Material flow analysis in indentation process by 3D Digital Image Correlation

Focusing in the application of the 3D Digital Image Correlation technique, this work proposes a material flow analysis in an indentation process. The study establishes the methodology for the calibration and implementation of the 3D image sensing technology for deformation measurements. The purpose is to continue with the validation of the DIC application to the indentation processes, where a deep penetration is achieved and extensive material flow is produced. With the 3D DIC technique is possible to perform accurate deformation measurements in not planar specimens and study the material emerging towards the exterior of the tested specimen, which is not possible with the 2D DIC technique. Although previous 2D studies were efficient detecting the flow field and von Mises strains on the specimens tested, the bulge emerging under the punch on the front surface (dead zone) could not be studied due to its predominantly 3D character. Therefore, present work implements a 3D methodology that carries out a complete study of the deformation, including the material flow that occurs on the Z axis, towards the exterior of the tested specimen, optimizing previous analyses.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Designing bioactive porous titanium interfaces to balance mechanical properties and in vitro cells behavior towards increased osseointegration

Titanium implant failures are mainly related to stress shielding phenomenon and the poor cell interaction with host bone tissue. The development of bioactive and biomimetic Ti scaffolds for bone regeneration remains a challenge which needs the design of Ti implants with enhanced osseointegration. In this context, 4 types of titanium samples were fabricated using conventional powder metallurgy, fully dense, dense etched, porous Ti, and porous etched Ti. Porous samples were manufactured by space holder technique, using ammonium bicarbonate particles as spacer in three different ranges of particle size (100–200 μm, 250–355 μm and 355–500 μm). Substrates were chemically etched by immersion in fluorhydric acid at different times (125 and 625 s) and subsequently, were characterized from a micro-structural, topographical and mechanical point of view. Etched surfaces showed an additional roughness preferentially located inside pores. In vitro tests showed that all substrates were biocompatible (80% of cell viability), confirming cell adhesion of premioblastic cells. Similarly, osteoblast showed similar cell proliferation rates at 4 days, however, higher cell metabolic activity was observed in fully dense and dense etched surfaces at 7 days. In contrast, a significant increase of alkaline phosphatase enzyme expression was observed in porous and porous etched samples compared to control surfaces (dense and dense etched), noticing the suitable surface modification parameters (porosity and roughness) to improve cell differentiation. Furthermore, the presence of pores and rough surfaces of porous Ti substrates remarkably decreased macrophage activation reducing the M1 phenotype polarization as well M1 cell marker expression. Thus, a successful surface modification of porous Ti scaffolds has been performed towards a reduction on stress shielding phenomenon and enhancement of bone osseointegration, achieving a biomechanical and biofunctional equilibrium.Ministry of Economy and Competitiveness of Spain grant MAT2015-71284-PJunta de Andalucía – FEDER (Spain) Project Ref. P12-TEP-140

Aberrant innate immune sensing leads to the rapid progression of idiopathic pulmonary fibrosis

Novel approaches are needed to define subgroups of patients with Idiopathic pulmonary fibrosis (IPF) at risk for acute exacerbations and/or accelerated progression of this generally fatal disease. Progression of disease is an integral component of IPF with a median survival of 3 to 5 years. Conversely, a high degree of variability in disease progression has been reported among series. The characteristics of patients at risk of earlier death predominantly rely on baseline HRCT appearance, but this concept that has been challenged. Disparate physiological approaches have also been taken to identify patients at risk of mortality, with varying results. We hypothesized that the rapid decline in lung function in IPF may be a consequence of an abnormal host response to pathogen-associated molecular patterns (PAMPs), leading to aberrant activation in fibroblasts and fibrosis. Analysis of upper and lower lobe surgical lung biopsies (SLBs) indicated that TLR9, a hypomethylated CpG DNA receptor, is prominently expressed at the transcript and protein level, most notably in biopsies from rapidly progressive IPF patients. Surprisingly, fibroblasts appeared to be a major cellular source of TLR9 expression in IPF biopsies from this group of progressors. Further, CpG DNA promoted profibrotic cytokine and chemokine synthesis in isolated human IPF fibroblasts, most markedly again in cells from patients with the rapidly progressive IPF phenotype, in a TLR9-dependent manner. Finally, CpG DNA exacerbated fibrosis in an in vivo model initiated by the adoptive transfer of primary fibroblasts derived from patients who exhibited rapidly progressing fibrosis. Together, these data suggested that TLR9 activation via hypomethylated DNA might be an important mechanism in promoting fibrosis particularly in patients prone to rapidly progressing IPF

