Pulmonary cryptococcosis induces chitinase in the rat

<p>Abstract</p> <p>Background</p> <p>We previously demonstrated that chronic pulmonary infection with <it>Cryptococcus neoformans </it>results in enhanced allergic inflammation and airway hyperreactivity in a rat model. Because the cell wall of <it>C. neoformans </it>consists of chitin, and since acidic mammalian chitinase (AMCase) has recently been implicated as a novel mediator of asthma, we sought to determine whether such infection induces chitinase activity and expression of AMCase in the rat.</p> <p>Methods</p> <p>We utilized a previously-established model of chronic <it>C. neoformans </it>pulmonary infection in the rat to analyze the activity, expression and localization of AMCase.</p> <p>Results</p> <p>Our studies indicate that intratracheal inoculation of <it>C. neoformans </it>induces chitinase activity within the lung and bronchoalveolar lavage fluid of infected rats. Chitinase activity is also elicited by pulmonary infection with other fungi (e.g. <it>C. albicans</it>), but not by the inoculation of dead organisms. Enhanced chitinase activity reflects increased AMCase expression by airway epithelial cells and alveolar macrophages. Systemic cryptococcosis is not associated with increased pulmonary chitinase activity or AMCase expression.</p> <p>Conclusion</p> <p>Our findings indicate a possible link between respiratory fungal infections, including <it>C. neoformans</it>, and asthma through the induction of AMCase.</p

An elliptically symmetric angular Gaussian distribution

We define a distribution on the unit sphere Sd−1 called the elliptically symmetric angular Gaussian distribution. This distribution, which to our knowledge has not been studied before, is a subfamily of the angular Gaussian distribution closely analogous to the Kent subfamily of the general Fisher–Bingham distribution. Like the Kent distribution, it has elliptical contours, enabling modelling of rotational asymmetry about the mean direction, but it has the additional advantages of being simple and fast to simulate from, and having a density and hence likelihood that is easy and very quick to compute exactly. These advantages are especially beneficial for computationally intensive statistical methods, one example of which is a parametric bootstrap procedure for inference for the directional mean that we describe

Simulation of impulse response for indoor visible light communications using 3D CAD models

n this article, a tool for simulating the channel impulse response for indoor visible light communications using 3D computer-aided design (CAD) models is presented. The simulation tool is based on a previous Monte Carlo ray-tracing algorithm for indoor infrared channel estimation, but including wavelength response evaluation. The 3D scene, or the simulation environment, can be defined using any CAD software in which the user specifies, in addition to the setting geometry, the reflection characteristics of the surface materials as well as the structures of the emitters and receivers involved in the simulation. Also, in an effort to improve the computational efficiency, two optimizations are proposed. The first one consists of dividing the setting into cubic regions of equal size, which offers a calculation improvement of approximately 50% compared to not dividing the 3D scene into sub-regions. The second one involves the parallelization of the simulation algorithm, which provides a computational speed-up proportional to the number of processors used

Widespread sex differences in gene expression and splicing in the adult human brain

There is strong evidence to show that men and women differ in terms of neurodevelopment, neurochemistry and susceptibility to neurodegenerative and neuropsychiatric disease. The molecular basis of these differences remains unclear. Progress in this field has been hampered by the lack of genome-wide information on sex differences in gene expression and in particular splicing in the human brain. Here we address this issue by using post-mortem adult human brain and spinal cord samples originating from 137 neuropathologically confirmed control individuals to study whole-genome gene expression and splicing in 12 CNS regions. We show that sex differences in gene expression and splicing are widespread in adult human brain, being detectable in all major brain regions and involving 2.5% of all expressed genes. We give examples of genes where sex-biased expression is both disease-relevant and likely to have functional consequences, and provide evidence suggesting that sex biases in expression may reflect sex-biased gene regulatory structures

A Jacobi-Davidson type method with a correction equation tailored for integral operators

