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The International Testbed of the CrossGrid Project has been in operation for the last three years, including 16 sites in 9 countries across Europe. The main achievements in installation and operation are described, and also the substantial experience gained on providing support to application and middleware developers in the project. Results are presented showing the availability of a realistic Grid framework to execute distributed interactive and parallel jobs.

Multi-jet production is observed in deep-inelastic electron proton scattering with the H1 detector at HERA. Jet rates for momentum transfers squared up to 500 GeV2 are determined using the JADE jet clustering algorithm. They are found to be in agreement with predictions from QCD based models.

The radiation hardness of different types of WLS fibers produced by BICRON, KURARAY and POL.HI.TECH has been systematically studied. Low dose rate irradiations (from 0.55 krad/h up to 4 krad/h and total dose of about 140 krad) were performed with a 60Co γ source. The results are compared with high dose rate irradiations (1.5 Mrad/h and total dose of 1 Mrad) in a mixed field of 20% of neutrons and 80% of γ's in a nuclear reactor. The degradation of the optical properties of fibers with different composition, namely different Ultraviolet absorber (UVA) concentration and different type of cladding are studied. Dose rate effects are investigated as well as the effect of irradiation with different type of particles. The UVA can help on the radiation hardness, but no permanent dose rate effects, or special effects due to the neutron component of the irradiation field were observed.

The energy loss spectrum of 150 GeV muons has been measured with a prototype of the ATLAS hadron calorimeter in the H8 beam of the CERN SPS. The differential probability ${\rm {d}}P/{\rm {d}}v$ per radiation length of a fractional energy loss $v = \Delta E_{\mu} / E_{\mu}$ has been measured in the range $v$ = 0.01 $\div$ 0.95; it is compared with the theoretical predictions for energy losses due to bremsstrahlung and production of electron-positron pairs or of energetic knock-on electrons. The integrated probability $\int_{0.01}^{0.95} ({\rm {d}}P/{\rm {d}}v) {\rm {d}}v$ is $(1.610\pm0.015_{{\rm {stat}}}\pm0.105_{{\rm {syst}}})\cdot10^{-3}$ in agreement with the theoretical predictions $1.556\cdot10^{-3}$ and $1.619\cdot10^{-3}$. Agreement with theory is also found in two intervals of $v$ where production of electron-positron pairs and knock-on electrons dominates. In the region of bremsstrahlung dominance ($v$ = 0.12 $\div$~0.95) the measured integrated probability $(1.160\pm0.040_{{\rm {stat}}}\pm0.075_{{\rm {syst}}})\cdot 10^{-4}$ is in agreement with the theoretical value of $1.185 \cdot 10^{-4} $, obtained using the Petrukhin and Shestakov description of the bremsstrahlung process. The same result is about 3.6 standard deviations (defined as the quadratic sum of statistical and systematic errors) lower than the theoretical prediction of $ 1.472\cdot 10^{-4}$, obtained using Tsai's description of bremsstrahlung.