Efficacy optimization of plasma-activated water for food sanitization through two reactor design configurations

The chemistry, antimicrobial efficacy and energy consumption of plasma-activated water (PAW) was optimized by altering the discharge frequency, ground-electrode configuration, gas flow rate and initial water conductivity for two reactor configurations, i.e., air pin-to-liquid discharge and air plasma-bubble discharge in water. The ratio of NO2− and NO3− formation was altered to optimise the antimicrobial effects of PAW, tested against two Gram-negative bacteria. An initial solution conductivity of 0.2 S·m−1 and 2000-Hz discharge frequency with the ground electrode positioned inside the pin reactor showed the highest antimicrobial effect resulting in a 3.99 ± 0.13-log10 reduction within 300 s against Escherichia coli and 5.90 ± 0.24-log10 reduction within 240 s for Salmonella Typhimurium. An excellent energy efficiency of reactive oxygen and nitrogen species (RONS) generation of 10.1 ± 0.1 g·kW−1·h−1 was achieved. Industrial relevance: Plasma-activated water (PAW) is deemed as an eco-friendly alternative to chemical disinfection because its bactericidal activity is temporary. Optimizing the design and operation of PAW reactors to achieve high inactivation rates of more than 5-log10 reductions, as demonstrated in this work, will support the industrial application of this technology and the scaleup at industrial level

SELECTIVIDAD DE LAS ISOFORMAS DE 140-180 KDA DE NCAM EN LA PAPILA ÓPTICA DEL EMBRIÓN DE POLLO

During embryonic development of chicken retina and retinotectal proyection, neural cells showed spatiotemporal patterns in the glycosidic residues located in the plasmatic membranes. Those glycidic components are related with adhesion and recognition cellular behaviours during the generation of nervous system cytoarchitecture. Thus those sugars are included both in usual glycoproteins as in a group of molecules called as cell adhesion molecules (CAM). The first isolated molecule in this group was the neural cell adhesion molecule (NCAM). This glycoprotein has a proteic core with diverse isoforms and it has a variable sialic acids chain. It was able to determine that 120 kDa NCAM isoform shows scarcely sialized chains in intermediate stages by using conventional techniques, lectins and immunohistochemistry. Meanwhile 140-180 kDa NCAM isoforms possess high content in sialic acid and they are present both in early and final stages. Other authors reported that human 120 kDa NCAM isoform was similar to that observed in the Gallus domesticus retina. Our results showed that 140- 180kDa isoforms were only presented in the nerve optic fibers when they were left the optic disc.Durante la embriogénesis de la retina del Gallus domesticus, los neuroblastos muestran variaciones temporales y espaciales de los residuos glucosilados a nivel de sus membranas plasmáticas. Se considera que estos componentes glucídicos están implicados en la organización de estructuras neurales inmaduras, mediante su participación en mecanismos de reconocimiento y adhesión celulares. Los componentes glucosilados van a formar parte de glucoproteínas convencionales, así como de un grupo de moléculas a las que genéricamente se han denominado moléculas de adhesión celular. La primera de estas moléculas aislada fue la neural cell adhesion molecule (NCAM), glucoproteína compuesta por un armazón proteico con diversas isoformas y una cadena más o menos variable de polímeros de ácidos siálicos. La combinación de técnicas convencionales his- toquímicas, de lectinas e inmunocitoquímicas han permitido determinar que las moléculas de NCAM de 120 kDa presentan cadenas pobremente sializadas en estadíos intermedios del desarrollo, mientras en estadíos tempranos y finales los ácidos siálicos están más abundantemente representados en las isoformas de 140-180 kDa. Algunos autores han determinado que la isoforma de NCAM presente durante el desarrollo de la retina del Gallus domesticus es similar a la humana de 120 kDa. Nuestros resultados indican que las isoformas de 140-180 kDa sólo se presentan en las fibras del nervio óptico una vez que estas abandonan la papila óptica

