Large-scale multielectrode recording and stimulation of neural activity

Large circuits of neurons are employed by the brain to encode and process information. How this encoding and processing is carried out is one of the central questions in neuroscience. Since individual neurons communicate with each other through electrical signals (action potentials), the recording of neural activity with arrays of extracellular electrodes is uniquely suited for the investigation of this question. Such recordings provide the combination of the best spatial (individual neurons) and temporal (individual action-potentials) resolutions compared to other large-scale imaging methods. Electrical stimulation of neural activity in turn has two very important applications: it enhances our understanding of neural circuits by allowing active interactions with them, and it is a basis for a large variety of neural prosthetic devices. Until recently, the state-of-the-art in neural activity recording systems consisted of several dozen electrodes with inter-electrode spacing ranging from tens to hundreds of microns. Using silicon microstrip detector expertise acquired in the field of high-energy physics, we created a unique neural activity readout and stimulation framework that consists of high-density electrode arrays, multi-channel custom-designed integrated circuits, a data acquisition system, and data-processing software. Using this framework we developed a number of neural readout and stimulation systems: (1) a 512-electrode system for recording the simultaneous activity of as many as hundreds of neurons, (2) a 61-electrode system for electrical stimulation and readout of neural activity in retinas and brain-tissue slices, and (3) a system with telemetry capabilities for recording neural activity in the intact brain of awake, naturally behaving animals. We will report on these systems, their various applications to the field of neurobiology, and novel scientific results obtained with some of them. We will also outline future directions

The Suaineadh Project : a stepping stone towards the deployment of large flexible structures in space

The Suaineadh project aims at testing the controlled deployment and stabilization of space web. The deployment system is based on a simple yet ingenious control of the centrifugal force that will pull each of the four daughters sections apart. The four daughters are attached onto the four corners of a square web, and will be released from their initial stowed configuration attached to a central hub. Enclosed in the central hub is a specifically designed spinning reaction wheel that controls the rotational speed with a closed loop control fed by measurements from an onboard inertial measurement sensor. Five other such sensors located within the web and central hub provide information on the surface curvature of the web, and progression of the deployment. Suaineadh is currently at an advanced stage of development: all the components are manufactured with the subsystems integrated and are presently awaiting full integration and testing. This paper will present the current status of the Suaineadh project and the results of the most recent set of tests. In particular, the paper will cover the overall mechanical design of the system, the electrical and sensor assemblies, the communication and power systems and the spinning wheel with its control system

Performance of bulk SiC radiation detectors

SiC is a wide-gap material with excellent electrical and physical properties that may make it an important material for some future electronic devices. The most important possible applications of SiC are in hostile environments, such as in car/jet engines, within nuclear reactors, or in outer space. Another area where the material properties, most notably radiation hardness, would be valuable is in the inner tracking detectors of particle physics experiments. Here, we describe the performance of SiC diodes irradiated in the 24 GeV proton beam at CERN. Schottky measurements have been used to probe the irradiated material for changes in I–V characteristics. Other methods, borrowed from III–V research, used to study the irradiated surface include atomic force microscope scans and Raman spectroscopy. These have been used to observe the damage to the materials surface and internal lattice structure. We have also characterised the detection capabilities of bulk semi-insulating SiC for α radiation. By measuring the charge collection efficiency (CCE) for variations in bias voltage, CCE values up to 100% have been measured

Polymyalgia rheumatica shows metabolomic alterations that are further altered by glucocorticoid treatment:Identification of metabolic correlates of fatigue

OBJECTIVE: In polymyalgia rheumatica (PMR), glucocorticoids (GCs) relieve pain and stiffness, but fatigue may persist. We aimed to explore the effect of disease, GCs and PMR symptoms in the metabolite signatures of peripheral blood from patients with PMR or the related disease, giant cell arteritis (GCA).METHODS: Nuclear magnetic resonance spectroscopy was performed on serum from 40 patients with untreated PMR, 84 with new-onset confirmed GCA, and 53 with suspected GCA who later were clinically confirmed non-GCA, and 39 age-matched controls. Further samples from PMR patients were taken one and six months into glucocorticoid therapy to explore relationship of metabolites to persistent fatigue. 100 metabolites were identified using Chenomx and statistical analysis performed in SIMCA-P to examine the relationship between metabolic profiles and, disease, GC treatment or symptoms.RESULTS: The metabolite signature of patients with PMR and GCA differed from that of age-matched non-inflammatory controls (R2 &gt; 0.7). There was a smaller separation between patients with clinically confirmed GCA and those with suspected GCA who later were clinically confirmed non-GCA (R2 = 0.135). In PMR, metabolite signatures were further altered with glucocorticoid treatment (R2 = 0.42) but did not return to that seen in controls. Metabolites correlated with CRP, pain, stiffness, and fatigue (R 2 ≥ 0.39). CRP, pain, and stiffness declined with treatment and were associated with 3-hydroxybutyrate and acetoacetate, but fatigue did not. Metabolites differentiated patients with high and low fatigue both before and after treatment (R2 &gt; 0.9). Low serum glutamine was predictive of high fatigue at both time points (0.79-fold change). CONCLUSION: PMR and GCA alter the metabolite signature. In PMR, this is further altered by glucocorticoid therapy. Treatment-induced metabolite changes were linked to measures of inflammation (CRP, pain and stiffness), but not to fatigue. Furthermore, metabolite signatures distinguished patients with high or low fatigue.</p

Position Reconstruction in Drift Chambers operated with Xe, CO2 (15%)

