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It has previously been shown that small peptide molecules derived from the apolipoprotein E (ApoE) receptor binding region are anti-inflammatory in nature and can improve outcome following head injury.

It has been shown that small nanoparticles can translocate through and accumulate in an in vitro blood brain barrier model composed of rat brain microvessel vascular endothelial cells [10].

By utilizing theoretical models and computer simulations, it has been shown that small changes in this model may shift a network from a relatively quiet state to some other state with highly complex dynamics.

It has been shown that small doses of antioxidant compounds decrease the incidence of diabetes in streptozotocin (STZ -induced diabetic mice [22].

Indeed, it has been shown that small particles can passively cross the sinusoidal endothelium of the liver through fenestrations with a size of approximately a few hundred nanometers [5], [6].

For locations in loop 2 and loop 4 (after Y63, G70 and I153 respectively), it has been shown that small (up to 21 residue) peptides can be inserted without any reduction in protein levels [3], [18] and membrane incorporation (after G70 and I153, [3]).

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Also, it has been shown that small-interference RNA (siRNA) and/or micro-RNA (miRNA) are other possible mechanisms to regulate translation process [ 30].

Recently, it has been shown that small-sized adipocytes had markedly increased pro-inflammatory activity as compared to larger adipocytes in epididymal fat pads of Zucker Obese rats [ 33, 34].

Indeed, it has been shown that smaller tidal volumes significantly reduce mortality in ARDS patients [ 1].

Generally, it has been shown that smaller (5-nm) carboxylated diamonds are slightly less biocompatible than larger diamonds (more than 100 nm) [ 107, 108].

This may be relevant in vivo, as it has been shown that smaller scFvs have greater tumor penetration ability than larger antibodies [ 32].

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