Matrix Metalloproteinases and their Tissue Inhibitors as Biomarkers in Ulcerative Colitis and Crohn s Disease

Matrix metalloproteinases (MMPs) represent a family of 23 metalloendopeptidases, collectively capable of degrading all components of the extracellular matrix. MMPs have been implicated in several inflammatory processes such as arthritis, atherosclerosis, and even carcinomas. They are also involved in several beneficial activities such as epithelial repair. MMPs are inhibited by endogenous tissue inhibitors of matrix metalloproteinases (TIMP). In this study, MMPs were investigated in intestinal mucosa of inflammatory bowel diseases (IBD), chronic intestinal disorders. The main focus was to characterize mucosal inflammation in the intestine, but also cutaneous pyoderma gangrenosum (PG), to assess similarites with IBD inflammation. MMPs and TIMPs were mainly examined in colonic mucosa, in adult Crohn s disease (CD), and paediatric CD, ulcerative colitis (UC), and indeterminate colitis (IC). Ileal pouch mucosa of proctocolectomized paediatric onset IBD patients was also investigated to characterize pouch mucosa. The focus was on finding specific MMPs that could act as markers to differentiate between different IBD disorders, and MMPs that could be implied as markers for tissue injury, potentially serving as targets for MMP-inhibitors. All examinations were performed using immunohistochemistry. The results show that immunosuppressive agents decrease stromal expression of MMP-9 and -26 that could serve as specific targets for MMP-inhibitors in treating CD. In paediatric colonic inflammation, MMP-10 and TIMP-3 present as molecular markers for IBD inflammation, and MMP-7 for CD. MMP expression in the the pouch mucosa could not be classified as strictly IBD- or non-IBD-like. For the first time, this study describes the expression of MMP-3, -7, -9, -12, and TIMP-2 and -3 in pouch mucosa. The MMP profile in PG bears resemblance to both intestinal IBD inflammation and cutaneous inflammation. Based on the results, MMPs and their inhibitors emerge as promising tools in the differential diagnosis of IBD and characterization of the disease subtype, although further research is necessary. Furthermore, the expression of several MMPs in pouch has been described for the first time. While further research is warranted, the findings contribute to a better understanding of events occurring in IBD mucosa, as well as pyoderma gangrenosum.

Genetic Variation and Clinical Manifestations in Inflammatory Bowel Disease

Crohn s disease (CD) and ulcerative colitis (UC), collectively known as inflammatory bowel disease (IBD), are characterised by chronic inflammation of the gastrointestinal tract. IBD prevalence in Finland is approximately 3-4 per 1000 inhabitants with a peak incidence in adolescence. The symptoms of IBD include diarrhoea, abdominal pain, fever, and weight loss. The precise aetiology of IBD is unknown but interplay of environmental risk factors and immunologic changes trigger the disease in a genetically susceptible individual. Twin and family studies have provided strong evidence for genetic factors in IBD susceptibility, and genetic factors may be more prominent in CD than UC. The first CD susceptibility gene was identified in 2001. Three common mutations R702W, G908R, and 1007fs of the CARD15/NOD2 gene are shown to associate independently with CD but the magnitude of association varies between different populations. The present study aimed at identifying mutations and genetic variations in IBD susceptibility and candidate genes. In addition, correlation to phenotype was also assessed. One of the main objectives of this study was to evaluate the role of CARD15 in a Finnish CD cohort. 271 CD patients were studied for the three common mutations and the results showed a lower mutation frequency than in other Caucasian populations. Only 16% of the patients carried one of the three mutations. Ileal location as well as stricturing and penetrating behaviour of the disease were associated with occurrence of the mutations. The whole protein coding region of CARD15 was screened for possible Finnish founder mutations. In addition to several sequence variants, five novel mutations (R38M, W355X, P727L, W907R, and R1019X) were identified in five patients. Functional consequences of these novel variants were studied in vitro, and these studies demonstrated a profound impairment of MDP response. Investigation of CARD15 mutation frequency in healthy people across three continents showed a large geographic fluctuation. No simple correlation between mutation frequency and disease incidence was seen in populations studied. The occurrence of double mutant carriers in healthy controls suggested that the penetrance of risk alleles is low. Other main objectives aimed at identifying other genetic variations that are involved in the susceptibility to IBD. We investigated the most plausible IBD candidate genes including TRAF6, SLC22A4, SLC22A5, DLG5, TLR4, TNFRSF1A, ABCB1/MDR1, IL23R, and ATG16L1. The marker for a chromosome 5 risk haplotype and the rare HLA-DRB1*0103 allele were also studied. The study cohort consisted of 699 IBD patients (240 CD and 459 UC), of which 23% had a first-degree relative with IBD. Of the several candidate genes studied, IL23R was associated with CD susceptibility, and TNFRSF1A as well as the HLA-DRB1*0103 allele with UC susceptibility. IL23R variants also showed association with the stricturing phenotype and longer disease duration in CD patients. In addition, TNFRSF1A variants were more common among familial UC and ileocolonic CD. In conclusion, the common CARD15 mutations were shown to account for 16% of CD cases in Finland. Novel CARD15 variants identified in the present study are most likely disease-causing mutations, as judged by the results of in vitro studies. The present study also confirms the IL23R association with CD susceptibility and, in addition, TNFRSF1A and HLA-DRB1*0103 allele association with UC of specific clinical phenotypes.

