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The purpose of this study was to evaluate CatWalk's capability for assessing the functional outcome after photothrombotic stroke affecting the motor cortex of mice. Mice were tested up to 21 days after photothrombosis or sham surgery using CatWalk, and a composite score assessing functional deficits (neuroscore). The neuroscore demonstrated deficits of the contralateral forelimb for more than two weeks after stroke. There were no asymmetric or coordinative dysfunctions of limbs detected by CatWalk. However, CatWalk data revealed impairment of locomotion speed and its depending parameters for one-week after stroke in strong correlation to the neuroscore. Data suggest that the composite neuroscore allows to more sensitively and precisely specify and quantify photothrombosis-induced hemisyndromes than CatWalk.

Low intensity transcranial electrical stimulation (TES) in humans, encompassing transcranial direct current (tDCS), transcutaneous spinal Direct Current Stimulation (tsDCS), transcranial alternating current (tACS), and transcranial random noise (tRNS) stimulation or their combinations, appears to be safe. No serious adverse events (SAES) have been reported so far in over 18,000 sessions administered to healthy subjects, neurological and psychiatric patients, as summarized here. Moderate adverse events (AEs), as defined by the necessity to intervene, are rare, and include skin burns with tDCS due to suboptimal electrode-skin contact. Very rarely mania or hypomania was induced in patients with depression (11 documented cases), yet a causal relationship is difficult to prove because of the low incidence rate and limited numbers of subjects in controlled trials. Mild AEs (MAEs) include headache and fatigue following stimulation as well as prickling and burning sensations occurring during tDCS at peak-to-baseline intensities of 1-2 mA and during tACS at higher peak-to-peak intensities above 2 mA.& para;& para;The prevalence of published AEs is different in studies specifically assessing AEs vs. those not assessing them, being higher in the former. AEs are frequently reported by individuals receiving placebo stimulation. The profile of AEs in terms of frequency, magnitude and type is comparable in healthy and clinical populations, and this is also the case for more vulnerable populations, such as children, elderly persons, or pregnant women. Combined interventions (e.g., co-application of drugs, electrophysiological measurements, neuroimaging) were not associated with further safety issues.& para;& para;Safety is established for low-intensity 'conventional' TES defined as <4 mA, up to 60 min duration per day. Animal studies and modeling evidence indicate that brain injury could occur at predicted current densities in the brain of 6.3-13 Afin(2) that are over an order of m

Low intensity transcranial electrical stimulation (TES) in humans, encompassing transcranial direct current (tDCS), transcutaneous spinal Direct Current Stimulation (tsDCS), transcranial alternating current (tACS), and transcranial random noise (tRNS) stimulation or their combinations, appears to be safe. No serious adverse events (SAEs) have been reported so far in over 18,000 sessions administered to healthy subjects, neurological and psychiatric patients, as summarized here. Moderate adverse events (AEs), as defined by the necessity to intervene, are rare, and include skin burns with tDCS due to suboptimal electrode-skin contact. Very rarely mania or hypomania was induced in patients with depression (11 documented cases), yet a causal relationship is difficult to prove because of the low incidence rate and limited numbers of subjects in controlled trials. Mild AEs (MAEs) include headache and fatigue following stimulation as well as prickling and burning sensations occurring during tDCS at peak-to-baseline intensities of 1–2 mA and during tACS at higher peak-to-peak intensities above 2 mA. The prevalence of published AEs is different in studies specifically assessing AEs vs. those not assessing them, being higher in the former. AEs are frequently reported by individuals receiving placebo stimulation. The profile of AEs in terms of frequency, magnitude and type is comparable in healthy and clinical populations, and this is also the case for more vulnerable populations, such as children, elderly persons, or pregnant women. Combined interventions (e.g., co-application of drugs, electrophysiological measurements, neuroimaging) were not associated with further safety issues. Safety is established for low-intensity ‘conventional’ TES defined as <4 mA, up to 60 min duration per day. Animal studies and modeling evidence indicate that brain injury could occur at predicted current densities in the brain of 6.3–13 A/m2 that are over an order of magnitude abo

Low intensity transcranial electrical stimulation (TES) in humans, encompassing transcranial direct current (tDCS), transcutaneous spinal Direct Current Stimulation (tsDCS), transcranial alternating current (tACS), and transcranial random noise (tRNS) stimulation or their combinations, appears to be safe. No serious adverse events (SAEs) have been reported so far in over 18,000 sessions administered to healthy subjects, neurological and psychiatric patients, as summarized here. Moderate adverse events (AEs), as defined by the necessity to intervene, are rare, and include skin burns with tDCS due to suboptimal electrode-skin contact. Very rarely mania or hypomania was induced in patients with depression (11 documented cases), yet a causal relationship is difficult to prove because of the low incidence rate and limited numbers of subjects in controlled trials. Mild AEs (MAEs) include headache and fatigue following stimulation as well as prickling and burning sensations occurring during tDCS at peak-to-baseline intensities of 1–2 mA and during tACS at higher peak-to-peak intensities above 2 mA. The prevalence of published AEs is different in studies specifically assessing AEs vs. those not assessing them, being higher in the former. AEs are frequently reported by individuals receiving placebo stimulation. The profile of AEs in terms of frequency, magnitude and type is comparable in healthy and clinical populations, and this is also the case for more vulnerable populations, such as children, elderly persons, or pregnant women. Combined interventions (e.g., co-application of drugs, electrophysiological measurements, neuroimaging) were not associated with further safety issues. Safety is established for low-intensity ‘conventional’ TES defined as <4 mA, up to 60 min duration per day. Animal studies and modeling evidence indicate that brain injury could occur at predicted current densities in the brain of 6.3–13 A/m2that are over an order of magnitude above

