Test of the local effect model using clinical data: tumour control probability for lung tumours after treatment with carbon ion beams

The treatment planning approach used within the heavy ion tumour therapy project at GSI Darmstadt includes a biological optimisation, which is based on a biophysical model, the Local Effect Model (LEM). Here we show that the predictions of the LEM are in good agreement with clinical data obtained at the HIMAC in Chiba for the treatment of non-small-cell lung cancer, and the steep dose response for carbon ions is reproduced correctly. This steeper increase corresponds to an increasing RBE with increasing dose, which apparently is in contradiction to the systematics observed in general for in vitro measurements. A possible explanation of this discrepancy is based on the interindividual variation of photon sensitivity.     

Planung und Ausführung des Ersatzneubaus einer U‐Bahn‐Brücke in Berlin unter hohem Zeitdruck

Design and construction of a new bridge for the Berlin underground to replace an old structure under high time pressure. This paper is about the design and construction of a new bridge for the underground in Berlin. A new structure was necessary due to insufficient stability and serviceability of the old one. The project had to be carried out under high time pressure to avoid a decommissioning of the underground traffic. As a result of this the planning and execution phases were significantly reduced. Besides, the client provided the construction firm with the structural steel to be used for the superstructure, a potential for conflict that would need to be tackled. The project will be described from the design point of view.     

Furan and Methylfurans in Foods: An Update on Occurrence,Mitigation, and Risk Assessment

The acceptance of many foods is related to traditional cooking practices, which create taste and texture and are important to digestibility, preservation, and the reduction of foodborne illnesses. A wide range of compounds are formed during the cooking of foods, a number of these have been shown to lead to adverse effects in classical toxicological models and are known as food processing contaminants (FPC). It is essential that the presence and effects of such compounds alone and in combination within the diet are understood such that proportionate risk management measures can be developed, while taking a holistic view across the whole value chain. Furan and alkylfurans (principally 2‐ and 3‐methylfuran) are highly volatile FPC, which are formed in a wide range of foods at low amounts. The focus of research to‐date has been on those foods, which have been identified to be most consequential in terms of being sources of exposure, namely jarred and canned foods for infants and young children (meals and drinks) and coffee (roast and ground, soluble). This report presents (i) new industry data on the occurrence of furan and methylfurans in selected food categories following previous coffee studies, (ii) the most salient parameters that impact furan formation, and (iii) aspects of importance for the risk assessment.     

Glycolaldehyde‐modified β‐lactoglobulin AGEs are unable to stimulate inflammatory signaling pathways in RAGE‐expressing human cell lines

Scope: Advanced glycation endproducts (AGEs) are suspected to stimulate inflammatory signaling pathways in target tissues via activation of the receptor for AGEs. Endotoxins are generally recognized as potential contamination of AGE preparations and stimulate biological actions that are very similar as or identical to those induced by AGEs. Methods and results: In our study, we used glycolaldehyde‐modified β‐lactoglobulin preparations as model AGEs and employed two methods to remove endotoxin using either affinity columns or extraction with Triton X‐114 (TX‐114). Affinity column‐purified AGEs retained their ability to stimulate inflammatory signaling as measured by mRNA expression of inflammatory cytokines in the human lung epithelial cell line Beas2b. However, glycolaldehyde‐modified AGEs purified by extraction with TX‐114 did not show any stimulation of mRNA expression of inflammatory cytokines. The presence of a cell stimulating endotoxin‐like activity was demonstrated in the detergent phase after extraction with TX‐114, thus indicating that not AGEs but a lipophilic contamination was responsible for the stimulation of inflammatory signaling. Conclusion: Our results demonstrate that glycolaldehyde‐modified AGEs are unable to induce inflammatory signaling in receptor for AGE‐expressing cells. The observed cell‐activating activity can be ascribed to an endotoxin‐like lipophilic contamination present in AGE preparations and affinity column purification was insufficient to remove this contamination.     

Assessment of Upstream Human Intervention Coupled with Climate Change Impact for a Transboundary River Flow Regime: Nile River Basin

Water Resources Management - The aim of this article is to determine how human interventions in upstream countries coupled with drought events are affecting the flow regime of downstream countries...     

Functional work breaks in a high-demanding work environment: an experimental field study

Work breaks are known to have positive effects on employees’ health, performance and safety. Using a sample of twelve employees working in a stressful and cognitively demanding working environment, this experimental field study examined how different types of work breaks (boxing, deep relaxation and usual breaks) affect participants’ mood, cognitive performance and neurophysiological state compared to a control condition without any break. In a repeated measures experimental design, cognitive performance was assessed using an auditory oddball test and a Movement Detection Test. Brain cortical activity was recorded using electroencephalography. Individual’s mood was analysed using a profile of mood state. Although neurophysiological data showed improved relaxation of cortical state after boxing (vs. ‘no break’ and ‘deep relaxation’), neither performance nor mood assessment showed similar results. It remains questionable whether there is a universal work break type that has beneficial effects for all individuals.

Practitioner Summary: Research on work breaks and their positive effects on employees’ health and performance often disregards break activities. This experimental field study in a stressful working environment investigated the effect of different work break activities. A universal work break type that is beneficial for this workplace could not be identified.     

Transformation of the Nonprocessive Fast Skeletal Myosin II into a Processive Motor

Myosin family motors play diverse cellular roles. Precise insights into how the light chains contribute to the functional variabilities among myosin motors, however, remain unresolved. Here, it is demonstrated that the fast skeletal muscle myosin II isoform myosin heavy chain (MHC‐IID) can be transformed into a processive motor, by simply replacing the native regulatory light chain MLC2f with the regulatory light chain variant MLC2v from the slow muscle myosin II. Single molecule kinetic analyses and optical trapping measurements of the hybrid motor reveal marked changes such as increased association rate of myosin toward adenosine triphosphate (ATP) and actin by more than twofold. The direct consequence of high adenosine diphosphate (ADP) affinity and increased actin rebinding is the altered overall actomyosin association time during the cross‐bridge cycle. The data indicate that the MLC2v influences the duty ratio in the hybrid motor, suggestive of promoting interhead communication and enabling processive movement. This finding establishes that the regulatory light chain fine‐tunes the motor's mechanical output that may have important implications under physiological conditions. Furthermore, the success of this approach paves the way to engineer motors from a known motor protein element to assemble highly specialized biohybrid machines for potential applications in nano‐biomedicine and engineering.