Toward personalized medicine in Bardet-Biedl syndrome

Personalized medicine is becoming routine in the treatment of common diseases such as cancer, but has lagged behind in the field of rare diseases. It is currently in the early stages for the treatment of Bardet–Biedl syndrome. Advances in the understanding of ciliary biology and diagnostic techniques have opened up the prospect of treating BBS in a patient-specific manner. Owing to their structure and function, cilia provide an attractive therapeutic target and genetic therapies are being explored in ciliopathy treatment. Promising avenues include gene therapy, gene editing techniques and splice-correcting and read-through therapies. Targeted drug design has been successful in the treatment of genetic disease and research is underway in the discovery of known and novel drugs to treat Bardet–Biedl syndrome

Solving the inhomogeneous Bethe-Salpeter equation

We develop an advanced method of solving homogeneous and inhomogeneous Bethe-Salpeter equations by using the expansion over the complete set of 4-dimensional spherical harmonics. We solve Bethe-Salpeter equations for bound and scattering states of scalar and spinor particles for the case of one meson exchange kernels. Phase shifts calculated for the scalar model are in agreement with the previously published results. We discuss possible manifestations of separability for one meson exchange interaction kernels.Comment: 9 pages, 11 eps-figures. Talk presented by S. S. Semikh at XVII International Baldin Seminar on High Energy Physics Problems "Relativistic Nuclear Physics and Quantum Chromodynamics", September 27 - October 2, 2004, Dubna, Russia; to appear in the proceedings of this conferenc

Bardet-Biedl Syndrome ciliopathy is linked to altered hematopoiesis and dysregulated self-tolerance

Bardet–Biedl Syndrome (BBS) is a pleiotropic genetic disease caused by the dysfunction of primary cilia. The immune system of patients with ciliopathies has not been investigated. However, there are multiple indications that the impairment of the processes typically associated with cilia may have influence on the hematopoietic compartment and immunity. In this study, we analyze clinical data of BBS patients and corresponding mouse models carrying mutations in Bbs4 or Bbs18. We find that BBS patients have a higher prevalence of certain autoimmune diseases. Both BBS patients and animal models have altered red blood cell and platelet compartments, as well as elevated white blood cell levels. Some of the hematopoietic system alterations are associated with BBS‐induced obesity. Moreover, we observe that the development and homeostasis of B cells in mice is regulated by the transport complex BBSome, whose dysfunction is a common cause of BBS. The BBSome limits canonical WNT signaling and increases CXCL12 levels in bone marrow stromal cells. Taken together, our study reveals a connection between a ciliopathy and dysregulated immune and hematopoietic systems

'Reclaiming the criminal' : the role and training of prison officers in England, 1877-1914

This article examines the role and training of prison officers in England, between 1877 and 1914. It is concerned with the changing penal philosophies and practices of this period and how these were implemented in local prisons, and the duties of the prison officer. More broadly, this article argues that the role of the prison officer and their training (from 1896) reflect wider ambiguities in prison policy and practice during this period

A unified approach for the solution of the Fokker-Planck equation

This paper explores the use of a discrete singular convolution algorithm as a unified approach for numerical integration of the Fokker-Planck equation. The unified features of the discrete singular convolution algorithm are discussed. It is demonstrated that different implementations of the present algorithm, such as global, local, Galerkin, collocation, and finite difference, can be deduced from a single starting point. Three benchmark stochastic systems, the repulsive Wong process, the Black-Scholes equation and a genuine nonlinear model, are employed to illustrate the robustness and to test accuracy of the present approach for the solution of the Fokker-Planck equation via a time-dependent method. An additional example, the incompressible Euler equation, is used to further validate the present approach for more difficult problems. Numerical results indicate that the present unified approach is robust and accurate for solving the Fokker-Planck equation.Comment: 19 page

Dark-in-Bright Solitons in Bose-Einstein Condensates with Attractive Interactions

