Impairments to Thermoregulation in the Elderly During Heat Exposure Events

Heat waves represent a public health risk to elderly people, and typically result in an increased rate of hospital admissions and deaths. Studies of thermoregulation in this cohort have generally focused on single elements such as sweating capacity. Sweating capacity and skin blood flow reduce with age, reducing ability to dissipate heat. Perception of effort during heat exposure is emerging as an area that needs further investigation as the elderly appear to lack the ability to adequately perceive increased physiological strain during heat exposure. The role of the gut and endotoxemia in heat stress has received attention in young adults, while the elderly population has been neglected. This shortcoming offers another potential avenue for identifying effective integrated health interventions to reduce heat illnesses. Increasing numbers of elderly individuals in populations worldwide are likely to increase the incidence of heat wave-induced deaths if adequate interventions are not developed, evaluated, and implemented. In this narrative-style review we identify and discuss health-related interventions for reducing the impact of heat illnesses in the elderly

Was Sinn Féin dying? A quantitative post-mortem of the party's decline and the emergence of Fianna Fáil

This article calls for a reappraisal of the consensus surrounding the split within Sinn Féin in 1926 that led to the foundation of Fianna Fáil. It demonstrates that quantitative factors cited to demonstrate Sinn Féin’s “terminal” decline – finances, cumann numbers, and election results – and to explain de Valera’s decision to leave Sinn Féin and establish a rival republican organisation, Fianna Fáil, do not provide sufficient objective grounds to explain the republican leader’s actions. This article demonstrates that Sinn Féin’s election results during the period in question (1923-1926) were encouraging and the decline in finances and cumann numbers can be explained by the fact that the base year used to compare progress was 1923, an election year. Moreover, this article compares the performance of Sinn Féin to the first five years of Fianna Fáil (1926-1931) to show that what has been interpreted as terminal decline can also be attributed to normal inter-election lulls in party activity. Correspondingly, subjective factors – e.g. personal rivalries, differences in ideology, organisational style and levels of patience in terms of achieving political power – were most likely the determining factors rather than organisational decline

Quasar Proper Motions and Low-Frequency Gravitational Waves

We report observational upper limits on the mass-energy of the cosmological gravitational-wave background, from limits on proper motions of quasars. Gravitational waves with periods longer than the time span of observations produce a simple pattern of apparent proper motions over the sky, composed primarily of second-order transverse vector spherical harmonics. A fit of such harmonics to measured motions yields a 95%-confidence limit on the mass-energy of gravitational waves with frequencies <2e-9 Hz, of <0.11/h*h times the closure density of the universe.Comment: 15 pages, 1 figure. Also available at http://charm.physics.ucsb.edu:80/people/cgwinn/cgwinn_group/index.htm

A computational framework to emulate the human perspective in flow cytometric data analysis

Background: In recent years, intense research efforts have focused on developing methods for automated flow cytometric data analysis. However, while designing such applications, little or no attention has been paid to the human perspective that is absolutely central to the manual gating process of identifying and characterizing cell populations. In particular, the assumption of many common techniques that cell populations could be modeled reliably with pre-specified distributions may not hold true in real-life samples, which can have populations of arbitrary shapes and considerable inter-sample variation. &lt;p/&gt;Results: To address this, we developed a new framework flowScape for emulating certain key aspects of the human perspective in analyzing flow data, which we implemented in multiple steps. First, flowScape begins with creating a mathematically rigorous map of the high-dimensional flow data landscape based on dense and sparse regions defined by relative concentrations of events around modes. In the second step, these modal clusters are connected with a global hierarchical structure. This representation allows flowScape to perform ridgeline analysis for both traversing the landscape and isolating cell populations at different levels of resolution. Finally, we extended manual gating with a new capacity for constructing templates that can identify target populations in terms of their relative parameters, as opposed to the more commonly used absolute or physical parameters. This allows flowScape to apply such templates in batch mode for detecting the corresponding populations in a flexible, sample-specific manner. We also demonstrated different applications of our framework to flow data analysis and show its superiority over other analytical methods. &lt;p/&gt;Conclusions: The human perspective, built on top of intuition and experience, is a very important component of flow cytometric data analysis. By emulating some of its approaches and extending these with automation and rigor, flowScape provides a flexible and robust framework for computational cytomics

