Automated four-dimensional long term imaging enables single cell tracking within organotypic brain slices to study neurodevelopment and degeneration.

Current approaches for dynamic profiling of single cells rely on dissociated cultures, which lack important biological features existing in tissues. Organotypic slice cultures preserve aspects of structural and synaptic organisation within the brain and are amenable to microscopy, but established techniques are not well adapted for high throughput or longitudinal single cell analysis. Here we developed a custom-built, automated confocal imaging platform, with improved organotypic slice culture and maintenance. The approach enables fully automated image acquisition and four-dimensional tracking of morphological changes within individual cells in organotypic cultures from rodent and human primary tissues for at least 3 weeks. To validate this system, we analysed neurons expressing a disease-associated version of huntingtin (HTT586Q138-EGFP), and observed that they displayed hallmarks of Huntington's disease and died sooner than controls. By facilitating longitudinal single-cell analyses of neuronal physiology, our system bridges scales necessary to attain statistical power to detect developmental and disease phenotypes

Non-Abelian Dark Sectors and Their Collider Signatures

Motivated by the recent proliferation of observed astrophysical anomalies, Arkani-Hamed et al. have proposed a model in which dark matter is charged under a non-abelian "dark" gauge symmetry that is broken at ~ 1 GeV. In this paper, we present a survey of concrete models realizing such a scenario, followed by a largely model-independent study of collider phenomenology relevant to the Tevatron and the LHC. We address some model building issues that are easily surmounted to accommodate the astrophysics. While SUSY is not necessary, we argue that it is theoretically well-motivated because the GeV scale is automatically generated. Specifically, we propose a novel mechanism by which mixed D-terms in the dark sector induce either SUSY breaking or a super-Higgs mechanism precisely at a GeV. Furthermore, we elaborate on the original proposal of Arkani-Hamed et al. in which the dark matter acts as a messenger of gauge mediation to the dark sector. In our collider analysis we present cross-sections for dominant production channels and lifetime estimates for primary decay modes. We find that dark gauge bosons can be produced at the Tevatron and the LHC, either through a process analogous to prompt photon production or through a rare Z decay channel. Dark gauge bosons will decay back to the SM via "lepton jets" which typically contain >2 and as many as 8 leptons, significantly improving their discovery potential. Since SUSY decays from the MSSM will eventually cascade down to these lepton jets, the discovery potential for direct electroweak-ino production may also be improved. Exploiting the unique kinematics, we find that it is possible to reconstruct the mass of the MSSM LSP. We also present decay channels with displaced vertices and multiple leptons with partially correlated impact parameters.Comment: 44 pages, 25 figures, version published in JHE

The Flexibility of Nonconsciously Deployed Cognitive Processes: Evidence from Masked Congruence Priming

Background: It is well accepted in the subliminal priming literature that task-level properties modulate nonconscious processes. For example, in tasks with a limited number of targets, subliminal priming effects are limited to primes that are physically similar to the targets. In contrast, when a large number of targets are used, subliminal priming effects are observed for primes that share a semantic (but not necessarily physical) relationship with the target. Findings such as these have led researchers to conclude that task-level properties can direct nonconscious processes to be deployed exclusively over central (semantic) or peripheral (physically specified) representations. Principal Findings: We find distinct patterns of masked priming for "novel" and "repeated" primes within a single task context. Novel primes never appear as targets and thus are not seen consciously in the experiment. Repeated primes do appear as targets, thereby lending themselves to the establishment of peripheral stimulus-response mappings. If the source of the masked priming effect were exclusively central or peripheral, then both novel and repeated primes should yield similar patterns of priming. In contrast, we find that both novel and repeated primes produce robust, yet distinct, patterns of priming. Conclusions: Our findings indicate that nonconsciously elicited cognitive processes can be flexibly deployed over both central and peripheral representations within a single task context. While we agree that task-level properties can influence nonconscious processes, our findings sharply constrain the extent of this influence. Specifically, our findings are inconsistent with extant accounts which hold that the influence of task-level properties is strong enough to restrict the deployment of nonconsciously elicited cognitive processes to a single type of representation (i.e. central or peripheral).13 page(s

Testing the Dark Matter Annihilation Model for the WMAP Haze

Analyses have found a "haze" of anomalous microwave emission surrounding the Galactic Center in the WMAP sky maps. A recent study using Fermi data detected a similar haze in the gamma-ray. Several studies have modeled these hazes as radiation from the leptonic byproducts of dark matter annihilations, and arguably no convincing astrophysical alternative has been suggested. We discuss the characteristics of astrophysical cosmic ray sources that could potentially explain this microwave and gamma-ray emission. The most promising astrophysical scenarios involve cosmic ray sources that are clustered such that many fall within ~1 kpc of the Galactic Center. For example, we show that several hundred Galactic Center supernovae in the last million years plus a diffusion-hardened electron spectrum may be consistent with present constraints on this emission. Alternatively, it could be due to a burst of activity probably associated with Sagittarius A* occurring ~1 Myr ago and producing >10^51 erg in cosmic ray electrons. Different models predict different trends for the spectral index of the microwave and gamma-ray spectrum as a function of angle from the Galactic Center that should be robust to cosmic ray propagation uncertainties. In particular, if the haze is from dark matter annihilations, it should have a very hard microwave and gamma-ray spectrum for which the spectral shape does not change significantly with angle, which we argue would be difficult to achieve with any astrophysical mechanism. Observations with the Planck and Fermi satellites can distinguish between viable haze models using these signatures.Comment: 15 pages, 7 figures, accepted to MNRA

