programação de baixo nível em microcontroladores, desenho e construção de circuitos impressos, desenho e construção mecânica.

Hogar digital para servicios FTTH : dispositivos, tecnologías y QoE

FTTH (fibra hasta el hogar) es actualmente, junto con la banda ancha móvil, la principal evolución tecnológica en Redes y Servicios de Telecomunicaciones. Se prevé que en los próximos años, el despliegue de las redes FTTH se vea incrementado de manera significativa, gracias al interés creciente tanto de Operadores de Telecomunicaciones como de Organismos Gubernamentales. Este despliegue (que en el año 2013 ya se está haciendo realidad) llevará servicios de muy alta velocidad (superiores a 100 Mbps, incluso 1 Gbps) de manera masiva a los hogares, exigiendo nuevos requisitos y prestaciones en la red del hogar de los clientes. Se abre aquí, por tanto, un campo de exploración novedoso, incipiente y de requerimientos cada vez más exigentes. De hecho, sin duda, la red del hogar es uno de los elementos fundamentales para el éxito de las redes y servicios en FTTH. Debido a todo lo anterior, se convierte en una necesidad para el sector de las Telecomunicaciones el encontrar soluciones a los problemas anteriormente mencionados. Con objeto de contribuir al análisis de soluciones, este proyecto se enfoca en dos temas, ambos relacionados con la problemática ya mencionada en la red del hogar:  Prospección e identificación de soluciones tecnológicas avanzadas para la red del hogar. Descrito en capítulos 2, 3 y 4. En ellos se realiza un estudio detallado de la situación actual y tendencias futuras de los dispositivos utilizados en la red del hogar. Este estudio está enfocado en la distribución de señales de muy alto ancho de banda (en torno a los 100 Mbps por segundo) en el hogar.  Diseño y desarrollo de una aplicación que permita determinar la calidad de experiencia de cliente (QoE) de un servicio de televisión IP (IPTV). Descrito en capítulos 5 y 6. Se ha seleccionado este tipo de servicios debido a que son los que requieren mayores prestaciones tanto de la red de transporte como de la red del hogar y, al mismo tiempo, son los más complicados de medir debido a la fuerte componente de subjetividad del usuario final. Una red del hogar correctamente diseñada debe cumplir de manera equilibrada los requisitos demandados tanto por el operador como por el cliente o usuario final del servicio. Los requisitos del operador se centran principalmente en el control de la inversión (CAPEX) y del gasto de mantenimiento de la red del hogar (OPEX). El usuario, por otra parte, requiere sencillez en la instalación y mínimo número de elementos a instalar (cero intrusismo, ausencia de cableado). Para adaptarse a estos requerimientos, existe una serie de dispositivos y tecnologías que buscan encontrar el punto de equilibrio entre necesidades de operadores y de clientes finales. Las soluciones actualmente utilizadas pueden dividirse en soluciones cableadas e inalámbricas. También existen soluciones híbridas. Todas ellas se describen en detalle en los capítulos 3 y 4. Al final del estudio se concluye que, con la tecnología actual, es preferible el uso de soluciones cableadas tipo Ethernet o POF. Es recomendable no usar soluciones PLC de manera extensiva (G.hn puede ser una alternativa a futuro) y, en caso de no requerir cableado, utilizar WiFi 11n con frecuencias de 5 GHz, así como sus evoluciones, WiFi 11ac y 11ad. La aplicación desarrollada, explicada en los capítulos 5 y 6, permite capturar y medir en tiempo real la señal de televisión IP que se entrega al usuario. Esta aplicación estimará, a partir de dichas medidas, la calidad de la señal entregada. Para ello tendrá en cuenta el tipo de descodificador utilizado por el usuario así como la red empleada (red FTTH de Telefónica). Esta aplicación podría ser utilizada en los centros de atención técnica de las operadoras de telecomunicaciones, determinando así la relación existente entre reclamaciones recibidas y calidad de servicio medida por la aplicación. Asimismo, aparte de realizar medidas en tiempo real, la aplicación vuelca las medidas realizadas y alarmas