El món de la medicina s'ha beneficiat molt de l'avenç tecnològic, però encara hi ha molt de camí per recórrer. La simulació clínica, tot i no ser imprescindible, és un element de gran impacte que cada cop s'està integrant més dins del món hospitalari. Una de les tecnologies innovadores que s'està implementant cada cop més dins de l'àmbit mèdic és la impressió 3D, un mètode de fabricació que actualment s'empra com a eina complementària per exemple de problemes clínics relacionat amb l'avaluació de tumors i malformacions, planificacions quirúrgiques que permetin fer els procediments clínics més propers als pacients i familiars. Incorpora també un gran ventall de materials que presenten característiques diverses capaces d'imitar els diferents teixits del cos humà. Totes aquestes qualitats fan que aquesta tecnologia sigui adient per la fabricació de models que permetin als usuaris aprendre a manejar nous instruments, practicar procediments de l'especialitat que fins ara aprenien de manera directa, i a agafar experiència i destresa a l'hora de desenvolupar les diferents tasques. Per aquest motiu, aquest treball fa servir la impressió 3D per dur a terme el disseny de dos models i els seus suports físics, un ginecològic i un urològic, elaborats additivament enfocats a la pràctica clínica. El projecte es caracteritza no només per la creació de models fisiològics, sinó pel disseny i fabricació d’elements capaços de mantenir estables i en la posició adient als models durant el transcurs del procediment clínic. Aquest avenç tecnològic de disseny tridimensional, suposa la possibilitat de continuar creant noves eines de treball destinades a la part més pràctica de la medicina, servint de pont entre aquesta disciplina i el món de l'enginyeria biomèdica. El mundo de la medicina se ha beneficiado mucho del avance tecnológico, pero todavía hay mucho camino por recorrer. La simulación clínica, aunque no es imprescindible, es un elemento de gran impacto que cada vez se está integrando más dentro del mundo hospitalario. Una de las tecnologías innovadoras que se está implementando cada vez más dentro del ámbito médico es la impresión 3D, un método de fabricación que actualmente se emplea como herramienta complementaria por ejemplo de problemas clínicos relacionados con la evaluación de tumores y malformaciones, planificaciones quirúrgicas que permitan realizar los procedimientos clínicos más cercanos a los pacientes y familiares. Incorpora también un gran abanico de materiales que presentan características diversas capaces de imitar a los diferentes tejidos del cuerpo humano. Todas estas cualidades hacen que esta tecnología sea adecuada para la fabricación de modelos que permitan a los médicos aprender a manejar nuevos instrumentos, practicar procedimientos de la especialidad que hasta ahora aprendían de manera directa, y a coger experiencia y destreza a la hora de desarrollar las diferentes tareas. Por este motivo, este trabajo utiliza la impresión 3D para llevar a cabo el diseño de dos modelos y sus soportes físicos, un ginecológico y un urológico, elaborados aditivamente enfocados a la práctica clínica. El proyecto se caracteriza no sólo por la creación de modelos fisiológicos, sino por el diseño y fabricación de elementos capaces de mantener estables y en la posición adecuada a los modelos durante el transcurso del procedimiento clínico. Este avance tecnológico de diseño tridimensional supone la posibilidad de continuar creando nuevas herramientas de trabajo destinadas a la parte más práctica de la medicina, sirviendo de puente entre esta disciplina y el mundo de la ingeniería biomédica. The world of medicine has benefited significantly from technological advancement, but there is still a long way to go. Clinical simulation, despite being unessential, represents an element of substantial impact that is becoming increasingly integrated within the hospital world. One of the innovative technologies that is being implemented more and more within the medical field is 3D printing. It consists of a manufacturing method currently used as a complementary tool for exemple from clinical problems related with the evaluation of tumors and malformations, surgical planning, and making clinical procedures easier to understand. It also incorporates an extensive range of materials that have diverse characteristics capable of imitating the different tissues of the human body. All these qualities make this technology suitable for the manufacture of models that allow doctors to learn to handle new instruments, practice specialty procedures that until now they learned directly and gain experience and skill when performing different tasks. For this reason, this work uses 3D printing to carry out the design of two physical models and their suports, one gynecological and one urological, produced additively to be used for clinical practice. The project is characterized not uniquely by the creation of physiological models, but also by the design and manufacture of the supports. These elements are capable of keeping the models stable and in the proper position during the course of the clinical procedure. This technological advance in three-dimensional design means the possibility of continuing to create new work tools for the most practical part of medicine. In conclusion, it serves as a bridge between medicine and the world of biomedical engineering.

