Backplate Screen Modding

Aquest article recull el desenvolupament de Backplate Screen Modding, una aplicació per l'early-startup Beyond The Tech (BYT) per la personalització d'interiors de torres d'ordinadors, convertint un producte de disseny estàtic a un de dinàmic i més tecnològic, permetent la reproducció d'imatges, GIF i vídeos a una pantalla incorporada sobre les targetes gràfiques a l'interior de les torres d'ordinadors. L'aplicació permet desar imatges i GIF dels usuaris a la base de dades, brindant un servei personalitzat. A més, hi ha dissenys predeterminats fets per creadors artístics, de manera que freqüentment els dissenys van rotant entre ells, per fer un dinamisme més actiu, esdeveniments i sorpreses que BYT vol fer en comunitat. Els resultats obtinguts compleixen amb una principal expectativa, tenint una primera versió funcional i assolint la majoria d'objectius plantejats del TFG. Addicionalment, es mostra la planificació amb un diagrama de Gantt i el model de negoci del projecte, que mostra els detalls imprescindibles per l'estudi de la seva viabilitat.This article reports the development of Backplate Screen Modding, an application for the early-startup Beyond The Tech (BYT) for the customization of computer tower interiors, converting a static design product to a dynamic and more technological one, allowing the reproduction of images, GIF and videos on a screen incorporated on the graphic cards inside the computer towers. The application allows users' images and GIF to be saved in the database, providing a personalized service. In addition, there are predetermined designs made by artistic creators, so the designs are frequently rotated among them, to make a more active dynamism, events and surprises that BYT wants to make in community. The results obtained fulfill a main expectation, having a first functional version and achieving most of the objectives of the TFG. Additionally, the planning is shown with a Gantt chart and the business model of the project, which shows the essential details for the study of its viability.Este artículo recoge el desarrollo de Backplate Screen Modding, una aplicación para el early-startup Beyond The Tech (BYT) para la personalización de interiores de torres de ordenadores, convirtiendo un producto de diseño estático a uno dinámico y más tecnológico, permitiendo la reproducción de imágenes, GIF y vídeos en una pantalla incorporada sobre las tarjetas gráficas interior de las torres de ordenadores. La aplicación permite guardar imágenes y GIF de los usuarios en la base de datos, brindando un servicio personalizado. Además, hay diseños predeterminados hechos por creadores artísticos, por lo que frecuentemente los diseños vanrotando entre ellos, para realizar un dinamismo más activo, eventos y sorpresas que BYT quiere hacer en comunidad. Los resultados obtenidos cumplen con una principal expectativa, con una primera versión funcional y logrando la mayoría de objetivos planteados del TFG. Adicionalmente, se muestra la planificación con un diagrama de Gantt y el modelo de negocio del proyecto, que muestra los detalles imprescindibles para el estudio de su viabilidad

P-Stereogenic Ir-MaxPHOX: A Step toward Privileged Catalysts for Asymmetric Hydrogenation of Nonchelating Olefins

The Ir-MaxPHOX-type catalysts demonstrated high catalytic performance in the hydrogenation of a wide range of nonchelating olefins with different geometries, substitution patterns, and degrees of functionalization. These air-stable and readily available catalysts have been successfully applied in the asymmetric hydrogenation of di-, tri-, and tetrasubstituted olefins (ee′s up to 99%). The combination of theoretical calculations and deuterium labeling experiments led to the uncovering of the factors responsible for the enantioselectivity observed in the reaction, allowing the rationalization of the most suitable substrates for these Ir-catalysts

Towards a shared agenda for EU reform

UIDB/04627/2020 UIDP/04627/2020Relations between southern European member states have often been marked by a loose cooperation or, worse, by logics of competition. Precisely when regional groupings within the EU are increasingly shaping the agenda, these dynamics have hindered the capacity of France, Greece, Italy, Portugal and Spain to pursue shared interests and objectives, while acting as a force for good for the European integration project. Recent events such as the post-pandemic recovery or the war in Ukraine show that, when cooperation occurs, positive results can be achieved. Southern member states can capitalise on a certain ideological affinity and a pro-European vision, despite their governments belonging to different political groups. They share converging interests in the areas of fiscal policy and economic governance, strategic autonomy in energy and technology and even foreign policy priorities, particularly towards the Mediterranean and relations with other global powers. This joint publication by six southern European think tanks identifies several policy areas for fruitful cooperation between southern European member states.publishersversionpublishe

Inherited functional variants of the lymphocyte receptor CD5 influence melanoma survival