detectadas en ficheros log, facilitando el análisis técnico de los problemas e incidencias registrados por dichos centros técnicos. Igualmente, esta aplicación puede ser utilizada para el proceso de certificación de equipamiento de red del hogar o incluso como herramienta para profundizar en parámetros teóricos y criterios de medida de calidad de servicio en IPTV. ABSTRACT. FTTH (Fiber To The Home) and mobile broadband are currently the main technological trend in the Network and Telecommunications Services area. In the next few years, the deployment of FTTH networks will experiment a significant increase, due to the growing interest of both telecommunications operators and government agencies. This deployment (that is becoming a reality) which will massively carry high-speed services to households (speeds of more than 100 Mbps, even 1 Gbps) will demand new requirements and features in the customer’s home network. It can be found here a new and emerging field of exploration, with increasingly demanding requirements. In fact, the home network is one of the key elements for the success of FTTH network and services. Due to the aforementioned, it is a necessity for the telecommunications industry to find solutions to these problems. In order to contribute into the solution analysis, this project focuses on two subjects, both related to the problems of home networking:  Exploratory research and identification of advanced technology solutions for the home network. Described in chapters 2, 3 and 4. These chapters show a detailed study of the current situation and future trends of the devices used at the home network. It focuses on the distribution of very high bandwidth signals (around 100 Mbps per second) in the customer’s home.  Design and development of an application to evaluate customer’s quality of experience (QoE) of an IP television service (IPTV). Described in chapters 5 and 6. IPTV service has been selected because it requires higher performance both from the transport and the home networks and, at the same time, it is the most difficult to measure due to the strong component of subjectivity of the end user. A correct design of the home network must meet the requirements demanded both by the network operator and the customer (end user of the service). Network operator requirements mainly focus on reduced capital expenditures (CAPEX) and operational expenditures (OPEX). Additionally, the final user requires a simple and easy installation and also the minimum number of items to install (zero intrusion, lack of wiring, etc.). Different devices and technologies seek to find a balance between these two requirements (network operators and final users requirements). Solutions available in the market can be divided into wired and wireless. There are also hybrid solutions. All of them are described thoroughly in the first part of the project. The conclusion at the end of the study recommends the use of wired technologies like Ethernet or POF. Additionally, the use of PLC is not advised (G.hn can be an alternative in the future) and, in the case of not requiring wiring, the use of 11ac and 11ad WiFi is advised. The application developed in the second part of the project allows capturing and measuring the real-time IPTV signal delivered to the user. This application will estimate the delivered signal quality from the captured measurements. For this purpose, it will also consider the type of decoder installed on the customer’s premises and the transport network (Telefonica’s FTTH network). This application could be used at the operator’s technical service centres, determining in this way the relationship between user’s complaints and the quality of service measured. Additionally, this application can write all the measurements and alarms in log files, making easier the technical analysis of problems and impairments recorded by the technical centres. Finally, the application can also be used for the certification process of home networking equipment (i.e. decoders) or even as a tool to deepen theoretical parameters and measuring criteria of quality of service in IPTV.

