Host cell invasion by apicomplexan parasites: the junction conundrum

No abstract available

Ariel - Volume 3 Number 5

Editors Richard J. Bonanno Robin A. Edwards Associate Editors Steven Ager Tom Williams Lay-out Editor Eugenia Miller Contributing Editors Paul Bialas Robert Breckenridge Lynne Porter David Jacoby Terry Burt Mark Pearlman Michael Leo Mike LeWitt Editors Emeritus Delvyn C. Case., Jr. Paul M. Fernhof

Impedance spectroscopy for in vitro toxicology

The impedance of biological material changes with frequency, a phenomenon that has been discovered more than 100 years ago. It is due to the fact that the cell membrane acts as a capacitor which filters out currents at low frequency and lets them pass at high frequency. This fundamental knowledge about biological dielectrics has incompletely been exploited to detect and distinguish toxicity effects on cell cultures, although impedance measurements have been used for long in this field. In this thesis, it was found that low frequency impedance signals are linked to initial stress responses of cells within cell populations when exposed to a toxin whereas high frequency measurements inform about major cell damage as is indicated by intracellular conductivity changes. In addition, when cells gain resistance to a toxin, they experience a higher cell stiffness which is expressed by an increased low frequency impedance. The study of impedance changes as a function of frequency and drug concentrations lead to the creation of an impedimetric concentration-response map which distinguishes cell responses within four concentration ranges without the use of any label. Although being inherently non-specific, this measurement method was shown to report on distinct toxicity effects, an important prerequisite when studying drug action on cancer cells where stimulating and lethal effects need to be distinguished rigorously. This thesis further encompasses the subject of three-dimensional impedance measurements, i.e. the screening of the entire depth of a three-dimensional tissue culture. Given the success of impedance measurements on cell monolayers, one would expect this development to continue with 3D cultures since the complex structure of in vivo tissues is mimicked more closely and, above all, since rapid and inexpensive techniques which are able to probe thick tissue samples are currently inexistent. Nevertheless, few studies have been carried out in this field. Here, the requirements of three-dimensional impedance sensors are discussed and challenged by the fabrication of a corresponding device, involving the development of so-called gel electrodes through a novel 2-step-soft-lithography process. Their specific design allows for the decrease of leak currents, a common problem when performing three-dimensional impedance measurements. The simultaneous measurement of multiple samples in parallel is an an essential condition when performing high throughput drug toxicity screening. Electrode switch systems are necessary which ultimately lead to setup complexity and signal noises. In this thesis, a method is introduced, enabling the simultaneous implementation of impedance measurements of multiple tissue samples with one electrode pair only. This is simply achieved by exploiting the frequency domain and finally contributed to reducing setup complexity

Strategies to Avert Ukraine's Emerging Power Crisis

Ongoing Russian attacks on Ukraine’s energy infrastructure are causing widespread blackouts. Without coordinated action, the situation is expected to worsen over the coming winter. While technical solutions are available to improve the supply situation, their rapid implementation requires the input of significant resources and effective coordination. To achieve this, we propose the creation of an ‘energy situation room’ to improve information sharing and the coordination of Ukraine’s energy resilience strategy, as well as mechanisms to empower local and private actors to invest in targeted, systemic solutions

Calmodulin Binding to the 3614–3643 Region of RyR1 Is Not Essential for Excitation–Contraction Coupling in Skeletal Myotubes

Calmodulin is a ubiquitous Ca2+ binding protein that modulates the in vitro activity of the skeletal muscle ryanodine receptor (RyR1). Residues 3614–3643 of RyR1 comprise the CaM binding domain and mutations within this region result in a loss of both high-affinity Ca2+-bound calmodulin (CaCaM) and Ca2+-free CaM (apoCaM) binding (L3624D) or only CaCaM binding (W3620A). To investigate the functional role of CaM binding to this region of RyR1 in intact skeletal muscle, we compared the ability of RyR1, L3624D, and W3620A to restore excitation–contraction (EC) coupling after expression in RyR1-deficient (dyspedic) myotubes. W3620A-expressing cells responded normally to 10 mM caffeine and 500 μM 4-chloro-m-cresol (4-cmc). Interestingly, L3624D-expressing cells displayed a bimodal response to caffeine, with a large proportion of cells (∼44%) showing a greatly attenuated response to caffeine. However, high and low caffeine-responsive L3624D-expressing myotubes exhibited Ca2+ transients of similar magnitude after activation by 4-cmc (500 μM) and electrical stimulation. Expression of either L3624D or W3620A in dyspedic myotubes restored both L-type Ca2+ currents (retrograde coupling) and voltage-gated SR Ca2+ release (orthograde coupling) to a similar degree as that observed for wild-type RyR1, although L-current density was somewhat larger and activated at more hyperpolarized potentials in W3620A-expressing myotubes. The results indicate that CaM binding to the 3614–3643 region of RyR1 is not essential for voltage sensor activation of RyR1

Electroweak Higgs as a pseudo-Goldstone boson of broken scale invariance

We point out that it is possible to associate the electroweak Higgs boson with the pseudo-Goldstone boson of broken scale invariance, thus resolving the hierarchy problem in a technically natural way. We illustrate this idea with two specific gauge models. Besides being consistent with all currently available experimental data, both models maintain the predictive power of the standard model, since the first model has only one additional parameter beyond the standard model, and the second has the same number of free parameters as the standard model.Comment: 11 pages, discussion added, the version to appear in Phys. Lett.

