Pyrimidine-Rich Region Mutations Compensate for a Stem-Loop V Lesion in the 5′ Noncoding Region of Poliovirus Genomic RNA

AbstractFive revertants of a linker-scanning mutation adjacent to the stem-loop V attenuation determinant (X472) in the 5′ noncoding region of poliovirus RNA were independently isolated from neuroblastoma cells and contained RNAs with seven nucleotide changes in the pyrimidine-rich region. Generation of the identical rare second-site mutations suggests the existence of a replicase-dependent mutagenesis mechanism during poliovirus replication. Enzymatic structure probing of the mutated pyrimidine-rich domain identified secondary structure changes between stem-loops V and VI. A consensus secondary structure model is presented for wild-type stem-loops V and VI and the pyrimidine-rich region located in the 5′ noncoding region of poliovirus RNA. A pyrimidine-rich region mutant (X472-R4N) produced large plaques in neuroblastoma cells and small plaques in HeLa cells, but the plaque size differences were not due to cell-type differences in viral translation or RNA replication. Release of X472-R4N from HeLa cells was 10-fold lower than release from neuroblastoma cells, which may explain the small plaque phenotype of X472-R4N in HeLa cells. Wild-type poliovirus was also released more efficiently from neuroblastoma cells (∼4-fold increase compared with release from HeLa cells), indicating that poliovirus neurotropism may be influenced by the cell-type efficiency of virus release. Thermal treatment increased the levels of infectious X472-R4N virions but not wild-type virus particles; thus RNA sequence and structural changes in the mutated 5′ noncoding region of X472-R4N may have altered RNA–protein interactions necessary for virus infectivity

Discovery of the Putative Pulsar and Wind Nebula Associated with the TeV Gamma-ray Source HESS J1813-178

We present a Chandra X-ray observation of G12.82-0.02, a shell-like radio supernova remnant coincident with the TeV gamma-ray source HESS J1813-178. We resolve the X-ray emission from the co-located ASCA source into a point source surrounded by structured diffuse emission that fills the interior of the radio shell. The morphology of the diffuse emission strongly resembles that of a pulsar wind nebula. The spectrum of the compact source is well-characterized by a power-law with index Gamma approx 1.3, typical of young and energetic rotation-powered pulsars. For a distance of 4.5 kpc, consistent with the X-ray absorption and an association with the nearby star formation region W33, the 2-10 keV X-ray luminosities of the putative pulsar and nebula are L(PSR) = 3.2E33 ergs/s and L(PWN) = 1.4E34 ergs/s, respectively. Both the flux ratio of L(PWN)/L(PSR) = 4.3 and the total luminosity of this system predict a pulsar spin-down power of Edot > 1E37 ergs/s, placing it within the ten most energetic young pulsars in the Galaxy. A deep search for radio pulsations using the Parkes telescope sets an upper-limit of approx 0.07 mJy at 1.4 GHz for periods >~ 50 ms. We discuss the energetics of this source, and consider briefly the proximity of bright H2 regions to this and several other HESS sources, which may produce their TeV emission via inverse Compton scattering.Comment: 7 pages, 6 figure, Latex, emulateapj style. To appear in the Astrophysical Journa

Optical Sky Brightness at Cerro Tololo Inter-American Observatory from 1992 to 2006

We present optical UBVRI sky brightness measures from 1992 through 2006. The data are based on CCD imagery obtained with the CTIO 0.9-m, 1.3-m, and 1.5-m telescopes. The B- and V-band data are in reasonable agreement with measurements previously made at Mauna Kea, though on the basis of a small number of images per year there are discrepancies for the years 1992 through 1994. Our CCD-based data are not significantly different than values obtained at Cerro Paranal. We find that the yearly averages of V-band sky brightness are best correlated with the 10.7-cm solar flux taken 5 days prior to the sky brightness measures. This implies an average speed of 350 km/sec for the solar wind. While we can measure an enhancement of the night sky levels over La Serena 10 degrees above the horizon, at elevation angles above 45 degrees we find no evidence that the night sky brightness at Cerro Tololo is affected by artificial light of nearby towns and cities.Comment: 24 pages, 5 figures, to be published in the June, 2007, issue of the Publications of the Astron. Society of the Pacifi