A ontologia espinosana se articula sob o prisma da imanência, o que consiste em pensar a causa - a substância única, eterna e infinita nomeada Deus ou natureza -não separada dos seus respectivos efeitos. Deste modo, propõe-se que otratamento dos temas concernentes ao político e ao direito seja desenvolvido a partir do exame da ontologia. Sendo assim, analisa-se o conceito espinosano de conatus - o esforço de cada coisa para perseverar em seu ser -, o qual constitui oelemento de passagem da ontologia para a política e o direito na obra deEspinosa. Do conatus, chega-se ao seu espelho na política: a noção de direito natural, compreendida enquanto potência individual ou coletiva. Em sua dimensão coletiva, o direito natural apresenta como sujeito político a multitudo (multidão), cuja potência cria o direito comum (ou da cidade) e, segundo Espinosa, respalda o mais natural dos regimes: o imperium democrático. Todo esse percurso deriva da ontologia, já que a política se conduz mais pelos afetos - responsáveis pelo aumento ou pela diminuição do conatus - do que pela razão humana. Logo, a política depende do campo dos afetos, os quais participam da condição humana. Continuando o percurso, cria-se o direito comum que, por seu turno, possibilita a concretização do direito natural de cada um. Tendo por parâmetro a ontologia espinosana, pensada sob a perspectiva da imanência, encontram-se os elementos para dimensionar a política e o direito na contemporaneidade. Conclui-se que, para a construção de ambos sob o crivo da imanência, a potência coletiva da multitudo precisa ser constantemente revigorada a fim de que a cidade sempre se incline mais para o polo da liberdade e dos afetos alegres. Spinoza\'s ontology is built under the prism of immanence, which consists of thinking the cause - the unique, eternal and infinite substance named God or nature - not separated from its respective effects. Therefore, it\'s proposed that the treatment of the themes concerning the political and the law be developed from the examination of the ontology. As such, we analyze the concept Spinoza\'s conatus - the effort of each thing to endure in its being - which constitutes the element of passage from ontology to politics and the right in Spinoza\"s work. From the conatus, it reaches its mirror in politics: the notion of natural right, understood as individual or collective power (potentia). In its collective dimension, natural right presents as political subject the multitudo (multitude), whose power creates the common right (or civil) and, according to Espinosa, supports the most natural of the regimes: the democratic imperium. This whole trajectory derives from ontology, as politics is more conducted by affects - responsible for the increase or decrease of the conatus - than by human reason. Therefore, the politics depends on the field of affects, which participate in the human condition. Continuing the journey is created the common right which, in turn, allows the realization of the natural right of each one. Taking as parameter the Spinoza\'s ontology, thought under the perspective of immanence, are the elements to measure the politics and the law in contemporaneity. It concludes that, for the construction of both under the of immanence, the collective power of the multitudo needs to be constantly reinvigorated in order to the city always lean more towards the pole of joyful affects and freedom.

Autophagy is an essential intracellular process involved in survival, differentiation, development and cellular homeostasis. This catabolic mechanism supplies to the cell nutrients and energy to do its vital functions and gets rid of non-needed cellular components such as lipids, misfolded proteins and damage organelles. It consists on a multistep process highly regulated, conducted by autophagy-related proteins (ATGs), which starts by the formation of a vesicle which engulfs the material to be degraded to form an autophagosome following by the fusion to the lysosome. It contains the hydrolytic enzymes which are involve in the degradation of the cargo in the presence of an acidic environment (Levine & Kroemer, 2008). Dysfunction in the autophagy flux has been implicated in the progression of several diseases such as neurodegeneration, cancer and immune diseases, even in the normal ageing process. It is known that cell inability to degrade the cargo may lead to a defective autophagosome-lysosome fusion and thus, accumulation of autophagosome with non-degraded material inside the cells. This is the molecular base of a set of pathological conditions, known as lysosome storage disorder (LSD). Lysosomal dysfunction in most of these diseases is associated with impaired autophagic flux and autophagosome-lysosome fusion and a secondary accumulation of autophagy substrates such as SQSTM1/p62 and damage mitochondria. The key regulator of autophagy is mTOR which is involved in protein, lipid and nucleotide synthesis, lysosomal biogenesis, transcription, cytoskeletal rearrangements, energy metabolism, cell proliferation and survival. The presence of nutrients, growth factors and hypoxia induce mTOR promoting protein synthesis and cell growth and repressing