A new perspective on the competitiveness of nations

The capability of firms to survive and to have a competitive advantage in global markets depends on, amongst other things, the efficiency of public institutions, the excellence of educational, health and communications infrastructures, as well as on the political and economic stability of their home country. The measurement of competitiveness and strategy development is thus an important issue for policy-makers. Despite many attempts to provide objectivity in the development of measures of national competitiveness, there are inherently subjective judgments that involve, for example, how data sets are aggregated and importance weights are applied. Generally, either equal weighting is assumed in calculating a final index, or subjective weights are specified. The same problem also occurs in the subjective assignment of countries to different clusters. Developed as such, the value of these type indices may be questioned by users. The aim of this paper is to explore methodological transparency as a viable solution to problems created by existing aggregated indices. For this purpose, a methodology composed of three steps is proposed. To start, a hierarchical clustering analysis is used to assign countries to appropriate clusters. In current methods, country clustering is generally based on GDP. However, we suggest that GDP alone is insufficient for purposes of country clustering. In the proposed methodology, 178 criteria are used for this purpose. Next, relationships between the criteria and classification of the countries are determined using artificial neural networks (ANNs). ANN provides an objective method for determining the attribute/criteria weights, which are, for the most part, subjectively specified in existing methods. Finally, in our third step, the countries of interest are ranked based on weights generated in the previous step. Beyond the ranking of countries, the proposed methodology can also be used to identify those attributes that a given country should focus on in order to improve its position relative to other countries, i.e., to transition from its current cluster to the next higher one

Lurasidone is not associated with risk of QTc prolongation

A critical appraisal and clinical application of Meltzer HY, Cucchiaro J, Silva R, Ogasa M, Phillips D, Xu J, Kalali AH, Scheizer E, Pikalov A, Loebel A. Lurasidone in the treatment of schizophrenia: a randomized, double-blind, placebo- and olanzapine-controlled study. Am J Psychiatry. 2011 Sep;168(9):957-67. doi: https://doi.org/10.1176/appi.ajp.2011.10060907

High sensitivity and multifunctional micro-Hall sensors fabricated using InAlSb/InAsSb/InAlSb heterostructures

Further diversification of Hall sensor technology requires development of materials with high electron mobility and an ultrathin conducting layer very close to the material's surface. Here, we describe the magnetoresistive properties of micro-Hall devices fabricated using InAlSb/InAsSb/InAlSb heterostructures where electrical conduction was confined to a 30 nm-InAsSb two-dimensional electron gas layer. The 300 K electron mobility and sheet carrier concentration were 36 500 cm(2) V-1 s(-1) and 2.5 x 10(11) cm(-2), respectively. The maximum current-related sensitivity was 2 750 V A(-1) T-1, which was about an order of magnitude greater than AlGaAs/InGaAs pseudomorphic heterostructures devices. Photolithography was used to fabricate 1 mu m x 1 mu m Hall probes, which were installed into a scanning Hall probe microscope and used to image the surface of a hard disk

Flow Induced Organization and Memory of a Vortex Lattice

We report on experiments probing the evolution of a vortex state in response to a driving current in 2H-NbSe$_2$ crystals. By following the vortex motion with fast transport measurements we find that the current enables the system to reorganize and access new configurations. During this process the system exhibits a long-term memory: if the current is turned off the vortices freeze in place remembering their prior motion. When the current is restored the motion resumes where it stopped. The experiments provide evidence for a dynamically driven structural change of the vortex lattice and a corresponding dynamic phase diagram that contains a previously unknown regime where the critical current can be either $increased$ or $decreased$ by applying an appropriate driving current.Comment: 5 pages, 4figure