Coder/decoder with an optical programmable logic cell

A major research area is the representation of knowledge for a given application in a compact manner such that desired information relating to this knowledge is easily recoverable. A complicated procedure may be required to recover the information from the stored representation and convert it back to usable form. Coder/decoder are the devices dedicated to that task. In this paper the capabilities that an Optical Programmable Logic Cell offers as a basic building block for coding and decoding are analyzed. We have previously published an Optically Programmable Logic Cells (OPLC), for applications as a chaotic generator or as basic element for optical computing. In optical computing previous studies these cells have been analyzed as full-adder units, being this element a basic component for the arithmetic logic structure in computing. Another application of this unit is reported in this paper. Coder and decoder are basic elements in computers, for example, in connections between processors and memory addressing. Moreover, another main application is the generation of signals for machine controlling from a certain instruction. In this paper we describe the way to obtain a coder/decoder with the OPLC and which type of applications may be the best suitable for this type of cell.

Mucopolysaccharidosis Type Ii: Identification Of 30 Novel Mutations Among Latin American Patients.

In this study, 103 unrelated South-American patients with mucopolysaccharidosis type II (MPS II) were investigated aiming at the identification of iduronate-2-sulfatase (IDS) disease causing mutations and the possibility of some insights on the genotype-phenotype correlation The strategy used for genotyping involved the identification of the previously reported inversion/disruption of the IDS gene by PCR and screening for other mutations by PCR/SSCP. The exons with altered mobility on SSCP were sequenced, as well as all the exons of patients with no SSCP alteration. By using this strategy, we were able to find the pathogenic mutation in all patients. Alterations such as inversion/disruption and partial/total deletions of the IDS gene were found in 20/103 (19%) patients. Small insertions/deletions/indels (<22 bp) and point mutations were identified in 83/103 (88%) patients, including 30 novel mutations; except for a higher frequency of small duplications in relation to small deletions, the frequencies of major and minor alterations found in our sample are in accordance with those described in the literature.

Pyrimidine-5'-nucleotidase Campinas, A New Mutation (p.r56g) In The Nt5c3 Gene Associated With Pyrimidine-5'-nucleotidase Type I Deficiency And Influence Of Gilbert's Syndrome On Clinical Expression.

Pyrimidine-5'-nucleotidase type I (P5'NI) deficiency is an autosomal recessive condition that causes nonspherocytic hemolytic anemia, characterized by marked basophilic stippling and pyrimidine nucleotide accumulation in erythrocytes. We herein present two African descendant patients, father and daughter, with P5'N deficiency, both born from first cousins. Investigation of the promoter polymorphism of the uridine diphospho glucuronosyl transferase 1A (UGT1A) gene revealed that the father was homozygous for the allele (TA7) and the daughter heterozygous (TA6/TA7). P5'NI gene (NT5C3) gene sequencing revealed a further change in homozygosity at amino acid position 56 (p.R56G), located in a highly conserved region. Both patients developed gallstones; however the father, who had undergone surgery for the removal of stones, had extremely severe intrahepatic cholestasis and, liver biopsy revealed fibrosis and siderosis grade III, leading us to believe that the homozygosity of the UGT1A polymorphism was responsible for the more severe clinical features in the father. Moreover, our results show how the clinical expression of hemolytic anemia is influenced by epistatic factors and we describe a new mutation in the P5'N gene associated with enzyme deficiency, iron overload, and severe gallstone formation. To our knowledge, this is the first description of P5'N deficiency in South Americans.

Elevated Micronucleus Frequency In Patients With Type 2 Diabetes, Dyslipidemia And Periodontitis.

