Limit theorems for empirical Fréchet means of independent and non-identically distributed manifold-valued random variables

We prove weak laws of large numbers and central limit theorems of Lindeberg type for empirical centres of mass (empirical Fréchet means) of independent nonidentically distributed random variables taking values in Riemannian manifolds. In order to prove these theorems we describe and prove a simple kind of Lindeberg–Feller central approximation theorem for vector-valued random variables, which may be of independent interest and is therefore the subject of a self-contained section. This vector-valued result allows us to clarify the number of conditions required for the central limit theorem for empirical Fréchet means, while extending its scope

Sticky central limit theorems on open books

Given a probability distribution on an open book (a metric space obtained by gluing a disjoint union of copies of a half-space along their boundary hyperplanes), we define a precise concept of when the Fr\'{e}chet mean (barycenter) is sticky. This nonclassical phenomenon is quantified by a law of large numbers (LLN) stating that the empirical mean eventually almost surely lies on the (codimension $1$ and hence measure $0$) spine that is the glued hyperplane, and a central limit theorem (CLT) stating that the limiting distribution is Gaussian and supported on the spine. We also state versions of the LLN and CLT for the cases where the mean is nonsticky (i.e., not lying on the spine) and partly sticky (i.e., is, on the spine but not sticky).Comment: Published in at http://dx.doi.org/10.1214/12-AAP899 the Annals of Applied Probability (http://www.imstat.org/aap/) by the Institute of Mathematical Statistics (http://www.imstat.org

Targeting HIF2α-ARNT hetero-dimerisation as a novel therapeutic strategy for pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a destructive disease of the pulmonary vasculature often leading to right heart failure and death. Current therapeutic intervention strategies only slow disease progression. The role of aberrant hypoxia-inducible factor (HIF)2α stability and function in the initiation and development of pulmonary hypertension (PH) has been an area of intense interest for nearly two decades. Here we determine the effect of a novel HIF2α inhibitor (PT2567) on PH disease initiation and progression, using two pre-clinical models of PH. Haemodynamic measurements were performed, followed by collection of heart, lung and blood for pathological, gene expression and biochemical analysis. Blood outgrowth endothelial cells from idiopathic PAH patients were used to determine the impact of HIF2α-inhibition on endothelial function. Global inhibition of HIF2a reduced pulmonary vascular haemodynamics and pulmonary vascular remodelling in both su5416/hypoxia prevention and intervention models. PT2567 intervention reduced the expression of PH-associated target genes in both lung and cardiac tissues and restored plasma nitrite concentration. Treatment of monocrotaline-exposed rodents with PT2567 reduced the impact on cardiovascular haemodynamics and promoted a survival advantage. In vitro, loss of HIF2α signalling in human pulmonary arterial endothelial cells suppresses target genes associated with inflammation, and PT2567 reduced the hyperproliferative phenotype and overactive arginase activity in blood outgrowth endothelial cells from idiopathic PAH patients. These data suggest that targeting HIF2α hetero-dimerisation with an orally bioavailable compound could offer a new therapeutic approach for PAH. Future studies are required to determine the role of HIF in the heterogeneous PAH population

Interaction of Stress, Lead Burden, and Age on Cognition in Older Men: The VA Normative Aging Study

BACKGROUND. Low-level exposure to lead and to chronic stress may independently influence cognition. However, the modifying potential of psychosocial stress on the neurotoxicity of lead and their combined relationship to aging-associated decline have not been fully examined. OBJECTIVES. We examined the cross-sectional interaction between stress and lead exposure on Mini-Mental State Examination (MMSE) scores among 811 participants in the Normative Aging Study, a cohort of older U.S. men. METHODS. We used two self-reported measures of stress appraisal-a self-report of stress related to their most severe problem and the Perceived Stress Scale (PSS). Indices of lead exposure were blood lead and bone (tibia and patella) lead. RESULTS. Participants with higher self-reported stress had lower MMSE scores, which were adjusted for age, education, computer experience, English as a first language, smoking, and alcohol intake. In multivariable-adjusted tests for interaction, those with higher PSS scores had a 0.57-point lower (95% confidence interval, -0.90 to 0.24) MMSE score for a 2-fold increase in blood lead than did those with lower PSS scores. In addition, the combination of high PSS scores and high blood lead categories on one or both was associated with a 0.05-0.08 reduction on the MMSE for each year of age compared with those with low PSS score and blood lead level (p < 0.05). CONCLUSIONS. Psychological stress had an independent inverse association with cognition and also modified the relationship between lead exposure and cognitive performance among older men. Furthermore, high stress and lead together modified the association between age and cognition.National Institutes of Health (R01ES07821, R01HL080674, R01HL080674-02S1, R01ES013744, ES05257-06A1, P20MD000501, P42ES05947, ES03918-02); National Center for Research Resources General Clinical Research Center (M01RR02635); Leaves of Grass Foundation; United States Department of Veterans Affair

Content Delivery Analysis in Multiple Devices to Single Device Communications

Content caching at mobile user devices (UDs) utilizing device to device (D2D) communications is a promising technology to enhance the performance of mobile networks, in terms of latency, throughput, energy consumption, and so on. In this paper, a novel method of content delivery using multiple devices to single device (MDSD) communications through D2D links is presented. In this method, the Zipf distribution with exponent shape parameter is adopted to model the content caching popularity for the analysis of the achievable signal to interference plus noise ratio (SINR). In order to investigate the advantage of the proposed MDSD method, firstly, a closedform expression of the outage probability is theoretically derived for a single D2D communication to evaluate the success of content delivery to a reference UD. Secondly, the expression of the outage probability for MDSD communication is derived, where the outage probability is modeled as a function of content caching popularity, the density of UDs, and the size of cooperative area. The research work is further extended to address the frequency reuse among different UDs in one cell, where a frequency band factor is introduced, and the optimal radius of the cooperative area is introduced and analysed. The analytical results, validated by the simulation results, show that the outage probability decreases drastically when the popularity of the content increases, or the radius of the cooperative area increases. Using the given closed-form expression of the outage probability, the area spectral efficiency (ASE) of the system is presented. Furthermore, the results show that as the frequency band factor increases, the outage probability decreases, as well as the ASE decreases. Finally, it is shown that the MDSD outperforms the single D2D-based method

Performance analysis of Mobile Content Delivery in Multiple Devices to Single Device Communication

In wireless communication networks, caching and delivering popular content via the device to device (D2D) communication has recently been proposed as an exciting and innovative technology in order to offload network data traffic. In this paper, a novel method of content delivery using multiple devices to the single device (MDSD) communication via D2D links is presented. An expression of the outage probability (Pout) is analytically derived and validated by simulation to determine the success of the content delivery to the user equipment (UE). Zipf distribution with exponent shape parameter p is adopted to model the UE requests and content caching popularity which affects the achievable link data rate (Ra). The results show that Pout decreases as the popularity of the content increases. Meanwhile, MDSD improves the UE experience in terms of Pout substantially compared to the single D2D link based method

The proteomic landscape of glioma stem-like cells

AbstractGlioma stem-like cells (GSCs) are hypothesized to provide a repository of cells in tumors that can self-replicate and are radio- and chemo-resistant. GSC lines, representing several glioma subtypes, have been isolated and characterized at the transcript level. We sought to characterize 35 GSC lines at the protein level using label-free quantitative proteomics. Resulting relative fold changes were used to drive unsupervised hierarchical clustering for the purpose of classifying the cell lines based on proteomic profiles. Bioinformatics analysis identified synoviolin, serine/arginine-rich splicing factor 2, symplekin, and IL-5 as molecules of interest in progression and/or treatment of glioma