Evaluating statistical methods used to estimate the number of postsynaptic receptors.

Calcium levels in spines play a significant role in determining the sign and magnitude of synaptic plasticity. The magnitude of calcium influx into spines is highly dependent on influx through N-methyl D-aspartate (NMDA) receptors, and therefore depends on the number of postsynaptic NMDA receptors in each spine. We have calculated previously how the number of postsynaptic NMDA receptors determines the mean and variance of calcium transients in the postsynaptic density, and how this alters the shape of plasticity curves. However, the number of postsynaptic NMDA receptors in the postsynaptic density is not well known. Anatomical methods for estimating the number of NMDA receptors produce estimates that are very different than those produced by physiological techniques. The physiological techniques are based on the statistics of synaptic transmission and it is difficult to experimentally estimate their precision. In this paper we use stochastic simulations in order to test the validity of a physiological estimation technique based on failure analysis. We find that the method is likely to underestimate the number of postsynaptic NMDA receptors, explain the source of the error, and re-derive a more precise estimation technique. We also show that the original failure analysis as well as our improved formulas are not robust to small estimation errors in key parameters.

Estimating the Reproduction Number of Ebola Virus (EBOV) During the 2014 Outbreak in West Africa

The 2014 Ebola virus (EBOV) outbreak in West Africa is the largest outbreak of the genus Ebolavirus to date. To better understand the spread of infection in the affected countries, it is crucial to know the number of secondary cases generated by an infected index case in the absence and presence of control measures, i.e., the basic and effective reproduction number. In this study, I describe the EBOV epidemic using an SEIR (susceptible-exposed-infectious-recovered) model and fit the model to the most recent reported data of infected cases and deaths in Guinea, Sierra Leone and Liberia. The maximum likelihood estimates of the basic reproduction number are 1.51 (95% confidence interval [CI]: 1.50-1.52) for Guinea, 2.53 (95% CI: 2.41-2.67) for Sierra Leone and 1.59 (95% CI: 1.57-1.60) for Liberia. The model indicates that in Guinea and Sierra Leone the effective reproduction number might have dropped to around unity by the end of May and July 2014, respectively. In Liberia, however, the model estimates no decline in the effective reproduction number by end-August 2014. This suggests that control efforts in Liberia need to be improved substantially in order to stop the current outbreak.

Kubo relations and radiative corrections for lepton number washout

The rates for lepton number washout in extensions of the Standard Model containing right-handed neutrinos are key ingredients in scenarios for baryogenesis through leptogenesis. We relate these rates to real-time correlation functions at finite temperature, without making use of any particle approximations. The relations are valid to quadratic order in neutrino Yukawa couplings and to all orders in Standard Model couplings. They take into account all spectator processes, and apply both in the symmetric and in the Higgs phase of the electroweak theory. We use the relations to compute washout rates at next-to-leading order in g, where g denotes a Standard Model gauge or Yukawa coupling, both in the non-relativistic and in the relativistic regime. Even in the non-relativistic regime the parametrically dominant radiative corrections are only suppressed by a single power of g. In the non-relativistic regime radiative corrections increase the washout rate by a few percent at high temperatures, but they are of order unity around the weak scale and in the relativistic regime.

More volunteers in football clubs. An evaluation of a method to increase the number of volunteers

An increasing number of clubs experience difficulties in recruiting and retaining sufficient numbers of volunteers to manage and staff their clubs (Lamprecht, Fischer, & Stamm, 2012). In order to facilitate volunteer recruitment, sport clubs need a specific strategy to recruit and retain volunteers for both formal positions and ad hoc tasks. Therefore, the intervention “More Volunteers in Football Clubs” was designed and its impact was evaluated in detail. The question this evaluation research wants to address is: Can football clubs recruit and retain volunteers successfully by implementing the intervention “More Volunteers in Football Clubs”? The designed intervention is based on the different expectations and needs of volunteers, as well as non-profit human resource management and organisational development management, with a strong emphasis on club-specific counseling and support. Task forces of the twelve participating football clubs attended four workshops in which they received tailor made counseling to reach the desired number of volunteers. The intervention has been implemented and its effectiveness tested in cooperation with the Swiss Football Federation with twelve Swiss football clubs following a pretest, intervention, posttest design Data have been gathered and analysed using a combination of qualitative and quantitative methods. Outcome measurements are: volunteer rate, number of recruited volunteers, number of filled volunteer positions and volunteer satisfaction. Four months after the intervention all clubs that completed the proposed intervention were successful in recruiting the desired number of volunteers. Further, all participating clubs found the intervention helpful and would recommend other clubs to participate as well. With the development of this practical intervention a solution for football clubs is provided to overcome the difficulties in recruiting and retaining sufficient numbers of volunteers. Lamprecht, M., Fischer, A., & Stamm, H.-P. (2012). Sportvereine in der Schweiz. Strukturen, Leistungen, Herausforderungen. Zürich, Switzerland: Seismo.

