Ultraviolet irradiation accelerates apoptosis in human polymorphonuclear leukocytes: protection by LPS and GM‐CSF

Polymorphonuclear leukocytes (PMN) play a central role in host response to injury and infection. Understanding factors that regulate PMN survival may therefore have a major influence on the development of novel treatment strategies for controlling life‐threatening infections, as well as local and systemic inflammatory responses. Unfortunately, the presently utilized in vitro culture model of PMN apoptosis makes the examination of early biochemical events surrounding PMN apoptosis very difficult. This study demonstrates that a short course of UV irradiation (15 min) can be used to induce rapid progression of PMN through the apoptotic process with 70–90% of PMN displaying features of apoptosis by 4 h after UV exposure. Bacterial lipopolysaccharide and granulocyte‐macrophage colony‐stimulating factor, which are known to prolong PMN survival during in vitro culture, also protected PMN from UV‐accelerated apoptosis. The UV‐accelerated model of PMN apoptosis provides another valuable tool for the investigation of early signaling pathways associated with inducing or delaying PMN apoptosis. J. Leukoc. Biol. 62: 517–523; 1997.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142305/1/jlb0517.pd

Mechanism of endothelial cell shape change in oxidant injury

Changes in endothelial cell morphology induced by neutrophil-generated hydrogen peroxide (H2O2) may account for the capillary leak of the adult respiratory distress syndrome (ARDS). The relationship of H2O2 effects on the concentration of intracellular Ca2+([Ca2+]i) and ATP to changes in microfilaments and microtubules, important determinants of cell shape, was examined. Bovine pulmonary artery endothelial cells were injured over a 2-hr time course with a range of H2O2 doses (0-20 mM). The higher concentrations of H2O2 consistently produced contraction and rounding of>50-75% of cells by 1-2 hr. The range of 1-20 mM H2O2 produced rapid, significant reductions in endothelial ATP levels over the time course of injury. Although there were significant increases in mean endothelial [Ca2+]i in response to 5, 10, and 20 mM H2O2, 1 mMH2O2 did not affect the [Ca2+]i. Fluorescence microscopy revealed that microfilament disruption occurred as ATP levels fell and preceded depolymerization of microtubules which developed after [Ca2+]1 approached 1 x 10-6 M. H2O2 at 1 mM injury caused microfilament disruption but did not depolymerize microtubules. Microfilament disruption occurred without oxidant exposure, when ATP levels were reduced by glucose depletion and mitochondrial inhibition with oligomycin (650 nM). If a Ca2+ ionophore, ionomycin (5 [mu]M), was then added, [Ca2+]i rose to > 1 x 10-6 M, microtubules fragmented and depolymerized, and cell contraction and rounding very similar to that induced by H2O2 occurred. These results suggest that endothelial cell dysfunction and capillary leak in ARDS may be due to H2O2-mediated changes in cellular ATP and [Ca2+]i.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27994/1/0000428.pd

Actin polymerization in cellular oxidant injury

Microfilaments undergo an ATP-dependent disruption into shortened bundles following cellular exposure to oxidants. This phenomenon does not require a net change in the amount of polymerized actin. However, increased amounts of polymerized actin have been detected in oxidant-injured cells and it was the purpose of this study to determine the conditions under which the actin polymerization may occur. Utilizing the formation of oxidized glutathione (GSSG) as an indicator of cellular sulfhydryl oxidation, conditions were chosen to accentuate sulfhydryl oxidation within the target P388D1 cell line following exposure to the oxidants, H2O2 and diamide. Using the DNase I and flow cytometric assays of actin polymerization, significant polymerization of actin was detected only under conditions in which sulfhydryl oxidation occurred after exposure to the two oxidizing agents. Greater sulfhydryl oxidation early in the course of injury was associated with a greater rate and extent of actin polymerization in the injured cells. Experiments with cells depleted of glutathione (GSH) demonstrated that neither loss of GSH nor absolute levels of GSSG formed during oxidant exposure were responsible for the polymerization of actin. The data presented are consistent with the hypothesis that oxidizing conditions which induce significant sulfhydryl oxidation in target cells are correlated with assembly of polymerized actin and that this represents a process which is distinct and separate from the ATP-dependent gross disruption of microfilaments.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29200/1/0000254.pd

