Asymptotically distribution-free goodness-of-fit testing for tail copulas

Let $(X_1,Y_1),\ldots,(X_n,Y_n)$ be an i.i.d. sample from a bivariate distribution function that lies in the max-domain of attraction of an extreme value distribution. The asymptotic joint distribution of the standardized component-wise maxima $\bigvee_{i=1}^nX_i$ and $\bigvee_{i=1}^nY_i$ is then characterized by the marginal extreme value indices and the tail copula $R$. We propose a procedure for constructing asymptotically distribution-free goodness-of-fit tests for the tail copula $R$. The procedure is based on a transformation of a suitable empirical process derived from a semi-parametric estimator of $R$. The transformed empirical process converges weakly to a standard Wiener process, paving the way for a multitude of asymptotically distribution-free goodness-of-fit tests. We also extend our results to the $m$-variate ($m>2$) case. In a simulation study we show that the limit theorems provide good approximations for finite samples and that tests based on the transformed empirical process have high power.Comment: Published at http://dx.doi.org/10.1214/14-AOS1304 in the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Mesenchymal Cells Affect Salivary Epithelial Cell Morphology on PGS/PLGA Core/Shell Nanofibers

Engineering salivary glands is of interest due to the damaging effects of radiation therapy and the autoimmune disease Sjögren’s syndrome on salivary gland function. One of the current problems in tissue engineering is that in vitro studies often fail to predict in vivo regeneration due to failure of cells to interact with scaffolds and of the single cell types that are typically used for these studies. Although poly (lactic co glycolic acid) (PLGA) nanofiber scaffolds have been used for in vitro growth of epithelial cells, PLGA has low compliance and cells do not penetrate the scaffolds. Using a core-shell electrospinning technique, we incorporated poly (glycerol sebacate) (PGS) into PLGA scaffolds to increase the compliance and decrease hydrophobicity. PGS/PLGA scaffolds promoted epithelial cell penetration into the scaffold and apical localization of tight junction proteins, which is necessary for epithelial cell function. Additionally, co-culture of the salivary epithelial cells with NIH3T3 mesenchymal cells on PGS/PLGA scaffolds facilitated epithelial tissue reorganization and apical localization of tight junction proteins significantly more than in the absence of the mesenchyme. These data demonstrate the applicability of PGS/PLGA nanofibers for epithelial cell self-organization and facilitation of co-culture cell interactions that promote tissue self-organization in vitro

Molecular genotyping of bacillus anthracis strains from Georgia and northeastern part of Turkey

Bacillus anthracis is the causal agent of anthrax and has a history of use as a biological weapon. Anthrax cases occur worldwide and the disease is endemic in certain regions. Here we describe a study of the genetic diversity of B. anthracis strains in two endemic areas: The country of Georgia and the Kars region of Turkey. Thirty Turkish isolates and thirty Georgian isolates were subjected to Single Nucleotide Polymorphism (SNP) sub typing, followed by higher-resolution genotyping using 25-loci variable-number tandem repeat analysis (MLVA-25). Canonical SNP typing indicated that Turkish strains belonged to both the A.Br.003 linage and the Australian 94 lineage. In light of a recent analysis that placed the majority of Georgian B. anthracis isolates in one phylogenetic group, we screened the Turkish strains using a previously developed Georgian SNP panel. Minimal diversity was observed among the Kars strains within the Georgian SNP lineage: all 30 of these strains grouped with A.Br.026, ten strains were derived from A.Br.028, and only two isolates belonged to A.Br.029. According to the results of MLVA-25 genotyping, all 30 Turkish strains belong to two clusters. Cluster A is more diverse than cluster B. Our results suggest that B. anthracis strains originating from Georgia and the northeastern part of Turkey are genetically interrelated, which could be explained by the geographic proximity of the countries

Molecular genotyping of bacillus anthracis strains from Georgia and northeastern part of Turkey