We demonstrate a possibility to generate localized states in effectively one-dimensional Bose-Einstein condensates with a negative scattering length in the form of a dark soliton in the presence of an optical lattice (OL) and/or a parabolic magnetic trap. We connect such structures with twisted localized modes (TLMs) that were previously found in the discrete nonlinear Schr{\"o}dinger equation. Families of these structures are found as functions of the OL strength, tightness of the magnetic trap, and chemical potential, and their stability regions are identified. Stable bound states of two TLMs are also found. In the case when the TLMs are unstable, their evolution is investigated by means of direct simulations, demonstrating that they transform into large-amplitude fundamental solitons. An analytical approach is also developed, showing that two or several fundamental solitons, with the phase shift $\pi$ between adjacent ones, may form stable bound states, with parameters quite close to those of the TLMs revealed by simulations. TLM structures are found numerically and explained analytically also in the case when the OL is absent, the condensate being confined only by the magnetic trap.Comment: 13 pages, 7 figures, New Journal of Physics (in press

Theory of Circle Maps and the Problem of One-Dimensional Optical Resonator with a Periodically Moving Wall

We consider the electromagnetic field in a cavity with a periodically oscillating perfectly reflecting boundary and show that the mathematical theory of circle maps leads to several physical predictions. Notably, well-known results in the theory of circle maps (which we review briefly) imply that there are intervals of parameters where the waves in the cavity get concentrated in wave packets whose energy grows exponentially. Even if these intervals are dense for typical motions of the reflecting boundary, in the complement there is a positive measure set of parameters where the energy remains bounded.Comment: 34 pages LaTeX (revtex) with eps figures, PACS: 02.30.Jr, 42.15.-i, 42.60.Da, 42.65.Y

Capsular profiling of the Cronobacter genus and the association of specific Cronobacter sakazakii and C. malonaticus capsule types with neonatal meningitis and necrotizing enterocolitis

Background: Cronobacter sakazakii and C. malonaticus can cause serious diseases especially in infants where they are associated with rare but fatal neonatal infections such as meningitis and necrotising enterocolitis. Methods: This study used 104 whole genome sequenced strains, covering all seven species in the genus, to analyse capsule associated clusters of genes involved in the biosynthesis of the O-antigen, colanic acid, bacterial cellulose, enterobacterial common antigen (ECA), and a previously uncharacterised K-antigen. Results: Phylogeny of the gnd and galF genes flanking the O-antigen region enabled the defining of 38 subgroups which are potential serotypes. Two variants of the colanic acid synthesis gene cluster (CA1 and CA2) were found which differed with the absence of galE in CA2. Cellulose (bcs genes) were present in all species, but were absent in C. sakazakii sequence type (ST) 13 and clonal complex (CC) 100 strains. The ECA locus was found in all strains. The K-antigen capsular polysaccharide Region 1 (kpsEDCS) and Region 3 (kpsMT) genes were found in all Cronobacter strains. The highly variable Region 2 genes were assigned to 2 homology groups (K1 and K2). C. sakazakii and C. malonaticus isolates with capsular type [K2:CA2:Cell+] were associated with neonatal meningitis and necrotizing enterocolitis. Other capsular types were less associated with clinical infections. Conclusion: This study proposes a new capsular typing scheme which identifies a possible important virulence trait associated with severe neonatal infections. The various capsular polysaccharide structures warrant further investigation as they could be relevant to macrophage survival, desiccation resistance, environmental survival, and biofilm formation in the hospital environment, including neonatal enteral feeding tubes

Algorithm for normal random numbers

We propose a simple algorithm for generating normally distributed pseudo random numbers. The algorithm simulates N molecules that exchange energy among themselves following a simple stochastic rule. We prove that the system is ergodic, and that a Maxwell like distribution that may be used as a source of normally distributed random deviates follows when N tends to infinity. The algorithm passes various performance tests, including Monte Carlo simulation of a finite 2D Ising model using Wolff's algorithm. It only requires four simple lines of computer code, and is approximately ten times faster than the Box-Muller algorithm.Comment: 5 pages, 3 encapsulated Postscript Figures. Submitted to Phys.Rev.Letters. For related work, see http://pipe.unizar.es/~jf