Subclinical infection of macaques and baboons with a baboon simarterivirus

Simarteriviruses (Arteriviridae: Simarterivirinae) are commonly found at high titers in the blood of African monkeys but do not cause overt disease in these hosts. In contrast, simarteriviruses cause severe disease in Asian macaques upon accidental or experimental transmission. Here, we sought to better understand the host-dependent drivers of simarterivirus pathogenesis by infecting olive baboons (n = 4) and rhesus monkeys (n = 4) with the simarterivirus Southwest baboon virus 1 (SWBV-1). Surprisingly, none of the animals in our study showed signs of disease following SWBV-1 inoculation. Three animals (two rhesus monkeys and one olive baboon) became infected and sustained high levels of SWBV-1 viremia for the duration of the study. The course of SWBV-1 infection was highly predictable: plasma viremia peaked between 1 × 107 and 1 × 108 vRNA copies/mL at 3–10 days post-inoculation, which was followed by a relative nadir and then establishment of a stable set-point between 1 × 106 and 1 × 107 vRNA copies/mL for the remainder of the study (56 days). We characterized cellular and antibody responses to SWBV-1 infection in these animals, demonstrating that macaques and baboons mount similar responses to SWBV-1 infection, yet these responses are ineffective at clearing SWBV-1 infection. SWBV-1 sequencing revealed the accumulation of non-synonymous mutations in a region of the genome that corresponds to an immunodominant epitope in the simarterivirus major envelope glycoprotein GP5, which likely contribute to viral persistence by enabling escape from host antibodies

Balanced Crystalloids versus Saline in Critically Ill Adults — A Systematic Review with Meta-Analysis

BACKGROUND: The comparative efficacy and safety of balanced crystalloid solutions and saline for fluid therapy in critically ill adults remain uncertain. METHODS: We systematically reviewed randomized clinical trials (RCTs) comparing the use of balanced crystalloids with saline in critically ill adults. The primary outcome was 90-day mortality after pooling data from low-risk-of-bias trials using a random-effects model. We also performed a Bayesian meta-analysis to describe the primary treatment effect in probability terms. Secondary outcomes included the incidence of acute kidney injury (AKI), new treatment with renal replacement therapy (RRT), and ventilator-free and vasopressor-free days to day 28. RESULTS: We identified 13 RCTs, comprising 35,884 participants. From six trials (34,450 participants) with a low risk of bias, the risk ratio (RR) for 90-day mortality with balanced crystalloids versus saline was 0.96 (95% confidence interval [CI], 0.91 to 1.01; I2 = 12.1%); using vague priors, the posterior probability that balanced crystalloids reduce mortality was 89.5%. The RRs of developing AKI and of being treated with RRT with balanced crystalloids versus saline were 0.96 (95% CI, 0.89 to 1.02) and 0.95 (95% CI, 0.81 to 1.11), respectively. Ventilator-free days (mean difference, 0.18 days; 95% CI, −0.45 to 0.81) and vasopressor-free days (mean difference, 0.19 days; 95% CI, −0.14 to 0.51) were similar between groups. CONCLUSIONS: The estimated effect of using balanced crystalloids versus saline in critically ill adults ranges from a 9% relative reduction to a 1% relative increase in the risk of death, with a high probability that the average effect of using balanced crystalloids is to reduce mortality

Review Article: When 'life itself' goes to work: Reviewing shifts in organizational life through the lens of biopower

This review article suggests the English publication of Foucault’s lectures on biopower, The Birth of Biopolitics (2008), might be useful for extending our understandings of how organizational power relations have changed over the last 20 years. Unlike disciplinary power, which constrains and delimits individuals, the concept of biopower emphasizes how our life abilities and extra-work qualities (bios or ‘life itself’) are now key objects of exploitation – particularly under neoliberalism. The term biocracy is introduced to analyse recent reports on workplace experiences symptomatic of biopower. Finally, the conceptual weaknesses of biopower for organizational theorizing are critically evaluated to help develop the idea for future scholarship

Exposing the Contradictory Claims, Myths and Illusions of the “Secrets of Business Success and Company Longevity†Genre

Over the last three decades, several management consultants, academics and business practitioners have laid claim to identifying “the secrets†of business success and company longevity. However, a systematic analysis of 24 studies in this genre revealed fundamental disagreements over the elements these authors claim are the primary drivers of business performance and longevity, and demonstrates that they share eight methodological and analytical flaws. Furthermore, many of the claims they made about “the secrets†of business success have not stood the test of time. The paper explains why business practitioners will find little in these studies to help their companies become more successful now and in the future, and also speculates why several of these studies became international best-sellers during the 1980s, 1990s and 2000s. It concludes by suggesting some new avenues for future research in this domain, and highlights the practical implications of these findings for business practitioners

Co-location as a catalyst for service innovation : a study of Scottish health and social care

Academic literature and policy on co-location of local public services focus on the cost benefits. Other benefits and outcomes of co-location, including service innovations benefiting users, are under-conceptualized. This paper suggests a framework for evaluating co-location as a learning environment for innovation, drawing on new case studies of five Community Health Partnerships in Scotland charged with more closely coordinating health and social care. We conclude that partnerships using co-location are benefiting from additional service innovations