A quality assurance reference model for object-orientation

Software quality assurance for object-oriented information systems development is the issue dealt with here. A Quality Assurance Reference Model is proposed based on the Revised Spiral Life Cycle Model. The Quality Assurance Reference Model associates quality criteria, quality factors and metrics into a matrix framework that may be used to achieve quality assurance for all cycles of the Revised Spiral Model

Mechanistic Modeling of Microtopographic Impacts on CO2 and CH4 Fluxes in an Alaskan Tundra Ecosystem Using the CLM-Microbe Model

Spatial heterogeneities in soil hydrology have been confirmed as a key control on CO2 and CH4 fluxes in the Arctic tundra ecosystem. In this study, we applied a mechanistic ecosystem model, CLM-Microbe, to examine the microtopographic impacts on CO2 and CH4 fluxes across seven landscape types in Utqiaġvik, Alaska: trough, low-centered polygon (LCP) center, LCP transition, LCP rim, high-centered polygon (HCP) center, HCP transition, and HCP rim. We first validated the CLM-Microbe model against static-chamber measured CO2 and CH4 fluxes in 2013 for three landscape types: trough, LCP center, and LCP rim. Model application showed that low-elevation and thus wetter landscape types (i.e., trough, transitions, and LCP center) had larger CH4 emissions rates with greater seasonal variations than high-elevation and drier landscape types (rims and HCP center). Sensitivity analysis indicated that substrate availability for methanogenesis (acetate, CO2 + H2) is the most important factor determining CH4 emission, and vegetation physiological properties largely affect the net ecosystem carbon exchange and ecosystem respiration in Arctic tundra ecosystems. Modeled CH4 emissions for different microtopographic features were upscaled to the eddy covariance (EC) domain with an area-weighted approach before validation against EC-measured CH4 fluxes. The model underestimated the EC-measured CH4 flux by 20% and 25% at daily and hourly time steps, suggesting the importance of the time step in reporting CH4 flux. The strong microtopographic impacts on CO2 and CH4 fluxes call for a model-data integration framework for better understanding and predicting carbon flux in the highly heterogeneous Arctic landscape

Natural and anthropogenic changes in atmospheric greenhouse gases over the past 2 millennia

Millennial changes in atmospheric trace gas composition are best determined from air enclosed in ice sheets. Air extracted from the open pores in firn and the bubbles in ice is measured to derive the past concentrations and isotopic ratios of the long lived trace gases. The significant increases observed in CO2, CH4 and N2O since about 1750 and the more recent appearance of synthetic gases such as the CFCs in the atmosphere are a key feature of the anthropocene. The millennia preceding the anthropocene, the Late Pre-Industrial Holocene (LPIH), show evidence of natural changes in trace gases that can be used to constrain models and improve their ability to predict future changes under scenarios of anthropogenic emissions and climate change. Precise measurements and ice core air samples that are accurately dated and highly resolved in time are required to record the small and rapid trace gas signals of this period. The atmospheric composition records produced by CSIRO and collaborators using the Law Dome, Antarctica ice cores are widely used in models of climate, atmospheric chemistry and the carbon cycle over the anthropocene and the LPIH. Results from these studies have been influential in informing global policies, including the Montreal and Kyoto Protocols. We will present the recently revised trace gas records from Law Dome and new measurements of tracers from these and other ice sites that reveal the causes of atmospheric changes over the anthropocene and the LPIH

ApoE influences regional white-matter axonal density loss in Alzheimer's disease

Mechanisms underlying phenotypic heterogeneity in young onset Alzheimer disease (YOAD) are poorly understood. We used diffusion tensor imaging and neurite orientation dispersion and density imaging (NODDI) with tract-based spatial statistics to investigate apolipoprotein (APOE) ε4 modulation of white-matter damage in 37 patients with YOAD (22, 59% APOE ε4 positive) and 23 age-matched controls. Correlation between neurite density index (NDI) and neuropsychological performance was assessed in 4 white-matter regions of interest. White-matter disruption was more widespread in ε4+ individuals but more focal (posterior predominant) in the absence of an ε4 allele. NODDI metrics indicate fractional anisotropy changes are underpinned by combinations of axonal loss and morphological change. Regional NDI in parieto-occipital white matter correlated with visual object and spatial perception battery performance (right and left, both p = 0.02), and performance (nonverbal) intelligence (WASI matrices, right, p = 0.04). NODDI provides tissue-specific microstructural metrics of white-matter tract damage in YOAD, including NDI which correlates with focal cognitive deficits, and APOEε4 status is associated with different patterns of white-matter neurodegeneration

The lung environment controls alveolar macrophage metabolism and responsiveness in type 2 inflammation

