Are Proto-Planetary Nebulae Shaped by a Binary? Results of a Long-Term Radial Velocity Study

The shaping of the nebula is currently one of the outstanding unsolved problems in planetary nebula (PN) research. Several mechanisms have been proposed, most of which require a binary companion. However, direct evidence for a binary companion is lacking in most PNs. We have addressed this problem by obtaining precise radial velocities of seven bright proto-planetary nebulae (PPNs), objects in transition from the asymptotic giant branch to the PN phases of stellar evolution. These have F-G spectral types and have the advantage over PNs of having more and sharper spectral lines, leading to better precision. Our observations were made in two observing intervals, 1991-1995 and 2007-2010, and we have included in our analysis some additional published and unpublished data. Only one of the PPNs, IRAS 22272+5435, shows a long-term variation that might tentatively be attributed to a binary companion, with P $>$ 22 years, and from this, limiting binary parameters are calculated. Selection effects are also discussed. These results set significant restrictions on the range of possible physical and orbital properties of any binary companions: they have periods greater than 25 years or masses of brown dwarfs or super-Jupiters. While not ruling out the binary hypothesis, it seems fair to say that these results do not support it.Comment: 14 pages, 3 figures, to appear Astrophys J, 734 (2011 June 10

On the nature of the galactic early-B hypergiants

Despite their importance to a number of astrophysical fields, the lifecycles of very massive stars are still poorly defined. In order to address this shortcoming, we present a detailed quantitative study of the physical properties of four early-B hypergiants (BHGs); Cyg OB2 #12, zeta Sco, HD190603 and BP Cru. These are combined with an analysis of their long-term spectroscopic and photometric behaviour in order to determine their evolutionary status. The long-term datasets revealed that they are remarkably stable over long periods (>40yr), with the possible exception of zeta Sco prior to the 20th century, in contrast to the typical excursions that characterise luminous blue variables (LBVs). Zeta Sco, HD190603 and BP Cru possess physical properties intermediate between B supergiants and LBVs; we therefore suggest that BHGs are the immediate descendants and progenitors (respectively) of such stars (for initial masses in the range ~30-60Msun). In contrast, while the wind properties of Cyg OB2 #12 are consistent with this hypothesis, the combination of extreme luminosity and spectroscopic mass (~110Msun) and comparatively low temperature means it cannot be accommodated in such a scheme. Likewise, despite its co-location with several LBVs above the Humphreys-Davidson (HD) limit, the lack of long term variability and its unevolved chemistry apparently excludes such an identification. Since such massive stars are not expected to evolve to such cool temperatures, the properties of Cyg OB2 #12 are difficult to understand under current evolutionary paradigms. [ABRIDGED]Comment: 36 pages, 19 figures (of which 17 pages are online supplemental material). Accepted for publication in Astronomy and Astrophysic

Control of tuberculosis in large cities in developed countries: an organizational problem

Tuberculosis (TB) is still a serious public health issue, even in large cities in developed countries. Control of this old disease is based on complicated programs that require completion of long treatments and contact tracing. In an accompanying research article published in BMC Public Health, Bothamley and colleagues found that areas with a ratio lower than one nurse per forty notifications had increased rates with respect to TB notifications, smear-positive cases, loss to follow-up and treatment abandonment across the UK. Furthermore, in these areas there was less opportunity for directly observed therapy, assistance with complex needs, educational outreach and new-entrant screening. In this commentary, we discuss the importance of improving organizational aspects and evaluating TB control programs. According to Bothamley and colleagues, a ratio of one nurse per forty notifications is an effective method of reducing the high TB incidences observed in London and in other cities in developed countries, or to maintain the decline in incidence in cities with lower incidences. It is crucial to evaluate TB programs every year to detect gaps early

Gender and respiratory factors associated with dyspnea in chronic obstructive pulmonary disease