Despite the recent progress in treatment options, malignant melanoma remains a deadly disease. Besides therapy, inherited factors might modulate clinical outcome, explaining in part widely varying survival rates. T-cell effector function regulators on antitumor immune responses could also influence survival. CD5, a T-cell receptor inhibitory molecule, contributes to the modulation of antimelanoma immune responses as deduced from genetically modified mouse models. The CD5 SNPs rs2241002 (NM_014207.3:c.671C > T, p.Pro224Leu) and rs2229177 (NM_014207.3:c.1412C > T, p.Ala471Val) constitute an ancestral haplotype (Pro224-Ala471) that confers T-cell hyper-responsiveness and worsens clinical autoimmune outcome. The assessment of these SNPs on survival impact from two melanoma patient cohorts (Barcelona, N = 493 and Essen, N = 215) reveals that p.Ala471 correlates with a better outcome (OR= 0.57, 95% CI = 0.33-0.99, Adj. p = 0.043, in Barcelona OR = 0.63, 95% CI = 0.40-1.01, Adj. p = 0.051, in Essen). While, p.Leu224 was associated with increased melanoma-associated mortality in both cohorts (OR = 1.87, 95% CI = 1.07-3.24, Adj. p = 0.030 in Barcelona and OR = 1.84, 95% CI = 1.04-3.26, Adj. p = 0.037, in Essen). Furthermore survival analyses showed that the Pro224-Ala471 haplotype in homozygosis improved melanoma survival in the entire set of patients (HR = 0.27, 95% CI 0.11-0.67, Adj. p = 0.005). These findings highlight the relevance of genetic variability in immune-related genes for clinical outcome in melanoma

Direct Democracy in the EU –The Myth of a Citizens’ Union. CEPS Paperback, November 2018

The European Union has a democracy problem. The polycrisis that has plagued the EU for years has led to a cacophony of voices calling for fundamental change to the integration project. Yet despite the shock of the Brexit referendum and the electoral upsets caused by nativist parties across the continent, few of the plans for EU reform include concrete proposals to address the perennial democratic deficit. This book looks at how the relationship between citizens, the state and EU institutions has changed in a multi-layered Union. As such, it focuses more on polity than on populism, and does not engage deeply with policy or output legitimacy. Building on the notion of increasing social, economic and political interdependence across borders, this book asks whether a sense of solidarity and European identity can be rescued from the bottom up by empowering citizens to ‘take back control’ of their Union. Direct Democracy in the EU: The Myth of a Citizens’ Union is part of the 'Towards a Citizens’ Union' project and is the product of collaboration with 20 renowned think tanks from the European Policy Institutes Network (EPIN). It is the first of three publications that will also cover the state of representative democracy in the EU and the accountability of democratic institutions

Identification and characterization of an oncogenic form of IKKα in colorectal cancer

L’IKKα nuclear regula la transcripció gènica i ha estat relacionada amb la progressió del càncer i la metàstasis, tot i que la connexió mecanística no s’entén massa bé. Hem observat que les cèl·∙lules tumorals tenen una forma d’IKKα activada (p45-­‐IKKα) al nucli. Aquesta p45-­‐IKKα activada i nuclear forma un complex amb IKKα no activada i NEMO que media la fosforilació d’SMRT i d’histona H3. La formació de p45-­‐IKKα és necessària per tal de prevenir l’apoptosis de les cèl·∙lules de càncer colorectal i per tal de mantenir el creixement tumoral. També hem observat que KRAS a través de BRAF indueix l’activació de p45-­‐IKKα mediada per TAK1, amb un mínim efecte sobre NF-­‐κB. Mecanísticament, BRAF promou la ubiquitinació de NEMO i l’associació de la forma activada de TAK1 al complex de p45-­‐IKKα. També hem desmostrat que p45-­‐IKKα és necessària per la transformació cel·∙lular mediada per KRAS/BRAF i que inhibidors de la funció endosomal suprimeixen l’activitat de TAK1 i de p45-­‐IKKα. Treient partit d’un model ortotòpic xenògraft humà hem demostrat l’eficàcia d’aquestes drogues en prevenir la capacitat metastàtica de cèl·∙lules primàries de càncer colorectal d’un pacient amb resistència adquirida al tractament quimioteràpic estàndardNuclear IKKα regulate gene transcription and it has been linked to cancer progression and metastasis, although the mechanistic connection remains poorly understood. We have found that nucleus of tumor cells contains an active IKKα isoform of 45kD (p45-­‐IKKα). Active nuclear p45-­‐ IKKα forms a complex with non-­‐active IKKα and NEMO that mediates phosphorylation of SMRT and Histone H3. Generation of p45-­‐IKKα is required to prevent apoptosis of CRC cells and to sustain tumor growth. We have observed that KRAS through BRAF induces TAK1-­‐mediated activation of p45-­‐IKKα, with minor impact on NF-­‐κB. Mechanistically, BRAF promotes NEMO ubiquitination and association of active TAK1 to the p45-­‐IKKα complex. We also demonstrate that p45-­‐IKKα is required for KRAS/BRAF-­‐mediated cell transformation and inhibitors of the endosomal function abolished TAK1 and p45-­‐IKKα activities. Using a human orthotopic xenograft model we demonstrate the efficacy of these drugs in preventing the metastatic capacity of primary CRC cells from a patient with acquired resistance to standard chemotherapy

