In order to compare a 96-well plate mini-tube SSF approach with larger scale methodologies, comparative experiments were carried out using standard shake flask methods [ 12- 15].
Genome-wide or large-scale methodologies employed in functional genomics such as DNA sequencing, transcription profiling, proteomics, and metabolite profiling have become important tools in many metabolic engineering strategies.
To tackle this challenge, several large-scale methodologies, under the term functional genomics, have been developed which aim at revealing putative gene functions [ 1- 3].
There is a belief that the genomic revolution triggered by full sequencing of the human genome and technological development of large-scale methodologies announces the future of personalized medicine.
Questions of amplification-induced error and template bias generated by these methods have previously been addressed through either small scale (SNPs) or large scale (CGH array, FISH) methodologies.
32, 35 A brief overview of methodologies using the structural consensus approach can be found in Table 2. Unfortunately, as of yet there has been no large scale comparison of different methodologies for representing binding sites by incorporating structural profiles.
QD skeleton has been introduced as a 'privileged template' to be a consequence of fragment-based drug discovery approaches (FDDA) that have already been penetrated into both pharmaceutical industry and academia on a large scale as an alternative methodology instead of combinatorial chemistry and high-throughput screening (HTS) techniques [9].
Other more recently described biomarkers such as procalcitonin [ 28- 30], glial fibrillary acidic protein [ 31], heparin binding protein [ 32] and brain-derived natriuretic factor [ 33] face the same methodological issues and further large scale studies with an accurate methodology are warranted.
However, the main challenge in this emerging area is still the strict control of the morphology (shapes) and dimensions of the NPs that is fundamental for the implementation at large scale of these cleaner synthetic methodologies.
Identification of the most appropriate cell sources for different potential applications, development of appropriate clinical grade methodologies and large scale well controlled clinical trials will be essential to assess safety and value of cell based therapies, which have been generating much hope, but are by and large not yet close to becoming standard clinical practice.
The report advocates "the need for a more integrated research funding system that can provide 'a ladder' for the progression of good collaborative research teams from small-scale intensive projects to test initial research ideas and methodologies to large scale projects that can provide rigorous evidence" (p. vii).
