Deficiency and Also Transgenic Overexpression of Timp-3 Both Lead to Compromised Bone Mass and Architecture In Vivo

Tissue inhibitor of metalloproteinases-3 (TIMP-3) regulates extracellular matrix via its inhibition of matrix metalloproteinases and membrane-bound sheddases. Timp-3 is expressed at multiple sites of extensive tissue remodelling. This extends to bone where its role, however, remains largely unresolved. In this study, we have used Micro-CT to assess bone mass and architecture, histological and histochemical evaluation to characterise the skeletal phenotype of Timp-3 KO mice and have complemented this by also examining similar indices in mice harbouring a Timp-3 transgene driven via a Col-2a-driven promoter to specifically target overexpression to chondrocytes. Our data show that Timp-3 deficiency compromises tibial bone mass and structure in both cortical and trabecular compartments, with corresponding increases in osteoclasts. Transgenic overexpression also generates defects in tibial structure predominantly in the cortical bone along the entire shaft without significant increases in osteoclasts. These alterations in cortical mass significantly compromise predicted tibial load-bearing resistance to torsion in both genotypes. Neither Timp-3 KO nor transgenic mouse growth plates are significantly affected. The impact of Timp-3 deficiency and of transgenic overexpression extends to produce modification in craniofacial bones of both endochondral and intramembranous origins. These data indicate that the levels of Timp-3 are crucial in the attainment of functionally-appropriate bone mass and architecture and that this arises from chondrogenic and osteogenic lineages

Bone Marrow Osteoblast Damage by Chemotherapeutic Agents

Hematopoietic reconstitution, following bone marrow or stem cell transplantation, requires a microenvironment niche capable of supporting both immature progenitors and stem cells with the capacity to differentiate and expand. Osteoblasts comprise one important component of this niche. We determined that treatment of human primary osteoblasts (HOB) with melphalan or VP-16 resulted in increased phospho-Smad2, consistent with increased TGF-β1 activity. This increase was coincident with reduced HOB capacity to support immature B lineage cell chemotaxis and adherence. The supportive deficit was not limited to committed progenitor cells, as human embryonic stem cells (hESC) or human CD34+ bone marrow cells co-cultured with HOB pre-exposed to melphalan, VP-16 or rTGF-β1 had profiles distinct from the same populations co-cultured with untreated HOB. Functional support deficits were downstream of changes in HOB gene expression profiles following chemotherapy exposure. Melphalan and VP-16 induced damage of HOB suggests vulnerability of this critical niche to therapeutic agents frequently utilized in pre-transplant regimens and suggests that dose escalated chemotherapy may contribute to post-transplantation hematopoietic deficits by damaging structural components of this supportive niche

Railway bridge structural health monitoring and fault detection: state-of-the-art methods and future challenges

Railway importance in the transportation industry is increasing continuously, due to the growing demand of both passenger travel and transportation of goods. However, more than 35% of the 300,000 railway bridges across Europe are over 100-years old, and their reliability directly impacts the reliability of the railway network. This increased demand may lead to higher risk associated with their unexpected failures, resulting safety hazards to passengers and increased whole life cycle cost of the asset. Consequently, one of the most important aspects of evaluation of the reliability of the overall railway transport system is bridge structural health monitoring, which can monitor the health state of the bridge by allowing an early detection of failures. Therefore, a fast, safe and cost-effective recovery of the optimal health state of the bridge, where the levels of element degradation or failure are maintained efficiently, can be achieved. In this article, after an introduction to the desired features of structural health monitoring, a review of the most commonly adopted bridge fault detection methods is presented. Mainly, the analysis focuses on model-based finite element updating strategies, non-model-based (data-driven) fault detection methods, such as artificial neural network, and Bayesian belief network–based structural health monitoring methods. A comparative study, which aims to discuss and compare the performance of the reviewed types of structural health monitoring methods, is then presented by analysing a short-span steel structure of a railway bridge. Opportunities and future challenges of the fault detection methods of railway bridges are highlighted

Telethon Network of Genetic Biobanks: a key service for diagnosis and research on rare diseases

Several examples have always illustrated how access to large numbers of biospecimens and associated data plays a pivotal role in the identification of disease genes and the development of pharmaceuticals. Hence, allowing researchers to access to significant numbers of quality samples and data, genetic biobanks are a powerful tool in basic, translational and clinical research into rare diseases. Recently demand for well-annotated and properly-preserved specimens is growing at a high rate, and is expected to grow for years to come. The best effective solution to this issue is to enhance the potentialities of well-managed biobanks by building a network.Here we report a 5-year experience of the Telethon Network of Genetic Biobanks (TNGB), a non-profit association of Italian repositories created in 2008 to form a virtually unique catalogue of biospecimens and associated data, which presently lists more than 750 rare genetic defects. The process of TNGB harmonisation has been mainly achieved through the adoption of a unique, centrally coordinated, IT infrastructure, which has enabled (i) standardisation of all the TNGB procedures and activities; (ii) creation of an updated TNGB online catalogue, based on minimal data set and controlled terminologies; (iii) sample access policy managed via a shared request control panel at web portal. TNGB has been engaged in disseminating information on its services into both scientific/biomedical - national and international - contexts, as well as associations of patients and families. Indeed, during the last 5-years national and international scientists extensively used the TNGB with different purposes resulting in more than 250 scientific publications. In addition, since its inception the TNGB is an associated member of the Biobanking and Biomolecular Resources Research Infrastructure and recently joined the EuroBioBank network. Moreover, the involvement of patients and families, leading to the formalization of various agreements between TNGB and Patients' Associations, has demonstrated how promoting Biobank services can be instrumental in gaining a critical mass of samples essential for research, as well as, raising awareness, trust and interest of the general public in Biobanks. This article focuses on some fundamental aspects of networking and demonstrates how the translational research benefits from a sustained infrastructure

