Properties of neutrality tests based on allele frequency spectrum

One of the main necessities for population geneticists is the availability of statistical tools that enable to accept or reject the neutral Wright-Fisher model with high power. A number of statistical tests have been developed to detect specific deviations from the null frequency spectrum in different directions (i.e., Tajima's D, Fu and Li's F and D test, Fay and Wu's H). Recently, a general framework was proposed to generate all neutrality tests that are linear functions of the frequency spectrum. In this framework, a family of optimal tests was developed to have almost maximum power against a specific alternative evolutionary scenario. Following these developments, in this paper we provide a thorough discussion of linear and nonlinear neutrality tests. First, we present the general framework for linear tests and emphasize the importance of the property of scalability with the sample size (that is, the results of the tests should not depend on the sample size), which, if missing, can guide to errors in data interpretation. The motivation and structure of linear optimal tests are discussed. In a further generalization, we develop a general framework for nonlinear neutrality tests and we derive nonlinear optimal tests for polynomials of any degree in the frequency spectrum.Comment: 42 pages, 3 figures, elsarticl

Does TCDD Exposure Alter β7-Integrin Expression on Mouse B Cells?

Activated aryl hydrocarbon receptor with ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters immune responses, including immunoglobulin A (IgA). Manipulation of antibody production via this ligand-activated receptor may provide a novel approach to enhance vaccination in the intestines. The present study aimed to explain the mechanism responsible for increased levels of fecal IgA in TCDD-treated mice. We hypothesized that TCDD enhances migration of B cells from non-intestinal tissue to the intestines. Here we predicted that β7-integrin, an essential protein for B cell migration into the intestines, would be upregulated by TCDD exposure on B cells. Female C57BL/6 mice were treated with a single dose of peanut oil (control) or TCDD at 40 µg/kg by gavage. After 1 week, splenic leukocytes were isolated and analyzed by flow cytometry. B cells in TCDD-treated mice did not express significantly higher β7-integrin levels than controls, although a significant increase of β7 integrin expression was observed on T cells. These results do not support our hypothesis; yet suggest that elevated β7 integrin expression allowed for preferential migration of B cells out of the spleen and into the intestines before analysis. In the future, we plan to address this possibility by examining β7 expression on B cells in the intestines

Spatiotemporal Stacked Sequential Learning for Pedestrian Detection

Pedestrian classifiers decide which image windows contain a pedestrian. In practice, such classifiers provide a relatively high response at neighbor windows overlapping a pedestrian, while the responses around potential false positives are expected to be lower. An analogous reasoning applies for image sequences. If there is a pedestrian located within a frame, the same pedestrian is expected to appear close to the same location in neighbor frames. Therefore, such a location has chances of receiving high classification scores during several frames, while false positives are expected to be more spurious. In this paper we propose to exploit such correlations for improving the accuracy of base pedestrian classifiers. In particular, we propose to use two-stage classifiers which not only rely on the image descriptors required by the base classifiers but also on the response of such base classifiers in a given spatiotemporal neighborhood. More specifically, we train pedestrian classifiers using a stacked sequential learning (SSL) paradigm. We use a new pedestrian dataset we have acquired from a car to evaluate our proposal at different frame rates. We also test on a well known dataset: Caltech. The obtained results show that our SSL proposal boosts detection accuracy significantly with a minimal impact on the computational cost. Interestingly, SSL improves more the accuracy at the most dangerous situations, i.e. when a pedestrian is close to the camera.Comment: 8 pages, 5 figure, 1 tabl

An integrative study of bird migration: From the migratory phenotype to its gene regulation mechanisms and back.

