Designing modern America: the Regional Planning Association of America and its members

(print) xvi, 247 p. ; 23 cmAcknowledgments -- Introduction -- I. The view from the Octagon: Charles Harris Whitaker. p.1 -- II. Idealism in peace and war: Frederick L. Ackerman and Robert D. Kohn. p.10 -- III. Green dimensions: Benton MacKaye. p.19 -- IV. Creation: Whitaker and Clarence Stein. p.31 -- V. Toward a golden day: Lewis Mumford. p.44 -- VI. Planning New York State: Stein and Henry Wright. p.57 -- VII. Giant power: Stuart Chase and Robert Bruere. p.66 -- VIII. Ups and downs, 1925-1926: Mumford et al. p.75 -- IX. The sage and the siege of Shirley Center: MacKaye. p.87 -- X. Sunnyside and Radburn: Stein, Wright, and Alexander M. Bing. p.101 -- XI. Regionalism: Mumford, MacKaye, et al. p.118 -- XII. Women on housing: Edith Elmer Wood and Catherine Bauer. p.131 -- XIII. Housing - for whom and where?: Kohn and Stein. p.142 -- XIV. Planning the Tennessee region: MacKaye. p.151 -- XV. New deal or new order?: Mumford. p.162 -- Three wise men: Chase, Ackerman, and Whitaker. p.171 -- XVII. The Wright way. p.182 -- XVIII. Fade out. p.191 -- Notes. p.199 -- Bibliography. p.227 -- Index. p.24

Differential neutrophil activation in viral infections: Enhanced TLR-7/8-mediated CXCL8 release in asthma

© 2015 The Authors. Respirology published by Wiley Publishing Asia Pty Ltd on behalf of Asian Pacific Society of Respirology. Background and objective Respiratory viral infections are a major cause of asthma exacerbations. Neutrophils accumulate in the airways and the mechanisms that link neutrophilic inflammation, viral infections and exacerbations are unclear. This study aims to investigate anti-viral responses in neutrophils from patients with and without asthma and to investigate if neutrophils can be directly activated by respiratory viruses. Methods Neutrophils from peripheral blood from asthmatic and non-asthmatic individuals were isolated and stimulated with lipopolysaccharide (LPS) (1 μg/mL), f-met-leu-phe (fMLP) (100 nM), imiquimod (3 μg/mL), R848 (1.5 μg/mL), poly I:C (10 μg/mL), RV16 (multiplicity of infection (MOI)1), respiratory syncytial virus (RSV) (MOI1) or influenza virus (MOI1). Cell-free supernatants were collected after 1 h of neutrophil elastase (NE) and matrix metalloproteinase (MMP)-9 release, or after 24 h for CXCL8 release. Results LPS, fMLP, imiquimod and R848 stimulated the release of CXCL8, NE and MMP-9 whereas poly I:C selectively induced CXCL8 release only. R848-induced CXCL8 release was enhanced in neutrophils from asthmatics compared with non-asthmatic cells (P < 0.01). RSV triggered the release of CXCL8 and NE from neutrophils, whereas RV16 or influenza had no effect. Conclusion Neutrophils release CXCL8, NE and MMP-9 in response to viral surrogates with R848-induced CXCL8 release being specifically enhanced in asthmatic neutrophils. Toll-like receptor (TLR7/8) dysregulation may play a role in neutrophilic inflammation in viral-induced exacerbations. We aimed to investigate and compare neutrophil responses to bacterial compounds and viral mimetics as well as compare responses between people with and without asthma. We also investigated neutrophil responses to live respiratory viruses. Here we provide a novel comprehensive comparison showing differential and specific activation in innate immune cells. See Editorial, page 1

Compensation for Spherical Geometric and Absorption Effects on Lower Thermospheric Emission Intensities Derived from High Earth Orbit Images