The over-production of reactive oxygen species (ROS) can cause oxidative damage to a large number of molecules, including DNA, and has been associated with the pathogenesis of several disorders, such as diabetes mellitus (DM), dyslipidemia and periodontitis (PD). We hypothesise that the presence of these diseases could proportionally increase the DNA damage. The aim of this study was to assess the micronucleus frequency (MNF), as a biomarker for DNA damage, in individuals with type 2 DM, dyslipidemia and PD. One hundred and fifty patients were divided into five groups based upon diabetic, dyslipidemic and periodontal status (Group 1 - poor controlled DM with dyslipidemia and PD; Group 2 - well-controlled DM with dyslipidemia and PD; Group 3 - without DM with dyslipidemia and PD; Group 4 - without DM, without dyslipidemia and with PD; and Group 5 - without DM, dyslipidemia and PD). Blood analyses were carried out for fasting plasma glucose, HbA1c and lipid profile. Periodontal examinations were performed, and venous blood was collected and processed for micronucleus (MN) assay. The frequency of micronuclei was evaluated by cell culture cytokinesis-block MN assay. The general characteristics of each group were described by the mean and standard deviation and the data were submitted to the Mann-Whitney, Kruskal-Wallis, Multiple Logistic Regression and Spearman tests. The Groups 1, 2 and 3 were similarly dyslipidemic presenting increased levels of total cholesterol, low density lipoprotein cholesterol and triglycerides. Periodontal tissue destruction and local inflammation were significantly more severe in diabetics, particularly in Group 1. Frequency of bi-nucleated cells with MN and MNF, as well as nucleoplasmic bridges, were significantly higher for poor controlled diabetics with dyslipidemia and PD in comparison with those systemically healthy, even after adjusting for age, and considering Bonferroni's correction. Elevated frequency of micronuclei was found in patients affected by type 2 diabetes, dyslipidemia and PD. This result suggests that these three pathologies occurring simultaneously promote an additional role to produce DNA impairment. In addition, the micronuclei assay was useful as a biomarker for DNA damage in individuals with chronic degenerative diseases.

Antioxidant And Anti-diabetic Potential Of Passiflora Alata Curtis Aqueous Leaves Extract In Type 1 Diabetes Mellitus (nod-mice).

Leaves of Passiflora alata Curtis were characterized for their antioxidant capacity. Antioxidant analyses of DPPH, FRAP, ABTS, ORAC and phenolic compounds were made in three different extracts: aqueous, methanol/acetone and ethanol. Aqueous extract was found to be the best solvent for recovery of phenolic compounds and antioxidant activity, when compared with methanol/acetone and ethanol. To study the anti-inflammatory properties of this extract in experimental type 1 diabetes, NOD mice were divided into two groups: the P. alata group, treated with aqueous extract of P. alata Curtis, and a non-treated control group, followed by diabetes expression analysis. The consumption of aqueous extract and water ad libitum lasted 28 weeks. The treated-group presented a decrease in diabetes incidence, a low quantity of infiltrative cells in pancreatic islets and increased glutathione in the kidney and liver (p<0.05), when compared with the diabetic and non-diabetic control-groups. In conclusion, our results suggest that the consumption of aqueous extract of P. alata may be considered a good source of natural antioxidants and compounds found in its composition can act as anti-inflammatory agents, helping in the control of diabetes.

Undulatory Physical Resistance Training Program Increases Maximal Strength In Elderly Type 2 Diabetics.

To investigate the effects of a specific protocol of undulatory physical resistance training on maximal strength gains in elderly type 2 diabetics. The study included 48 subjects, aged between 60 and 85 years, of both genders. They were divided into two groups: Untrained Diabetic Elderly (n=19) with those who were not subjected to physical training and Trained Diabetic Elderly (n=29), with those who were subjected to undulatory physical resistance training. The participants were evaluated with several types of resistance training's equipment before and after training protocol, by test of one maximal repetition. The subjects were trained on undulatory resistance three times per week for a period of 16 weeks. The overload used in undulatory resistance training was equivalent to 50% of one maximal repetition and 70% of one maximal repetition, alternating weekly. Statistical analysis revealed significant differences (p<0.05) between pre-test and post-test over a period of 16 weeks. The average gains in strength were 43.20% (knee extension), 65.00% (knee flexion), 27.80% (supine sitting machine), 31.00% (rowing sitting), 43.90% (biceps pulley), and 21.10% (triceps pulley). Undulatory resistance training used with weekly different overloads was effective to provide significant gains in maximum strength in elderly type 2 diabetic individuals.

Brooke-spiegler Syndrome Clinically Misdiagnosed As Neurofibromatosis Type 1.