The Main Belt Comets and ice in the Solar System

We review the evidence for buried ice in the asteroid belt; specifically the questions around the so-called Main Belt Comets (MBCs). We summarise the evidence for water throughout the Solar System, and describe the various methods for detecting it, including remote sensing from ultraviolet to radio wavelengths. We review progress in the first decade of study of MBCs, including observations, modelling of ice survival, and discussion on their origins. We then look at which methods will likely be most effective for further progress, including the key challenge of direct detection of (escaping) water in these bodies

A Multiwell Platform for Studying Stiffness-Dependent Cell Biology

Adherent cells are typically cultured on rigid substrates that are orders of magnitude stiffer than their tissue of origin. Here, we describe a method to rapidly fabricate 96 and 384 well platforms for routine screening of cells in tissue-relevant stiffness contexts. Briefly, polyacrylamide (PA) hydrogels are cast in glass-bottom plates, functionalized with collagen, and sterilized for cell culture. The Young's modulus of each substrate can be specified from 0.3 to 55 kPa, with collagen surface density held constant over the stiffness range. Using automated fluorescence microscopy, we captured the morphological variations of 7 cell types cultured across a physiological range of stiffness within a 384 well plate. We performed assays of cell number, proliferation, and apoptosis in 96 wells and resolved distinct profiles of cell growth as a function of stiffness among primary and immortalized cell lines. We found that the stiffness-dependent growth of normal human lung fibroblasts is largely invariant with collagen density, and that differences in their accumulation are amplified by increasing serum concentration. Further, we performed a screen of 18 bioactive small molecules and identified compounds with enhanced or reduced effects on soft versus rigid substrates, including blebbistatin, which abolished the suppression of lung fibroblast growth at 1 kPa. The ability to deploy PA gels in multiwell plates for high throughput analysis of cells in tissue-relevant environments opens new opportunities for the discovery of cellular responses that operate in specific stiffness regimes

Trends in self-reported prevalence and management of hypertension, hypercholesterolemia and diabetes in Swiss adults, 1997-2007

Switzerland has a low mortality rate from cardiovascular diseases, but little is known regarding prevalence and management of cardiovascular risk factors (CV RFs: hypertension, hypercholesterolemia and diabetes) in the general population. In this study, we assessed 10-year trends in self-reported prevalence and management of cardiovascular risk factors in Switzerland. data from three national health interview surveys conducted between 1997 and 2007 in representative samples of the Swiss adult population (49,261 subjects overall). Self-reported CV RFs prevalence, treatment and control levels were computed. The sample was weighted to match the sex - and age distribution, geographical location and nationality of the entire adult population of Switzerland. self-reported prevalence of hypertension, hypercholesterolemia and diabetes increased from 22.1%, 11.9% and 3.3% in 1997 to 24.1%, 17.4% and 4.8% in 2007, respectively. Prevalence of self-reported treatment among subjects with CV RFs also increased from 52.1%, 18.5% and 50.0% in 1997 to 60.4%, 38.8% and 53.3% in 2007 for hypertension, hypercholesterolemia and diabetes, respectively. Self-reported control levels increased from 56.4%, 52.9% and 50.0% in 1997 to 80.6%, 75.1% and 53.3% in 2007 for hypertension, hypercholesterolemia and diabetes, respectively. Finally, screening during the last 12 months increased from 84.5%, 86.5% and 87.4% in 1997 to 94.0%, 94.6% and 94.1% in 2007 for hypertension, hypercholesterolemia and diabetes, respectively. in Switzerland, the prevalences of self-reported hypertension, hypercholesterolemia and diabetes have increased between 1997 and 2007. Management and screening have improved, but further improvements can still be achieved as over one third of subjects with reported CV RFs are not treated

