Effect of Dilution on Microstructure and Wear Resistance of a Fe-Based Hardfacing Alloy with a High Amount of Carbide-Forming Elements

Hardfacing is a widely diffused technique adopted to increase service life of parts for heavy-duty applications. Even though hardfacing alloys feature optimized chemistry and microstructure for specific service conditions, dilution with substrate modifies the resulting properties along a significant fraction of the deposit thickness. In particular, C and B diffusion to the substrate alters hypereutectic alloys reducing the carbide-forming ability andmodifying the solidification sequence. In the present paper, the effect of dilution on a hypereutectic Fe-C-B based alloy containing Cr and Mo was investigated. The effect of dilution on the reference alloy was studied by producing laboratory castings with an increased amount of Fe, up to 50 mass %. The obtained results were compared with the dilution of the hardfacing alloy cast on steel substrates. The microstructural evolution was analyzed by XRD (X-ray diffraction), differential scanning calorimetry (DSC), optical microscopy (OM), and scanning electron microscopy (SEM), whereas mechanical behaviour was evaluated by hardness measurements and wear resistance by pin-on-disc tests

Texturizzazione laser della lega di magnesio AZ31 per migliorare l’adesione nelle applicazioni biomedicali

"Laser surface texturing of AZ31 Magnesium Alloy to improve adhesion in biomedical application Cardiovascular stent have assumed a primary role to solve heart problems related to constraints that lead to the malfunctioning of a hollow organ. The research is shifting more and more towards the creations of less invasive stent having biocompatibility and biodegradability as primary requirements. Metal that best meets both these requirements and also the structural ones is Magnesium and its alloys. The greatest limit to the use of this material comes from its low corrosion resistance that it is manifested at the body pH. The idea at the basis of this work is to cover the Magnesium stent with a biodegradable polymer to increase its resistance to corrosion. The following paper focuses the study on the texturing surface treatments, achievable by a laser beam, in order to optimize the adhesion between the substrate and the polymer. The Magnesium alloy used is AZ31. Studies of surface modification through the mechanisms of the remelting and microdrilling by laser have been performed on the AZ31 surface. The characterization of the selected surfaces in terms of roughness variations, changes in wettability, oxides formation and geometry of the obtained structures, led to the identification of a limited number of conditions that will be further investigated.

Laser surface structuring of AZ31 Mg alloy for controlled wettability

Structured surfaces exhibit functional properties that can enhance the performance of a bioimplant in terms of biocompatibility, adhesion, or corrosion behavior. In order to tailor the surface property, chemical and physical methods can be used in a sequence of many steps. On the other hand, laser surface processing can provide a single step solution to achieve the designated surface function with the use of simpler equipment and high repeatability. This work provides the details on the surface structuring of AZ31, a biocompatible and biodegradable Mg alloy, by a single-step laser surface structuring based on remelting. The surfaces are characterized in terms of topography, chemistry, and physical integrity, as well as the effective change in the surface wetting behavior is demonstrated. The results imply a great potential in local or complete surface structuring of medical implants for functionalization by the flexible positioning of the laser beam

Type 2 diabetes mellitus, physical activity, exercise self-efficacy, and body satisfaction. An application of the transtheoretical model in older adults

Physical activity (PA) is a relevant component of the treatment of Type 2 diabetes mellitus (T2DM). However, to prevent its related morbidities, PA requires an immediate and lasting change of lifestyle. Exercise self-efficacy and body satisfaction were used in a sample of older adults with T2DM, classified in different stages of change, to predict levels of PA. Results show that exercise self-efficacy increases linearly from precontemplation to maintenance stage, while body satisfaction shows an inverted U shape. However, only stages of change, other than exercise self-efficacy, add a significant and noticeable contribution to prediction of levels of PA. This evidence claims a tailored approach to PA in older adults with T2DM and advises behavioural health interventions based on exercise self- efficacy

Wild or Domestic? Biometric Variation in the Cat Felis silvestris Schreber

Investigation of modern biometric data indicates that it may be possible to distinguish wildcats from house cats in many instances. Applying the log-ratio (log-difference) technique to archaeological samples from medieval northern Europe, and to mixed samples of wildcats and house cats, shows that the differentiation may not always be clear, and the possibility that some samples include hybrids is discussed. The technique is applied to samples from the Orkney Islands to demonstrate that single wildcat specimens can be identified in small samples. Copyright (C) 2007 John Wiley & Sons, Ltd

Inter-individual variability in psychological outcomes of supervised exercise in adults with Type 2 Diabetes

Exercise is a key component in the management of Type 2 Diabetes Mellitus (T2DM), however despite the strong evidence of its protective effects, a majority of the population with this diagnosis remains inactive and those who start an exercise program are not willing to train themselves over the long-term. Self-ef cacy and perceived stress are related to barriers to exercise in T2DM, therefore the aim of this longitudinal study is to investigate variations across time and individual differences in both variables as effects of a supervised exercise training (6 months) in a small sample of persons diagnosed with T2DM. Results show a general decline in the mean values of self-ef cacy and perceived stress at 6 months and a high individual variability in both variables. These results support the need to develop customized pro- grams of exercise in T2DM that take into account different phases of the exercise process and individual variability.El ejercicio es un componente clave en la prevención y el tratamiento de Diabetes Mellitus Tipo 2 (DMT2); sin embargo, a pesar de la fuerte evidencia de sus efectos protectores, la mayoría de las personas con este diagnóstico permanece inactiva y aquellos que comienzan un programa de ejercicio no están dispuestos a entrenar a largo plazo. La autoefcacia y la percepción de estrés se relacionan con las barreras para realizar ejercicio en pacientes T2DM; por lo tanto, el objetivo de este estudio longitudinal consiste en investigar las variaciones a través del tiempo y las diferencias individuales en ambas variables, como efectos de un entrenamiento de ejercicio supervisado (6 meses), en una muestra pequeña de pacientes diagnosticados con TD2M. Los resultados muestran una disminución general de los valores promedio de la autoefcacia y del estrés percibido a los 6 meses y una alta variabilidad individual en ambas variables. Estos resultados apoyan la necesidad de desarrollar programas personalizados de ejercicio en pacientes T2DM con el objetivo de considerar las diferentes fases del proceso de ejercicio y de la variabilidad individual