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Post Hoc Analysis Of The Patricia Randomized Trial Of The Efficacy Of Human Papillomavirus Type 16 (hpv-16)/hpv-18 As04-adjuvanted Vaccine Against Incident And Persistent Infection With Nonvaccine Oncogenic Hpv Types Using An Alternative Multiplex Type-specific Pcr Assay For Hpv Dna.

The efficacy of the human papillomavirus type 16 (HPV-16)/HPV-18 AS04-adjuvanted vaccine against cervical infections with HPV in the Papilloma Trial against Cancer in Young Adults (PATRICIA) was evaluated using a combination of the broad-spectrum L1-based SPF10 PCR-DNA enzyme immunoassay (DEIA)/line probe assay (LiPA25) system with type-specific PCRs for HPV-16 and -18. Broad-spectrum PCR assays may underestimate the presence of HPV genotypes present at relatively low concentrations in multiple infections, due to competition between genotypes. Therefore, samples were retrospectively reanalyzed using a testing algorithm incorporating the SPF10 PCR-DEIA/LiPA25 plus a novel E6-based multiplex type-specific PCR and reverse hybridization assay (MPTS12 RHA), which permits detection of a panel of nine oncogenic HPV genotypes (types 16, 18, 31, 33, 35, 45, 52, 58, and 59). For the vaccine against HPV types 16 and 18, there was no major impact on estimates of vaccine efficacy (VE) for incident or 6-month or 12-month persistent infections when the MPTS12 RHA was included in the testing algorithm versus estimates with the protocol-specified algorithm. However, the alternative testing algorithm showed greater sensitivity than the protocol-specified algorithm for detection of some nonvaccine oncogenic HPV types. More cases were gained in the control group than in the vaccine group, leading to higher point estimates of VE for 6-month and 12-month persistent infections for the nonvaccine oncogenic types included in the MPTS12 RHA assay (types 31, 33, 35, 45, 52, 58, and 59). This post hoc analysis indicates that the per-protocol testing algorithm used in PATRICIA underestimated the VE against some nonvaccine oncogenic HPV types and that the choice of the HPV DNA testing methodology is important for the evaluation of VE in clinical trials. (This study has been registered at ClinicalTrials.gov under registration no. NCT00122681.).

Exercise Increases Pancreatic β-cell Viability In A Model Of Type 1 Diabetes Through Il-6 Signaling.

Type 1 diabetes (T1D) is provoked by an autoimmune assault against pancreatic β cells. Exercise training enhances β-cell mass in T1D. Here, we investigated how exercise signals β cells in T1D condition. For this, we used several approaches. Wild-type and IL-6 knockout (KO) C57BL/6 mice were exercised. Afterward, islets from control and trained mice were exposed to inflammatory cytokines (IL-1β plus IFN-γ). Islets from control mice and β-cell lines (INS-1E and MIN6) were incubated with serum from control or trained mice or medium obtained from 5-aminoimidazole-4 carboxamide1-β-d-ribofuranoside (AICAR)-treated C2C12 skeletal muscle cells. Subsequently, islets and β cells were exposed to IL-1β plus IFN-γ. Proteins were assessed by immunoblotting, apoptosis was determined by DNA-binding dye propidium iodide fluorescence, and NO(•) was estimated by nitrite. Exercise reduced 25, 75, and 50% of the IL-1β plus IFN-γ-induced iNOS, nitrite, and cleaved caspase-3 content, respectively, in pancreatic islets. Serum from trained mice and medium from AICAR-treated C2C12 cells reduced β-cell death, induced by IL-1β plus IFN-γ treatment, in 15 and 38%, respectively. This effect was lost in samples treated with IL-6 inhibitor or with serum from exercised IL-6 KO mice. In conclusion, muscle contraction signals β-cell survival in T1D through IL-6.-Paula, F. M. M., Leite, N. C., Vanzela, E. C., Kurauti, M. A., Freitas-Dias, R., Carneiro, E. M., Boschero, A. C., and Zoppi, C. C. Exercise increases pancreatic β-cell viability in a model of type 1 diabetes through IL-6 signaling.

