Intracellularly selected recombinant antibodies targeting \u3b2 Amyloid Oligomers

Targeting beta Amyloid (A\u3b2) peptide, in relation to the degenerative processes of Alzheimer Disease (AD), and studying the mechanisms of A\u3b2 misfolding, oligomerization and aggregation are currently two hot-topics in AD research. Both these aspects can be preferentially approached by the use of anti-A\u3b2 antibodies, in particular of those which are conformation specific, as demonstrated by in vitro studies and by in vivo immunotherapy. Here, we describe the generation of a large panel of anti-A\u3b2 scFvs recombinant antibodies, exploiting a novel in vivo, yeast two hybrid-based, approach developed in our laboratory: the \u201cIntracellular Antibody Capture Technology\u201d (IACT). In this way, we have selected and characterized a panel of 18 different anti-A\u3b2 scFvs, which show interesting features in vitro and in cells. IACT-selected anti-A\u3b2 scFvs are conformation specific versus A\u3b2 oligomers and show peculiar immunoreactivity pattern versus the in vivo produced A\u3b2 deposits in human AD brains. Moreover, our anti-A\u3b2 scFvs, being in vivo selected in the yeast cytoplasm, can be readily expressed as intracellular antibodies in mammalian cells, targeted to different cellular compartments, allowing new promising strategies to study the emerging role of intracellular A\u3b2 processing and oligomerization in AD pathology. The panel of IACT-selected scFvs under study represents a new tool in the survey of existing anti-A\u3b2 antibodies, and the unique characteristics of the selection strategy used for their isolation appear to be particularly suited for the selection of oligomeric specific anti-A\u3b2 antibodies. Furthermore, the recombinant nature of the antibodies makes them ideally suited for extracellular and for intracellular delivery, in vitro as well as in vivo

EFFECTS OF SUPPORT STRUCTURE DYNAMICS ON CENTRIFUGAL COMPRESSOR ROTOR RESPONSE

LectureAccurate modeling of complicated dynamic phenomena characterizing rotating machineries represents a critical aspect in the rotor dynamic field. A correct prediction of rotor behavior is fundamental to identify safe operating conditions avoiding unstable operating range that may lead to erroneous project solution or possible unwanted consequences for the plant. Considering generic rotating machineries as mainly partitioned in four components (rotors, bearings, stator and supporting structure), most research activities have been addressed so far with strong focus more on the single components rather than on the whole system assembly. The importance of a combined analysis of rotors and elastic supporting structure (Kruger 2013) arises with the continuous development of turbo machinery applications, in particular in the Oil & Gas field, where a wide variety of solutions, such as off-shore installations or modularized turbo compression and turbo generator trains, lead to the need of a more complete study not only limited to the rotor-bearing system