Paradero 14

Paradero 14 of La Florida is a commercial sub-center of Santiago, interchange hub between the center and the southern periphery of the city. This research aims to complement the studies that have been made of the place proposing a systemic vision that understands the different elements that give character to the space used by the users who visit the place. The focus is on the different commercial typologies complemented by transport infrastructures, which, along the historical evolution of the sub-center, have conditioned the intense use of the spaces of Paradero 14. This study seeks to contribute to the investigation of urban sub-centers that define important interchange hubs, and the way in which these places should develop harmoniously with the city and its inhabitants

Shadow of your former self: Exploring project leaders’ post-failure behaviors (resilience, self-esteem and self-efficacy) in high-tech startup projects

Globally, demands for sustainable strategies in the ICT industry have attracted greater momentum as high-tech projects continue to fail in large numbers. Recent studies have underpinned project resilience as a major factor for overcoming these increasing project failures, delays, or ter-mination. However, the complex behaviors of resilient project leaders, especially in post-failure conditions, have been largely overlooked. To address this critical research gap, the present study identifies the direct relationships between three potential behavioral traits of project leaders (i.e., resilience, self-esteem, and self-efficacy) and examines how they move forward beyond project failures. The present study also explored whether self-esteem mediates project leaders’ resilience and self-efficacy. Drawing on data from 232 project leaders in Pakistan’s high-tech start-ups, the new findings suggest that there are significant positive effects of project leaders’ resilience and self-esteem on their self-efficacy, and that project leaders’ resilience and self-efficacy is significantly mediated by their self-esteem. As the project resilience theory gains traction, the present study findings have pinpointed major steps for meeting project challenges ahead of time, allowing leaders and teams to learn from failures, and also for improving organisations’ ability to implement successful and sustainable high-tech projects especially in emerging economies

Modeling the β-secretase cleavage site and humanizing amyloid-beta precursor protein in rat and mouse to study Alzheimer's disease

BACKGROUND: Three amino acid differences between rodent and human APP affect medically important features, including β-secretase cleavage of APP and Aβ peptide aggregation (De Strooper et al., EMBO J 14:4932-38, 1995; Ueno et al., Biochemistry 53:7523-30, 2014; Bush, 2003, Trends Neurosci 26:207-14). Most rodent models for Alzheimer's disease (AD) are, therefore, based on the human APP sequence, expressed from artificial mini-genes randomly inserted in the rodent genome. While these models mimic rather well various biochemical aspects of the disease, such as Aβ-aggregation, they are also prone to overexpression artifacts and to complex phenotypical alterations, due to genes affected in or close to the insertion site(s) of the mini-genes (Sasaguri et al., EMBO J 36:2473-87, 2017; Goodwin et al., Genome Res 29:494-505, 2019). Knock-in strategies which introduce clinical mutants in a humanized endogenous rodent APP sequence (Saito et al., Nat Neurosci 17:661-3, 2014) represent useful improvements, but need to be compared with appropriate humanized wildtype (WT) mice. METHODS: Computational modelling of the human β-CTF bound to BACE1 was used to study the differential processing of rodent and human APP. We humanized the three pivotal residues we identified G676R, F681Y and R684H (labeled according to the human APP770 isoform) in the mouse and rat genomes using a CRISPR-Cas9 approach. These new models, termed mouse and rat Apphu/hu, express APP from the endogenous promotor. We also introduced the early-onset familial Alzheimer's disease (FAD) mutation M139T into the endogenous Rat Psen1 gene. RESULTS: We show that introducing these three amino acid substitutions into the rodent sequence lowers the affinity of the APP substrate for BACE1 cleavage. The effect on β-secretase processing was confirmed as both humanized rodent models produce three times more (human) Aβ compared to the original WT strain. These models represent suitable controls, or starting points, for studying the effect of transgenes or knock-in mutations on APP processing (Saito et al., Nat Neurosci 17:661-3, 2014). We introduced the early-onset familial Alzheimer's disease (FAD) mutation M139T into the endogenous Rat Psen1 gene and provide an initial characterization of Aβ processing in this novel rat AD model. CONCLUSION: The different humanized APP models (rat and mouse) expressing human Aβ and PSEN1 M139T are valuable controls to study APP processing in vivo allowing the use of a human Aβ ELISA which is more sensitive than the equivalent system for rodents. These animals will be made available to the research community