Surgical Treatment Of Type 2 Diabetes In Subjects With Mild Obesity: Mechanisms Underlying Metabolic Improvements.

This study aims to assess the clinical and physiological effects of Roux-en-Y gastric bypass (RYGBP) on type 2 diabetes associated with mild obesity (body mass index [BMI] 30-34.9 kg/m(2)) over 24 months postsurgery. In this prospective trial, 36 mildly obese subjects (19 males) with type 2 diabetes using oral antidiabetic drugs with (n = 24) or without insulin (n = 12) underwent RYGBP. Follow-up was conducted at baseline and 3, 6, 12, and 24 months postsurgery. The following endpoints were considered: changes in HbA1c, fasting glucose and insulin, antidiabetic therapy, BMI, oral glucose insulin sensitivity [OGIS, from meal tolerance test (MTT)], beta-cell secretory function [ΔCP(0-30)/ΔGlu(0-30) (ΔC-peptide/Δglucose ratio, MTT 0-30 min), disposition index (DI = OGIS [Symbol: see text] ΔCP(0-30)/ΔGlu(0-30)], glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) [incremental area under the curve (AUCi)], adiponectin, C-reactive protein, and lipids. All subjects achieved normal-to-overweight BMI after 3 months. Over 24 months, 31/36 (86 %) subjects presented HbA1c <7 % [complete and partial remission of diabetes in 9/36 (22 %) and 1/36 (3 %), respectively]. Since 3 months postsurgery, improvements were observed in OGIS [290 (174) to 373 (77) ml/min/m(2), P = 0.009], ΔCP(0-30)/ΔGlu(0-30) [0.24 (0.19) to 0.52 (0.34) ng/mg, P = 0.001], DI [7.16 (8.53) to 19.8 (15.4) (ng/mg) (ml/min/m(2)), P = 0.001], GLP-1 AUCi [0.56 (0.64) to 3.97 (3.86) ng/dl [Symbol: see text] 10 min [Symbol: see text] 103, P = 0.000], and GIP AUCi [30.2 (12.6) to 27.0 (20.2) ng/dl [Symbol: see text] 10 min [Symbol: see text] 103, P = 0.004]. At baseline and after 12 months, subjects with diabetes nonremission had longer diabetes duration, higher HbA1c, lower beta-cell secretory function, and higher first 30-min GIP AUCi, compared with those with remission. RYGBP improves the glucose metabolism in subjects with type 2 diabetes and mild obesity. This effect is associated with improvement of insulin sensitivity, beta-cell secretory function, and incretin secretion.

Properties Of Bologna-type Sausages With Pork Back-fat Replaced With Pork Skin And Amorphous Cellulose.

Bologna-type sausages were produced with 50% of their pork back-fat content replaced with gels elaborated with different ratios of pork skin, water, and amorphous cellulose (1:1:0, 1:1:0.1, 1:1:0.2, 1:1:0.3, and 1:1:0.4). The impact of such replacement on the physico-chemical characteristics and the consumer sensory profiling was evaluated. The modified treatments had 42% less fat, 18% more protein, and 8% more moisture than the control group. Treatments with amorphous cellulose had a lower cooking loss and higher emulsion stability. High amorphous cellulose content (1:1:0.3 and 1:1:0.4) increased hardness, gumminess, and chewiness. The gel formulated with the ratio of 1:1:0.2 (pork skin: water: amorphous cellulose gel) provided a sensory sensation similar to that provided by fat and allowed products of good acceptance to be obtained. Therefore, a combination of pork skin and amorphous cellulose is useful in improving technological quality and producing healthier and sensory acceptable bologna-type sausages.

Association Of Single Nucleotide Polymorphisms In The Gene Encoding Glut1 And Diabetic Nephropathy In Brazilian Patients With Type 1 Diabetes Mellitus.

