IL6/sIL6R Regulates TNFα-Inflammatory Response in Synovial Fibroblasts Through Modulation of Transcriptional and Post-Transcriptional Mechanisms

[Abstract] Introduction: The clinical efficacy of specific interleukin-6 inhibitors has confirmed the central role of IL6 in rheumatoid arthritis (RA). However the local role of IL6, in particular in synovial fibroblasts (SF) as a direct cellular target to IL6/sIL6R signal is not well characterized. The purpose of the study was to characterize the crosstalk between TNFα and IL6/sIL6R signaling to the effector pro-inflammatory response of SF. Methods: SF lines were stimulated with either TNFα, IL6/sIL6R, or both together, for the time and dose indicated for each experiment, and where indicated, cells were treated with inhibitors actinomycin D, adalimumab, ruxolitinib and cycloheximide. mRNA expression of cytokines, chemokines and matrix metalloproteases (MMPs) were analyzed by quantitative RT-PCR. Level of IL8/CXCL8 and CCL8 in culture supernatants was measured by ELISA. Mononuclear and polymorphonuclear cells migration assays were assessed by transwell using conditioned medium from SF cultures. Statistical analyses were performed as indicated in the corresponding figure legends and a p-value < 0.05 was considered statistically significant. Results: The stimulation of SF with IL6/sIL6R and TNFα, cooperatively promotes the expression of mono- and lymphocytic chemokines such as IL6, CCL8 and CCL2, as well as matrix degrading enzymes such as MMP1, while inhibiting the induction of central neutrophil chemokines such as IL8/CXCL8. These changes in the pattern of chemokines expression resulted in reduced polymorphonuclear (PMN) and increased mononuclear cells (MNC) chemoattraction by SF. Mechanistic analyses of the temporal expression of genes demonstrated that the cooperative regulation mediated by these two factors is mostly induced through de novo transcriptional mechanisms activated by IL6/sIL6R. Furthermore, we also demonstrate that TNFα and IL6/sIL6R cooperation is partially mediated by the expression of secondary factors signaling through JAK/STAT pathways. Conclusions: These results point out to a highly orchestrated response to IL6 in TNFα-induced SF and provide additional insights into the role of IL6/sIL6R in the context of RA, highlighting the contribution of IL6/sIL6R to the interplay of SF with other inflammatory cells.Instituto de Salud Carlos III; FIS 16/00032Instituto de Salud Carlos III; RETICS RD16/0012 RIE

Qualification of biomass in forest stands of Pinus taeda

The multiple use of planted forests can increase the availability of forest biomass for energy generation systems. To increase its potential energy is necessary to control properties such as moisture content and calorific value, which directly influence the energy capacity of fuel. In this context, this paper attempts to evaluate the variation of moisture content and calorific value of needles, branches, canopies and barks of Pinus taeda in different ages; to investigate the relationship between the moisture content and the net calorific value; and to define a regression model that best explains the behavior of the net calorific value. For the analysis was applied a completely randomized design with factorial arrangement with four components of trees in four ages of Pinus taeda. In the results, the model selected had only moisture content as independent variable; there was a high negative correlation between moisture content and net calorific value, and significant difference of these variables for all components and ages. Barks at different ages and branches from 14 years of age are the most suitable components for power generation.O uso múltiplo das florestas plantadas pode aumentar a disponibilidade da biomassa destinada a sistemas de geração de energia. Para intensificar o potencial energético dessa fonte é necessário controlar propriedades como o teor de umidade e poder calorífico, que influem diretamente na capacidade energética do combustível. Neste contexto, o trabalho buscou avaliar a variação do teor de umidade e poder calorífico em acículas, galhos, copas e cascas de Pinus taeda em diferentes idades; verificar a relação entre o teor de umidade e o poder calorífico líquido; e definir um modelo de regressão que melhor explique o comportamento do poder calorífico líquido. Para a análise foi aplicado um delineamento experimental inteiramente casualizado, com arranjo fatorial contendo quatro componentes de árvores em quatro idades de Pinus taeda. Nos resultados, o modelo selecionado apresentou apenas o teor de umidade como variável independente; observou-se elevada correlação negativa entre teor de umidade e poder calorífico líquido, além de diferença significativa destas variáveis para todos os componentes e idades. As cascas em diferentes idades e galhos a partir dos 14 anos de idade são os componentes mais indicados para geração de energia

