301 research outputs found

    Structure-function studies of the Parkinsonism-linked protein DJ-1

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    DJ-1 is a multifunctional protein linked to familial Parkinson’s disease. DJ-1 has been suggested to exert its cytoprotective function, in part, by acting as a copper carrier that can sequester the reactive metal and/or provide the copper cofactor for the activation of the Cu-Zn superoxide dismutase (SOD1). Using absorption spectroscopy and mass spectrometry, we found that DJ-1 binds one Cu(I) ion per DJ-1 homodimer. The structure of Cu(I)-bound DJ-1 reveals a new biscysteinate metal binding motif formed by juxtaposed Cys-53 at the homodimer interface. We calculated a subfemtomolar dissociation constant (Kd = 6.41 x 10-16 M) for Cu(I) that supports the physiological intracellular retention of the metal. Cu(I)-bound DJ-1 was not capable of interacting and activating SOD1 in vitro. We posit that DJ-1 sequester copper to protect against metal-induced cytotoxicity. Our results illuminate the molecular basis on how disease-linked mutations that impairs homodimerisation could disrupt the metal binding site. In the second part of this dissertation, we sought to determine the impact of a Parkinsonism-linked A107P mutation on DJ-1 structure and glyoxalase activity. The A107P variant abrogates the ability of DJ-1 to protect against glyoxal-induced cytotoxicity and carboxymethyllysine protein modification. A crystal structure of DJ-1 C106S variant with glycerol and sulphate bound in the active site suggests that Ala-107 is critical for the stabilization of the transition state of the nucleophilic addition step. In our hands, the protein levels of DJ-1 A107P mutant in SH-SH5Y cells were ostensibly similar to the wild-type level but reduced levels were found in HEK 293E and MEF cells. Using CD and NMR spectroscopy, we found that the structural defect caused by the mutation extends beyond the active site. The A107P mutation resulted in a remarkable misfolding of the protein providing a basis for the reduced intracellular protein level and the abrogation of enzymatic activity

    Rapid assessment of the riparian zone habitat of river

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    Some riparian areas of the country are in danger of deterioration due to uncontrolled exploitation coupled with loose implementation of environmental protection policies and regulations. Muleta River, a major watershed in Bukidnon, Philippines, was assessed to determine the present condition of its riparian habitat. Abiotic and biotic conditions of the river were assessed. Other factors including land cover, population density, and river geomorphologic characteristics contributing to the river condition were also evaluated. Results revealed that Muleta Watershed is in sub-optimal condition signifying favorable condition for floral and faunal habitat. However, considerable degradation in some isolated cases was likewise spotted. Biotic condition has shown greater degradation approaching marginal condition compared to the abiotic condition which is yet in the upper sub-optimal condition. It was found out that the midstream portion of the watershed is the most disturbed, followed by the downstream area and lastly by the upstream portion. The extent of agricultural cultivation is found as one of the significant factors affecting the health of the riparian habitat areas. It is recommended that riparian protection policies must be formulated and implemented to abate, if not prevent, the impact of anthropogenic interventions resulting to overexploitation in the riparian areas especially in midstream portion of the river

    Hydrologic responses of watershed assessment to land cover and climate change using soil and water assessment tool model

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    Predicting the impact of land cover and climate change on hydrologic responses using modeling tools are essential in understanding the movement and pattern of hydrologic processes within the watershed. The paper provided potential implications of land conversions and climate change scenarios on the hydrologic processes of Muleta watershed using soil and water assessment tool model. Model inputs used include interferometric synthetic aperture radar-digital elevation model, 2016 land cover map, soil map, meteorological and hydrologic data. The model was calibrated using appropriate statistical parameters (R2=0.80, NS=0.80 and RSR=0.45). Model validation using observed streamflow with the same statistical parameters (R2 = 0.79, NS = 0.67 and RSR = 0.57) showed that the result was statistically acceptable. The model provided potential implications of land conversions and climate change adversely affecting hydrologic processes of critical watersheds. Climate change projections with a 13% decrease in rainfall directly influenced the decrease in hydrologic processes. Meanwhile, urbanization had influenced the increase in surface runoff, evapotranspiration, and baseflow. The increase of forest vegetation resulted in a minimal decrease in baseflow and surface runoff. The watershed hydrologic processes were influenced by changes in land cover and climate. Results of this study are useful by the localities and policy makers in coming up with a more informed decision relative to the issues and concern on hydrological responses in the uplands

    Hospital to home: Interoperability in the health ecosystem

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    Proyecto Educativo Regional concertado de Puno 2017-2025

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    El Proyecto Educativo Regional Concertado Puno 2017–2025 (PERCP 2017–2025) es el instrumento de gestión estratégica con lineamientos de política educativa, emanados de consulta constante con los actores de la comunidad educativa puneña. El equipo gestor organizó talleres, mesas de trabajo y reuniones en las 14 UGELs de la Región; de igual modo, se coordinó con el Consejo de Participación Regional (COPARE), UGELs, sociedad civil organizada, autoridades e instituciones vinculadas con la labor educativa para lograr su legitimación. La propuesta concentra opiniones de expertos de diversas ramas y especialidades, instituciones, empresarios, productores, líderes de opinión, jóvenes, dirigentes de organizaciones sociales y filósofos para consolidar una propuesta coherente a la realidad regional. Visionando os retos que plantea la sociedad del conocimiento, considera además factores esenciales referentes a: cultura, sociedad, medio ambiente, tecnología, ciencia, lingüística, económica y política. En este contexto, proponemos el desarrollo de aprendizajes de calidad con equidad, como una condición para educar ciudadanos íntegros, emprendedores, críticos, creativos, innovadores e investigadores. Aspiramos lograr la certificación y acreditación de las instituciones educativas, garantizando para ello docentes de excelencia, asegurando calidad de vida con servicios básicos e infraestructura educativa, acordes al avance de la ciencia, tecnología, información y comunicación propios a cada contexto