Remote sensing of the atmosphere from high earth orbit is very attractive due to the large field of view obtained and a true global perspective. This viewpoint is complicated by earth curvature effects so that slant path enhancement and absorption effects, small from low earth orbit, become dominant even at small nadir view angles. The effect is further complicated by the large range of local times and solar zenith angles in a single image leading to a modulation of the image intensity by a significant portion of the diurnal height variation of the absorbing layer. The latter effect is significant in particular for mesospheric, stratospheric and auroral emissions due to their depth in the atmosphere. As a particular case, the emissions from atomic oxygen (130.4 and 135.6 nm) and molecular nitrogen (two LBH bands, LBHS from 140 to 160 nm and LBHL from 160 to 180 nm) as viewed from the Ultraviolet Imager (UVI) are examined. The LBH emissions are of particular interest since LBHS has significant 02 absorption while LBHL does not, In the case of auroral emissions this differential absorption, well examined in the nadir, gives information about the height of the emission and therefore the energy of the precipitating particles. Using simulations of the viewing geometry and images from the UVI we examine these effects and obtain correction factors to adjust to the nadir case with a significant improvement of the derived characteristic energy. There is a surprisingly large effect on the images from the 02 diurnal layer height changes. An empirical compensation to the nadir case is explored based on the local nadir and local zenith angles for each portion of the image. These compensations are demonstrated as applied to the above emissions in both auroral and dayglow images and compared to models. The extension of these findings to other instruments, emissions and spectral regions is examined

Space Environments and Spacecraft Effects Organization Concept

The National Aeronautics and Space Administration (NASA) is embarking on a course to expand human presence beyond Low Earth Orbit (LEO) while also expanding its mission to explore the solar system. Destinations such as Near Earth Asteroids (NEA), Mars and its moons, and the outer planets are but a few of the mission targets. Each new destination presents an opportunity to increase our knowledge of the solar system and the unique environments for each mission target. NASA has multiple technical and science discipline areas specializing in specific space environments disciplines that will help serve to enable these missions. To complement these existing discipline areas, a concept is presented focusing on the development of a space environments and spacecraft effects (SENSE) organization. This SENSE organization includes disciplines such as space climate, space weather, natural and induced space environments, effects on spacecraft materials and systems and the transition of research information into application. This space environment and spacecraft effects organization will be composed of Technical Working Groups (TWG). These technical working groups will survey customers and users, generate products, and provide knowledge supporting four functional areas: design environments, engineering effects, operational support, and programmatic support. The four functional areas align with phases in the program mission lifecycle and are briefly described below. Design environments are used primarily in the mission concept and design phases of a program. Engineering effects focuses on the material, component, sub-system and system-level selection and the testing to verify design and operational performance. Operational support provides products based on real time or near real time space weather to mission operators to aid in real time and near-term decision-making. The programmatic support function maintains an interface with the numerous programs within NASA, other federal government agencies, and the commercial sector to ensure that communications are well established and the needs of the programs are being met. The programmatic support function also includes working in coordination with the program in anomaly resolution and generation of lessons learned documentation. The goal of this space environment and spacecraft effects organization is to develop decision-making tools and engineering products to support all mission phases from mission concept through operations by focusing on transitioning research to application. Products generated by this space environments and effects application are suitable for use in anomaly investigations. This paper will describe the scope of the TWGs and their relationship to the functional areas, and discuss an organizational structure for this space environments and spacecraft effects organization

Mechanisms underlying divergent responses of genetically distinct macrophages to IL-4

