464 research outputs found

    MULTISCALE CHARACTERIZATION OF ΑLPHA-BETA TITANIUM ALLOYS USING HIGH THROUGHPUT SPHERICAL INDENTATION TEST PROTOCOLS

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    Traditionally, new materials follow well stablished paths from their manufacturing beginnings to their final application. Development, evaluation, certification and deployment are some of the steps in these processes. However, some of these stages are characterized for very specialized protocols, resulting in prolonged timelines from beginning to end. The design process of materials can sometimes be defined as ambiguous due to the lack of fundamental knowledge at salient length-scales. This can be attributed to the absence of trustworthy testing methods that provide meaningful and reliable knowledge on the behavior of materials at length-scales over different orders of magnitude. In addition to this characteristic, cost and time efficiency are also crucial attributes in the materials design field, as large amounts of data covering wide ranges or parameters provide stronger bases for physics-based models that can reverse-engineer the whole process. The work presented here, evaluates spherical nano-indentation protocols as a high-throughput approach for the mechanically characterization of several α- and α/β titanium alloys at the grain-scale level. We start by the exploring the mechanical response of primary-α grains, and their dependence on the HCP lattice orientation and the corresponding grain chemical composition. Next, we move into the mechanical behavior of single grains in fully basket-weave titanium microstructures. By looking into the grain responses, a reduction on the multiple microstructural features in this type of morphologies is accomplished, leading to better statements of the influence of lath-microstructure and α-lath orientations on the indentation properties. This work is accompanied by a thorough microstructural characterization/quantification of the basket-weave morphology that is later subjected to a dimensionality reduction for a simplified understanding. And finally, we aim to bridge multiresolution indentation measurements form a bimodal titanium microstructure for the subsequent evaluation of composite theories in the prediction of the effective indentation yield.Ph.D

    Trigemino vascular systemand primary headache

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    La fisiopatología de las cefaleas primarias es compleja e incluye un sinnúmero de interacciones que regulan el proceso nociceptivo. Dentro de los principales responsables de generar el dolor se encuentra el sistema trigémino vascular, que es un conjunto de estructuras que integran vías tanto centrales corticosubcorticales como periféricas, que desempeñan un papel activo no solo en la génesis del dolor, sino en las manifestaciones autonómicas y visuales que acompañan la cefalea. Así mismo, este sistema es el responsable de los mecanismos de sensibilización central característicos del dolor. En el artículo se desarrollan brevemente las principales estructuras que participan en la génesis de las cefaleas primarias y sus interacciones en las diferentes partes del sistema nervioso.Artículo de revisión92-103The pathophysiology of primary headache is complex and it includes several interactions that regulate the nociceptive process. The tri-geminal-vascular system is perhaps one of the principal structures that generate pain due to the integration of several pathways both central and peripheral. In addition to this, the trigemi-nal vascular system also plays a central role in the autonomic and visual symptoms that affect individuals with headache and in the central sensitization process. In this article we briefly discuss the main structures that participate in the pathophysiology of primary headaches and their interactions in the different levels of the central nervous system

    Conocimientos circulares ancestrales: Despertó nuestro Mapuzungun

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    El presente Proyecto es la integración de saberes y diálogos interculturales en una creación Artístico- Literaria y comunitaria, donde se ponen en valor lo simbólico como patrimonio cultural del pueblo mapuche, resignificando lo ancestral en el contexto contemporáneo bonaerense.Fil: Aramburú, Guillermo José. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Sociales; ArgentinaFil: Millan, Mirta Fabiana. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Sociales; ArgentinaFil: Puñalef, Darío Rafael. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Sociales; ArgentinaFil: Acosta, Maia Bárbara. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Sociales; ArgentinaFil: Antieco, Juana Estela. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Sociales; ArgentinaFil: Arispe, Camila. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Sociales; ArgentinaFil: Brizuela, Agustina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Sociales; ArgentinaFil: Lencina, Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Investigaciones Arqueológicas y Paleontológicas del Cuaternario Pampeano. Universidad Nacional del Centro de la Provincia de Buenos Aires. Investigaciones Arqueológicas y Paleontológicas del Cuaternario Pampeano; ArgentinaFil: Mendoza, Graciela Beatriz. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Sociales; ArgentinaFil: Merlo, Julio Fabián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Investigaciones Arqueológicas y Paleontológicas del Cuaternario Pampeano. Universidad Nacional del Centro de la Provincia de Buenos Aires. Investigaciones Arqueológicas y Paleontológicas del Cuaternario Pampeano; ArgentinaFil: Pioppi, Natalia. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Sociales; ArgentinaFil: Rubiolo, Ana. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Sociales; ArgentinaFil: Sansone, Cristina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Sociales; ArgentinaFil: Silva, Sandra Elizabeth. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Sociales; ArgentinaFil: Thea, Alba. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Sociales; Argentin

    Trace metals and micronutrients in bone tissues of the red fox Vulpes vulpes (L., 1758)