Improving Aircraft Maintenance Performance through Prescriptive Maintenance Strategies

In the past couple of years, predictive maintenance has arguably been the most discussed maintenance strategy in academia and industry. While it promises a significant operational easing and cost saving potential through the projection of system failures, it is characterized by a strong asset centricity; thus, it often only focuses on a system’s (projected) condition for issuing a maintenance task. Furthermore, the realized savings potential depends heavily on the performance of the underlying condition monitoring technologies. A recent study by (Haarman et al. 2018) among manufacturing companies from the Netherlands, Belgium, and Germany showed that many of these companies struggle in the identification of viable business case scenarios with predictive maintenance; mostly due to the limited maturity of the underlying condition monitoring technologies. Subsequently, this lack of business cases increases their hesitance to (further) invest in the development of the associated technologies, slowing the technological advancement unnecessarily. An integral part in the development of post-prognostics maintenance strategies is the identification of suitable systems to apply a prognostics-based maintenance strategy to and the determination of necessary minimum performance criteria of the underlying monitoring technology. However, the majority of research publications and industry efforts focusses on the development of condition-monitoring techniques itself and often oversimplifies this identification of business case scenarios and the subsequent integration of derived maintenance actions within the existing maintenance process environment. With these challenges in mind, we propose the next step in the evolution of post-prognostics maintenance strategies – the prescriptive maintenance approach. With this step, the scope of maintenance scheduling will be extended beyond the asset itself and incorporate the associated stakeholder’s objectives in the planning process, e.g. for the operator, a reduction in flight irregularities or, for the maintenance provider, a reduction in unjustified component removals (Wheeler et al. 2010). Thus, individual improvements (or possible drawbacks) – due to different maintenance strategies – can be attributed to the respective stakeholder. With this presentation, we will demonstrate the expected benefits for an automated tire condition monitoring system using our discrete-event simulation framework PreMaDe (Prescriptive Maintenance Developer). In particular, we are going to focus on the effects that different Prognostics and Health Management (PHM) technologies have on the operations of a short-/medium-haul aircraft fleet, the associated on-wing maintenance, and the spare parts inventory management. The presented results will provide a holistic view on the expected maintenance performance and not solely focus on monetary aspects – since real-life decision always require a trade-off between competing objectives or among multiple stakeholders. This will, subsequently, help maintenance practitioners to define suitable business case scenarios and determine necessary payments for stakeholders to be financially compensated for adversarial effects of such a prognostics-based maintenance strategy. Ultimately, this approach will enable the swift identification of systems that promise a significant optimization potential through the introduction of an adjusted maintenance strateg

Ariel - Volume 3 Number 6

Editors Richard J. Bonanno Robin A. Edwards Associate Editors Steven Ager Tom Williams Lay-out Editor Eugenia Miller Contributing Editors Paul Bialas Robert Breckenridge Lynne Porter David Jacoby Mike LeWitt Terry Burt Mark Pearlman Michael Leo Editors Emeritus Delvyn C. Case, Jr. Paul M. Fernhof

Ralph Kirsch

Emeritus Professor Ralph Kirsch was a distinguished, well-known and much admired medical personality in South Africa and internationally. His eminence is founded on a lifetime of contribution and achievement in the arena of internal medicine, liver research, medical education, administration and leadership. He served South African health sciences at the highest professional, organisational and institutional levels. A 1964 medical graduate of the University of Cape Town (UCT), he obtained his MD in 1968 for his studies on malnutrition, and the FCP (SA) in 1970. In 1972 and 1973 he was a Fogarty Post-Doctoral Research Fellow in the Division of Gastroenterology and Liver Diseases of the Albert Einstein College of Medicine in New York – this appointment cementing his lifelong interest in chronic and acute liver disease (refer to Terblanche and Saunders – obituary SAMJ, this issue). His scientific and research career spanned many topics. He published in such fields as the modelling and regulation of protein metabolism, ‘ligandin’ and the glutathione transferases, the role of fibrin(ogen)-derived products in disease, angiotensin-converting enzyme, viral hepatitis, hepatic iron and liver injury, portal hypertension and porphyria. His prolific research was documented in several hundred papers in international medical journals, and many chapters in books. He was awarded a DSc (Med) from UCT in 1993 for his work on metabolic and clinical aspects of liver disease and especially for his work on ligandin and fibrinogen metabolism

Developing prescriptive maintenance strategies in the aviation industry based on a discrete-event simulation framework for post-prognostics decision making

The aviation industry is facing an ever-increasing competition to lower its operating cost. Simultaneously, new factors, such as sustainability and customer experience, become more important to differentiate from competitors. As aircraft maintenance contributes about 20% to the overall cost of airline operations and can significantly influence other objectives of an airline as well, maintenance providers are required to constantly lower their cost share and contribute to a more reliable and sustainable aircraft operation. Subsequently, new condition-monitoring technologies have emerged that are expected to improve maintenance operations by reducing cost and increasing the aircraft’s availability. As many of these technologies are still in their technological infancy, it is necessary to determine the expected benefit for the airline operations with the given technological maturity and to develop suitable maintenance strategies that incorporate the newly gained insights. With this paper, a discrete-event simulation framework is developed that uses established parameters to describe a condition-monitoring technology’s performance and subsequently develops a suitable prescriptive maintenance strategy. Therefore, it enables the adjustment of the optimization goal for the developed strategy to incorporate performance features beyond the frequently used financial indicators. The developed capabilities will be demonstrated for the tire pressure measurement task of an Airbus A320