Decreased myocardial injury and improved contractility after administration of a peptide derived against the alpha-interacting domain of the L-type calcium channel.

BackgroundMyocardial infarction remains the leading cause of morbidity and mortality associated with coronary artery disease. The L-type calcium channel (IC a-L) is critical to excitation and contraction. Activation of the channel also alters mitochondrial function. Here, we investigated whether application of a alpha-interacting domain/transactivator of transcription (AID-TAT) peptide, which immobilizes the auxiliary β2 subunit of the channel and decreases metabolic demand, could alter mitochondrial function and myocardial injury.Methods and resultsTreatment with AID-TAT peptide decreased ischemia-reperfusion injury in guinea-pig hearts ex vivo (n=11) and in rats in vivo (n=9) assessed with uptake of nitroblue tetrazolium, release of creatine kinase, and lactate dehydrogenase. Contractility (assessed with catheterization of the left ventricle) was improved after application of AID-TAT peptide in hearts ex vivo (n=6) and in vivo (n=8) up to 12 weeks before sacrifice. In search of the mechanism for the effect, we found that intracellular calcium ([Ca(2+)]i, Fura-2), superoxide production (dihydroethidium fluorescence), mitochondrial membrane potential (Ψm, JC-1 fluorescence), reduced nicotinamide adenine dinucleotide production, and flavoprotein oxidation (autofluorescence) are decreased after application of AID-TAT peptide.ConclusionsApplication of AID-TAT peptide significantly decreased infarct size and supported contractility up to 12 weeks postcoronary artery occlusion as a result of a decrease in metabolic demand during reperfusion

Managing Operating Procedures in Distributed Collaborative Projects

In recent years, large distributed collaborative projects have become very prominent in scientific research, allowing exchanges between laboratories located in different institutions and countries and between various domains of competence. Particularly the work on nanotoxicity – a field which has only been under investigation for a few years and is still lacking regulatory framework – highlighted the need for well-controlled methods, as well as rules for the handling and disposal of used materials. To obtain comparable and reproducible results of experiments conducted in a distributed context, the standardisation and proper documentation of the applied methods is crucial. The European project NanoDiaRA, whose aim is to develop nanoparticles and biomarkers for the early diagnosis of inflammatory disease, faces this situation as it involves 15 European partners and brings together different scientific cultures and professional backgrounds. Protocols especially developed for Superparamagnetic Iron Oxide Nanoparticles and a management system were designed and implemented within the NanoDiaRA project to fulfil those needs. The main goals were the establishment of standardised Standard Operating Procedures assuring transparency and reproducibility and the provision of access to these protocols to every project partner, as well as their clear allocation to carry out precise measurements and production steps

Nanotechnology in medicine: European research and its implications

In this study, we explore and discuss nanoparticles and nanoscale materials and their use in medicine (nanomedicine) and pharmaceutics (nanopharmaceutics). The study is aimed at shedding light on this highly multidisciplinary research field and at examining the influence of research funding, industrial applications, and legal and regulatory frameworks on the research in this field, a clear understanding of which is essential to efficiently support the translation of research findings into industrial and clinical applications and to enable access to a larger society

Local coefficients of skin friction and heat transfer for turbulent boundary layers on two-dimensional diffusers

This report considers the changes of local coefficients of skin friction and heat transfer for turbulent boundary layers in two-dimensional subsonic air streams under rising pressure gradients. The values of the local coefficients of skin friction and heat transfer are compared on the basis of Reynolds' Analogy, von Karman's improvement to Reynolds' Analogy, and on the basis of similar velocity and temperature boundary-layer profiles. Tests on diffusers at total angles of 4 deg and 7 deg showed that the local coefficients of heat transfer based on the measured heat transfer values, increased with increase of the strealn velocity and diffuser angle relative to the local coefficients of heat transfer, based on Reynolds' analogy and on von Karman's improvement to Reynolds' analogy. The local coefficients of heat transfer calculated on an assumed similarity of velocity and temperature distributions were unsatisfactory

“Nanostandardization” in action: implementing standardization processes in a multidisciplinary nanoparticle-based research and development project