Health-related quality of life, symptoms and comorbidity in inflammatory bowel disease

Health-related quality of life (HRQoL) measurement has become an important outcome in treatment trials and in health policy decisions. HRQoL can be measured by using generic or disease-specific tools. Generic instruments can be used for comparing health status among patients in different health states and conditions but they do not focus specifically on the issues relevant in a particular disease. Disease-specific tools may be more responsive to changes within a specific condition. In earlier studies, impairment of HRQoL has been evident in patients with inflammatory bowel disease (IBD), especially when the disease is active. Data about the impact of comorbidity or demographic characteristics of the patients on HRQoL are partly controversial. This study, which comprised 2913 adult IBD patients, examined HRQoL using the disease-specific IBDQ and the general 15D instruments. The 15D scores of IBD patients were compared with scores of a gender and age matched general population sample. Frequency of IBD symptoms and arrangement of therapy were studied and compared with those of IBD patients in an earlier European study. Furthermore, data of other chronic diseases of the patients were obtained from the Social Insurance Institution s reimbursement register and comorbidity of IBD patients was compared with that of age and gender matched controls. --- Of the respondents, 37% reported that they suffered from disturbing IBD symptoms weekly. In 17% of the patients, the symptoms greatly affected the ability to enjoy leisure activities, and 14% stated that these symptoms greatly affected their capacity to work. Despite that, the great majority (93%) of patients expressed satisfaction with their current treatment, which exceeded the rate observed in the other European patients. The mean IBDQ score was 163, as the possible range is 32-224, and disease activity was strongly correlated with HRQoL. Older age, comorbid diseases, and female gender were also related to impairment of HRQoL. Lower HRQoL scores were seen also in newly-diagnosed patients and in those with a history of surgery, especially after stoma or ileal pouch-anal anastomosis (IPAA) operation. The range of 15D scores was 0.30-1.00, with mean of 0.87. As with the IBDQ, disease activity, older age and history of surgery were correlated with the score. Both the newly-diagnosed patients and patients with a long-lasting disease had lower scores than average even after adjusting for age. The 15D scores of IBD patients were significantly lower than those of the control group. A strong correlation was seen between the 15D and the IBDQ scores. Comorbidity with other chronic diseases was observed in 29% of IBD patients. Connective tissue diseases, chronic obstructive pulmonary diseases, pernicious anaemia, and coronary heart disease (CHD) were significantly increased in patients with IBD. Especially female IBD patients appeared to be at increased risk for CHD, and patients who reported weekly IBD symptoms had a higher risk for having other chronic diseases in addition to IBD. Comorbidity impaired HRQoL, as measured with both generic and disease-specific tools. In conclusion, HRQoL is impaired in IBD patients. An understanding of predictors of HRQoL will help to recognise patients who will need special support.

