Phosphofructokinase 1 Glycosylation Regulates Cell Growth and Metabolism

Cancer cells must satisfy the metabolic demands of rapid cell growth within a continually changing microenvironment. We demonstrated that the dynamic posttranslational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAcylation) is a key metabolic regulator of glucose metabolism. O-GlcNAcylation was induced at serine 529 of phosphofructokinase 1 (PFK1) in response to hypoxia. Glycosylation inhibited PFK1 activity and redirected glucose flux through the pentose phosphate pathway, thereby conferring a selective growth advantage on cancer cells. Blocking glycosylation of PFK1 at serine 529 reduced cancer cell proliferation in vitro and impaired tumor formation in vivo. These studies reveal a previously uncharacterized mechanism for the regulation of metabolic pathways in cancer and a possible target for therapeutic intervention

XMM-Newton observations of 3C 273

A series of nine XMM-Newton observations of the radio-loud quasar 3C 273 are presented, concentrating mainly on the soft excess. Although most of the individual observations do not show evidence for iron emission, co-adding them reveals a weak, broad line (EW ~ 56 eV). The soft excess component is found to vary, confirming previous work, and can be well fitted with multiple blackbody components, with temperatures ranging between ~40 and ~330 eV, together with a power-law. Alternatively, a Comptonisation model also provides a good fit, with a mean electron temperature of ~350 eV, although this value is higher when the soft excess is more luminous over the 0.5-10 keV energy band. In the RGS spectrum of 3C 273, a strong detection of the OVII He-alpha absorption line at zero redshift is made; this may originate in warm gas in the local intergalactic medium, consistent with the findings of both Fang et al. (2003) and Rasmussen et al. (2003).Comment: 12 pages, 19 figures, accepted for publication in MNRA

Electrical Components for Marine Renewable Energy Arrays: A Techno-Economic Review

This paper presents a review of the main electrical components that are expected to be present in marine renewable energy arrays. The review is put in context by appraising the current needs of the industry and identifying the key components required in both device and array-scale developments. For each component, electrical, mechanical and cost considerations are discussed; with quantitative data collected during the review made freely available for use by the community via an open access online repository. This data collection updates previous research and addresses gaps specific to emerging offshore technologies, such as marine and floating wind, and provides a comprehensive resource for the techno-economic assessment of offshore energy arrays

The structure and radiation spectra of illuminated accretion disks in AGN. II. Flare/spot model of X-ray variability

We discuss a model of X-ray variability of active galactic nuclei (AGN). We consider multiple spots which originate on the surface of an accretion disk following intense irradiation by coronal flares. The spots move with the disk around the central black hole and eventually decay while new spots continuously emerge. We construct time sequences of the spectra of the spotted disk and compute the corresponding energy-dependent fractional variability amplitude. We explore the dependence on the disk inclination and other model parameters. AGN seen at higher inclination with respect to the observer, such as Seyfert 2 galaxies, are expected to have fractional variability amplitude of the direct emission by a factor of a few higher than objects seen face on, such as the Seyfert 1s.Comment: Astronomy and Astrophysics (in press

Magnetic resonance imaging for the differentiation of neoplastic, inflammatory, and cerebrovascular brain disease in dogs

BACKGROUND: The reliability and validity of magnetic resonance imaging (MRI) for detecting neoplastic, inflammatory, and cerebrovascular brain lesions in dogs are unknown. OBJECTIVES: To estimate sensitivity, specificity, and inter-rater agreement of MRI for classifying histologically confirmed neoplastic, inflammatory, and cerebrovascular brain disease in dogs. ANIMALS: One hundred and twenty-one client-owned dogs diagnosed with brain disease (n = 77) or idiopathic epilepsy (n = 44). METHODS: Retrospective, multi-institutional case series; 3 investigators analyzed MR images for the presence of a brain lesion with and without knowledge of case clinical data. Investigators recorded most likely etiologic category (neoplastic, inflammatory, cerebrovascular) and most likely specific disease for all brain lesions. Sensitivity, specificity, and inter-rater agreement were calculated to estimate diagnostic performance. RESULTS: MRI was 94.4% sensitive (95% confidence interval [CI] = 88.7, 97.4) and 95.5% specific (95% CI = 89.9, 98.1) for detecting a brain lesion with similarly high performance for classifying neoplastic and inflammatory disease, but was only 38.9% sensitive for classifying cerebrovascular disease (95% CI = 16.1, 67.0). In general, high specificity but not sensitivity was retained for MR diagnosis of specific brain diseases. Inter-rater agreement was very good for overall detection of structural brain lesions (j = 0.895, 95% CI = 0.792, 0.998, P < .001) and neoplastic lesions, but was only fair for cerebrovascular lesions (j = 0.299, 95% CI = 0, 0.761, P = .21). CONCLUSIONS AND CLINICAL IMPORTANCE: MRI is sensitive and specific for identifying brain lesions and classifying disease as inflammatory or neoplastic in dogs. Cerebrovascular disease in general and specific inflammatory, neoplastic, and cerebrovascular brain diseases were frequently misclassified.http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1939-1676ab201

