An Observational Determination of the Proton to Electron Mass Ratio in the Early Universe

In an effort to resolve the discrepancy between two measurements of the fundamental constant mu, the proton to electron mass ratio, at early times in the universe we reanalyze the same data used in the earlier studies. Our analysis of the molecular hydrogen absorption lines in archival VLT/UVES spectra of the damped Lyman alpha systems in the QSOs Q0347-383 and Q0405-443 yields a combined measurement of a (Delta mu)/mu value of (-7 +/- 8) x 10^{-6}, consistent with no change in the value of mu over a time span of 11.5 gigayears. Here we define (Delta mu) as (mu_z - mu_0) where mu_z is the value of mu at a redshift of z and mu_0 is the present day value. Our null result is consistent with the recent measurements of King et al. 2009, (Delta mu)/u = (2.6 +/- 3.0) x 10^{-6}, and inconsistent with the positive detection of a change in mu by Reinhold et al. 2006. Both of the previous studies and this study are based on the same data but with differing analysis methods. Improvements in the wavelength calibration over the UVES pipeline calibration is a key element in both of the null results. This leads to the conclusion that the fundamental constant mu is unchanged to an accuracy of 10^{-5} over the last 80% of the age of the universe, well into the matter dominated epoch. This limit provides constraints on models of dark energy that invoke rolling scalar fields and also limits the parameter space of Super Symmetric or string theory models of physics. New instruments, both planned and under construction, will provide opportunities to greatly improve the accuracy of these measurements.Comment: Accepted for publication in the Astrophysical Journa

NICMOS Imaging of a Damped Lyman-alpha Absorber at z=1.89 toward LBQS 1210+1731 : Constraints on Size and Star Formation Rate

We report results of a high-resolution imaging search (in rest frame H-$\alpha$ and optical continuum) for the galaxy associated with the damped Lyman-$\alpha$ (DLA) absorber at $z=1.892$ toward the $z_{em}=2.543$ quasar LBQS 1210+1731, using HST/NICMOS. After PSF subtraction, a feature is seen in both the broad-band and narrow-band images, at a projected separation of 0.25\arcsec from the quasar. If associated with the DLA, the object would be $\approx 2-3$ $h_{70}^{-1}$ kpc in size with a flux of $9.8 \pm 2.4$ $\mu$Jy in the F160W filter, implying a luminosity at $\lambda_{central}=5500$ {\AA} in the rest frame of $1.5 \times 10^{10}$ $h_{70}^{-2}$ L$_{\odot}$ at $z=1.89$, for $q_{0}=0.5$. However, no significant H-$\alpha$ emission is seen, suggesting a low star formation rate (SFR) (3 $\sigma$ upper limit of 4.0 $h_{70}^{-2}$ M$_{\odot}$ yr$^{-1}$), or very high dust obscuration. Alternatively, the object may be associated with the host galaxy of the quasar. H-band images obtained with the NICMOS camera 2 coronagraph show a much fainter structure $\approx 4-5$ $h_{70}^{-1}$ kpc in size and containing four knots of continuum emission, located 0.7\arcsec away from the quasar. We have probed regions far closer to the quasar sight-line than in most previous studies of high-redshift intervening DLAs. The two objects we report mark the closest detected high-redshift DLA candidates yet to any quasar sight line. If the features in our images are associated with the DLA, they suggest faint, compact, somewhat clumpy objects rather than large, well-formed proto-galactic disks or spheroids.Comment: 52 pages of text, 19 figures, To be published in Astrophysical Journal (accepted Dec. 8, 1999

Functional characterisation of human pulmonary monocyte-like cells in lipopolysaccharide-mediated acute lung inflammation.

