Lentiviral vector-mediated overexpression of mutant ataxin-7 recapitulates SCA7 pathology and promotes accumulation of the FUS/TLS and MBNL1 RNA-binding proteins

International audienceBackground: We used lentiviral vectors (LVs) to generate a new SCA7 animal model overexpressing a truncated mutant ataxin-7 (MUT ATXN7) fragment in the mouse cerebellum, in order to characterize the specific neuropathological and behavioral consequences of the genetic defect in this brain structure. Results: LV-mediated overexpression of MUT ATXN7 into the cerebellum of C57/BL6 adult mice induced neuropathological features similar to that observed in patients, such as intranuclear aggregates in Purkinje cells (PC), loss of synaptic markers, neuroinflammation, and neuronal death. No neuropathological changes were observed when truncated wild-type ataxin-7 (WT ATXN7) was injected. Interestingly, the local delivery of LV-expressing mutant ataxin-7 (LV-MUT-ATXN7) into the cerebellum of wild-type mice also mediated the development of an ataxic phenotype at 8 to 12 weeks post-injection. Importantly, our data revealed abnormal levels of the FUS/TLS, MBNL1, and TDP-43 RNA-binding proteins in the cerebellum of the LV-MUT-ATXN7 injected mice. MUT ATXN7 overexpression induced an increase in the levels of the pathological phosphorylated TDP-43, and a decrease in the levels of soluble FUS/TLS, with both proteins accumulating within ATXN7-positive intranuclear inclusions. MBNL1 also co-aggregated with MUT ATXN7 in most PC nuclear inclusions. Interestingly, no MBNL2 aggregation was observed in cerebellar MUT ATXN7 aggregates. Immunohistochemical studies in postmortem tissue from SCA7 patients and SCA7 knock-in mice confirmed SCA7-induced nuclear accumulation of FUS/TLS and MBNL1, strongly suggesting that these proteins play a physiopathological role in SCA7. Conclusions: This study validates a novel SCA7 mouse model based on lentiviral vectors, in which strong and sustained expression of MUT ATXN7 in the cerebellum was found sufficient to generate motor defects

CMB polarimetry with BICEP: instrument characterization, calibration, and performance

BICEP is a ground-based millimeter-wave bolometric array designed to target the primordial gravity wave signature on the polarization of the cosmic microwave background (CMB) at degree angular scales. Currently in its third year of operation at the South Pole, BICEP is measuring the CMB polarization with unprecedented sensitivity at 100 and 150 GHz in the cleanest available 2% of the sky, as well as deriving independent constraints on the diffuse polarized foregrounds with select observations on and off the Galactic plane. Instrument calibrations are discussed in the context of rigorous control of systematic errors, and the performance during the first two years of the experiment is reviewed.Comment: 12 pages, 15 figures, updated version of a paper accepted for Millimeter and Submillimeter Detectors and Instrumentation for Astronomy IV, Proceedings of SPIE, 7020, 200

Laminate polyethylene window development for large aperture millimeter receivers

New experiments that target the B-mode polarization signals in the Cosmic Microwave Background require more sensitivity, more detectors, and thus larger-aperture millimeter-wavelength telescopes, than previous experiments. These larger apertures require ever larger vacuum windows to house cryogenic optics. Scaling up conventional vacuum windows, such as those made of High Density Polyethylene (HDPE), require a corresponding increase in the thickness of the window material to handle the extra force from the atmospheric pressure. Thicker windows cause more transmission loss at ambient temperatures, increasing optical loading and decreasing sensitivity. We have developed the use of woven High Modulus Polyethylene (HMPE), a material 100 times stronger than HDPE, to manufacture stronger, thinner windows using a pressurized hot lamination process. We discuss the development of a specialty autoclave for generating thin laminate vacuum windows and the optical and mechanical characterization of full scale science grade windows, with the goal of developing a new window suitable for BICEP Array cryostats and for future CMB applications

Ultra-thin large-aperture vacuum windows for millimeter wavelengths receivers

Targeting faint polarization patterns arising from Primordial Gravitational Waves in the Cosmic Microwave Background requires excellent observational sensitivity. Optical elements in small aperture experiments such as Bicep3 and Keck Array are designed to optimize throughput and minimize losses from transmission, reflection and scattering at millimeter wavelengths. As aperture size increases, cryostat vacuum windows must withstand larger forces from atmospheric pressure and the solution has often led to a thicker window at the expense of larger transmission loss. We have identified a new candidate material for the fabrication of vacuum windows: with a tensile strength two orders of magnitude larger than previously used materials, woven high-modulus polyethylene could allow for dramatically thinner windows, and therefore significantly reduced losses and higher sensitivity. In these proceedings we investigate the suitability of high-modulus polyethylene windows for ground-based CMB experiments, such as current and future receivers in the Bicep/Keck Array program. This includes characterizing their optical transmission as well as their mechanical behavior under atmospheric pressure. We find that such ultra-thin materials are promising candidates to improve the performance of large-aperture instruments at millimeter wavelengths, and outline a plan for further tests ahead of a possible upcoming field deployment of such a science-grade window

Absolute polarization angle calibration using polarized diffuse Galactic emission observed by BICEP