Effect of sliding speed on friction and wear of uni-directional aramid fibre-phenolic resin composite

A previous study on the tribological performance of a compression-moulded aramid fibre-phenolic resin composite, containing 30% continuous fibre, showed that this composite provides a reasonable combination of the friction coefficient and wear rate to be used as a friction component, such as a brake shoe. In the present work, the effect of sliding speed on the friction and wear behaviour of this composite has been investigated. The sliding experiments were conducted in a speed range of 0.1-6 m s(-1) at two normal pressure levels of 1.0 and 4.9 MPa. The coefficient of friction was found to be stable over a wide range of sliding speeds and normal pressures. The wear of the composite was found to be insensitive to changes in the speed in the higher speed range. The results have been supplemented with scanning electron micrographs to help understand possible friction and wear mechanisms.

Tribological characteristics of A356 Al alloy-SiC(P) composite discs

The dry sliding wear and friction behaviour of A356 Al alloy and its composites containing 10 and 20 vol.% SiC(P) have been studied using pin-on-disc set up. In these tests, A356 Al alloy and its composites are used as disc whereas brake pad was used in the form of pins. Wear tests were carried out at a load of 192 N and the sliding speed was varied from 1 to 5 m/s. Tests were done for a sliding distance of 15 km. The effects of sliding velocity on the wear rate, coefficient of friction and nature of tribolayers formed on discs have been studied. Wear rates of composites as calculated by weight loss method, found to be negative at sliding speed of more than 2 m/s. Worn surfaces of pins and discs have been analyzed using scanning electron microscope. SEM and EDAX analysis of worn surfaces of composite discs showed formation of tribolayers, consisting of mixture of oxides of Al, Si, Cu, Ca, Ba, Mg, and Fe. In these layers, copper and barium content found to be increase with sliding speed in the case of composites. (C) 2011 Elsevier B.V. All rights reserved.

Adaptation of small capacity natural gas engine for producer gas operation

This article addresses the adaptation of a low-power natural gas engine for using producer gas as a fuel. The 5.9 L natural gas engine with a compression ratio of 10.5:1, rated at 55 kW shaft power, delivered 30 kW using producer gas as fuel in the naturally aspirated mode. Optimal ignition timing for peak power was found to be 20 degrees before top dead centre. Air-to-fuel ratio (A/F) was found to be 1.2 +/- 0.1 over a range of loads. Critical evaluation of the energy flows in the engine resulted in identifying losses and optimizing the engine cooling. The specific fuel consumption was found to be 1.2 +/- 0.1 kg of biomass per kilowatt hour. A reduction of 40 per cent in brake mean effective pressure was observed compared with natural gas operation. Governor response to load variations has been studied with respect to frequency recovery time. The study also attempts to adopt a turbocharger for higher power output. Preliminary results suggest a possibility of about 30 per cent increase in the output.

Strategies for high efficiency and stability in biogas-fuelled small engines

This work assesses the performance of small biogas-fuelled engines and explores high-efficiency strategies for power generation in the very low power range of less than 1000 W. Experiments were performed on a small 95-cc, single-cylinder, four-stroke spark-ignition engine operating on biogas. The engine was operated in two modes, i.e., `premixed' and `fuel injection' modes, using both single and dual spark plug configurations. Measurements of in-cylinder pressure, crank angle, brake power, air and fuel flow rates, and exhaust emissions were conducted. Cycle-to-cycle variations in engine in-cylinder pressure and power were also studied and assessed quantitatively for various loading conditions. Results suggest that biogas combustion can be fairly sensitive to the ignition strategies thereby affecting the power output and efficiency. Further, results indicate that continuous fuel injection shows superior performance compared to the premixed case especially at low loads owing to possible charge stratification in the engine cylinder. Overall, this study has demonstrated for the first time that a combination of technologies such as lean burn, fuel injection, and dual spark plug ignition can provide highly efficient and stable operation in a biogas-fuelled small S.I. engine, especially in the low power range of 450-1000W. (C) 2014 Elsevier Inc. All rights reserved.

Selection and thermodynamic analysis of a turbocharger for a producer gas-fuelled multi-cylinder engine

The current work addresses the use of producer gas, a bio-derived gaseous alternative fuel, in engines designed for natural gas, derived from diesel engine frames. Impact of the use of producer gas on the general engine performance with specific focus on turbo-charging is addressed. The operation of a particular engine frame with diesel, natural gas and producer gas indicates that the peak load achieved is highest with diesel fuel (in compression ignition mode) followed by natural gas and producer gas (both in spark ignite mode). Detailed analysis of the engine power de-rating on fuelling with natural gas and producer gas indicates that the change in compression ratio (migration from compression to spark ignited mode), difference in mixture calorific value and turbocharger mismatch are the primary contributing factors. The largest de-rating occurs due to turbocharger mismatch. Turbocharger selection and optimization is identified as the strategy to recover the non-thermodynamic power loss, identified as the recovery potential (the loss due to mixture calorific value and turbocharger mismatch) on operating the engine with a fuel different from the base fuel. A turbocharged after-cooled six cylinder, 5.9 l, 90 kWe (diesel rating) engine (12.2 bar BMEP) is available commercially as a naturally aspirated natural gas engine delivering a peak load of 44.0 kWe (6.0 bar BMEP). The engine delivers a load of 27.3 kWe with producer gas under naturally aspirated mode. On charge boosting the engine with a turbocharger similar in configuration to the diesel engine turbocharger, the peak load delivered with producer gas is 36 kWe (4.8 bar BMEP) indicating a de-rating of about 60% over the baseline diesel mode. Estimation of knock limited peak load for producer gas-fuelled operation on the engine frame using a Wiebe function-based zero-dimensional code indicates a knock limited peak load of 76 kWe, indicating the potential to recover about 40 kWe. As a part of the recovery strategy, optimizing the ignition timing for maximum brake torque based on both spark sweep tests and established combustion descriptors and engine-turbocharger matching for producer gas-fuelled operation resulted in a knock limited peak load of 72.8 kWe (9.9 bar BMEP) at a compressor pressure ratio of 2.30. The de-rating of about 17.0 kWe compared to diesel rating is attributed to the reduction in compression ratio. With load recovery, the specific biomass consumption reduces from 1.2 kg/kWh to 1.0 kg/kWh, an improvement of over 16% while the engine thermal efficiency increases from 28% to 32%. The thermodynamic analysis of the compressor and the turbine indicates an isentropic efficiency of 74.5% and 73%, respectively.

Influence of fuel hydrogen fraction on syngas fueled SI engine: Fuel thermo-physical property analysis and in-cylinder experimental investigations

Hydrogen, either in pure form or as a gaseous fuel mixture specie enhances the fuel conversion efficiency and reduce emissions in an internal combustion engine. This is due to the reduction in combustion duration attributed to higher laminar flame speeds. Hydrogen is also expected to increase the engine convective heat flux, attributed (directly or indirectly) to parameters like higher adiabatic flame temperature, laminar flame speed, thermal conductivity and diffusivity and lower flame quenching distance. These factors (adversely) affect the thermo-kinematic response and offset some of the benefits. The current work addresses the influence of mixture hydrogen fraction in syngas on the engine energy balance and the thermo-kinematic response for close to stoichiometric operating conditions. Four different bio-derived syngas compositions with fuel calorific value varying from 3.14 MJ/kg to 7.55 MJ/kg and air fuel mixture hydrogen fraction varying from 7.1% to 14.2% by volume are used. The analysis comprises of (a) use of chemical kinetics simulation package CHEMKIN for quantifying the thermo-physical properties (b) 0-D model for engine in-cylinder analysis and (c) in-cylinder investigations on a two-cylinder engine in open loop cooling mode for quantifying the thermo-kinematic response and engine energy balance. With lower adiabatic flame temperature for Syngas, the in-cylinder heat transfer analysis suggests that temperature has little effect in terms of increasing the heat flux. For typical engine like conditions (700 K and 25 bar at CR of 10), the laminar flame speed for syngas exceeds that of methane (55.5 cm/s) beyond mixture hydrogen fraction of 11% and is attributed to the increase in H based radicals. This leads to a reduction in the effective Lewis number and laminar flame thickness, potentially inducing flame instability and cellularity. Use of a thermodynamic model to assess the isolated influence of thermal conductivity and diffusivity on heat flux suggests an increase in the peak heat flux between 2% and 15% for the lowest (0.420 MW/m(2)) and highest (0.480 MW/m(2)) hydrogen containing syngas over methane (0.415 MW/m(2)) fueled operation. Experimental investigations indicate the engine cooling load for syngas fueled engine is higher by about 7% and 12% as compared to methane fueled operation; the losses are seen to increase with increasing mixture hydrogen fraction. Increase in the gas to electricity efficiency is observed from 18% to 24% as the mixture hydrogen fraction increases from 7.1% to 9.5%. Further increase in mixture hydrogen fraction to 14.2% results in the reduction of efficiency to 23%; argued due to the changes in the initial and terminal stages of combustion. On doubling of mixture hydrogen fraction, the flame kernel development and fast burn phase duration decrease by about 7% and 10% respectively and the terminal combustion duration, corresponding to 90%-98% mass burn, increases by about 23%. This increase in combustion duration arises from the cooling of the near wall mixture in the boundary layer attributed to the presence of hydrogen. The enhancement in engine cooling load and subsequent reduction in the brake thermal efficiency with increasing hydrogen fraction is evident from the engine energy balance along with the cumulative heat release profiles. Copyright (C) 2015, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.

