Granulin Knock Out Zebrafish Lack Frontotemporal Lobar Degeneration and Neuronal Ceroid Lipofuscinosis Pathology

Loss of function mutations in granulin (GRN) are linked to two distinct neurological disorders, frontotemporal lobar degeneration (FTLD) and neuronal ceroid lipofuscinosis (NCL). It is so far unknown how a complete loss of GRN in NCL and partial loss of GRN in FTLD can result in such distinct diseases. In zebrafish, there are two GRN homologues, Granulin A (Grna) and Granulin B (Grnb). We have generated stable Grna and Grnb loss of function zebrafish mutants by zinc finger nuclease mediated genome editing. Surprisingly, the grna and grnb single and double mutants display neither spinal motor neuron axonopathies nor a reduced number of myogenic progenitor cells as previously reported for Grna and Grnb knock down embryos. Additionally, grna-/-;grnb-/- double mutants have no obvious FTLD- and NCL-related biochemical and neuropathological phenotypes. Taken together, the Grna and Grnb single and double knock out zebrafish lack any obvious morphological, pathological and biochemical phenotypes. Loss of zebrafish Grna and Grnb might therefore either be fully compensated or only become symptomatic upon additional challenge

Finite element analysis of gradient coil deformation and vibration in NMR microscopy

Resolution degradation due to gradient coil deformation and vibration in NMR microscopy is investigated using finite element analysis. From the analysis, deformations due to the Lorentz force can be as large as 1-10 μm depending on the gradient strength and coil frame material. Thus, these deformations can be one of the major resolution limiting factors in NMR microscopy. Coil vibration, which depends on the input current waveform and resolution degradation due to time-variant deformation and time-invariant deformation are investigated by numerical simulations

Inside the Bondi radius of M87

Chandra X-ray observations of the nearby brightest cluster galaxy M87 resolve the hot gas structure across the Bondi accretion radius of the central supermassive black hole, a measurement possible in only a handful of systems but complicated by the bright nucleus and jet emission. By stacking only short frame-time observations to limit pileup, and after subtracting the nuclear PSF, we analysed the X-ray gas properties within the Bondi radius at 0.12-0.22 kpc (1.5-2.8 arcsec), depending on the black hole mass. Within 2 kpc radius, we detect two significant temperature components, which are consistent with constant values of 2 keV and 0.9 keV down to 0.15 kpc radius. No evidence was found for the expected temperature increase within ~0.25 kpc due to the influence of the SMBH. Within the Bondi radius, the density profile is consistent with $\rho\propto r^{-1}$. The lack of a temperature increase inside the Bondi radius suggests that the hot gas structure is not dictated by the SMBH's potential and, together with the shallow density profile, shows that the classical Bondi rate may not reflect the accretion rate onto the SMBH. If this density profile extends in towards the SMBH, the mass accretion rate onto the SMBH could be at least two orders of magnitude less than the Bondi rate, which agrees with Faraday rotation measurements for M87. We discuss the evidence for outflow from the hot gas and the cold gas disk and for cold feedback, where gas cooling rapidly from the hot atmosphere could feed the cirumnuclear disk and fuel the SMBH. At 0.2 kpc radius, the cooler X-ray temperature component represents ~20% of the total X-ray gas mass and, by losing angular momentum to the hot gas component, could provide a fuel source of cold clouds within the Bondi radius.Comment: 14 pages, 8 figures, accepted by MNRA

THE ROLE OF DIAPHRAGMATIC BREATHING IN SELF-REGULATION SKILLS TRAINING

A central component of many psychological interventions is breathing training. Breathing training protocols based on a mindfulness or a cognitive behavioral therapy (CBT) have demonstrated value in the management of psychological and medical ailments. Yet, despite the wealth of literature examining each approach, little direct comparison exists. An additional concern is the proliferation of smart phone health (mHealth) applications (apps) providing breathing training with little empirical evidence to support their clinical use. A possible explanation for the interest in breathing and mHealth apps is the growing body of literature indicating breathing training provides wide ranging health benefits through improved stasis of the autonomic nervous system (ANS). As ANS dysregulation underlies many chronic health conditions such as persistent temporomandibular disorders (TMDs), there is a need for empirical research to identify the most effective modality of breathing training and validate the clinical efficacy of breathing based mHealth apps. Study One compared the effectiveness of a mindfulness breathing meditation (MB) and a CBT based protocol teaching diaphragmatic breathing (DB) to improve biomarkers of ANS stasis. An attention control approach based on the Nolen-Hoeksema task (C) was included as a comparison group. Ninety participants were randomly assigned to either the MB, DB, or C condition. Within each condition, 30 participants were provided skills training with practice time and completed a behavioral self-regulation task. Participants in the DB condition approach had significantly lower breathing rates than those in the MB and C conditions (p \u3c .001). DB condition participants experienced improvements on high-frequency heart rate variability (p \u3c .05) and the standard deviation in NN intervals (p \u3c .001), which served as indicators for ANS stasis. No differences were found between conditions on the behavioral self-regulation task (p’s \u3e .05). Given these results, the DB training protocol was converted into a mHealth app to facilitate a clinical trial with patients suffering persistent TMDs. Study Two examined the additive benefits of including the mHealth app with standard dental care (SDC+) versus standard dental care alone (SDC). Nineteen patients seeking care for persistent TMDs were recruited. All participants were asked to track daily ratings of pain (VAS), relaxation (RR), and complete weekly assessments on several comorbid psycho-social factors. Within the SDC+ condition participants were asked to track the proximate effects of each breathing practice on VAS and RR ratings. Given a high drop-out rate (nine participants) and low overall sample size (N = 10), results are exploratory at best. Within the SDC+ condition, results indicated reliable improvements in average VAS and RR ratings from before and after SDC+ participants used the mHealth app (p’s \u3c .05). Within a one session training paradigm, results supported the use of a DB based intervention above the use of a MB or C intervention. Future research should consider the effects of having multiple training sessions. Study Two results were complicated by a limited sample size and failed to provide a clear picture of whether the conjunctive treatment in the SDC+ condition provided additional symptom relief above traditional dental care alone. Although exploratory results indicated the mHealth app provided temporary improvements in pain and feelings of relaxation, a well powered trial is needed to clarify whether the finding represents an enduring treatment effect

