The Tumor Suppressor HHEX Inhibits Axon Growth when Prematurely Expressed in Developing Central Nervous System Neurons

Neurons in the embryonic and peripheral nervoussystem respond to injury by activating transcriptional programs supportive of axon growth, ultimately resulting in functional recovery. In contrast, neurons in the adult central nervous system (CNS) possess a limited capacity to regenerate axons after injury, fundamentally constraining repair. Activating pro-regenerative gene expression in CNS neurons is a promising therapeutic approach, but progress is hampered by incomplete knowledge of the relevant transcription factors. An emerging hypothesis is that factors implicated in cellular growth and motility outside the nervous system may also control axon growth in neurons. We therefore tested sixty-nine transcription factors, previously identified as possessing tumor suppressive or oncogenic properties in non-neuronal cells, in assays of neurite outgrowth. This screen identified YAP1 and E2F1 as enhancers of neurite outgrowth, and PITX1, RBM14, ZBTB16, and HHEX as inhibitors. Follow-up experiments are focused on the tumor suppressor HHEX, one of the strongest growth inhibitors. HHEX is widely expressed in adult CNS neurons, including corticospinal tract neurons after spinal injury, but is present only in trace amounts in immature cortical neurons and adult peripheral neurons. HHEX overexpression in early postnatal cortical neurons reduced both initial axonogenesis and the rate of axon elongation, and domain deletion analysis strongly implicated transcriptional repression as the underlying mechanism. These findings suggest a role for HHEX in restricting axon growth in the developing CNS, and substantiate the hypothesis that previously identified oncogenes and tumor suppressors can play conserved roles in axon extension

Development of a Cryptosporidium oocyst assay using an automated fiber optic-based biosensor

An intestinal protozoan parasite, Cryptosporidium parvum, is a major cause of waterborne gastrointestinal disease worldwide. Detection of Cryptosporidium oocysts in potable water is a high priority for the water treatment industry to reduce potential outbreaks among the consumer populace. Anti-Cryptosporidium oocyst polyclonal and monoclonal antibodies were tested as capture and detection reagents for use in a fiber optic biosensor assay for the detection of Cryptosporidium oocysts. Antibodies were validated using enzyme-linked immunosorbent assays, flow cytometry, Western blotting and fluorescent microscopy. Oocysts could be detected at a concentration of 105 oocysts/ml when the polyclonal antibodies were used as the capture and detection reagents. When oocysts were boiled prior to detection, a ten-fold increase in sensitivity was achieved using the polyclonal antibody. Western blotting and immunofluorescence revealed that both the monoclonal and polyclonal antibodies recognize a large (>300 kDa) molecular weight mucin-like antigen present on the surface of the oocyst wall. The polyclonal antibody also reacted with a small (105 kDa) molecular weight antigen that was present in boiled samples of oocysts. Preliminary steps to design an in-line biosensor assay system have shown that oocysts would have to be concentrated from water samples and heat treated to allow detection by a biosensor assay

Cooperative sequential adsorption models on a Cayley tree: analytical results and applications

We present a class of cooperative sequential adsorption models on a Cayley tree with constant and variable attachment rates and their possible applications for ionic self-assembly of thin films and drug encapsulation of nanoparticles. Using the empty interval method, and generalizing results known from reaction-diffusion processes on Cayley trees, we calculate a variety of quantities such as time-dependent surface coverage and time-dependent probabilities of certain particle configurations

The Stride program: Feasibility and pre-to-post program change of an exercise service for university students experiencing mental distress

Rates of mental illness are disproportionately high for young adult and higher education (e.g., university student) populations. As such, universities and tertiary institutions often devote significant efforts to services and programs that support and treat mental illness and/or mental distress. However, within that portfolio of treatment approaches, structured exercise has been relatively underutilised and greater research attention is needed to develop this evidence base. The Stride program is a structured 12-week exercise service for students experiencing mental distress. We aimed to explore the feasibility of the program and assess pre- and post-program change, through assessments of student health, lifestyle, and wellbeing outcomes. Drawing from feasibility and effectiveness-implementation hybrid design literatures, we conducted a non-randomised feasibility trial of the Stride program. Participants were recruited from the Stride program (N = 114, Mage = 24.21 years). Feasibility results indicated the program was perceived as acceptable and that participants reported positive perceptions of program components, personnel, and sessions. Participants’ pre-to-post program change in depressive symptomatology, physical activity levels, mental health-related quality of life, and various behavioural outcomes were found to be desirable. Our results provide support for the feasibility of the Stride program, and more broadly for the delivery and potential effectiveness of structured exercise programs to support university students experiencing mental distress

Convergence calls: multimedia storytelling at British news websites

This article uses qualitative interviews with senior editors and managers from a selection of the UK's national online news providers to describe and analyse their current experimentation with multimedia and video storytelling. The results show that, in a period of declining newspaper readership and TV news viewing, editors are keen to embrace new technologies, which are seen as being part of the future of news. At the same time, text is still reported to be the cornerstone for news websites, leading to changes in the grammar and function of news video when used online. The economic rationale for convergence is examined and the article investigates the partnerships sites have entered into in order to be able to serve their audience with video content. In-house video is complementing syndicated content, and the authors examine the resulting developments in newsroom training and recruitment practices. The article provides journalism and interactive media scholars with case studies on the changes taking place in newsrooms as a result of the shift towards multimedia, multiplatform news consumption

