New Insights into the Structural Roles of Nebulin in Skeletal Muscle

One important feature of muscle structure and function that has remained relatively obscure is the mechanism that regulates thin filament length. Filament length is an important aspect of muscle function as force production is proportional to the amount of overlap between thick and thin filaments. Recent advances, due in part to the generation of nebulin KO models, reveal that nebulin plays an important role in the regulation of thin filament length. Another structural feature of skeletal muscle that is not well understood is the mechanism involved in maintaining the regular lateral alignment of adjacent sarcomeres, that is, myofibrillar connectivity. Recent studies indicate that nebulin is part of a protein complex that mechanically links adjacent myofibrils. Thus, novel structural roles of nebulin in skeletal muscle involve the regulation of thin filament length and maintaining myofibrillar connectivity. When these functions of nebulin are absent, muscle weakness ensues, as is the case in patients with nemaline myopathy with mutations in nebulin. Here we review these new insights in the role of nebulin in skeletal muscle structure

Quantum theory of the low-frequency linear susceptibility of interferometer-type superconducting qubits

We use the density matrix formalism to analyze the interaction of interferometer-type superconducting qubits with a high quality tank circuit, which frequency is well below the gap frequency of a qubit. We start with the ground state characterization of the superconducting flux and charge qubits. Then, by making use of a dressed state approach we describe the qubits' spectroscopy when the qubit is irradiated by a microwave field which is tuned to the gap frequency. The last section of the paper is devoted to continuous monitoring of qubit states by using a DC SQUID in the inductive mode.Comment: 11 pages, 5 figures; the title and abstract are slightly changed; several typos are corrected; in order to make our argumentation more clear we added some comments in the introduction and other section

Conceptualizing throughput legitimacy: procedural mechanisms of accountability, transparency, inclusiveness and openness in EU governance

This symposium demonstrates the potential for throughput legitimacy as a concept for shedding empirical light on the strengths and weaknesses of multi-level governance, as well as challenging the concept theoretically. This article introduces the symposium by conceptualizing throughput legitimacy as an ‘umbrella concept’, encompassing a constellation of normative criteria not necessarily empirically interrelated. It argues that in order to interrogate multi-level governance processes in all their complexity, it makes sense for us to develop normative standards that are not naïve about the empirical realities of how power is exercised within multilevel governance, or how it may interact with legitimacy. We argue that while throughput legitimacy has its normative limits, it can be substantively useful for these purposes. While being no replacement for input and output legitimacy, throughput legitimacy offers distinctive normative criteria— accountability, transparency, inclusiveness and openness— and points towards substantive institutional reforms.Published versio

Metformin:A Narrative Review of Its Potential Benefits for Cardiovascular Disease, Cancer and Dementia

The biguanide metformin has been used as first-line therapy in type 2 diabetes mellitus (T2DM) treatment for several decades. In addition to its glucose-lowering properties and its prevention of weight gain, the landmark UK Prospective Diabetes Study (UKPDS) demonstrated cardioprotective properties in obese T2DM patients. Coupled with a favorable side effect profile and low cost, metformin has become the cornerstone in the treatment of T2DM worldwide. In addition, metformin is increasingly being investigated for its potential anticancer and neuroprotective properties both in T2DM patients and non-diabetic individuals. In the meantime, new drugs with powerful cardioprotective properties have been introduced and compete with metformin for its place in the treatment of T2DM. In this review we will discuss actual insights in the various working mechanisms of metformin and the evidence for its beneficial effects on (the prevention of) cardiovascular disease, cancer and dementia. In addition to observational evidence, emphasis is placed on randomized trials and recent meta-analyses to obtain an up-to-date overview of the use of metformin in clinical practice

SmartTools: a generator of interactive environments tools

SmartTools is a development environment generator that provides a structure editor and semantic tools as main features. The well-known visitor pattern technique is commonly used for designing semantic analysis, it has been automated and extended. SmartTools is easy to use thanks to its graphical user interface designed with the Java Swing APIs. It is built with an open architecture convinient for a partial or total integration of SmartTools in other environments. It makes the addition of new software components in SmartTools easy. As a result of the modular architecture, we built a distributed instance of SmartTools which required minimal effort. Being open to the XML technologies offers all the features of Smart Tools to any language defined with those technologies. But most of all, with its open architecture, SmartTools takes advantage of all the developments made around those technologies, like DOM, through the XML APIs. The fast development of SmartTools (which is a young project, one year old) validates our choices of being open and generic. The main goal of this tool is to provide help and support for designing software development environments for programming languages as well as application languages defined with XML technologies