A Measurement of Arcminute Anisotropy in the Cosmic Microwave Background with the Sunyaev-Zel'dovich Array

We present 30 GHz measurements of the angular power spectrum of the cosmic microwave background (CMB) obtained with the Sunyaev-Zel'dovich Array. The measurements are sensitive to arcminute angular scales, where secondary anisotropy from the Sunyaev-Zel'dovich effect (SZE) is expected to dominate. For a broad bin centered at multipole 4066 we find 67+77-50 uK^2, of which 26+/-5 uK^2 is the expected contribution from primary CMB anisotropy and 80+/-54 uK^2 is the expected contribution from undetected radio sources. These results imply an upper limit of 155 uK^2 (95% CL) on the secondary contribution to the anisotropy in our maps. This level of SZE anisotropy power is consistent with expectations based on recent determinations of the normalization of the matter power spectrum, i.e., sigma_8~0.8.Comment: ApJ, 713, 82-89, (2010

De Novo Formation of Insulin-Producing “Neo-β Cell Islets” from Intestinal Crypts

SUMMARY The ability to interconvert terminally differentiated cells could serve as a powerful tool for cell-based treatment of degenerative diseases, including diabetes mellitus. To determine which, if any, adult tissues are competent to activate an islet β cell program, we performed an in vivo screen by expressing three β cell “reprogramming factors” in a wide spectrum of tissues. We report that transient intestinal expression of these factors—Pdx1, MafA, and Ngn3 (PMN)—promotes rapid conversion of intestinal crypt cells into endocrine cells, which coalesce into “neoislets” below the crypt base. Neoislet cells express insulin and show ultrastructural features of β cells. Importantly, intestinal neoislets are glucose-responsive and able to ameliorate hyperglycemia in diabetic mice. Moreover, PMN expression in human intestinal “organoids” stimulates the conversion of intestinal epithelial cells into β-like cells. Our results thus demonstrate that the intestine is an accessible and abundant source of functional insulin-producing cells

The WiggleZ Dark Energy Survey: Direct constraints on blue galaxy intrinsic alignments at intermediate redshifts

Correlations between the intrinsic shapes of galaxy pairs, and between the intrinsic shapes of galaxies and the large-scale density field, may be induced by tidal fields. These correlations, which have been detected at low redshifts (z<0.35) for bright red galaxies in the Sloan Digital Sky Survey (SDSS), and for which upper limits exist for blue galaxies at z~0.1, provide a window into galaxy formation and evolution, and are also an important contaminant for current and future weak lensing surveys. Measurements of these alignments at intermediate redshifts (z~0.6) that are more relevant for cosmic shear observations are very important for understanding the origin and redshift evolution of these alignments, and for minimising their impact on weak lensing measurements. We present the first such intermediate-redshift measurement for blue galaxies, using galaxy shape measurements from SDSS and spectroscopic redshifts from the WiggleZ Dark Energy Survey. Our null detection allows us to place upper limits on the contamination of weak lensing measurements by blue galaxy intrinsic alignments that, for the first time, do not require significant model-dependent extrapolation from the z~0.1 SDSS observations. Also, combining the SDSS and WiggleZ constraints gives us a long redshift baseline with which to constrain intrinsic alignment models and contamination of the cosmic shear power spectrum. Assuming that the alignments can be explained by linear alignment with the smoothed local density field, we find that a measurement of \sigma_8 in a blue-galaxy dominated, CFHTLS-like survey would be contaminated by at most +/-0.02 (95% confidence level, SDSS and WiggleZ) or +/-0.03 (WiggleZ alone) due to intrinsic alignments. [Abridged]Comment: 18 pages, 12 figures, accepted to MNRAS; v2 has correction to one author's name, NO other changes; v3 has minor changes in explanation and calculations, no significant difference in results or conclusions; v4 has an additional footnote about model interpretation, no changes to data/calculations/result

The Atacama Cosmology Telescope: A Measurement of the Cosmic Microwave Background Power Spectrum at 148 and 218 GHz from the 2008 Southern Survey

We present measurements of the cosmic microwave background (CMB) power spectrum made by the Atacama Cosmology Telescope at 148 GHz and 218 GHz, as well as the cross-frequency spectrum between the two channels. Our results clearly show the second through the seventh acoustic peaks in the CMB power spectrum. The measurements of these higher-order peaks provide an additional test of the {\Lambda}CDM cosmological model. At l > 3000, we detect power in excess of the primary anisotropy spectrum of the CMB. At lower multipoles 500 < l < 3000, we find evidence for gravitational lensing of the CMB in the power spectrum at the 2.8{\sigma} level. We also detect a low level of Galactic dust in our maps, which demonstrates that we can recover known faint, diffuse signals.Comment: 19 pages, 13 figures. Submitted to ApJ. This paper is a companion to Hajian et al. (2010) and Dunkley et al. (2010