The final publication is available at Springer via http://dx.doi.org/10.1007/s11075-012-9656-9We propose two iterative numerical methods for eigenvalue computations of large dimensional problems arising from finite approximations of integral operators, and describe their parallel implementation. A matrix representation of the problem on a space of moderate dimension, defined from an infinite dimensional one, is computed along with its eigenpairs. These are taken as initial approximations and iteratively refined, by means of a correction equation based on the reduced resolvent operator and performed on the moderate size space, to enhance their quality. Each refinement step requires the prolongation of the correction equation solution back to a higher dimensional space, defined from the infinite dimensional one. This approach is particularly adapted for the computation of eigenpair approximations of integral operators, where prolongation and restriction matrices can be easily built making a bridge between coarser and finer discretizations. We propose two methods that apply a Jacobi–Davidson like correction: Multipower Defect-Correction (MPDC), which uses a single-vector scheme, if the eigenvalues to refine are simple, and Rayleigh–Ritz Defect-Correction (RRDC), which is based on a projection onto an expanding subspace. Their main advantage lies in the fact that the correction equation is performed on a smaller space while for general solvers it is done on the higher dimensional one. We discuss implementation and parallelization details, using the PETSc and SLEPc packages. Also, numerical results on an astrophysics application, whose mathematical model involves a weakly singular integral operator, are presented.This work was partially supported by European Regional Development Fund through COMPETE, FCT-Fundacao para a Ciencia e a Tecnologia through CMUP-Centro de Matematica da Universidade do Porto and Spanish Ministerio de Ciencia e Innovacion under projects TIN2009-07519 and AIC10-D-000600.Vasconcelos, PB.; D'almeida, FD.; Román Moltó, JE. (2013). A Jacobi-Davidson type method with a correction equation tailored for integral operators. Numerical Algorithms. 64(1):85-103. doi:10.1007/s11075-012-9656-9S85103641Absil, P.A., Mahony, R., Sepulchre, R., Dooren, P.V.: A Grassmann–Rayleigh quotient iteration for computing invariant subspaces. SIAM Rev. 44(1), 57–73 (2002)Ahues, M., Largillier, A., Limaye, B.V.: Spectral Computations with Bounded Operators. Chapman and Hall, Boca Raton (2001)Ahues, M., d’Almeida, F.D., Largillier, A., Titaud, O., Vasconcelos, P.: An L 1 refined projection approximate solution of the radiation transfer equation in stellar atmospheres. J. Comput. Appl. Math. 140(1–2), 13–26 (2002)Ahues, M., d’Almeida, F.D., Largillier, A., Vasconcelos, P.B.: Defect correction for spectral computations for a singular integral operator. Commun. Pure Appl. Anal. 5(2), 241–250 (2006)Bai, Z., Demmel, J., Dongarra, J., Ruhe, A., van der Vorst, H. (eds.): Templates for the Solution of Algebraic Eigenvalue Problems: A Practical Guide. Society for Industrial and Applied Mathematics, Philadelphia (2000)Balay, S., Buschelman, K., Eijkhout, V., Gropp, W.D., Kaushik, D., Knepley, M., McInnes, L.C., Smith, B.F., Zhang, H.: PETSc Users Manual. Tech. Rep. ANL-95/11 - Revision 3.1, Argonne National Laboratory (2010)Chatelin, F.: Spectral Approximation of Linear Operators. SIAM, Philadelphia (2011)d’Almeida, F.D., Vasconcelos, P.B.: Convergence of multipower defect correction for spectral computations of integral operators. Appl. Math. Comput. 219(4), 1601–1606 (2012)Falgout, R.D., Yang, U.M.: Hypre: A library of high performance preconditioners. In: Sloot, P.M.A., Tan, C.J.K., Dongarra, J., Hoekstra, A.G. (eds.) Computational Science - ICCS 2002, International Conference, Amsterdam, The Netherlands, April 21–24, 2002. Proceedings, Part III, Lecture Notes in Computer Science, vol. 2331, pp. 632–641. Springer (2002)Henson, V.E., Yang, U.M.: BoomerAMG: A parallel algebraic multigrid solver and preconditioner. Appl. Numer. Math. 41(1), 155–177 (2002)Hernandez, V., Roman, J.E., Vidal, V.: SLEPc: A scalable and flexible toolkit for the solution of eigenvalue problems. ACM Trans. Math. Softw. 31(3), 351–362 (2005)Hernandez, V., Roman, J.E., Tomas, A., Vidal, V.: SLEPc Users Manual. Tech. Rep. DSIC-II/24/02 - Revision 3.1, D. Sistemas Informáticos y Computación, Universidad Politécnica de Valencia (2010)Saad, Y.: Iterative methods for sparse linear systems, 2nd edn. Society for Industrial and Applied Mathematics, Philadelphia (2003)Simoncini, V., Eldén, L.: Inexact Rayleigh quotient-type methods for eigenvalue computations. BIT 42(1), 159–182 (2002)Sleijpen, G.L.G., van der Vorst, H.A.: A Jacobi–Davidson iteration method for linear eigenvalue problems. SIAM Rev. 42(2), 267–293 (2000)Sorensen, D.C.: Implicit application of polynomial filters in a k-step Arnoldi method. SIAM J. Matrix Anal. Appl. 13, 357–385 (1992)Stewart, G.W.: A Krylov–Schur algorithm for large eigenproblems. SIAM J. Matrix Anal. Appl. 23(3), 601–614 (2001

Microtubules gate tau condensation to spatially regulate microtubule functions.

