Towards understanding the mechanism of action of the multidrug resistance-linked half-ABC transporter ABCG2: a molecular modeling study

The ATP-binding cassette protein ABCG2 is a member of a broad family of ABC transporters with potential clinical importance as a mediator of multidrug resistance. We carried out a homology and knowledge-based, and mutationally improved molecular modeling study to establish a much needed structural framework for the protein, which could serve as guidance for further genetic, biochemical, and structural analyses. Based on homology with known structures of both full-length and nucleotide-binding domains (NBD) of ABC transporters and structural knowledge of integral membrane proteins, an initial model of ABCG2 was established. Subsequent refinement to conform to the lipophilic index distributions in the transmembrane domain (TMD) and to the results of site-directed mutagenesis experiments led to an improved model. The complete ABCG2 model consists of two identical subunits facing each other in a closed conformation. The dimeric interface in the nucleotide-binding domain (NBD) involves a characteristic nucleotide sandwich and the interface in the TMD consists of the TM helices 1–3 of one subunit and the helices 5 and 6 of the other. The interface between the NBD and the TMD is bridged by the conserved structural motif between TM2 and TM3, the intracellular domain 1 (ICD1), and the terminal β-strand (S6) of the central β-sheet in the NBD. The apparent flexibility of the ICD1 may play a role in transmitting conformational changes from the NBD to the TMD or from the TMD to the NBD.     

Design for Timing Predictability

A large part of safety-critical embedded systems has to satisfy hard real-time constraints. These need sound methods and tools to derive run-time guarantees that are not only reliable but also precise. The achievable precision highly depends on characteristics of the target architecture, the implementation methods and system layers of the software. Trends in hardware and software design run contrary to predictability. This article describes threats to timing predictability of systems, and proposes design principles that support timing predictability. The ultimate goal is to design performant systems with sharp upper and lower bounds on execution times.     

Nanoporous gold bumps for low temperature bonding

Nanoporous gold bumps have been deposited on silicon wafers by electroplating a silver–gold alloy followed by etching the silver. An open-porous cellular structure of gold at meso-scale is left on top of the bumps. For flip chip bonding we found low temperature and low force bonding conditions. The porous interconnects have very promising properties, like compressibility and reduced stiffness, which should result in higher bond yield and extended reliability.     

Real-time worst-case temperature analysis with temperature-dependent parameters

With the evolution of today’s semiconductor technology, chip temperature increases rapidly mainly due to the growth in power density. Therefore, for modern embedded real-time systems it is crucial to estimate maximal temperatures early in the design in order to avoid burnout and to guarantee that the system can meet its real-time constraints. This paper provides answers to a fundamental question: What is the worst-case peak temperature of a real-time embedded system under all feasible scenarios of task arrivals? A novel thermal-aware analytic framework is proposed that combines a general event/resource model based on network and real-time calculus with system thermal equations. This analysis framework has the capability to handle a broad range of uncertainties in terms of task execution times, task invocation periods, jitter in task arrivals, and resource availability. The considered model takes both dynamic and leakage power as well as thermal dependent conductivity into consideration. Thorough simulation experiments validate the theoretical results.     

The effect of temperature and radiation on flavonol aglycones and flavonol glycosides of kale (Brassica oleracea var. sabellica)

The winter crop kale has a complex profile of different glycosylated and acylated flavonol glycosides which may be affected by global warming. To the best of our knowledge, compound–climate relationships for flavonol aglycones and flavonol glycosides were established for the first time. The investigated 10 major flavonol glycosides responded structure-dependent in the investigated temperature range between 0 and 12 °C and the photosynthetic active radiation range between 4 and 20 mol m⁻² d⁻¹, e.g. the decrease in temperature led to an increase in sinapic acid monoacylated and diacylated quercetin glycosides, while the sinapic acid monoacylated kaempferol glycosides showed a maximum at 4.5 °C. Furthermore, the hydroxycinnamic acid residues and the different number of glucose moieties in the 7-O position affected the response of kaempferol triglucosides. Consequently, global warming would result in lower concentrations of antioxidant-relevant quercetin glycosides in winter crops, suggesting a production at e.g. higher altitudes due to lower temperature.     

Paper‐Derived Bioactive Glass Tape

Porous bioactive glass (BaG) structures were manufactured applying novel preceramic paper process. Preceramic papers were produced for aqueous suspensions loaded with different contents of pulp fiber and BaG filler. Pressure loading was applied in order to increase the packing density in the paper sheets. The paper sheets were sintered at 630 °C for 1 h. The porous glass–ceramic specimens were characterized for density, porosity, composition, microstructure, and mechanical properties. A pronounced volumetric shrinkage was observed, but no surface flaws or inhomogeneous areas were detected. The mechanical strength using the ball on three balls test and elastic modulus of sintered specimens vary between 21 and 33 MPa and 0.30–0.85 GPa, respectively.     

Zinc Status Impacts the Epidermal Growth Factor Receptor and Downstream Protein Expression in A549 Cells

Zinc has been suggested to play a role in carcinogenesis and tumor progression. Serum zinc levels of lung cancer patients are for example lower than in healthy individuals. The activation and expression of the epidermal growth factor receptor (EGFR), which plays a role in tumor biology, are presumably influenced by zinc. EGFR activation influences cell adhesion and immune escape. This study provides insights into the impacts of zinc on the EGFR activation and expression of downstream proteins such as E-cadherin and PD-L1 in the alveolar carcinoma cell line A549. To model chronic changes in zinc homeostasis, A549 cells were cultured in media with different zinc contents. EGFR surface expression of unstimulated and stimulated A549 cells was determined by flow cytometry. EGFR phosphorylation as well as the protein expression of E-cadherin and PD-L1 were analyzed by Western blot. In our hands, chronic zinc deficiency led to increased EGFR surface expression, decreased E-cadherin protein expression and increased PD-L1 protein expression. Zinc supplementation decreased EGFR surface expression and PD-L1 protein expression. In summary, zinc-deficient A549 cells may display a more malignant phenotype. Thus, future clinical research should further focus on the possible benefits of restoring disturbed zinc homeostasis, especially in lung cancer patients.     

A preamble-based approach for providing quality of service support in wireless sensor networks

Medium Access Control (MAC) protocols for Wireless Sensor Networks (WSN) are usually designed as random access protocols that apply different kinds of backoff strategies since Time Division Multiple Access (TDMA) based protocols with admission control are very complex and require additional mechanisms for synchronization. Without such mechanisms, fair or priority based medium access with Quality of Service (QoS) guarantees can hardly be achieved by existing protocols. Therefore, we developed a random access protocol which uses a new preamble-based medium access strategy that enables collision-free priority based access without the need of synchronization. In this paper we introduce different QoS strategies and their use cases. All strategies can be easily integrated in our protocol to meet the requirements of different target applications. Furthermore, we compare the performance of the strategies with a typical carrier-sense based protocol.