Retinal blood vessels extraction using probabilistic modelling

© 2014 Kaba et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.The analysis of retinal blood vessels plays an important role in detecting and treating retinal diseases. In this review, we present an automated method to segment blood vessels of fundus retinal image. The proposed method could be used to support a non-intrusive diagnosis in modern ophthalmology for early detection of retinal diseases, treatment evaluation or clinical study. This study combines the bias correction and an adaptive histogram equalisation to enhance the appearance of the blood vessels. Then the blood vessels are extracted using probabilistic modelling that is optimised by the expectation maximisation algorithm. The method is evaluated on fundus retinal images of STARE and DRIVE datasets. The experimental results are compared with some recently published methods of retinal blood vessels segmentation. The experimental results show that our method achieved the best overall performance and it is comparable to the performance of human experts.The Department of Information Systems, Computing and Mathematics, Brunel University

Multi-tissue transcriptomic-informed in silico investigation of drugs for the treatment of dengue fever disease

Transcriptomics, proteomics and pathogen-host interactomics data are being explored for the in silico–informed selection of drugs, prior to their functional evaluation. The effectiveness of this kind of strategy has been put to the test in the current COVID-19 pandemic, and it has been paying off, leading to a few drugs being rapidly repurposed as treatment against SARS-CoV-2 infection. Several neglected tropical diseases, for which treatment remains unavailable, would benefit from informed in silico investigations of drugs, as performed in this work for Dengue fever disease. We analyzed transcriptomic data in the key tissues of liver, spleen and blood profiles and verified that despite transcriptomic differences due to tissue specialization, the common mechanisms of action, “Adrenergic receptor antagonist”, “ATPase inhibitor”, “NF-kB pathway inhibitor” and “Serotonin receptor antagonist”, were identified as druggable (e.g., oxprenolol, digoxin, auranofin and palonosetron, respectively) to oppose the effects of severe Dengue infection in these tissues. These are good candidates for future functional evaluation and clinical trials.Funding was provided by FEDER, Fundo Europeu de Desenvolvimento Regional funds, through the COMPETE 2020, Competitiveness and Internationalization Operational Programme (POCI), Portugal 2020, and by Portuguese funds through FCT/Ministério da Ciência, Tecnologia e Inovação, in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274)

Intestinal parasitosis and anemia in children 6 to 60 months of age treated in the period 2015 to 2020, in a health center in the Highlands of Peru

Objetivo: Evaluar la anemia y la parasitosis en niños de 6 a 60 meses de edad, atendidos en un Centro de Salud Alto andina de Perú, durante periodo 2015 al 2020. Método: El estudio fue descriptivo – retrospectivo, se aplicó el método científico, con un diseño no experimental, la población y la muestra fueron compuestos por 1097 niños atendidos en el Centro de Salud de Ascensión, durante los años 2015 al 2020, se incluyó todo niño que padezca anemia y/o parasitosis. Resultado:  515 niñas que componen un 46.9%, y 582 niños que componen 53.1 % padecen de anemia, de los cuales el 83% padecen anemia leve, y un 17 % padecen de anemia moderada; en cuanto a género 83,7% niñas y 82,3% niños presentan anemia, en relación a edad   los de  6 a 12 mes   presentaron anemia  leve en un 37.5%  y moderado 48.1% ; Por otro lado de un total de 240 niños, un 53.3 % fueron niñas y un 46.7 fueron niños que padecen parasitosis intestinal. Conclusión:  En las zonas alto andinas de Perú, de niños y niñas que presentan anemia, predomina la anemia leve, así mismo este problema de salud no diferencia en su afección al género; en relación a la edad predomina de 6 a 12 meses con anemia leve y moderado. Por otro lado, se evidencia un porcentaje considerable de parasitosis intestinal, de igual forma esta enfermedad en cuanto al género no diferencia; sin embargo en cuanto a la edad se evidencia   mayor parasitosis intestinal en niños y niñas de 24, 36 y 60 meses; lo que implica que la parasitosis intestinal no necesariamente es un factor predominante para la anemia.Objective: To evaluate anemia and parasitosis in children from 6 to 60 months of age, attended in a Peruvian High Andean Health Center, during the period 2015 to 2020. Method: The study was descriptive - retrospective, the scientific method was applied, with a non-experimental design, the population and the sample were composed of 1097 children attended at the Ascension Health Center, during the years 2015 to 2020, all children suffering from anemia and/or parasitosis were included. Result: 515 girls comprising 46.9%, and 582 boys comprising 53.1% suffer from anemia, of which 83% suffer from mild anemia, and 17% suffer from moderate anemia; in terms of gender 83.7% girls and 82.3% boys present anemia, in relation to age those from 6 to 12 months presented mild anemia in 37. On the other hand, out of a total of 240 children, 53.3% were girls and 46.7% were boys suffering from intestinal parasitosis. Conclusion: In the high Andean zones of Peru, children with anemia are predominantly mildly anemic, and this health problem does not differentiate between genders; in relation to age, children between 6 and 12 months are predominantly mildly and moderately anemic. On the other hand, there is a considerable percentage of intestinal parasitosis, likewise this disease does not differentiate by gender; however, in terms of age, there is more intestinal parasitosis in children aged 24, 36 and 60 months, which implies that intestinal parasitosis is not necessarily a predominant factor for anemi

