Search results for "Down"
showing 10 items of 1658 documents
Paediatric Emergencies During the COVID-19 Pandemic
2021
The state of alarm decreed by the Spanish Government, due to the Coronavirus Disease-19 (COVID-19) pandemic, has demanded the lockdown of children and has conditioned a new organization of the Emergency Departments (ED). A pre-triage station and 2 independent circuits were established: suspected COVID-19 and not suspected COVID-19. The ED visits decreased 84,5% from pre-alarm with no increase in the level of urgencies. During the alarm state, 40.97% of the children were classified as suspected COVID-19. Fever and respiratory symptoms, used as discriminators, generated 2 groups of patients with different characteristics. Although the interruption of sports activities and isolation of childr…
Retinoic-Acid-Induced Downregulation of the 67 KDa Laminin Receptor Correlates with Reduced Biological Aggressiveness of Human Neuroblastoma Cells
2012
Neuroblastoma is a common tumor of the childhood arising from embryonal sympathetic neural cell precursors. Despite of the improved therapeutic strategies, the survival rate of high-risk neuroblastoma patients is poor. Although complete clinical remissions can be achieved, relapse is relatively frequent, indicating a role for the persistence of the minimal residual disease (for review, Maris, 2010). Treatments with derivatives of retinoic acid (RA), the biologically active form of vitamin A, produce significant improvements on the therapy of high-risk neuroblastoma patients, when used together with intensive multimodal therapies (Reynolds et al., 2003, for review). Despite some controversy …
Different approaches to marriage downgrading : from an anti-elusive measure to an antidiscriminatory claim
2021
The essay focuses on the different mechanisms of marriage downgrading. Given the principle of ?cross-border continuity? of statuses, limits to this continuity are sometimes admitted and they are placed through downgrading mechanisms. That can occour in the case of same-sex marriages transcription in a Member State which does not allow such marriages, but which does allow samesex registered partnerships. Downgrading mechanism has an anti-elusive function, but it is not without problems in terms of discrimination on the grounds of sexual orientation. A different approach is taken in the case of an opposite-sex couple requesting the downgrading of their marriage, celebrated before the Member S…
Self-Organized Linguistic Systems: From traditional AI to bottom-up generative processes
2018
Este trabajo busca explorar el potencial de los procesos generativos bottom-up en el contexto de la producción conlang, con el objetivo de describir las bases de un nuevo campo de investigación: los Sistemas Lingüísticos Autoorganizados o SOLS, específicamente bajo la perspectiva doble de sistemas autoorganizados y lenguajes construidos. El enfoque SOLS proporciona un marco para la creación de lenguajes artificiales autogenerados y puede servir como punto de partida para el desarrollo de lenguajes dependientes del contexto o específicos del dominio. Reconoce que el desarrollo de conlangs puede ocurrir en sociedades artificiales de agentes simples, como resultado de interacciones sociales en…
Impacto de la crisis en las entidades de acción social. Asindown, un ejemplo de superación
2013
La situación económica actual obliga a organismos públicos y empresas a adoptar medidas extraordinarias con el objetivo de mantener los servicios que prestan. En este contexto, las entidades (Fundaciones y Asociaciones) que atienden a personas con discapacidad y otros colectivos en riesgo de exclusión social, y que dependen en gran medida de las subvenciones públicas y privadas, sufren graves problemas de financiación que dificultan el normal desarrollo de sus actividades, y en consecuencia, son perjudicados aquellos usuarios y familias con las que trabajan. Asindown es parte de esta realidad y trabaja desde todos los ámbitos para mantener los servicios que presta con los mayores estándares…
Abstract C75: Overcoming KRAS/LKB1 mutant NSCLC resistance to BET bromodomain inhibitors with gemcitabine or Mcl-1 inhibition
2015
Abstract The purpose of our study was to define a method and mechanism for overcoming the resistance of clinically relevant KRAS-mutant/LKB1-deficient NSCLC cells to the BET-bromodomain inhibitor JQ1. LKB1 (Serine/threonine kinase 11) is mutated with loss of function in conjunction with mutated KRAS in 7-10% of NSCLC. Importantly, KRAS-mutant/LKB1-deficiency is associated with tumor aggressiveness and poor survival in human patients as well as in genetically engineered mouse models. Indeed, although the BET bromodomain inhibitor JQ1 dramatically reduces tumor volume in KRAS mutant mice, it has little effect in KRAS-mutant/LKB1-deficient mice. BET bromodomain proteins are chromatin readers t…
Quantum-chemical determination of Born–Oppenheimer breakdown parameters for rotational constants: the open-shell species CN, CO+ and BO
2013
The quantum-chemical protocol for computing Born-Oppenheimer breakdown corrections to rotational constants in the case of diatomic molecules is extended to open-shell species. The deviation from the Born-Oppenheimer equilibrium rotational constant is obtained by considering three contributions: the adiabatic correction to the equilibrium bond distance, the electronic contribution to the moment of inertia requiring the computation of the rotational g-tensor, and the so-called Dunham correction. Values for the Born-Oppenheimer breakdown parameters of CN, CO+, and BO in their (2)sigma(+) electronic ground states are reported based on coupled-cluster calculations of the involved quantities and …
Strategies to gain novel Alzheimer’s disease diagnostics and therapeutics using modulators of ABCA transporters
2021
Adenosine-triphosphate-(ATP)-binding cassette (ABC) transport proteins are ubiquitously present membrane-bound efflux pumps that distribute endo- and xenobiotics across intra- and intercellular barriers. Discovered over 40 years ago, ABC transporters have been identified as key players in various human diseases, such as multidrug-resistant cancer and atherosclerosis, but also neurodegenerative diseases, such as Alzheimer���s disease (AD). Most prominent and well-studied are ABCB1, ABCC1, and ABCG2, not only due to their contribution to the multidrug resistance (MDR) phenotype in cancer, but also due to their contribution to AD. However, our understanding of other ABC transporters is limited…
Shedding of the amyloid precursor protein-like protein APLP2 by disintegrin-metalloproteinases
2005
Cleavage of the amyloid precursor protein (APP) within the amyloid-beta (Aβ) sequence by the α-secretase prevents the formation of toxic Aβ peptides. It has been shown that the disintegrin-metalloproteinases ADAM10 and TACE (ADAM17) act as α-secretases and stimulate the generation of a soluble neuroprotective fragment of APP, APPsα. Here we demonstrate that the related APP-like protein 2 (APLP2), which has been shown to be essential for development and survival of mice, is also a substrate for both proteinases. Overexpression of either ADAM10 or TACE in HEK293 cells increased the release of neurotrophic soluble APLP2 severalfold. The strongest inhibition of APLP2 shedding in neuroblastoma c…
Down-regulation of Endogenous Amyloid Precursor Protein Processing due to Cellular Aging
2005
Processing of amyloid precursor protein (APP) is a well acknowledged central pathogenic mechanism in Alzheimer disease. However, influences of age-associated cellular alterations on the biochemistry of APP processing have not been studied in molecular detail so far. Here, we report that processing of endogenous APP is down-regulated during the aging of normal human fibroblasts (IMR-90). The generation of intracellular APP cleavage products C99, C83, and AICD gradually declines with increasing life span and is accompanied by a reduced secretion of soluble APP (sAPP) and sAPPalpha. Further, the maturation of APP was reduced in senescent cells, which has been shown to be directly mediated by a…