RAG-1 Mutations Associated with B-Cell-Negative SCID Dissociate the Nicking and Transesterification Steps of V(D)J Recombination

Some patients with B-cell-negative severe combined immune deficiency (SCID) carry mutations in RAG-1 or RAG-2 that impair V(D)J recombination. Two recessive RAG-1 mutations responsible for B-cell-negative SCID, R621H and E719K, impair V(D)J recombination without affecting formation of single-site recombination signal sequence complexes, specific DNA contacts, or perturbation of DNA structure at the heptamer-coding junction. The E719K mutation impairs DNA cleavage by the RAG complex, with a greater effect on nicking than on transesterification; a conservative glutamine substitution exhibits a similar effect. When cysteine is substituted for E719, RAG-1 activity is enhanced in Mn2+ but remains impaired in Mg2+, suggesting an interaction between this residue and an essential metal ion. The R621H mutation partially impairs nicking, with little effect on transesterification. The residual nicking activity of the R621H mutant is reduced at least 10-fold upon a change from pH 7.0 to pH 8.4. Site-specific nicking is severely impaired by an alanine substitution at R621 but is spared by substitution with lysine. These observations are consistent with involvement of a positively charged residue at position 621 in the nicking step of the RAG-mediated cleavage reaction. Our data provide a mechanistic explanation for one form of hereditary SCID. Moreover, while RAG-1 is directly involved in catalysis of both nicking and transesterification, our observations indicate that these two steps have distinct catalytic requirements

Financial Restrictions, Personal Income Tax (PIT) and Demand for a Permanent Home in a Dynamic Model. An analysis with Panel Data for Spain

This paper analyzes the way in which income tax and liquidity determine the purchase or rental of a permanent home in Spain. To do this, we have developed a theoretical dynamic model based on Euler’s equation. This model is verified using a sample from the 1991-1995 Panel of income taxpayers. Results suggest that the degree of financial restriction is the most relevant variable when determining the possibility of purchasing a home, while tax incentives increase their relative weighting once this asset has been acquired. Incentives for renting a home are relatively insignificant particularly for taxpayers who habitually rent their homes.personal income tax, liquidity, permanent home, tax incentives

Theory and implementation of H\mathcal{H}-matrix based iterative and direct solvers for Helmholtz and elastodynamic oscillatory kernels

In this work, we study the accuracy and efficiency of hierarchical matrix ($\mathcal{H}$-matrix) based fast methods for solving dense linear systems arising from the discretization of the 3D elastodynamic Green's tensors. It is well known in the literature that standard $\mathcal{H}$-matrix based methods, although very efficient tools for asymptotically smooth kernels, are not optimal for oscillatory kernels. $\mathcal{H}^2$-matrix and directional approaches have been proposed to overcome this problem. However the implementation of such methods is much more involved than the standard $\mathcal{H}$-matrix representation. The central questions we address are twofold. (i) What is the frequency-range in which the $\mathcal{H}$-matrix format is an efficient representation for 3D elastodynamic problems? (ii) What can be expected of such an approach to model problems in mechanical engineering? We show that even though the method is not optimal (in the sense that more involved representations can lead to faster algorithms) an efficient solver can be easily developed. The capabilities of the method are illustrated on numerical examples using the Boundary Element Method

Metáfora

Tercer premio del Certame

Pattern formation induced by a differential shear flow

Fluid flow advecting one substance while others are immobilized can generate an instability in a homogeneous steady state of a reaction-diffusion-advection system. This differential-flow instability leads to the formation of steady spatial patterns in a moving reference frame. We study the effects of shear flow on this instability by considering two layers of fluid moving independently from each other, but allowing the substances to diffuse along and across the layers.We find that shear flow can generate instabilities even if the average flow velocity is zero for both substances. These instabilities are strongly dependent on which substance is advected by the shear flow.We explain these effects using the results of Taylor dispersion, where an effective diffusivity is enhanced by shear flow

The possibility of a “quantum neuroscience” in according to Roger Penrose

El artículo expone los elementos fundamentales de la “interpretación Penrose-Hameroff” sobre el colapso de función de onda, un hecho de la física cuántica estándar, que los autores introducen en neurofisiología a través de la llamada “teoría de la reducción objetiva orquestada”. La consecuencia de este postulado es un planteamiento novedoso que abre nuevas vías de investigación en la disciplina incipiente de la “nano-fisología”, con importantes aportaciones a la cuestión mente-cerebro y las neurociencias en general.This article presents the elements of the “interpretation of Penrose-Hameroff” about the collapse of wave function. Which it´s a fact of standard quantum physics, that was introduced into neurophysiology through the hypothesis of “orchestrated objective reduction” (Orch-OR). The consequence of this postulate is a new approach that opens up new lines of research in the emerging discipline of “nano-physiology”, with important contributions to the mind-brain question and neuroscience in general