Cleveland: Confused City on a Seesaw

No detached, scholarly, objective examination of the past, this is an eyewitness account of Cleveland during Phil Porter\u27s fifty-year career as a working newspaperman in the city, told in his own blunt, subjective, often controversial style. Phil Porter retired in 1966 as executive editor of The Plain Dealer. Original publication date 1976.https://engagedscholarship.csuohio.edu/clevmembks/1051/thumbnail.jp

Methods for Diagnosing and Treating Alzheimer\u27s Disease (AD) Using the Molecules that Stabilize Intracellular Calcium (CA\u3csub\u3e2+\u3c/sub\u3e) Release

The subject technology relates, in part, to a method of treating Alzheimer\u27s Disease (AD), early-stage AD, elevated risk of AD, mild cognitive impairment (MCI), or other forms of age-related cognitive decline in a subject in need thereof by administering to the subject a molecule that promotes calcium-release stabilization in ryanodine receptors (RyRs) and/or inosital triphosphate receptors (InsP3Rs) in brain cells. Diagnostic methods using calcium-release stabilizing immunophilins, junctophilins or calmodulin are also disclosed

Reversal of Aging-Related Neuronal Ca\u3csup\u3e2+\u3c/sup\u3e Dysregulation and Cognitive Impairment by Delivery of a Transgene Encoding FK506-Binding Protein 12.6/1b to the Hippocampus

Brain Ca(2+) regulatory processes are altered during aging, disrupting neuronal, and cognitive functions. In hippocampal pyramidal neurons, the Ca(2+)-dependent slow afterhyperpolarization (sAHP) exhibits an increase with aging, which correlates with memory impairment. The increased sAHP results from elevated L-type Ca(2+) channel activity and ryanodine receptor (RyR)-mediated Ca(2+) release, but underlying molecular mechanisms are poorly understood. Previously, we found that expression of the gene encoding FK506-binding protein 12.6/1b (FKBP1b), a small immunophilin that stabilizes RyR-mediated Ca(2+) release in cardiomyocytes, declines in hippocampus of aged rats and Alzheimer\u27s disease subjects. Additionally, knockdown/disruption of hippocampal FKBP1b in young rats augments neuronal Ca(2+) responses. Here, we test the hypothesis that declining FKBP1b underlies aging-related hippocampal Ca(2+) dysregulation. Using microinjection of adeno-associated viral vector bearing a transgene encoding FKBP1b into the hippocampus of aged male rats, we assessed the critical prediction that overexpressing FKBP1b should reverse Ca(2+)-mediated manifestations of brain aging. Immunohistochemistry and qRT-PCR confirmed hippocampal FKBP1b overexpression 4-6 weeks after injection. Compared to aged vector controls, aged rats overexpressing FKBP1b showed dramatic enhancement of spatial memory, which correlated with marked reduction of sAHP magnitude. Furthermore, simultaneous electrophysiological recording and Ca(2+) imaging in hippocampal neurons revealed that the sAHP reduction was associated with a decrease in parallel RyR-mediated Ca(2+) transients. Thus, hippocampal FKBP1b overexpression reversed key aspects of Ca(2+) dysregulation and cognitive impairment in aging rats, supporting the novel hypothesis that declining FKBP1b is a molecular mechanism underlying aging-related Ca(2+) dysregulation and unhealthy brain aging and pointing to FKBP1b as a potential therapeutic target. Significance Statement This paper reports critical tests of a novel hypothesis that proposes a molecular mechanism of unhealthy brain aging and possibly, Alzheimer\u27s disease. For more than 30 years, evidence has been accumulating that brain aging is associated with dysregulation of calcium in neurons. Recently, we found that FK506-binding protein 12.6/1b (FKBP1b), a small protein that regulates calcium, declines with aging in the hippocampus, a brain region important for memory. Here we used gene therapy approaches and found that raising FKBP1b reversed calcium dysregulation and memory impairment in aging rats, allowing them to perform a memory task as well as young rats. These studies identify a potential molecular mechanism of brain aging and may also have implications for treatment of Alzheimer\u27s disease