Topology & Typology depends: visions d'arquitectura

“Que és l’arquitectura contemporània? Entenem com a contemporani tot allò que existeix en el present. Llavors, com podem definir l’arquitectura contemporània? És molt difícil en el present definir el que es pot considerar com arquitectura contemporània i que no. Si ho definim de manera literal i temporal, qualsevol edifici construït en el present es pot considerar com arquitectura contemporània, alhora, una vegada hagi passat el temps, aquests edificis poden ser rellevats d’aquesta categoria. L’arquitectura moderna té un llenguatge arquitectònic molt definit; no tan sols implica l’arquitectura construïda durant el període modern, sinó que engloba tota l’arquitectura que segueix un mateix vocabulari. D’aquesta mateixa manera, si som capaços de definir el que és l’arquitectura moderna a través d’un cert llenguatge, potser podem definir també l’arquitectura contemporània si busquem el seu propi llenguatge.” Així comença l’article publicat per l’estudi PRAUD i anomenat TOPOLOGIA & TIPOLOGIA (2016), amb el subtítol “Cap al Contemporanisme”, on a través de l’estudi tipològic i topològic es busca trobar resposta a aquestes qüestions

IKKα is required in the intestinal epithelial cells for tumour stemness

BACKGROUND: Colorectal cancer is a common cause of death in developed countries. Progression from adenoma to invasive carcinoma requires accumulation of mutations starting with the Adenomatous Polyposis Coli (Apc) gene. NF-κB signalling is a key element in cancer, mainly related to the activity of IKKβ. IKKα kinase also participates in this process by mechanisms that are primarily unknown. METHODS: We generated a compound mouse model with mutation in Apc and lacking intestinal epithelial IKKα, produced intestinal organoids and tumour spheroids with different genetic backgrounds, and performed immunohistochemistry and RNA-seq analysis. RESULTS: Deficiency of IKKα prevents adenoma formation, with adenomas lacking IKKα showing reduced proliferation. In contrast, IKKα status did not affect normal intestinal function. The same divergent phenotype was found in the organoid-spheroid model. We also found that epithelial IKKα controls stemness, proliferation and apoptosis-related expression. CONCLUSIONS: IKKα is a potential therapeutic target for Apc mutant colorectal cancer patient

RTEL1 Regulates G4/R-Loops to Avert Replication-Transcription Collisions

Regulator of telomere length 1 (RTEL1) is an essential helicase that maintains telomere integrity and facilitates DNA replication. The source of replication stress in Rtel1-deficient cells remains unclear. Here, we report that loss of RTEL1 confers extensive transcriptional changes independent of its roles at telomeres. The majority of affected genes in Rtel1 -/- cells possess G-quadruplex (G4)-DNA-forming sequences in their promoters and are similarly altered at a transcriptional level in wild-type cells treated with the G4-DNA stabilizer TMPyP4 (5,10,15,20-Tetrakis-(N-methyl-4-pyridyl)porphine). Failure to resolve G4-DNAs formed in the displaced strand of RNA-DNA hybrids in Rtel1 -/- cells is suggested by increased R-loops and elevated transcription-replication collisions (TRCs). Moreover, removal of R-loops by RNaseH1 overexpression suppresses TRCs and alleviates the global replication defects observed in Rtel1 -/- and Rtel1 PIP_box knockin cells and in wild-type cells treated with TMPyP4. We propose that RTEL1 unwinds G4-DNA/R-loops to avert TRCs, which is important to prevent global deregulation in both transcription and DNA replication

CDK phosphorylation of TRF2 controls t-loop dynamics during the cell cycle

The protection of telomere ends by the shelterin complex prevents DNA damage signalling and promiscuous repair at chromosome ends. Evidence suggests that the 3′ single-stranded telomere end can assemble into a lasso-like t-loop confguration1,2 , which has been proposed to safeguard chromosome ends from being recognized as DNA double-strand breaks2 . Mechanisms must also exist to transiently disassemble t-loops to allow accurate telomere replication and to permit telomerase access to the 3′ end to solve the end-replication problem. However, the regulation and physiological importance of t-loops in the protection of telomere ends remains unknown. Here we identify a CDK phosphorylation site in the shelterin subunit at Ser365 of TRF2, whose dephosphorylation in S phase by the PP6R3 phosphatase provides a narrow window during which the RTEL1 helicase can transiently access and unwind t-loops to facilitate telomere replication. Re-phosphorylation of TRF2 at Ser365 outside of S phase is required to release RTEL1 from telomeres, which not only protects t-loops from promiscuous unwinding and inappropriate activation of ATM, but also counteracts replication conficts at DNA secondary structures that arise within telomeres and across the genome. Hence, a phospho-switch in TRF2 coordinates the assembly and disassembly of t-loops during the cell cycle, which protects telomeres from replication stress and an unscheduled DNA damage response