Functional Characterisation of Alpha-Galactosidase A Mutations as a Basis for a New Classification System in Fabry Disease

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The study has been supported partially by an unrestricted scientific grant from Shire Human Genetic Therapies (Germany

Scaling, Multiscaling, and Nontrivial Exponents in Inelastic Collision Processes

We investigate velocity statistics of homogeneous inelastic gases using the Boltzmann equation. Employing an approximate uniform collision rate, we obtain analytic results valid in arbitrary dimension. In the freely evolving case, the velocity distribution is characterized by an algebraic large velocity tail, P(v,t) ~ v^{-sigma}. The exponent sigma(d,epsilon), a nontrivial root of an integral equation, varies continuously with the spatial dimension, d, and the dissipation coefficient, epsilon. Although the velocity distribution follows a scaling form, its moments exhibit multiscaling asymptotic behavior. Furthermore, the velocity autocorrelation function decays algebraically with time, A(t)= ~ t^{-alpha}, with a non-universal dissipation-dependent exponent alpha=1/epsilon. In the forced case, the steady state Fourier transform is obtained via a cumulant expansion. Even in this case, velocity correlations develop and the velocity distribution is non-Maxwellian.Comment: 10 pages, 3 figure

Glucosylsphingosine Is a Highly Sensitive and Specific Biomarker for Primary Diagnostic and Follow-Up Monitoring in Gaucher Disease in a Non-Jewish, Caucasian Cohort of Gaucher Disease Patients

Gaucher disease (GD) is the most common lysosomal storage disorder (LSD). Based on a deficient β-glucocerebrosidase it leads to an accumulation of glucosylceramide. Standard diagnostic procedures include measurement of enzyme activity, genetic testing as well as analysis of chitotriosidase and CCL18/PARC as biomarkers. Even though chitotriosidase is the most well-established biomarker in GD, it is not specific for GD. Furthermore, it may be false negative in a significant percentage of GD patients due to mutation. Additionally, chitotriosidase reflects the changes in the course of the disease belatedly. This further enhances the need for a reliable biomarker, especially for the monitoring of the disease and the impact of potential treatments.Here, we evaluated the sensitivity and specificity of the previously reported biomarker Glucosylsphingosine with regard to different control groups (healthy control vs. GD carriers vs. other LSDs).Only GD patients displayed elevated levels of Glucosylsphingosine higher than 12 ng/ml whereas the comparison controls groups revealed concentrations below the pathological cut-off, verifying the specificity of Glucosylsphingosine as a biomarker for GD. In addition, we evaluated the biomarker before and during enzyme replacement therapy (ERT) in 19 patients, demonstrating a decrease in Glucosylsphingosine over time with the most pronounced reduction within the first 6 months of ERT. Furthermore, our data reveals a correlation between the medical consequence of specific mutations and Glucosylsphingosine.In summary, Glucosylsphingosine is a very promising, reliable and specific biomarker for GD

Regional age structure, human capital and innovation - is demographic ageing increasing regional disparities?

Demographic change is expected to affect labour markets in very different ways on a regional scale. The objective of this paper is to explore the spatio-temporal patterns of recent distributional changes in the workers age structure, innovation output and skill composition for German regions by conducting an Exploratory Space-Time Data Analysis (ESTDA). Beside commonly used tools, we apply newly developed approaches which allow investigating the space-time dynamics of the spatial distributions. We include an analysis of the joint distributional dynamics of the patenting variable with the remaining interest variables. Overall, we find strong clustering tendencies for the demographic variables and innovation that constitute a great divide across German regions. The detected clusters partly evolve over time and suggest a demographic polarization trend among regions that may further reinforce the observed innovation divide in the future

Towards a Proof Theory of G\"odel Modal Logics

Analytic proof calculi are introduced for box and diamond fragments of basic modal fuzzy logics that combine the Kripke semantics of modal logic K with the many-valued semantics of G\"odel logic. The calculi are used to establish completeness and complexity results for these fragments

Quantum dynamics in strong fluctuating fields

A large number of multifaceted quantum transport processes in molecular systems and physical nanosystems can be treated in terms of quantum relaxation processes which couple to one or several fluctuating environments. A thermal equilibrium environment can conveniently be modelled by a thermal bath of harmonic oscillators. An archetype situation provides a two-state dissipative quantum dynamics, commonly known under the label of a spin-boson dynamics. An interesting and nontrivial physical situation emerges, however, when the quantum dynamics evolves far away from thermal equilibrium. This occurs, for example, when a charge transferring medium possesses nonequilibrium degrees of freedom, or when a strong time-dependent control field is applied externally. Accordingly, certain parameters of underlying quantum subsystem acquire stochastic character. Herein, we review the general theoretical framework which is based on the method of projector operators, yielding the quantum master equations for systems that are exposed to strong external fields. This allows one to investigate on a common basis the influence of nonequilibrium fluctuations and periodic electrical fields on quantum transport processes. Most importantly, such strong fluctuating fields induce a whole variety of nonlinear and nonequilibrium phenomena. A characteristic feature of such dynamics is the absence of thermal (quantum) detailed balance.Comment: review article, Advances in Physics (2005), in pres

Complex life forms may arise from electrical processes

There is still not an appealing and testable model to explain how single-celled organisms, usually following fusion of male and female gametes, proceed to grow and evolve into multi-cellular, complexly differentiated systems, a particular species following virtually an invariant and unique growth pattern. An intrinsic electrical oscillator, resembling the cardiac pacemaker, may explain the process. Highly auto-correlated, it could live independently of ordinary thermodynamic processes which mandate increasing disorder, and could coordinate growth and differentiation of organ anlage