Evaluación del riesgo de inundación a múltiples componentes en la costa del Maresme

The coast is one of the areas most affected by natural hazards, with floods being the most frequent and significant of these in terms of their induced impacts, so any management scheme requires their evaluation. In coastal areas, flooding is a hazard associated with different processes acting at different scales: coastal storms, flash floods and sea level rise (SLR). To address the problem as a whole, this study presents a methodology to undertake a preliminary integrated risk assessment of the magnitude of each flood component, taking into account their scope (extension of the affected area) and their temporal scale. The risk is quantified using specific indicators to assess the hazard magnitude (for each component) and the consequences. This allows for a robust comparison of the spatial risk distribution along the coast in order to identify both the most at-risk areas and the most influential risk components. This methodology is applied to a stretch of coastline (Maresme, Catalonia) representative of the Spanish Mediterranean coast. The results obtained characterise this coastline as an area with a relatively low overall risk, although some hotspots are identified as having high-risk values. Resumen: La costa es una de las zonas más sometidas a riesgos naturales, siendo la inundación uno de los más frecuentes e importantes en términos de daños inducidos, por lo que cualquier esquema de gestión requiere evaluación. La inundación en zonas costeras es una amenaza natural asociada a diferentes procesos que actúan a distintas escalas: tormentas costeras, riadas y subida del nivel del mar (SNM). Para abarcar la totalidad del problema, este trabajo propone una metodología para la evaluación preliminar del riesgo integrado de inundación costera a una escala regional que permite evaluar la magnitud de cada componente teniendo en cuenta su alcance (extensión de la zona afectada) y su escala temporal. El riesgo se cuantifica en función de unos indicadores específicos que valoran la magnitud de la amenaza para cada componente y las consecuencias. Esto permite comparar robustamente la distribución espacial del riesgo a lo largo de la costa, para identificar tanto zonas de mayor riesgo como las componentes que más contribuyen al mismo. Aplicamos esta metodología a un tramo de costa característica del Mediterráneo español (Maresme, Cataluña). Los resultados permiten caracterizar esta costa como un área con un riesgo global relativamente bajo, pero algunos puntos singulares con riesgo alto

Cystatin D locates in the nucleus at sites of active transcription and modulates gene and protein expression

Cystatin D is an inhibitor of lysosomal and secreted cysteine proteases. Strikingly, cystatin D has been found to inhibit proliferation, migration, and invasion of colon carcinoma cells indicating tumor suppressor activity that is unrelated to protease inhibition. Here, we demonstrate that a proportion of cystatin D locates within the cell nucleus at specific transcriptionally active chromatin sites. Consistently, transcriptomic analysis show that cystatin D alters gene expression, including that of genes encoding transcription factors such as RUNX1, RUNX2, and MEF2C in HCT116 cells. In concordance with transcriptomic data, quantitative proteomic analysis identified 292 proteins differentially expressed in cystatin D-expressing cells involved in cell adhesion, cytoskeleton, and RNA synthesis and processing. Furthermore, using cytokine arrays we found that cystatin D reduces the secretion of several protumor cytokines such as fibroblast growth factor-4, CX3CL1/fractalkine, neurotrophin 4 oncostatin-M, pulmonary and activation-regulated chemokine/CCL18, and transforming growth factor B3. These results support an unanticipated role of cystatin D in the cell nucleus, controlling the transcription of specific genes involved in crucial cellular functions, which may mediate its protective action in colon cancer

Gene-Expression Profiling Suggests Impaired Signaling via the Interferon Pathway in Cstb(-/-) Microglia

Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1, OMIM254800) is an autosomal recessive neurodegenerative disorder characterized by stimulus-sensitive and action-activated myoclonus, tonic-clonic epileptic seizures, and ataxia. Loss-of-function mutations in the gene encoding the cysteine protease inhibitor cystatin B (CSTB) underlie EPM1. The deficiency of CSTB in mice (Cstb(-/-) mice) generates a phenotype resembling the symptoms of EPM1 patients and is accompanied by microglial activation at two weeks of age and an upregulation of immune system-associated genes in the cerebellum at one month of age. To shed light on molecular pathways and processes linked to CSTB deficiency in microglia we characterized the transcriptome of cultured Cstb(-/-) mouse microglia using microarray hybridization and RNA sequencing (RNA-seq). The gene expression profiles obtained with these two techniques were in good accordance and not polarized to either pro- or anti-inflammatory status. In Cstb(-/-) microglia, altogether 184 genes were differentially expressed. Of these, 33 genes were identified by both methods. Several interferon-regulated genes were weaker expressed in Cstb(-/-) microglia compared to control. This was confirmed by quantitative real-time PCR of the transcripts Irf7 and Stat1. Subsequently, we explored the biological context of CSTB deficiency in microglia more deeply by functional enrichment and canonical pathway analysis. This uncovered a potential role for CSTB in chemotaxis, antigen-presentation, and in immune-and defense response-associated processes by altering JAK-STAT pathway signaling. These data support and expand the previously suggested involvement of inflammatory processes to the disease pathogenesis of EPM1 and connect CSTB deficiency in microglia to altered expression of interferon-regulated genes.Peer reviewe

Pathways to entrepreneurial growth: The influence of management, marketing, and money

Business growth is considered a worthy goal for firms and a measure of entrepreneurial success, as well as important for economic development. Why some firms grow and others do not, though, remains a subject of debate. Of the small proportion of firms that do grow, it is often assumed that they follow a similar growth trajectory and/or encounter certain stage thresholds; however, the evidence base on this is wanting. The new study of business growth presented here provides an in-depth analysis of 19 New England-based firms. Our findings reveal that fast-growing companies exhibit different rates and patterns of growth: some display rapid growth trajectories (Rapid Growth Pattern); some, slower, more measured rates (Incremental Growth Pattern); others, episodic periods of quick growth followed by sharp retrenchment (Episodic Growth Pattern); and, while no firm actively chose to stop growing, some reached points of stagnation (Plateau Growth Pattern). We found that three key factors--management, marketing, and money--affected company growth across these patterns. While not every factor was critical at each moment of growth for each firm, every entrepreneur cited the relative importance of each factor at some time during the growth of their firm. Thus, fast-growing firms do not grow in the same manner, at the same rate, or with the same outcomes. This article has implications for those seeking to understand the processes of development and patterns of fast-growth businesses.Entrepreneurial growth Patterns of growth Management decision-making Growth strategies