The role of atrial natriuretic peptide to attenuate inflammation in a mouse skin wound and individually perfused rat mesenteric microvessels.

We tested the hypothesis that the anti-inflammatory actions of atrial natriuretic peptide (ANP) result from the modulation of leukocyte adhesion to inflamed endothelium and not solely ANP ligation of endothelial receptors to stabilize endothelial barrier function. We measured vascular permeability to albumin and accumulation of fluorescent neutrophils in a full-thickness skin wound on the flank of LysM-EGFP mice 24 h after formation. Vascular permeability in individually perfused rat mesenteric microvessels was also measured after leukocytes were washed out of the vessel lumen. Thrombin increased albumin permeability and increased the accumulation of neutrophils. The thrombin-induced inflammatory responses were attenuated by pretreating the wound with ANP (30 min). During pretreatment ANP did not lower permeability, but transiently increased baseline albumin permeability concomitant with the reduction in neutrophil accumulation. ANP did not attenuate acute increases in permeability to histamine and bradykinin in individually perfused rat microvessels. The hypothesis that anti-inflammatory actions of ANP depend solely on endothelial responses that stabilize the endothelial barrier is not supported by our results in either individually perfused microvessels in the absence of circulating leukocytes or the more chronic skin wound model. Our results conform to the alternate hypothesis that ANP modulates the interaction of leukocytes with the inflamed microvascular wall of the 24 h wound. Taken together with our previous observations that ANP reduces deformability of neutrophils and their strength of attachment, rolling, and transvascular migration, these observations provide the basis for additional investigations of ANP as an anti-inflammatory agent to modulate leukocyte-endothelial cell interactions

Simplicity of eigenvalues in Anderson-type models

We show almost sure simplicity of eigenvalues for several models of Anderson-type random Schr\"odinger operators, extending methods introduced by Simon for the discrete Anderson model. These methods work throughout the spectrum and are not restricted to the localization regime. We establish general criteria for the simplicity of eigenvalues which can be interpreted as separately excluding the absence of local and global symmetries, respectively. The criteria are applied to Anderson models with matrix-valued potential as well as with single-site potentials supported on a finite box.Comment: 20 page

Towards quantum superpositions of a mirror

We propose a scheme for creating quantum superposition states involving of order $10^{14}$ atoms via the interaction of a single photon with a tiny mirror. This mirror, mounted on a high-quality mechanical oscillator, is part of a high-finesse optical cavity which forms one arm of a Michelson interferometer. By observing the interference of the photon only, one can study the creation and decoherence of superpositions involving the mirror. All experimental requirements appear to be within reach of current technology.Comment: 5 pages, 2 figures, submitted to Phys. Rev. Let

The p110 delta structure: mechanisms for selectivity and potency of new PI(3)K inhibitors.

Deregulation of the phosphoinositide-3-OH kinase (PI(3)K) pathway has been implicated in numerous pathologies including cancer, diabetes, thrombosis, rheumatoid arthritis and asthma. Recently, small-molecule and ATP-competitive PI(3)K inhibitors with a wide range of selectivities have entered clinical development. In order to understand the mechanisms underlying the isoform selectivity of these inhibitors, we developed a new expression strategy that enabled us to determine to our knowledge the first crystal structure of the catalytic subunit of the class IA PI(3)K p110 delta. Structures of this enzyme in complex with a broad panel of isoform- and pan-selective class I PI(3)K inhibitors reveal that selectivity toward p110 delta can be achieved by exploiting its conformational flexibility and the sequence diversity of active site residues that do not contact ATP. We have used these observations to rationalize and synthesize highly selective inhibitors for p110 delta with greatly improved potencies

MKID development for SuperSpec: an on-chip, mm-wave, filter-bank spectrometer

SuperSpec is an ultra-compact spectrometer-on-a-chip for millimeter and submillimeter wavelength astronomy. Its very small size, wide spectral bandwidth, and highly multiplexed readout will enable construction of powerful multibeam spectrometers for high-redshift observations. The spectrometer consists of a horn-coupled microstrip feedline, a bank of narrow-band superconducting resonator filters that provide spectral selectivity, and Kinetic Inductance Detectors (KIDs) that detect the power admitted by each filter resonator. The design is realized using thin-film lithographic structures on a silicon wafer. The mm-wave microstrip feedline and spectral filters of the first prototype are designed to operate in the band from 195-310 GHz and are fabricated from niobium with at Tc of 9.2K. The KIDs are designed to operate at hundreds of MHz and are fabricated from titanium nitride with a Tc of 2K. Radiation incident on the horn travels along the mm-wave microstrip, passes through the frequency-selective filter, and is finally absorbed by the corresponding KID where it causes a measurable shift in the resonant frequency. In this proceedings, we present the design of the KIDs employed in SuperSpec and the results of initial laboratory testing of a prototype device. We will also briefly describe the ongoing development of a demonstration instrument that will consist of two 500-channel, R=700 spectrometers, one operating in the 1-mm atmospheric window and the other covering the 650 and 850 micron bands.Comment: As submitted, except that "in prep" references have been update

Application of artificial sunlight for the elderly as a possible environmental nursing practice

Aging and aged societies have arrived in many countries where significant development of medicine and the economy has been achieved. Japan is a highly aged society with a shortage of carers both at home and in long-term care settings. In fact, more persons of advanced age who do not need intensive care in hospitals strongly desire health care to be delivered in their own home with their family. Environmental nursing practice, which means that nurses improve the environment of patients or the elderly properly in accordance with healthcare considerations, is currently playing a more important role, not only to prevent the elderly from contracting various diseases, but also to provide a facility for supporting an aged person to live a fulfilling life, preferably one that includes independence. This approach will lead to a reduction in medical expenditure by increasing the number of aged people with healthy longevity without the need for hospitalization or intensive care. This short communication focuses on healthy lighting for the elderly based on our research and experience regarding the beneficial effects of artificial sunlight on nonalcoholic steatohepatitis (NASH), asthma and food allergy, and ulcerative colitis in experimental animal models and clinical settings. Then, we review other studies and discuss how artificial sunlight would be useful for the elderly as one of the environmental nursing practices

Effects of beta-alanine supplementation on brain homocarnosine/carnosine signal and cognitive function: an exploratory study

Objectives: Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d-1 on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1) and on cognitive function before and after exercise in trained cyclists (Study 2). Methods: In Study 1, seven healthy vegetarians (3 women and 4 men) and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen trained male cyclists completed four 20-Km cycling time trials (two pre supplementation and two post supplementation), with a battery of cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual Information Processing task) being performed before and after exercise on each occasion. Results: In Study 1, there were no within-group effects of beta-alanine supplementation on brain homocarnosine/carnosine signal in either vegetarians (p = 0.99) or omnivores (p = 0.27); nor was there any effect when data from both groups were pooled (p = 0.19). Similarly, there was no group by time interaction for brain homocarnosine/carnosine signal (p = 0.27). In study 2, exercise improved cognitive function across all tests (P0.05) of beta-alanine supplementation on response times or accuracy for the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise. Conclusion: 28 d of beta-alanine supplementation at 6.4g d-1 appeared not to influence brain homocarnosine/ carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists