A combined inverse finite element – elastoplastic modelling method to simulate the size-effect in nanoindentation and characterise materials from the nano to micro-scale

Material properties such as hardness can be dependent on the size of the indentation load when that load is small, a phenomenon known as the indentation size effect (ISE). In this work an inverse finite element method (IFEM) is used to investigate the ISE, with reference to experiments with a Berkovich indenter and an aluminium test material. It was found that the yield stress is highly dependent on indentation depth and in order to simulate this, an elastoplastic constitutive relation in which yielding varies with indentation depth/load was developed. It is shown that whereas Young's modulus and Poisson's ratio are not influenced by the length scale over the range tested, the amplitude portion of yield stress, which is independent of hardening and corresponds to the initial stress for a bulk material, changes radically at small indentation depths. Using the proposed material model and material parameters extracted using IFEM, the indentation depth-time and load-depth plots can be predicted at different loads with excellent agreement to experiment; the relative residual achieved between FE modelling displacement and experiment being less than 0.32%. An improved method of determining hardness from nanoindentation test data is also presented, which shows goof agreement with that determined using the IFEM

Planta de pur? instant?neo de papas nativas en Cajamarca

El Per? tiene una gran diversidad de condiciones naturales que le otorgan una importante riqueza biol?gica. Esto genera ventajas comparativas, como ocurre en el caso de las papas nativas que se cultivan sobre los 2 mil m.s.n.m. y de las cuales existen alrededor de 2500 tipos diferentes. Una de estas variedades es la papa nativa Huagalina, que posee caracter?sticas morfol?gicas y nutritivas que la hacen ideal para la industrializaci?n y el procesamiento en forma de pur? instant?neo. El prop?sito de la presente investigaci?n es el dise?o de un modelo de negocios sostenible para este producto, centrado en el mercado interno. La iniciativa parti? de la ONG Aders Per?, especializada en el desarrollo sostenible de comunidades agr?colas, que consigui? por donaci?n la maquinaria necesaria para el procesamiento de pur? instant?neo de la papa Huagalina y la cedi? a la Central de Productores Agr?colas de Huanico, en Cajamarca. Pero como la planta no operaba, el Ministerio de la Producci?n y la mencionada ONG solicitaron este trabajo. El estudio se divide en dos grandes bloques. El primero, analiza y diagnostica el esquema asociativo del consorcio entre una empresa privada (Delinka's) y una comunidad campesina (la asociaci?n productiva Huanico). El segundo bloque consiste en un estudio de mercado entre amas de casa de los sectores A y B sobre el consumo de pur? de papa en Lima y Callao, lo que permite establecer el p?blico objetivo, el tama?o del mercado y el precio que el potencial consumidor estar?a dispuesto a pagar por el nuevo producto

Immunomodulating activity of Celosia argentea Linn aerial parts

Aerial parts of Celosia argentea Linn. (Amaranthaceae) were extracted with 70 % ethanol and water to produce respective extracts. These extracts were screened for delayed type hypersensitivity (DTH), neutrophil adhesion test and cyclophosphamide-induced myelosuppression to assess the effect on immunity in Swiss albino mice at the dose of 50 and 100 mg/kg, i.p. Results showed significant immunomodulating activity of aqueous extract.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Dise?o, procura, construcci?n y puesta en marcha de la ampliaci?n del taller de mantenimiento - fase A

El proyecto de ?Dise?o, procura, construcci?n y puesta en marcha de taller de mantenimiento Fase A?, considera incrementar la flota de camiones de 80 a 120 para el a?o 2025, y como consecuencia, la capacidad del actual taller de mantenimiento quedar? subdimensionada; siendo necesario ampliar sus instalaciones para garantizar la confiabilidad y disponibilidad mec?nica de los camiones mineros. Incluye el desarrollo de ingenier?a b?sica, ingenier?a de detalle, contrataciones, adquisici?n de equipos, suministro de materiales, construcci?n y puesta en marcha de la ampliaci?n del taller de mantenimiento que brinden servicio a los equipos de la flota minera. El alcance del trabajo incluye la ejecuci?n de trabajos tempranos en el patio de rescate y en la plataforma principal del taller, construcci?n de construcci?n de plataformas y accesos, desmontaje de instalaciones existentes, construcci?n de 7 bah?as de mantenimiento de camiones, infraestructura auxiliar, instalaci?n de redes de servicio, precomisionamiento y cominsionamiento. Para una adecuada ejecuci?n y entrega del proyecto, se desarrollan los planes de gesti?n de proyectos siguiendo los lineamientos de la gu?a est?ndar del PMBOK y 6ta. Edici?n, los cuales describen la metodolog?a, actividades y consideraciones que deber? tener el equipo para la gesti?n exitosa de este proyect

