21 research outputs found
A novel compartment, the 'subqpical stem' of the aerial hyphae, is the location of a sigN-dependent, developmentally distinct transcription in Streptomyces coelicolor.
Streptomyces coelicolor has nine SigB-like RNA polymerase sigma factors, several of them implicated in morphological differentiation and/or responses to different stresses. One of the nine, SigN, is the focus of this article. A constructed sigN null mutant was delayed in development and exhibited a bald phenotype when grown on minimal medium containing glucose as carbon source. One of two distinct sigN promoters, sigNP1, was active only during growth on solid medium, when its activation coincided with aerial hyphae formation. Transcription from sigNP1 was readily detected in several whi mutants (interrupted in morphogenesis of aerial mycelium into spores), but was absent from all bld mutants tested, suggesting that sigNP1 activity was restricted to the aerial hyphae. It also depended on sigN, thus sigN was autoregulated. Mutational and transcription studies revealed no functional significance to the location of sigN next to sigF, encoding another SigB-like sigma factor. We identified another potential SigN target, nepA, encoding a putative small secreted protein. Transcription of nepA originated from a single, aerial hyphae-specific and sigN-dependent promoter. While in vitro run-off transcription using purified SigN on the Bacillus subtilis ctc promoter confirmed that SigN is an RNA polymerase sigma factor, SigN failed to initiate transcription from sigNP1 and from the nepA promoter in vitro. Additional in vivo data indicated that further nepA upstream sequences, which are likely to bind a potential activator, are required for successful transcription. Using a nepA–egfp transcriptional fusion we located nepA transcription to a novel compartment, the ‘subapical stem’ of the aerial hyphae. We suggest that this newly recognized compartment defines an interface between the aerial and vegetative parts of the Streptomyces colony and might also be involved in communication between these two compartments
Forecasting Intermittent Demand by Hyperbolic-Exponential Smoothing
Croston's method is generally viewed as superior to exponential smoothing
when demand is intermittent, but it has the drawbacks of bias and an inability
to deal with obsolescence, in which an item's demand ceases altogether. Several
variants have been reported, some of which are unbiased on certain types of
demand, but only one recent variant addresses the problem of obsolescence. We
describe a new hybrid of Croston's method and Bayesian inference called
Hyperbolic-Exponential Smoothing, which is unbiased on non-intermittent and
stochastic intermittent demand, decays hyperbolically when obsolescence occurs
and performs well in experiments.Comment: Earlier versions of this work were presented at the 25th European
Conference on Operations Research, 2012; and at the 54th Annual Conference of
the UK Operational Research Society, 2012. A journal version is in
preparatio
PATRIOT: A phase I study to assess the tolerability, safety and biological effects of a specific ataxia telangiectasia and Rad3-related (ATR) inhibitor (AZD6738) as a single agent and in combination with palliative radiation therapy in patients with solid tumours.
PATRIOT is a phase I study of the ATR inhibitor, AZD6738, as monotherapy, and in combination with palliative radiotherapy. Here, we describe the protocol for this study, which opened in 2014 and is currently recruiting and comprises dose escalation of both drug and radiotherapy, and expansion cohorts
Developing a predictive modelling capacity for a climate change-vulnerable blanket bog habitat: Assessing 1961-1990 baseline relationships
Aim: Understanding the spatial distribution of high priority habitats and
developing predictive models using climate and environmental variables to
replicate these distributions are desirable conservation goals. The aim of this
study was to model and elucidate the contributions of climate and topography to
the distribution of a priority blanket bog habitat in Ireland, and to examine how
this might inform the development of a climate change predictive capacity for
peat-lands in Ireland.
Methods: Ten climatic and two topographic variables were recorded for grid
cells with a spatial resolution of 1010 km, covering 87% of the mainland
land surface of Ireland. Presence-absence data were matched to these variables
and generalised linear models (GLMs) fitted to identify the main climatic and
terrain predictor variables for occurrence of the habitat. Candidate predictor
variables were screened for collinearity, and the accuracy of the final fitted GLM
was evaluated using fourfold cross-validation based on the area under the curve
(AUC) derived from a receiver operating characteristic (ROC) plot. The GLM
predicted habitat occurrence probability maps were mapped against the actual
distributions using GIS techniques.
Results: Despite the apparent parsimony of the initial GLM using only climatic
variables, further testing indicated collinearity among temperature and precipitation
variables for example. Subsequent elimination of the collinear variables and
inclusion of elevation data produced an excellent performance based on the AUC
scores of the final GLM. Mean annual temperature and total mean annual
precipitation in combination with elevation range were the most powerful
explanatory variable group among those explored for the presence of blanket
bog habitat.
Main conclusions: The results confirm that this habitat distribution in general
can be modelled well using the non-collinear climatic and terrain variables tested
at the grid resolution used. Mapping the GLM-predicted distribution to the
observed distribution produced useful results in replicating the projected
occurrence of the habitat distribution over an extensive area. The methods
developed will usefully inform future climate change predictive modelling for
Irelan
Delineamentos para uma teoria da Museologia
The guiding principles in the formulation of a Museology theory were established\ud
and disseminated internationally from the mid-1980s, and are related to the creation of the\ud
International Committee for Museology (Icofom), associated with the International Council of\ud
Museums (Icom). The opinions regarding the nature of so-called museological knowledge\ud
were issued under the very specific conditions of each groups composition and of the intellectual\ud
work undertook in the occasion. Despite the difficulties with the wording, risen in tandem with\ud
the exercise (the terminology problem), we focused on the conjuncture that surrounded the\ud
formulation: the environment, the aims, the way in which it was composed and the foundations\ud
that characterise it, as well as some of the discussions that took place, which revealed aspects\ud
that have been handed down as a legacy in this field of specialization