Global diversity, population stratification and selection of human copy number variation

In order to explore the diversity and selective signatures of duplication and deletion human copy number variants (CNVs), we sequenced 236 individuals from 125 distinct human populations. We observed that duplications exhibit fundamentally different population genetic and selective signatures than deletions and are more likely to be stratified between human populations. Through reconstruction of the ancestral human genome, we identify megabases of DNA lost in different human lineages and pinpoint large duplications that introgressed from the extinct Denisova lineage now found at high frequency exclusively in Oceanic populations. We find that the proportion of CNV base pairs to single nucleotide variant base pairs is greater among non-Africans than it is among African populations, but we conclude that this difference is likely due to unique aspects of non-African population history as opposed to differences in CNV load.

Clinical relevance of polymorphic DNA copy number variation (CNV) in African American women with stage I-II breast cancer

Objectives. The chief goal of this study was to analyze copy number variation (CNV) in breast cancer tumors from 25 African American women with early stage breast cancer (BC) using molecular inversion probes (MIP) in order to: (1) compare the degree of CNV in tumors compared to normal lymph nodes, and (2) determine whether gains and/or losses of genes in specific chromosomes differ between pathologic subtypes of breast cancer defined by known prognostic markers, (3) determine whether gains/losses in CN are associated with known oncogenes or tumor suppressor genes, and (4) determine whether increased gains/losses in CN for specific chromosomes were associated with differences in breast cancer recurrence. ^ Methods. Twenty to 37 nanograms of DNA extracted from 25 formalin-fixed paraffin embedded (FFPE) tumor samples and matched normal lymph nodes were added to individual tubes. Oligonucleotide probes with recognition sequences at each terminus were hybridized with a genomic target sequence to form a circular structure. Probes are released from genomic DNA obtained from FFPE samples, and those which have been correctly "circularized" in the proper allele/nucleotide reaction combination are amplified using polymerase chain reaction (PCR) primers. Amplicons were fluorescently labeled and the tag sequences released from the genome homology regions by treatment with uracil-N-glycosylase to cleave the probe at the site where uracils are present, and detected using a complementary tag array developed by Affymetrix. ^ Results. Analysis of CN gains and losses from tumors and normal tissues showed marked differences in tumors with numerous chromosomes affected. Similar changes were not observed in normal lymph nodes. When tumors were stratified into four groups based on expression or lack of expression of the estrogen receptor and HER2/neu, distinct patterns of CNV for different chromosomes were observed. Gains or losses in CN for specific chromosomes correlated with amplifications/deletions of particular oncogenes or tumor suppressor genes (i.e. such as found on chromosome 17) known to be associated with aggressive tumor phenotype and poor prognosis. There was a trend for increases in CN observed for chromosome 17 to correlate inversely with time to recurrence of BC (p=0.14 for trend). CNV was also observed for chromosomes 5, 8, 10, 11, and 16, which are known sites for several breast cancer susceptibility alleles. ^ Conclusions. This study is the first to validate the MIP technique, to correlate differences in gene expression with known prognostic tumor markers, and to correlate significant increases/decreases in CN with known tumor markers associated with prognosis. The results of this study may have far reaching public health implications towards identifying new high-risk groups based on genomic differences in CNP, both with respect to prognosis and response to therapy, and to eventually identify new therapeutic targets for prevention and treatment of this disease. ^

Total number of benthic foraminifera in sediments below the K/T boundary in the Atlantic and Pacific Ocean