Evaluation of standard magnetic resonance characteristics used to differentiate neoplastic, inflammatory, and vascular brain lesions in dogs

Magnetic resonance (MR) imaging characteristics are commonly used to help predict intracranial disease categories in dogs, however, few large studies have objectively evaluated these characteristics. The purpose of this retrospective study was to evaluate MR characteristics that have been used to differentiate neoplastic, inflammatory, and vascular intracranial diseases in a large, multi-institutional population of dogs. Medical records from three veterinary teaching hospitals were searched over a 6-year period for dogs that had diagnostic quality brain MR scans and histologically confirmed intracranial disease. Three examiners who were unaware of histologic diagnosis independently evaluated 19 MR lesion characteristics totaling 57 possible responses. A total of 75 dogs with histologically confirmed intracranial disease were included in analyses: 51 with neoplasia, 18 with inflammatory disease, and six with cerebrovascular disease. Only strong contrast enhancement was more common in neoplasia than other disease categories. A multivariable statistical model suggested that extra-axial origin, T2-FLAIR mixed intensity, and defined lesion margins were also predictive of neoplasia. Meningeal enhancement, irregular lesion shape, and multifocal location distinguished inflammatory diseases from the other disease categories. No MR characteristics distinguished vascular lesions and these appeared most similar to neoplasia. These results differed from a previous report describing seven MR characteristics that were predictive of neoplasia in dogs and cats. Findings from the current study indicated that the high performance of MR for diagnosing canine intracranial diseases might be due to evaluator recognition of combinations of MR characteristics vs. relying on any one MR characteristic alone.http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1740-8261hb201

Optical emission line properties of Narrow Line Seyfert 1s and comparison AGN

Based on a new spectroscopic sample observed using the WHT, we examine the kinematic properties of the various emission line regions in narrow line Seyfert 1 galaxies (NLS1s) by modelling their profiles using multiple component fits. We interpret these results by comparison with velocity components observed for different lines species covered in the same spectrum, and equivalent components measured in the spectra of some broad line Seyfert 1s and a representative Seyfert 2 galaxy. We find that the fits to the Halpha and Hbeta line profiles in NLS1s require an additional broad (~3000km/s) component that might correspond to a suppressed broad line region with similar kinematics to those of typical broad line Seyfert 1s. From the profiles of the forbidden high ionisation lines (FHILs) in NLS1s, we find evidence that they appear to trace an `intermediate' velocity region with kinematics between the standard broad and narrow line regions. Weaker evidence of this region is also present in the profiles of the permitted Balmer lines. Finally, we note that despite having similar ionisation potentials, the relative intensities of the highly ionised lines of [Fe X]6374 and [FeXI]7892 show considerable dispersion from one galaxy to another. The interpretation of this requires further modelling, but suggests the possibility of using the ratio as a diagnostic to constrain the physical conditions of the FHIL emitting region and possibly the shape of the spectral energy distribution in the vicinity of 200eV. This spectral region is very difficult to observe directly due to photoelectric absorption both in our Galaxy and intrinsic to the source.Comment: 24 pages, 13 figures, 5 tables, Accepted for publication in MNRA

Integrating organizational, social, and individual perspectives in Web 2.0-based workplace e-learning

From the issue entitled 'Special Issue: Emerging Social and Legal Aspect'E-learning is emerging as a popular approach of education in the workplace by virtue of its flexibility to access, just-in-time delivery, and cost-effectiveness. To improve social interaction and knowledge sharing in e-learning, Web 2.0 is increasingly utilized and integrated with e-learning applications. However, existing social learning systems fail to align learning with organizational goals and individual needs in a systemic way. The dominance of technology-oriented approaches makes elearning applications less goal-effective and poor in quality and design. To solve the problem, we address the requirement of integrating organizational, social, and individual perspectives in the development of Web 2.0 elearning systems. To fulfill the requirement, a key performance indicator (KPI)-oriented approach is presented in this study. By integrating a KPI model with Web 2.0 technologies, our approach is able to: 1) set up organizational goals and link the goals with expertise required for individuals; 2) build a knowledge network by linking learning resources to a set of competences to be developed and a group of people who learn and contribute to the knowledge network through knowledge creation, sharing, and peer evaluation; and 3) improve social networking and knowledge sharing by identifying each individual's work context, expertise, learning need, performance, and contribution. The mechanism of the approach is explored and elaborated with conceptual frameworks and implementation technologies. A prototype system for Web 2.0 e-learning has been developed to demonstrate the effectiveness of the approach. © Springer Science + Business Media, LLC 2009.postprin

A Comprehensive Spectral and Variability Study of Narrow-Line Seyfert 1 Galaxies Observed by ASCA: II. Spectral Analysis and Correlations

(Abridged) I present a comprehensive and uniform analysis of 25 {\it ASCA} observations from 23 Narrow-line Seyfert 1 galaxies. The spectral analysis and correlations are presented in this paper, Part 2; the reduction and time series analysis is presented in the companion paper, Part 1.Comment: 73 pages, 31 figures, accepted for publication in ApJS. Report also available at http://www.astro.columbia.edu/~leighly/research.htm