Bayesian Optimisation for Safe Navigation under Localisation Uncertainty

In outdoor environments, mobile robots are required to navigate through terrain with varying characteristics, some of which might significantly affect the integrity of the platform. Ideally, the robot should be able to identify areas that are safe for navigation based on its own percepts about the environment while avoiding damage to itself. Bayesian optimisation (BO) has been successfully applied to the task of learning a model of terrain traversability while guiding the robot through more traversable areas. An issue, however, is that localisation uncertainty can end up guiding the robot to unsafe areas and distort the model being learnt. In this paper, we address this problem and present a novel method that allows BO to consider localisation uncertainty by applying a Gaussian process model for uncertain inputs as a prior. We evaluate the proposed method in simulation and in experiments with a real robot navigating over rough terrain and compare it against standard BO methods.Comment: To appear in the proceedings of the 18th International Symposium on Robotics Research (ISRR 2017

Euler-Bessel and Euler-Fourier Transforms

We consider a topological integral transform of Bessel (concentric isospectral sets) type and Fourier (hyperplane isospectral sets) type, using the Euler characteristic as a measure. These transforms convert constructible \zed-valued functions to continuous $\real$-valued functions over a vector space. Core contributions include: the definition of the topological Bessel transform; a relationship in terms of the logarithmic blowup of the topological Fourier transform; and a novel Morse index formula for the transforms. We then apply the theory to problems of target reconstruction from enumerative sensor data, including localization and shape discrimination. This last application utilizes an extension of spatially variant apodization (SVA) to mitigate sidelobe phenomena

The Human Adenovirus Type 5 E4orf6/E1B55K E3 Ubiquitin Ligase Complex Enhances E1A Functional Activity

Human adenovirus (Ad) E1A proteins have long been known as the central regulators of virus infection as well as the major source of adenovirus oncogenic potential. Not only do they activate expression of other early viral genes, they make viral replication possible in terminally differentiated cells, at least in part, by binding to the retinoblastoma (Rb) tumor suppressor family of proteins to activate E2F transcription factors and thus viral and cellular DNA synthesis. We demonstrate in an accompanying article (F. Dallaire et al., mSphere 1:00014-15, 2016) that the human adenovirus E3 ubiquitin ligase complex formed by the E4orf6 and E1B55K proteins is able to mimic E1A activation of E2F transactivation factors. Acting alone in the absence of E1A, the Ad5 E4orf6 protein in complex with E1B55K was shown to bind E2F, disrupt E2F/Rb complexes, and induce hyperphosphorylation of Rb, leading to induction of viral and cellular DNA synthesis, as well as stimulation of early and late viral gene expression and production of viral progeny. While these activities were significantly lower than those exhibited by E1A, we report here that this ligase complex appeared to enhance E1A activity in two ways. First, the E4orf6/E1B55K complex was shown to stabilize E1A proteins, leading to higher levels in infected cells. Second, the complex was demonstrated to enhance the activation of E2F by E1A products. These findings indicated a new role of the E4orf6/E1B55K ligase complex in promoting adenovirus replication

Active removal of inorganic phosphate from cerebrospinal fluid by the choroid plexus

The P-i concentration of mammalian cerebrospinal fluid (CSF) is about one-half that of plasma, a phenomenon also shown here in the spiny dogfish, Squalus acanthias. The objective of the present study was to characterize the possible role of the choroid plexus (CP) in determining CSF P-i concentration. The large sheet-like fourth CP of the shark was mounted in Ussing chambers where unidirectional P-33(i) fluxes revealed potent active transport from CSF to the blood side under short-circuited conditions. The flux ratio was 8: 1 with an average transepithelial resistance of 87 +/- 17.9 Omega . cm(2) and electrical potential difference of + 0.9 +/- 0.17 mV (CSF side positive). Active P-i absorption from CSF was inhibited by 10 mM arsenate, 0.2 mM ouabain, Na+ -free medium, and increasing the K+ concentration from 5 to 100 mM. Li+ stimulated transport twofold compared with Na+-free medium. Phosphonoformic acid (1 mM) had no effect on active Pi transport. RT-PCR revealed both P-i transporter (PiT) 1 and PiT2 (SLC20 family) gene expression, but no Na+ -P-i cotransporter II (SLC34 family) expression, in the shark CP. PiT2 immunoreactivity was shown by immunoblot analysis and localized by immunohistochemistry in (or near) the CP apical microvillar membranes of both the shark and rat. PiT1 appeared to be localized primarily to vascular endothelial cells. Taken together, these data indicate that the CP actively removes P-i from CSF. This process has transport properties consistent with a PiT2, Na+-dependent transporter that is located in the apical region of the CP epithelium.National Science Foundation [0843253]; Fundacao para a Ciencia e a Tecnologia, Portuga

