Paul Grady and his contributions to accounting and auditing

Paul Franklin Grady (1900-1984) was one of those leaders whose contributions to accounting will remain the subject of intensive study for future guidance. The purpose of this paper is to examine Paul Grady\u27s significant contributions to accounting and auditing and to take the reader into Grady\u27s mind as he was writing his most influential works. Grady strongly believed that in order for accounting to gain respect in society, it must be based on solid principles. His works showed this conviction

Binding to medium and long chain fatty acyls is a common property of HEAT and ARM repeat modules.

Covalent post-translational modification (PTM) of proteins with acyl groups of various carbon chain-lengths regulates diverse biological processes ranging from chromatin dynamics to subcellular localization. While the YEATS domain has been found to be a prominent reader of acetylation and other short acyl modifications, whether additional acyl-lysine reader domains exist, particularly for longer carbon chains, is unclear. Here, we employed a quantitative proteomic approach using various modified peptide baits to identify reader proteins of various acyl modifications. We discovered that proteins harboring HEAT and ARM repeats bind to lysine myristoylated peptides. Recombinant HEAT and ARM repeats bind to myristoylated peptides independent of the peptide sequence or the position of the myristoyl group. Indeed, HEAT and ARM repeats bind directly to medium- and long-chain free fatty acids (MCFA and LCFA). Lipidomic experiments suggest that MCFAs and LCFAs interact with HEAT and ARM repeat proteins in mammalian cells. Finally, treatment of cells with exogenous MCFAs and inhibitors of MCFA-CoA synthases increase the transactivation activity of the ARM repeat protein β-catenin. Taken together, our results suggest an unappreciated role for fatty acids in the regulation of proteins harboring HEAT or ARM repeats

The Analysis of Iterative Elliptic PDE Solvers Based on The Cubic Hermite Collocation Discretization

Abstract. Collocation methods based on bicubic Hermite piecewise polynomials have been proven effective t.echniques for solving second-order linear elliptic PDEs with mixed boundary conditions. The corresponding linear system is in general non-symmetric and non-diagonally dominant. Iterative methods for their solution arc not known and they aTC currently solved using Gauss elimination with scaling and partial pivoting. Point iterat.ive methods do not convcrge even for the collocation equations obtained from model PDE problems. The del/elopment of efficient iterative solvers for these equations is necessary for three-dimensional problems and their parallel solution, since direct solvers tend to be space bound and their parallelization is difficult. In this thesis, we develop block iterative methods for the collocation equations of elliptic PDEs defined on a rectangle and subject to uncoupled mixed boundary conditions. For model problems of this type, we derive analytic expressions for the eigenvalues of the block Jacobi iteration matrix: and determine the optimal parameter for the block SOR method. For the case of general domains, the iterative solution of tile collocation equations is still an open problem. We address this open problem b

A small molecule ApoE4-targeted therapeutic candidate that normalizes sirtuin 1 levels and improves cognition in an Alzheimer's disease mouse model.

We describe here the results from the testing of a small molecule first-in-class apolipoprotein E4 (ApoE4)-targeted sirtuin1 (SirT1) enhancer, A03, that increases the levels of the neuroprotective enzyme SirT1 while not affecting levels of neurotoxic sirtuin 2 (SirT2) in vitro in ApoE4-transfected cells. A03 was identified by high-throughput screening (HTS) and found to be orally bioavailable and brain penetrant. In vivo, A03 treatment increased SirT1 levels in the hippocampus of 5XFAD-ApoE4 (E4FAD) Alzheimer's disease (AD) model mice and elicited cognitive improvement while inducing no observed toxicity. We were able to resolve the enantiomers of A03 and show using in vitro models that the L-enantiomer was more potent than the corresponding D-enantiomer in increasing SirT1 levels. ApoE4 expression has been shown to decrease the level of the NAD-dependent deacetylase and major longevity determinant SirT1 in brain tissue and serum of AD patients as compared to normal controls. A deficiency in SirT1 level has been recently implicated in increased tau acetylation, a dominant post-translational modification and key pathological event in AD and tauopathies. Therefore, as a novel approach to therapeutic development for AD, we targeted identification of compounds that enhance and normalize brain SirT1 levels