Most species of Late Cretaceous deep-sea benthic foraminifera are believed to be cosmopolitan and therefore to exhibit only minor biogeographical differences. In this preliminary report, six Deep Sea Drilling Project (DSDP) sites from different oceans, paleolatitudes, and paleodepths were analyzed for terminal Cretaceous abyssal-bathyal benthic foraminifera in order to investigate their assumed cosmopolitan distribution and the question of whether different faunal compositions are related to time, different paleolatitudes, and/or different paleodepths. The material studied was obtained from the low-latitude Site 465 (Pacific Ocean), and the intermediate-latitude Sites 384 (North Atlantic) and 356, 516, 525, and 527 (South Atlantic). The material analyzed represents a time slice encompassing the last 20-50 k.y. of the Cretaceous. The faunas contain numerous "Velasco-type" species, such as Gavelinella beccariiformis (White), Cibicidoides velascoensis (Cushman), Nuttallides truempyi (Nuttall), Gaudryina pyramidata Cushman, and various gyroidinoids and buliminids. The results contradict the general assumption of the cosmopolitan nature of Late Cretaceous deep-sea benthic foraminifera advocated in the literature. Only about 9% of the taxa identified were found to be truly "cosmopolitan" through their occurrence at all the sites analyzed. On the basis of correspondence analysis and relative abundance data, three assemblages and three subassemblages were recognized: (1) a bathyal-abyssal assemblage [Nuttallinella sp. A, Cibicidoides hyphalus (Fisher), Valvalabamina sp. evolute form, and Gyroidinoides spp.] at the South Atlantic Sites 356, 516, 525, and 527, divided into three subassemblages, namely (a) a middle bathyal subassemblage [Eouvigerina subsculptura McNeil and Caldwell, Truaxia aspera (Cushman), and G. pyramidata] at Sites 516 and 525, (b) a lower bathyal subassemblage [Osangularia? sp., Pyramidina rudita (Cushman and Parker), and Quadrimorphina camerata (Brotzen)] at Site 356, and (c) an abyssal subassemblage [Gyroidinoides sp. C, Hyperammina-Bathysiphon, Gyroidinoides beisseli (White), and Globorotalites sp. B] at Site 527; (2) an abyssal assemblage [Buliminella cf. plana (Cushman and Parker) and Bulimina incisa Cushman] at the North Atlantic Site 384; and (3) a middle bathyal assemblage [Vulvulina sp. A, Osangularia navarroana (Cushman), Alabamina? sp., Bulimina velascoensis (Cushman), Spiroplectammina spp. calcareous forms, and Bulimina trinitatensis Cushman and Jarvis] at the Pacific Site 465.

Neutrality in the choice of number of firms or level of fixed costs in calibrating an Armington-Krugman-Melitz encompassing module for applied general equilibrium models

This paper shows how an Armington-Krugman-Melitz encompassing module based on Dixon and Rimmer (2012) can be calibrated, and clarifies the choice of initial levels for two kinds of number of firms, or parameter values for two kinds of fixed costs, that enter a Melitz-type specification can be set freely to any preferred value, just as the cases we derive quantities from given value data assuming some of the initial prices to be unity. In consequence, only one kind of additional information, which is on the shape parameter related to productivity, just is required in order to incorporate Melitz-type monopolistic competition and heterogeneous firms into a standard applied general equilibrium model. To be a Krugman-type, nothing is needed. This enables model builders in applied economics to fully enjoy the featured properties of the theoretical models invented by Krugman (1980) and Melitz (2003) in practical policy simulations at low cost.

