Treatment of Neuroblastoma with an Engineered “Obligate” Anaerobic Salmonella typhimurium Strain YB1

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A totally Self-Checking Dynamic Asynchronous Datapath

This paper investigates the inherent totally self-checking (TSC) property of one type of dynamic asynchronous datapath based on Differential Cascode Voltage Logic (DCVSL). As a result, a totally self-checking dynamic asynchronous datapath architecture is proposed. It is simpler than other similar approaches and represents a new approach to fault tolerant design.published_or_final_versio

Differentiation of Human Embryonic Stem Cells into Cells with Corneal Keratocyte Phenotype

Corneal transparency depends on a unique extracellular matrix secreted by stromal keratocytes, mesenchymal cells of neural crest lineage. Derivation of keratocytes from human embryonic stem (hES) cells could elucidate the keratocyte developmental pathway and open a potential for cell-based therapy for corneal blindness. This study seeks to identify conditions inducing differentiation of pluripotent hES cells to the keratocyte lineage. Neural differentiation of hES cell line WA01(H1) was induced by co-culture with mouse PA6 fibroblasts. After 6 days of co-culture, hES cells expressing cell-surface NGFR protein (CD271, p75NTR) were isolated by immunoaffinity adsorption, and cultured as a monolayer for one week. Keratocyte phenotype was induced by substratum-independent pellet culture in serum-free medium containing ascorbate. Gene expression, examined by quantitative RT-PCR, found hES cells co-cultured with PA6 cells for 6 days to upregulate expression of neural crest genes including NGFR, SNAI1, NTRK3, SOX9, and MSX1. Isolated NGFR-expressing cells were free of PA6 feeder cells. After expansion as a monolayer, mRNAs typifying adult stromal stem cells were detected, including BMI1, KIT, NES, NOTCH1, and SIX2. When these cells were cultured as substratum-free pellets keratocyte markers AQP1, B3GNT7, PTDGS, and ALDH3A1 were upregulated. mRNA for keratocan (KERA), a cornea-specific proteoglycan, was upregulated more than 10,000 fold. Culture medium from pellets contained high molecular weight keratocan modified with keratan sulfate, a unique molecular component of corneal stroma. These results show hES cells can be induced to differentiate into keratocytes in vitro. Pluripotent stem cells, therefore, may provide a renewable source of material for development of treatment of corneal stromal opacities. © 2013 Chan et al

Nonparametric estimation in economics: Bayesian and frequentist approaches

© 2017 Wiley Periodicals, Inc. We review Bayesian and classical approaches to nonparametric density and regression estimation and illustrate how these techniques can be used in economic applications. On the Bayesian side, density estimation is illustrated via finite Gaussian mixtures and a Dirichlet Process Mixture Model, while nonparametric regression is handled using priors that impose smoothness. From the frequentist perspective, kernel-based nonparametric regression techniques are presented for both density and regression problems. Both approaches are illustrated using a wage dataset from the Current Population Survey. WIREs Comput Stat 2017, 9:e1406. doi: 10.1002/wics.1406. For further resources related to this article, please visit the WIREs website

A clinically relevant in vivo model for the assessment of scaffold efficacy in abdominal wall reconstruction

Copyright © The Author(s) 2017. An animal model that allows for assessment of the degree of stretching or contraction of the implant area and the in vivo degradation properties of biological meshes is required to evaluate their performance in vivo. Adult New Zealand rabbits underwent full thickness subtotal unilateral rectus abdominis muscle excision and were reconstructed with the non-biodegradable Peri-Guard®, Prolene® or biodegradable Surgisis® meshes. Following 8 weeks of recovery, the anterior abdominal wall tissue samples were collected for measurement of the implant dimensions. The Peri-Guard and Prolene meshes showed a slight and obvious shrinkage, respectively, whereas the Surgisis mesh showed stretching, resulting in hernia formation. Surgisis meshes showed in vivo biodegradation and increased collagen formation. This surgical rabbit model for abdominal wall defects is advantageous for evaluating the in vivo behaviour of surgical meshes. Implant area stretching and shrinkage were detected corresponding to mesh properties, and histological analysis and stereological methods supported these findings.This study was financially supported by the Enterprise Ireland (Technology Development Grant). This publication has emanated from research conducted with the financial support of Science Foundation Ireland (SFI) and is co-funded under the European Regional Development Fund under grant no. 13/RC/2073. This study was also supported by the Centre for Microscopy & Imaging funded by NUI Galway and PRTLI, Cycles 4 and 5, National Development Plan 2007–2013

The effect of normal and abnormal ageing on prospective memory showed increased cognitive conflict: a functional MRI study