The TAIGA project is aimed at solving the fundamental problems of gamma-ray astronomy and physics of ultrahigh energy cosmic rays with the help of the complex of detectors, located in the Tunka valley (Siberia, Russia). TAIGA includes a wide-angle large area Tunka-HiSCORE array, designed to detect gamma-rays of ultrahigh energies in the range 20 - 1000 TeV and charged cosmic rays with energies of 100 TeV - 100 PeV, large area muon detector to improve the rejection of background EAS protons and nuclei and a network of imaging atmospheric Cherenkov telescopes for gamma radiation detection. We discuss the goals and objectives of the complex features of each detector and the results obtained in the first stage of the HiSCORE installation., Peer Reviewed

The gamma-ray energy regime beyond 10 TeV is crucial for the search for the most energetic Galactic accelerators. The energy spectra of most known gamma-ray emitters only reach up to few 10s of TeV, with 80 TeV from the Crab Nebula being the highest energy so far observed significantly. Uncovering their spectral shape up to few 100 TeV could answer the question whether some of these objects are cosmic ray Pevatrons, i.e. Galactic PeV accelerators. Sensitive observations in this energy range and beyond require very large effective detector areas of several 10s to 100 square-km. While imaging air Cherenkov telescopes have proven to be the instruments of choice in the GeV to TeV energy range, very large area telescope arrays are limited by the number of required readout channels per instrumented square-km (due to the large number of channels per telescope). Alternatively, the shower-front sampling technique allows to instrument large effective areas and also naturally provides large viewing angles of the instrument. Solely measuring the shower front light density and timing (hence timing- arrays), the primary particle properties are reconstructed on the basis of the measured lateral density function and the shower front arrival times. This presentation gives an overview of the technique, its goals, and future perspective., Peer Reviewed

Strategies for non-invasive and quantitative imaging of gene expression in vivo have been developed over the past decade. Non-invasive assessment of the dynamics of gene regulation is of interest for the detection of endogenous disease-specific biological alterations (e.g., signal transduction) and for monitoring the induction and regulation of therapeutic genes (e.g., gene therapy). To demonstrate that non-invasive imaging of regulated expression of any type of gene after in vivo transduction by versatile vectors is feasible, we generated regulatable herpes simplex virus type 1 (HSV-1) amplicon vectors carrying hormone (mifepristone) or antibiotic (tetracycline) regulated promoters driving the proportional co-expression of two marker genes. Regulated gene expression was monitored by fluorescence microscopy in culture and by positron emission tomography (PET) or bioluminescence (BLI) in vivo. The induction levels evaluated in glioma models varied depending on the dose of inductor. With fluorescence microscopy and BLI being the tools for assessing gene expression in culture and animal models, and with PET being the technology for possible application in humans, the generated vectors may serve to non-invasively monitor the dynamics of any gene of interest which is proportionally co-expressed with the respective imaging marker gene in research applications aiming towards translation into clinical application.

To further develop gene therapy for patients with glioblastomas, an experimental gene therapy protocol was established comprising a series of imaging parameters for (i) noninvasive assessment of viable target tissue followed by (ii) targeted application of herpes simplex virus type 1 (HSV-1) amplicon vectors and (iii) quantification of treatment effects by imaging. We show that viable target tissue amenable for application of gene therapy vectors can be identified by multitracer positron emission tomography (PET) using 2-18F-fluoro-2- deoxy-D-glucose, methyl-11C-L-methionine, or 3¶-deoxy-3¶-18Ffluoro- L-thymidine ([18F]FLT). Targeted application of HSV-1 amplicon vectors containing two therapeutic genes with synergistic antitumor activity (Escherichia coli cytosine deaminase, cd, and mutated HSV-1 thymidine kinase, tk39, fused to green fluorescent protein gene, gfp) leads to an overall response rate of 68%, with 18% complete responses and 50% partial responses. Most importantly, we show that the ‘‘tissue dose’’ of HSV-1 amplicon vector–mediated gene expression can be noninvasively assessed by -[4-18F-fluoro-3- (hydroxymethyl)butyl]guanine ([18F]FHBG) PET. Therapeutic effects could be monitored by PET with significant differences in [18F]FLT accumulation in all positive control tumors and 72% in vivo transduced tumors (P = 0.01) as early as 4 days after prodrug therapy. For all stably and in vivo transduced tumors, cdIREStk39gfp gene expression as measured by [18F]FHBG-PET correlated with therapeutic efficiency as measured by [18F]FLT-PET. These data indicate that imagingguided vector application with determination of tissue dose of vector-mediated gene expression and correlation to induced therapeutic effect using multimodal imaging is feasible. This strategy will help in the development of safe and efficient gene therapy protocols for clinical application.