APROVECHAMIENTO DE ESCORIAS METÁLICAS EN LADRILLOS CERÁMICOS: UNA REVISIÓN

Este documento presenta una revisión de la literatura sobre el aprovechamiento de diversas escorias metálicas en la fabricación de ladrillos cerámicos, con el objetivo de describir y analizar el comportamiento de estas unidades de ladrillo modificados, que consiste en sustituir un porcentaje del total de arcilla para una unidad de ladrillo, buscando mejorar sus propiedades mecánicas, en investigaciones realizadas, han dado muestra de óptimos resultados, al utilizar escorias de plomo, acero, bronce, ferrocromo, lodos, entre otros, pudiéndose reciclar y darlo el uso ya antes mencionado, así poder disminuir los impactos ambientales, provocadas por la contaminación que dichos residuos generan y agregar un plus en el rubro de la construcción. Se revisaron 35 artículos indexados entre los años 2012 al 2020 los cuales se distribuyen de la siguiente manera: 5 artículos son de Scopus, 3 de ResearchGate, 11 de ScienceDirect y 6 de Scielo, 8 de ProQuest, 2 de Latindex 2.0, sobre escorias metálicas, caracterización de arcillas y ladrillo cerámico

A prospective metagenomic and metabolomic analysis of the impact of exercise and/or whey protein supplementation on the gut microbiome of sedentary adults

Many components of modern living exert influence on the resident intestinal microbiota of humans with resultant impact on host health. For example, exercise-associated changes in the diversity, composition, and functional profiles of microbial populations in the gut have been described in cross-sectional studies of habitual athletes. However, this relationship is also affected by changes in diet, such as changes in dietary and supplementary protein consumption, that coincide with exercise. To determine whether increasing physical activity and/or increased protein intake modulates gut microbial composition and function, we prospectively challenged healthy but sedentary adults with a short-term exercise regime, with and without concurrent daily whey protein consumption. Metagenomics- and metabolomics-based assessments demonstrated modest changes in gut microbial composition and function following increases in physical activity. Significant changes in the diversity of the gut virome were evident in participants receiving daily whey protein supplementation. Results indicate that improved body composition with exercise is not dependent on major changes in the diversity of microbial populations in the gut. The diverse microbial characteristics previously observed in long-term habitual athletes may be a later response to exercise and fitness improvement. IMPORTANCE The gut microbiota of humans is a critical component of functional development and subsequent health. It is important to understand the lifestyle and dietary factors that affect the gut microbiome and what impact these factors may have. Animal studies suggest that exercise can directly affect the gut microbiota, and elite athletes demonstrate unique beneficial and diverse gut microbiome characteristics. These characteristics are associated with levels of protein consumption and levels of physical activity. The results of this study show that increasing the fitness levels of physically inactive humans leads to modest but detectable changes in gut microbiota characteristics. For the first time, we show that regular whey protein intake leads to significant alterations to the composition of the gut virome

