Two novel missense mutations in the myelin protein zero gene causes Charcot-Marie-Tooth type 2 and Déjérine-Sottas syndrome

<p>Abstract</p> <p>Background</p> <p>The Charcot-Marie-Tooth (CMT) phenotype caused by mutation in the <it>myelin protein zero (MPZ) </it>gene varies considerably, from early onset and severe forms to late onset and milder forms. The mechanism is not well understood. The myelin protein zero (P₀) mediates adhesion in the spiral wraps of the Schwann cell's myelin sheath. The crystalline structure of the extracellular domain of the myelin protein zero (P₀ex) is known, while the transmembrane and intracellular structure is unknown.</p> <p>Findings</p> <p>One novel missense mutation caused a milder late onset CMT type 2, while the second missense mutation caused a severe early onset phenotype compatible with Déjérine-Sottas syndrome.</p> <p>Conclusions</p> <p>The phenotypic variation caused by different missense mutations in the <it>MPZ </it>gene is likely caused by different conformational changes of the MPZ protein which affects the functional tetramers. Severe changes of the MPZ protein cause dysfunctional tetramers and predominantly uncompacted myelin, i.e. the severe phenotypes congenital hypomyelinating neuropathy and Déjérine-Sottas syndrome, while milder changes cause the phenotypes CMT type 1 and 2.</p

Outsourcing with debt financing

This paper investigates the effect of capital structure on a firm’s choice between vertical integration and outsourcing. We model the production decision in a Principal-Agent framework and show that suppliers use debt as a strategic instrument to collect the surplus from outsourcing as their wealth constraint or limited liability ensures them more attractive compensation schemes. Investigating the buyer’s capital structure, we find that outsourcing with risky debt is more likely to occur for high values of the outsourcing surplus.info:eu-repo/semantics/publishedVersio

A Systemic Approach to Multi-Party Relationship Modeling

Socio-economic systems exist in a wide variety of activity domains and are composed of multiple stakeholder groups. These groups pursue objectives which are often entirely motivated from within their local context. Domain specificities in the form of institutional design, for example the deregulation of Public Utility systems, can further fragment this context. Nevertheless, for these systems to be viable, a management subsystem that maintains a holistic view of the system is required. From a Systems perspective, this highlights the need to invest in methods that capture the interactions between the different stakeholders of the system. It is the understanding of the individual interactions that can help piece together a holistic view of the system thereby enabling system level discourse. In this paper we present a modeling technique that models industry interactions as a multi-party value realization process and takes a Systems approach in analyzing them. Every interaction is analyzed both from outside – system as a black box and from within – system as a white box. The design patterns that emerge from this whole/composite view of value realization provide the necessary foundation to analyze the working of multi-stakeholder systems. An explicit specification of these concepts is presented as Regulation Enabling Ontology, REGENT. As an example, we instantiate REGENT for the urban residential electricity market and demonstrate its effectiveness in identifying the requirements for time-based electricity supply systems

Laser excitation of the 1s-hyperfine transition in muonic hydrogen

The CREMA collaboration is pursuing a measurement of the ground-state hyperfine splitting (HFS) in muonic hydrogen ($\mu$p) with 1 ppm accuracy by means of pulsed laser spectroscopy to determine the two-photon-exchange contribution with $2\times10^{-4}$ relative accuracy. In the proposed experiment, the $\mu$p atom undergoes a laser excitation from the singlet hyperfine state to the triplet hyperfine state, {then} is quenched back to the singlet state by an inelastic collision with a H$_2$ molecule. The resulting increase of kinetic energy after the collisional deexcitation is used as a signature of a successful laser transition between hyperfine states. In this paper, we calculate the combined probability that a $\mu$p atom initially in the singlet hyperfine state undergoes a laser excitation to the triplet state followed by a collisional-induced deexcitation back to the singlet state. This combined probability has been computed using the optical Bloch equations including the inelastic and elastic collisions. Omitting the decoherence effects caused by {the laser bandwidth and }collisions would overestimate the transition probability by more than a factor of two in the experimental conditions. Moreover, we also account for Doppler effects and provide the matrix element, the saturation fluence, the elastic and inelastic collision rates for the singlet and triplet states, and the resonance linewidth. This calculation thus quantifies one of the key unknowns of the HFS experiment, leading to a precise definition of the requirements for the laser system and to an optimization of the hydrogen gas target where $\mu$p is formed and the laser spectroscopy will occur.Comment: 21 pages, 4 figure