FK506-Binding Protein 12.6/1b, a Negative Regulator of [Ca\u3csup\u3e2+\u3c/sup\u3e], Rescues Memory and Restores Genomic Regulation in the Hippocampus of Aging Rats

Hippocampal overexpression of FK506-binding protein 12.6/1b (FKBP1b), a negative regulator of ryanodine receptor Ca2+ release, reverses aging-induced memory impairment and neuronal Ca2+ dysregulation. Here, we tested the hypothesis that FKBP1b also can protect downstream transcriptional networks from aging-induced dysregulation. We gave hippocampal microinjections of FKBP1b-expressing viral vector to male rats at either 13 months of age (long-term, LT) or 19 months of age (short-term, ST) and tested memory performance in the Morris water maze at 21 months of age. Aged rats treated ST or LT with FKBP1b substantially outperformed age-matched vector controls and performed similarly to each other and young controls (YCs). Transcriptional profiling in the same animals identified 2342 genes with hippocampal expression that was upregulated/downregulated in aged controls (ACs) compared with YCs (the aging effect). Of these aging-dependent genes, 876 (37%) also showed altered expression in aged FKBP1b-treated rats compared with ACs, with FKBP1b restoring expression of essentially all such genes (872/876, 99.5%) in the direction opposite the aging effect and closer to levels in YCs. This inverse relationship between the aging and FKBP1b effects suggests that the aging effects arise from FKBP1b deficiency. Functional category analysis revealed that genes downregulated with aging and restored by FKBP1b were associated predominantly with diverse brain structure categories, including cytoskeleton, membrane channels, and extracellular region. Conversely, genes upregulated with aging but not restored by FKBP1b associated primarily with glial–neuroinflammatory, ribosomal, and lysosomal categories. Immunohistochemistry confirmed aging-induced rarefaction and FKBP1b-mediated restoration of neuronal microtubular structure. Therefore, a previously unrecognized genomic network modulating diverse brain structural processes is dysregulated by aging and restored by FKBP1b overexpression

Managing the delivery of iconic football stadiums in England

The English football premier league has become the most popular sports league in the world; with ardent fans and audiences all over the world. The potential business opportunities that this growth holds have therefore attracted investors who are keen to buy shares in the clubs and sign up the best footballers that money can buy. Underpinning the growth in all of the premier league clubs is a desire to make a distinct statement of identity as part of a competitive strategy. One way to achieve this is through the design and construction of iconic football stadiums. This paper explores the specific project management challenges associated with delivery of iconic football stadiums in England and draws lessons for the management of similar iconic infrastructure projects. A study of project management best practice and some case studies shows that key issues which are common to these projects are centred on design management; choice of procurement route; client management; and stakeholder expectation management. These issues are not necessarily unique to the project management of iconic football stadiums but are amplified by the context of these projects. The emphasis on iconic status in a competitive market also means that stadium projects should be conceived and delivered in the context of other strategic projects which should be clearly understood by the project management team

Time‐lapse photogrammetry reveals hydrological controls of fine‐scale High‐Arctic glacier surface roughness evolution

In a warming Arctic, as glacier snowlines rise, short- to medium-term increases in seasonal bare-ice extent are forecast for the next few decades. These changes will enhance the importance of turbulent energy fluxes for surface ablation and glacier mass balance. Turbulent energy exchanges at the ice surface are conditioned by its topography, or roughness, which has been hypothesized to be controlled by supraglacial hydrology at the glacier scale. However, current understanding of the dynamics in surface topography, and the role of drainage development, remains incomplete, particularly for the transition between seasonal snow cover and well-developed, weathered bare-ice. Using time-lapse photogrammetry, we report a daily timeseries of fine (millimetre)-scale supraglacial topography at a 2 m2 plot on the Lower Foxfonna glacier, Svalbard, over two 9-day periods in 2011. We show traditional kernel-based morphometric descriptions of roughness were ineffective in describing temporal change, but indicated fine-scale albedo feedbacks at depths of ~60 mm contributed to conditioning surface topography. We found profile-based and two-dimensional estimates of roughness revealed temporal change, and the aerodynamic roughness parameter, z0, showed a 22–32% decrease from ~1 mm following the exposure of bare-ice, and a subsequent 72–77% increase. Using geostatistical techniques, we identified ‘hole effect’ properties in the surface elevation semivariograms, and demonstrated that hydrological drivers control the plot-scale topography: degradation of superimposed ice reduces roughness while the inception of braided rills initiates a subsequent development and amplification of topography. Our study presents an analytical framework for future studies that interrogate the coupling between ice surface roughness and hydro-meteorological variables and seek to improve parameterizations of topographically evolving bare-ice areas

