Nebivolol, a beta adrenergic receptor antagonist blocks angiotensin II-mediated signaling in heart [abstract]

We recently showed that Nebivolol, a [beta]-adrenergic receptor (AR) antagonist attenuates myocardial oxidative stress and promotes insulin metabolic signaling in 9 week old Zucker obese (ZO) insulin resistant rats. Here, we demonstrate that Nebivolol suppresses angiotensin II type I receptor (AT1R)-mediated signaling in ZO hearts as well as in HL-1 cardiomyocytes

Convergence of Prognostic Gene Signatures Suggests Underlying Mechanisms of Human Prostate Cancer Progression.

The highly heterogeneous clinical course of human prostate cancer has prompted the development of multiple RNA biomarkers and diagnostic tools to predict outcome for individual patients. Biomarker discovery is often unstable with, for example, small changes in discovery dataset configuration resulting in large alterations in biomarker composition. Our hypothesis, which forms the basis of this current study, is that highly significant overlaps occurring between gene signatures obtained using entirely different approaches indicate genes fundamental for controlling cancer progression. For prostate cancer, we found two sets of signatures that had significant overlaps suggesting important genes (p < 10-34 for paired overlaps, hypergeometrical test). These overlapping signatures defined a core set of genes linking hormone signalling (HES6-AR), cell cycle progression (Prolaris) and a molecular subgroup of patients (PCS1) derived by Non Negative Matrix Factorization (NNMF) of control pathways, together designated as SIG-HES6. The second set (designated SIG-DESNT) consisted of the DESNT diagnostic signature and a second NNMF signature PCS3. Stratifications using SIG-HES6 (HES6, PCS1, Prolaris) and SIG-DESNT (DESNT) classifiers frequently detected the same individual high-risk cancers, indicating that the underlying mechanisms associated with SIG-HES6 and SIG-DESNT may act together to promote aggressive cancer development. We show that the use of combinations of a SIG-HES6 signature together with DESNT substantially increases the ability to predict poor outcome, and we propose a model for prostate cancer development involving co-operation between the SIG-HES6 and SIG-DESNT pathways that has implication for therapeutic design

Serialised holography for brand protection and authentication

The problems presented by counterfeit products and documentation are discussed. Limitations of existing holograms for anti-counterfeit applications are described. We describe the advantages of full holographic serialisation and the requirements in terms of materials and techniques for mass production of true serialised holograms. These requirements having been met, we report for the first time the mass production of fully serialised holograms. The novelty of approach consists of the direct use of product manufacturer’s information as the object in a holographic recording system along with a self-processing photopolymer and modular optical system to facilitate mass production of truly serialised volume holograms. Various types of serialised holograms for overt and covert authentication are described. We discuss briefly the application of Optrace’s manufacturing methods for future generation holographic device

Association football and the representation of homosexuality by the print media: a case study of Anton Hysén

In March 2011 Anton Hysén (a semi-professional footballer currently playing in the Swedish fourth division) became only the second association football (soccer) player of any professional disposition to publicly declare his homosexuality whilst still playing the game. This article provides a textual analysis of the print media’s reaction to Hysén coming out and examines whether, in 2011, they portray more inclusive notions towards homosexuality than they did in 1990 when British footballer Justin Fashanu came out. The results advance inclusive masculinity theory as a number of print media sources (mostly British) interview Hysén in the weeks immediately after he came out and publish articles that challenge homophobia. Highlighting a change since 1990, a significant number of articles stress the need for the key stakeholders in football (players, fans, clubs, agents, the authorities and the media) to accept gay players

Mineralocorticoid receptor antagonism attenuates vascular apoptosis and injury via rescuing protein kinase B activation

