A probabilistic fatigue crack growth life approach to the definition of inspection intervals for railway axles

Different options that rely on fracture mechanics are currently used in engineering during the design and assessment of components. One of the most important aspects is the time taken for a crack to extend to its critical size. If this time is long enough, a design concept based on inspection intervals can be applied, as is it the case of a railway axle component. To define inspection intervals that ensure the continuous and safe operation of a damage-tolerant railway axle, a reliable estimation of its fatigue crack growth life is required. Due to the uncertainties involved in the fatigue process, inspections must be devised not only considering the uncertainties in the performance of the inspection technique, but also based on a probabilistic lifespan prediction. From this premise, this paper presents a procedure for determination of inspection intervals that uses a conservative fatigue crack growth life estimation based on the lifespan probability distribution. A practical example to illustrate the reliability-based inspection planning methodology in a railway axle under random bending loading is given. The inspection intervals are further assessed in terms of overall probability of detecting cracks in successive inspections and in terms of probability of failure, considering the probability of detection curve of the non-destructive testing technique. The procedure developed provides recommendation for the definition of inspection intervals and associated inspection techniques

Whole-Slide Image Analysis of Human Pancreas Samples to Elucidate the Immunopathogenesis of Type 1 Diabetes Using the QuPath Software

Type 1 diabetes is a chronic disease of the pancreas characterized by the loss of insulin-producing beta cells. Access to human pancreas samples for research purposes has been historically limited, restricting pathological analyses to animal models. However, intrinsic differences between animals and humans have made clinical translation very challenging. Recently, human pancreas samples have become available through several biobanks worldwide, and this has opened numerous opportunities for scientific discovery. In addition, the use of new imaging technologies has unraveled many mysteries of the human pancreas not merely in the presence of disease, but also in physiological conditions. Nowadays, multiplex immunofluorescence protocols as well as sophisticated image analysis tools can be employed. Here, we described the use of QuPath—an open-source platform for image analysis—for the investigation of human pancreas samples. We demonstrate that QuPath can be adequately used to analyze whole-slide images with the aim of identifying the islets of Langerhans and define their cellular composition as well as other basic morphological characteristics. In addition, we show that QuPath can identify immune cell populations in the exocrine tissue and islets of Langerhans, accurately localizing and quantifying immune infiltrates in the pancreas. Therefore, we present a tool and analysis pipeline that allows for the accurate characterization of the human pancreas, enabling the study of the anatomical and physiological changes underlying pancreatic diseases such as type 1 diabetes. The standardization and implementation of these analysis tools is of critical importance to understand disease pathogenesis, and may be informative for the design of new therapies aimed at preserving beta cell function and halting the inflammation caused by the immune attack

Use of aequorin-based indicators for monitoring Ca2+ in acidic organelles

Over the last years, there is accumulating evidence that acidic organelles can accumulate and release Ca2+ upon cell activation. Hence, reliable recording of Ca2+ dynamics in these compartments is essential for understanding the physiopathological aspects of acidic organelles. Genetically encoded Ca2+ indicators (GECIs) are valuable tools to monitor Ca2+ in specific locations, although their use in acidic compartments is challenging due to the pH sensitivity of most available fluorescent GECIs. By contrast, bioluminescent GECIs have a combination of features (marginal pH sensitivity, low background, no phototoxicity, no photobleaching, high dynamic range and tunable affinity) that render them advantageous to achieve an enhanced signal-to-noise ratio in acidic compartments. This article reviews the use of bioluminescent aequorin-based GECIs targeted to acidic compartments. A need for more measurements in highly acidic compartments is identified

Exploration of the treatment of fish-canning industry effluents by aqueous-phase reforming using Pt/C catalysts