Tau is an abundant microtubule-associated protein in neurons. Tau aggregation into insoluble fibrils is a hallmark of Alzheimer's disease and other types of dementia1, yet the physiological state of tau molecules within cells remains unclear. Using single-molecule imaging, we directly observe that the microtubule lattice regulates reversible tau self-association, leading to localized, dynamic condensation of tau molecules on the microtubule surface. Tau condensates form selectively permissible barriers, spatially regulating the activity of microtubule-severing enzymes and the movement of molecular motors through their boundaries. We propose that reversible self-association of tau molecules, gated by the microtubule lattice, is an important mechanism of the biological functions of tau, and that oligomerization of tau is a common property shared between the physiological and disease-associated forms of the molecule

Strings in AdS_4 x CP^3: finite size spectrum vs. Bethe Ansatz

We compute the first curvature corrections to the spectrum of light-cone gauge type IIA string theory that arise in the expansion of $AdS_4\times \mathbb{CP}^3$ about a plane-wave limit. The resulting spectrum is shown to match precisely, both in magnitude and degeneration that of the corresponding solutions of the all-loop Gromov--Vieira Bethe Ansatz. The one-loop dispersion relation correction is calculated for all the single oscillator states of the theory, with the level matching condition lifted. It is shown to have all logarithmic divergences cancelled and to leave only a finite exponentially suppressed contribution, as shown earlier for light bosons. We argue that there is no ambiguity in the choice of the regularization for the self-energy sum, since the regularization applied is the only one preserving unitarity. Interaction matrices in the full degenerate two-oscillator sector are calculated and the spectrum of all two light magnon oscillators is completely determined. The same finite-size corrections, at the order 1/J, where $J$ is the length of the chain, in the two-magnon sector are calculated from the all loop Bethe Ansatz. The corrections obtained by the two completely different methods coincide up to the fourth order in $\lambda' =\lambda/J^2$. We conjecture that the equivalence extends to all orders in $\lambda$ and to higher orders in 1/J.Comment: 32 pages. Published version; journal reference adde

Quantitative trait loci conferring grain mineral nutrient concentrations in durum wheat 3 wild emmer wheat RIL population

Mineral nutrient malnutrition, and particularly deficiency in zinc and iron, afflicts over 3 billion people worldwide. Wild emmer wheat, Triticum turgidum ssp. dicoccoides, genepool harbors a rich allelic repertoire for mineral nutrients in the grain. The genetic and physiological basis of grain protein, micronutrients (zinc, iron, copper and manganese) and macronutrients (calcium, magnesium, potassium, phosphorus and sulfur) concentration was studied in tetraploid wheat population of 152 recombinant inbred lines (RILs), derived from a cross between durum wheat (cv. Langdon) and wild emmer (accession G18-16). Wide genetic variation was found among the RILs for all grain minerals, with considerable transgressive effect. A total of 82 QTLs were mapped for 10 minerals with LOD score range of 3.2–16.7. Most QTLs were in favor of the wild allele (50 QTLs). Fourteen pairs of QTLs for the same trait were mapped to seemingly homoeologous positions, reflecting synteny between the A and B genomes. Significant positive correlation was found between grain protein concentration (GPC), Zn, Fe and Cu, which was supported by significant overlap between the respective QTLs, suggesting common physiological and/or genetic factors controlling the concentrations of these mineral nutrients. Few genomic regions (chromosomes 2A, 5A, 6B and 7A) were found to harbor clusters of QTLs for GPC and other nutrients. These identified QTLs may facilitate the use of wild alleles for improving grain nutritional quality of elite wheat cultivars, especially in terms of protein, Zn and Fe

Spatial heterogeneity of habitat suitability for Rift Valley fever occurrence in Tanzania: an ecological niche modelling approach

Despite the long history of Rift Valley fever (RVF) in Tanzania, extent of its suitable habitat in the country remains unclear. In this study we investigated potential effects of temperature, precipitation, elevation, soil type, livestock density, rainfall pattern, proximity to wild animals, protected areas and forest on the habitat suitability for RVF occurrence in Tanzania. Presence-only records of 193 RVF outbreak locations from 1930 to 2007 together with potential predictor variables were used to model and map the suitable habitats for RVF occurrence using ecological niche modelling. Ground-truthing of the model outputs was conducted by comparing the levels of RVF virus specific antibodies in cattle, sheep and goats sampled from locations in Tanzania that presented different predicted habitat suitability values. Habitat suitability values for RVF occurrence were higher in the northern and central-eastern regions of Tanzania than the rest of the regions in the country. Soil type and precipitation of the wettest quarter contributed equally to habitat suitability (32.4% each), followed by livestock density (25.9%) and rainfall pattern (9.3%). Ground-truthing of model outputs revealed that the odds of an animal being seropositive for RVFV when sampled from areas predicted to be most suitable for RVF occurrence were twice the odds of an animal sampled from areas least suitable for RVF occurrence (95% CI: 1.43, 2.76, p < 0.001). The regions in the northern and central-eastern Tanzania were more suitable for RVF occurrence than the rest of the regions in the country. The modelled suitable habitat is characterised by impermeable soils, moderate precipitation in the wettest quarter, high livestock density and a bimodal rainfall pattern. The findings of this study should provide guidance for the design of appropriate RVF surveillance, prevention and control strategies which target areas with these characteristics