The traditional estimated return for the Markowitz mean-variance optimization has been demonstrated to seriously depart from its theoretic optimal return. We prove that this phenomenon is natural and the estimated optimal return is always √ γ times larger than its theoretic counterpart where γ = 1 1−y with y as the ratio of the dimension to sample size. Thereafter, we develop new bootstrap-corrected estimations for the optimal return and its asset allocation and prove that these bootstrap-corrected estimates are proportionally consistent with their theoretic counterparts. Our theoretical results are further confirmed by our simulations, which show that the essence of the portfolio analysis problem could be adequately captured by our proposed approach. This greatly enhances the practical uses of the Markowitz mean-variance optimization procedure.

Objective: Glucocorticoid excess leads to insulin resistance. This study explores the effects of glucocorticoids on the glucose transport system and insulin signalling in rat adipocytes. The interaction between glucocorticoids and high levels of insulin and glucose is also addressed. Design and Methods: Isolated rat adipocytes were cultured for 24 h at different glucose concentrations (5 and 15 mmol/l) with or without the glucocorticoid analogue dexamethasone (0.3 mmol/l) and insulin (10 4 mU/ml). After the culture period, the cells were washed and then basal and insulin-stimulated glucose uptake, insulin binding and lipolysis as well as cellular content of insulin signalling proteins (insulin receptor substrate-1 (IRS-1), IRS-2, phosphatidylinositol 3-kinase (PI3-K) and protein kinase B (PKB)) and glucose transporter isoform GLUT4 were measured. Results: Dexamethasone in the medium markedly decreased both basal and insulin-stimulated glucose uptake at both 5 and 15 mmol/l glucose (by ,40-50%, P , 0:001 and P , 0:05 respectively). Combined long-term treatment with insulin and dexamethasone exerted additive effects in decreasing basal, and to a lesser extent insulin-stimulated, glucose uptake capacity ðP , 0:05Þ compared with dexamethasone alone, but this was seen only at high glucose (15 mmol/l). Insulin binding was decreased (by ,40%, P , 0:05) in dexamethasone-treated cells independently of surrounding glucose concentration. Following dexamethasone treatment a ,75% decrease ðP , 0:001Þ in IRS-1 expression and an increase in IRS-2 (by ,150%, P , 0:001) was shown. Dexamethasone also induced a subtle decrease in PI3-K (by ,20%, P , 0:01) and a substantial decrease in PKB content (by ,45%, P , 0:001). Insulin-stimulated PKB phosphorylation was decreased (by ,40%, P , 0:01) in dexamethasone-treated cells. Dexamethasone did not alter the amount of total cellular membrane-associated GLUT4 protein. The effects of dexamethasone per se on glucose transport and insulin signalling proteins were mainly unaffected by the surrounding glucose and insulin levels. Dexamethasone increased the basal lipolytic rate (,4-fold, P , 0:05), but did not alter the antilipolytic effect of insulin. Conclusions: These results suggest that glucocorticoids, independently of the surrounding glucose and insulin concentration, impair glucose transport capacity in fat cells. This is not due to alterations in GLUT4 abundance. Instead dexamethasone-induced insulin resistance may be mediated via reduced cellular content of IRS-1 and PKB accompanied by a parallel reduction in insulin-stimulated activation of PKB.

Aptamers are single-stranded oligonucleotides of DNA or RNA that bind to target molecules with high affinity and specificity. Typically, aptamers are generated by an iterative selection process, called systematic evolution of ligands by exponential enrichment (SELEX). Recent advancements in SELEX technology have extended aptamer selection from comparatively simple mixtures of purified proteins to whole living cells, and now cell-based SELEX (or cell-SELEX) can isolate aptamers that bind to specific target cells. Combined with nanotechnology, microchips, microfluidic devices, RNAi and other advanced technologies, cell-SELEX represents an integrated platform providing ultrasensitive and highly specific tools for clinical medicine. In this review, we describe the recent progress made in the application of cell-SELEX for diagnosis, therapy and biomarker discovery. OPEN ACCESSInt. J. Mol. Sci. 2012, 13 3342

This paper describes a simple and sensitive aptamer/graphene oxide (GO) based assay for insulin detection. GO can protect DNA from nuclease cleavage, but aptamers can be detached from the GO surface by specific target binding. This exposes the aptamers to enzymatic cleavage and releases the target for a new cycle. Cycling of targets leads to significant signal amplification and low LOD.

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