The emerging role of epigenetics in therapeutic targeting of cardiomyopathies

Cardiomyopathies (CMPs) are a heterogeneous group of myocardial diseases accountable for the majority of cases of heart failure (HF) and/or sudden cardiac death (SCD) worldwide. With the recent advances in genomics, the original classification of CMPs on the basis of morphological and functional criteria (dilated (DCM), hypertrophic (HCM), restrictive (RCM), and arrhythmogenic ventricular cardiomyopathy (AVC)) was further refined into genetic (inherited or familial) and acquired (non-inherited or secondary) forms. Despite substantial progress in the identification of novel CMP-associated genetic variations, as well as improved clinical recognition diagnoses, the functional consequences of these mutations and the exact details of the signaling pathways leading to hypertrophy, dilation, and/or contractile impairment remain elusive. To date, global research has mainly focused on the genetic factors underlying CMP pathogenesis. However, growing evidence shows that alterations in molecular mediators associated with the diagnosis of CMPs are not always correlated with genetic mutations, suggesting that additional mechanisms, such as epigenetics, may play a role in the onset or progression of CMPs. This review summarizes published findings of inherited CMPs with a specific focus on the potential role of epigenetic mechanisms in regulating these cardiac disorders

Global Value Chains during the Great Trade Collapse: A Bullwhip Effect?

This paper analyzes the performance of global value chains during the trade collapse. To do so, it exploits a unique transaction-level dataset on French firms containing information on cross-border monthly transactions matched with data on worldwide intra-firm linkages as defined by property rights (multinational business groups, hierarchies of firms). This newly assembled dataset allows us to distinguish firm-level transactions among two alternative organizational modes of global value chains: internalization of activities (intra-group trade/trade among related parties) or establishment of supply contracts (arm’s length trade/trade among unrelated parties). After an overall assessment of the role of global value chains during the trade collapse, we document that intra-group trade in intermediates was characterized by a faster drop followed by a faster recovery than arm’s length trade. Amplified fluctuations in terms of trade elasticities by value chains have been referred to as the "bullwhip effect" and have been attributed to the adjustment of inventories within supply chains. In this paper we first confirm the existence of such an effect due to trade in intermediates, and we underline the role that different organizational modes can play in driving this adjustment.trade collapse, multinational firms, global value chains, hierarchies of firms, vertical integration.

Revisiting Sovereign Bankruptcy

Sovereign debt crises occur regularly and often violently. Yet there is no legally and politically recognized procedure for restructuring the debt of bankrupt sovereigns. Procedures of this type have been periodically debated, but so far been rejected, for two main reasons. First, countries have been reluctant to give up power to supranational rules or institutions, and creditors and debtors have felt that there were sufficient instruments for addressing debt crises at hoc. Second, fears that making debt easier to restructure would raise the costs and reduce the amounts of sovereign borrowing in many countries. This was perceived to be against the interests of both the providers of both creditors and major borrowers. This report argues that both the nature and our understanding of sovereign debt problems have changed, over the course of the last decade, in a direction that creates a much stronger case for an orderly sovereign bankruptcy regime today than ten years ago. Pre-crisis policy mistakes are now recognized to be a much more severe problem for borrowing countries than the costs or limited availability of private financing. Recent court rulings – particularly a recent U.S. ruling that gives holdout creditors that decline a restructuring offer the right to interfere with payments to the creditors that accept such an offer. This will complicate efforts to resolve future debt crises on an ad hoc basis. Finally, sovereign debt crises are no longer just a problem in emerging markets, but a core concern in advanced countries as well – particularly in the Euro area. If the Euro is to survive, this will require both better ways to resolve debt crises and stronger, market-based incentives that prevent debt problems from occurring in the first place. To address these problems, policy proposals are presented at two levels: for the Euro area, and globally. A Euro area sovereign debt restructuring regime could be developed by amending the Treaty establishing the European Stability Mechanism (ESM). This would both restrict the scope for lending to highly indebted countries without also restructuring their debts, and protect Euro area members receiving ESM financial assistance from legal action by holdout creditors. At the global level, a number of proposals are discussed, ranging from a coordinated introduction of aggregate collective action clauses that would allow a supermajority of bondholders across all bonds to amend bond payment terms to an amendment of the IMF articles that would limit the legal remedies of holdouts when a debt restructuring proposal has been accepted both by a majority of creditors and endorsed by the IMF

Industrial risk in the Lombardy Region (Italy): what people perceive and what are the gaps to improve the risk communication and the participatory processes

