Status of the profession

The number of astronomers has grown by about 40 percent over the past decade. The number of astronomers with jobs in industry, or with long-term, non-tenured, jobs has increased dramatically compared with traditional faculty positions. The increase in the number of astronomers and the declining share of the NSF budget going to astronomy has led to extreme difficulties in the NSF grant program and in support of the National Observatories. In 1989, direct NASA support of astronomers through the grants program exceeds that of NSF, although the total of the NSF grants program over decade far exceeds that of NASA. Access to major new telescopes will be important issue for the 1990s. US astronomers, who once had a monopoly on telescopes larger than 3 meters, will, by the year 2000, have access to just half of the world's optical telescope area

A free-response evaluation determining value in the computed tomography attenuation correction image for revealing pulmonary incidental findings : a phantom study

RATIONALE AND OBJECTIVES: The purpose of this study was to compare lesion-detection performance when interpreting computed tomography (CT) images that are acquired for attenuation correction when performing single photon emission computed tomography/computed tomography (SPECT/CT) myocardial perfusion studies. In the United Kingdom, there is a requirement that these images be interpreted; thus, it is necessary to understand observer performance on these images. MATERIALS AND METHODS: An anthropomorphic chest phantom with inserted spherical lesions of different sizes and contrasts was scanned on five different SPECT/CT systems using site-specific CT protocols for SPECT/CT myocardial perfusion imaging. Twenty-one observers (0-4years of CT experience) searched 26 image slices (17 abnormal, containing 1-3 lesions, and 9 normal, containing no lesions) for each CT acquisition. The observers marked and rated perceived lesions under the free-response paradigm. Four analyses were conducted using jackknife alternative free-response receiver operating characteristic (JAFROC) analysis: (1) 20-pixel acceptance radius (AR) with all 21 readers, abbreviated to 20/ALL analysis, (2) 40-pixel AR with 21 readers (40/ALL), (3) 20-pixel AR with 14 readers experienced in CT (20/EXP), and (4) 20-pixel AR with 7 readers with no CT experience (20/NOT). The significance level of the test was set so as to conservatively control the overall probability of a type I error to <0.05. RESULTS: The mean JAFROC figure of merit (FOM) for the five CT acquisitions for the 20/ALL study were 0.602, 0.639, 0.372, 0.475,and 0.719 with a significant difference in lesion-detection performance evident between all individual treatment pairs (P<.0001) with the exception of the 1-2 pairing, which was not significant (these differed only in milliamp seconds). System 5, which had the highest performance, had the smallest slice thickness and the largest matrix size. For the other analyses, the system orderings remained unchanged, and the significance of FOM difference findings remained identical to those for 20/ALL, with oneexception: for 20/EXP analysis the 1-2 difference became significant with the higher milliamp seconds superior. Improved detection performance was associated with a smaller slice thickness, increased matrix size, and, to a lesser extent, increased tube charge. CONCLUSIONS: Protocol variations for CT-based attenuation correction (AC) in SPECT/CT imaging have a measurable impact on lesion-detection performance. The results imply that z-axis resolution and matrix size had the greatest impact on lesion detection, with a weaker but detectable dependence on the product of milliamp and seconds

Mouse CD94/NKG2A Is a Natural Killer Cell Receptor for the Nonclassical Major Histocompatibility Complex (MHC) Class I Molecule Qa-1b

Natural killer (NK) cells preferentially lyse targets that express reduced levels of major histocompatibility complex (MHC) class I proteins. To date, the only known mouse NK receptors for MHC class I belong to the Ly49 family of C-type lectin homodimers. Here, we report the cloning of mouse NKG2A, and demonstrate it forms an additional and distinct class I receptor, a CD94/NKG2A heterodimer. Using soluble tetramers of the nonclassical class I molecule Qa-1b, we provide direct evidence that CD94/NKG2A recognizes Qa-1b. We further demonstrate that NK recognition of Qa-1b results in the inhibition of target cell lysis. Inhibition appears to depend on the presence of Qdm, a Qa-1b-binding peptide derived from the signal sequences of some classical class I molecules. Mouse NKG2A maps adjacent to CD94 in the heart of the NK complex on mouse chromosome six, one of a small cluster of NKG2-like genes. Our findings suggest that mouse NK cells, like their human counterparts, use multiple mechanisms to survey class I expression on target cells

Cultural and leadership predictors of corporate social responsibility values of top management: A GLOBE study of 15 countries.