Plasma anandamide concentrations are lower in children with autism spectrum disorder

Background: Autism spectrum disorder (ASD) is a neurodevelopmentaldisorder characterized by restricted, stereotyped behaviors and impairments in social communication. Although the underlying biological mechanisms of ASD remain poorly understood, recent preclinical research has implicated the endogenous cannabinoid (or endocannabinoid), anandamide, as a significant neuromodulator in rodent models of ASD. Despite this promising preclinical evidence, no clinical studies to date have tested whether endocannabinoids are dysregulated in individuals with ASD. Here, we addressed this critical gap in knowledge by optimizing liquid chromatography-tandem mass spectrometry methodology to quantitatively analyze anandamide concentrations in banked blood samples collected from a cohort of children withand without ASD (N= 112). Findings: Anandamide concentrations significantly differentiated ASD cases (N= 59) from controls (N= 53), such that children with lower anandamide concentrations were more likely to have ASD (p= 0.041). In keeping with this notion, anandamide concentrations were also significantly lower in ASD compared to control children (p= 0.034). Conclusions: These findings are the first empirical human data to translate preclinical rodent findings to confirm a link between plasma anandamide concentrations in children with ASD. Although preliminary, these data suggest that impaired anandamide signaling may be involved in the pathophysiology of ASD

Indications of decreasing human PTS concentrations in North West Russia

The Russian Arctic covers an enormous landmass with diverse environments. It inhabits more than 20 different ethnic groups, all of them with various living conditions and food traditions. Indigenous populations with a traditional way of living are exposed to a large number of anthropogenic pollutants, such as persistent organic pollutants (POPs) and toxic metals, mainly through the diet. Human monitoring of persistent organic pollutants (POPs) and heavy metals in the Russian Arctic has only been performed on irregular intervals over the past 15 years, thus, there is still a lack of baseline data from many ethnic groups and geographical regions. The aim of the current study was to investigate concentrations of POPs and toxic metals in three groups of indigenous people from the Russian Arctic. Plasma concentrations of POPs were measured in one of the locations (Nelmin-Nos) in 2001–2003 which gave the unique opportunity to compare concentrations over time in a small Russian arctic community. During 2009 and early 2010, 209 blood samples were collected from three different study sites in North West Russia; Nelmin-Nos, Izhma and Usinsk. The three study sites are geographically separated and the inhabitants are expected to have different dietary habits and living conditions. All blood samples were analyzed for POPs and toxic metals. PCB 153 was present in highest concentrations of the 18 PCBs analyzed. p,p′-DDE and HCB were the two most dominating OC pesticides. Males had higher concentrations of PCB 138, 153 and 180 than women and age was a significant predictor of PCB 153, 180, HCB and p,p′-DDD. Males from Izhma had significantly higher concentrations of HCB than males from the other study sites and women from Usinsk had higher concentrations of p,p′-DDE. Parity was a significant predictor of p,p′-DDE. Hg and Pb concentrations increased with increasing age and males had significantly higher concentrations of Pb than women. The study group from Izhma had significantly higher concentrations of Cd when controlling for age and gender and the study group from Usinsk had higher concentrations of Se than the others. Compared to the results from Nelmin-Nos in 2001–2003, a clear decrease in p,p′-DDE concentrations for both women and men was observed. The current study indicates a significant reduction of several PTSs in human blood samples from North West Russia over the past 10 years

A cardinal role for cathepsin D in co-ordinating the host-mediated apoptosis of macrophages and killing of pneumococci

The bactericidal function of macrophages against pneumococci is enhanced by their apoptotic demise, which is controlled by the anti-apoptotic protein Mcl-1. Here, we show that lysosomal membrane permeabilization (LMP) and cytosolic translocation of activated cathepsin D occur prior to activation of a mitochondrial pathway of macrophage apoptosis. Pharmacological inhibition or knockout of cathepsin D during pneumococcal infection blocked macrophage apoptosis. As a result of cathepsin D activation, Mcl-1 interacted with its ubiquitin ligase Mule and expression declined. Inhibition of cathepsin D had no effect on early bacterial killing but inhibited the late phase of apoptosis-associated killing of pneumococci in vitro. Mice bearing a cathepsin D-/- hematopoietic system demonstrated reduced macrophage apoptosis in vivo, with decreased clearance of pneumococci and enhanced recruitment of neutrophils to control pulmonary infection. These findings establish an unexpected role for a cathepsin D-mediated lysosomal pathway of apoptosis in pulmonary host defense and underscore the importance of apoptosis-associated microbial killing to macrophage function