Molecular Ultrasound Imaging of Junctional Adhesion Molecule A Depicts Acute Alterations in Blood Flow and Early Endothelial Dysregulation

Objective: The junctional adhesion molecule A (JAM-A) is physiologically located in interendothelial tight junctions and focally redistributes to the luminal surface of blood vessels under abnormal shear and flow conditions accompanying atherosclerotic lesion development. Therefore, JAM-A was evaluated as a target for molecularly targeted ultrasound imaging of transient endothelial dysfunction under acute blood flow variations. Approach and Results: Flow-dependent endothelial dysfunction was induced in apolipoprotein E-deficient mice (n=43) by carotid partial ligation. JAM-A expression was investigated by molecular ultrasound using antibody-targeted poly(n-butyl cyanoacrylate) microbubbles and validated with immunofluorescence. Flow disturbance and arterial remodeling were assessed using functional ultrasound. Partial ligation led to an immediate drop in perfusion at the ligated side and a direct compensatory increase at the contralateral side. This was accompanied by a strongly increased JAM-A expression and JAM-A-targeted microbubbles binding at the partially ligated side and by a moderate and temporary increase in the contralateral artery (approximate to 14x [P<0.001] and approximate to 5x [P<0.001] higher than control, respectively), both peaking after 2 weeks. Subsequently, although JAM-A expression and JAM-A-targeted microbubbles binding persisted at a higher level at the partially ligated side, it completely normalized within 4 weeks at the contralateral side. Conclusions: Temporary blood flow variations induce endothelial rearrangement of JAM-A, which can be visualized using JAM-A-targeted microbubbles. Thus, JAM-A may be considered as a marker of acute endothelial activation and dysfunction. Its imaging may facilitate the early detection of cardiovascular risk areas, and it enables the therapeutic prevention of their progression toward an irreversible pathological state

Process Control For Ozonation Systems: A Novel Real-Time Approach

For real-time control of ozonation processes in water works, a sequencing batch reactor was constructed to measure the ozone decay rate constant (k(O3)) in short time intervals of about 15 min. The batch reactor is filled during the production process, immediately after dissolving ozone in water by a static mixer. On the basis of k(O3) and the initial ozone concentration ([O-3](0)), and the experimentally determined ratio of the concentrations of (OH)-O-center dot radicals to ozone (R-ct), the degradation of micropollutants in ozone reactors (modeled as Continuously Stirred Tank Reactors - CSTRs) were calculated for compounds with known reaction rate constants with ozone and (OH)-O-center dot radicals. Calculated degradation of atrazine, iopromide, benzotriazole and acesulfame are in good agreement with measured data. For acesulfame the following rate constants were determined in this study at 20 C-o: reaction rate constant with ozone = 88 M(1)s(1), reaction rate constant with (OH)-O-center dot radical = 4.55x10(9) M(1)s(1). For the ozone reaction an activation energy of 35 kJ/mol was determined. Similarly to micropollutants, the relative inactivation of microorganisms (N/N-0) can be calculated based on the inactivation rate constant for ozone and if applicable the lag phase. The pI-value (=logN/N-0) was introduced and implemented in the process management system to calculate online the log inactivation of reference microorganisms such as B. subtilis spores. The system was tested for variation of pH (6.58.5), DOC (1.24.2 mg/L) flowrate 3.212 m(3)/h and temperature (5.79 C-o). Furthermore, a given pI-value, e.g. 1 for a 1-log inactivation of B. subtilis spores, can be set as control parameter in the process management system. The ozone gas flow is then adjusted until the set pI-value is reached. The process control concept was validated with B. subtilis spores. Generally, a good agreement was found between calculated and measured inactivation data. It was also demonstrated, that a constant ozone residual may lead to insufficient disinfection or overdosing of ozone. The new process control concept for ozonations based on onsite measurement of the ozone decay rate constant and the pI-value allows to assess disinfection and degradation processes quantitatively in real-time