Inhibiting ERK Activation with CI-1040 Leads to Compensatory Upregulation of Alternate MAPKs and Plasminogen Activator Inhibitor-1 following Subtotal Nephrectomy with No Impact on Kidney Fibrosis

Extracellular-signal regulated kinase (ERK) activation by MEK plays a key role in many of the cellular processes that underlie progressive kidney fibrosis including cell proliferation, apoptosis and transforming growth factor β1-mediated epithelial to mesenchymal transition. We therefore assessed the therapeutic impact of ERK1/2 inhibition using a MEK inhibitor in the rat 5/6 subtotal nephrectomy (SNx) model of kidney fibrosis. There was a twentyfold upregulation in phospho-ERK1/2 expression in the kidney after SNx in Male Wistar rats. Rats undergoing SNx became hypertensive, proteinuric and developed progressive kidney failure with reduced creatinine clearance. Treatment with the MEK inhibitor, CI-1040 abolished phospho- ERK1/2 expression in kidney tissue and prevented phospho-ERK1/2 expression in peripheral lymphocytes during the entire course of therapy. CI-1040 had no impact on creatinine clearance, proteinuria, glomerular and tubular fibrosis, and α-smooth muscle actin expression. However, inhibition of ERK1/2 activation led to significant compensatory upregulation of the MAP kinases, p38 and JNK in kidney tissue. CI-1040 also increased the expression of plasminogen activator inhibitor-1 (PAI-1), a key inhibitor of plasmin-dependent matrix metalloproteinases. Thus inhibition of ERK1/2 activation has no therapeutic effect on kidney fibrosis in SNx possibly due to increased compensatory activation of the p38 and JNK signalling pathways with subsequent upregulation of PAI-1

Generalized Chaplygin gas model: Cosmological consequences and statefinder diagnosis

The generalized Chaplygin gas (GCG) model in spatially flat universe is investigated. The cosmological consequences led by GCG model including the evolution of EoS parameter, deceleration parameter and dimensionless Hubble parameter are calculated. We show that the GCG model behaves as a general quintessence model. The GCG model can also represent the pressureless CDM model at the early time and cosmological constant model at the late time. The dependency of transition from decelerated expansion to accelerated expansion on the parameters of model is investigated. The statefinder parameters $r$ and $s$ in this model are derived and the evolutionary trajectories in $s-r$ plane are plotted. Finally, based on current observational data, we plot the evolutionary trajectories in $s-r$ and $q-r$ planes for best fit values of the parameters of GCG model. It has been shown that although, there are similarities between GCG model and other forms of chaplygin gas in statefinder plane, but the distance of this model from the $\Lambda$CDM fixed point in $s-r$ diagram is shorter compare with standard chaplygin gas model.Comment: 10 pages, 5 figures, accepted in Astrophys Space Sci. (2011

New Models for Wolf-Rayet and O Star Populations in Young Starbursts

Using the latest stellar evolution models, theoretical stellar spectra, and a compilation of observed emission line strengths from Wolf-Rayet (WR) stars, we construct evolutionary synthesis models for young starbursts. We explicitly distinguish between the various WR subtypes (WN, WC, WO), and we treat O and Of stars separately. We provide detailed predictions of UV and optical emission line strengths for both the WR stellar lines and the major nebular hydrogen and helium emission lines, as a function of several input parameters related to the starburst episode. We also derive the theoretical frequency of WR-rich starbursts. We then discuss: nebular HeII 4686 emission, the contribution of WR stars to broad Balmer line emission, techniques used to derive the WR and O star content from integrated spectra, and explore the implications of the formation of WR stars through mass transfer in close binary systems in instantaneous bursts. The observational features predicted by our models allow a detailed quantitative determination of the massive star population in a starburst region (particularly in so-called "WR galaxies") from its integrated spectrum and provide a means of deriving the burst properties (e.g., duration, age) and the parameters of the initial mass function of young starbursts. (Abridged abstract)Comment: Accepted by ApJ Supplements. LaTeX using aasmp4, psfigs macros. 49 pages including 23 figures. Paper (full, or text/figures separated) and detailed model results available at http://www.stsci.edu/ftp/science/starburst/sv97.htm

Performance of prototypes for the ALICE electromagnetic calorimeter

The performance of prototypes for the ALICE electromagnetic sampling calorimeter has been studied in test beam measurements at FNAL and CERN. A $4\times4$ array of final design modules showed an energy resolution of about 11% /$\sqrt{E(\mathrm{GeV})}$ $\oplus$ 1.7 % with a uniformity of the response to electrons of 1% and a good linearity in the energy range from 10 to 100 GeV. The electromagnetic shower position resolution was found to be described by 1.5 mm $\oplus$ 5.3 mm /$\sqrt{E \mathrm{(GeV)}}$. For an electron identification efficiency of 90% a hadron rejection factor of $>600$ was obtained.Comment: 10 pages, 10 figure

Highlights from the Pierre Auger Observatory

The Pierre Auger Observatory is the world's largest cosmic ray observatory. Our current exposure reaches nearly 40,000 km$^2$ str and provides us with an unprecedented quality data set. The performance and stability of the detectors and their enhancements are described. Data analyses have led to a number of major breakthroughs. Among these we discuss the energy spectrum and the searches for large-scale anisotropies. We present analyses of our X$_{max}$ data and show how it can be interpreted in terms of mass composition. We also describe some new analyses that extract mass sensitive parameters from the 100% duty cycle SD data. A coherent interpretation of all these recent results opens new directions. The consequences regarding the cosmic ray composition and the properties of UHECR sources are briefly discussed.Comment: 9 pages, 12 figures, talk given at the 33rd International Cosmic Ray Conference, Rio de Janeiro 201

The Pierre Auger Observatory III: Other Astrophysical Observations

Astrophysical observations of ultra-high-energy cosmic rays with the Pierre Auger ObservatoryComment: Contributions to the 32nd International Cosmic Ray Conference, Beijing, China, August 201

Astrophysically Triggered Searches for Gravitational Waves: Status and Prospects

In gravitational-wave detection, special emphasis is put onto searches that focus on cosmic events detected by other types of astrophysical observatories. The astrophysical triggers, e.g. from gamma-ray and X-ray satellites, optical telescopes and neutrino observatories, provide a trigger time for analyzing gravitational wave data coincident with the event. In certain cases the expected frequency range, source energetics, directional and progenitor information is also available. Beyond allowing the recognition of gravitational waveforms with amplitudes closer to the noise floor of the detector, these triggered searches should also lead to rich science results even before the onset of Advanced LIGO. In this paper we provide a broad review of LIGO's astrophysically triggered searches and the sources they target

Operations of and Future Plans for the Pierre Auger Observatory

Technical reports on operations and features of the Pierre Auger Observatory, including ongoing and planned enhancements and the status of the future northern hemisphere portion of the Observatory. Contributions to the 31st International Cosmic Ray Conference, Lodz, Poland, July 2009.Comment: Contributions to the 31st ICRC, Lodz, Poland, July 200