In the current work, an exploratory study on the application of catalytic aqueous phase reforming (APR) to the treatment of fish-canning wastewater was performed for the first time. Pt/C (3%, w) catalysts were supported on different commercial carbon supports (two activated carbons and a carbon black) and tested in the APR of tuna-cooking wastewater. The effect of the supports and the reaction systems (batch vs. semi-continuous) on the performance of the catalysts was tested. The stability of the catalysts upon 3 successive reuse cycles was checked. TOC and COD removal ranged within 45-60%, which was ascribed to adsorption on the supports, hydrothermal carbonization and APR. The percentage of valuable gases (H2 and alkanes) reached up to 18% of the gas production showing the potential of APR for the valorization and treatment of wastewater. The production of gases is affected by the high chloride, acetate and phosphate concentrations, which may provoke catalyst deactivation. The use of a catalyst with a basic support significantly increased the production of gases and the H2 percentage in the gas fraction. Gas production was higher in semi-continuous compared to batch operation, maybe because the withdrawn gas displaces the reaction towards the products. The percentage of alkanes in the gas phase decreased upon successive catalyst reuse cycles at the expense of H2, which is probably due to sintering of Pt nanoparticles with the corresponding decrease of the number of low-coordinated Pt sites promoting methanation reactionsThe authors greatly appreciate financial support from Spanish MINECO (CTQ2015-65491-R). A. S. Oliveira thanks the Spanish MINECO for a research grant (BES-2016-077244

Matrix metalloproteinase-10 is upregulated by thrombin in endothelial cells and increased in patients with enhanced thrombin generation

OBJECTIVE: Thrombin is a multifunctional serine protease that promotes vascular proinflammatory responses whose effect on endothelial MMP-10 expression has not previously been evaluated. METHODS AND RESULTS: Thrombin induced endothelial MMP-10 mRNA and protein levels, through a protease-activated receptor-1 (PAR-1)-dependent mechanism, in a dose- and time-dependent manner. This effect was mimicked by a PAR-1 agonist peptide (TRAP-1) and antagonized by an anti-PAR-1 blocking antibody. MMP-10 induction was dependent on extracellular regulated kinase1/2 (ERK1/2) and c-jun N-terminal kinase (JNK) pathways. By serial deletion analysis, site-directed mutagenesis and electrophoretic mobility shift assay an AP-1 site in the proximal region of MMP-10 promoter was found to be critical for thrombin-induced MMP-10 transcriptional activity. Thrombin and TRAP-1 upregulated MMP-10 in murine endothelial cells in culture and in vivo in mouse aorta. This effect of thrombin was not observed in PAR-1-deficient mice. Interestingly, circulating MMP-10 levels (P<0.01) were augmented in patients with endothelial activation associated with high (disseminated intravascular coagulation) and moderate (previous acute myocardial infarction) systemic thrombin generation. CONCLUSIONS: Thrombin induces MMP-10 through a PAR-1-dependent mechanism mediated by ERK1/2, JNK, and AP-1 activation. Endothelial MMP-10 upregulation could be regarded as a new proinflammatory effect of thrombin whose pathological consequences in thrombin-related disorders and plaque stability deserve further investigation

Impact of HCV infection in a HIV cohort followed over18 years: past and present

Pôster abstrac

Use of aequorin-based indicators for monitoring Ca2+ in acidic organelles

Producción CientíficaOver the last years, there is accumulating evidence that acidic organelles can accumulate and release Ca2+ upon cell activation. Hence, reliable recording of Ca2+ dynamics in these compartments is essential for understanding the physiopathological aspects of acidic organelles. Genetically encoded Ca2+ indicators (GECIs) are valuable tools to monitor Ca2+ in specific locations, although their use in acidic compartments is challenging due to the pH sensitivity of most available fluorescent GECIs. By contrast, bioluminescent GECIs have a combination of features (marginal pH sensitivity, low background, no phototoxicity, no photobleaching, high dynamic range and tunable affinity) that render them advantageous to achieve an enhanced signal-to-noise ratio in acidic compartments. This article reviews the use of bioluminescent aequorin-based GECIs targeted to acidic compartments. A need for more measurements in highly acidic compartments is identified.Ministerio de Ciencia e Innovación (PID2020-116086RB-I00 )Junta de Castilla y León (Ref. CLU- 2019-02)Biotechnology and Biological Sciences Research Council, Reino Unido (BB/T015853/1 y BB/W01551X/1

