Interferon-λ restricts West Nile virus neuroinvasion by tightening the blood-brain barrier

Although interferon-λ [also known as type III interferon or interleukin-28 (IL-28)/IL-29] restricts infection by several viruses, its inhibitory mechanism has remained uncertain. We used recombinant interferon-λ and mice lacking the interferon-λ receptor (IFNLR1) to evaluate the effect of interferon-λ on infection with West Nile virus, an encephalitic flavivirus. Cell culture studies in mouse keratinocytes and dendritic cells showed no direct antiviral effect of exogenous interferon-λ, even though expression of interferon-stimulated genes was induced. We observed no differences in West Nile virus burden between wild-type and Ifnlr1-/- mice in the draining lymph nodes, spleen, or blood. We detected increased West Nile virus infection in the brain and spinal cord of Ifnlr1-/- mice, yet this was not associated with a direct antiviral effect in mouse neurons. Instead, we observed an increase in blood-brain barrier permeability in Ifnlr1-/- mice. Treatment of mice with pegylated interferon-λ2 resulted in decreased blood-brain barrier permeability, reduced West Nile virus infection in the brain without affecting viremia, and improved survival against lethal virus challenge. An in vitro model of the blood-brain barrier showed that interferon-λ signaling in mouse brain microvascular endothelial cells increased transendothelial electrical resistance, decreased virus movement across the barrier, and modulated tight junction protein localization in a protein synthesis- and signal transducer and activator of transcription 1 (STAT1)-independent manner. Our data establish an indirect antiviral function of interferon-λ in which noncanonical signaling through IFNLR1 tightens the blood-brain barrier and restricts viral neuroinvasion and pathogenesis

Valence electronic structure of Mn in undoped and doped lanthanum manganites from relative K x-ray intensity studies

Relative $K$ x-ray intensities of $Mn$ in $Mn$, $MnO_{2}$, $LaMnO_{3}$ and $La_{0.7}B_{0.3}MnO_{3}$ ($B$ = $Ca$, $Sr$, and $Ce$) systems have been measured following excitation by 59.54 keV $\gamma$-rays from a 200 mCi $^{241}$Am point-source. The measured results for the compounds deviate significantly from the results of pure $Mn$. Comparison of the experimental data with the multiconfiguration Dirac-Fock (MCDF) effective atomic model calculations indicates reasonable agreement with the predictions of ionic model for the doped {manganites except} that the electron doped $La_{0.7}Ce_{0.3}MnO_{3}$ and hole doped $La_{0.7}Ca_{0.3}MnO_{3}$ compounds show some small deviations. The results of $MnO_{2}$ and $LaMnO_{3}$ deviate considerably from the predictions of the ionic model. Our measured $K\beta/K\alpha$ ratio of $Mn$ in $La_{0.7}Ca_{0.3}MnO_{3}$ cannot be explained as a linear superposition of $K\beta/K\alpha$ ratios of $Mn$ for the end members which is in contrast to the recent proposal by Tyson et al. from their $Mn$ $K\beta$ spectra.Comment: 14 pages, 4 figures. to appear in NIM-B.Please send an e-mail for figure

High Altitude test of RPCs for the ARGO-YBJ experiment

A 50 m**2 RPC carpet was operated at the YangBaJing Cosmic Ray Laboratory (Tibet) located 4300 m a.s.l. The performance of RPCs in detecting Extensive Air Showers was studied. Efficiency and time resolution measurements at the pressure and temperature conditions typical of high mountain laboratories, are reported.Comment: 16 pages, 10 figures, submitted to Nucl. Instr. Met

Long-term wind resource assessment for small and medium-scale turbines using operational forecast data and measure-correlate-predict

Output from a state-of-the-art, 4 km resolution, operational forecast model (UK4) was investigated as a source of long-term historical reference data for wind resource assessment. The data were used to implement measure-correlate-predict (MCP) approaches at 37 sites throughout the United Kingdom (UK). The monthly and hourly linear correlation between the UK4-predicted and observed wind speeds indicates that UK4 is capable of representing the wind climate better than the nearby meteorological stations considered. Linear MCP algorithms were implemented at the same sites using reference data from UK4 and nearby meteorological stations to predict the long-term (10-year) wind resource. To obtain robust error statistics, MCP algorithms were applied using onsite measurement periods of 1-12 months initiated at 120 different starting months throughout an 11 year data record. Using linear regression MCP over 12 months, the average percentage errors in the long-term predicted mean wind speed and power density were 3.0% and 7.6% respectively, using UK4, and 2.8% and 7.9% respectively, using nearby meteorological stations. The results indicate that UK4 is highly competitive with nearby meteorological observations as an MCP reference data source. UK4 was also shown to systematically improve MCP predictions at coastal sites due to better representation of local diurnal effects

Identifying patient-important outcomes in polycystic kidney disease: An international nominal group technique study

AIM: Patients with autosomal dominant polycystic kidney disease (ADPKD) are at increased risk of premature mortality, morbidities and complications, which severely impair quality of life. However, patient-centered outcomes are not consistently reported in trials in ADPKD, which can limit shared decision-making. We aimed to identify outcomes important to patients and caregivers and the reasons for their priorities. METHODS: Nominal group technique was adopted involving patients with ADPKD and caregivers who were purposively selected from eight centres across Australia, France and the Republic of Korea. Participants identified, ranked and discussed outcomes for trials in ADPKD. We calculated an importance score (0-1) for each outcome and conducted thematic analyses. RESULTS: Across 17 groups, 154 participants (121 patients, 33 caregivers) aged 19 to 78 (mean 54.5 years) identified 55 outcomes. The 10 highest ranked outcomes were: kidney function (importance score 0.36), end-stage kidney disease (0.32), survival (0.21), cyst size/growth (0.20), cyst pain/bleeding (0.18), blood pressure (0.17), ability to work (0.16), cerebral aneurysm/stroke (0.14), mobility/physical function (0.12), and fatigue (0.12). Three themes were identified: threatening semblance of normality, inability to control and making sense of diverse risks. CONCLUSION: For patients with ADPKD and their caregivers, kidney function, delayed progression to end-stage kidney disease and survival were the highest priorities, and were focused on achieving normality, and maintaining control over health and lifestyle. Implementing these patient-important outcomes may improve the meaning and relevance of trials to inform clinical care in ADPKD

Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy

We review HB stars in a broad astrophysical context, including both variable and non-variable stars. A reassessment of the Oosterhoff dichotomy is presented, which provides unprecedented detail regarding its origin and systematics. We show that the Oosterhoff dichotomy and the distribution of globular clusters (GCs) in the HB morphology-metallicity plane both exclude, with high statistical significance, the possibility that the Galactic halo may have formed from the accretion of dwarf galaxies resembling present-day Milky Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the second-parameter problem is presented. A technique is proposed to estimate the HB types of extragalactic GCs on the basis of integrated far-UV photometry. The relationship between the absolute V magnitude of the HB at the RR Lyrae level and metallicity, as obtained on the basis of trigonometric parallax measurements for the star RR Lyrae, is also revisited, giving a distance modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are studied. Finally, the conductive opacities used in evolutionary calculations of low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and Space Scienc