La ley del suelo del País Vasco : un paso más hacia la protección del suelo rural

[ES]La Ley del suelo del País Vasco del 2007 nace con el objeto de favorecer el acceso a una vivienda digna. Sin embargo, en la medida en que apuesta por frenar la especulación y la sostenibilidad del medio legisla sobre el tratamiento que se le ha de aportar al suelo no urbanizable. En este caso, no altera sustancialmente la regulación del suelo rural pero sí incorpora nuevas obligaciones dirigidas a frenar la intensidad de la urbanización en este suelo. Se regula la construcción de nueva vivienda, el desarrollo urbanístico de núcleos y barrios rurales y se obliga a profundizar en la calificación del suelo no urbanizable. La aplicación de los nuevos contenidos quedan en manos de los municipios e instituciones sectoriales y los primeros resultados parecen denotar un cambio de tendencia en municipios que han observado la pérdida de calidad paisajística del medio rural, la creciente especulación y la desagrarización de este entorno.

Disko-balaztaren fabrikazio prozesuaren deskribapena eta mekanizaziorako CAM bidezko programazioa

[EU]Lan honetan auto baten disko-balaztaren fabrikazio prozesua deskribatzen da, mekanizazio prozesuaren CAM bidezko programazioan sakonduz. Disko-balaztaren fabrikazioarekin hasi aurretik, informazio osagarri bezala, honek historian zehar izan duen garapena eta piezaren deskribapen zein funtzionamenduaren azalpena ematen dira. Jarraian, disko-balaztaren fabrikazioaren alderdi ezberdinak azaltzen dira, prozesu honek aurkezten dituen aukera desberdinak adieraziz. Azkenik, CAM bidezko programazioaren funtzionamendua erakusten da disko-balaztaren mekanizazio prozesurako aplikatuta.

Generación de energía eléctrica por combustión de biomasa forestal mediante ciclo rankine. Central de 2MW

[ES]Este proyecto se centra en el estudio y diseño de una central de generación de energía eléctrica por medio de biomasa forestal. La motivación para la realización de este proyecto reside en la gran importancia que en los últimos años están tomando las energías renovables. El Calentamiento Global es un hecho que durante los últimos años ha llevado a la investigación y desarrollo de las energías alternativas, que frenan o contribuyen al ralentizamiento de este fenómeno. Por su parte la implantación de una planta como la que se estudia a continuación, no solo ayudaría a la reducción de emisiones netas de CO2 a la atmósfera, sino que también tendría numerosas ventajas como son la creación de empleo, la limpieza de bosques, lo que ayuda a la prevención de incendios y plagas, y proporcionaría una independencia energética. Los pasos que se van a seguir en el proyecto son los siguientes:  Explicar el alcance y los objetivos del proyecto. Desarrollar las posibles alternativas que existen para la valorización de la biomasa forestal, incluyendo un resumen de las ventajas y desventajas que cada una presenta. Informe detallado de la alternativa seleccionada, la combustión, que incluye la explicación del proceso en la planta desde que el residuo sale del bosque, hasta la obtención de la energía eléctrica. Análisis económico y rentabilidad de la planta. Realizar el cronograma del proyecto. Por último se realizará un análisis de los posibles riesgos.

Legitimidade constitucional da cognição sumária: limites impostos pelo contraditório participativo.