Airports at Risk: The Impact of Information Sources on Security Decisions

Security decisions in high risk organizations such as airports involve obtaining ongoing and frequent information about potential threats. Utilizing questionnaire survey data from a sample of airport employees in European Airports across the continent, we analyzed how both formal and informal sources of security information affect employee's decisions to comply with the security rules and directives. This led us to trace information network flows to assess its impact on the degree employees making security decisions comply or deviate with the prescribed security rules. The results of the multivariate analysis showed that security information obtained through formal and informal networks differentially determine if employee will comply or not with the rules. Information sources emanating from the informal network tends to encourage employees to be more flexible in their security decisions while formal sources lead to be more rigid with complying with rules and protocols. These results suggest that alongside the formal administrative structure of airports, there exists a diverse and pervasiveness set of informal communications networks that are a potent factor in determining airport security levels

Measuring and explaining the diversity of voices and viewpoints in the news

News media can be considered to fulfil their democratic role as a “marketplace of ideas” only if they present a diverse content that gives space to a wider range of ideas and viewpoints. But how can content diversity be assessed? And what determines actor and viewpoint diversity in the first place? By employing measurements of actor and viewpoint diversity at the article and newspaper level, this study provides a complete overview on the content diversity of immigration news, and it investigates factors that have an impact on content diversity of immigration newspaper articles in Belgium, Germany, Italy and the United Kingdom (2013-2014). The results of a multilevel analysis indicate that both the articles’ size and the elite character of a newspaper play a key role in enhancing news’ multiperspectivalness. Also, the findings show that these two measurements of content diversity are different yet related to each other

A comparison of collision cross section values obtained via travelling wave ion mobility-mass spectrometry and ultra high performance liquid chromatography-ion mobility-mass spectrometry : application to the characterisation of metabolites in rat urine

A comprehensive Collision Cross Section (CCS) library was obtained via Travelling Wave Ion Guide mobility measurements through direct infusion (DI). The library consists of CCS and Mass Spectral (MS) data in negative and positive ElectroSpray Ionisation (ESI) mode for 463 and 479 endogenous metabolites, respectively. For both ionisation modes combined, TWCCSN2 data were obtained for 542 non-redundant metabolites. These data were acquired on two different ion mobility enabled orthogonal acceleration QToF MS systems in two different laboratories, with the majority of the resulting TWCCSN2 values (from detected compounds) found to be within 1% of one another. Validation of these results against two independent, external TWCCSN2 data sources and predicted TWCCSN2 values indicated to be within 1-2% of these other values. The same metabolites were then analysed using a rapid reversed-phase ultra (high) performance liquid chromatographic (U(H)PLC) separation combined with IM and MS (IM-MS) thus providing retention time (tr), m/z and TWCCSN2 values (with the latter compared with the DI-IM-MS data). Analytes for which TWCCSN2 values were obtained by U(H)PLC-IM-MS showed good agreement with the results obtained from DI-IM-MS. The repeatability of the TWCCSN2 values obtained for these metabolites on the different ion mobility QToF systems, using either DI or LC, encouraged the further evaluation of the U(H)PLC-IM-MS approach via the analysis of samples of rat urine, from control and methotrexate-treated animals, in order to assess the potential of the approach for metabolite identification and profiling in metabolic phenotyping studies. Based on the database derived from the standards 63 metabolites were identified in rat urine, using positive ESI, based on the combination of tr, TWCCSN2 and MS data.</p

An Algebraic Approach to Linear-Optical Schemes for Deterministic Quantum Computing

Linear-Optical Passive (LOP) devices and photon counters are sufficient to implement universal quantum computation with single photons, and particular schemes have already been proposed. In this paper we discuss the link between the algebraic structure of LOP transformations and quantum computing. We first show how to decompose the Fock space of N optical modes in finite-dimensional subspaces that are suitable for encoding strings of qubits and invariant under LOP transformations (these subspaces are related to the spaces of irreducible unitary representations of U(N)). Next we show how to design in algorithmic fashion LOP circuits which implement any quantum circuit deterministically. We also present some simple examples, such as the circuits implementing a CNOT gate and a Bell-State Generator/Analyzer.Comment: new version with minor modification