A window to quantum gravity phenomena in the emergence of the seeds of cosmic structure

Inflationary cosmology has, in the last few years,received a strong dose of support from observations. The fact that the fluctuation spectrum can be extracted from the inflationary scenario through an analysis that involves quantum field theory in curved space-time, and that it coincides with the observational data has lead to a certain complacency in the community, which prevents the critical analysis of the obscure spots in the derivation. We argue here briefly, as we have discussed in more detail elsewhere, that there is something important missing in our understanding of the origin of the seeds of Cosmic Structure, as is evidenced by the fact that in the standard accounts the inhomogeneity and anisotropy of our universe seems to emerge from an exactly homogeneous andisotropic initial state through processes that do not break those symmetries. This article gives a very brief recount of the problems faced by the arguments based on established physics. The conclusion is that we need some new physics to be able to fully address the problem. The article then exposes one avenue that has been used to address the central issue and elaborates on the degree to which, the new approach makes different predictions from the standard analyses. The approach is inspired on Penrose's proposals that Quantum Gravity might lead to a real, dynamical collapse of the wave function, a process that we argued has the properties needed to extract us from the theoretical impasse described above.Comment: 13 pages, 3 figures. To appear in DICE 2008 conference proceeding

Hepatocellular oxidant stress following intestinal ischemia-reperfusion injury,

Reperfusion of ischemic intestine results in acute liver dysfunction characterized by hepatocellular enzyme release into plasma, reduction in bile flow rate, and neutrophil sequestration within the liver. The pathophysiology underlying this acute hepatic injury is unknown. This study was undertaken to determine whether oxidants are associated with the hepatic injury and to determine the relative value of several indirect methods of assessing oxidant exposure in vivo. Rats were subjected to a standardized intestinal ischemia-reperfusion injury. Hepatic tissue was assayed for lipid peroxidation products and oxidized and reduced glutathione. There was no change in hepatic tissue total glutathione following intestinal ischemia--reperfusion injury. Oxidized glutathione (GSSG) increased significantly following 30 and 60 min of reperfusion. There was no increase in any of the products of lipid peroxidation associated with this injury. An increase in GSSG within hepatic tissue during intestinal reperfusion suggests exposure of hepatocytes to an oxidant stress. The lack of a significant increase in products of lipid peroxidation suggests that the oxidant stress is of insufficient magnitude to result in irreversible injury to hepatocyte cell membranes. These data also suggest that the measurement of tissue GSSG may be a more sensitive indicator of oxidant stress than measurement of products of lipid peroxidation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29014/1/0000043.pd

The Atacama Cosmology Telescope: Data Characterization and Map Making

We present a description of the data reduction and mapmaking pipeline used for the 2008 observing season of the Atacama Cosmology Telescope (ACT). The data presented here at 148 GHz represent 12% of the 90 TB collected by ACT from 2007 to 2010. In 2008 we observed for 136 days, producing a total of 1423 hours of data (11 TB for the 148 GHz band only), with a daily average of 10.5 hours of observation. From these, 1085 hours were devoted to a 850 deg^2 stripe (11.2 hours by 9.1 deg) centered on a declination of -52.7 deg, while 175 hours were devoted to a 280 deg^2 stripe (4.5 hours by 4.8 deg) centered at the celestial equator. We discuss sources of statistical and systematic noise, calibration, telescope pointing, and data selection. Out of 1260 survey hours and 1024 detectors per array, 816 hours and 593 effective detectors remain after data selection for this frequency band, yielding a 38% survey efficiency. The total sensitivity in 2008, determined from the noise level between 5 Hz and 20 Hz in the time-ordered data stream (TOD), is 32 micro-Kelvin sqrt{s} in CMB units. Atmospheric brightness fluctuations constitute the main contaminant in the data and dominate the detector noise covariance at low frequencies in the TOD. The maps were made by solving the least-squares problem using the Preconditioned Conjugate Gradient method, incorporating the details of the detector and noise correlations. Cross-correlation with WMAP sky maps, as well as analysis from simulations, reveal that our maps are unbiased at multipoles ell > 300. This paper accompanies the public release of the 148 GHz southern stripe maps from 2008. The techniques described here will be applied to future maps and data releases.Comment: 20 pages, 18 figures, 6 tables, an ACT Collaboration pape

