Fluid Dynamics at Connections in Paediatric Cardiac Surgery*

The modified Blalock-Taussig shunt is a connection created between the systemic and pulmonary arterial circulations to improve pulmonary perfusion in children with congenital heart diseases. Survival of these patients is critically dependent on blood flow distribution between the pulmonary and systemic circulations, that in turn depends upon the fluid dynamic behaviour of the shunt. Computational fluid dynamics, structural analyses as well as in vitro experiments were carried out to derive a quantitative relationship between the shunt flow and the corresponding pressure drop. While computational fluid dynamics simulations were based on the assumption of rigid wall for the shunt and the arteries, proper distensible conduits were used in the in vitro study and the structural analysis of the anastomosis deformation. The results indicated that the internal pressure combined with wall distensibility modifies the cross-sectional area of the distal anastomosis (between the shunt and the pulmonary artery). This fact affects the pressure drop across the shunt, especially at low pressures. Based on the results from the computational analyses and the in vitro experiments, a relationship between pressure drop and flow in the shunt was obtained, which matches data from clinical measurements.     

Easy oxidation and nitration of human myoglobin by nitrite and hydrogen peroxide

The modification of human myoglobin (HMb) by reaction with nitrite and hydrogen peroxide has been investigated. This reaction is important because NO(2) (-) and H(2)O(2) are formed in vivo under conditions of oxidative and nitrative stress, where protein derivatization has been often observed. The abundance of HMb in tissues and in the heart makes it a potential source and target of reactive species generated in the body. The oxidant and nitrating species produced by HMb/H(2)O(2)/NO(2) (-) are nitrogen dioxide and peroxynitrite, which can react with exogenous substrates and endogenous protein residues. Tandem mass analysis of HMb modified by stoichiometric amounts of H(2)O(2) and NO(2) (-) indicated the presence of two endogenous derivatizations: oxidation of C110 to sulfinic acid (76 %) and nitration of Y103 to 3-nitrotyrosine (44 %). When higher concentrations of NO(2) (-) and H(2)O(2) were used, nitration of Y146 and of the heme were also observed. The two-dimensional gel-electrophoretic analysis of the modified HMbs showed spots more acidic than that of wild-type HMb, a result in agreement with the formation of sulfinic acid and nitrotyrosine residues. By contrast, the reaction showed no evidence for the formation of protein homodimers, as observed in the reaction of HMb with H(2)O(2) alone. Both HMb and the modified HMb are active in the H(2)O(2)/NO(2) (-)-dependent nitration of exogenous phenols. Their catalytic activity is quite similar and the endogenous modifications of HMb therefore have little effect on the reactivity of the protein intermediates.     

Indoor testing of road vehicle suspensions

The paper presents a method for the indoor testing of road vehicle suspension systems. A car suspension is positioned on a rotating drum located in the Laboratory for the Safety of Transport at the Politecnico di Milano and it is excited as the wheel passes over a cleat fixed on the drum. The wheel accelerations, displacements and the forces/moments acting at the suspension-chassis joints are measured in the frequency range 0–120 Hz. Five special six-axis load cells have been designed and used. Transient wheel motions have been recorded. The influence of the running conditions on the relevant performance indexes related to the vibration behavior of the tire/suspension system has been assessed.     

Elastomeric Compounds with Silica. Lower Hysteresis in the Presence of Functionalised Isoprene Oligomers

Silica as reinforcing filler brings about a low hysteresis in elastomeric compounds. Aim of this work was to promote a better silica-elastomer interaction by using, as minor ingredients of a compound, isoprene oligomers having a functional group as the chain end. The effect of the functionality was investigated by analysing the complex viscosity of silica-oligomers binary mixtures as well as the morphological and rheological properties of masterbatches and compounds based on isoprene rubbers. A better silica dispersion and a lower Payne effect were clearly observed in the presence of functionalized oligomers.     

Parameter Sensitivity Analysis of a Passenger/Seat Model for Ride Comfort Assessment

The paper deals with the parameter sensitivity analysis of a passenger/seat model that can be used for ride comfort assessments. The final aim is to produce a comprehensive framework for enabling vehicle seat designers to develop comfortable (and healthy) seats, especially for those people who spend their lives while working on vehicles. In this paper a seated passenger proprietary model has been proposed and validated either by comparing it with a mathematical model derived by means of commercial software, either by experimental activities. On the basis of the validated model a sensitivity analysis has been performed, aiming to identify the key parameters affecting the ride comfort. A total of 47 parameters were accounted for. Many parameters seem relevant to describe the ride comfort of a seated road vehicle passenger. The most important conclusion of the research is that the parameters referring to posture have proved to influence ride comfort to a great extent. Other relevant but less important parameters are: the stiffness and damping of the seat, the geometry of the seat, the size and inertia properties of the body segments, and the stiffness and damping of the different parts of the human body. Different running conditions have been considered, i.e. vehicle passing over cleats or running on a randomly profiled road. Different running conditions influence differently the ride comfort, so care has to be used when performing either experimental or numerical simulations.     

Activation of Hsp90 Enzymatic Activity and Conformational Dynamics through Rationally Designed Allosteric Ligands

Hsp90 is a molecular chaperone of pivotal importance for multiple cell pathways. ATP‐regulated internal dynamics are critical for its function and current pharmacological approaches block the chaperone with ATP‐competitive inhibitors. Herein, a general approach to perturb Hsp90 through design of new allosteric ligands aimed at modulating its functional dynamics is proposed. Based on the characterization of a first set of 2‐phenylbenzofurans showing stimulatory effects on Hsp90 ATPase and conformational dynamics, new ligands were developed that activate Hsp90 by targeting an allosteric site, located 65 Å from the active site. Specifically, analysis of protein responses to first‐generation activators was exploited to guide the design of novel derivatives with improved ability to stimulate ATP hydrolysis. The molecules’ effects on Hsp90 enzymatic, conformational, co‐chaperone and client‐binding properties were characterized through biochemical, biophysical and cellular approaches. These designed probes act as allosteric activators of the chaperone and affect the viability of cancer cell lines for which proper functioning of Hsp90 is necessary.