Resolving IRAS 09111-1007 at 350 microns - a different path to ULIRG formation?

We have resolved the ultraluminous infrared galaxy (ULIRG), IRAS 09111-1007, with the new 350 micron-optimised Second Generation Submillimeter High Angular Resolution Camera (SHARC II) and present the first submillimetre fluxes and images for the system. IRAS 09111-1007 comprises two interacting luminous infrared galaxies (LIRGs) with a projected nuclear separation of 39 kpc. The Western galaxy is roughly four times more luminous in the submillimetre than its Eastern counterpart. It is an extremely bright LIRG with an AGN. The classification of the Eastern source is uncertain: it could be a Seyfert 2 galaxy or a LINER. We highlight IRAS 09111-1007 as a system that necessitates further study: a double AGN ULIRG whose molecular gas content differs from other widely separated pairs and whose ULIRG phase might not be explained by current multiple merger and/or final stage ULIRG scenarios.Comment: 6 pages, 4 figures. Accepted for publication in MNRAS Letter

Design and Fabrication Highlights Enabling a 2mm, 128 Element Bolometer Array for GISMO

The design and fabrication of a background limited, 128 pixel Transition Edge Sensor (TES) bolometer array for the Goddard IRAM Super-conducting 2-mm Observer (GISMO) is presented

An academic hospitalist model to improve healthcare worker communication and learner education: Results from a quasi‐experimental study at a veterans affairs medical center

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102160/1/jhm2105.pd

First Constraints on Source Counts at 350 Microns

We have imaged a $\sim$6 arcminute$^2$ region in the Bo\"otes Deep Field using the 350 $\mu$m-optimised second generation Submillimeter High Angular Resolution Camera (SHARC II), achieving a peak 1$\sigma$ sensitivity of $\sim$5 mJy. We detect three sources above 3$\sigma$, and determine a spurious source detection rate of 1.09 in our maps. In the absence of $5\sigma$ detections, we rely on deep 24 $\mu$m and 20 cm imaging to deduce which sources are most likely to be genuine, giving two real sources. From this we derive an integral source count of 0.84$^{+1.39}_{-0.61}$ sources arcmin$^{-2}$ at $S>13$ mJy, which is consistent with 350 $\mu$m source count models that have an IR-luminous galaxy population evolving with redshift. We use these constraints to consider the future for ground-based short-submillimetre surveys.Comment: accepted for publication in The Astrophysical Journa

The Primordial Inflation Polarization Explorer (PIPER)

The Primordial Inflation Polarization Explorer (PIPER) is a balloon-borne cosmic microwave background (CMB) polarimeter designed to search for evidence of inflation by measuring the large-angular scale CMB polarization signal. BICEP2 recently reported a detection of B-mode power corresponding to the tensor-to-scalar ratio r = 0.2 on ~2 degree scales. If the BICEP2 signal is caused by inflationary gravitational waves (IGWs), then there should be a corresponding increase in B-mode power on angular scales larger than 18 degrees. PIPER is currently the only suborbital instrument capable of fully testing and extending the BICEP2 results by measuring the B-mode power spectrum on angular scales $\theta$ = ~0.6 deg to 90 deg, covering both the reionization bump and recombination peak, with sensitivity to measure the tensor-to-scalar ratio down to r = 0.007, and four frequency bands to distinguish foregrounds. PIPER will accomplish this by mapping 85% of the sky in four frequency bands (200, 270, 350, 600 GHz) over a series of 8 conventional balloon flights from the northern and southern hemispheres. The instrument has background-limited sensitivity provided by fully cryogenic (1.5 K) optics focusing the sky signal onto four 32x40-pixel arrays of time-domain multiplexed Transition-Edge Sensor (TES) bolometers held at 140 mK. Polarization sensitivity and systematic control are provided by front-end Variable-delay Polarization Modulators (VPMs), which rapidly modulate only the polarized sky signal at 3 Hz and allow PIPER to instantaneously measure the full Stokes vector (I, Q, U, V) for each pointing. We describe the PIPER instrument and progress towards its first flight.Comment: 11 pages, 7 figures. To be published in Proceedings of SPIE Volume 9153. Presented at SPIE Astronomical Telescopes + Instrumentation 2014, conference 915

Preclinical Evaluation of Novel Fatty Acid Synthase Inhibitors in Primary Colorectal Cancer Cells and a Patient-Derived Xenograft Model of Colorectal Cancer

