Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques.

HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across mucosal epithelium to infect CD4+ T cells. Although broadly neutralizing antibodies (bnAbs) are the type of HIV-1 antibodies that are most likely protective, they are not induced with current vaccine candidates. In contrast, antibodies that do not neutralize primary HIV-1 strains in the TZM-bl infection assay are readily induced by current vaccine candidates and have also been implicated as secondary correlates of decreased HIV-1 risk in the RV144 vaccine efficacy trial. Here, we have studied the capacity of anti-Env monoclonal antibodies (mAbs) against either the immunodominant region of gp41 (7B2 IgG1), the first constant region of gp120 (A32 IgG1), or the third variable loop (V3) of gp120 (CH22 IgG1) to modulate in vivo rectal mucosal transmission of a high-dose simian-human immunodeficiency virus (SHIV-BaL) in rhesus macaques. 7B2 IgG1 or A32 IgG1, each containing mutations to enhance Fc function, was administered passively to rhesus macaques but afforded no protection against productive clinical infection while the positive control antibody CH22 IgG1 prevented infection in 4 of 6 animals. Enumeration of transmitted/founder (T/F) viruses revealed that passive infusion of each of the three antibodies significantly reduced the number of T/F genomes. Thus, some antibodies that bind HIV-1 Env but fail to neutralize virus in traditional neutralization assays may limit the number of T/F viruses involved in transmission without leading to enhancement of viral infection. For one of these mAbs, gp41 mAb 7B2, we provide the first co-crystal structure in complex with a common cyclical loop motif demonstrated to be critical for infection by other retroviruses.

Comparative analyses of seven algorithms for copy number variant identification from single nucleotide polymorphism arrays.

Determination of copy number variants (CNVs) inferred in genome wide single nucleotide polymorphism arrays has shown increasing utility in genetic variant disease associations. Several CNV detection methods are available, but differences in CNV call thresholds and characteristics exist. We evaluated the relative performance of seven methods: circular binary segmentation, CNVFinder, cnvPartition, gain and loss of DNA, Nexus algorithms, PennCNV and QuantiSNP. Tested data included real and simulated Illumina HumHap 550 data from the Singapore cohort study of the risk factors for Myopia (SCORM) and simulated data from Affymetrix 6.0 and platform-independent distributions. The normalized singleton ratio (NSR) is proposed as a metric for parameter optimization before enacting full analysis. We used 10 SCORM samples for optimizing parameter settings for each method and then evaluated method performance at optimal parameters using 100 SCORM samples. The statistical power, false positive rates, and receiver operating characteristic (ROC) curve residuals were evaluated by simulation studies. Optimal parameters, as determined by NSR and ROC curve residuals, were consistent across datasets. QuantiSNP outperformed other methods based on ROC curve residuals over most datasets. Nexus Rank and SNPRank have low specificity and high power. Nexus Rank calls oversized CNVs. PennCNV detects one of the fewest numbers of CNVs.

Ill-Posedness, Regularization and Number of Degrees of Freedom

info:eu-repo/semantics/published

Superresolution and number of degrees of freedom in inverse diffraction with subwavelength sources

info:eu-repo/semantics/published

Number of degrees of freedom in inverse diffraction

The problem of inverse diffraction from plane to plane is considered in the case where a finite aperture exists in the boundary plane. Singular values and singular functions for the problem are introduced, and the number of degrees of freedom is defined in terms of the distribution of the singular values. Numerical computations are presented for the one-dimensional problem, and it is shown that the effect of evanescent waves disappears at a distance of approximately one wavelength from the boundary plane, even when the dimension of the slit is comparable with the wavelength of the diffracted field. © 1983 Taylor & Francis Group, LLC.

High number of antigen binding cells in unimmunized mice and possible occurrence of multispecific lymphocytes

A high frequency of Tobacco Mosaic virus (TMV) binding cells was found in spleen cells from unimmunized mice (about 3 to 4%). TMV binding is strongly inhibited by previous incubation with anti immunoglobulin antisera. After stripping of membrane receptors, a full recovery for antigen binding capacity can be observed after 24 hr culture. Experiments are presented to exclude artefactual fluorescent cells: interaction of TMV with some non immunoglobulin membrane components; interaction of fluorescent anti TMV antibody with the Fc receptor of B cells; the binding of TMV to cytophilic immunoglobulins. The occurrence of lymphocytes able to bind several non crossreactive antigens is suggested by three lines of evidence: the high number of antigen binding cells in unimmunized mice, presence of surface immunoglobulins on some TMV binding cells after complete capping of TMV receptors and the direct demonstration of lymphocytes binding TMV and hemocyanin at different membrane sites.

Difficulties and errors in number reasoning development

The detailed study of difficulties and errors in young learner comprehension is a relevant and productive research field in Mathematics Education. Studies in the field are numerous although somewhat too varied. The present paper is suggesting methodological perspectives and principles applying to the field of research; we also show an example with school work. The use of figurate numbers as a representation system gives richer conceptual values, boosts visual reasoning and facilitates learner understanding.

