Armitage and Doll first laid out a multistage theory of carcinogenesis in 1954 (19), and by 1990, initiation and promotion were well established as discrete steps in the evolution towards malignancy, along with the influence of 'free radicals', proto-oncogenes, oncogenes, epigenetic mechanisms and other synergistic or antagonistic factors (20).
For many applications, local time stepping offers an interesting and worthwhile alternative to the by now well established global time step control.
It is well established that these process steps can significantly influence product quality attributes (PQA).
Furthermore, the role of SEA in PBMC proliferation has been well established as an initial step for angiogenesis and granuloma formation in Schistosomiasis patients by up-regulation of vascular endothelial cell growth factor.
It is well established that an essential step in the progression of FN-matrix assembly involves α5β1 integrin binding of the RGD loop on FNIII10 and the neighboring PHSRN sequence in FNIII9 in the CBD of FN [ 116, 141- 146].
In addition to aviation, oil and nuclear industries, the formal investigation of incidents, consisting of a series of routinely followed steps, is well established.
The experimental steps are well established in a number of vendor-specific and published protocols [ 144], and there are robust computational pipelines available for analyzing read counts to quantify RNA abundance and differential gene expression among different conditions [ 145].
(13) Although relatively efficient Gibbs sampling schemes for step 1 are well established (we use those provided in Plummer 2003; see Implementation details), step 2 requires special consideration.
Some of these steps are now well established, but others remain elusive.
While the broad principles of length regulation are well established, the molecular mechanism of how these steps occur is not fully understood.
The theory of ATP synthesis in the F1 sector, through a mechanism of an asymmetric three-step rotation, has been well established (Nakamoto et al., 2008).