RATIONALE: We had shown that COPD women expressed more dyspnea than men for the same degree of airway obstruction. OBJECTIVES: Evaluate gender differences in respiratory factors associated with dyspnea in COPD patients. METHODS: In a FEV(1 )% matched population of 100 men and women with COPD we measured: age, MMRC, FEV(1), FVC, TLC, IC/TLC, PaO(2), PaCO(2), D(LCO), P(imax), P(0.1), Ti/Ttot, BMI, ffmi, 6MWD and VAS scale before and after the test, the Charlson score and the SGRQ. We estimated the association between these parameters and MMRC scores. Multivariate analysis determined the independent strength of those associations. RESULTS: MMRC correlated with: BMI (men:-0.29, p = 0.04; women:-0.28, p = 0.05), ffmi (men:-0.39, p = 0.01), FEV(1 )% (men:-0.64, p < 0.001; women:-0.29, p = 0.04), FVC % (men:-0.45, p = 0.001; women:-0.33, p = 0.02), IC/TLC (men:-0.52, p < 0.001; women: -0.27, p = 0.05), PaO(2 )(men:-0.59, p < 0.001), PaCO(2 )(men:0.27, p = 0.05), D(LCO )(men:-0.54, p < 0.001), P(0.1)/P(imax )(men:0.46, p = 0.002; women:0.47, p = 0.005), dyspnea measured with the Visual Analog Scale before (men:0.37, p = 0.04; women:0.52, p = 0.004) and after 6MWD (men:0.52, p = 0.002; women:0.48, p = 0.004) and SGRQ total (men:0.50, p < 0.001; women:0.59, p < 0.001). Regression analysis showed that P(0.1)/P(imax )in women (r(2 )= 0.30) and BMI, DL(CO), PaO(2 )and P(0.1)/P(imax )in men (r(2 )= 0.81) were the strongest predictors of MMRC scores. CONCLUSION: In mild to severe COPD patients attending a pulmonary clinic, P(0.1)/P(imax )was the unique predictor of MMRC scores only in women. Respiratory factors explain most of the variations of MMRC scores in men but not in women. Factors other than the respiratory ones should be included in the evaluation of dyspnea in women with COPD

A Sensitive In Vitro Approach to Assess the Hybridization-Dependent Toxic Potential of High Affinity Gapmer Oligonucleotides

The successful development of high-affinity gapmer antisense oligonucleotide (ASO) therapeutics containing locked nucleic acid (LNA) or constrained ethyl (cEt) substitutions has been hampered by the risk of hepatotoxicity. Here, we present an in vitro approach using transfected mouse fibroblasts to predict the potential hepatic liabilities of LNA-modified ASOs (LNA-ASOs), validated by assessing 236 different LNA-ASOs with known hepatotoxic potential. This in vitro assay accurately reflects in vivo findings and relates hepatotoxicity to RNase H1 activity, off-target RNA downregulation, and LNA-ASO-binding affinity. We further demonstrate that the hybridization-dependent toxic potential of LNA-ASOs is also evident in different cell types from different species, which indicates probable translatability of the in vitro results to humans. Additionally, we show that the melting temperature (Tm) of LNA-ASOs maintained below a threshold level of about 55°C greatly diminished the hepatotoxic potential. In summary, we have established a sensitive in vitro screening approach for assessing the hybridization-dependent toxic potential of LNA-ASOs, enabling prioritization of candidate molecules in drug discovery and early development

Efficient oxygen transfer by surface aeration in shaken cylindrical containers for mammalian cell cultivation at volumetric scales up to 1000 L

Cylindrical containers agitated by orbital shaking are being developed as simple and cost-effective bioreactor systems for the cultivation of mammalian cells. Here the oxygen transfer capacities of containers with nominal volumes from 50 mL to 2000 L were determined, and the operating parameters influencing oxygen transfer were investigated. In general, the shaking speed necessary for efficient oxygen transfer diminished as the container size increased. At shaking speeds suitable for the growth of shear-sensitive cells, kLa values between 10 and 30 h−1 were typically achieved in small-scale (<1 L nominal volume) containers at shaking speeds above 120 rpm. A kLa value of 8 h−1 was measured at 75 rpm in a 200-L container with a working volume that was 50% of the nominal volume. In a 2000-L container with a working volume of 1000 L, a moderate kLa of 3 h−1 was obtained with a shaking speed of only 47 rpm. The free-surface area in 50-mL and 30-L containers was determined by photographic image analysis and computational fluid dynamic (CFD) simulation, respectively. The results showed that the increase in kLa at higher shaking speeds was mainly due to an increased kL value, highlighting the dominant effect of free-surface turbulence on gas transfer in orbitally shaken containers. The results demonstrated the feasibility of orbital shaking technology for the cultivation of mammalian cells at scales up to 1000 L