El problema de basilea. El año de Euler: 1707-2007

El pasado 15 de abril se cumplían 300 años del nacimiento de uno de los cuatro matemáticos más geniales de la historia, Leonhard Euler. Para mí, los otros tres, y que cada cual elija su orden, son Arquímedes, Newton y Gauss. Si la calificación la hiciésemos atendiendo a la cantidad de los trabajos de primer orden realizados por cada uno de ellos, sin duda Euler ocuparía el primer lugar. A lo largo de su extensa vida Euler produjo más de ochocientos libros y miles de artículos y trabajos. Sus obras completas Opera Omnia ocupan más de 80 volúmenes. Sin lugar a dudas es el matemático más prolífico de la Historia. Pero, con ser importante la cantidad de trabajos, el aprecio de los matemáticos contemporáneos y posteriores a él se debe más a la riqueza, originalidad, belleza y genial agudeza de su obra que a su volumen.

Euler y el número π

Uno de los más prolíficos matemáticos, sino el que más, que han existido a lo largo de toda la historia, ha sido el suizo Leonhard Euler (1707-1783). Además de, en nuestro caso, introducir el uso de la letra griega π (inicial de perímetro) para nuestro número, dió numerosas aproximaciones mediante desarrollos en serie de la relación existente entre la circunferencia y su diámetro. El presente articulo trata de explicar el ingenioso procedimiento de dos de dichas series: la serie de Jacques Bernouilli y, la serie de Leibniz.

Recta de Euler en cuadriláteros

El circuncentro (O), baricentro (G) y ortocentro (H) de todo triangulo estan alineados en la recta de Euler y verifican la relación mGH = 2 · mOG. En el presente artıculo se define baricentro (G) y ortocentro (H) de un cuadrilátero inscriptible de circuncentro (O) y se demuestra que dichos puntos están alineados y verifican la relación mGH = 3 · mOG.

Revisiting the carrier-phase source-term formulation in mixed Lagrangian-Eulerian particle models

The formulation of the carrier-phase momentum and enthalpy source terms in mixed Lagrangian-Eulerian models of particle-laden flows is frequently reported inaccurately. Under certain circumstances, this can lead to erroneous implementations, which violate physical laws. A particle- rather than carrier-based approach is suggested for a consistent treatment of these terms.

Monotone scheme and boundary conditions for finite volume simulation of magnetohydrodynamic internal flows at high Hartmann number

A monotone scheme for finite volume simulation of magnetohydrodynamic internal flows at high Hartmann number is presented. The numerical stability is analysed with respect to the electromagnetic force. Standard central finite differences applied to finite volumes can only be numerically stable if the vector products involved in this force are computed with a scheme using a fully staggered grid. The electromagnetic quantities (electric currents and electric potential) must be shifted by half the grid size from the mechanical ones (velocity and pressure). An integral treatment of the boundary layers is used in conjunction with boundary conditions for electrically conducting walls. The simulations are performed with inhomogeneous electrical conductivities of the walls and reach high Hartmann numbers in three-dimensional simulations, even though a non-adaptive grid is used.

The implementation of an aeronautical CFD flow code onto distributed memory parallel systems

The parallelization of an industrially important in-house computational fluid dynamics (CFD) code for calculating the airflow over complex aircraft configurations using the Euler or Navier–Stokes equations is presented. The code discussed is the flow solver module of the SAUNA CFD suite. This suite uses a novel grid system that may include block-structured hexahedral or pyramidal grids, unstructured tetrahedral grids or a hybrid combination of both. To assist in the rapid convergence to a solution, a number of convergence acceleration techniques are employed including implicit residual smoothing and a multigrid full approximation storage scheme (FAS). Key features of the parallelization approach are the use of domain decomposition and encapsulated message passing to enable the execution in parallel using a single programme multiple data (SPMD) paradigm. In the case where a hybrid grid is used, a unified grid partitioning scheme is employed to define the decomposition of the mesh. The parallel code has been tested using both structured and hybrid grids on a number of different distributed memory parallel systems and is now routinely used to perform industrial scale aeronautical simulations. Copyright © 2000 John Wiley & Sons, Ltd.

Viscoelastic flow through a planar contraction using a semi-Lagrangian finite volume method

A semi-Lagrangian finite volume scheme for solving viscoelastic flow problems is presented. A staggered grid arrangement is used in which the dependent variables are located at different mesh points in the computational domain. The convection terms in the momentum and constitutive equations are treated using a semi-Lagrangian approach in which particles on a regular grid are traced backwards over a single time-step. The method is applied to the 4 : 1 planar contraction problem for an Oldroyd B fluid for both creeping and inertial flow conditions. The development of vortex behaviour with increasing values of We is analyzed.