TLR9-induced interferon β is associated with protection from gammaherpesvirus-induced exacerbation of lung fibrosis

Abstract Background We have shown previously that murine gammaherpesvirus 68 (γHV68) infection exacerbates established pulmonary fibrosis. Because Toll-like receptor (TLR)-9 may be important in controlling the immune response to γHV68 infection, we examined how TLR-9 signaling effects exacerbation of fibrosis in response to viral infection, using models of bleomycin- and fluorescein isothiocyanate-induced pulmonary fibrosis in wild-type (Balb/c) and TLR-9-/- mice. Results We found that in the absence of TLR-9 signaling, there was a significant increase in collagen deposition following viral exacerbation of fibrosis. This was not associated with increased viral load in TLR-9-/- mice or with major alterations in T helper (Th)1 and Th2 cytokines. We examined alveolar epithelial-cell apoptosis in both strains, but this could not explain the altered fibrotic outcomes. As expected, TLR-9-/- mice had a defect in the production of interferon (IFN)-β after viral infection. Balb/c fibroblasts infected with γHV68 in vitro produced more IFN-β than did infected TLR-9-/- fibroblasts. Accordingly, in vitro infection of Balb/c fibroblasts resulted in reduced proliferation rates whereas infection of TLR-9-/- fibroblasts did not. Finally, therapeutic administration of CpG oligodeoxynucleotides ameliorated bleomycin-induced fibrosis in wild-type mice. Conclusions These results show a protective role for TLR-9 signaling in murine models of lung fibrosis, and highlight differences in the biology of TLR-9 between mice and humans.http://deepblue.lib.umich.edu/bitstream/2027.42/112877/1/13069_2011_Article_57.pd

RARE-Bestpractices: a platform for sharing best practices for the management of rare diseases

From 7th European Conference on Rare Diseases and Orphan Products (ECRD 2014).Rare diseases; clinical practice guidelines; recommendations. RARE-Bestpractices (http://www.rarebestpractices.eu) is a 4-year project (2013-2016) funded by the EC FP7. The project aims at improving clinical management of patients with rare diseases (RD) and at narrowing the existing gap in quality of healthcare among countries. Methods: RARE-Bestpractices (http://www.rarebestpractices.eu) involves 9 EU countries, including 15 partners from academic institutions, governmental bodies, patient organizations and networks, which will exploit the added value of integrating different contributions and viewpoints. The platform is developed involving both experts in RD research as well as experts in clinical practice guidelines (CPG) and systematic reviews. Results: Project expected outputs include: 1) identification of challenges to be considered in deriving high quality standards for CPG on RD; 2) transparent procedures and criteria for the evaluation of CPG and their collection in a publicly searchable database; 3) identification of notation criteria to improve user understandability and implementation of CPG; 4) production of mechanisms to assess RD clinical research needs; 5) development of training activities targeted to key stakeholders to disseminate process and tools for developing and evaluating CPG; 6) the publication of a new scientific journal (http://rarejournal.org). Discussion: RARE-Bestpractices addresses the demands from both patients and health care providers for updated and high quality CPG on RD. The project will meet the requirements laid down by to the Directive 2011/24/EU, which endorses EU MS to develop European Reference Networks (ERNs) for RD; in fact, one main criterion for ERNs should be the competence to produce CPG and actively disseminate them among Centers of Expertise.N