autophagy. (Villanueva-Paz et al., 2016), (Munson & Ganley, 2015). Tay-Sachs and Sandhoff are two rare inherit LSDs which affect the nervous system and are characterized by early neuronal cell death and progressive neurodegeneration. They are caused by a mutation in a gene which encodes for the α (Tay-Sachs) and β (Sandhoff) subunit for the lysosome enzyme β-hexosaminidase A (HexA). This is the unique enzyme which is able to degrade a type of glycosphingolipids known as GM2 ganglioside. Consequently, there is an accumulation of them leading to cell death (Schuchman & Simonaro, 2013). The severity and progression of the diseases depend on the activity level of the dysfunctional enzyme and can be presented in infantile, juvenile and adult form with progressive neurodegeneration, hypotension, dysphagia, spasms, eye movement abnormalities, etc (Munson & Ganley, 2015). Nowadays, there is not an effective treatment beyond the palliative care. Although many mutations have been described, the molecular and cellular implications are still unknown. In the recent study, working with patient fibroblasts, it have been found low levels of mTOR pathway activation with the subsequent decreasing of protein synthesis and high levels of autophagy. However, it has been determined that the autophagy flux is impaired, with the accumulation of autophagosome with non-degrade material leading to the lysosomal permeabilization. Treatment of patient fibroblasts with L-arginine showed a partial recovery of cellular pathological alterations. La autofagia es un proceso intracelular esencial para la supervivencia, diferenciación, desarrollo y homeostasis celular. Este mecanismo catabólico provee a las células de energía y nutrientes necesarios para la realización de sus funciones vitales y la eliminación de componentes innecesarios para la célula como son lípidos, proteínas mal plegadas o agregadas y organelas dañadas. La autofagia es un proceso guiado por una serie de proteínas asociadas a la autofagia (ATGs), el cual comienza con la formación de una vesícula que engloba el material a degradar formando el autofagosoma. A continuación, tienen lugar la fusión entre el autofagosoma y el lisosoma el cual contiene las enzimas (hidrolasas) y el pH acido para la eliminación del cargo (Levine & Kroemer, 2008). La disfunción en la autofagia está implicada en la progresión de muchas enfermedades como neurodegeneración, cáncer, enfermedades inmunes e incluso en el envejecimiento. Una de las causas de la incapacidad de la degradación del cargo es consecuencia del fallo en la fusión del autofagosoma con el lisosoma que conlleva a la acumulación intracelular de material no degradado. Esto constituye la base de una serie de condiciones patológicas llamadas enfermedades de acumulación lisosomal (LSDs). La disfunción en el lisosoma en la mayoría de estas enfermedades está asociada a un defecto en la autofagia, así como en la fusión del autofagosoma y lisosoma, daño mitocondrial y acumulación de sustratos de la autofagia como SQSTM1/p62. El regulador clave de este proceso es la ruta mTOR la cual está implicada en la síntesis de proteínas, lípidos y nucleótidos, biogénesis lisosomal, trascripción, reordenamiento del citoesqueleto, metabolismo energético, proliferación celular y supervivencia. La presencia de nutrientes, factores de crecimiento o hipoxia inducen mTOR dando lugar al aumento en la síntesis proteica y crecimiento celular, así como con la inhibición de la autofagia (Villanueva-Paz et al., 2016), (Munson & Ganley, 2015). Tay-Sachs y Sandhoff son dos enfermedades raras hereditarias de acumulación lisosomal (LSD) que afecta al sistema nervioso y se caracterizan por muerte neuronal temprana y neurodegeneración progresiva. Están causadas por mutaciones en el gen que codifica la subunidad α (Tay-Sachs) y la subunidad β (Sandhoff) de la enzima β-Hexosaminidasa A (HexA). Esta enzima es la única capaz de degradar un tipo de glicoesfingolípidos conocidos como gangliósidos GM2. Como consecutiva, hay una acumulación intracelular que lleva a la muerte celular (Schuchman & Simonaro, 2013). La severidad y la progresión de estas enfermedades dependen del nivel de actividad de la HexA y pueden ser presentadas en forma infantil, juvenil o adulta. Entre sus síntomas destacan la hipotensión, disfagia, espasmos, movimiento anormal de los ojos y progresiva neurodegeneración (Munson & Ganley, 2015). Actualmente no existe ninguna cura o tratamiento efectivo para estas enfermedades, solo cuidados paliativos. Aunque se han descrito muchas mutaciones asociadas, las implicaciones celulares y moleculares siguen siendo desconocidas. En este estudio, trabajando a partir de fibroblastos de pacientes, se han descrito bajos niveles de activación de mTOR con la subsecuente disminución de la síntesis proteica y altos niveles de autofagia. Sin embargo, esta autofagia lejos de ser positiva en estas enfermedades sufre un bloqueo en el flujo con la acumulación de autofagosoma con material no degradado lo cual lleva a la aparición de permeabilización lisosoma. El tratamiento de las células de los pacientes con L-arginina mostró una parcial recuperación de las alteraciones celulares patológicas.

