Optimising the multiplex factor of the frequency domain multiplexed readout of the TES-based microcalorimeter imaging array for the X-IFU instrument on the Athena Xray observatory

Athena is a space-based X-ray observatory intended for exploration of the hot and energetic universe. One of the science instruments on Athena will be the X-ray Integrated Field Unit (X-IFU), which is a cryogenic X-ray spectrometer, based on a large cryogenic imaging array of Transition Edge Sensors (TES) based microcalorimeters operating at a temperature of 100mK. The imaging array consists of 3800 pixels providing 2.5 eV spectral resolution, and covers a field of view with a diameter of of 5 arc minutes. Multiplexed readout of the cryogenic microcalorimeter array is essential to comply with the cooling power and complexity constraints on a space craft. Frequency domain multiplexing has been under development for the readout of TES-based detectors for this purpose, not only for the X-IFU detector arrays but also for TES-based bolometer arrays for the Safari instrument of the Japanese SPICA observatory. This paper discusses the design considerations which are applicable to optimise the multiplex factor within the boundary conditions as set by the space craft. More specifically, the interplay between the science requirements such as pixel dynamic range, pixel speed, and cross talk, and the space craft requirements such as the power dissipation budget, available bandwidth, and electromagnetic compatibility will be discussed

Development of frequency domain multiplexing for the X-ray Integral Field Unit (X-IFU) on the Athena

We are developing the frequency domain multiplexing (FDM) read-out of transition-edge sensor (TES) microcalorimeters for the X-ray Integral Field Unit (X-IFU) instrument on board of the future European X-Ray observatory Athena. The X-IFU instrument consists of an array of $\sim$3840 TESs with a high quantum efficiency ($>$90 \%) and spectral resolution $\Delta E$=2.5 eV $@$ 7 keV ($E/\Delta E\sim$2800). FDM is currently the baseline readout system for the X-IFU instrument. Using high quality factor LC filters and room temperature electronics developed at SRON and low-noise two stage SQUID amplifiers provided by VTT, we have recently demonstrated good performance with the FDM readout of Mo/Au TES calorimeters with Au/Bi absorbers. An integrated noise equivalent power resolution of about 2.0 eV at 1.7 MHz has been demonstrated with a pixel from a new TES array from NASA/Goddard (GSFC-A2). We have achieved X-ray energy resolutions $\sim$2.5 eV at AC bias frequency at 1.7 MHz in the single pixel read-out. We have also demonstrated for the first time an X-ray energy resolution around 3.0 eV in a 6 pixel FDM read-out with TES array (GSFC-A1). In this paper we report on the single pixel performance of these microcalorimeters under MHz AC bias, and further results of the performance of these pixels under FDM.Comment: 8 pages, 4 figures, Proceedings of the SPIE Astronomical Instrumentation "Space Telescopes and Instrumentation 2014: Ultraviolet to Gamma Ray

Soluble activin type IIB receptor improves fracture healing in a closed tibial fracture mouse model

Fractures still present a significant burden to patients due to pain and periods of unproductivity. Numerous growth factors have been identified to regulate bone remodeling. However, to date, only the bone morphogenetic proteins (BMPs) are used to enhance fracture healing in clinical settings. Activins are pleiotropic growth factors belonging to the TGF-beta superfamily. We and others have recently shown that treatment with recombinant fusion proteins of activin receptors greatly increases bone mass in different animal models by trapping activins and other ligands thus inhibiting their signaling pathways. However, their effects on fracture healing are less known. Twelve-week old male C57Bl mice were subjected to a standardized, closed tibial fracture model. Animals were divided into control and treatment groups and were administered either PBS control or a soluble activin type IIB receptor (ActRIIB-Fc) intraperitoneally once a week for a duration of two or four weeks. There were no significant differences between the groups at two weeks but we observed a significant increase in callus mineralization in ActRIIB-Fc-treated animals by microcomputed tomography imaging at four weeks. Bone volume per tissue volume was 60%, trabecular number 55% and bone mineral density 60% higher in the 4-week calluses of the ActRIIB-Fc-treated mice (p< 0.05 in all). Biomechanical strength of 4-week calluses was also significantly improved by ActRIIBFc treatment as stiffness increased by 64% and maximum force by 45% (p< 0.05) compared to the PBS-injected controls. These results demonstrate that ActRIIB-Fc treatment significantly improves healing of closed long bone fractures. Our findings support the previous reports of activin receptors increasing bone mass but also demonstrate a novel approach for using ActRIIB-Fc to enhance fracture healing