Nanomaterials have attracted much interest in the medical field and related applications as their distinct properties in the nano-range enable new and improved diagnosis and therapies. Owing to these properties and their potential interactions with the human body and the environment, the impact of nanomaterials on humans and their potential toxicity have been regarded a very significant issue. Consequently, nanomaterials are the subject of a wide range of cutting-edge research efforts in the medical and related fields to thoroughly probe their potential beneficial utilizations and their more negative effects. We posit that the lack of standardization in the field is a serious shortcoming as it has led to the establishment of methods and results that do not ensure sufficient consistency and thus in our view can possibly result in research outputs that are not as robust as they should be. The main aim of this article is to present how NanoDiaRA, a large FP7 European multidisciplinary project that seeks to investigate and develop nanotechnology-based diagnostic systems, has developed and implemented robust, standardized methods to support research practices involving the engineering and manipulation of nanomaterials. First, to contextualize this research, an overview of the measures defined by different regulatory bodies concerning nano-safety is presented. Although these authorities have been very active in the past several years, many questions remain unanswered in our view. Second, a number of national and international projects that attempted to ensure more reliable exchanges of methods and results are discussed. However, the frequent lack of publication of procedures and protocols in research can often be a hindrance for sharing those good practices. Subsequently, the efforts made through NanoDiaRA to introduce standardized methods and techniques to support the development and utilization of nanomaterials are discussed in depth. A series of semi-structured interviews were conducted with the partners of this project, and the interviews were analyzed thematically to highlight the determined efforts of the researchers to standardize their methods. Finally, some recommendations are made towards the setting up of well-defined methods to support the high-quality work of collaborative nanoparticle-based research and development projects and to enhance standardization processes

What If States Realized Their Societal Goals Through Alliances Built on Critical Raw Materials?

This scenario explores what could happen if groups of states joined forces with like-minded allies to realize societal goals that can only be attained through an ample supply of raw materials: decarbonization, militarization, digitalization, and securing enough energy to bolster emerging middle classes. By 2030, four alliances emerge. Each one aims to accomplish its own discrete goals, and all are alienated from the others. The EU, which belongs to an alliance of circular economies, asks itself what steps it can take to promote the global stewardship of public goods and civil liberties

Challenges and opportunities of the European Critical Raw Materials Act

Abstract The Critical Raw Materials Act (CRMA) is an essential regulatory framework designed to address the pressing challenges faced by the European Union (EU) in the strategic sectors of decarbonization, digitalization, and aerospace and defense. It aims to tackle the lack of secure and sustainable access to critical raw materials (CRMs) by increasing anticipation and mitigation of supply risks, fostering domestic CRM potential, and promoting sustainable sourcing practices. Part of a broader “Green Industrial Plan” and aligned with the “Net-Zero Industry Act” (NZIA), the CRMA strives to position the EU as a leading hub for clean tech industries. The NZIA and CRMA packages respond to international trends of protecting clean energy technology and resources, akin to the US Inflation Reduction Act. Defining materials as “strategic” based on their relevance and expected demand for strategic technologies, the CRMA regulation establishes benchmarks for minimum shares of EU demand to be covered by domestically sourced and processed as well as recycled raw materials and aims at reducing dependencies on single third country suppliers in all steps of the supply chain. A communication complements the regulation by focusing on increasing CRM supply security and sustainability through circularity, standardization efforts, skill development, and strategic actions for research and innovation. Establishing a “CRM Club” and partnerships with like-minded countries intend to strengthen international partnerships to safeguard CRM supply security and facilitate sustainable investment in resource-rich nations. Challenges arise concerning the concept of “strategic raw materials” and meeting benchmarks, particularly in materials availability, recycling targets, diversification, and the establishment of necessary skills. Data gaps, potential national differences, coherence with national legislation, long-term economic viability, and potential fuelling of international tensions also pose significant challenges to the effective implementation of the CRMA. Addressing these challenges and embracing the opportunities presented by the CRMA are crucial steps toward achieving sustainable resource management and advancing the EU’s clean tech industries