392 research outputs found

    Climate model simulation of the South Indian Ocean Convergence Zone: mean state and variability

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    Evaluation of climate model performance at regional scales is essential in determining confidence in simulations of present and future climate. Here we developed a process-based approach focussing on the South Indian Ocean Convergence Zone (SIOCZ), a large-scale, austral summer rainfall feature extending across southern Africa into the southwest Indian Ocean. Simulation of the SIOCZ was evaluated for the Coupled Model Intercomparison Project (CMIP5). Comparison was made between CMIP5 and Atmospheric Model Intercomparison Project (AMIP) models to diagnose sources of biases associated with coupled ocean-atmosphere processes. Models were assessed in terms of mean SIOCZ characteristics and processes of interannual variability. Most models simulated a SIOCZ feature, but were typically too zonally oriented. A systematic bias of excessive precipitation was found over southern Africa and the Indian Ocean, but not particularly along the SIOCZ. Excessive precipitation over the continent may be associated with excessively high low-level moisture flux around the Angola Low found in most models, which is almost entirely due to circulation biases in models. AMIP models represented precipitation more realistically over the Indian Ocean, implying a potential coupling error. Interannual variability in the SIOCZ was evaluated through empirical orthogonal function analysis, where results showed a clear dipole pattern, indicative of a northeast-southwest movement of the SIOCZ. The drivers of this shift were significantly related to the El Niño Southern Oscillation and the subtropical Indian Ocean dipole in observations. However, the models did not capture these teleconnections well, limiting our confidence in model representation of variability

    A Quadruple Knockout of lasIR and rhlIR of Pseudomonas aeruginosa PAO1 That Retains Wild-Type Twitching Motility Has Equivalent Infectivity and Persistence to PAO1 in a Mouse Model of Lung Infection

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    It has been widely reported that quorum-sensing incapable strains of Pseudomonas aeruginosa are less virulent than wild type strains. However, quorum sensing mutants of P. aeruginosa have been shown to develop other spontaneous mutations under prolonged culture conditions, and one of the phenotypes of P. aeruginosa that is frequently affected by this phenomenon is type IV pili-dependent motility, referred to as twitching motility. As twitching motility has been reported to be important for adhesion and colonisation, we aimed to generate a quorum-sensing knockout for which the heritage was recorded and the virulence factor production in areas unrelated to quorum sensing was known to be intact. We created a lasIRrhlIR quadruple knockout in PAO1 using a published technique that allows for the deletion of antibiotic resistance cartridges following mutagenesis, to create an unmarked QS knockout of PAO1, thereby avoiding the need for use of antibiotics in culturing, which can have subtle effects on bacterial phenotype. We phenotyped this mutant demonstrating that it produced reduced levels of protease and elastase, barely detectable levels of pyoverdin and undetectable levels of the quorum sensing signal molecules N-3-oxododecanoly-L-homoserine lactone and N-butyryl homoserine lactone, but retained full twitching motility. We then used a mouse model of acute lung infection with P. aeruginosa to demonstrate that the lasIRrhlIR knockout strain showed equal persistence to wild type parental PAO1, induced equal or greater neutrophil infiltration to the lungs, and induced similar levels of expression of inflammatory cytokines in the lungs and similar antibody responses, both in terms of magnitude and isotype. Our results suggest, in contrast to previous reports, that lack of quorum sensing alone does not significantly affect the immunogenicity, infectiveness and persistence of P. aeruginosa in a mouse model of acute lung infection. © 2013 Lazenby et al

    Future precipitation projections over central and southern Africa and the adjacent Indian Ocean: what causes the changes and the uncertainty?

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    Future projections of precipitation at regional scales are vital to inform climate change adaptation activities. Therefore, is it important to quantify projected changes and associated uncertainty, and understand model processes responsible. This paper addresses these challenges for Southern Africa and adjacent Indian Ocean focusing on the local wet season. Precipitation projections for the end of the 21st century indicate a pronounced dipole pattern in the CMIP5 multi-model mean. The dipole indicates future wetting (drying) to the north (south) of the climatological axis of maximum rainfall, implying a northward shift of the ITCZ and South Indian Ocean Convergence Zone, and therefore not consistent with a simple ‘wet-get-wetter’ pattern. This pattern is most pronounced in early Austral summer suggesting a later and shorter wet season over much of southern Africa. Using a decomposition method we determine physical mechanisms underlying this dipole pattern of projected change, and the associated inter-model uncertainty. The projected dipole pattern is largely associated with the dynamical component of change indicative of shifts in the location of convection. Over the Indian Ocean, this apparent northward shift in the ITCZ may reflect the response to changes in the north-south SST gradient over the Indian Ocean, consistent with a ‘warmest-get-wetter’ mechanism. Over land subtropical drying is relatively robust, particularly in the early wet season. This has contributions from dynamical shifts in location of convection, which may be related to regional SST structures in the Southern Indian Ocean, and the thermodynamic decline in relative humidity. Implications for understanding and potentially constraining uncertainty in projections are discussed

    Complete Genome Sequence of Stenotrophomonas maltophilia Strain CF13, Recovered from Sputum from an Australian Cystic Fibrosis Patient.