Laser Microdissection of the Alveolar Duct Enables Single-Cell Genomic Analysis

Complex tissues such as the lung are composed of structural hierarchies such as alveoli, alveolar ducts, and lobules. Some structural units, such as the alveolar duct, appear to participate in tissue repair as well as the development of bronchioalveolar carcinoma. Here, we demonstrate an approach to conduct laser microdissection of the lung alveolar duct for single-cell PCR analysis. Our approach involved three steps. (1) The initial preparation used mechanical sectioning of the lung tissue with sufficient thickness to encompass the structure of interest. In the case of the alveolar duct, the precision-cut lung slices were 200 μm thick; the slices were processed using near-physiologic conditions to preserve the state of viable cells. (2) The lung slices were examined by transmission light microscopy to target the alveolar duct. The air-filled lung was sufficiently accessible by light microscopy that counterstains or fluorescent labels were unnecessary to identify the alveolar duct. (3) The enzymatic and microfluidic isolation of single cells allowed for the harvest of as few as several thousand cells for PCR analysis. Microfluidics based arrays were used to measure the expression of selected marker genes in individual cells to characterize different cell populations. Preliminary work suggests the unique value of this approach to understand the intra- and intercellular interactions within the regenerating alveolar duct

Regulation of cell survival by sphingosine-1-phosphate receptor S1P1 via reciprocal ERK-dependent suppression of bim and PI-3-kinase/protein kinase C-mediated upregulation of Mcl-1

Although the ability of bioactive lipid sphingosine-1-phosphate (S1P) to positively regulate anti-apoptotic/pro-survival responses by binding to S1P1 is well known, the molecular mechanisms remain unclear. Here we demonstrate that expression of S1P1 renders CCL39 lung fibroblasts resistant to apoptosis following growth factor withdrawal. Resistance to apoptosis was associated with attenuated accumulation of pro-apoptotic BH3-only protein Bim. However, although blockade of extracellular signal-regulated kinase (ERK) activation could reverse S1P1-mediated suppression of Bim accumulation, inhibition of caspase-3 cleavage was unaffected. Instead S1P1-mediated inhibition of caspase-3 cleavage was reversed by inhibition of phosphatidylinositol-3-kinase (PI3K) and protein kinase C (PKC), which had no effect on S1P1 regulation of Bim. However, S1P1 suppression of caspase-3 was associated with increased expression of anti-apoptotic protein Mcl-1, the expression of which was also reduced by inhibition of PI3K and PKC. A role for the induction of Mcl-1 in regulating endogenous S1P receptor-dependent pro-survival responses in human umbilical vein endothelial cells was confirmed using S1P receptor agonist FTY720-phosphate (FTY720P). FTY720P induced a transient accumulation of Mcl-1 that was associated with a delayed onset of caspase-3 cleavage following growth factor withdrawal, whereas Mcl-1 knockdown was sufficient to enhance caspase-3 cleavage even in the presence of FTY720P. Consistent with a pro-survival role of S1P1 in disease, analysis of tissue microarrays from ER+ breast cancer patients revealed a significant correlation between S1P1 expression and tumour cell survival. In these tumours, S1P1 expression and cancer cell survival were correlated with increased activation of ERK, but not the PI3K/PKB pathway. In summary, pro-survival/anti-apoptotic signalling from S1P1 is intimately linked to its ability to promote the accumulation of pro-survival protein Mcl-1 and downregulation of pro-apoptotic BH3-only protein Bim via distinct signalling pathways. However, the functional importance of each pathway is dependent on the specific cellular context