Life goes out of equilibrium; it is in constant movement. Animals, especially, move as part of their life cycle. An outstanding example is bird migration. Some birds adopt migration as a strategy to survive the harsh conditions of weather seasonality in temperate regions. Different sources of evidence indicate that seasonal migration is innate, and it can be inherited. Mutations in such heritable behaviour create an array of diversity in migratory traits: timing, orientation and distance. The diversity of migratory traits can affect ecological speciation. Migratory divides, for instance, are geographical areas where birds with different migratory orientations hybridise. If the differences in migratory behaviour are strong enough to create reproductive barriers, this could evolve into population divergence and eventually, speciation. However, to understand the potential processes of divergence caused by migratory behaviours, a crucial element is missing: the identity of the molecular mechanisms involved in migration. Genome-wide studies in bird species with migratory divides find several different genomic regions with species-specific signature. Similarly, gene expression approaches in different organs and species find groups of individual differentially expressed genes. These results suggest an intricate mechanism for the genetics of migration with potential species-specific characteristics. This thesis analyses the migratory behaviour from different angles spanning the phenotype to gene regulation, to contribute to the identification of mechanisms and evolution of migration. Most of the chapters of this thesis use the Eurasian blackcap ( Sylvia atricapilla) a species that comprise an extensive repertoire of orientation and distance traits, including entirely resident populations. With blackcaps, we studied the phenotypic variability of migration tracking individuals ithroughout the year (Chapter 2). We used light-level geolocators to obtain migratory routes of individuals from populations in Central Europe and the United Kingdom. We describe for the first time the orientation and timing patterns of individuals from a migratory divide and a recently adapted population in the UK. In chapter 4, we analyse the genomics and evolution patterns of blackcaps. Using whole-genome resequencing of populations covering all the differences in migratory traits, we describe population structure and demography in this species. We found that blackcaps show very little genomic differentiation. The most divergent populations are residents, while migratory populations comprise a single population at the genetic level. Chapter 5 is the first study of gene regulatory mechanisms in the context of bird migration. We characterised the chromatin accessibility landscape in three brain areas contrasting individuals during migration with individuals out of the migratory season. One of the findings is a general pattern of gene repression in relevant brain regions like the Cluster N. Moreover; we found cis-regulatory modules with particular evolutionary trajectories that may play a role in migration. Lastly, we did two comparative approaches to study macroevolutionary patterns related to migration. First, we analysed phylogenetic patterns and structural characteristics of previously proposed candidate genes (chapter 3). We found that the candidate genes do not have structural characteristics correlated with the presence of migration across the avian clade as it does within some species. The second comparative approach (Chapter 6), evaluates the repeatability patterns of genomic divergence in pairs of populations from migratory divides. Our results suggests that the degree of repeatability is mainly driven by how apart in the speciation continuum is the population pair located: if the pair is recently diverging, iifew repeatability is detected, while if the populations are further apart, repeatability is more plausible. Overall, this thesis highlights an essential feature for the study of complex traits like migration: integration of different sources of evidence. Ideally, in these cases, the analysis of phenotype, evolutionary patterns and regulatory mechanisms in the same individuals, should be the standard procedure. We are aware that this is an implausible scenario. However, the integration of different studies, help to guide the search of molecular elements involved in bird migration. This thesis is the first - at least that we are aware of - study compilating research on a variety of topics to understand bird migration. We are still far from getting a definitive understanding of bird migration. Nevertheless, confirming the heritability of the phenotype, describing macro and microevolutionary patterns of migration and specific regulatory elements, will improve the search for new candidate genes for this behaviou

Decomposing the site frequency spectrum: the impact of tree topology on neutrality tests

We investigate the dependence of the site frequency spectrum (SFS) on the topological structure of genealogical trees. We show that basic population genetic statistics - for instance estimators of $\theta$ or neutrality tests such as Tajima's $D$ - can be decomposed into components of waiting times between coalescent events and of tree topology. Our results clarify the relative impact of the two components on these statistics. We provide a rigorous interpretation of positive or negative values of an important class of neutrality tests in terms of the underlying tree shape. In particular, we show that values of Tajima's $D$ and Fay and Wu's $H$ depend in a direct way on a peculiar measure of tree balance which is mostly determined by the root balance of the tree. We present a new test for selection in the same class as Fay and Wu's $H$ and discuss its interpretation and power. Finally, we determine the trees corresponding to extreme expected values of these neutrality tests and present formulae for these extreme values as a function of sample size and number of segregating sites.Comment: 23 pages, 8 figure

