Molecular imaging of inflammation and intraplaque vasa vasorum: A step forward to identification of vulnerable plaques?

Current developments in cardiovascular biology and imaging enable the noninvasive molecular evaluation of atherosclerotic vascular disease. Intraplaque neovascularization sprouting from the adventitial vasa vasorum has been identified as an independent predictor of intraplaque hemorrhage and plaque rupture. These intraplaque vasa vasorum result from angiogenesis, most likely under influence of hypoxic and inflammatory stimuli. Several molecular imaging techniques are currently available. Most experience has been obtained with molecular imaging using positron emission tomography and single photon emission computed tomography. Recently, the development of targeted contrast agents has allowed molecular imaging with magnetic resonance imaging, ultrasound and computed tomography. The present review discusses the use of these molecular imaging techniques to identify inflammation and intraplaque vasa vasorum to identify vulnerable atherosclerotic plaques at risk of rupture and thrombosis. The available literature on molecular imaging techniques and molecular targets associated with inflammation and angiogenesis is discussed, and the clinical applications of molecular cardiovascular imaging and the use of molecular techniques for local drug delivery are addressed

First Results from a High Precision Indoor & Outdoor PV Module Monitoring Campaign

To aid the design and parameterization of risk models used in insurance solutions for the PV industry, we introduced an innovative combination of repeated laboratory measurements and ongoing test field monitoring. This approach aims at the relationship between the real life experience and the STC based performance warranties. Each four samples of ten different module brands and types have been exposed for five years now. In this contribution, we compare the results of indoor module characterization to module parameters derived from outdoor operation, where IV curves are acquired in regular intervals. Dependent on the time scale, this comparison needs different approaches. When looking at the major influences on a PV module\u92s long term yield, a clear ranking is visible after 5 years of exposition. Deviations from rated values as given in the data sheet have the biggest influence on long-term yield, followed by initial degradation. Differences in cell and module technology are next in the ranking: low light behaviour, angular response and spectral response may help some products to perform better than others. Finally, long term degradation may cause different life time yields, as this (typically small) effect will increase differences in module characteristics with time. In this experiment, degradation rates between 0% and 1% per year have been deduced

Improvements in world-wide intercomparison of PV module calibration

The calibration of the electrical performance of seven photovoltaic (PV) modules was compared between four reference laboratories on three continents. The devices included two samples in standard and two in high-efficiency crystalline silicon technology, two CI(G)S and one CdTe module. The reference value for each PV module parameter was calculated from the average of the results of all four laboratories, weighted by the respective measurement uncertainties. All single results were then analysed with respect to this reference value using the En number approach. For the four modules in crystalline silicon technology, the results agreed in general within ±0.5%, with all values within ±1% and all En numbers well within [−1, 1], indicating further scope for reducing quoted measurement uncertainty. Regarding the three thin-film modules, deviations were on average roughly twice as large, i.e. in general from ±1% to ±2%. A number of inconsistent results were observable, although within the 5% that can be statistically expected on the basis of the En number approach. Most inconsistencies can be traced to the preconditioning procedure of one participant, although contribution of other factors cannot be ruled out. After removing these obvious inconsistent results, only two real outliers remained, representing less than 2% of the total number of measurands. The results presented show improved agreement for the calibration of PV modules with respect to previous international exercises. For thin-film PV modules, the preconditioning of the devices prior to calibration measurements is the most critical factor for obtaining consistent results, while the measurement processes seem consistent and repeatable

Structurally sophisticated octahedral metal complexes as highly selective protein kinase inhibitors.

The generation of synthetic compounds with exclusive target specificity is an extraordinary challenge of molecular recognition and demands novel design strategies, in particular for large and homologous protein families such as protein kinases with more than 500 members. Simple organic molecules often do not reach the necessary sophistication to fulfill this task. Here, we present six carefully tailored, stable metal-containing compounds in which unique and defined molecular geometries with natural-product-like structural complexity are constructed around octahedral ruthenium(II) or iridium(III) metal centers. Each of the six reported metal compounds displays high selectivity for an individual protein kinase, namely GSK3α, PAK1, PIM1, DAPK1, MLCK, and FLT4. Although being conventional ATP-competitive inhibitors, the combination of the unusual globular shape and rigidity characteristics, of these compounds facilitates the design of highly selective protein kinase inhibitors. Unique structural features of the octahedral coordination geometry allow novel interactions with the glycine-rich loop, which contribute significantly to binding potencies and selectivities. The sensitive correlation between metal coordination sphere and inhibition properties suggests that in this design, the metal is located at a "hot spot" within the ATP binding pocket, not too close to the hinge region where globular space is unavailable, and at the same time not too far out toward the solvent where the octahedral coordination sphere would not have a significant impact on potency and selectivity. This study thus demonstrates that inert (stable) octahedral metal complexes are sophisticated structural scaffolds for the design of highly selective chemical probes

Structurally sophisticated octahedral metal complexes as highly selective protein kinase inhibitors.

The generation of synthetic compounds with exclusive target specificity is an extraordinary challenge of molecular recognition and demands novel design strategies, in particular for large and homologous protein families such as protein kinases with more than 500 members. Simple organic molecules often do not reach the necessary sophistication to fulfill this task. Here, we present six carefully tailored, stable metal-containing compounds in which unique and defined molecular geometries with natural-product-like structural complexity are constructed around octahedral ruthenium(II) or iridium(III) metal centers. Each of the six reported metal compounds displays high selectivity for an individual protein kinase, namely GSK3α, PAK1, PIM1, DAPK1, MLCK, and FLT4. Although being conventional ATP-competitive inhibitors, the combination of the unusual globular shape and rigidity characteristics, of these compounds facilitates the design of highly selective protein kinase inhibitors. Unique structural features of the octahedral coordination geometry allow novel interactions with the glycine-rich loop, which contribute significantly to binding potencies and selectivities. The sensitive correlation between metal coordination sphere and inhibition properties suggests that in this design, the metal is located at a "hot spot" within the ATP binding pocket, not too close to the hinge region where globular space is unavailable, and at the same time not too far out toward the solvent where the octahedral coordination sphere would not have a significant impact on potency and selectivity. This study thus demonstrates that inert (stable) octahedral metal complexes are sophisticated structural scaffolds for the design of highly selective chemical probes

Repurposing CPAP machines as stripped-down ventilators

Abstract The worldwide shortage of medical-grade ventilators is a well-known issue, that has become one of the central topics during the COVID-19 pandemic. Given that these machines are expensive and have long lead times, one approach is to vacate them for patients in critical conditions while patients with mild to moderate symptoms are treated with stripped-down ventilators. We propose a mass-producible solution that can create such ventilators with minimum effort. The central part is a module that can be attached to CPAP machines and repurpose them as low-pressure ventilators. Here, we describe the concept and first measurements which underline the potential of our solution. Our approach may serve as a starting point for open-access ventilator technologies