MIR376A is a regulator of starvation-induced autophagy

Background: Autophagy is a vesicular trafficking process responsible for the degradation of long-lived, misfolded or abnormal proteins, as well as damaged or surplus organelles. Abnormalities of the autophagic activity may result in the accumulation of protein aggregates, organelle dysfunction, and autophagy disorders were associated with various diseases. Hence, mechanisms of autophagy regulation are under exploration. Methods: Over-expression of hsa-miR-376a1 (shortly MIR376A) was performed to evaluate its effects on autophagy. Autophagy-related targets of the miRNA were predicted using Microcosm Targets and MIRanda bioinformatics tools and experimentally validated. Endogenous miRNA was blocked using antagomirs and the effects on target expression and autophagy were analyzed. Luciferase tests were performed to confirm that 3’ UTR sequences in target genes were functional. Differential expression of MIR376A and the related MIR376B was compared using TaqMan quantitative PCR. Results: Here, we demonstrated that, a microRNA (miRNA) from the DlkI/Gtl2 gene cluster, MIR376A, played an important role in autophagy regulation. We showed that, amino acid and serum starvation-induced autophagy was blocked by MIR376A overexpression in MCF-7 and Huh-7 cells. MIR376A shared the same seed sequence and had overlapping targets with MIR376B, and similarly blocked the expression of key autophagy proteins ATG4C and BECN1 (Beclin 1). Indeed, 3’ UTR sequences in the mRNA of these autophagy proteins were responsive to MIR376A in luciferase assays. Antagomir tests showed that, endogenous MIR376A was participating to the control of ATG4C and BECN1 transcript and protein levels. Moreover, blockage of endogenous MIR376A accelerated starvation-induced autophagic activity. Interestingly, MIR376A and MIR376B levels were increased with different kinetics in response to starvation stress and tissue-specific level differences were also observed, pointing out to an overlapping but miRNA-specific biological role. Conclusions: Our findings underline the importance of miRNAs encoded by the DlkI/Gtl2 gene cluster in stress-response control mechanisms, and introduce MIR376A as a new regulator of autophagy

IBMPFD disease-causing mutant VCP/p97 proteins are targets of autophagic-lysosomal degradation

The ubiquitin-proteasome system (UPS) degrades soluble proteins and small aggregates, whereas macroautophagy (autophagy herein) eliminates larger protein aggregates, tangles and even whole organelles in a lysosome-dependent manner. VCP/p97 was implicated in both pathways. VCP/p97 mutations cause a rare multisystem disease called IBMPFD (Inclusion Body Myopathy with Paget's Disease and Frontotemporal Dementia). Here, we studied the role IBMPFD-related mutants of VCP/p97 in autophagy. In contrast with the wild-type VCP/p97 protein or R155C or R191Q mutants, the P137L mutant was aggregate-prone. We showed that, unlike commonly studied R155C or R191Q mutants, the P137L mutant protein stimulated both autophagosome and autolysosome formation. Moreover, P137L mutant protein itself was a substrate of autophagy. Starvation- and mTOR inhibition-induced autophagy led to the degradation of the P137L mutant protein, while preserving the wild-type and functional VCP/p97. Strikingly, similar to the P137L mutant, other IBMPFD-related VCP/p97 mutants, namely R93C and G157R mutants induced autophagosome and autolysosome formation; and G157R mutant formed aggregates that could be cleared by autophagy. Therefore, cellular phenotypes caused by P137L mutant expression were not isolated observations, and some other IBMPFD disease-related VCP/p97 mutations could lead to similar outcomes. Our results indicate that cellular mechanisms leading to IBMPFD disease may be various, and underline the importance of studying different disease-associated mutations in order to better understand human pathologies and tailor mutation-specific treatment strategies

Experiments in vortex avalanches

Avalanche dynamics is found in many phenomena spanning from earthquakes to the evolution of species. It can be also found in vortex matter when a type II superconductor is externally driven, for example, by increasing the magnetic field. Vortex avalanches associated with thermal instabilities can be an undesirable effect for applications, but "dynamically driven" avalanches emerging from the competition between intervortex interactions and quenched disorder constitute an interesting scenario to test theoretical ideas related with non-equilibrium dynamics. However, differently from the equilibrium phases of vortex matter in type II superconductors, the study of the corresponding dynamical phases - in which avalanches can play a role - is still in its infancy. In this paper we critically review relevant experiments performed in the last decade or so, emphasizing the ability of different experimental techniques to establish the nature and statistical properties of the observed avalanche behavior.Comment: To be published in Reviews of Modern Physics April 2004. 17 page