BACKGROUND: We have previously reported the presence of novel subpopulations of pulmonary monocyte-like cells (PMLC) in the human lung; resident PMLC (rPMLC, HLA-DR(+)CD14(++)CD16(+)cells) and inducible PMLC (iPMLC, HLA-DR(+)CD14(++)CD16(-) cells). iPMLC are significantly increased in bronchoalveolar lavage (BAL) fluid following inhalation of lipopolysaccharide (LPS). We have carried out the first functional evaluation of PMLC subpopulations in the inflamed lung, following the isolation of these cells, and other lineages, from BAL fluid using novel and complex protocols. METHODS: iPMLC, rPMLC, alveolar macrophages (AM), neutrophils, and regulatory T cells were quantified in BAL fluid of healthy subjects at 9 hours post-LPS inhalation (n = 15). Cell surface antigen expression by iPMLC, rPMLC and AM and the ability of each lineage to proliferate and to undergo phagocytosis were investigated using flow cytometry. Basal cytokine production by iPMLC compared to AM following their isolation from BAL fluid and the responsiveness of both cell types following in vitro treatment with the synthetic corticosteroid dexamethasone were assessed. RESULTS: rPMLC have a significantly increased expression of mature macrophage markers and of the proliferation antigen Ki67, compared to iPMLC. Our cytokine data revealed a pro-inflammatory, corticosteroid-resistant phenotype of iPMLC in this model. CONCLUSIONS: These data emphasise the presence of functionally distinct subpopulations of the monocyte/macrophage lineage in the human lung in experimental acute lung inflammation

Understanding young people's transitions in university halls through space and time

This article contributes to the theoretical discussion about young people's transitions through space and time. Space and time are complex overarching concepts that have creative potential in deepening understanding of transition. The focus of this research is young people's experiences of communal living in university halls. It is argued that particular space-time concepts draw attention to different facets of experience and in combination deepen the understanding of young people's individual and collective transitions. The focus of the article is the uses of the space-time concepts 'routine', 'representation', 'rhythm' and 'ritual' to research young people's experiences. The article draws on research findings from two studies in the North of England. © 2010 SAGE Publications

The Farthest Known Supernova: Support for an Accelerating Universe and a Glimpse of the Epoch of Deceleration

We present photometric observations of an apparent Type Ia supernova (SN Ia) at a redshift of ~1.7, the farthest SN observed to date. SN 1997ff, was discovered in a repeat observation by the HST of the HDF-), and serendipitously monitored with NICMOS on HST throughout the GTO campaign. The SN type can be determined from the host galaxy type:an evolved, red elliptical lacking enough recent star formation to provide a significant population of core-collapse SNe. The class- ification is further supported by diagnostics available from the observed colors and temporal behavior of the SN, both of which match a typical SN Ia. The photo- metric record of the SN includes a dozen flux measurements in the I, J, and H bands spanning 35 days in the observed frame. The redshift derived from the SN photometry, z=1.7+/-0.1, is in excellent agreement with the redshift estimate of z=1.65+/-0.15 derived from the U_300,B_450,V_606,I_814,J_110,J_125,H_160, H_165,K_s photometry of the galaxy. Optical and near-infrared spectra of the host provide a very tentative spectroscopic redshift of 1.755. Fits to observations of the SN provide constraints for the redshift-distance relation of SNe~Ia and a powerful test of the current accelerating Universe hypothesis. The apparent SN brightness is consistent with that expected in the decelerating phase of the preferred cosmological model, Omega_M~1/3, Omega_Lambda~2/3. It is inconsistent with grey dust or simple luminosity evolution, candidate astro- physical effects which could mimic past evidence for an accelerating Universe from SNe Ia at z~0.5.We consider several sources of possible systematic error including lensing, SN misclassification, selection bias, and calibration errors. Currently, none of these effects appears likely to challenge our conclusions.Comment: Accepted to the Astrophysical Journal 38 pages, 15 figures, Pretty version available at http://icarus.stsci.edu/~stefano/ariess.tar.g

Extreme energetic electron fluxes in low Earth orbit: Analysis of POES E > 30, E > 100 and E > 300 keV electrons