This paper examines cultural and leadership variables associated with corporate social responsibility values that managers apply to their decision-making. In this longitudinal study, we analyze data from 561 firms located in 15 countries on five continents to illustrate how the cultural dimensions of institutional collectivism and power distance predict social responsibility values on the part of top management team members. CEO visionary leadership and integrity were also uniquely predictive of such values. Journal of International Business Studies (2006) 37, 823–837. doi:10.1057/palgrave.jibs.8400230

A novel, non-canonical mechanism of regulation of MST3 (mammalian Sterile20-related kinase 3)

The canonical pathway of regulation of the germinal centre kinase (GCK) III subgroup member, mammalian Sterile20-related kinase 3 (MST3), involves a caspase-mediated cleavage between N-terminal catalytic and C-terminal regulatory domains with possible concurrent autophosphorylation of the activation loop MST3(Thr178-), induction of Ser-/Thr-protein kinase activity and nuclear localisation. We identified an alternative ‘non-canonical’ pathway of MST3 activation (regulated primarily through dephosphorylation) which may also be applicable to other GCKIII (and GCKVI) subgroup members. In the basal state, inactive MST3 co-immunoprecipitated with the Golgi protein, GOLGA2/gm130. Activation of MST3 by calyculin A (a protein Ser-/Thr- phosphatase 1/2A inhibitor) stimulated (auto)phosphorylation of MST3(Thr178-) in the catalytic domain with essentially simultaneous cis-autophosphorylation of MST3(Thr328-) in the regulatory domain, an event also requiring the MST3(341-376) sequence which acts as a putative docking domain. MST3(Thr178-) phosphorylation increased MST3 kinase activity but this activity was independent of MST3(Thr328-) phosphorylation. Interestingly, MST3(Thr328-) lies immediately C-terminal to a STRAD pseudokinase-like site recently identified as being involved in binding of GCKIII/GCKVI members to MO25 scaffolding proteins. MST3(Thr178- /Thr328-) phosphorylation was concurrent with dissociation of MST3 from GOLGA2/gm130 and association of MST3 with MO25, and MST3(Thr328-) phosphorylation was necessary for formation of the activated MST3-MO25 holocomplex

Suppression of circulating IgD+CD27+ memory B cells in infants living in a malaria-endemic region of Kenya

Background: Plasmodium falciparum infection leads to alterations in B cell subset distribution. During infancy, development of peripheral B cell subsets is also occurring. However, it is unknown if infants living a malaria endemic region have alterations in B cell subsets that is independent of an age effect. Methods: To evaluate the impact of exposure to P. falciparum on B cell development in infants, flow cytometry was used to analyse the distribution and phenotypic characteristic of B cell subsets in infant cohorts prospectively followed at 12, 18 and 24 months from two geographically proximate regions in western Kenya with divergent malaria exposure i.e. Kisumu (malaria-endemic, n = 24) and Nandi (unstable malaria transmission, n = 21). Results: There was significantly higher frequency and absolute cell numbers of CD19+ B cells in Kisumu relative to Nandi at 12(p = 0.0440), 18(p = 0.0210) and 24 months (p = 0.0493). No differences were observed between the infants from the two sites in frequencies of naïve B cells (IgD+CD27-) or classical memory B cells (IgD-CD27+). However, immature transitional B cells (CD19+CD10+CD34-) were higher in Kisumu relative to Nandi at all three ages. In contrast, the levels of non-class switched memory B cells (CD19+IgD+CD27+) were significantly lower overall in Kisumu relative to Nandi at significantly at 12 (p = 0.0144), 18 (p = 0.0013) and 24 months (p = 0.0129). Conclusions: These data suggest that infants living in malaria endemic regions have altered B cell subset distribution. Further studies are needed to understand the functional significance of these changes and long-term impact on ability of these infants to develop antibody responses to P. falciparum and heterologous infections