The NIKA instrument: results and perspectives towards a permanent KID based camera for the Pico Veleta observatory

The New IRAM KIDs Array (NIKA) is a pathfinder instrument devoted to millimetric astronomy. In 2009 it was the first multiplexed KID camera on the sky; currently it is installed at the focal plane of the IRAM 30-meters telescope at Pico Veleta (Spain). We present preliminary data from the last observational run and the ongoing developments devoted to the next NIKA-2 kilopixels camera, to be commissioned in 2015. We also report on the latest laboratory measurements, and recent improvements in detector cosmetics and read-out electronics. Furthermore, we describe a new acquisition strategy allowing us to improve the photometric accuracy, and the related automatic tuning procedure.Comment: 24th International Symposium on Space Terahertz Technology, ISSTT 2013, April 8 to 10, 2013, Groningen, the Netherland

NIKA 2: next-generation continuum/polarized camera at the IRAM 30 m telescope and its prototype

NIKA 2 (New Instrument of Kids Array) is a next generation continuum and polarized instrument successfully installed in October 2015 at the IRAM 30 m telescope on Pico-Veleta (Granada, Spain). NIKA 2 is a high resolution dual-band camera, operating with frequency multiplexed LEKIDs (Lumped Element Kinetic Inductance Detectors) cooled at 100 mK. Dual color images are obtained thanks to the simultaneous readout of a 1020 pixels array at 2 mm and 1140 x 2 pixels arrays at 1.15 mm with a final resolution of 18 and 12 arcsec respectively, and 6.5 arcmin of Field of View (FoV). The two arrays at 1.15 mm allow us to measure the linear polarization of the incoming light. This will place NIKA 2 as an instrument of choice to study the role of magnetic fields in the star formation process. The NIKA experiment, a prototype for NIKA 2 with a reduced number of detectors (about 400 LEKIDs) and FoV (1.8 arcmin), has been successfully operated at the IRAM 30 telescope in several open observational campaigns. The performance of the NIKA 2 polarization setup has been successfully validated with the NIKA prototype.Comment: 5 pages, 4 figures, proceeding for the conference: Extragalactic radio surveys 201

Non-parametric deprojection of NIKA SZ observations: Pressure distribution in the Planck-discovered cluster PSZ1 G045.85+57.71

The determination of the thermodynamic properties of clusters of galaxies at intermediate and high redshift can bring new insights into the formation of large-scale structures. It is essential for a robust calibration of the mass-observable scaling relations and their scatter, which are key ingredients for precise cosmology using cluster statistics. Here we illustrate an application of high resolution $(< 20$ arcsec) thermal Sunyaev-Zel'dovich (tSZ) observations by probing the intracluster medium (ICM) of the \planck-discovered galaxy cluster \psz\ at redshift $z = 0.61$, using tSZ data obtained with the NIKA camera, which is a dual-band (150 and 260~GHz) instrument operated at the IRAM 30-meter telescope. We deproject jointly NIKA and \planck\ data to extract the electronic pressure distribution from the cluster core ($R \sim 0.02\, R_{500}$) to its outskirts ($R \sim 3\, R_{500}$) non-parametrically for the first time at intermediate redshift. The constraints on the resulting pressure profile allow us to reduce the relative uncertainty on the integrated Compton parameter by a factor of two compared to the \planck\ value. Combining the tSZ data and the deprojected electronic density profile from \xmm\ allows us to undertake a hydrostatic mass analysis, for which we study the impact of a spherical model assumption on the total mass estimate. We also investigate the radial temperature and entropy distributions. These data indicate that \psz\ is a massive ($M_{500} \sim 5.5 \times 10^{14}$ M$_{\odot}$) cool-core cluster. This work is part of a pilot study aiming at optimizing the treatment of the NIKA2 tSZ large program dedicated to the follow-up of SZ-discovered clusters at intermediate and high redshifts. (abridged)Comment: 16 pages, 10 figure