Bacillus anthracis is the causal agent of anthrax and has a history of use as a biological weapon. Anthrax cases occur worldwide and the disease is endemic in certain regions. Here we describe a study of the genetic diversity of B. anthracis strains in two endemic areas: The country of Georgia and the Kars region of Turkey. Thirty Turkish isolates and thirty Georgian isolates were subjected to Single Nucleotide Polymorphism (SNP) sub typing, followed by higher-resolution genotyping using 25-loci variable-number tandem repeat analysis (MLVA-25). Canonical SNP typing indicated that Turkish strains belonged to both the A.Br.003 linage and the Australian 94 lineage. In light of a recent analysis that placed the majority of Georgian B. anthracis isolates in one phylogenetic group, we screened the Turkish strains using a previously developed Georgian SNP panel. Minimal diversity was observed among the Kars strains within the Georgian SNP lineage: all 30 of these strains grouped with A.Br.026, ten strains were derived from A.Br.028, and only two isolates belonged to A.Br.029. According to the results of MLVA-25 genotyping, all 30 Turkish strains belong to two clusters. Cluster A is more diverse than cluster B. Our results suggest that B. anthracis strains originating from Georgia and the northeastern part of Turkey are genetically interrelated, which could be explained by the geographic proximity of the countries

Circadian Modulation of Neurons and Astrocytes Controls Synaptic Plasticity in Hippocampal Area CA1

Most animal species operate according to a 24-h period set by the suprachiasmatic nucleus (SCN) of the hypothalamus. The rhythmic activity of the SCN modulates hippocampal-dependent memory, but the molecular and cellular mechanisms that account for this effect remain largely unknown. Here, we identify cell-type-specific structural and functional changes that occur with circadian rhythmicity in neurons and astrocytes in hippocampal area CA1. Pyramidal neurons change the surface expression of NMDA receptors. Astrocytes change their proximity to synapses. Together, these phenomena alter glutamate clearance, receptor activation, and integration of temporally clustered excitatory synaptic inputs, ultimately shaping hippocampal-dependent learning in vivo. We identify corticosterone as a key contributor to changes in synaptic strength. These findings highlight important mechanisms through which neurons and astrocytes modify the molecular composition and structure of the synaptic environment, contribute to the local storage of information in the hippocampus, and alter the temporal dynamics of cognitive processing

Raman Spectroscopy and Regenerative Medicine: A Review

The field of regenerative medicine spans a wide area of the biomedical landscape—from single cell culture in laboratories to human whole-organ transplantation. To ensure that research is transferrable from bench to bedside, it is critical that we are able to assess regenerative processes in cells, tissues, organs and patients at a biochemical level. Regeneration relies on a large number of biological factors, which can be perturbed using conventional bioanalytical techniques. A versatile, non-invasive, non-destructive technique for biochemical analysis would be invaluable for the study of regeneration; and Raman spectroscopy is a potential solution. Raman spectroscopy is an analytical method by which chemical data are obtained through the inelastic scattering of light. Since its discovery in the 1920s, physicists and chemists have used Raman scattering to investigate the chemical composition of a vast range of both liquid and solid materials. However, only in the last two decades has this form of spectroscopy been employed in biomedical research. Particularly relevant to regenerative medicine are recent studies illustrating its ability to characterise and discriminate between healthy and disease states in cells, tissue biopsies and in patients. This review will briefly outline the principles behind Raman spectroscopy and its variants, describe key examples of its applications to biomedicine, and consider areas of regenerative medicine that would benefit from this non-invasive bioanalytical tool

Asymptotic behaviour of a number of repeated records

Given a sequence of i.i.d. random variables with continuous distribution function we study the number of [var epsilon]-repetitions of the current record value from the time it occurs up to some n, as n --> [infinity]. This number of repetitions typically does not converge, but oscillates indefinitely. However, if it does converge, it can do so only to 1 or to [infinity]. For deterministic choices of [var epsilon], we give exact and asymptotic distributions and set conditions on the tail of F for convergence in probability to 1 and to [infinity] and for a.s. convergence to 1. For one choice of [var epsilon] as a radom variable, we obtain a never converging sequence of [var epsilon]-repetitions with limiting distribution being the so called Zipf's law, famous in an entirely different context.Regularly varying functions Repetitions of record Zipf's law Point processes Independent random walks