El trabajo de investigación está orientado a proponer un Modelo de Gestión de Incidentes, aplicando las buenas prácticas de ITIL v3.0 con elpropósito de mejorar la calidad de los servicios de tecnología de la información (TI) ofrecidos por la entidad en estudio. La aplicación del nuevo modelo de gestión de incidentes implicó la formalización del proceso de gestión de incidentes de tal manera que de modificaran algunos procedimientos que se esfecifican en el presente trabajo. La aplicación del modelo propuesto estuvo respaldada por la gerencia que permitió organizar mejor al personal en el proceso de gestión de incidentes, permitiendoles capacitarse y entender la aplicación del modelo propuesto. de los resultados de la aplicación del modelo, se puede observar que la atención de incidentes y la satisfacción del usuario final mejoraron. La creación de una linea base de indicadores permitirá hacer los ajustes necesarios al modelo con el objetivo de buscar la mejora continua del modelo.

Aging constitutes the major risk factor for metabolic disabilities onset and cardiovascular disease. Clinically, is associated with an increase in IL1β and IL18, which are cytokines released after inflammasome-dependent caspase-1 activation. This suggests that prevalence and severity of age-related diseases is partly due to chronic inflammasome activation and its contribution to increased inflammatory state. Age-related systemic inflammation is overall produced in numerous organs, including the heart and metabolic tissues such as liver. It is widely believed that a common mechanism drives to several declining disorders triggering adverse impact on healthy aging and affecting therefore, the quality of life and healthspan. This common nexus is termed inflamm-aging. The idea of inflammaging refers to a progressive increase of a proinflammatory state, a systemic low-grade inflammatory process that contributes to the onset and development of chronic diseases and degenerative changes as we age. Interestingly, age-related chronic low-grade inflammation leads to functional decline in many organs even in the absence of a particular disease. Inflammation could be defined as an acute reaction in response to infection or tissue damage to point out a particular injury. Nonetheless, when inflammation becomes chronic, it may trigger collateral damage and in some cases, autoimmune pathologies. Sometimes, inflammatory responses are stress-associated or host-derived signals that are known as damage-associated molecular patterns (DAMPs), which are released as a result of tissue homeostasis imbalance, such as self-derived ATP, cholesterol crystals, uric acid, glucose or environment-derived silica, among others. The inflammasome is a complex of multimeric proteins that consist of an intracellular sensor protein, the Nod-like receptor (NLR); the adaptor apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and, the proinflammatory caspase-1 precursor. The most in depth studied inflammasome is NLRP3, which is activated by a wide spectrum of stress and danger signals. Additionally, NLRP3 is special among innate immunity sensors, since is the only inflammasome that can be activated in response to a diverse gamut of host-derived metabolic “danger signals” to trigger “sterile inflammation”, which means an inflammatory response not caused by microbes. NLRP3- inflammasome mediated processes are therefore, crucial for both immunological and metabolic regulation. Importantly, it has been demonstrated that a large number of host-derived NLRP3-inflammasome activators tend to accumulate during the aging process, such as cholesterol crystals, resulting from acquired dietary patterns that maintain the chronic inflammatory state over time, together with the chronic lowgrade inflammation that aging itself involves, highly contribute to cardiometabolic diseases prevalence and severity. Autophagy is the main mechanism in charge of damaged organelles accumulation clearance, and its regulation depends on both intracellular and extracellular signals. AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) are genes involved in longevity and central regulators of autophagic machinery. Under nutrient limiting conditions autophagy becomes active by AMPK, via various mechanisms. However, when mTOR is activated autophagy gets