Cancer-Associated Fibroblasts Modify the Response of Prostate Cancer Cells to Androgen and Anti-Androgens in Three-Dimensional Spheroid Culture

Androgen receptor (AR) targeting remains the gold standard treatment for advanced prostate cancer (PCa); however, treatment resistance remains a major clinical problem. To study the therapeutic effects of clinically used anti-androgens we characterized herein a tissue-mimetic three-dimensional (3D) in vitro model whereby PCa cells were cultured alone or with PCa-associated fibroblasts (CAFs). Notably, the ratio of PCa cells to CAFs significantly increased in time in favor of the tumor cells within the spheroids strongly mimicking PCa in vivo. Despite this loss of CAFs, the stromal cells, which were not sensitive to androgen and even stimulated by the anti-androgens, significantly influenced the sensitivity of PCa cells to androgen and to the anti-androgens bicalutamide and enzalutamide. In particular, DuCaP cells lost sensitivity to enzalutamide when co-cultured with CAFs. In LAPC4/CAF and LNCaP/CAF co-culture spheroids the impact of the CAFs was less pronounced. In addition, 3D spheroids exhibited a significant increase in E-cadherin and substantial expression of vimentin in co-culture spheroids, whereas AR levels remained unchanged or even decreased. In LNCaP/CAF spheroids we further found increased Akt signaling that could be inhibited by the phosphatidyl-inositol 3 kinase (PI3K) inhibitor LY294002, thereby overcoming the anti-androgen resistance of the spheroids. Our data show that CAFs influence drug response of PCa cells with varying impact and further suggest this spheroid model is a valuable in vitro drug testing tool.     

Applicability of ToF-SIMS for monitoring compositional changes in bone in a long-term animal model

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is a well-established technique in material sciences but has not yet been widely explored for implementation in life sciences. Here, we demonstrate the applicability and advantages of ToF-SIMS analysis for the study of minerals and biomolecules in osseous tissue. The locally resolved analysis of fragment ions deriving from the sample surface enables imaging and differentiation of bone tissue and facilitates histology on non-stained cross sections. In a rat model, bilateral ovariectomy combined with either a multi-deficiency diet or steroid treatment was carried out to create osteoporotic conditions. We focused our study on the Ca content of the mineralized tissue and monitored its decline. Calcium mass images of cross sections show the progressive degenerative changes in the bone. We observed a decreased Ca concentration in the edge region of the trabeculae and a decline in the Ca/P ratio. Additionally, we focused on the non-mineralized matrix and identified fragment ions that are characteristic for the collagen matrix. We observed trabeculae with wide ranges of non-mineralized collagen for the diet group owing to an impaired mineralization process. Here, the advantage of coeval monitoring of collagen and minerals indicated an osteomalacic model rather than an osteoporotic one.     

Change detection for new food labels

The amount of information on food packages (e.g., environment- and health-related) has increased in Europe and other regions in recent years. It is therefore important to understand to what extent this information attracts the attention of and is processed by consumers, considering characteristics of the product information as well as person-specific variables such as age. In two studies we tested whether the change detection task is a useful paradigm for studying how individuals attend to and process recently introduced formats and contents of food labels. In the change detection tasks presented here, 133 participants were shown two photographs of a food package that differed in one label and were asked to identify as quickly as possible which information was constantly changing. We found systematic differences in change detection times for different types of product label content and format, representing the amount of attention habitually paid to the specific labels. Interestingly, the detection times for each label did not correlate with participants’ self-report measures of how much attention they give to this specific label during typical grocery shopping. In both studies we also found a positive correlation between age and time needed to detect change in label format and content, but only for labels that were introduced on packages in recent years (such as the ‘organic’ label) not on longer established information (such as the ‘best-before’ date).     