Mitochondrial permeabilization engages NF-κB-dependent anti-tumour activity under caspase deficiency

Apoptosis represents a key anti-cancer therapeutic effector mechanism. During apoptosis, mitochondrial outer membrane permeabilization (MOMP) typically kills cells even in the absence of caspase activity. Caspase activity can also have a variety of unwanted consequences that include DNA damage. We therefore investigated whether MOMP-induced caspase-independent cell death (CICD) might be a better way to kill cancer cells. We find that cells undergoing CICD display potent pro-inflammatory effects relative to apoptosis. Underlying this, MOMP was found to stimulate NF-κB activity through the downregulation of inhibitor of apoptosis proteins. Strikingly, engagement of CICD displays potent anti-tumorigenic effects, often promoting complete tumour regression in a manner dependent on intact immunity. Our data demonstrate that by activating NF-κB, MOMP can exert additional signalling functions besides triggering cell death. Moreover, they support a rationale for engaging caspase-independent cell death in cell-killing anti-cancer therapies

Inhibitors of Apoptosis Proteins (IAPs) as Targets for Anti-Cancer Treatment

Smac mimetics (SMs) constitute a class of compounds that target the inhibitor of apoptosis proteins (IAPs) and enhance the cytotoxic activity of several drugs. In our work, we built and characterized a library of about 140 SMs and focused on SM83 due to its high affinity for the targets, cytotoxic activity and good pharmacokinetic profile. In vivo, SM83 reduced in monotherapy the primary tumor growth of two triple negative breast cancer xenografts. Furthermore, SM83 treatment, alone or in combinations with TRAIL-armed CD34+cell, resulted in the reduction of spontaneous lung metastasis formation. Mechanistically, by depleting cIAP1, SM83 affects the expression of the tumor genes and inhibits the metastasis-promoting gene Snai2, thus preventing cancer cell motility. Moreover, we tested SM83 as a standalone in ascites cancer models and described an in vivo anti-tumor effect against cancer cell lines that are intrinsically resistant to SM treatment in vitro. In the in vivo settings, SM83, in fact, triggered an inflammation event of the host, characterized by macrophage secretion of TNF, IL-1β and interferon-γ (IFNγ), and rapidly killed floating tumor cells within the ascites by a non-apoptotic mechanism. Of note, SM83 treatment caused the massive accumulation of neutrophils within the ascites and tumor nodules, which, however, was not responsible for cancer cell killing. Finally, we described the capability of SM83 to enhance the cytotoxic activity of camptothecin especially in human epithelial cells expressing oncogenic KRAS. The increased sensitivity of these premalignant cells is caused by an ERK2-dependent up-regulation of NOXA. Of note, oncogenic KRAS fails to sensitize a panel of isogenic cancer cell lines with wild type and mutated KRAS, and we demonstrated that this unresponsiveness could be reverted by concomitant inhibition of AKT. Therefore, our work suggests that the activation of AKT is capable of counterbalancing the potential pro-death stimulus triggered by oncogenic KRAS

Antibody-mediated blockade of JMJD6 interaction with collagen I exerts antifibrotic and antimetastatic activities

JMJD6 is known to localize in the nucleus, exerting histone arginine demethylase and lysyl hydroxylase activities. A novel localization of JMJD6 in the extracellular matrix, resulting from its secretion as a soluble protein, was unveiled by a new anti-JMJD6 mAb called P4E11, which was developed to identify new targets in the stroma. Recombinant JMJD6 binds with collagen type I (Coll-I), and distinct JMJD6 peptides interfere with collagen fibrillogenesis, collagen-fibronectin interaction, and adhesion of human tumor cells to the collagen substrate. P4E11 and collagen binding to JMJD6 are mutually exclusive because the amino acid sequences of JMJD6 necessary for the interaction with Coll-I are part of the conformational epitope recognized by P4E11. In mice injected with mouse 4T1 breast carcinoma cells, treatment with P4E11 reduced fibrosis at the primary tumor and prevented lung metastases. Reduction of fibrosis has also been documented in human breast and ovarian tumors (MDA-MB-231 and IGROV1, respectively) xenotransplanted into immunodeficient mice treated with P4E11. In summary, this study uncovers a new localization and function for JMJD6 that is most likely independent from its canonical enzymatic activities, and demonstrates that JMJD6 can functionally interact with Coll-I. P4E11 mAb, inhibiting JMJD6/Coll-I interaction, represents a new opportunity to target fibrotic and tumor diseases

Editor's Introduction

The issue is a result of the research programme about ‘The problem of indeterminacy. Meaning, knowledge, action’ (‘Il problema dell’indeterminatezza. Significato, conoscenza, azione’, PRIN 2015, national coordinator Luigi Perissinotto). The project was developed by a Cagliari research team that worked on the indeterminacy problem concerning the linguistic, conceptual and interpretative mechanisms actively involved in the construction of the images of the past. These concepts and other themes were the subject of a conference in May 2019. The outcomes are now mostly presented in this number. The great questions of representation, fancy, figurative languages, image (as a form shaping matter and not merely reproducing a given structure) and time (and the relationship amongst past, present and future) are preeminently but not exclusively linked to the past as it is investigated by historians (past human actions and resulting chains of events)..