We present a method of cross-calibrating the polarization angle of a polarimeter using BICEP Galactic observations. \bicep\ was a ground based experiment using an array of 49 pairs of polarization sensitive bolometers observing from the geographic South Pole at 100 and 150 GHz. The BICEP polarimeter is calibrated to +/-0.01 in cross-polarization and less than +/-0.7 degrees in absolute polarization orientation. BICEP observed the temperature and polarization of the Galactic plane (R.A= 100 degrees ~ 270 degrees and Dec. = -67 degrees ~ -48 degrees). We show that the statistical error in the 100 GHz BICEP Galaxy map can constrain the polarization angle offset of WMAP Wband to 0.6 degrees +\- 1.4 degrees. The expected 1 sigma errors on the polarization angle cross-calibration for Planck or EPIC are 1.3 degrees and 0.3 degrees at 100 and 150 GHz, respectively. We also discuss the expected improvement of the BICEP Galactic field observations with forthcoming BICEP2 and Keck observations.Comment: 13 pages, 10 figures and 2 tables. To appear in Proceedings of SPIE Astronomical Telescopes and Instrumentation 201

Characterization of the BICEP Telescope for High-precision Cosmic Microwave Background Polarimetry

The Background Imaging of Cosmic Extragalactic Polarization (BICEP) experiment was designed specifically to search for the signature of inflationary gravitational waves in the polarization of the cosmic microwave background (CMB). Using a novel small-aperture refractor and 49 pairs of polarization-sensitive bolometers, BICEP has completed three years of successful observations at the South Pole beginning in 2006 February. To constrain the amplitude of the inflationary B-mode polarization, which is expected to be at least 7 orders of magnitude fainter than the 3 K CMB intensity, precise control of systematic effects is essential. This paper describes the characterization of potential systematic errors for the BICEP experiment, supplementing a companion paper on the initial cosmological results. Using the analysis pipelines for the experiment, we have simulated the impact of systematic errors on the B-mode polarization measurement. Guided by these simulations, we have established benchmarks for the characterization of critical instrumental properties including bolometer relative gains, beam mismatch, polarization orientation, telescope pointing, sidelobes, thermal stability, and timestream noise model. A comparison of the benchmarks with the measured values shows that we have characterized the instrument adequately to ensure that systematic errors do not limit BICEP's two-year results, and identifies which future refinements are likely necessary to probe inflationary B-mode polarization down to levels below a tensor-to-scalar ratio r = 0.1.Astronom

Ultra-thin large-aperture vacuum windows for millimeter wavelengths receivers

Targeting faint polarization patterns arising from Primordial Gravitational Waves in the Cosmic Microwave Background requires excellent observational sensitivity. Optical elements in small aperture experiments such as Bicep3 and Keck Array are designed to optimize throughput and minimize losses from transmission, reflection and scattering at millimeter wavelengths. As aperture size increases, cryostat vacuum windows must withstand larger forces from atmospheric pressure and the solution has often led to a thicker window at the expense of larger transmission loss. We have identified a new candidate material for the fabrication of vacuum windows: with a tensile strength two orders of magnitude larger than previously used materials, woven high-modulus polyethylene could allow for dramatically thinner windows, and therefore significantly reduced losses and higher sensitivity. In these proceedings we investigate the suitability of high-modulus polyethylene windows for ground-based CMB experiments, such as current and future receivers in the Bicep/Keck Array program. This includes characterizing their optical transmission as well as their mechanical behavior under atmospheric pressure. We find that such ultra-thin materials are promising candidates to improve the performance of large-aperture instruments at millimeter wavelengths, and outline a plan for further tests ahead of a possible upcoming field deployment of such a science-grade window

First attempt at measuring the CMB cross-polarization

We compute upper limits on CMB cross-polarization by cross-correlating the PIQUE and Saskatoon experiments. We also discuss theoretical and practical issues relevant to measuring cross-polarization and illustrate them with simulations of the upcoming BOOMERanG 2002 experiment. We present a method that separates all six polarization power spectra (TT, EE, BB, TE, TB, EB) without any other "leakage" than the familiar EE-BB mixing caused by incomplete sky coverage. Since E and B get mixed, one might expect leakage between TE and TB, between EE and EB and between BB and EB - our method eliminates this by preserving the parity symmetry under which TB and EB are odd and the other four power spectra are even.Comment: Polarization movies can be found at http://www.hep.upenn.edu/~angelica/polarization.htm

Receiver development for BICEP Array, a next-generation CMB polarimeter at the South Pole

A detection of curl-type (B-mode) polarization of the primary CMB would be direct evidence for the inflationary paradigm of the origin of the Universe. The Bicep/Keck Array (BK) program targets the degree angular scales, where the power from primordial B-mode polarization is expected to peak, with ever-increasing sensitivity and has published the most stringent constraints on inflation to date. Bicep Array (BA) is the Stage-3 instrument of the BK program and will comprise four Bicep3-class receivers observing at 30/40, 95, 150 and 220/270 GHz with a combined 32,000+ detectors; such wide frequency coverage is necessary for control of the Galactic foregrounds, which also produce degree-scale B-mode signal. The 30/40 GHz receiver is designed to constrain the synchrotron foreground and has begun observing at the South Pole in early 2020. By the end of a 3-year observing campaign, the full Bicep Array instrument is projected to reach σr between 0.002 and 0.004, depending on foreground complexity and degree of removal of B-modes due to gravitational lensing (delensing). This paper presents an overview of the design, measured on-sky performance and calibration of the first BA receiver. We also give a preview of the added complexity in the time-domain multiplexed readout of the 7,776-detector 150 GHz receiver