This article may also be found at the publisher's website at http://hyper.ahajournals.org/cgi/content/abstract/53/2/158?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=habibi&searchid=1&FIRSTINDEX=0&resourcetype=HWCITEmerging evidence indicates that mineralocorticoid receptor (MR) blockade reduces the risk of cardiovascular events beyond those predicted by its blood pressure-lowering actions; however, the underlying mechanisms remain unclear. To investigate whether protection elicited by MR blockade is through attenuation of vascular apoptosis and injury, independently of blood pressure lowering, we administered a low dose of the MR antagonist spironolactone or vehicle for 21 days to hypertensive transgenic Ren2 rats with elevated plasma aldosterone levels. Although Ren2 rats developed higher systolic blood pressures compared with Sprague-Dawley littermates, low-dose spironolactone treatment did not reduce systolic blood pressure compared with untreated Ren2 rats. Ren2 rats exhibited vascular injury as evidenced by increased apoptosis, hemidesmosome-like structure loss, mitochondrial abnormalities, and lipid accumulation compared with Sprague-Dawley rats, and these abnormalities were attenuated by MR antagonism. Protein kinase B activation is critical to vascular homeostasis via regulation of cell survival and expression of apoptotic genes. Protein kinase B serine473 phosphorylation was impaired in Ren2 aortas and restored with MR antagonism. In vivo MR antagonist treatment promoted antiapoptotic effects by increasing phosphorylation of BAD serine136 and expression of Bcl-2 and Bcl-xL, decreasing cytochrome c release and BAD expression, and suppressing caspase-3 activation. Furthermore, MR antagonism substantially reduced the elevated NADPH oxidase activity and lipid peroxidation, expression of angiotensin II, angiotensin type 1 receptor, and MR in Ren2 vasculature. These results demonstrate that MR antagonism protects the vasculature from aldosterone-induced vascular apoptosis and structural injury via rescuing protein kinase B activation, independent of blood pressure effects

Distinction between the Poole-Frenkel and tunneling models of electric field-stimulated carrier emission from deep levels in semiconductors

The enhancement of the emission rate of charge carriers from deep-level defects in electric field is routinely used to determine the charge state of the defects. However, only a limited number of defects can be satisfactorily described by the Poole-Frenkel theory. An electric field dependence different from that expected from the Poole-Frenkel theory has been repeatedly reported in the literature, and no unambiguous identification of the charge state of the defect could be made. In this article, the electric field dependencies of emission of carriers from DX centers in AlxGa1-xAs:Te, Cu pairs in silicon, and Ge:Hg have been studied applying static and terahertz electric fields, and analyzed by using the models of Poole-Frenkel and phonon assisted tunneling. It is shown that phonon assisted tunneling and Poole-Frenkel emission are two competitive mechanisms of enhancement of emission of carriers, and their relative contribution is determined by the charge state of the defect and by the electric-field strength. At high-electric field strengths carrier emission is dominated by tunneling independently of the charge state of the impurity. For neutral impurities, where Poole-Frenkel lowering of the emission barrier does not occur, the phonon assisted tunneling model describes well the experimental data also in the low-field region. For charged impurities the transition from phonon assisted tunneling at high fields to Poole-Frenkel effect at low fields can be traced back. It is suggested that the Poole-Frenkel and tunneling models can be distinguished by plotting logarithm of the emission rate against the square root or against the square of the electric field, respectively. This analysis enables one to unambiguously determine the charge state of a deep-level defect

Attenuation of NADPH Oxidase Activation and Glomerular Filtration Barrier Remodeling With Statin Treatment