Electrospun PVA fibers loaded with antioxidant fillers extracted from Durvillaea antarctica algae and their effect on plasticized PLA bionanocomposites

Marine algae are important biomass source which can be used as sources for the extraction of interesting reinforcing materials with antioxidant activity. An extraction protocol was developed to determine the extraction yield (%), the total phenolic compounds and the antioxidant activity of Durvillaea antarctica algae extract, a Chilean brown algae. D. antarctica extract was added to plasticized poly(lactic acid) (PLA) matrices with triethyl citrate (TEC) to produce antioxidant bionanocomposites for active food packaging. Two different approaches were followed: the direct incorporation of D. antarctica, as well as its introduction encapsulated into electrospun poly(vinyl alcohol) (PVA) fibers. Flexible and optically transparent bionanocomposite films were obtained by solvent casting method. The effects of D. antarctica concentration and its incorporation into electrospun PVA fibers on the structural, thermal, mechanical and barrier properties of PLA based films were studied. D. antarctica protected plasticized PLA matrix from thermal degradation. The synergic effect of the D. antarctica and electrospun PVA fibers enhanced the PLA crystallinity, the oxygen barrier and mechanical performance. The antioxidant effectiveness of bionanocomposites was confirmed by release studies into a fatty food simulant, and the antimicrobial activity was also tested against Escherichia coli. The successful production of bionanocomposites incorporating D. antarctica extracted from biomass and the improved mechanical resistance, enhanced oxygen barrier as well as the antioxidant activity suggest potential applications as sustainable active food packaging.M.P. Arrieta thanks Santander Universidades Project (S2016C0025) for the financial support as well as Spanish Ministry of Economy and Competitiveness, MINECO, for Juan de la Cierva Post-Doctoral contract (FJCI-2014-20630). Authors also acknowledge Project Basal USA 1555 – Vridei O81771GL_CONT from the University of Santiago de Chile and “Programa de Financiamiento Basal para Centros Científicos y Tecnológicos de Excelencia” (Project FB0807).Peer Reviewe

Genetic Algorithm-Based Commutation Angle Control for Torque Ripple Mitigation in Switched Reluctance Motor Drives

This work addresses the application of the Genetic Algorithm (GA) technique to optimize the commutation angles of a 2 kW 8/6 switched reluctance machine (SRM). The primary goal is to reduce the well-known drawback of SRMs: the torque ripple. Firstly, the machine was modeled in Matlab /Simulink Ⓡ using lookup tables obtained via finite element method (FEM) simulations. Subsequently, the model was used to perform the GA routine aiming to find the optimal phase commutation angles that minimize the torque ripple factor. Notably, the torque performance of the SRM was significantly affected by the commutation angles during the search for the optimal solution. Afterwards, the GA results for four different operation points were verified experimentally through a developed drive platform with digital signal processor-based (DSP) control and an asymmetric bridge converter. As showed by the experiments, the proposed approach was suitable to reduce the torque ripple by more than 50% for one of the evaluated operating points. Furthermore, it was confirmed that the torque ripple mitigation led to acoustic noise improvement

Elaboration of Energy Balance: A Model for the Brazilian States

The energy balance constitutes a powerful management instrument for government agencies, as it offers an overview of the energy situation of the country (or region) and serves as a guide for energy policies and monitoring of these policies. Although Brazil has published the national energy balance for more than half a century, the national publication does not adequately address energy statistics at the level of the states. This occurs either due to the lack of specific data or the absence of total disaggregation. Accordingly, the elaboration and implementation of public policies for the energy sector in the Brazilian states lack consistent energy statistics. Therefore, this paper aims to present a model for the Brazilian states to elaborate the energy balance. The proposed model consists of applying internationally referenced methodologies to develop a user-friendly software, which includes automatic energy unit conversions, different chart styles, high-level data organization, and Sankey diagrams. As a result, the software can be adopted by local governments as a tool to maintain the state energy balance publication periodically, and hence obtain the detailed information necessary to manage and formulate energy policies. The advantage of the software is that it can be operated by non-experts and the energy flow as well as the entire report can be generated automatically. The proposed software was successfully used to generate the energy balance of the Mato Grosso do Sul state

Microencapsulation of maqui ( Aristotelia chilensis [Molina] Stuntz) leaf extracts to preserve and control antioxidant properties

Microencapsulation technology is an alternative to stabilize stress factors and protect food ingredients or additives, which include environmentally sensitive bioactive principles in protective matrices to increase their functionality and life span. The objective of this research was to study conditions to obtain microcapsules with antioxidant capacity from a maqui ( Aristotelia chilensis [Molina] Stuntz, Elaeocarpaceae) leaf extract by emulsification and subsequent retention after microencapsulation. Microcapsules were produced by water-in-oil emulsion (W/O) using a phase of the aqueous maqui leaf extract and gum arabic, and a liquid vaseline phase. Maqui leaf extract antioxidant capacity was 99.66% compared with the aqueous phase of the emulsion at 94.38 and 93.06% for 5% and 15% gum arabic, respectively. The mean yield of maqui leaf extract microencapsulation with 5% gum arabic varied between 38 and 48%, whereas with 15% gum arabic it was 39%. Once the antioxidant microcapsules were formed, mean extract antioxidant capacity ranged between 30 and 35%. Both yields responded similarly to changes in gum arabic concentrations (5% and 15%) in the aqueous phase of the emulsion; 5% concentration produced a microcapsule size from 1.0 to 10 μm. Maqui leaf extracts with high phenolic compound levels, which can be stabilized and protected by the microencapsulation process, produce new natural preservative systems as compared with their synthetic counterparts