A tese objetiva estruturar os pressupostos constitucionais impostos pelo conteúdo atual e humanizado do contraditório participativo às técnicas de sumarização da cognição. A primeira parte do estudo volta-se ao descortínio do papel do contraditório no sistema processual civil, do seu conteúdo mínimo atual, a partir da experiência internacional, em especial das Cortes de proteção dos direitos humanos, em confronto com o estágio evolutivo da jurisprudência brasileira. A segunda parte estuda as pressões exercidas pela celeridade sobre as fronteiras do contraditório, passando pelo exame dos dados disponibilizados pelo Conselho Nacional de Justiça e por outros institutos, pelo conteúdo do direito à razoável duração dos processos, também com amparo na experiência das Cortes internacionais de proteção dos direitos humanos, com o exame detido das condenações impostas ao Brasil pela Corte Interamericana de Direitos Humanos e da urisprudência interna sobre o tema, que nega aos prejudicados o direito à reparação dos danos sofridos pelos retardos injustificados. Definidas as bases, segue-se a análise das técnicas de sumarização da cognição, seus fundamentos, objetivos e espécies. A cognição sumária é definida em contraposição à cognição plena, segundo a qual as partes podem exercer, plenamente, em Juízo, os direitos inerentes ao contraditório participativo. O último quadrante se volta à estruturação dos pressupostos constitucionais legitimadores do emprego das técnicas de sumarização da cognição, impostos pelo contraditório como freio às pressões constantes da celeridade. O emprego legítimo das técnicas de tutela diferenciadas que se valem da cognição sumária para acelerar os resultados pressupõe, no quadro constitucional atual, (i) a observância do núcleo essencial do contraditório, identificado na audiência bilateral, em todo o iter da relação processual, (ii) a predeterminação legislativa, para que os cortes cognitivos não venham a ser casuisticamente realizados, (iii) a oportunidade, assegurada às partes, para integrar o contraditório em outra fase ou processo, em cognição plena, bem como (iv) a manutenção do equilíbrio na estabilização dos resultados, não podendo a cognição sumária, porque marcada pela incompletude, ser exaustiva em si. Ao final, depois do exame do caráter renunciável das garantias, é realizada a análise de alguns institutos processuais vigentes, nos quais é possível verificar o traço da sumarização da cognição, seguida da indicação das correções legislativas necessárias à conformação dos modelos aos padrões legitimadores propostos, reequilibrando as bases do sistema processual civil.

Diseño del sistema de tensor de cadena y acople de pinza de freno trasero para moto de competición.

[ES]En este documento se propone el diseño de dos sistemas imprescindibles en el tren trasero de una moto de competición, el sistema de tensor de cadena y el del acople de pinza de freno trasero. Junto a estos sistemas se diseñará, dada su relevancia, el basculante de la moto. Estos diseños se realizarán de tal manera que cumplan una serie de requisitos geométricos y de resistencia, garantizando en todo momento la estabilidad y seguridad del piloto. Se realizará también el estudio de la fabricación de cada uno de los elementos que componen los sistemas, con el fin de realizar diseños viables, que resulten económicamente factibles y mantengan un alto grado de calidad. En el proyecto se analizarán las diferentes alternativas de los sistemas que se puedan adoptar, sus ventajas y desventajas, para así poder escoger, con un alto grado de seguridad, la opción que mejor cumpla los objetivos y condiciones establecidos. Cabe destacar que este proyecto se encuentra dentro de otro de mayor envergadura consistente en el diseño y la fabricación de una motocicleta de competición para participar en el campeonato internacional llamado “MotoStudent”. Esta competición se realiza entre universidades de todo el mundo y en ella los equipos de estudiantes se enfrentan al desafío de diseñar y desarrollar un prototipo de motocicleta de competición similar a la categoría mundialista de “Moto3”.

Auto karrozeria pieza baten elementu finituen bidezko konformaketaren simulazioa.

[EN]The aim of this project is to show how important PamStamp program might be when engineers have to design different parts of a car without producing them. On the one hand, they do not have to waste time producing different elements in those enormous stamping presses. In this case, designing the door of a car with this program they could calculate in a very accurately way the force that the press have to do to obtain our final product. In this way employees do not have to use steel sheets every time they want to change small parameters in the press such as the position of the brake or a little angle of the die. All they need to carry out this project is a computer, with this tool and some licenses we could save thousands of euros and avoid paying for expensive materials every time we want to test something in the project.