Smart Swarms of Bacteria-Inspired Agents with Performance Adaptable Interactions

Collective navigation and swarming have been studied in animal groups, such as fish schools, bird flocks, bacteria, and slime molds. Computer modeling has shown that collective behavior of simple agents can result from simple interactions between the agents, which include short range repulsion, intermediate range alignment, and long range attraction. Here we study collective navigation of bacteria-inspired smart agents in complex terrains, with adaptive interactions that depend on performance. More specifically, each agent adjusts its interactions with the other agents according to its local environment – by decreasing the peers' influence while navigating in a beneficial direction, and increasing it otherwise. We show that inclusion of such performance dependent adaptable interactions significantly improves the collective swarming performance, leading to highly efficient navigation, especially in complex terrains. Notably, to afford such adaptable interactions, each modeled agent requires only simple computational capabilities with short-term memory, which can easily be implemented in simple swarming robots

Reliability of a novel thermal imaging system for temperature assessment of healthy feet

Abstract Background Thermal imaging is a useful modality for identifying preulcerative lesions (“hot spots”) in diabetic foot patients. Despite its recognised potential, at present, there is no readily available instrument for routine podiatric assessment of patients at risk. To address this need, a novel thermal imaging system was recently developed. This paper reports the reliability of this device for temperature assessment of healthy feet. Methods Plantar skin foot temperatures were measured with the novel thermal imaging device (Diabetic Foot Ulcer Prevention System (DFUPS), constructed by Photometrix Imaging Ltd) and also with a hand-held infrared spot thermometer (Thermofocus® 01500A3, Tecnimed, Italy) after 20 min of barefoot resting with legs supported and extended in 105 subjects (52 males and 53 females; age range 18 to 69 years) as part of a multicentre clinical trial. The temperature differences between the right and left foot at five regions of interest (ROIs), including 1st and 4th toes, 1st, 3rd and 5th metatarsal heads were calculated. The intra-instrument agreement (three repeated measures) and the inter-instrument agreement (hand-held thermometer and thermal imaging device) were quantified using intra-class correlation coefficients (ICCs) and the 95% confidence intervals (CI). Results Both devices showed almost perfect agreement in replication by instrument. The intra-instrument ICCs for the thermal imaging device at all five ROIs ranged from 0.95 to 0.97 and the intra-instrument ICCs for the hand-held-thermometer ranged from 0.94 to 0.97. There was substantial to perfect inter-instrument agreement between the hand-held thermometer and the thermal imaging device and the ICCs at all five ROIs ranged between 0.94 and 0.97. Conclusions This study reports the performance of a novel thermal imaging device in the assessment of foot temperatures in healthy volunteers in comparison with a hand-held infrared thermometer. The newly developed thermal imaging device showed very good agreement in repeated temperature assessments at defined ROIs as well as substantial to perfect agreement in temperature assessment with the hand-held infrared thermometer. In addition to the reported non-inferior performance in temperature assessment, the thermal imaging device holds the potential to provide an instantaneous thermal image of all sites of the feet (plantar, dorsal, lateral and medial views). Trial registration Diabetic Foot Ulcer Prevention System NCT02317835, registered December 10, 201

Shifted Symplectic Structures

This is the first of a series of papers about \emph{quantization} in the context of \emph{derived algebraic geometry}. In this first part, we introduce the notion of \emph{$n$-shifted symplectic structures}, a generalization of the notion of symplectic structures on smooth varieties and schemes, meaningful in the setting of derived Artin n-stacks. We prove that classifying stacks of reductive groups, as well as the derived stack of perfect complexes, carry canonical 2-shifted symplectic structures. Our main existence theorem states that for any derived Artin stack $F$ equipped with an $n$-shifted symplectic structure, the derived mapping stack $\textbf{Map}(X,F)$ is equipped with a canonical $(n-d)$-shifted symplectic structure as soon a $X$ satisfies a Calabi-Yau condition in dimension $d$. These two results imply the existence of many examples of derived moduli stacks equipped with $n$-shifted symplectic structures, such as the derived moduli of perfect complexes on Calabi-Yau varieties, or the derived moduli stack of perfect complexes of local systems on a compact and oriented topological manifold. We also show that Lagrangian intersections carry canonical (-1)-shifted symplectic structures.Comment: 52 pages. To appear in Publ. Math. IHE

Search for Point Sources of Ultra-High Energy Cosmic Rays Above 40 EeV Using a Maximum Likelihood Ratio Test

We present the results of a search for cosmic ray point sources at energies above 40 EeV in the combined data sets recorded by the AGASA and HiRes stereo experiments. The analysis is based on a maximum likelihood ratio test using the probability density function for each event rather than requiring an a priori choice of a fixed angular bin size. No statistically significant clustering of events consistent with a point source is found.Comment: 7 pages, 7 figures. Accepted for publication in The Astrophysical Journa