Radiation performance of AlGaAs concentrator cells and expected performance of cascade structures

Aluminum gallium arsenide, GaAs, silicon and InGaAs cells have been irradiated with 1 MeV electrons and 37 MeV protons. These cells are candidates for individual cells in a cascade structure. Data is presented for both electron and proton irradiation studies for one sun and a concentration level of 100X AMO. Results of calculations on the radiation resistance of cascade cell structures based on the individual cell data are also presented. Both series connected and separately connected structures are investigated

The Effect of Variation of Ruling Section on the Mechanical Properties of Carburizing Steels

Tensile and impact tests have been made on various carburizing steels heat -treated in sizes ranging from l/2 in. up to 4 in. diameter. The materials covered the older standard steels generally used in Britain, and the various standard ` substitute' steels which have been introduced because of alloy shortages, and a comparison has been made between them

Improved simulation of aerosol, cloud, and density measurements by shuttle lidar

Data retrievals are simulated for a Nd:YAG lidar suitable for early flight on the space shuttle. Maximum assumed vertical and horizontal resolutions are 0.1 and 100 km, respectively, in the boundary layer, increasing to 2 and 2000 km in the mesosphere. Aerosol and cloud retrievals are simulated using 1.06 and 0.53 microns wavelengths independently. Error sources include signal measurement, conventional density information, atmospheric transmission, and lidar calibration. By day, tenuous clouds and Saharan and boundary layer aerosols are retrieved at both wavelengths. By night, these constituents are retrieved, plus upper tropospheric, stratospheric, and mesospheric aerosols and noctilucent clouds. Density, temperature, and improved aerosol and cloud retrievals are simulated by combining signals at 0.35, 1.06, and 0.53 microns. Particlate contamination limits the technique to the cloud free upper troposphere and above. Error bars automatically show effect of this contamination, as well as errors in absolute density nonmalization, reference temperature or pressure, and the sources listed above. For nonvolcanic conditions, relative density profiles have rms errors of 0.54 to 2% in the upper troposphere and stratosphere. Temperature profiles have rms errors of 1.2 to 2.5 K and can define the tropopause to 0.5 km and higher wave structures to 1 or 2 km

‘Cruel and unusual punishment’: an inter-jurisdictional study of the criminalisation of young people with complex support needs

Although several criminologists and social scientists have drawn attention to the high rates of mental and cognitive disability amongst populations of young people embroiled in youth justice systems, less attention has been paid to the ways in which young people with disability are disproportionately exposed to processes of criminalisation and how the same processes serve to further disable them. In this paper, we aim to make a contribution towards filling this gap by drawing upon qualitative findings from the Comparative Youth Penality Project - an empirical inter-jurisdictional study of youth justice and penality in England and Wales and in four Australian states. We build on, integrate and extend theoretical perspectives from critical disability studies and from critical criminology to examine the presence of, and responses to, socio-economically disadvantaged young people with multiple disabilities (complex support needs) in youth justice systems in our selected jurisdictions. Four key findings emerge from our research pertaining to: (i) the criminalisation of disability and disadvantage; (ii) the management of children and young people with disabilities by youth justice agencies; (iii) the significance of early and holistic responses for children and young people with complex support needs; and (iv) the inadequate nature of community based support

Multiple spacecraft observations of interplanetary shocks: Characteristics of the upstream ULF turbulence

All interplanetary shocks observed by ISEE-3 and either ISEE-1 or ISEE-2 or both in 1978 and 1979 are examined for evidence of upstream waves. In order to characterize the properties of these shocks it is necessary to determine accurate shock normals. An overdetermined set of equations were inverted to obtain shock normals, velocities and error estimates for all these shocks. Tests of the method indicate it is quite reliable. Using these normals the Mach number and angle were between the interplanetary magnetic field and the shock normal for each shock. The upstream waves were separated into two classes: whistler mode precursors which occur at low Mach numbers and upstream turbulence whose amplitude at Mach numbers greater than 1.5 is controlled by the angle of the field to the shock normal. The former waves are right hand circularly polarized and quite monochromatic. The latter waves are more linearly polarized and have a broadband featureless spectrum