Energetic electrons are an important space weather hazard. Electrons with energies less than about 100 keV cause surface charging while higher energy electrons can penetrate materials and cause internal charging. In this study we conduct an extreme value analysis of the maximum 3-hourly flux of E> 30 keV, E> 100 keV and E> 300 keV electrons in low Earth orbit as a function of L∗, for geomagnetic field lines that map to the outer radiation belt, using data from the National Oceanic and Atmospheric Administration (NOAA) Polar Operational Environmental Satellites (POES) from July 1998 to June 2014. The 1 in 10 year flux of E> 30 keV electrons shows a general increasing trend with distance ranging from 1.8×107 cm−2s−1sr−1 at L∗ = 3.0 to 6.6×107 cm−2s−1sr−1 at L∗ = 8.0. The 1 in 10 year flux of E> 100 keV electrons peaks at L∗= 4.5 - 5.0 at 1.9×107 cm−2s−1sr−1 decreasing to minima of 7.1×106 and 8.7×106 cm−2s−1sr−1 at L∗ = 3.0 and 8.0 respectively. In contrast to the E> 30 keV electrons, the 1 in 10 year flux of E> 300 keV electrons shows a general decreasing trend with distance, ranging from 2.4×106 cm−2s−1sr−1 at L∗ = 3.0 to 1.2×105 cm−2s−1sr−1 at L∗= 8.0. Our analysis suggests that there is a limit to the E> 30 keV electrons with an upper bound in the range 5.1×107- 8.8×107 cm−2s−1sr−1. However, the results suggest that there is no upper bound for the E> 100 keV and E> 300 keV electrons

Flavones induce neutrophil apoptosis by down-regulation of Mcl-1 via a proteasomal-dependent pathway

Neutrophil apoptosis and subsequent nonphlogistic clearance by surrounding phagocytes are key to the successful resolution of neutrophilic inflammation, with dysregulated apoptosis reported in multiple human inflammatory diseases. Enhancing neutrophil apoptosis has proresolution and anti-inflammatory effects in preclinical models of inflammation. Here we investigate the ability of the flavones apigenin, luteolin, and wogonin to induce neutrophil apoptosis in vitro and resolve neutrophilic inflammation in vivo. Human neutrophil apoptosis was assessed morphologically and by flow cytometry following incubation with apigenin, luteolin, and wogonin. All three flavones induced time- and concentration-dependent neutrophil apoptosis (apigenin, EC(50)=12.2 μM; luteolin, EC(50)=14.6 μM; and wogonin, EC(50)=28.9 μM). Induction of apoptosis was caspase dependent, as it was blocked by the broad-spectrum caspase inhibitor Q-VD-OPh and was associated with both caspase-3 and caspase-9 activation. Flavone-induced apoptosis was preceded by down-regulation of the prosurvival protein Mcl-1, with proteasomal inhibition preventing flavone-induced Mcl-1 down-regulation and apoptosis. The flavones abrogated the survival effects of mediators that prolong neutrophil life span, including lipoteichoic acid, peptidoglycan, dexamethasone, and granulocyte-macrophage colony stimulating factor, by driving apoptosis. Furthermore, wogonin enhanced resolution of established neutrophilic inflammation in a zebrafish model of sterile tissue injury. Wogonin-induced resolution was dependent on apoptosis in vivo as it was blocked by caspase inhibition. Our data show that the flavones induce neutrophil apoptosis and have potential as neutrophil apoptosis-inducing anti-inflammatory, proresolution agents.—Lucas, C. D., Allen, K. C., Dorward, D. A., Hoodless, L. J., Melrose, L. A., Marwick, J. A., Tucker, C. S., Haslett, C., Duffin, R., Rossi, A. G. Flavones induce neutrophil apoptosis by down-regulation of Mcl-1 via a proteasomal-dependent pathway

Mechanism, assessment and management of pain in chronic pancreatitis: Recommendations of a multidisciplinary study group