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    In this study we determined the levels of trace elements (zinc, copper, lead, cadmium and mercury) in three layers of bones of the hip joint (cartilage, compact bone and spongy bone) of 30 red foxes (Vulpes vulpes) from north-western Poland. Concentrations of Cu, Zn, Pb and Cd were determined by atomic absorption spectrophotometry (ICP-AES) in inductively coupled argon plasma using a Perkin-Elmer Optima 2000 DV. Determination of Hg concentration was performed by atomic absorption spectroscopy. In cartilage, compact bone and spongy bone samples from the red fox, median concentrations of the metals studied could be arranged in the following descending series: Zn > Cu > Pb > Cd > Hg, the values ranging from 142 to 0.002 mg/kg dw. There was a significant difference in Cu concentrations, among all the materials analyzed, with much more Cu found in spongy bone than in compact bone. Significant differences were also noted in the case of Hg concentrations in cartilage with compact bone and the spongy bone, and between concentrations of this metal in compact bone and spongy bone. In males, the concentration of Hg in spongy bone was greater than in females. Younger foxes had a higher concentration of this metal in cartilage than adults. The strongest synergistic relationships were observed in spongy bone between the Zn and Cu, Zn and Cd, as well as between Cu and Cd. Statistically significant antagonistic relationships were detected between zinc and lead in compact bone. In addition to monitoring studies conducted on the abiotic environment, an urgent need exists for long-term monitoring of concentrations of heavy metals with long-term effects on living organisms. An important addition is provided by biomonitoring studies on domesticated and free-living mammals, including Canidae

    Sprouty2 and Spred1-2 Proteins Inhibit the Activation of the ERK Pathway Elicited by Cyclopentenone Prostanoids

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    Sprouty and Spred proteins have been widely implicated in the negative regulation of the fibroblast growth factor receptor-extracellular regulated kinase (ERK) pathway. In considering the functional role of these proteins, we explored their effects on ERK activation induced by cyclopentenone prostanoids, which bind to and activate Ras proteins. We therefore found that ectopic overexpression in HeLa cells of human Sprouty2, or human Spred1 or 2, inhibits ERK1/2 and Elk-1 activation triggered by the cyclopentenone prostanoids PGA1 and 15d-PGJ2. Furthermore, we found that in HT cells that do not express Sprouty2 due to hypermethylation of its gene-promoter, PGA1-provoked ERK activation was more intense and sustained compared to other hematopoietic cell lines with unaltered Sprouty2 expression. Cyclopentenone prostanoids did not induce Sprouty2 tyrosine phosphorylation, in agreement with its incapability to activate tyrosine-kinase receptors. However, Sprouty2 Y55F, which acts as a defective mutant upon tyrosine-kinase receptor stimulation, did not inhibit cyclopentenone prostanoids-elicited ERK pathway activation. In addition, Sprouty2 did not affect the Ras-GTP levels promoted by cyclopentenone prostanoids. These results unveil both common and differential features in the activation of Ras-dependent pathways by cyclopentenone prostanoids and growth factors. Moreover, they provide the first evidence that Sprouty and Spred proteins are negative regulators of the ERK/Elk-1 pathway activation induced not only by growth-factors, but also by reactive lipidic mediators