Advantageous and detrimental effects of air sparging in membrane filtration: Bubble movement, exerted shear and particle classification

In various membrane applications air scour is applied to minimise fouling and to remove cake layers. Optimisation of module design and operating conditions (e.g., geometry and aeration intensity) requires knowledge of the most suited hydrodynamic conditions for the filtration task. However, many fundamentals of this multiphase flow in membrane modules are still unknown and difficult to access experimentally. Using experimental and numerical investigations it was shown that air sparging can have advantageous but also detrimental effects: depending on membrane plate spacing, wall shear can decrease with bubble size. Additionally, particle classification or segregation which increases the cake’s hydraulic resistance must be taken into account. Based on such findings, it will be possible to derive optimum bubble sizes, membrane spacing, aeration intensities and start-up strategies.     

High performance computing of the Darmstadt stratified burner by means of large eddy simulation and a joint ATF-FGM approach

Current trend in design and operation of industrial gas turbines or internal combustion engines implies using the lean-fuel and stratified conditions aiming at the reduction of the harmful emissions and efficiency improvement. This has led to an increasing use of computational methodology, which allows detailed insight into combustion physics and processes controlling the emission formation. In the present work, the Darmstadt stratified burner is investigated by means of Large Eddy Simulation, implemented into the in-house, finite-volume-based numerical code FASTEST. The code solves the incompressible, variable-density Navier–Stokes equations coupled with the species transport equations. It is parallelized via domain decomposition technique using message passing interface (MPI). The complex chemical mechanisms are described by tabulated detailed chemistry utilizing the Flamelet Generated Manifolds (FGM) approach combined with the Artificially Thickened Flame model (ATF). The results obtained are comparatively assessed along with the complementary measurements. In-depth analysis of the flow field is conducted based on numerical simulations. Further studies have been carried out with respect to grid resolution and scalability.     

Designing beyond habit: opening space for improved recycling and food waste behaviors through processes of persuasion, social influence and aversive affect

Disposing of waste is a common part of our everyday life, yet we do not pay much attention to the process. For many it can be considered a habitual, unconscious process. Disposed goods and materials, however, do not simply disappear. This issue has been approached widely and in a variety of disciplines and arenas, including HCI. We add to this growing literature by considering recycling and food waste as habitual behavior and investigate the potential to design toward conscious reflection on waste disposal intentions and behaviors through social influence and aversive affect. That is, we aim to design beyond habitual performance of waste disposal behavior in two phases of (1) awareness raising and (2) supporting subsequent intentions for behavior change. We present results of a rich qualitative and explorative evaluation of the BinCam system, a two-part persuasive technology, which replaces an everyday waste bin with one enabled to capture and share images of disposed of waste on an online social network. Findings suggest that awareness raising leads to self-reflection and re-evaluation. The re-evaluation causes feelings of shame, where individuals perceive a disparity between their attitudes and their behaviors. Results also highlight the importance of a person’s perceived behavioral control (e.g., a person’s recycling competences or facilities) for enabling behavioral change and confirm the significance of providing “signal triggers” to individuals to remind them about performing the desirable behavior in its required context. Furthermore, as the present research extends its focus beyond the lone individual, it contributes to our understanding and study of social influence processes and group movements.     

Thermal degradation of sucralose and its potential in generating chloropropanols in the presence of glycerol

Sucralose, a polychlorinated synthetic high-intensity sweetener is being increasingly used in relatively large amounts in baked products under high temperature environments. This necessitates understanding its thermal decomposition and studying the consequences of hydrogen chloride release from sucralose and its ability to chlorinate various food related ingredients such as glycerol to generate chloropropanols a potentially toxic class of compounds. Studies conducted on the thermal degradation of sucralose under dry heating conditions have indicated that the glycosidic cleavage occurs through the formation of a galactopyranosyl cation contrary to sucrose where fructofuranosyl cation dictates the major breakdown products. Consequently the major product detected was levoglucosenone and its precursor. Subsequent degradation of the two monosaccharide derivatives causes dehydrochlorination and dehydration reactions to produce furan-related products. In addition, pyrolysis of sucralose in the presence of glycerol generated significant amounts of 3-monochloropropanediol and 1,2- and 1,3-dichloropropanols based on the relative intensities of their chromatographic peaks which amounted to 15% of the total chromatographic peak area.