Hierarchical approach for fatigue cracking performance evaluation in asphalt pavements

In this paper, a hierarchical approach is proposed for the evaluation of fatigue cracking in asphalt concrete pavements considering three different levels of complexities in the representation of the material behaviour, design parameters characterization and the determination of the pavement response as well as damage computation. Based on the developed hierarchical approach, three damage computation levels are identified and proposed. The levels of fatigue damage analysis provides pavement engineers a variety of tools that can be used for pavement analysis depending on the availability of data, required level of prediction accuracy and computational power at their disposal. The hierarchical approach also provides a systematic approach for the understanding of the fundamental mechanisms of pavement deterioration, the elimination of the empiricism associated with pavement design today and the transition towards the use of sound principles of mechanics in pavement analysis and design

Preclinical Evidence Supporting Early Initiation of Citalopram Treatment in Machado-Joseph Disease

Spinocerebellar ataxias are dominantly inherited neurodegenerative disorders with no disease-modifying treatment. We previously identified the selective serotonin reuptake inhibitor citalopram as a safe and effective drug to be repurposed for Machado-Joseph disease. Pre-symptomatic treatment of transgenic (CMVMJD135) mice strikingly ameliorated mutant ataxin-3 (ATXN3) pathogenesis. Here, we asked whether citalopram treatment initiated at a post-symptomatic age would still show efficacy. We used a cohort of CMVMJD135 mice that shows increased phenotypic severity and faster disease progression (CMVMJD135hi) compared to the mice used in the first trial. Groups of hemizygous CMVMJD135hi mice were orally treated with citalopram. Behavior, protein analysis, and pathology assessment were performed blindly to treatment. Our results show that even when initiated after symptom onset, treatment of CMVMJD135hi mice with citalopram ameliorated motor coordination and balance, attenuating disease progression, albeit to a lesser extent than that seen with pre-symptomatic treatment initiation. There was no impact on ATXN3 aggregation, which contrasts with the robust reduction in ATXN3-positive inclusions observed in CMVMJD135 mice, when treated pre-symptomatically. Post-symptomatic treatment of CMVMJD135hi mice revealed, however, a limited neuroprotective effect by showing a tendency to repair cerebellar calbindin staining, and to increase the number of motor neurons and of NeuN-positive cells in certain brain regions. While supporting that early initiation of treatment with citalopram leads to a marked increase in efficacy, these results strengthen our previous observation that modulation of serotonergic signaling by citalopram is a promising therapeutic approach for Machado-Joseph disease even after symptom onset.European Regional Development Funds (FEDER), through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038. This article has been developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the FEDER. This work was also supported by FCT and COMPETE through the projects [PTDC/SAU-GMG/112617/2009] (to PM) and [EXPL/BIM-MEC/0239/2012] (to AT-C), by FCT through the project [POCI-01-0145-FEDER-016818 (PTDC/NEU-NMC/3648/2014)] (to PM), by National Ataxia foundation (to PM and to AT-C), and by Ataxia UK (to PM). SE, SD-S, SO, and AT-C were supported by the FCT individual fellowships, SFRH/BD/78554/2011, SFRH/BD/78388/2011, PD/BD/127818/2016, and SFRH/BPD/102317/2014, respectively. FCT fellowships are co-financed by POPH, QREN, Governo da República Portuguesa, and EU/FSEinfo:eu-repo/semantics/publishedVersio

Antimicrobial and antioxidant properties of methanol extract, fractions and compounds from the stem bark of Entada abyssinica Stend ex A. Satabie

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to evaluate the antimicrobial and antioxidant activities of the methanol extract, fractions and isolated compounds from <it>Entada abyssinica </it>stem bark, plant used traditionally against gastrointestinal infections.</p> <p>Methods</p> <p>The methanol extract of <it>E. abyssinica </it>stem bark was pre-dissolved in a mixture of methanol and water, and then partitioned between <it>n</it>-hexane, ethyl acetate and <it>n</it>-butanol. The ethyl acetate portion was fractionated by column chromatography and the structures of isolated compounds elucidated by analysis of spectroscopic data and comparison with literature data. Antimicrobial activity was assayed by broth microdilution techniques on bacteria and yeasts. The antioxidant activity was determined by DPPH radical scavenging method.</p> <p>Results</p> <p>Four known compounds [(5<it>S</it>,6<it>R</it>,8a<it>R</it>)-5-(carboxymethyl)-3,4,4a,5,6,7,8,8a-octahydro-5,6,8a-trimethylnaphthalenecarboxylic acid (<b>1</b>), methyl 3,4,5-trihydroxybenzoate (<b>2</b>), benzene-1,2,3-triol (<b>3</b>) and 2,3-dihydroxypropyltriacontanoate (<b>4</b>)] were isolated. Compared to the methanol extract, fractionation increased the antibacterial activities of the <it>n</it>-hexane and ethyl acetate fractions, while the antifungal activities increased in ethyl acetate, <it>n</it>-butanol and aqueous residue fractions. The isolated compounds were generally more active on bacteria (9.7 to 156.2 μg/ml) than yeasts (78.1 to 312.5 μg/ml). Apart from compound <b>1</b>, the three others displayed DPPH^·scavenging activity (RSa), with RSa₅₀values of 1.45 and 1.60 μg/ml.</p> <p>Conclusion</p> <p>The results obtained from this study support the ethnomedicinal use of <it>E. abyssinica </it>in the treatment of gastrointestinal infections and the isolated compounds could be useful in the standardisation of antimicrobial phytomedicine from this plant.</p