Efecto del ataque de Leptocybe invasa en plantaciones de eucalipto destinadas a la producción de pulpa de celulosa kraft

El objetivo de la investigación fue evaluar el efecto del ataque de Leptocybe invasa en las propiedades dendrométricas de la madera de dos clones de eucalipto (Eucalyptus urophylla y Eucalyptus tereticornis), cultivados en los municipios de Imperatriz (Estado do Maranhão) y Darcinópolis (Estado de Tocantins), Brasil, destinados para la producción de pulpa kraft. Se analizaron 10 árboles de 3 años de edad atacados por Leptocybe invasa, para cada clon. El diagnóstico fue basado en la formación de grandes agallas en la copa, y con orificio de emergencia (cerrando el ciclo). Los resultados fueron constatados por la variación de las características de las especies evaluadas con relación a su altura total, diámetro, volumen de corteza, frecuencia de vasos, longitud de fibras, perfil radial de densidad y contenido de cenizas. Los árboles hospederos presentaron alteraciones en las variables dendrométricas, contenido de pentosanos y cenizas en la madera para ambos materiales genéticos, no siendo observadas variaciones en la densidad básica, dimensión de vasos y fibras, así como en los contenidos de lignina y extractivos de la madera

The Use of Antihypertensive Medication and the Risk of Breast Cancer in a Case-Control Study in a Spanish Population: The MCC-Spain Study

The evidence on the relationship between breast cancer and different types of antihypertensive drugs taken for at least 5 years is limited and inconsistent. Furthermore, the debate has recently been fueled again with new data reporting an increased risk of breast cancer among women with a long history of use of antihypertensive drugs compared with nonusers

TFG 2012/2013

Amb aquesta publicació, EINA, Centre universitari de Disseny i Art adscrit a la Universitat Autònoma de Barcelona, dóna a conèixer el recull dels Treballs de Fi de Grau presentats durant el curs 2012-2013. Voldríem que un recull com aquest donés una idea més precisa de la tasca que es realitza a EINA per tal de formar nous dissenyadors amb capacitat de respondre professionalment i intel·lectualment a les necessitats i exigències de la nostra societat. El treball formatiu s’orienta a oferir resultats que responguin tant a paràmetres de rigor acadèmic i capacitat d’anàlisi del context com a l’experimentació i la creació de nous llenguatges, tot fomentant el potencial innovador del disseny.Con esta publicación, EINA, Centro universitario de diseño y arte adscrito a la Universidad Autónoma de Barcelona, da a conocer la recopilación de los Trabajos de Fin de Grado presentados durante el curso 2012-2013. Querríamos que una recopilación como ésta diera una idea más precisa del trabajo que se realiza en EINA para formar nuevos diseñadores con capacidad de responder profesional e intelectualmente a las necesidades y exigencias de nuestra sociedad. El trabajo formativo se orienta a ofrecer resultados que respondan tanto a parámetros de rigor académico y capacidad de análisis, como a la experimentación y la creación de nuevos lenguajes, al tiempo que se fomenta el potencial innovador del diseño.With this publication, EINA, University School of Design and Art, ascribed to the Autonomous University of Barcelona, brings to the public eye the Final Degree Projects presented during the 2012-2013 academic year. Our hope is that this volume might offer a more precise idea of the task performed by EINA in training new designers, able to speak both professionally and intellectually to the needs and demands of our society. The educational task is oriented towards results that might respond to the parameters of academic rigour and the capacity for contextual analysis, as well as to considerations of experimentation and the creation of new languages, all the while reinforcing design’s innovative potential

Research and Design of a Routing Protocol in Large-Scale Wireless Sensor Networks