Mechanisms by which noncoding genetic variation influences gene expression remain only partially understood but are considered to be major determinants of phenotypic diversity and disease risk. Here, we evaluated effects of >50 million single-nucleotide polymorphisms and short insertions/deletions provided by five inbred strains of mice on the responses of macrophages to interleukin-4 (IL-4), a cytokine that plays pleiotropic roles in immunity and tissue homeostasis. Of >600 genes induced >2-fold by IL-4 across the five strains, only 26 genes reached this threshold in all strains. By applying deep learning and motif mutation analyses to epigenetic data for macrophages from each strain, we identified the dominant combinations of lineage-determining and signal-dependent transcription factors driving IL-4 enhancer activation. These studies further revealed mechanisms by which noncoding genetic variation influences absolute levels of enhancer activity and their dynamic responses to IL-4, thereby contributing to strain-differential patterns of gene expression and phenotypic diversity

An Overview of the Space Environments and Spacecraft Effects Organization Concept

The National Aeronautics and Space Administration (NASA) is embarking on a course to expand human presence beyond Low Earth Orbit (LEO) while also expanding its mission to explore our Earth, and the solar system. Destinations such as Near Earth Asteroids (NEA), Mars and its moons, and the outer planets are but a few of the mission targets. Each new destination presents an opportunity to increase our knowledge on the solar system and the unique environments for each mission target. NASA has multiple technical and science discipline areas specializing in specific space environments fields that will serve to enable these missions. To complement these existing discipline areas, a concept is presented focusing on the development of a space environment and spacecraft effects (SESE) organization. This SESE organization includes disciplines such as space climate, space weather, natural and induced space environments, effects on spacecraft materials and systems, and the transition of research information into application. This space environment and spacecraft effects organization will be composed of Technical Working Groups (TWG). These technical working groups will survey customers and users, generate products, and provide knowledge supporting four functional areas: design environments, engineering effects, operational support, and programmatic support. The four functional areas align with phases in the program mission lifecycle and are briefly described below. Design environments are used primarily in the mission concept and design phases of a program. Environment effects focuses on the material, component, sub-system, and system-level response to the space environment and include the selection and testing to verify design and operational performance. Operational support provides products based on real time or near real time space weather to mission operators to aid in real time and near-term decision-making. The programmatic support function maintains an interface with the numerous programs within NASA, other federal government agencies, and the commercial sector to ensure that communications are well established and the needs of the programs are being met. The programmatic support function also includes working in coordination with the program in anomaly resolution and generation of lessons learned documentation. The goal of this space environment and spacecraft effects organization is to develop decision-making tools and engineering products to support all mission phases from mission concept through operations by focusing on transitioning research to application. Products generated by this space environments and effects application are suitable for use in anomaly investigations. This paper will describe the scope and purpose of the space environments and spacecraft effects organization and describe the TWG's and their relationship to the functional areas

Cell-specific discrimination of desmosterol and desmosterol mimetics confers selective regulation of LXR and SREBP in macrophages.

Activation of liver X receptors (LXRs) with synthetic agonists promotes reverse cholesterol transport and protects against atherosclerosis in mouse models. Most synthetic LXR agonists also cause marked hypertriglyceridemia by inducing the expression of sterol regulatory element-binding protein (SREBP)1c and downstream genes that drive fatty acid biosynthesis. Recent studies demonstrated that desmosterol, an intermediate in the cholesterol biosynthetic pathway that suppresses SREBP processing by binding to SCAP, also binds and activates LXRs and is the most abundant LXR ligand in macrophage foam cells. Here we explore the potential of increasing endogenous desmosterol production or mimicking its activity as a means of inducing LXR activity while simultaneously suppressing SREBP1c-induced hypertriglyceridemia. Unexpectedly, while desmosterol strongly activated LXR target genes and suppressed SREBP pathways in mouse and human macrophages, it had almost no activity in mouse or human hepatocytes in vitro. We further demonstrate that sterol-based selective modulators of LXRs have biochemical and transcriptional properties predicted of desmosterol mimetics and selectively regulate LXR function in macrophages in vitro and in vivo. These studies thereby reveal cell-specific discrimination of endogenous and synthetic regulators of LXRs and SREBPs, providing a molecular basis for dissociation of LXR functions in macrophages from those in the liver that lead to hypertriglyceridemia