The expected neutral frequency spectrum of linked sites

We present an exact, closed expression for the expected neutral Site Frequency Spectrum for two neutral sites, 2-SFS, without recombination. This spectrum is the immediate extension of the well known single site $\theta/f$ neutral SFS. Similar formulae are also provided for the case of the expected SFS of sites that are linked to a focal neutral mutation of known frequency. Formulae for finite samples are obtained by coalescent methods and remarkably simple expressions are derived for the SFS of a large population, which are also solutions of the multi-allelic Kolmogorov equations. Besides the general interest of these new spectra, they relate to interesting biological cases such as structural variants and introgressions. As an example, we present the expected neutral frequency spectrum of regions with a chromosomal inversion.Comment: 26 pages, 5 figure

Cálculo de la maquinaria de ordeño

La Norma UNE 68050:1998, publicada hace casi tres años, sustituye a la antigua Norma UNE de 1986. Al igual que ésta, la actual es equivalente a la Norma Internacional ISO 5707:1996 y viene a cubrir las necesidades que las nuevas instalaciones de ordeño, más grandes, con más elementos y con mayor consumo, estaban demandando. El nuevo procedimiento de cálculo se complica enormemente, al incorporar parámetro y variables no considerados anteriormente. Así, para el cálculo del diámetro de la conducción de leche se tiene en cuenta el número de unidades, el intervalo de colocación de las mismas, la pendiente con la que se instala, el flujo máximo de leche de las vacas, la forma de montaje, su longitud y las entradas intermitentes de aire. En el caso de la determinación del caudal de la bomba, el cálculo de las necesidades de aire para el lavado de la instalación es una novedad de la Norma, así como la consideración del consumo de los elementos auxiliares y una nueva fórmula para calcular la reserva real de la instalación. Finalmente, el diámetro interior de las conducciones de vacío se calcula en función de la longitud de las mismas, del material con que están fabricadas, la caída de vacío prevista y el caudal de aire que circula por ellas. Sin olvidar que se consideran las pérdidas de vacío que pueden provocar los codos de la tubería, las piezas especiales u otros recipientes de la instalación

Mlcoalsim: Multilocus Coalescent Simulations

Coalescent theory is a powerful tool for population geneticists as well as molecular biologists interested in understanding the patterns and levels of DNA variation. Using coalescent Monte Carlo simulations it is possible to obtain the empirical distributions for a number of statistics across a wide range of evolutionary models; these distributions can be used to test evolutionary hypotheses using experimental data. The mlcoalsim application presented here (based on a version of the ms program, Hudson, 2002) adds important new features to improve methodology (uncertainty and conditional methods for mutation and recombination), models (including strong positive selection, finite sites and heterogeneity in mutation and recombination rates) and analyses (calculating a number of statistics used in population genetics and P-values for observed data). One of the most important features of mlcoalsim is the analysis of multilocus data in linked and independent regions. In summary, mlcoalsim is an integrated software application aimed at researchers interested in molecular evolution. mlcoalsim is written in ANSI C and is available at: http://www.ub.es/softevol/mlcoalsim

The Cityscapes Dataset for Semantic Urban Scene Understanding

Visual understanding of complex urban street scenes is an enabling factor for a wide range of applications. Object detection has benefited enormously from large-scale datasets, especially in the context of deep learning. For semantic urban scene understanding, however, no current dataset adequately captures the complexity of real-world urban scenes. To address this, we introduce Cityscapes, a benchmark suite and large-scale dataset to train and test approaches for pixel-level and instance-level semantic labeling. Cityscapes is comprised of a large, diverse set of stereo video sequences recorded in streets from 50 different cities. 5000 of these images have high quality pixel-level annotations; 20000 additional images have coarse annotations to enable methods that leverage large volumes of weakly-labeled data. Crucially, our effort exceeds previous attempts in terms of dataset size, annotation richness, scene variability, and complexity. Our accompanying empirical study provides an in-depth analysis of the dataset characteristics, as well as a performance evaluation of several state-of-the-art approaches based on our benchmark.Comment: Includes supplemental materia