Reduced order models for industrial thermo-fluid problems

A new method is presented to generate reduced order models (ROMs) in Fluid Dynamics problems of industrial interest. The method is based on the expansion of the flow variables in a Proper Orthogonal Decomposition (POD) basis, calculated from a limited number of snapshots, which are obtained via Computational Fluid Dynamics (CFD). Then, the POD-mode amplitudes are calculated as minimizers of a properly defined overall residual of the equations and boundary conditions. The method includes various ingredients that are new in this field. The residual can be calculated using only a limited number of points in the flow field, which can be scattered either all over the whole computational domain or over a smaller projection window. The resulting ROM is both computationally efficient(reconstructed flow fields require, in cases that do not present shock waves, less than 1 % of the time needed to compute a full CFD solution) and flexible(the projection window can avoid regions of large localized CFD errors).Also, for problems related with aerodynamics, POD modes are obtained from a set of snapshots calculated by a CFD method based on the compressible Navier Stokes equations and a turbulence model (which further more includes some unphysical stabilizing terms that are included for purely numerical reasons), but projection onto the POD manifold is made using the inviscid Euler equations, which makes the method independent of the CFD scheme. In addition, shock waves are treated specifically in the POD description, to avoid the need of using a too large number of snapshots. Various definitions of the residual are also discussed, along with the number and distribution of snapshots, the number of retained modes, and the effect of CFD errors. The method is checked and discussed on several test problems that describe (i) heat transfer in the recirculation region downstream of a backwards facing step, (ii) the flow past a two-dimensional airfoil in both the subsonic and transonic regimes, and (iii) the flow past a three-dimensional horizontal tail plane. The method is both efficient and numerically robust in the sense that the computational effort is quite small compared to CFD and results are both reasonably accurate and largely insensitive to the definition of the residual, to CFD errors, and to the CFD method itself, which may contain artificial stabilizing terms. Thus, the method is amenable for practical engineering applications. Resumen Se presenta un nuevo método para generar modelos de orden reducido (ROMs) aplicado a problemas fluidodinámicos de interés industrial. El nuevo método se basa en la expansión de las variables fluidas en una base POD, calculada a partir de un cierto número de snapshots, los cuales se han obtenido gracias a simulaciones numéricas (CFD). A continuación, las amplitudes de los modos POD se calculan minimizando un residual global adecuadamente definido que combina las ecuaciones y las condiciones de contorno. El método incluye varios ingredientes que son nuevos en este campo de estudio. El residual puede calcularse utilizando únicamente un número limitado de puntos del campo fluido. Estos puntos puede encontrarse dispersos a lo largo del dominio computacional completo o sobre una ventana de proyección. El modelo ROM obtenido es tanto computacionalmente eficiente (en aquellos casos que no presentan ondas de choque reconstruir los campos fluidos requiere menos del 1% del tiempo necesario para calcular una solución CFD) como flexible (la ventana de proyección puede escogerse de forma que evite contener regiones con errores en la solución CFD localizados y grandes). Además, en problemas aerodinámicos, los modos POD se obtienen de un conjunto de snapshots calculados utilizando un código CFD basado en la versión compresible de las ecuaciones de Navier Stokes y un modelo de turbulencia (el cual puede incluir algunos términos estabilizadores sin sentido físico que se añaden por razones puramente numéricas), aunque la proyección en la variedad POD se hace utilizando las ecuaciones de Euler, lo que hace al método independiente del esquema utilizado en el código CFD. Además, las ondas de choque se tratan específicamente en la descripción POD para evitar la necesidad de utilizar un número demasiado grande de snapshots. Varias definiciones del residual se discuten, así como el número y distribución de los snapshots,el número de modos retenidos y el efecto de los errores debidos al CFD. El método se comprueba y discute para varios problemas de evaluación que describen (i) la transferencia de calor en la región de recirculación aguas abajo de un escalón, (ii) el flujo alrededor de un perfil bidimensional en regímenes subsónico y transónico y (iii) el flujo alrededor de un estabilizador horizontal tridimensional. El método es tanto eficiente como numéricamente robusto en el sentido de que el esfuerzo computacional es muy pequeño comparado con el requerido por el CFD y los resultados son razonablemente precisos y muy insensibles a la definición del residual, los errores debidos al CFD y al método CFD en sí mismo, el cual puede contener términos estabilizadores artificiales. Por lo tanto, el método puede utilizarse en aplicaciones prácticas de ingeniería.

Two Novel Methods For The Determination Of The Number Of Components In Independent Components Analysis Models

Independent Components Analysis is a Blind Source Separation method that aims to find the pure source signals mixed together in unknown proportions in the observed signals under study. It does this by searching for factors which are mutually statistically independent. It can thus be classified among the latent-variable based methods. Like other methods based on latent variables, a careful investigation has to be carried out to find out which factors are significant and which are not. Therefore, it is important to dispose of a validation procedure to decide on the optimal number of independent components to include in the final model. This can be made complicated by the fact that two consecutive models may differ in the order and signs of similarly-indexed ICs. As well, the structure of the extracted sources can change as a function of the number of factors calculated. Two methods for determining the optimal number of ICs are proposed in this article and applied to simulated and real datasets to demonstrate their performance.

Evidence of charge carrier number fluctuations in InN thin films?