Fatty Acid Synthase (FASN), a key enzyme of de novo lipogenesis, is upregulated in many cancers including colorectal cancer (CRC); increased FASN expression is associated with poor prognosis. Potent FASN inhibitors (TVBs) developed by 3-V Biosciences demonstrate anti-tumor activity in vitro and in vivo and a favorable tolerability profile in a Phase I clinical trial. However, CRC characteristics associated with responsiveness to FASN inhibition are not fully understood. We evaluated the effect of TVB-3664 on tumor growth in nine CRC patient-derived xenografts (PDXs) and investigated molecular and metabolic changes associated with CRC responsiveness to FASN inhibition. CRC cells and PDXs showed a wide range of sensitivity to FASN inhibition. TVB-3664 treatment showed significant response (reduced tumor volume) in 30% of cases. Anti-tumor effect of TVB-3664 was associated with a significant decrease in a pool of adenine nucleotides and alterations in lipid composition including a significant reduction in fatty acids and phospholipids and an increase in lactosylceramide and sphingomyelin in PDXs sensitive to FASN inhibition. Moreover, Akt, Erk1/2 and AMPK were major oncogenic pathways altered by TVBs. In summary, we demonstrated that novel TVB inhibitors show anti-tumor activity in CRC and this activity is associated with a decrease in activation of Akt and Erk1/2 oncogenic pathways and significant alteration of lipid composition of tumors. Further understanding of genetic and metabolic characteristics of tumors susceptible to FASN inhibition may enable patient selection and personalized medicine approaches in CRC

Multipotential stromal cell abundance in cellular bone allograft: comparison with fresh age-matched iliac crest bone and bone marrow aspirate

Aim: To enumerate and characterize multipotential stromal cells (MSCs) in a cellular bone allograft and compare with fresh age-matched iliac crest bone and bone marrow (BM) aspirate. Materials and methods: MSC characterization used functional assays, confocal/scanning electron microscopy and whole-genome microarrays. Resident MSCs were enumerated by flow cytometry following enzymatic extraction. Results: Allograft material contained live osteocytes and proliferative bone-lining cells defined as MSCs by phenotypic and functional capacities. Without cultivation/expansion, the allograft displayed an 'osteoinductive' molecular signature and the presence of CD45-CD271+CD73+CD90+CD105+ MSCs; with a purity over 100-fold that of iliac crest bone. In comparison with BM, MSC numbers enzymatically released from 1 g of cellular allograft were equivalent to approximately 45 ml of BM aspirate. Conclusion: Cellular allograft bone represents a unique nonimmune material rich in MSCs and osteocytes. This osteoinductive graft represents an attractive alternative to autograft bone or composite/synthetic grafts in orthopedics and broader regenerative medicine settings

The GISMO Two-millimeter Deep Field in GOODS-N

We present deep continuum observations using the GISMO camera at a wavelength of 2 mm centered on the Hubble Deep Field in the GOODS-N field. These are the first deep field observations ever obtained at this wavelength. The 1σ sensitivity in the innermost ~4' of the 7' diameter map is ~135 μJy beam^(−1), a factor of three higher in flux/beam sensitivity than the deepest available SCUBA 850 μm observations, and almost a factor of four higher in flux/beam sensitivity than the combined MAMBO/AzTEC 1.2 mm observations of this region. Our source extraction algorithm identifies 12 sources directly, and another 3 through correlation with known sources at 1.2 mm and 850 μm. Five of the directly detected GISMO sources have counterparts in the MAMBO/AzTEC catalog, and four of those also have SCUBA counterparts. HDF850.1, one of the first blank-field detected submillimeter galaxies, is now detected at 2 mm. The median redshift of all sources with counterparts of known redshifts is med(z) = 2.91±0.94. Statistically, the detections are most likely real for five of the seven 2 mm sources without shorter wavelength counterparts, while the probability for none of them being real is negligible

RNA Gain-of-Function in Spinocerebellar Ataxia Type 8

Microsatellite expansions cause a number of dominantly-inherited neurological diseases. Expansions in coding-regions cause protein gain-of-function effects, while non-coding expansions produce toxic RNAs that alter RNA splicing activities of MBNL and CELF proteins. Bi-directional expression of the spinocerebellar ataxia type 8 (SCA8) CTG CAG expansion produces CUG expansion RNAs (CUGexp) from the ATXN8OS gene and a nearly pure polyglutamine expansion protein encoded by ATXN8 CAGexp transcripts expressed in the opposite direction. Here, we present three lines of evidence that RNA gain-of-function plays a significant role in SCA8: 1) CUGexp transcripts accumulate as ribonuclear inclusions that co-localize with MBNL1 in selected neurons in the brain; 2) loss of Mbnl1 enhances motor deficits in SCA8 mice; 3) SCA8 CUGexp transcripts trigger splicing changes and increased expression of the CUGBP1-MBNL1 regulated CNS target, GABA-A transporter 4 (GAT4/Gabt4). In vivo optical imaging studies in SCA8 mice confirm that Gabt4 upregulation is associated with the predicted loss of GABAergic inhibition within the granular cell layer. These data demonstrate that CUGexp transcripts dysregulate MBNL/CELF regulated pathways in the brain and provide mechanistic insight into the CNS effects of other CUGexp disorders. Moreover, our demonstration that relatively short CUGexp transcripts cause RNA gain-of-function effects and the growing number of antisense transcripts recently reported in mammalian genomes suggest unrecognized toxic RNAs contribute to the pathophysiology of polyglutamine CAG CTG disorders