AbstractDescriptionPain in patients with chronic pancreatitis (CP) remains the primary clinical complaint and source of poor quality of life. However, clear guidance on evaluation and treatment is lacking.MethodsPancreatic Pain working groups reviewed information on pain mechanisms, clinical pain assessment and pain treatment in CP. Levels of evidence were assigned using the Oxford system, and consensus was based on GRADE. A consensus meeting was held during PancreasFest 2012 with substantial post-meeting discussion, debate, and manuscript refinement.ResultsTwelve discussion questions and proposed guidance statements were presented. Conference participates concluded: Disease Mechanism: Pain etiology is multifactorial, but data are lacking to effectively link symptoms with pathologic feature and molecular subtypes. Assessment of Pain: Pain should be assessed at each clinical visit, but evidence to support an optimal approach to assessing pain character, frequency and severity is lacking. Management: There was general agreement on the roles for endoscopic and surgical therapies, but less agreement on optimal patient selection for medical, psychological, endoscopic, surgical and other therapies.ConclusionsProgress is occurring in pain biology and treatment options, but pain in patients with CP remains a major problem that is inadequately understood, measured and managed. The growing body of information needs to be translated into more effective clinical care

Welfare conditionality and social marginality: the folly of the tutelary state?

In a contemporarnb 1`vby evolution of the tutelary state, welfare reform in the United Kingdom has been characterised by moves towards greater conditionality and sanctioning. This is influenced by the attributing responsibility for poverty and unemployment to the behaviour of marginalised individuals. Mead (1992) has argued that the poor are dependants who ought to receive support on condition of certain restrictions imposed by a protective state that will incentivise engagement with support mechanisms. This article examines how the contemporary tutelary and therapeutic state has responded to new forms of social marginality. Drawing on a series of in-depth interviews conducted with welfare claimants with an offending background in England and Scotland, the article examines their encounters with the welfare system and argues that alienation, rather than engagement with support, increasingly characterises their experiences

Induction of Eosinophil Apoptosis by the Cyclin-Dependent Kinase Inhibitor AT7519 Promotes the Resolution of Eosinophil-Dominant Allergic Inflammation

Eosinophils not only defend the body against parasitic infection but are also involved in pathological inflammatory allergic diseases such as asthma, allergic rhinitis and contact dermatitis. Clearance of apoptotic eosinophils by macrophages is a key process responsible for driving the resolution of eosinophilic inflammation and can be defective in allergic diseases. However, enhanced resolution of eosinophilic inflammation by deliberate induction of eosinophil apoptosis using pharmacological agents has not been previously demonstrated. Here we investigated the effect of a novel cyclin-dependent kinase inhibitor drug, AT7519, on human and mouse eosinophil apoptosis and examined whether it could enhance the resolution of a murine model of eosinophil-dominant inflammation in vivo.Eosinophils from blood of healthy donors were treated with AT7519 and apoptosis assessed morphologically and by flow-cytometric detection of annexin-V/propidium iodide staining. AT7519 induced eosinophil apoptosis in a concentration dependent manner. Therapeutic administration of AT7519 in eosinophil-dominant allergic inflammation was investigated using an established ovalbumin-sensitised mouse model of allergic pleurisy. Following ovalbumin challenge AT7519 was administered systemically at the peak of pleural inflammation and inflammatory cell infiltrate, apoptosis and evidence of macrophage phagocytosis of apoptotic eosinophils assessed at appropriate time points. Administration of AT7519 dramatically enhanced the resolution of allergic pleurisy via direct induction of eosinophil apoptosis without detriment to macrophage clearance of these cells. This enhanced resolution of inflammation was shown to be caspase-dependent as the effects of AT7519 were reduced by treatment with a broad spectrum caspase inhibitor (z-vad-fmk).Our data show that AT7519 induces human eosinophil apoptosis and enhances the resolution of a murine model of allergic pleurisy by inducing caspase-dependent eosinophil apoptosis and enhancing macrophage ingestion of apoptotic eosinophils. These findings demonstrate the utility of cyclin-dependent kinase inhibitors such as AT7519 as potential therapeutic agents for the treatment of eosinophil dominant allergic disorders