Activation of reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase by angiotensin II is integral to the formation of oxidative stress in the vasculature and the kidney. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibition is associated with reductions of oxidative stress in the vasculature and kidney and associated decreases in albuminuria. Effects of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibition on oxidative stress in the kidney and filtration barrier integrity are poorly understood. To investigate, we used transgenic TG(mRen2)27(Ren2) rats, which harbor the mouse renin transgene and renin-angiotensin system activation, and an immortalized murine podocyte cell line. We treated young, male Ren2 and Sprague-Dawley rats with rosuvastatin (20 mg/kg IP) or placebo for 21 days. Compared with controls, we observed increases in systolic blood pressure, albuminuria, renal NADPH oxidase activity, and 3-nitrotryosine staining, with reductions in the rosuvastatin-treated Ren2. Structural changes on light and transmission electron microscopy, consistent with periarteriolar fibrosis and podocyte foot-process effacement, were attenuated with statin treatment. Nephrin expression was diminished in the Ren2 kidney and trended to normalize with statin treatment. Angiotensin II- dependent increases in podocyte NADPH oxidase activity and subunit expression (NOX2, NOX4, Rac, and p22phox) and reactive oxygen species generation were decreased after in vitro statin treatment. These data support a role for increased NADPH oxidase activity and subunit expression with resultant reactive oxygen species formation in the kidney and podocyte. Furthermore, statin attenuation of NADPH oxidase activation and reactive oxygen species formation in the kidney/podocyte seems to play roles in the abrogation of oxidative stress-induced filtration barrier injury and consequent albuminuria

Knitting Together Communities - Designing the Heart of Six Corners and Old Hill

Knitting together Communities -Designing the Heart of Six Corners and Old Hill Knitting Together Communities – Designing the Heart of Six Corners and Old Hill provides a framework to knit together assets and opportunities for creating a strong identity and sense of coherence for a transformative urban district in Springfield, MA. The Senior Urban Design Studio 2019 created six proposals that were searching for design opportunities that enhance the aesthetic quality of the neighborhood and increase services for the wellbeing of the residents. The two neighborhoods are characterized by strong neighborhood leadership through committed residents, community centers and active religious organizations, and a lively culture of urban agriculture (GTC) that keeps growing and fosters a positive spirit in the community. The studio analyzed the assets of the district, engaged with residents through site visits, personal interviews with community leaders and groups, and a neighborhood engagement workshop. Design Objectives The design program was developed through the engagement with stakeholders, area observations and classical analysis of the area: • More entrances, accessibility and programming for active and passive recreation for the centrally located Ruth Elizabeth Park • Gerrish Park near roundabout needs to be more usable for markets and events • Historic Mill River and Watershops Pond should be connected to the larger green network; Harriet Tubman Park needs to be connected to the water’s edge. • Public art on exterior walls through education at schools and local artists • Synergies between Springfield College neighborhood to create new student housing and provide amenities that integrate this population for mutual benefits • Complete streets through extensive street tree plantings, widening of sidewalks and bicycle lanes • Stormwater management strategies: bioswales along streets, green roofs, infiltration areas in new parks, porous pavement. • Multiple housing opportunities: vacant small lots for infill, mix housing with retail and commercial on upper floors of new buildings, adaptive reuse of historic buildings as live-work spaces • Neighborhood amenities like a grocery store and pharmacy • Spaces for a cultural and commercial hub including all-year activities outsid

Relativistic Calculation of the Meson Spectrum: a Fully Covariant Treatment Versus Standard Treatments

A large number of treatments of the meson spectrum have been tried that consider mesons as quark - anti quark bound states. Recently, we used relativistic quantum "constraint" mechanics to introduce a fully covariant treatment defined by two coupled Dirac equations. For field-theoretic interactions, this procedure functions as a "quantum mechanical transform of Bethe-Salpeter equation". Here, we test its spectral fits against those provided by an assortment of models: Wisconsin model, Iowa State model, Brayshaw model, and the popular semi-relativistic treatment of Godfrey and Isgur. We find that the fit provided by the two-body Dirac model for the entire meson spectrum competes with the best fits to partial spectra provided by the others and does so with the smallest number of interaction functions without additional cutoff parameters necessary to make other approaches numerically tractable. We discuss the distinguishing features of our model that may account for the relative overall success of its fits. Note especially that in our approach for QCD, the resulting pion mass and associated Goldstone behavior depend sensitively on the preservation of relativistic couplings that are crucial for its success when solved nonperturbatively for the analogous two-body bound-states of QED.Comment: 75 pages, 6 figures, revised content