The mPower Study, Parkinson Disease Mobile Data Collected Using Researchkit

Current measures of health and disease are often insensitive, episodic, and subjective. Further, these measures generally are not designed to provide meaningful feedback to individuals. The impact of high-resolution activity data collected from mobile phones is only beginning to be explored. Here we present data from mPower, a clinical observational study about Parkinson disease conducted purely through an iPhone app interface. The study interrogated aspects of this movement disorder through surveys and frequent sensor-based recordings from participants with and without Parkinson disease. Benefitting from large enrollment and repeated measurements on many individuals, these data may help establish baseline variability of real-world activity measurement collected via mobile phones, and ultimately may lead to quantification of the ebbs-and-flows of Parkinson symptoms. App source code for these data collection modules are available through an open source license for use in studies of other conditions. We hope that releasing data contributed by engaged research participants will seed a new community of analysts working collaboratively on understanding mobile health data to advance human health

The Massive Progenitor of the Possible Type II-Linear Supernova 2009hd in Messier 66

We present observations of SN2009hd in the nearby galaxy M66. This SN is one of the closest to us in recent years but heavily obscured by dust, rendering it unusually faint in the optical, given its proximity. We find that the observed properties of SN2009hd support its classification as a possible Type II-L SN, a relatively rare subclass of CC-SNe. High-precision relative astrometry has been employed to attempt to identify a SN progenitor candidate, based on a pixel-by-pixel comparison between HST F555W and F814W images of the SN site prior to explosion and at late times. A progenitor candidate is identified in the F814W images only; this object is undetected in F555W. Significant uncertainty exists in the astrometry, such that we cannot definitively identify this object as the SN progenitor. Via insertion of artificial stars into the pre-SN HST images, we are able to constrain the progenitor's properties to those of a possible supergiant, with M(F555W)0>-7.6 mag and (V-I) 0>0.99 mag. The magnitude and color limits are consistent with a luminous RSG; however, they also allow for the possibility that the star could have been more yellow than red. From a comparison with theoretical massive-star evolutionary tracks, which include rotation and pulsationally enhanced mass loss, we can place a conservative upper limit on the initial mass for the progenitor of <20 M_sun. If the actual mass of the progenitor is near the upper range allowed by our derived mass limit, then it would be consistent with that for the identified progenitors of the SNII-L 2009kr and the high-luminosity SNII-P 2008cn. The progenitors of these three SNe may possibly bridge the gap between lower-mass RSG that explode as SNeII-P and LBV, or more extreme RSG, from which the more exotic SNeII-n may arise. Very late-time imaging of the SN2009hd site may provide us with more clues regarding the true nature of its progenitor.Comment: 19 pages, 9 figures, 3 tables, accepted for publication in Ap

Europe’s perennial "outsiders": a processual approach to Roma stigmatization and ghettoization

This paper draws on the theoretical work of Norbert Elias and Loïc Wacquant in seeking to understand the stigmatized and marginalized position of the Roma population within Europe. The paper argues that the persistent persecution of Roma, reflected in social policy, cannot be understood without reference to long-term social processes, which shape the nature of the asymmetric power relations between Roma and non-Roma. Elias's theory of established-outsider relations is applied at the intra-state European level in arguing that Roma constitute a cross-border "outsider" group; with their intense stigmatization explained and perpetuated by a common set of collective fantasies which are maintained through complex group processes of disidentification, and which result in Roma being seen as of lesser human worth. Wacquant's theoretical concept of the "ghetto" is then drawn upon to show how the manifestations of stigmatization for the stigmatized are at once psychological, social and spatial. The paper suggests that the synthesis of the two theorists' relational, theoretical concepts allows for an approach that can expose the way in which power is exercised within and through group relations. Such an approach emphasizes the centrality of the interdependence between Roma and non-Roma, and the fluctuating power balance that characterises that relationship across time and space. The paper concludes that, while existing research focused on policy and outcomes is useful in understanding the negative contemporary experiences of Roma populations, they need to be understood in the context of wider social processes and historical continuities in seeking to elucidate how these processes shape policies and contribute to social and spatial marginalization

Triggered star formation and the creation of the supergiant H 1 in shell in IC 2574

Based on deep imaging from the Advanced Camera for Surveys aboard the Hubble Space Telescope (HST), we present new evidence that stellar feedback created a ~1 kpc supergiant H I shell (SGS) and triggered star formation (SF) around its rim in the M81 Group dwarf irregular galaxy IC 2574. Using photometry of the resolved stars from the HST images, we measure the star formation history of a region including the SGS, focusing on the past 500 Myr, and employ the unique properties of blue helium-burning stars to create a movie of SF in the SGS. We find two significant episodes of SF inside the SGS from 200-300 Myr and ~25 Myr ago. Comparing the timing of the SF events to the dynamic age of the SGS and the energetics from the H I and SF, we find compelling evidence that stellar feedback is responsible for creating the SGS and triggering secondary SF around its rim