Citalopram reduces aggregation of ATXN3 in a YAC transgenic mouse model of Machado-Joseph disease

Machado-Joseph disease, also known as spinocerebellar ataxia type 3, is a fatal polyglutamine disease with no disease-modifying treatment. The selective serotonin reuptake inhibitor citalopram was shown in nematode and mouse models to be a compelling repurposing candidate for Machado-Joseph disease therapeutics. We sought to confirm the efficacy of citalopram to decrease ATXN3 aggregation in an unrelated mouse model of Machado-Joseph disease. Four-week-old YACMJD84.2 mice and non-transgenic littermates were given citalopram 8 mg/kg in drinking water or water for 10 weeks. At the end of treatment, brains were collected for biochemical and pathological analyses. Brains of citalopram-treated YACMJD84.2 mice showed an approximate 50% decrease in the percentage of cells containing ATXN3-positive inclusions in the substantia nigra and three examined brainstem nuclei compared to controls. No differences in ATXN3 inclusion load were observed in deep cerebellar nuclei of mice. Citalopram effect on ATXN3 aggregate burden was corroborated by immunoblotting analysis. While lysates from the brainstem and cervical spinal cord of citalopram-treated mice showed a decrease in all soluble forms of ATXN3 and a trend toward reduction of insoluble ATXN3, no differences in ATXN3 levels were found between cerebella of citalopram-treated and vehicle-treated mice. Citalopram treatment altered levels of select components of the cellular protein homeostatic machinery that may be expected to enhance the capacity to refold and/or degrade mutant ATXN3. The results here obtained in a second independent mouse model of Machado-Joseph disease further support citalopram as a potential drug to be repurposed for this fatal disorder.This work was funded by Becky Babcox Research Fund/pilot research award G015617, University of Michigan to M.C.C. and NINDS/NIH R01NS038712 to H.L.P. The work performed at the University of Minho was funded by the European Regional Development Funds (FEDER), through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038. This article was developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Program (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the FEDER. This work was also supported by FCT and COMPETE through the projects [PTDC/SAU-GMG/112617/2009] (to P.M.) and [EXPL/BIM-MEC/ 0239/2012] (to A.T.C.); by FCT through the project [POCI-01-0145- FEDER-016818 (PTDC/NEU-NMC/3648/2014)] (to P.M.); by National Ataxia Foundation (to P.M. and to A.T.C.); and by Ataxia UK (to P.M.). S.D.S. and A.T.C. were supported by fellowships from FCT, SFRH/BD/ 78388/2011 and SFRH/BPD/102317/2014, respectively. FCT fellowships are co-financed by POPH, QREN, Governo da República Portuguesa and EU/FSE

Innate Killing of Leishmania donovani by Macrophages of the Splenic Marginal Zone Requires IRF-7

Highly phagocytic macrophages line the marginal zone (MZ) of the spleen and the lymph node subcapsular sinus. Although these macrophages have been attributed with a variety of functions, including the uptake and clearance of blood and lymph-borne pathogens, little is known about the effector mechanisms they employ after pathogen uptake. Here, we have combined gene expression profiling and RNAi using a stromal macrophage cell line with in situ analysis of the leishmanicidal activity of marginal zone macrophages (MZM) and marginal metallophilic macrophages (MMM) in wild type and gene targeted mice. Our data demonstrate a critical role for interferon regulatory factor-7 (IRF-7) in regulating the killing of intracellular Leishmania donovani by these specialised splenic macrophage sub-populations. This study, therefore, identifies a new role for IRF-7 as a regulator of innate microbicidal activity against this, and perhaps other, non-viral intracellular pathogens. This study also highlights the importance of selecting appropriate macrophage populations when studying pathogen interactions with this functionally diverse lineage of cells