Antiepileptic drugs’ tolerability and safety – a systematic review and meta-analysis of adverse effects in dogs

<p>Various anti-epileptic drugs (AEDs) are used for the management of idiopathic epilepsy (IE) in dogs. Their safety profile is an important consideration for regulatory bodies, owners and prescribing clinicians. However, information on their adverse effects still remains limited with most of it derived from non-blinded non-randomized uncontrolled trials and case reports.</p><p><span>This poster won third place, which was presented at the Veterinary Evidence Today conference, Edinburgh November 1-3, 2016. </span></p><br /> <img src="https://www.veterinaryevidence.org/rcvskmod/icons/oa-icon.jpg" alt="Open Access" /

Overexpression of cathepsin K in mice decreases collagen deposition and lung resistance in response to bleomycin-induced pulmonary fibrosis

<p>Abstract</p> <p>Background</p> <p>Lung fibrosis is a devastating pulmonary disorder characterized by alveolar epithelial injury, extracellular matrix deposition and scar tissue formation. Due to its potent collagenolytic activity, cathepsin K, a lysosomal cysteine protease is an interesting target molecule with therapeutic potential to attenuate bleomycin-induced pulmonary fibrosis in mice. We here tested the hypothesis that over-expression of cathepsin K in the lungs of mice is protective in bleomycin-induced pulmonary fibrosis.</p> <p>Methods</p> <p>Wild-type and cathepsin K overexpressing (cathepsin K transgenic; cath K tg) mice were challenged intratracheally with bleomycin and sacrificed at 1, 2, 3 and 4 weeks post-treatment followed by determination of lung fibrosis by estimating lung collagen content, lung histopathology, leukocytic infiltrates and lung function. In addition, changes in cathepsin K protein levels in the lung were determined by immunohistochemistry, real time RT-PCR and western blotting.</p> <p>Results</p> <p>Cathepsin K protein levels were strongly increased in alveolar macrophages and lung parenchymal tissue of mock-treated cathepsin K transgenic (cath K tg) mice relative to wild-type mice and further increased particularly in cath K tg but also wild-type mice in response to bleomycin. Moreover, cath K tg mice responded with a lower collagen deposition in their lungs, which was accompanied by a significantly lower lung resistance (R_L) compared to bleomycin-treated wild-type mice. In addition, cath K tg mice responded with a lower degree of lung fibrosis than wild-type mice, a process that was found to be independent of inflammatory leukocyte mobilization in response to bleomycin challenge.</p> <p>Conclusion</p> <p>Over-expression of cathepsin K reduced lung collagen deposition and improved lung function parameters in the lungs of transgenic mice, thereby providing at least partial protection against bleomycin-induced lung fibrosis.</p

International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible

Fourier Transform Infrared Spectroscopic Imaging and Multivariate Regression for Prediction of Proteoglycan Content of Articular Cartilage

Fourier Transform Infrared (FT-IR) spectroscopic imaging has been earlier applied for the spatial estimation of the collagen and the proteoglycan (PG) contents of articular cartilage (AC). However, earlier studies have been limited to the use of univariate analysis techniques. Current analysis methods lack the needed specificity for collagen and PGs. The aim of the present study was to evaluate the suitability of partial least squares regression (PLSR) and principal component regression (PCR) methods for the analysis of the PG content of AC. Multivariate regression models were compared with earlier used univariate methods and tested with a sample material consisting of healthy and enzymatically degraded steer AC. Chondroitinase ABC enzyme was used to increase the variation in PG content levels as compared to intact AC. Digital densitometric measurements of Safranin O –stained sections provided the reference for PG content. The results showed that multivariate regression models predict PG content of AC significantly better than earlier used absorbance spectrum (i.e. the area of carbohydrate region with or without amide I normalization) or second derivative spectrum univariate parameters. Increased molecular specificity favours the use of multivariate regression models, but they require more knowledge of chemometric analysis and extended laboratory resources for gathering reference data for establishing the models. When true molecular specificity is required, the multivariate models should be used