    Implementation of linear analysis in the early stages of performance-based design for steel structures

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    Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Civil and Environmental Engineering, 2012.Cataloged from PDF version of thesis.Includes bibliographical references (p. 38-39).In the aftermath of the destructive 1994 Northridge Earthquake in Southern California, the earthquake engineering industry experienced a shift towards expanding seismic requirements beyond surviving global collapse to include performance criteria. As a part of this effort, the Pacific Earthquake Engineering Research Center has developed a performance-based earthquake engineering (PBEE) procedure that outputs relevant non-technical data to aid major building stakeholders in making important decisions. While PBEE has made great strides in the last decade, its current standing as a verification tool has prevented it from being fully adopted by the seismic design industry. In order for PBEE to be fully integrated into the seismic design process, a method that circumvents the problems associated with the preferred method of nonlinear analysis must be developed. The following study compares interstory drift results from linear and nonlinear analysis to gain insight into their relationship and determine conditions for which linear analysis is an appropriate substitute, yielding a much faster and computationally cheaper procedure. It is hoped that this study will contribute to the adoption of linear analysis in the early seismic design stages, allowing for an optimal structural system selection procedure that integrates performance metrics from the beginning.by Antonio Ayala.M.Eng

    Flood hazard mapping in an urban area using combined hydrologic-hydraulic models and geospatial technologies

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    Flooding is one of the most occurring natural hazards every year risking the lives and properties of the affected communities, especially in Philippine context. To visualize the extent and mitigate the impacts of flood hazard in Malingon River in Valencia City, Bukidnon, this paper presents the combination of Geographic Information System, high-resolution Digital Elevation Model, land cover, soil, observed hydro-meteorological data; and the combined Hydrologic Engineering Center-Hydrologic Modeling System and River Analysis System models. The hydrologic model determines the precipitation-runoff relationships of the watershed and the hydraulic model calculates the flood depth and flow pattern in the floodplain area. The overall performance of hydrologic model during calibration was “very good fit” based on the criterion of Nash-Sutcliffe Coefficient of Model Efficiency, Percentage Bias and Root Mean Square Error – Observations Standard Deviation Ratio with the values of 0.87, -8.62 and 0.46, respectively. On the other hand, the performance of hydraulic model during error computation was “intermediate fit” using F measure analysis with a value of 0.56, using confusion matrix with 80.5% accuracy and the Root Mean Square Error of 0.47 meters. Flood hazard maps in 2, 5, 10, 25, 50 and 100-year return periods were generated as well as the number of flooded buildings in each flood hazard level and in different return periods were determined. The output of the study served as an important basis for a more informed decision and science-based recommendations in formulating local and regional policies for more effective and cost-efficient strategies relative to flood hazards

    Flood hazard zones using 2d hydrodynamic modeling and remote sensing approaches

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    Increasing frequency and severity of flooding demands identification of flood hazard zones in Kalilangan, Bukidnon in response to the echoing need of better disaster preparedness via enhancing the understanding and awareness of the public on flood characteristics by integrating the use of two-dimensional hydrodynamic modeling and remote sensing. Flood simulation was carried out in a two-dimensional hydrodynamic model using hydrologic engineering center-river analysis system to derive the flood inundation area and flood depth of Kalilangan, Bukidnon. Thus, it was preceded by pre-processing of the model using software packages of hydrologic engineering center-hydrologic modeling system and ArcGIS along with interferometric synthetic aperture radar–digital elevation model, Manning’s roughness coefficient and precipitation data. Five different rain return flooding scenarios were simulated using rainfall intensity duration frequency data. Three zones of flood hazard were then set as low, medium and high. The result shows that most areas of Kalilangan are within the zones of medium to high hazard with residential buildings as the most flooded type of built-up structures. Flood hazard zone areas could be mapped at an accuracy of 79.51%. Thus, harnessing this potential approach offers cost-effective way of flood preparedness viewing hazard-prone areas with special attention and utmost importance

    Optimización de la oferta educativa de la educación superior tecnológica pública al 2021 : diagnóstico de la Oferta Educativa Superior Tecnológica Pública de la Región Puno

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    El presente diagnóstico determina y describe las condiciones en las que se provee actualmente el servicio educativo en los IEST públicos a nivel regional. La información que este documento provee permite reflexionar y discutir sobre el actual funcionamiento y desarrollo de la oferta formativa. En tal sentido, contribuye a una futura toma de decisiones informada por parte del Gobierno Regional, en el marco del proceso de optimización. Para la identificación de brechas en la oferta formativa (estudio de sostenibilidad), se revisaron 5 aspectos: 1) Gestión institucional, 2) Gestión académica, 3) Infraestructura y equipamiento, 4) Personal docente y 5) Previsión económica y financiera. Así, el presente documento reporta un porcentaje alcanzado de 86% en los 4 primeros aspectos2 por parte de los 23 IEST públicos de la región Puno. Al revisar cada aspecto se observó diferencias importantes entre las instituciones, tanto a nivel agregado, como a nivel de cada subindicador. Por ejemplo, de manera comparada, los aspectos referidos a Infraestructura y equipamiento y Gestión académica, presentan los niveles más bajos de cumplimiento en los IEST públicos de la región (73% y 78% respectivamente)
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