inhibited. Both longevity genes are masters’ regulators of metabolism and there is existing evidence reporting that rather the activation of AMPK or mTOR attenuation enhance cardiac function. AMPK is essential to maintain cardio-metabolic homeostasis. This kinase has shown to be cardioprotective during ischemia. According to some research, mouse models lacking AMPK functionality, had exarcebated myocardial infarction. Activation of AMPK by metformin reduced overload- induced cardiac hypertrophy. Interestingly, it has been recently reported that nutraceutical compounds, including resveratrol, hydroxytyrosol or some flavonols among others, have AMPK-mediated therapeutic effects on diabetes mellitus and CVD, which gives a natural approach to AMPK pathway activation and cardio-metabolic events control. Cardio-metabolic events, such as type 2 diabetes mellitus, insulin resistance, metabolic syndrome, or cardiovascular disease, are determined by an individual’s age. Age-associated chronic inflammatory responses together with western-type lifestyle and certain acquired behavioral habits may induce autophagy impairment, shortened healthspan and a bad quality of life during aging. Data from the World Health Organization (WHO), estimate that by 2050 the proportion of the world’s population over 60 years old, will nearly double, which will represent an increase of 10%. Getting older is the major risk factor for the development of chronic diseases and represents an extraordinary financial burden on the health care systems, constituting a sanitary and a socioeconomic matter. Developing new strategies to attenuate chronic inflammatory state during aging might be a potential target to avoid many age-related cardiometabolic diseases. Here, we demonstrate that either the ablation of NLRP3-inflammasome or its specific pharmacological inhibition with the molecule MCC950, not only might contribute to lifespan, but also to extend healthspan, which is ultimately, the most appealing interest of becoming older. Premio Extraordinario de Doctorado US

El agrandamiento gingival es una entidad patológica englobada dentro de la clasificación de la enfermedad periodontal. Las causas más comunes son en primer lugar como manifestación secundaria al consumo de fármacos - hidantoínas, ciclosporina y bloqueantes de los canales del calcio – y en segundo lugar, la forma idiopática asociada a un síndrome denominado fibromatosis gingival hereditaria. La clínica de este agrandamiento gingival está bien definida, pero las vías moleculares no quedan del todo claras a pesar del gran número de ensayos que la han abordado. En general se habla de una etiopatogenia multifactorial en la que se asocian proliferación de fibroblastos con descenso en su apoptosis, disminución de la degradación de la matriz con aumento de su depósito y la presencia de diversos factores de crecimiento. En el presente estudio hemos tratado de aclarar el papel que juega la mitocondria en este proceso. Se conoce la importancia que esta organela toma en procesos como la inflamación y distintas enfermedades sistémicas, entre ellas la enfermedad periodontal. Además, al tratarse de fármacos cuya diana principal no va a ser la encía pero que actúan a este nivel, queremos ver cómo afectan a otro órgano de vital importancia, pero del que no tenemos una visión clínica directa, como es el corazón. Para lograr nuestros objetivos hemos usado en primer lugar un modelo animal en el que inducimos la patología con fármacos (ciclosporina A o nifedipina) comparándolos con un grupo control, y en segundo lugar hemos evaluado el tejido gingival de dos pacientes diagnosticados de fibromatosis gingival hereditaria. Así, hemos estudiado los tejidos a nivel histológico, ultraestructural y bioquímico con diversas técnicas. Analizando los resultados hemos encontrado que los cambios morfológicos y funcionales en la mitocondria y el estrés oxidativo podrían estar involucrados en la etiopatogenia de este proceso. El tratamiento con ciclosporina produjo un incremento del estrés oxidativo a nivel cardiaco, por lo que el paciente podría beneficiarse de un cotratamiento con antioxidantes para el control de este efecto secundario al fármaco. Seguimos necesitando más estudios que nos permitan aclarar las vías moleculares en este proceso.

Investigadores Estudiantes