Plan de negocios para determinar la viabilidad del desarrollo de un asistente virtual de ventas (Chatbot) : caso Gamarra

El presente plan de negocios nace de identificar una carencia importante en el emporio comercial de Gamarra: la falta de implementaci?n de herramientas tecnol?gicas que favorezcan sus procesos de venta. As?, la introducci?n de un Asistente Virtual (Chatbot) se presenta como una oportunidad para los empresarios textiles de Gamarra. El an?lisis contextual arroj? que existen circunstancias favorables, a nivel de mercado, para el desarrollo y venta del Asistente Virtual. Sin embargo, tambi?n se destac? que la falta de conocimiento y las barreras de adopci?n tecnol?gica por parte de los empresarios de Gamarra es una barrera importante para el proyecto. Estos datos se consolidaron con los resultados de la investigaci?n de mercado. Empero, los resultados del estudio se?alaron que el empresario textil de Gamarra s? estar?a dispuesto a adquirir el Asistente Virtual, pues lo identifica como ?til para expandir las ventas de su negocio. Para lograr dicho objetivo se desarrollaron planes estrat?gicos, que conclu?an la necesidad de entrar en un mercado no penetrado, creando intimidad con el cliente, educ?ndolo en las bondades de la implantaci?n de tecnolog?a en sus empresas con un producto innovador. Finalmente, las proyecciones financieras se mostraron positivas, generando un VAN de S/259,937 y un TIR de 28%

Non-reciprocal interactions between K+ and Na+ ions in barley (Hordeum vulgare L.)

The interaction of sodium and potassium ions in the context of the primary entry of Na+ into plant cells, and the subsequent development of sodium toxicity, has been the subject of much recent attention. In the present study, the technique of compartmental analysis with the radiotracers 42K+ and 24Na+ was applied in intact seedlings of barley (Hordeum vulgare L.) to test the hypothesis that elevated levels of K+ in the growth medium will reduce both rapid, futile Na+ cycling at the plasma membrane, and Na+ build-up in the cytosol of root cells, under saline conditions (100 mM NaCl). We reject this hypothesis, showing that, over a wide (400-fold) range of K+ supply, K+ neither reduces the primary fluxes of Na+ at the root plasma membrane nor suppresses Na+ accumulation in the cytosol. By contrast, 100 mM NaCl suppressed the cytosolic K+ pool by 47–73%, and also substantially decreased low-affinity K+ transport across the plasma membrane. We confirm that the cytosolic [K+]:[Na+] ratio is a poor predictor of growth performance under saline conditions, while a good correlation is seen between growth and the tissue ratios of the two ions. The data provide insight into the mechanisms that mediate the toxic influx of sodium across the root plasma membrane under salinity stress, demonstrating that, in the glycophyte barley, K+ and Na+ are unlikely to share a common low-affinity pathway for entry into the plant cell

NH4+-stimulated and -inhibited components of K+ transport in rice (Oryza sativa L.)

The disruption of K+ transport and accumulation is symptomatic of NH4+ toxicity in plants. In this study, the influence of K+ supply (0.02–40 mM) and nitrogen source (10 mM NH4+ or NO3–) on root plasma membrane K+ fluxes and cytosolic K+ pools, plant growth, and whole-plant K+ distribution in the NH4+-tolerant plant species rice (Oryza sativa L.) was examined. Using the radiotracer 42K+, tissue mineral analysis, and growth data, it is shown that rice is affected by NH4+ toxicity under high-affinity K+ transport conditions. Substantial recovery of growth was seen as [K+]ext was increased from 0.02 mM to 0.1 mM, and, at 1.5 mM, growth was superior on NH4+. Growth recovery at these concentrations was accompanied by greater influx of K+ into root cells, translocation of K+ to the shoot, and tissue K+. Elevating the K+ supply also resulted in a significant reduction of NH4+ influx, as measured by 13N radiotracing. In the low-affinity K+ transport range, NH4+ stimulated K+ influx relative to NO3– controls. It is concluded that rice, despite its well-known tolerance to NH4+, nevertheless displays considerable growth suppression and disruption of K+ homeostasis under this N regime at low [K+]ext, but displays efficient recovery from NH4+ inhibition, and indeed a stimulation of K+ acquisition, when [K+]ext is increased in the presence of NH4+

