The emerging role of insulin-like growth factor 1 receptor (IGF1r) in gastrointestinal stromal tumors (GISTs)

Recent years have seen a growing interest in insulin-like growth factor 1 receptor (IGF1R) in medical oncology. Interesting data have been reported also on IGF1r in gastrointestinal stromal tumors (GISTs) especially in children and in young adult patients whose disease does not harbour mutations on KIT and PDGFRA and are poorly responsive to conventional therapies. However, it is too early to reach conclusions on IGF1R as a novel therapeutic target in GIST because the receptor's biological role is still to be defined and the clinical significance in patients needs to be studied in larger studies. We update and comment the current literature on IGF1R in GISTs and discuss the future perspectives in this promising field

Effects of ranolazine on astrocytes and neurons in primary culture

Ranolazine (Rn) is an antianginal agent used for the treatment of chronic angina pectoris when angina is not adequately controlled by other drugs. Rn also acts in the central nervous system and it has been proposed for the treatment of pain and epileptic disorders. Under the hypothesis that ranolazine could act as a neuroprotective drug, we studied its effects on astrocytes and neurons in primary culture. We incubated rat astrocytes and neurons in primary cultures for 24 hours with Rn (10−7, 10−6 and 10−5 M). Cell viability and proliferation were measured using trypan blue exclusion assay, MTT conversion assay and LDH release assay. Apoptosis was determined by Caspase 3 activity assay. The effects of Rn on proinflammatory mediators IL-β and TNF-α was determined by ELISA technique, and protein expression levels of Smac/Diablo, PPAR-γ, Mn-SOD and Cu/Zn-SOD by western blot technique. In cultured astrocytes, Rn significantly increased cell viability and proliferation at any concentration tested, and decreased LDH leakage, Smac/Diablo expression and Caspase 3 activity indicating less cell death. Rn also increased anti-inflammatory PPAR-γ protein expression and reduced pro-inflammatory proteins IL-1 β and TNFα levels. Furthermore, antioxidant proteins Cu/Zn-SOD and Mn-SOD significantly increased after Rn addition in cultured astrocytes. Conversely, Rn did not exert any effect on cultured neurons. In conclusion, Rn could act as a neuroprotective drug in the central nervous system by promoting astrocyte viability, preventing necrosis and apoptosis, inhibiting inflammatory phenomena and inducing anti-inflammatory and antioxidant agents

Modular third-order analysis of planar linkages with applications

This paper reports analysis equations for the computerized third-order analysis of dyads. Such equations are an extension of those reported by C.H. Suh and C.W. Radcliffe. Examples of tracing cubic of stationary curvature and quartic of derivative curvature for multi-loop linkages are herein described

Application of the ellipse of elasticity theory to the functional analysis of planar compliant mechanisms

In the last decades, a wide range of methods have been proposed for the analysis of compliant mechanisms. In this investigation, the theory of the ellipse of elasticity is tailored to the linear kinetostatic analysis of flexible systems. The proposed approach exploits the antiprojective polarity transformations of the conic associated to the generic two-port elastic suspension. According to the presented method, the elastostatic features of flexible elements with complex geometries, and of compliant mechanisms with serial, parallel, and hybrid topologies, can be represented by a unique geometric entity. As a consequence, the deflection analysis problem is reduced to a geometric problem with a straightforward solution. A specific procedure is developed both at the element and at the mechanism levels, to completely describe field of displacements and loads distribution in the elastic suspension. The application of the method is exemplified considering the analysis of different flexures and of a compliant four-bar linkage

A new NEMS Based Linear-to-Rotary Displacement-Capacity Transducer

This paper presents a new NEMS-Technology based device, which transduces micro-metric linear displacements of a tip probe into capacity variations of a rotary comb-drive. The mechanical structure of this device is obtained through three basic steps. Firstly, the pseudo-rigid body equivalent mechanism (PRBM) is obtained by optimizing a straight-line path generator (D-gauge mechanism). Then, the PRBM is transformed into a compliant structure by replacing revolute joints with flexure hinges and by adding a differential comb-drive sensible to variation capacity. Finally, the geometry is transferred to the device by means of a process based on electron beam lithography

Stiffness characterization of biological tissues by means of MEMS-technology based micro grippers under position control

This paper presents a method for detecting the mechanical stiffness of micro-metric biological tissues by means of compliance tests performed with a MEMS-Technology based microgripper. Thanks to an actuating rotary comb drive working in cooperation with another sensing rotary comb drive, the system is able to recognize the tissue sample stiffness. Such characterization is possible thanks to a proper control system that is applied to the whole mechanical structure

Development of a NEMS-technology based nano gripper

This paper presents the first prototype of a new concept nanogripper whose overall size has been reduced as much as permitted by a new fabrication process based on Nano Technology. The jaws lumen size is adequate to the mechanical manipulation of microorganisms colonies