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    Stenotrophomonas maltophilia isolate CF13 is a multidrug-resistant isolate that was recovered in Sydney, Australia, in 2011, from a sputum sample from an individual with cystic fibrosis. The genome sequence of CF13 was completed using long- and short-read technologies

    Psychosocial predictors of hope two years after diagnosis of colorectal cancer: Implications for nurse-led hope programmes

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    © 2019 John Wiley & Sons Ltd Objective: To prospectively explore predictors of hope in people with colorectal cancer at 24 months post-diagnosis. Methods: The present study is a secondary analysis of two waves within a longitudinal survey of patients newly diagnosed with colorectal cancer in Queensland, Australia. Baseline predictors (sociodemographic, disease, lifestyle characteristics, cancer threat appraisal and quality of life domains) were measured via mailed surveys and telephone interviews at 6 months post-diagnosis. Hope was measured via mailed surveys at 24 months post-diagnosis. Results: At 24 months post-diagnosis, 1,265 participants completed the hope measure. Hope was predicted by higher education, physical activity, cancer threat appraisal and each quality of life domain (i.e., physical, social, emotional and functional well-being; and colorectal cancer-specific concerns), which explained 23.63% of the total variance in hope, F(14, 1,081) = 23.89, p < 0.001. Conclusion: At 24 months post-diagnosis, hope was associated with greater functional, social and emotional well-being, and less threatened cancer appraisals. As hope programmes continue to be developed, designers should include activities that increase well-being and reduce cancer threat appraisal for people with colorectal cancer

    The validity of the Distress Thermometer in female partners of men with prostate cancer

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    © 2018 John Wiley & Sons Ltd Female partners of prostate cancer (PCa) survivors experience heightened psychological distress that may be greater than that expressed by PCa patients. However, optimal approaches to detect distressed, or at risk of distress, partners are unclear. This study applied receiver operating characteristics analysis to evaluate diagnostic accuracy, sensitivity and specificity of the Distress Thermometer (DT) compared to widely used measures of general (Hospital Anxiety and Depression Scale) and cancer-specific (Impact of Events Scale-Revised) distress. Participants were partners of men with localised PCa (recruited around diagnosis) about to undergo or had received surgical treatment (N = 189), and partners of men diagnosed with PCa who were 2–4 years post-treatment (N = 460). In both studies, diagnostic utility of the DT overall was not optimal. Although area under the curve scores were acceptable (ranges: 0.71–0.92 and 0.83–0.94 for general and cancer-specific distress, respectively), sensitivity, specificity and optimal DT cut-offs for partner distress varied for general (range: ≄2 to ≄5) and cancer-specific (range: ≄3 to ≄5) distress both across time and between cohorts. Thus, it is difficult to draw firm conclusions about the diagnostic capabilities of the DT for partners or recommend its use in this population. More comprehensive screening measures may be needed to detect partners needing psychological intervention

    Cell wall deficiency – an alternate bacterial lifestyle?

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    Historically, many species of bacteria have been reported to produce viable, cell wall deficient (CWD) variants. A variety of terms have been used to refer to CWD bacteria and a plethora of methods described in which to induce, cultivate and propagate them. In this review, we will examine the long history of scientific research on CWD bacteria examining the methods by which CWD bacteria are generated; the requirements for survival in a CWD state; the replicative processes within a CWD state; and the reversion of CWD bacteria into a walled state, or lack thereof. In doing so, we will present evidence that not all CWD variants are alike and that, at least in some cases, CWD variants arise through an adaptive lifestyle switch that enables them to live and thrive without a cell wall, often to avoid antimicrobial activity. Finally, the implications of CWD bacteria in recurring infections, tolerance to antibiotic therapy and antimicrobial resistance will be examined to illustrate the importance of greater understanding of the CWD bacteria in human health and disease

    The HSP90 inhibitor ganetespib: a potential effective agent for Acute Myeloid Leukemia in combination with cytarabine

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    HSP90 is a multi-client chaperone involved in regulating a large array of cellular processes and is commonly overexpressed in many different cancer types including hematological malignancies. Inhibition of HSP90 holds promise for targeting multiple molecular abnormalities and is therefore an attractive target for heterogeneous malignancies such as Acute Myeloid Leukemia (AML). Ganetespib is a highly potent second generation HSP90 inhibitor which we show is significantly more effective against primary AML blasts at nanomolar concentrations when compared with cytarabine (p < 0.001). Dose dependant cytotoxicity was observed with an apoptotic response coordinate with the loss of pro-survival signaling through the client protein AKT. Combination treatment of primary blasts with ganetespib and cytarabine showed good synergistic interaction (combination index (CI): 0.47) across a range of drug effects with associated reduction in HSP70 feedback and AKT signaling levels. In summary, we show ganetespib to have high activity in primary AMLs as a monotherapy and a synergistic relationship with cytarabine when combined. The combination of cytotoxic cell death, suppression of cytoprotective/drug resistance mechanisms such as AKT and reduced clinical toxicity compared to other HSP90 inhibitors provide strong rationale for the clinical assessment of ganetespib in AML

    Model-Based Systems Engineering and F’: Proof of Concept Via the Creation of an On-Orbit Textual Command Parsing Component for the ABEX Mission

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    The Alabama Burst Energetics eXplorer (ABEX) mission is defining spacecraft architecture, behavior, mission phases, operational states, risks, and requirements in a Model-Based Systems Engineering (MBSE) Integrated Systems Model (ISM) using SysML in Cameo Enterprise Architecture (CEA). The satellite structural design can be exported from CEA as Extensible Markup Language (XML) specifications and imported to F’, an open-source Flight Software (FSW) framework from NASA’s Jet Propulsion Laboratory. F’ contains background components intended to be connected to user-defined components in the XML after it is exported from the ISM; in this work, ABEX is representing F’ background components in SysML Internal Block Diagrams from which the XML is generated. As a proof of concept for this MBSE-centric FSW implementation, the ABEX FSW team has created a Command Reader component from MBSE-generated XML and tested command enaction on a Raspberry Pi breadboard system for three test cases representing on-orbit command triggers
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