We present measurements of position and angular resolution of drift chambers operated with a Xe,CO$_2$(15%) mixture. The results are compared to Monte Carlo simulations and important systematic effects, in particular the dispersive nature of the absorption of transition radiation and non-linearities, are discussed. The measurements were carried out with prototype drift chambers of the ALICE Transition Radiation Detector, but our findings can be generalized to other drift chambers with similar geometry, where the electron drift is perpendicular to the wire planes.Comment: 30 pages, 18 figure

Space charge in drift chambers operated with the Xe,CO2(15%) mixture

Using prototype modules of the ALICE Transition Radiation Detector we investigate space charge effects and the dependence of the pion rejection performance on the incident angle of the ionizing particle. The average pulse height distributions in the drift chambers operated with the Xe,CO2(15%) mixture provide quantitative information on the gas gain reduction due to space charge accumulating during the drift of the primary ionization. Our results demonstrate that the pion rejection performance of a TRD is better for tracks which are not at normal incidence to the anode wires. We present detailed simulations of detector signals, which reproduce the measurements and lend strong support to our interpretation of the measurements in terms of space charge effects.Comment: 18 pages, 10 figures, accepted for publication in Nucl.Instrum.Meth. A. Data files available at http://www-alice.gsi.de/tr

The CERES/NA45 Radial Drift Time Projection Chamber

The design, calibration, and performance of the first radial drift Time Projection Chamber (TPC) are presented. The TPC was built and installed at the CERES/NA45 experiment at the CERN SPS in the late nineties, with the objective to improve the momentum resolution of the spectrometer. The upgraded experiment took data twice, in 1999 and in 2000. After a detailed study of residual distortions a spatial resolution of 340 um in the azimuthal and 640 um in the radial direction was achieved, corresponding to a momentum resolution of Dp/p = sqrt{(1% * p/GeV)^2 + (2%)^2}.Comment: 57 pages, 59 figure

Characterizing the heterogeneity of triple-negative breast cancers using microdissected normal ductal epithelium and RNA-sequencing

Triple-negative breast cancers (TNBCs) are a heterogeneous set of tumors defined by an absence of actionable therapeutic targets (ER, PR, and HER-2). Microdissected normal ductal epithelium from healthy volunteers represents a novel comparator to reveal insights into TNBC heterogeneity and to inform drug development. Using RNA-sequencing data from our institution and The Cancer Genome Atlas (TCGA) we compared the transcriptomes of 94 TNBCs, 20 microdissected normal breast tissues from healthy volunteers from the Susan G. Komen for the Cure Tissue Bank, and 10 histologically normal tissues adjacent to tumor. Pathway analysis comparing TNBCs to optimized normal controls of microdissected normal epithelium versus classic controls composed of adjacent normal tissue revealed distinct molecular signatures. Differential gene expression of TNBC compared with normal comparators demonstrated important findings for TNBC-specific clinical trials testing targeted agents; lack of over-expression for negative studies and over-expression in studies with drug activity. Next, by comparing each individual TNBC to the set of microdissected normals, we demonstrate that TNBC heterogeneity is attributable to transcriptional chaos, is associated with non-silent DNA mutational load, and explains transcriptional heterogeneity in addition to known molecular subtypes. Finally, chaos analysis identified 146 core genes dysregulated in >90 % of TNBCs revealing an over-expressed central network. In conclusion, use of microdissected normal ductal epithelium from healthy volunteers enables an optimized approach for studying TNBC and uncovers biological heterogeneity mediated by transcriptional chaos

Consumer behaviour in tourism: Concepts, influences and opportunities

Although consumer behaviour (CB) is one of the most researched areas in the field of tourism, few extensive reviews of the body of knowledge in this area exist. This review article examines what we argue are the key concepts, external influences and opportune research contexts in contemporary tourism CB research. Using a narrative review, we examine the CB literature published in three major tourism journals from 2000 to 2012. Of 519 articles identified and reviewed, 191 are included in this article. We examine the development of and scope for future research on nine key concepts, including decision-making, values, motivations, self-concept and personality, expectations, attitudes, perceptions, satisfaction, trust and loyalty. We then examine three important external influences on tourism behaviour, technology, Generation Y and the rise in concern over ethical consumption. Finally, we identify and discuss five research contexts that represent major areas for future scholarship: group and joint decision-making, under-researched segments, cross-cultural issues in emerging markets, emotions and consumer misbehaviour. Our examination of key research gaps is concluded by arguing that the hedonic and affective aspects of CB research in tourism must be brought to bear on the wider CB and marketing literature

Scans for signatures of selection in Russian cattle breed genomes reveal new candidate genes for environmental adaptation and acclimation

Domestication and selective breeding has resulted in over 1000 extant cattle breeds. Many of these breeds do not excel in important traits but are adapted to local environments. These adaptations are a valuable source of genetic material for efforts to improve commercial breeds. As a step toward this goal we identified candidate regions to be under selection in genomes of nine Russian native cattle breeds adapted to survive in harsh climates. After comparing our data to other breeds of European and Asian origins we found known and novel candidate genes that could potentially be related to domestication, economically important traits and environmental adaptations in cattle. The Russian cattle breed genomes contained regions under putative selection with genes that may be related to adaptations to harsh environments (e.g., AQP5, RAD50, and RETREG1). We found genomic signatures of selective sweeps near key genes related to economically important traits, such as the milk production (e.g., DGAT1, ABCG2), growth (e.g., XKR4), and reproduction (e.g., CSF2). Our data point to candidate genes which should be included in future studies attempting to identify genes to improve the extant breeds and facilitate generation of commercial breeds that fit better into the environments of Russia and other countries with similar climates