Ucma/GRP inhibits phosphate-induced vascular smooth muscle cell calcification via SMAD-dependent BMP signalling

Vascular calcification (VC) is the process of deposition of calcium phosphate crystals in the blood vessel wall, with a central role for vascular smooth muscle cells (VSMCs). VC is highly prevalent in chronic kidney disease (CKD) patients and thought, in part, to be induced by phosphate imbalance. The molecular mechanisms that regulate VC are not fully known. Here we propose a novel role for the mineralisation regulator Ucma/GRP (Upper zone of growth plate and Cartilage Matrix Associated protein/Gla Rich Protein) in phosphate-induced VSMC calcification. We show that Ucma/GRP is present in calcified atherosclerotic plaques and highly expressed in calcifying VSMCs in vitro. VSMCs from Ucma/GRP(-/-) mice showed increased mineralisation and expression of osteo/chondrogenic markers (BMP-2, Runx2, beta-catenin, p-SMAD1/5/8, ALP, OCN), and decreased expression of mineralisation inhibitor MGP, suggesting that Ucma/GRP is an inhibitor of mineralisation. Using BMP signalling inhibitor noggin and SMAD1/5/8 signalling inhibitor dorsomorphin we showed that Ucma/GRP is involved in inhibiting the BMP-2-SMAD1/5/8 osteo/chondrogenic signalling pathway in VSMCs treated with elevated phosphate concentrations. Additionally, we showed for the first time evidence of a direct interaction between Ucma/GRP and BMP-2. These results demonstrate an important role of Ucma/GRP in regulating osteo/chondrogenic differentiation and phosphate-induced mineralisation of VSMCs.NWO ZonMw [MKMD 40-42600-98-13007]; FCT [SFRH/BPD/70277/2010]info:eu-repo/semantics/publishedVersio

Polyfunctional T cell responses in children in early stages of chronic Trypanosoma cruzi infection contrast with monofunctional responses of long-term infected adults

Background: Adults with chronic Trypanosoma cruzi exhibit a poorly functional T cell compartment, characterized by monofunctional (IFN-γ-only secreting) parasite-specific T cells and increased levels of terminally differentiated T cells. It is possible that persistent infection and/or sustained exposure to parasites antigens may lead to a progressive loss of function of the immune T cells. Methodology/Principal Findings: To test this hypothesis, the quality and magnitude of T. cruzi-specific T cell responses were evaluated in T. cruzi-infected children and compared with long-term T. cruzi-infected adults with no evidence of heart failure. The phenotype of CD4+ T cells was also assessed in T. cruzi-infected children and uninfected controls. Simultaneous secretion of IFN-γ and IL-2 measured by ELISPOT assays in response to T. cruzi antigens was prevalent among T. cruzi-infected children. Flow cytometric analysis of co-expression profiles of CD4+ T cells with the ability to produce IFN-γ, TNF-α, or to express the co-stimulatory molecule CD154 in response to T. cruzi showed polyfunctional T cell responses in most T. cruzi-infected children. Monofunctional T cell responses and an absence of CD4+TNF-α+-secreting T cells were observed in T. cruzi-infected adults. A relatively high degree of activation and differentiation of CD4+ T cells was evident in T. cruzi-infected children. Conclusions/Significance: Our observations are compatible with our initial hypothesis that persistent T. cruzi infection promotes eventual exhaustion of immune system, which might contribute to disease progression in long-term infected subjects.Fil: Albareda, María Cecilia. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: de Rissio, Ana María. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Tomas, Gonzalo. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Serjan, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Alvarez, María Gabriela. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Viotti, Rodolfo Jorge. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Fichera, Laura Edith. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Esteva, Mónica Inés. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Potente, Daniel Fernando. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Armenti, Alejandro. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Tarleton, Rick L.. University of Georgia; Estados UnidosFil: Laucella, Susana Adriana. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin