7,083 research outputs found

    Indian summer monsoon prediction and simulation in CFSv2 coupled model

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    Using carefully designed coupled model experiments, we have demonstrated that the prediction skill of the all India summer monsoon rainfall (AISMR) in Climate Forecast System version 2 (CFSv2) model basically comes from the El-Niňo Southern Oscillation-Monsoon teleconnection. On the other hand, contrary to observations, the Indian Ocean coupled dynamics do not have a crucial role in controlling the prediction skill of the AISMR in CFSv2. We show that the inadequate representation of the Indian Ocean coupled dynamics in CFSv2 is responsible for this dichotomy. Hence, the improvement of the Indian Ocean coupled dynamics is essential for further improvement of the AISMR prediction skill in CFSv2

    Models of Experimental Competitive Intensities Predict Home and Away Differences in Invasive Impact and the Effects of an Endophytic Mutualist

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    Understanding the role of competition in the organization of communities is limited in part by the difficulty of extrapolating the outcomes of small-scale experiments to how such outcomes might affect the distribution and abundance of species. We modeled the community-level outcomes of competition, using experimentally derived competitive effects and responses between an exotic invasive plant, Centaurea stoebe, and species from both its native and nonnative ranges and using changes in these effects and responses elicited by experimentally establishing symbioses between C. stoebe and fungal endophytes. Using relative interaction intensities (RIIs) and holding other life-history factors constant, individual-based and spatially explicit models predicted competitive exclusion of all but one North American species but none of the European species, regardless of the endophyte status of C. stoebe. Concomitantly, C. stoebe was eliminated from the models with European natives but was codominant in models with North American natives. Endophyte symbiosis predicted increased dominance of C. stoebe in North American communities but not in European communities. However, when experimental variation was included, some of the model outcomes changed slightly. Our results are consistent with the idea that the effects of competitive intensity and mutualisms measured at small scales have the potential to play important roles in determining the larger-scale outcomes of invasion and that the stabilizing indirect effects of competition may promote species coexistence

    Extragenic suppressor mutations that restore twitching motility to fimL mutants of Pseudomonas aeruginosa are associated with elevated intracellular cyclic AMP levels

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    Cyclic AMP (cAMP) is a signaling molecule that is involved in the regulation of multiple virulence systems of the opportunistic pathogen Pseudomonas aeruginosa. The intracellular concentration of cAMP in P. aeruginosa cells is tightly controlled at the levels of cAMP synthesis and degradation through regulation of the activity and/or expression of the adenylate cyclases CyaA and CyaB or the cAMP phosphodiesterase CpdA. Interestingly, mutants of fimL, which usually demonstrate defective twitching motility, frequently revert to a wild-type twitching-motility phenotype presumably via the acquisition of an extragenic suppressor mutation(s). In this study, we have characterized five independent fimL twitching-motility revertants and have determined that all have increased intracellular cAMP levels compared with the parent fimL mutant. Whole-genome sequencing revealed that only one of these fimL revertants has acquired a loss-of-function mutation in cpdA that accounts for the elevated levels of intracellular cAMP. As mutation of cpdA did not account for the restoration of twitching motility observed in the other four fimL revertants, these observations suggest that there is at least another, as yet unidentified, site of extragenic suppressor mutation that can cause phenotypic reversion in fimL mutants and modulation of intracellular cAMP levels of P. aeruginosa

    The magnitude of educational disadvantage amongst indigenous minority groups in Australia.

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    Indigenous groups are amongst the most disadvantaged minority groups in the developed world. This paper examines the educational disadvantage of indigenous Australians by assessing academic performance at a relatively early age. We find that, by the age of 10, indigenous Australians are substantially behind non-indigenous Australians in academic achievement. Their relative performance deteriorates further over the next 2 years. School and locality do not appear to be important determinants of the indigenous to non-indigenous achievement gap. However, geographic remoteness, indigenous ethnicity and language use at home have a marked influence on educational achievement. A current focus of Australian indigenous policy is to increase school resources. Our results suggest that this will not eliminate indigenous educational disadvantage on its own

    Retreatment with anti-EGFR based therapies in metastatic colorectal cancer: impact of intervening time interval and prior anti-EGFR response.

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    BackgroundThis retrospective study aims to investigate the activity of retreatment with anti-EGFR-based therapies in order to explore the concept of clonal evolution by evaluating the impact of prior activity and intervening time interval.MethodsEighty-nine KRAS exon 2-wild-type metastatic colorectal patients were retreated on phase I/II clinical trials containing anti-EGFR therapies after progressing on prior cetuximab or panitumumab. Response on prior anti-EGFR therapy was defined retrospectively per physician-records as response or stable disease ≥6 months. Multivariable statistical methods included a multiple logistic regression model for response, and Cox proportional hazards model for progression-free survival.ResultsRetreatment anti-EGFR agents were cetuximab (n = 76) or cetuximab plus erlotinib (n = 13). The median interval time between prior and retreatment regimens was 4.57 months (range: 0.46-58.7). Patients who responded to the prior cetuximab or panitumumab were more likely to obtain clinical benefit to the retreatment compared to the non-responders in both univariate (p = 0.007) and multivariate analyses (OR: 3.38, 95 % CI: 1.27, 9.31, p = 0.019). The clinical benefit rate on retreatment also showed a marginally significant association with interval time between the two anti-EGFR based therapies (p = 0.053). Median progression-free survival on retreatment was increased in prior responders (4.9 months, 95 % CI: 3.6, 6.2) compared to prior non-responders (2.5 months, 95 % CI, 1.58, 3.42) in univariate (p = 0.064) and multivariate analysis (HR: 0.70, 95 % CI: 0.43-1.15, p = 0.156).ConclusionOur data lends support to the concept of clonal evolution, though the clinical impact appears less robust than previously reported. Further work to determine which patients benefit from retreatment post progression is needed

    Level of clinical evidence presented at the open and closed American Shoulder and Elbow Surgeons annual meeting over 10 years (2005-2014)

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    © 2016 The Author(s). Background: The American Shoulder and Elbow Surgeons (ASES) annual scientific meetings are premier forums whereby orthopaedic surgeons are informed of the latest research advances in shoulder and elbow surgery. The purpose of the present study was to assess the Level of evidence (LOE) in the clinical papers presented at both the open and closed ASES annual scientific meetings from 2005 to 2014. Secondarily, the study evaluated whether there were any changes in the distribution of LOE over this period of time. Methods: Two reviewers independently evaluated the abstracts of 532 paper presentations at either the open or closed ASES annual meetings. The independent reviewers first screened the abstracts for clinical evidence and excluded cadaveric, biomechanical, technique, and review studies. The included abstracts were then independently graded for methodological quality using LOE from Level I (highest quality) to IV (lowest quality) based on the classification system created by The American Academy of Orthopaedic Surgeons (AAOS). Results: Overall, 421 presentations were included and graded for LOE. In general, 17% of the presentations were graded level I; 15% level II; 25% level III; and 43% assigned a LOE of IV. Chi-square analysis demonstrated a statistically significant improvement in the LOE of presentations at the open and closed ASES meetings combined (p = 0.028) between the years 2005 and 2014. In particular, the proportion of presentations graded as level IV significantly decreased over this period (p = \u3c0.001). Conclusions: While most presentations at the ASES annual scientific meetings were of lower LOEs the percentage of level I evidence is greater than that reported at other Orthopaedic meetings. There has been a significant improvement in the LOE of clinical research at open and closed ASES meetings from 2005 to 2014. Specifically, the proportion of level IV studies have dramatically decreased over time

    Kinetic Characterisation of a Single Chain Antibody against the Hormone Abscisic Acid: Comparison with Its Parental Monoclonal

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    A single-chain Fv fragment antibody (scFv) specific for the plant hormone abscisic acid (ABA) has been expressed in the bacterium Escherichia coli as a fusion protein. The kinetics of ABA binding have been measured using surface plasmon resonance spectrometry (BIAcore 2000) using surface and solution assays. Care was taken to calculate the concentration of active protein in each sample using initial rate measurements under conditions of partial mass transport limitation. The fusion product, parental monoclonal antibody and the free scFv all have low nanomolar affinity constants, but there is a lower dissociation rate constant for the parental monoclonal resulting in a three-fold greater affinity. Analogue specificity was tested and structure-activity binding preferences measured. The biologically-active (+)-ABA enantiomer is recognised with an affinity three orders of magnitude higher than the inactive (-)-ABA. Metabolites of ABA including phaseic acid, dihydrophaseic acid and deoxy-ABA have affinities over 100-fold lower than that for (+)-ABA. These properties of the scFv make it suitable as a sensor domain in bioreporters specific for the naturally occurring form of ABA
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