无线传感器网络，作为全球未来十大技术之一，集成了传感器技术、嵌入式计算技术、分布式信息处理和自组织网技术，可实时感知、采集、处理、传输网络分布区域内的各种信息数据，在军事国防、生物医疗、环境监测、抢险救灾、防恐反恐、危险区域远程控制等领域具有十分广阔的应用前景。 本文研究分析了无线传感器网络的已有路由协议，并针对大规模的无线传感器网络设计了一种树状路由协议，它根据节点地址信息来形成路由，从而简化了复杂繁冗的路由表查找和维护，节省了不必要的开销，提高了路由效率，实现了快速有效的数据传输。 为支持此路由协议本文提出了一种自适应动态地址分配算——ADAR（AdaptiveDynamicAddre...As one of the ten high technologies in the future, wireless sensor network, which is the integration of micro-sensors, embedded computing, modern network and Ad Hoc technologies, can apperceive, collect, process and transmit various information data within the region. It can be used in military defense, biomedical, environmental monitoring, disaster relief, counter-terrorism, remote control of haz...学位：工学硕士院系专业：信息科学与技术学院通信工程系_通信与信息系统学号：2332007115216

Variables of briquetting process and quality of forestry biomass briquettes Variáveis do processo de briquetagem e qualidade de briquetes de biomassa florestal

&lt;p&gt;In the quest for recovery of waste generated from forest production to the process of industrial transformation of the biomass it was developed the process of briquetting. The cluster of wood particles facilitates the operations of handling of combustible material in addition to concentrating the available energy in terms of volume. The purpose of this study was to evaluate whether the raw material affects the quality of the briquette and verify the effect of pressure applied during the mechanical and energy  characteristics of the final product, and to evaluate the behavior of the material mix (MIX) compared to pure materials. The briquettes were produced in a pilot  briquetter, hydraulic piston, 120 °C with a constant pressure of 50 bar for eight minutes and 65, 95 or&lt;br /&gt;130 bar for two minutes. Six briquettes were used for each treatment. The characteristics evaluated were calorific value (GCV), bulk density and compressive strength. The raw material has a greater influence on the quality of briquettes than the compaction pressure. The low pressure is the most suitable for Pinus sp forest biomass briquettes. In this, MIX submitted satisfactory quality of briquettes with PCS 4,773 kcal kg-1, density 1220 kg m-³ and compressive strength of 167 kgf cm-2.&lt;/p&gt;&lt;p&gt; &lt;/p&gt;&lt;p&gt;doi: 10.4336/2010.pfb.30.62.101&lt;/p&gt;<br>Na busca pelo aproveitamento dos resíduos gerados desde a produção florestal até os processos de transformação industrial da biomassa, desenvolveu-se o processo de briquetagem. A aglomeração de partículas de madeira facilita as operações de  manuseio do material combustível, além de concentrar a energia disponível em termos de volume. O objetivo do presente trabalho foi avaliar se a matéria-prima tem influência na qualidade do briquete e verificar o efeito da pressão aplicada durante o processo nas  características energéticas e mecânicas do produto final, além de avaliar o comportamento da  mistura de materiais (MIX) em relação aos materiais puros. Os briquetes foram produzidos em uma briquetadeira piloto, tipo pistão hidráulico, a 120 ºC com pressão constante de 50 bar por oito minutos e 65, 95 ou 130 bar por dois minutos. Foram utilizados seis briquetes para cada tratamento. As características avaliadas foram poder calorífico superior (PCS), densidade aparente e resistência à compressão. A matéria-prima tem maior influência na qualidade dos briquetes do que a pressão de compactação. A baixa pressão é a mais indicada para briquetes de biomassa florestal de Pinus sp. Nesta, o MIX apresentou qualidade satisfatória de briquetes com PCS de 4.773 kcal kg-1, densidade aparente de 1.220 kg m-³ e resistência à compressão de 167 kgf cm-2.&lt;br /&gt;&lt;p&gt;&lt;br /&gt;doi: 10.4336/2010.pfb.30.62.101&lt;/p&gt

Efecto del ataque de "Leptocybe invasa" en plantaciones de eucalipto destinadas a la producción de pulpa de celulosa kraft