The Atacama Cosmology Telescope: A Measurement of the Cosmic Microwave Background Power Spectrum at 148 and 218 GHz from the 2008 Southern Survey

We present measurements of the cosmic microwave background (CMB) power spectrum made by the Atacama Cosmology Telescope at 148 GHz and 218 GHz, as well as the cross-frequency spectrum between the two channels. Our results clearly show the second through the seventh acoustic peaks in the CMB power spectrum. The measurements of these higher-order peaks provide an additional test of the {\Lambda}CDM cosmological model. At l > 3000, we detect power in excess of the primary anisotropy spectrum of the CMB. At lower multipoles 500 < l < 3000, we find evidence for gravitational lensing of the CMB in the power spectrum at the 2.8{\sigma} level. We also detect a low level of Galactic dust in our maps, which demonstrates that we can recover known faint, diffuse signals.Comment: 19 pages, 13 figures. Submitted to ApJ. This paper is a companion to Hajian et al. (2010) and Dunkley et al. (2010

Working with wood in rivers in the Western United States

Recognition of the important physical and ecological roles played by large wood in channels and on floodplains has grown substantially during recent decades. Although large wood continues to be routinely removed from many river corridors worldwide, the practice of wood reintroduction has spread across the United States, the United Kingdom and western Europe, Australia, and New Zealand. The state-of-science regarding working with wood in rivers was discussed during a workshop held in Colorado, USA, in September 2022 with 40 participants who are scientists and practitioners from across the USA, UK, Europe, and Japan. The objectives of this paper are to present the findings from the workshop; summarize two case studies of wood in river restoration in the western United States; and provide suggestions for advancing the practice of wood in river management. We summarize the workshop results based on participant judgements and recommendations with respect to: (i) limitations and key barriers to using wood, which reflect perceptions and practicalities; (ii) gaps in the use of large wood in river management; (iii) scenarios in which wood is generally used effectively; and (iv) scenarios in which wood is generally not used effectively. The case studies illustrate the importance of the local geomorphic context, the configuration complexity of the wood, and the potential for modification of river corridor morphology to enhance desired benefits. Moving forward, we stress the importance of collaboration across disciplines and across communities of research scientists, practitioners, regulators, and potential stakeholders; accounting for stakeholder perceptions of the use of large wood; and increasing non-scientist access to the latest state-of-science knowledge

Cosmological parameters from SDSS and WMAP

We measure cosmological parameters using the three-dimensional power spectrum P(k) from over 200,000 galaxies in the Sloan Digital Sky Survey (SDSS) in combination with WMAP and other data. Our results are consistent with a ``vanilla'' flat adiabatic Lambda-CDM model without tilt (n=1), running tilt, tensor modes or massive neutrinos. Adding SDSS information more than halves the WMAP-only error bars on some parameters, tightening 1 sigma constraints on the Hubble parameter from h~0.74+0.18-0.07 to h~0.70+0.04-0.03, on the matter density from Omega_m~0.25+/-0.10 to Omega_m~0.30+/-0.04 (1 sigma) and on neutrino masses from <11 eV to <0.6 eV (95%). SDSS helps even more when dropping prior assumptions about curvature, neutrinos, tensor modes and the equation of state. Our results are in substantial agreement with the joint analysis of WMAP and the 2dF Galaxy Redshift Survey, which is an impressive consistency check with independent redshift survey data and analysis techniques. In this paper, we place particular emphasis on clarifying the physical origin of the constraints, i.e., what we do and do not know when using different data sets and prior assumptions. For instance, dropping the assumption that space is perfectly flat, the WMAP-only constraint on the measured age of the Universe tightens from t0~16.3+2.3-1.8 Gyr to t0~14.1+1.0-0.9 Gyr by adding SDSS and SN Ia data. Including tensors, running tilt, neutrino mass and equation of state in the list of free parameters, many constraints are still quite weak, but future cosmological measurements from SDSS and other sources should allow these to be substantially tightened.Comment: Minor revisions to match accepted PRD version. SDSS data and ppt figures available at http://www.hep.upenn.edu/~max/sdsspars.htm