Estudio de la expresión de Apolipoproteína D en células de astrocitoma humano. Un gen supresor de tumores peculiar

Las modificaciones epigenéticas son fundamentales para la diferenciación celular tanto en el periodo embrionario como en la edad adulta. Estas modificaciones incluyen la metilación del DNA y modificaciones en la acetilación de las histonas. La combinación de ambos fenómenos permite mantener un equilibrio en la expresión génica de nuestras células. Pero en ciertas ocasiones, como en la oncogénesis, este equilibrio se rompe, apareciendo represión en los genes supresores de tumores por medio de hipermetilación y una sobreexpresión de proto-oncogenes gracias a su hipometilación. Uno de estos genes que en el seno de los tejidos neoplásicos sufre una regulación a la baja es APOD. Un gen que codifica para una lipocalina a la que se le atribuyen múltiples funciones antioxidantes y antiproliferativas. En este trabajo se quiso estudiar la expresión del gen APOD en un cultivo celular de astrocitoma humano (1321N1) y ver si en condiciones basales el gen está reprimido a expensas de hipermetilación y cómo varia su expresión ante el estrés oxidativo (un inductor conocido de la transcripción de APOD). Mediante el uso de un agente desmetilante se demostró que, en efecto, el gen APOD en condiciones basales está regulado a la baja en esta línea celular. Pudimos observar además que el estrés oxidativo genera un cambio en la distribución intracelular de ApoD hacia organelas de pequeño tamaño. Por último, pero no por ello menos relevante, se observó un importante incremento en la transcripción de APOD en condiciones de escasez nutricional. Esto último hace sospechar que este incremento en los niveles de ApoD pudiera tener que ver con el papel antiproliferativo de dicha proteína, razón por la cual se le ha incluido en el grupo de genes supresores de tumores.Grado en Medicin

Web application for monitoring automated flowerpots

[EN] Nowadays, caring for your plants (that grow in gardens or flowerpots) has become more difficult and this can lead to slowing the growing process or even death of the plant. In order to help for the prevention of this problem so far has been created several devices which offer full control and automatization and can take care of your plants for you. Those systems however need to be managed easily as well as remotely. The usefulness of the mobile phones is well proven over the years and is one of the best solutions for the problem with the management of the automated systems. Developing a mobile application and making it user-friendly is a long process, but surely provides a great solution to the problem. The main purpose of the current work was to create a prototype of a mobile application for remote monitoring and control of those automated systems. In order to carry out this project, a research of similar systems have been done and from them the functionalities that are desired for the application have been extracted. All of them were described using Use-Case diagrams and tables. For the design of the application it was chosen to use the ThreeLayer architecture, because it is a part of another bigger project done by other students and this way it would provide bigger flexibility, but later it was developed using the MVC architecture in a local environment. The main goal of this project was to offer a way to visualize the data coming from the chombos, also a way to move it. Another objective that was achieved is to make the design of the application user-friendly and lightweight as well as responsive to be able to run on different devices. Most of the functionalities that were described are only visually implemented, but not functional, while only some of them were fully implemented to make the application feel alive.[ES] Actualmente, el cuidado de las plantas domésticas (que crecen en jardines o en macetas) es complicado para mucha gente, lo cual puede ocasionar un crecimiento más lento de las plantas o incluso que mueran. Para ayudar a prevenir este problema, se han creado dispositivos que ofrecen un control total y automático para el cuidado de las plantas. Sin embargo, estos sistemas necesitan ser gestionados fácilmente y de modo remoto. En los últimos años se ha demostrado la versatilidad de los teléfonos móviles, de modo que están siendo una de las mejores soluciones para el problema de manejar sistemas automáticos. El desarrollo de una aplicación web que sea fácil de usar es un proceso complejo, pero sin duda proporciona una solución adecuada al problema planteado. El propósito principal del trabajo actual fue crear un prototipo de una aplicación móvil para el monitoreo y control remoto de esos sistemas automatizados. Para llevar a cabo este proyecto, se ha realizado una investigación de sistemas similares y de ellos se han extraído las funcionalidades que se desean para la aplicación. Todos ellos se describieron utilizando diagramas de casos de uso y tablas. Para el diseño de la aplicación se optó por utilizar la arquitectura Tres Capas, ya que es parte de otro proyecto más grande realizado por otros estudiantes y de esta manera se obtendría una mayor flexibilidad, pero más tarde se desarrolló utilizando la arquitectura MVC en un entorno local. El objetivo principal de este proyecto era ofrecer una forma de visualizar los datos procedentes de los chombos, también una forma de moverlo. Otro objetivo que se logró es hacer que el diseño de la aplicación sea fácil de usar y ligero, además de responder a la posibilidad de ejecutar en diferentes dispositivos. La mayoría de las funcionalidades que se describieron sólo se implementan visualmente, pero no son funcionales, mientras que sólo algunas de ellas se implementaron completamente para que la aplicación se sintiera viva.Toshkov Yordanov, V. (2017). Web application for monitoring automated flowerpots. http://hdl.handle.net/10251/86927.TFG