The aim of the research was to evaluate the effect of the attack Leptocybe invasa in dendrometric variables and wood properties of two clones of eucalyptus (Eucalyptus urophylla and Eucalyptus tereticornis), grown in the municipalities of Imperatriz (state of Maranhão) and Darcinopolis (state of Tocantins), Brazil, for Kraft pulping. Data were collected 10 trees for each clone, the 3-year-old attacked by L. invasa. The diagnosed was based on formation of large guts all over the glass, and emergency hole (closing the loop). The results were confirmed by the variation of the characteristics of species assessed relative to their total height, diameter, volume of bark, vessel frequency, fiber size, radial density profile vessel frequency, fiber size, radial density profile, and ash content. Host trees obtained alterations in dendrometric variables, content of pentosans and wood ashes for both genetic materials, not being observed variations in specific gravity, and size of vessels and fibers, as well as the contents of lignin and wood extractives. Keywords: Biotic stress, Eucalyptus tereticornis, Eucalyptus urophylla, gall wasp, woody qualityEl objetivo de la investigación fue evaluar el efecto del ataque de Leptocybe invasa en las propiedades dendrométricas de la madera de dos clones de eucalipto (Eucalyptus urophylla y Eucalyptus tereticornis), cultivados en los municipios de Imperatriz (Estado do Maranhão) y Darcinópolis (Estado de Tocantins), Brasil, destinados para la producción de pulpa kraft. Se analizaron 10 árboles de 3 años de edad atacados por Leptocybe invasa, para cada clon. El diagnóstico fue basado en la formación de grandes agallas en la copa, y con orificio de emergencia (cerrando el ciclo). Los resultados fueron constatados por la variación de las características de las especies evaluadas con relación a su altura total, diámetro, volumen de corteza, frecuencia de vasos, longitud de fibras, perfil radial de densidad y contenido de cenizas. Los árboles hospederos presentaron alteraciones en las variables dendrométricas, contenido de pentosanos y cenizas en la madera para ambos materiales genéticos, no siendo observadas variaciones en la densidad básica, dimensión de vasos y fibras, así como en los contenidos de lignina y extractivos de la madera

A New Mechanism of Resistance of Human Immunodeficiency Virus Type 2 to Integrase Inhibitors: A 5-Amino-Acid Insertion in the Integrase C-Terminal Domain

BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are crucial for the treatment of human immunodeficiency virus (HIV) type 2 infection, due to limited available therapeutic options. Recently, bictegravir has been approved for HIV-1, but no data are currently available for HIV-2. METHODS: We assessed the phenotypic susceptibility of 12 HIV-2 clinical isolates, obtained from 2 antiretroviral-naive and 10 antiretroviral-experienced patients, to 5 INSTIs (bictegravir, cabotegravir, dolutegravir, elvitegravir, and raltegravir) at the virological failure of an INSTI-based regimen. The 50% inhibitory concentrations (IC50s) were determined. Phenotypic inhibitory quotients were determined using trough INSTI plasma concentrations. RESULTS: Wild-type viruses were susceptible to the 5 INSTIs, with IC50s in the nanomolar range. Bictegravir had a lower IC50 than the other INSTIs on those HIV-2 isolates bearing major, resistance-associated mutations (codons 143, 148, and 155). We identified a new resistance profile-a 5-amino-acid insertion at codon 231 of the HIV-2 integrase (231INS)-in 6 patients at the virological failure of a raltegravir-based regimen. Those patients had adequate raltegravir concentrations, but harbored multiresistant viruses with low genotypic susceptibility scores (median = 1.5). This insertion rendered isolates highly resistant to raltegravir and elvitegravir, and moderately resistant to dolutegravir and cabotegravir. Regarding bictegravir, 2 isolates remained susceptible and 2 had a slight increase in IC50 (3- to 5-fold change). CONCLUSIONS: Our results confirm the potency of INSTI on HIV-2 clinical isolates with wild-type integrase. In addition, we identified a new resistance pathway, 231INS, selected in antiretroviral-experienced patients with multiresistant HIV-2 viruses. This highlights the need of close follow-up of those patients initiating an INSTI-based regimen