INTRODUCTION: Prospective memory (PM) is memory for planned intention, which needs to be executed appropriately in the future. PM task is usually embedded in ongoing activities. The neural correlates of PM have not been elucidated. To date, no functional imaging study has been conducted to examine the relevant functional change of PM during the processes of ageing and ...published_or_final_versio

Systematic study of constitutive cyclo-oxygenase-2 expression: role of NFκB and NFAT transcriptional pathways

Cyclooxygenase-2 (COX-2) is an inducible enzyme that drives inflammation and is the therapeutic target for widely used nonsteroidal antiinflammatory drugs (NSAIDs). However, COX-2 is also constitutively expressed, in the absence of overt inflammation, with a specific tissue distribution that includes the kidney, gastrointestinal tract, brain, and thymus. Constitutive COX-2 expression is therapeutically important because NSAIDs cause cardiovascular and renal side effects in otherwise healthy individuals. These side effects are now of major concern globally. However, the pathways driving constitutive COX-2 expression remain poorly understood. Here we show that in the kidney and other sites, constitutive COX-2 expression is a sterile response, independent of commensal microorganisms and not associated with activity of the inflammatory transcription factor NF-κB. Instead, COX-2 expression in the kidney but not other regions colocalized with nuclear factor of activated T cells (NFAT) transcription factor activity and was sensitive to inhibition of calcineurin-dependent NFAT activation. However, calcineurin/NFAT regulation did not contribute to constitutive expression elsewhere or to inflammatory COX-2 induction at any site. These data address the mechanisms driving constitutive COX-2 and suggest that by targeting transcription it may be possible to develop antiinflammatory therapies that spare the constitutive expression necessary for normal homeostatic functions, including those important to the cardiovascular-renal system

Orthogonal Range Reporting and Rectangle Stabbing for Fat Rectangles

In this paper we study two geometric data structure problems in the special case when input objects or queries are fat rectangles. We show that in this case a significant improvement compared to the general case can be achieved. We describe data structures that answer two- and three-dimensional orthogonal range reporting queries in the case when the query range is a \emph{fat} rectangle. Our two-dimensional data structure uses $O(n)$ words and supports queries in $O(\log\log U +k)$ time, where $n$ is the number of points in the data structure, $U$ is the size of the universe and $k$ is the number of points in the query range. Our three-dimensional data structure needs $O(n\log^{\varepsilon}U)$ words of space and answers queries in $O(\log \log U + k)$ time. We also consider the rectangle stabbing problem on a set of three-dimensional fat rectangles. Our data structure uses $O(n)$ space and answers stabbing queries in $O(\log U\log\log U +k)$ time.Comment: extended version of a WADS'19 pape

Relevance of short-range connectivity to brain compensation and cognitive efficiency in healthy and pathological ageing: a combined functional magnetic resonance imaging and tractography study on prospective memory

INTRODUCTION: Cognition and its efficiency are related to the activities of specific brain regions and their interactions. The brain function and structure are vulnerable to both healthy and pathological ageing, and these processes may underlie the impaired cognitive functions in daily life …published_or_final_versio

Characterisation of diesel vehicle emissions and determination of remote sensing cutpoints for diesel high-emitters

© 2019 Elsevier Ltd Diesel vehicles are a major source of air pollutants in cities and have caused significant health risks to the public globally. This study used both on-road remote sensing and transient chassis dynamometer to characterise emissions of diesel light goods vehicles. A large sample size of 183 diesel vans were tested on a transient chassis dynamometer to evaluate the emission levels of in-service diesel vehicles and to determine a set of remote sensing cutpoints for diesel high-emitters. The results showed that 79% and 19% of the Euro 4 and Euro 5 diesel vehicles failed the transient cycle test, respectively. Most of the high-emitters failed the NO limits, while no vehicle failed the HC limits and only a few vehicles failed the CO limits. Vehicles that failed NO limits occurred in both old and new vehicles. NO/CO2 ratios of 57.30 and 22.85 ppm/% were chosen as the remote sensing cutpoints for Euro 4 and Euro 5 high-emitters, respectively. The cutpoints could capture a Euro 4 and Euro 5 high-emitter at a probability of 27% and 57% with one snapshot remote sensing measurement, while only producing 1% of false high-emitter detections. The probability of high-emitting events was generally evenly distributed over the test cycle, indicating that no particular driving condition produced a higher probability of high-emitting events. Analysis on the effect of cutpoints on real-driving diesel fleet was carried out using a three-year remote sensing program. Results showed that 36% of Euro 4 and 47% of Euro 5 remote sensing measurements would be detected as high-emitting using the proposed cutpoints. In-service diesel vehicles emit low CO and HC but high NO