CHANG-ES IV: Radio continuum emission of 35 edge-on galaxies observed with the Karl G. Jansky Very Large Array in D-configuration, Data Release 1

We present the first part of the observations made for the Continuum Halos in Nearby Galaxies, an EVLA Survey (CHANG-ES) project. The aim of the CHANG-ES project is to study and characterize the nature of radio halos, their prevalence as well as their magnetic fields, and the cosmic rays illuminating these fields. This paper reports observations with the compact D configuration of the Karl G. Jansky Very Large Array (VLA) for the sample of 35 nearby edge-on galaxies of CHANG-ES. With the new wide bandwidth capabilities of the VLA, an unprecedented sensitivity was achieved for all polarization products. The beam resolution is an average of 9.6" and 36" with noise levels reaching approximately 6 and 30 microJy per beam for C- and L-bands, respectively (robust weighting). We present intensity maps in these two frequency bands (C and L), with different weightings, as well as spectral index maps, polarization maps, and new measurements of star formation rates (SFRs). The data products described herein are available to the public in the CHANG-ES data release available at www.queensu.ca/changes. We also present evidence of a trend among galaxies with larger halos having higher SFR surface density, and we show, for the first time, a radio continuum image of the median galaxy, taking advantage of the collective signal-to-noise ratio of 30 of our galaxies. This image shows clearly that a typical spiral galaxy is surrounded by a halo of magnetic fields and cosmic rays.Comment: 70 pages, of which 35 pages present the data of each galax

Continuum Halos in Nearby Galaxies -- an EVLA Survey (CHANG-ES) -- II: First Results on NGC 4631

We present the first results from the CHANG-ES survey, a new survey of 35 edge-on galaxies to search for both in-disk as well as extra-planar radio continuum emission. The motivation and science case for the survey are presented in a companion paper (Paper I). In this paper (Paper II), we outline the observations and data reduction steps required for wide-band calibration and mapping of EVLA data, including polarization, based on C-array test observations of NGC 4631. With modest on-source observing times (30 minutes at 1.5 GHz and 75 minutes at 6 GHz for the test data) we have achieved best rms noise levels of 22 and 3.5 $\mu$Jy beam$^{-1}$ at 1.5 GHz and 6 GHz, respectively. New disk-halo features have been detected, among them two at 1.5 GHz that appear as loops in projection. We present the first 1.5 GHz spectral index map of NGC 4631 to be formed from a single wide-band observation in a single array configuration. This map represents tangent slopes to the intensities within the band centered at 1.5 GHz, rather than fits across widely separated frequencies as has been done in the past and is also the highest spatial resolution spectral index map yet presented for this galaxy. The average spectral index in the disk is $\bar\alpha_{1.5 GHz}\,=\,-0.84\,\pm\,0.05$ indicating that the emission is largely non-thermal, but a small global thermal contribution is sufficient to explain a positive curvature term in the spectral index over the band. Two specific star forming regions have spectral indices that are consistent with thermal emission. Polarization results (uncorrected for internal Faraday rotation) are consistent with previous observations and also reveal some new features. On broad scales, we find strong support for the notion that magnetic fields constrain the X-ray emitting hot gas.Comment: Accepted to the Astronomical Journal, Version 2 changes: Added acknowledgement to NRA