Due to its small band-gap and its high mobility, InN is a promising material for a large number of key applications like band-gap engineering for high efficiency solar cells, light emitting diodes, and high speed devices. Unfortunately, it has been reported that this material exhibits strong surface charge accumulation which may depend on the type of surface. Current investigations are conducted in order to explain the mechanisms which govern such a behavior and to look for ways of avoiding it and/or finding applications that may use such an effect. In this framework, low frequency noise measurements have been performed at different temperatures on patterned MBE grown InN layers. The evolution of the 1/f noise level with temperature in the 77 K-300 K range is consistent with carrier number fluctuations thus indicating surface mechanisms: the surface charge accumulation is confirmed by the noise measurements.

An optimization method for conceptual design in engineering systems based on high order singular value decomposition

Se presenta un nuevo método de diseño conceptual en Ingeniería Aeronáutica basado el uso de modelos reducidos, también llamados modelos sustitutos (‘surrogates’). Los ingredientes de la función objetivo se calculan para cada indiviudo mediante la utilización de modelos sustitutos asociados a las distintas disciplinas técnicas que se construyen mediante definiciones de descomposición en valores singulares de alto orden (HOSVD) e interpolaciones unidimensionales. Estos modelos sustitutos se obtienen a partir de un número limitado de cálculos CFD. Los modelos sustitutos pueden combinarse, bien con un método de optimización global de tipo algoritmo genético, o con un método local de tipo gradiente. El método resultate es flexible a la par que mucho más eficiente, computacionalmente hablando, que los modelos convencionales basados en el cálculo directo de la función objetivo, especialmente si aparecen un gran número de parámetros de diseño y/o de modelado. El método se ilustra considerando una versión simplificada del diseño conceptual de un avión. Abstract An optimization method for conceptual design in Aeronautics is presented that is based on the use of surrogate models. The various ingredients in the target function are calculated for each individual using surrogates of the associated technical disciplines that are constructed via high order singular value decomposition and one dimensional interpolation. These surrogates result from a limited number of CFD calculated snapshots. The surrogates are combined with an optimization method, which can be either a global optimization method such as a genetic algorithm or a local optimization method, such as a gradient-like method. The resulting method is both flexible and much more computationally efficient than the conventional method based on direct calculation of the target function, especially if a large number of free design parameters and/or tunablemodeling parameters are present. The method is illustrated considering a simplified version of the conceptual design of an aircraft empennage.

Aerodynamic Analysis of Open Trailing Edge Airfoils at Low Reynolds Number

A study has been made on the influence of the open trailing edge in airfoils used in different devices relating their aerodynamic performances. Wind tunnel tests have been made at different Reynolds numbers and angles of attack in order to show this effect. Besides, a quantitative study of the aerodynamic properties has been made based on the different trailing edge thickness

Reduced order modeling of three dimensional external aerodynamic flows

A method is presented to construct computationally efficient reduced-order models (ROMs) of three-dimensional aerodynamic flows around commercial aircraft components. The method is based on the proper orthogonal decomposition (POD) of a set of steady snapshots, which are calculated using an industrial solver based on some Reynolds averaged Navier-Stokes (RANS) equations. The POD-mode amplitudes are calculated by minimizing a residual defined from the Euler equations, even though the snapshots themselves are calculated from viscous equations. This makes the ROM independent of the peculiarities of the solver used to calculate the snapshots. Also, both the POD modes and the residual are calculated using points in the computational mesh that are concentrated in a close vicinity of the aircraft, which constitute a much smaller number than the total number of mesh points. Despite these simplifications, the method provides quite good approximations of the flow variables distributions in the whole computational domain, including the boundary layer attached to the aircraft surface and the wake. Thus, the method is both robust and computationally efficient, which is checked considering the aerodynamic flow around a horizontal tail plane, in the transonic range 0.4?Mach number?0.8, ?3°?angle of attack?3°.

Self-consistent, nonlocal electron heat flux at arbitrary ion charge number

A single, nonlocal expression for the electron heat flux, which closely reproduces known results at high and low ion charge number 2, and “exact” results for the local limit at all 2, is derived by solving the kinetic equation in a narrow, tail-energy range. The solution involves asymptotic expansions of Bessel functions of large argument, and (Z-dependent)order above or below it, corresponding to the possible parabolic or hyperbolic character of the kinetic equation; velocity space diffusion in self-scattering is treated similarly to isotropic thermalization of tail energies in large Z analyses. The scale length H characterizing nonlocal effects varies with Z, suggesting an equal dependence of any ad hoc flux limiter. The model is valid for all H above the mean-free path for thermal electrons.