Tau – an inhibitor of deacetylase HDAC6 function

Analysis of brain microtubule protein from patients with Alzheimer’s disease showed decreased alpha tubulin levels along with increased acetylation of the alpha tubulin subunit, mainly in those microtubules from neurons containing neurofibrillary tau pathology. To determine the relationship of tau protein and increased tubulin acetylation, we studied the effect of tau on the acetylation-deacetylation of tubulin. Our results indicate that tau binds to the tubulin-deacetylase, histone deacetylase 6 (HDAC6), decreasing its activity with a consequent increase in tubulin acetylation. As expected, increased acetylation was also found in tubulin from wild-type mice compared with tubulin from mice lacking tau because of the tau-mediated inhibition of the deacetylase. In addition, we found that an excess of tau protein, as a HDAC6 inhibitor, prevents induction of autophagy by inhibiting proteasome function.This work was supported by grants from Spanish Plan Nacional, Comunidad de Madrid, Fundación Botín, CIBERNED, and an institutional grant Fundación Areces.Peer reviewe

Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia

T-cell acute lymphoblastic leukaemia (T-ALL) is a haematological malignancy with a dismal overall prognosis, including a relapse rate of up to 25%, mainly because of the lack of non-cytotoxic targeted therapy options. Drugs that target the function of key epigenetic factors have been approved in the context of haematopoietic disorders, and mutations that affect chromatin modulators in a variety of leukaemias have recently been identified; however, ‘epigenetic’ drugs are not currently used for T-ALL treatment. Recently, we described that the polycomb repressive complex 2 (PRC2) has a tumour-suppressor role in T-ALL. Here we delineated the role of the histone 3 lysine 27 (H3K27) demethylases JMJD3 and UTX in T-ALL. We show that JMJD3 is essential for the initiation and maintenance of T-ALL, as it controls important oncogenic gene targets by modulating H3K27 methylation. By contrast, we found that UTX functions as a tumour suppressor and is frequently genetically inactivated in T-ALL. Moreover, we demonstrated that the small molecule inhibitor GSKJ4 (ref. 5) affects T-ALL growth, by targeting JMJD3 activity. These findings show that two proteins with a similar enzymatic function can have opposing roles in the context of the same disease, paving the way for treating haematopoietic malignancies with a new category of epigenetic inhibitors.National Institutes of Health (U.S.) (Grant R37-HD04502

Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types

Abstract Background A healthy immune system requires immune cells that adapt rapidly to environmental challenges. This phenotypic plasticity can be mediated by transcriptional and epigenetic variability. Results We apply a novel analytical approach to measure and compare transcriptional and epigenetic variability genome-wide across CD14+CD16− monocytes, CD66b+CD16+ neutrophils, and CD4+CD45RA+ naïve T cells from the same 125 healthy individuals. We discover substantially increased variability in neutrophils compared to monocytes and T cells. In neutrophils, genes with hypervariable expression are found to be implicated in key immune pathways and are associated with cellular properties and environmental exposure. We also observe increased sex-specific gene expression differences in neutrophils. Neutrophil-specific DNA methylation hypervariable sites are enriched at dynamic chromatin regions and active enhancers. Conclusions Our data highlight the importance of transcriptional and epigenetic variability for the key role of neutrophils as the first responders to inflammatory stimuli. We provide a resource to enable further functional studies into the plasticity of immune cells, which can be accessed from: http://blueprint-dev.bioinfo.cnio.es/WP10/hypervariability