Mesangial cells subject to high extracellular glucose concentrations, as occur in hyperglycaemic states, are unable to down regulate glucose influx, resulting in intracellular activation of deleterious biochemical pathways. A high expression of GLUT1 participates in the development of diabetic glomerulopathy. Variants in the gene encoding GLUT1 (SLC2A1) have been associated to this diabetic complication. The aim of this study was to test whether polymorphisms in SLC2A1 confer susceptibility to diabetic nephropathy (DN) in Brazilian type 1 diabetes patients. Four polymorphisms (rs3820589, rs1385129, rs841847 and rs841848) were genotyped in a Brazilian cohort comprised of 452 patients. A prospective analysis was performed in 155 patients. Mean duration of follow-up was 5.6±2.4years and the incidence of renal events was 18.0%. The rs3820589 presented an inverse association with the prevalence of incipient DN (OR: 0.36, 95% CI: 0.16 - 0.80, p=0.01) and with progression to renal events (HR: 0.20; 95% CI: 0.03 - 0.70; p=0.009). AGGT and AGAC haplotypes were associated with the prevalence of incipient DN and the AGAC haplotype was also associated with the prevalence of established/advanced DN. In conclusion, rs3820589 in the SLC2A1 gene modulates the risk to DN in Brazilian patients with inadequate type 1 diabetes control.

Oropouche Virus Infection And Pathogenesis Is Restricted By Mavs, Irf-3, Irf-7, And Type I Ifn Signaling Pathways In Non-myeloid Cells.

Oropouche virus (OROV) is a member of the Orthobunyavirus genus in the Bunyaviridae family and a prominent cause of insect-transmitted viral disease in Central and South America. Despite its clinical relevance, little is known about OROV pathogenesis. To define the host defense pathways that control OROV infection and disease, we evaluated OROV pathogenesis and immune responses in primary cells and mice that were deficient in the RIG-I-like receptor signaling pathway (MDA5, RIG-I, or MAVS), downstream regulatory transcription factors (IRF-3 or IRF-7), IFN-β, or the receptor for type I IFN signaling (IFNAR). OROV replicated to higher levels in primary fibroblasts and dendritic cells lacking MAVS signaling, the transcription factors IRF-3 and IRF-7, or IFNAR. In mice, deletion of IFNAR, MAVS, or IRF-3 and IRF-7 resulted in uncontrolled OROV replication, hypercytokinemia, extensive liver damage, and death whereas wild-type (WT) congenic animals failed to develop disease. Unexpectedly, mice with a selective deletion of IFNAR on myeloid cells (CD11c Cre(+) Ifnar(f/f) or LysM Cre(+) Ifnar(f/f)) did not sustain enhanced disease with OROV or La Crosse virus, a closely related encephalitic orthobunyavirus. In bone marrow chimera studies, recipient irradiated Ifnar(-/-) mice reconstituted with WT hematopoietic cells sustained high levels of OROV replication and liver damage, whereas WT mice reconstituted with Ifnar(-/-) bone marrow were resistant to disease. Collectively, these results establish a dominant protective role for MAVS, IRF-3 and IRF-7, and IFNAR in restricting OROV virus infection and tissue injury, and suggest that IFN signaling in non-myeloid cells contributes to the host defense against orthobunyaviruses. Oropouche virus (OROV) is an emerging arthropod-transmitted orthobunyavirus that causes episodic outbreaks of a debilitating febrile illness in humans in countries of South and Central America. The continued expansion of the range and number of its arthropod vectors increases the likelihood that OROV will spread into new regions. At present, the pathogenesis of OROV in humans or other vertebrate animals remains poorly understood. To define cellular mechanisms of control of OROV infection, we performed infection studies in a series of primary cells and mice that were deficient in key innate immune genes involved in pathogen recognition and control. Our results establish that a MAVS-dependent type I IFN signaling pathway has a dominant role in restricting OROV infection and pathogenesis in vivo.