Optimization of the Hot-Pressing Regime in the Production of Eco-Friendly Fibreboards Bonded with Hydrolysis Lignin

This research was aimed at studying the potential of using residual lignin from acid hydrolysis as a binder in manufacturing eco-friendly, dry-process fibreboards. For that purpose, a modification of the adhesive system and hot-pressing regime was conducted. The adhesive system applied was composed of 2 % phenol-formaldehyde (PF) resin and 10 % hydrolysis lignin (based on the dry fibres). The PF resin does not only act as a binder but generally contributes to the even distribution and good retention of the main binder – hydrolysis lignin. A specific hot-pressing cycle was used. In the first stage, the pressure was 1.0 MPa, followed by an increased pressure of 4.0 MPa, and subsequent cooling. The purpose of the initial lower pressure was softening the lignin and reduction of the material moisture content. The effect of the second stage of hot-pressing on the properties of eco-friendly fibreboards was investigated. It was determined that the fibreboards produced with 2 % PF resin and 10 % hydrolysis lignin have similar physical and mechanical properties to those of the control panels, produced with 10 % PF resin at a standard hot-pressing cycle. The findings of this work demonstrate that residual hydrolysis lignin can be effectively utilized as a binder in the production of eco-friendly, dry-process fibreboards with acceptable physical and mechanical properties

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Effect of the Adhesive System on the Properties of Fiberboard Panels Bonded with Hydrolysis Lignin and Phenol-Formaldehyde Resin

This study aimed to propose an alternative technological solution for manufacturing fiberboard panels using a modified hot-pressing regime and hydrolysis lignin as the main binder. The main novelty of the research is the optimized adhesive system composed of unmodified hydrolysis lignin and reduced phenol–formaldehyde (PF) resin content. The fiberboard panels were fabricated in the laboratory with a very low PF resin content, varying from 1% to 3.6%, and hydrolysis lignin addition levels varying from 7% to 10.8% (based on the dry wood fibers). A specific two-stage hot-pressing regime, including initial low pressure of 1.2 MPa and subsequent high pressure of 4 MPa, was applied. The effect of binder content and PF resin content in the adhesive system on the main properties of fiberboards (water absorption, thickness swelling, bending strength, modulus of elasticity, and internal bond strength) was investigated, and appropriate optimization was performed to define the optimal content of PF resin and hydrolysis lignin for complying with European standards. It was concluded that the proposed technology is suitable for manufacturing fiberboard panels fulfilling the strictest EN standard. Markedly, it was shown that for the production of this type of panels, the minimum total content of binders should be 10.6%, and the PF resin content should be at least 14% of the adhesive system

Homogenizace aerosolu při sprayové depozici polyfenylenvinylenu.