Human PAPS Synthase Isoforms Are Dynamically Regulated Enzymes with Access to Nucleus and Cytoplasm

In higher eukaryotes, PAPS synthases are the only enzymes producing the essential sulphate-donor 3′-phospho-adenosine-5′-phosphosulphate (PAPS). Recently, PAPS synthases have been associated with several genetic diseases and retroviral infection. To improve our understanding of their pathobiological functions, we analysed the intracellular localisation of the two human PAPS synthases, PAPSS1 and PAPSS2. For both enzymes, we observed pronounced heterogeneity in their subcellular localisation. PAPSS1 was predominantly nuclear, whereas PAPSS2 localised mainly within the cytoplasm. Treatment with the nuclear export inhibitor leptomycin B had little effect on their localisation. However, a mutagenesis screen revealed an Arg-Arg motif at the kinase interface exhibiting export activity. Notably, both isoforms contain a conserved N-terminal basic Lys-Lys-Xaa-Lys motif indispensable for their nuclear localisation. This nuclear localisation signal was more efficient in PAPSS1 than in PAPSS2. The activities of the identified localisation signals were confirmed by microinjection studies. Collectively, we describe unusual localisation signals of both PAPS synthase isoforms, mobile enzymes capable of executing their function in the cytoplasm as well as in the nucleus

A meta-analysis of the investment-uncertainty relationship

In this article we use meta-analysis to investigate the investment-uncertainty relationship. We focus on the direction and statistical significance of empirical estimates. Specifically, we estimate an ordered probit model and transform the estimated coefficients into marginal effects to reflect the changes in the probability of finding a significantly negative estimate, an insignificant estimate, or a significantly positive estimate. Exploratory data analysis shows that there is little empirical evidence for a positive relationship. The regression results suggest that the source of uncertainty, the level of data aggregation, the underlying model specification, and differences between short- and long-run effects are important sources of variation in study outcomes. These findings are, by and large, robust to the introduction of a trend variable to capture publication trends in the literature. The probability of finding a significantly negative relationship is higher in more recently published studies. JEL Classification: D21, D80, E22 1

A novel lung disease phenotype adjusted for mortality attrition for cystic fibrosis Genetic modifier studies

Genetic studies of lung disease in Cystic Fibrosis are hampered by the lack of a severity measure that accounts for chronic disease progression and mortality attrition. Further, combining analyses across studies requires common phenotypes that are robust to study design and patient ascertainment

A Generic Bio-Economic Farm Model for Environmental and Economic Assessment of Agricultural Systems

Bio-economic farm models are tools to evaluate ex-post or to assess ex-ante the impact of policy and technology change on agriculture, economics and environment. Recently, various BEFMs have been developed, often for one purpose or location, but hardly any of these models are re-used later for other purposes or locations. The Farm System Simulator (FSSIM) provides a generic framework enabling the application of BEFMs under various situations and for different purposes (generating supply response functions and detailed regional or farm type assessments). FSSIM is set up as a component-based framework with components representing farmer objectives, risk, calibration, policies, current activities, alternative activities and different types of activities (e.g., annual and perennial cropping and livestock). The generic nature of FSSIM is evaluated using five criteria by examining its applications. FSSIM has been applied for different climate zones and soil types (criterion 1) and to a range of different farm types (criterion 2) with different specializations, intensities and sizes. In most applications FSSIM has been used to assess the effects of policy changes and in two applications to assess the impact of technological innovations (criterion 3). In the various applications, different data sources, level of detail (e.g., criterion 4) and model configurations have been used. FSSIM has been linked to an economic and several biophysical models (criterion 5). The model is available for applications to other conditions and research issues, and it is open to be further tested and to be extended with new components, indicators or linkages to other models