    Assessment of gene-by-sex interaction effect on bone mineral density

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    To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Sexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however, the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene-by-sex autosomal interactions genome-wide, and performed expression quantitative trait loci (eQTL) analysis and bioinformatics network analysis. We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction on lumbar spine (LS) and femoral neck (FN) BMD in 25,353 individuals from 8 cohorts. In a second stage, we followed up the 12 top single-nucleotide polymorphisms (SNPs; p < 1 × 10(-5) ) in an additional set of 24,763 individuals. Gene-by-sex interaction and sex-specific effects were examined in these 12 SNPs. We detected one novel genome-wide significant interaction associated with LS-BMD at the Chr3p26.1-p25.1 locus, near the GRM7 gene (male effect = 0.02 and p = 3.0 × 10(-5) ; female effect = -0.007 and p = 3.3 × 10(-2) ), and 11 suggestive loci associated with either FN- or LS-BMD in discovery cohorts. However, there was no evidence for genome-wide significant (p < 5 × 10(-8) ) gene-by-sex interaction in the joint analysis of discovery and replication cohorts. Despite the large collaborative effort, no genome-wide significant evidence for gene-by-sex interaction was found to influence BMD variation in this screen of autosomal markers. If they exist, gene-by-sex interactions for BMD probably have weak effects, accounting for less than 0.08% of the variation in these traits per implicated SNP. © 2012 American Society for Bone and Mineral Research.Medtronic NIH R01 AG18728 R01HL088119 R01AR046838 U01 HL084756 R01 AR43351 P01-HL45522 R01-MH-078111 R01-MH-083824 Nutrition and Obesity Research Center of Maryland P30DK072488 NIAMS/NIH F32AR059469 Instituto de Salud Carlos III-FIS (Spanish Health Ministry) PI 06/0034 PI08/0183 Canadian Institutes of Health Research (CIHR) NHLBI HHSN268201200036C N01-HC-85239 N01-HC-85079 N01-HC-85086 N01-HC-35129 N01 HC15103 N01 HC-55222 N01-HC-75150 N01-HC-45133 HL080295 HL087652 HL105756 NIA AG-023629 AG-15928 AG-20098 AG-027058 N01AG62101 N01AG62103 N01AG62106 1R01AG032098-01A1 National Center of Advancing Translational Technologies CTSI UL1TR000124 National Institute of Diabetes and Digestive and Kidney Diseases DK063491 EUROSPAN (European Special Populations Research Network) European Commission FP6 STRP grant 018947 LSHG-CT-2006-01947 Netherlands Organisation for Scientific Research Erasmus MC Centre for Medical Systems Biology (CMSB) Netherlands Brain Foundation (HersenStichting Nederland) US National Institute for Arthritis, Musculoskeletal and Skin Diseases National Institute on Aging R01 AR/AG41398 R01 AR050066 R21 AR056405 National Heart, Lung, and Blood Institute's Framingham Heart Study N01-HC-25195 Affymetrix, Inc. N02-HL-6-4278 Canadian Institutes of Health Research from Institute of Aging 165446 Institute of Genetics 179433 Institute of Musculoskeletal health 221765 Intramural Research Program of the NIH, National Institute on Aging National Institutes of Health HHSN268200782096C Hong Kong Research Grant Council HKU 768610M Bone Health Fund of HKU Foundation KC Wong Education Foundation Small Project Funding 201007176237 Matching Grant CRCG Grant Osteoporosis and Endocrine Research Fund Genomics Strategic Research Theme of The University of Hong Kong Netherlands Organisation of Scientific Research NWO Investments 175.010.2005.011 911-03-012 Research Institute for Diseases in the Elderly 014-93-015 Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) 050-060-810 Erasmus Medical Center and Erasmus University, Rotterdam Netherlands Organization for the Health Research and Development (ZonMw) Research Institute for Diseases in the Elderly (RIDE) Ministry of Education, Culture and Science Ministry for Health, Welfare and Sports European Commission (DG XII) Municipality of Rotterdam German Bundesministerium fur Forschung und Technology 01 AK 803 A-H 01 IG 07015

    The clinical and genetic spectrum of autosomal-recessive TOR1A-related disorders.

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    In the field of rare diseases, progress in molecular diagnostics led to the recognition that variants linked to autosomal-dominant neurodegenerative diseases of later onset can, in the context of biallelic inheritance, cause devastating neurodevelopmental disorders and infantile or childhood-onset neurodegeneration. TOR1A-associated arthrogryposis multiplex congenita 5 (AMC5) is a rare neurodevelopmental disorder arising from biallelic variants in TOR1A, a gene that in the heterozygous state is associated to torsion dystonia-1 (DYT1 or DYT-TOR1A), an early-onset dystonia with reduced penetrance. While 15 individuals with TOR1A-AMC5 have been reported (less than 10 in detail), a systematic investigation of the full disease-associated spectrum has not been conducted. Here, we assess the clinical, radiological and molecular characteristics of 57 individuals from 40 families with biallelic variants in TOR1A. Median age at last follow-up was 3 years (0-24 years). Most individuals presented with severe congenital flexion contractures (95%) and variable developmental delay (79%). Motor symptoms were reported in 79% and included lower limb spasticity and pyramidal signs, as well as gait disturbances. Facial dysmorphism was an integral part of the phenotype, with key features being a broad/full nasal tip, narrowing of the forehead and full cheeks. Analysis of disease-associated manifestations delineated a phenotypic spectrum ranging from normal cognition and mild gait disturbance to congenital arthrogryposis, global developmental delay, intellectual disability, absent speech and inability to walk. In a subset, the presentation was consistent with fetal akinesia deformation sequence with severe intrauterine abnormalities. Survival was 71% with higher mortality in males. Death occurred at a median age of 1.2 months (1 week - 9 years) due to respiratory failure, cardiac arrest, or sepsis. Analysis of brain MRI studies identified non-specific neuroimaging features, including a hypoplastic corpus callosum (72%), foci of signal abnormality in the subcortical and periventricular white matter (55%), diffuse white matter volume loss (45%), mega cisterna magna (36%) and arachnoid cysts (27%). The molecular spectrum included 22 distinct variants, defining a mutational hotspot in the C-terminal domain of the Torsin-1A protein. Genotype-phenotype analysis revealed an association of missense variants in the 3-helix bundle domain to an attenuated phenotype, while missense variants near the Walker A/B motif as well as biallelic truncating variants were linked to early death. In summary, this systematic cross-sectional analysis of a large cohort of individuals with biallelic TOR1A variants across a wide age-range delineates the clinical and genetic spectrum of TOR1A-related autosomal-recessive disease and highlights potential predictors for disease severity and survival
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