Two different spray deposition (SD) techniques were compared on polyvinylene (MDMO-PPV) used as a model material. SD and homogenized (h-SD) techniques were compared. Films of about 1 micron thickness were prepared by SD and h-SD and normal techniques from toluene solution with a concentration of 0.5 g/l. It was found that the ITO|MDMO-PPV|Al structures with h-SD MDMO-PPV films behave as a photovoltaic cell. Optical micrograph images show structure with typical discs. Current - voltage characteristics measured on samples with h-SD films show that an exposure to a white light increases the current two orders of magnitude.Dvě různé techniky sprajové depozice (SD) byly porovnány na polyvinylenu (MDMO-PPV) použité jako modelové materiály. Techniky SD a sprayové depozice z homogenizovaného aerosolu (h-SD) byly porovnány. Filmy o tloušťce přibližně 1 mikrometru byly připraveny metodami SD a h-SD a normálními technikami z roztoku v toluenu o koncentraci 0.5 g/l. Bylo zjištěno, že struktura ITO|MDMO-PPV|Al připravená metodou h-SD se chová jako fotovoltaický článek. Na fotografiích z mikroskopu vzorky vykazovaly typickou diskovou strukturu. Na voltampérových charakteristikách se projevilo zvýšení proudu o dva řády při ozáření bílým světlem

Towards Neural Charged Particle Tracking in Digital Tracking Calorimeters With Reinforcement Learning

We propose a novel technique for reconstructing charged particles in digital tracking calorimeters using reinforcement learning aiming to benefit from the rapid progress and success of neural network architectures without the dependency on simulated or manually-labeled data. Here we optimize by trial-and-error a behavior policy acting as an approximation to the full combinatorial optimization problem, maximizing the physical plausibility of sampled trajectories. In modern processing pipelines used in high energy physics and related applications, tracking plays an essential role allowing to identify and follow charged particle trajectories traversing particle detectors. Due to the high multiplicity of charged particles and their physical interactions, randomly deflecting the particles, the reconstruction is a challenging undertaking, requiring fast, accurate and robust algorithms. Our approach works on graph-structured data, capturing track hypotheses through edge connections between particles in the detector layers. We demonstrate in a comprehensive study on simulated data for a particle detector used for proton computed tomography, the high potential as well as the competitiveness of our approach compared to a heuristic search algorithm and a model trained on ground truth. Finally, we point out limitations of our approach, guiding towards a robust foundation for further development of reinforcement learning based tracking.publishedVersio

G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling

Ras GTPase-activating protein-binding proteins 1 and 2 (G3BP1 and G3BP2, respectively) are widely recognized as core components of stress granules (SGs). We report that G3BPs reside at the cytoplasmic surface of lysosomes. They act in a non-redundant manner to anchor the tuberous sclerosis complex (TSC) protein complex to lysosomes and suppress activation of the metabolic master regulator mechanistic target of rapamycin complex 1 (mTORC1) by amino acids and insulin. Like the TSC complex, G3BP1 deficiency elicits phenotypes related to mTORC1 hyperactivity. In the context of tumors, low G3BP1 levels enhance mTORC1-driven breast cancer cell motility and correlate with adverse outcomes in patients. Furthermore, G3bp1 inhibition in zebrafish disturbs neuronal development and function, leading to white matter heterotopia and neuronal hyperactivity. Thus, G3BPs are not only core components of SGs but also a key element of lysosomal TSC-mTORC1 signaling

Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo

BACKGROUND: Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagon-like peptide 1 receptor agonist, lixisenatide, improves glycemia, but its effects on CV events have not been thoroughly evaluated. METHODS: ELIXA (www.clinicaltrials.gov no. NCT01147250) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of lixisenatide in patients with T2DM and a recent ACS event. The primary aim is to evaluate the effects of lixisenatide on CV morbidity and mortality in a population at high CV risk. The primary efficacy end point is a composite of time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Data are systematically collected for safety outcomes, including hypoglycemia, pancreatitis, and malignancy. RESULTS: Enrollment began in July 2010 and ended in August 2013; 6,068 patients from 49 countries were randomized. Of these, 69% are men and 75% are white; at baseline, the mean ± SD age was 60.3 ± 9.7 years, body mass index was 30.2 ± 5.7 kg/m(2), and duration of T2DM was 9.3 ± 8.2 years. The qualifying ACS was a myocardial infarction in 83% and unstable angina in 17%. The study will continue until the positive adjudication of the protocol-specified number of primary CV events. CONCLUSION: ELIXA will be the first trial to report the safety and efficacy of a glucagon-like peptide 1 receptor agonist in people with T2DM and high CV event risk