Familial hypercholesterolemia in St.-Petersburg: the known and novel mutations found in the low density lipoprotein receptor gene in Russia

BACKGROUND: Familial hypercholesterolemia is a human monogenic disease caused by population-specific mutations in the low density lipoprotein (LDL) receptor gene. Despite thirteen different mutations of the LDL receptor gene were reported from Russia prior to 2003, the whole spectrum of disease-causing gene alterations in this country is poorly known and requires further investigation provided by the current study. METHODS: Forty-five patients with clinical diagnosis of FH were tested for the apolipoprotein B (apoB) mutation R3500Q by restriction fragment length analysis. After exclusion of R3500Q mutation high-sensitive fluorescent single-strand conformation polymorphism (SSCP) analysis and automatic DNA sequencing were used to search for mutations in the LDL receptor gene. RESULTS: We found twenty one rare sequence variations of the LDL receptor gene. Nineteen were probably pathogenic mutations, and two (P518P, T705I) were considered as neutral ones. Among the mutations likely to be pathogenic, eight were novel (c.670-671insG, C249X, c.936-940del5, c.1291-1331del41, W422X, c.1855-1856insA, D601N, C646S), and eleven (Q12X, IVS3+1G>A, c.651-653del3, E207X, c.925-931del7, C308Y, L380H, c.1302delG, IVS9+1G>A, V776M, V806I) have already been described in other populations. None of the patients had the R3500Q mutation in the apoB gene. CONCLUSIONS: Nineteen pathogenic mutations in the LDL receptor gene in 23 probands were identified. Two mutations c.925-931del7 and L380H are shared by St.-Petersburg population with neighbouring Finland and several other mutations with Norway, Sweden or Denmark, i.e. countries from the Baltic Sea region. Only four mutations (c.313+1G>A, c.651-653del3, C308Y and W422X) were recurrent as all those were found in two unrelated families. By this study the number of known mutations in the LDL receptor gene in St.-Petersburg area was increased nearly threefold. Analysis of all 34 low density lipoprotein receptor gene mutations found in St.-Petersburg argues against strong founder effect in Russian familial hypercholesterolemia

Dynamic light diffusion, Anderson localization and lasing in disordered inverted opals: 3D ab-initio Maxwell-Bloch computation

We report on 3D time-domain parallel simulations of Anderson localization of light in inverted disordered opals displaying a complete photonic band-gap. We investigate dynamic diffusion processes induced by femtosecond laser excitations, calculate the diffusion constant and the decay-time distribution versus the strength of the disorder. We report evidence of the transition from delocalized Bloch oscillations to strongly localized resonances in self-starting laser processes.Comment: 4 pages, 5 figure

When Learners Surpass Their Models: Mathematical Modeling of Learning from an Inconsistent Source

It has been reported in the literature that both adults and children can, to a different degree, modify and regularize the often-inconsistent linguistic input they receive. We present a new algorithm to model and investigate the learning process of a learner mastering a set of (grammatical or lexical) forms from an inconsistent source. The algorithm is related to reinforcement learning and drift-diffusion models of decision making, and possesses several psychologically relevant properties such as fidelity, robustness, discounting, and computational simplicity. It demonstrates how a learner can successfully learn from or even surpass its imperfect source. We use the data collected by Singleton and Newport (Cognit Psychol 49(4):370-407, 2004) on the performance of a 7-year-boy Simon, who mastered the American Sign Language (ASL) by learning it from his parents, both of whom were imperfect speakers of ASL. We show that the algorithm possesses a frequency boosting property, whereby the frequency of the most common form of the source is increased by the learner. We also explain several key features of Simon's ASL. © 2014 Society for Mathematical Biology

Further generalization and numerical implementation of pseudo-time Schroedinger equations for quantum scattering calculations

We review and further develop the recently introduced numerical approach for scattering calculations based on a so called pseudo-time Schroedinger equation, which is in turn a modification of the damped Chebyshev polynomial expansion scheme. The method utilizes a special energy-dependent form for the absorbing potential in the time-independent Schroedinger equation, in which the complex energy spectrum E_k is mapped to u_k inside the unit disk, where u_k are the eigenvalues of some explicitly known sparse matrix U. Most importantly for the numerical implementation, all the physical eigenvalues u_k are extreme eigenvalues of U, which allows one to extract these eigenvalues very efficiently by harmonic inversion of a pseudo-time autocorrelation function using the filter diagonalization method. The computation of 2T steps of the autocorrelation function requires only T sparse real matrix-vector multiplications. We describe and compare different schemes, effectively corresponding to different choices of the energy-dependent absorbing potential, and test them numerically by calculating resonances of the HCO molecule. Our numerical tests suggest an optimal scheme that provide accurate estimates for most resonance states