Fine control of macrophage activation is needed to prevent inflammatory disease, particularly at barrier sites such as the lungs. However, the dominant mechanisms that regulate the activation of pulmonary macrophages during inflammation are poorly understood. We found that alveolar macrophages (AlvMs) were much less able to respond to the canonical type 2 cytokine IL-4, which underpins allergic disease and parasitic worm infections, than macrophages from lung tissue or the peritoneal cavity. We found that the hyporesponsiveness of AlvMs to IL-4 depended upon the lung environment but was independent of the host microbiota or the lung extracellular matrix components surfactant protein D (SP-D) and mucin 5b (Muc5b). AlvMs showed severely dysregulated metabolism relative to that of cavity macrophages. After removal from the lungs, AlvMs regained responsiveness to IL-4 in a glycolysis-dependent manner. Thus, impaired glycolysis in the pulmonary niche regulates AlvM responsiveness during type 2 inflammation

Metal-macrofauna interactions determine microbial community structure and function in copper contaminated sediments

Peer reviewedPublisher PD

Celecoxib exerts protective effects in the vascular endothelium via COX-2-independent activation of AMPK-CREB-Nrf2 signalling

Although concern remains about the athero-thrombotic risk posed by cyclo-oxygenase (COX)-2-selective inhibitors, recent data implicates rofecoxib, while celecoxib appears equivalent to NSAIDs naproxen and ibuprofen. We investigated the hypothesis that celecoxib activates AMP kinase (AMPK) signalling to enhance vascular endothelial protection. In human arterial and venous endothelial cells (EC), and in contrast to ibuprofen and naproxen, celecoxib induced the protective protein heme oxygenase-1 (HO-1). Celecoxib derivative 2,5-dimethyl-celecoxib (DMC) which lacks COX-2 inhibition also upregulated HO-1, implicating a COX-2-independent mechanism. Celecoxib activated AMPKα(Thr172) and CREB-1(Ser133) phosphorylation leading to Nrf2 nuclear translocation. Importantly, these responses were not reproduced by ibuprofen or naproxen, while AMPKα silencing abrogated celecoxib-mediated CREB and Nrf2 activation. Moreover, celecoxib induced H-ferritin via the same pathway, and increased HO-1 and H-ferritin in the aortic endothelium of mice fed celecoxib (1000 ppm) or control chow. Functionally, celecoxib inhibited TNF-α-induced NF-κB p65(Ser536) phosphorylation by activating AMPK. This attenuated VCAM-1 upregulation via induction of HO-1, a response reproduced by DMC but not ibuprofen or naproxen. Similarly, celecoxib prevented IL-1β-mediated induction of IL-6. Celecoxib enhances vascular protection via AMPK-CREB-Nrf2 signalling, a mechanism which may mitigate cardiovascular risk in patients prescribed celecoxib. Understanding NSAID heterogeneity and COX-2-independent signalling will ultimately lead to safer anti-inflammatory drugs

Patent abdominal subcutaneous veins caused by congenital absence of the inferior vena cava: a case report

<p>Abstract</p> <p>Introduction</p> <p>Patent paraumbilical and abdominal subcutaneous veins are found frequently as collaterals in patients due to portal hypertension mainly in liver cirrhosis.</p> <p>Case presentation</p> <p>For evaluation of portal hypertension in a 72-year-old Caucasian man without liver cirrhosis, magnetic resonance imaging with gadolinium contrast-enhancement was performed and demonstrated a missing inferior vena cava. A blood return from the lower extremities was shown through enlarged collateral veins of the abdominal wall, vena azygos and hemiazygos continuation, and multiple liver veins emptying into the right cardiac atrium. We describe a rare case of abdominal subcutaneous wall veins as collaterals caused by a congenitally absent infrarenal inferior vena cava with preservation of a hypoplastic suprarenal segment.</p> <p>Conclusion</p> <p>Knowledge of these congenital variations can be of clinical importance and it is imperative for the reporting radiologist to identify these anomalies as they can have a significant impact on the clinical management of the patient.</p

Interleukin-1β sequesters hypoxia inducible factor 2α to the primary cilium.

BACKGROUND: The primary cilium coordinates signalling in development, health and disease. Previously we have shown that the cilium is essential for the anabolic response to loading and the inflammatory response to interleukin-1β (IL-1β). We have also shown the primary cilium elongates in response to IL-1β exposure. Both anabolic phenotype and inflammatory pathology are proposed to be dependent on hypoxia-inducible factor 2 alpha (HIF-2α). The present study tests the hypothesis that an association exists between the primary cilium and HIFs in inflammatory signalling. RESULTS: Here we show, in articular chondrocytes, that IL-1β-induces primary cilia elongation with alterations to cilia trafficking of arl13b. This elongation is associated with a transient increase in HIF-2α expression and accumulation in the primary cilium. Prolyl hydroxylase inhibition results in primary cilia elongation also associated with accumulation of HIF-2α in the ciliary base and axoneme. This recruitment and the associated cilia elongation is not inhibited by blockade of HIFα transcription activity or rescue of basal HIF-2α expression. Hypomorphic mutation to intraflagellar transport protein IFT88 results in limited ciliogenesis. This is associated with increased HIF-2α expression and inhibited response to prolyl hydroxylase inhibition. CONCLUSIONS: These findings suggest that ciliary sequestration of HIF-2α provides negative regulation of HIF-2α expression and potentially activity. This study indicates, for the first time, that the primary cilium regulates HIF signalling during inflammation