Risk communication is of vital importance in today\u2019s society, as audiences become ever more questioning about the causes and effects of risk. However, the communication of risk is a complex activity involving many different types of communicators and destinataries, from scientists, to the media, to government agencies, industry and consumer groups, each of which having its own agendas to fulfil. Such variation across the communication of the same risk can lead to confusion, misunderstandings, misreporting in the media and subsequent conflicts. The goal of risk communication is to produce an informed public. The personal nature of risk issues and the uncertainty associated with estimating risk can provoke considerable anxiety for the public and make adopted risk management strategies less acceptable. Lombardy is one of the most densely populated and industrialized regions in Europe and nearly 280 Seveso sites interest it. The Seveso Directive requires specific measures on risk communication to the population. Nevertheless, the Lombardy Region Authorities consider that the implementation of such provisions is too weak. Therefore an exploratory research has been concluded, in order to estimate the gaps in risk communication and to improve the participation of the population in the emergency preparedness activities. The paper reports the main results of the research and illustrates the potential strategies to improve the risk communication and the population participation and preparedness (\uc9upolis Lombardia 2011)

On generation of jets for vector bundles

Sin resume

Genetic divergence in the cave cricket Troglophilus neglectus (Orthoptera Rhaphidophoridae): mitochondrial and nuclear DNA data.

In this study we used sequence polymorphisms at one mitochondrial and one nuclear gene (Cytochrome Oxidase subunit I and Internal Transcribed Spacer 1, respectively) to assess the degree of genetic divergence among 21 populations of the cave cricket Troglophilus neglectus (Orthoptera, Rhaphidophoridae), a species whose currently known range extends from the Balkan Peninsula to Southern Bavaria. Nineteen populations were sampled in Northern Italy, Slovenia, Croatia and Bosnia and Herzegovina, while two populations came from Germany (Lower Saxony) and Czech Republic, thus well outside the species range. Molecular data revealed a high level of fragmentation, with most of the study populations bearing exclusive haplotypes, the sole exception being the German and Czech specimens, which carried haplotypes also occurring at Slovenian locations. Spatial distribution of genetic heterogeneity and pattern of genetic divergence argue in favor of a recent origin of the two Central European populations, possibly through man-mediated dispersal event(s). These populations being not considered, our data are in remarkable agreement with a previous study based on allozymes conducted on a subset of populations of the same species and, more generally, with what is known on the population genetics of peri-Mediterranean Rhaphidophorids

Design optimization of a high-speed synchronous reluctance machine

Synchronous reluctance machines, including the per¬manent magnet assisted variants are competitive motor topologies if the application requires high efficiency and a cost effective solution with a high flux weakening capability. However, increas¬ing operating speeds incur challenging design and development decisions, mainly in order to find design solutions that ensure the machines structural integrity without compromising the overall performance. In this paper, a comprehensive design procedure for high speed synchronous reluctance machines is presented. In order to validate the procedure, a 5 kW, 80000 rpm machine is considered. The proposed strategy consists of a two-step procedure in which the electromagnetic and structural designs have been properly decoupled dividing the design space in two subsets. Each subset mainly affects the electromagnetic or the structural performances. Several structural design optimizations have been then performed with the aim of finding the optimal trade-off between the rotor geometrical complexity (that defines the required computational resources) and the electromagnetic performance. The reported experimental tests of the prototyped machine validate the proposed design strategy which can be used as general guidelines on the structural design of synchronous reluctance machines

Efficiency of microsatellite markers in assisted selection for resistance to soybean cyst nematode (race 3).

Four microsatellite sequences were tested in soybean DNA from cultivars and segregating genotypes. Three of them were close to the resistance locus rhg 1 on molecular linkage group G (Satt 309, Sat_168, Sat_163) and one was close to Rhg4 locus on group A2 (Sat_162). Progenies previously classified as cyst nematode (SNC) resistant and others with unknown reaction were tested, using the resistant cultivars Liderança, and Renascença and the susceptibles 'Cristalina' and 'OCEPAR-4' as control. The best primer for resistance to SCN was Sat_162. Twenty segregant progenies tested with Sat_162 presented a 150 bp band for homozygous resistant genotypes and 200 bp for susceptible ones, and both for the heterozigous genotypes. Previous studies have shown that this microsatellite marker is efficient to select genotypes carrying Peking-derivative resistance. 'Peking' takes part in the in the genealogy of all segregant progenies evaluated in this study. Thus, the obtained results showed that Sat_162 distinguished resistant and susceptible soybean genotypes to SCN, race 3