21 research outputs found
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