Cosmic optical activity in the spacetime of a scalar-tensor screwed cosmic string

Measurements of radio emission from distant galaxies and quasars verify that the polarization vectors of these radiations are not randomly oriented as naturally expected. This peculiar phenomenon suggests that the spacetime intervening between the source and observer may be exhibiting some sort of optical activity, the origin of which is not known. In the present paper we provide a plausible explanation to this phenomenon by investigating the r\^ole played by a Chern-Simons-like term in the background of an ordinary or superconducting screwed cosmic string in a scalar-tensor gravity. We discuss the possibility that the excess in polarization of the light from radio-galaxies and quasars can be understood as if the electromagnetic waves emitted by these cosmic objects interact with a scalar-tensor screwed cosmic string through a Chern-Simons coupling. We use current astronomical data to constrain possible values for the coupling constant of this theory, and show that it turns out to be: $\lambda \sim 10^{-26}$ eV, which is two orders of magnitude larger than in string-inspired theories.Comment: Revised version, to appear in Phys. Rev.

The Angular Trispectra of CMB Temperature and Polarization

We develop the formalism necessary to study four-point functions of the cosmic microwave background (CMB) temperature and polarization fields. We determine the general form of CMB trispectra, with the constraints imposed by the assumption of statistical isotropy of the CMB fields, and derive expressions for their estimators, as well as their Gaussian noise properties. We apply these techniques to initial non-Gaussianity of a form motivated by inflationary models. Due to the large number of four-point configurations, the sensitivity of the trispectra to initial non-Gaussianity approaches that of the temperature bispectrum at high multipole moment. These trispectra techniques will also be useful in the study of secondary anisotropies induced for example by the gravitational lensing of the CMB by the large scale structure of the universe.Comment: 16 pages, 4 figures; typographical errors correcte

Continuous image distortion by astrophysical thick lenses

Image distortion due to weak gravitational lensing is examined using a non-perturbative method of integrating the geodesic deviation and optical scalar equations along the null geodesics connecting the observer to a distant source. The method we develop continuously changes the shape of the pencil of rays from the source to the observer with no reference to lens planes in astrophysically relevant scenarios. We compare the projected area and the ratio of semi-major to semi-minor axes of the observed elliptical image shape for circular sources from the continuous, thick-lens method with the commonly assumed thin-lens approximation. We find that for truncated singular isothermal sphere and NFW models of realistic galaxy clusters, the commonly used thin-lens approximation is accurate to better than 1 part in 10^4 in predicting the image area and axes ratios. For asymmetric thick lenses consisting of two massive clusters separated along the line of sight in redshift up to \Delta z = 0.2, we find that modeling the image distortion as two clusters in a single lens plane does not produce relative errors in image area or axes ratio more than 0.5%Comment: accepted to GR

Nonlinear Effects in the Cosmic Microwave Background

Major advances in the observation and theory of cosmic microwave background anisotropies have opened up a new era in cosmology. This has encouraged the hope that the fundamental parameters of cosmology will be determined to high accuracy in the near future. However, this optimism should not obscure the ongoing need for theoretical developments that go beyond the highly successful but simplified standard model. Such developments include improvements in observational modelling (e.g. foregrounds, non-Gaussian features), extensions and alternatives to the simplest inflationary paradigm (e.g. non-adiabatic effects, defects), and investigation of nonlinear effects. In addition to well known nonlinear effects such as the Rees-Sciama and Ostriker-Vishniac effects, further nonlinear effects have recently been identified. These include a Rees-Sciama-type tensor effect, time-delay effects of scalar and tensor lensing, nonlinear Thomson scattering effects and a nonlinear shear effect. Some of the nonlinear effects and their potential implications are discussed.Comment: Invited contribution to Relativistic Cosmology Symposium (celebrating the 60th year of GFR Ellis); to appear Gen. Rel. Gra