The Fight against Cancer by Microgravity: The Multicellular Spheroid as a Metastasis Model

Cancer is a disease exhibiting uncontrollable cell growth and spreading to other parts of the organism. It is a heavy, worldwide burden for mankind with high morbidity and mortality. Therefore, groundbreaking research and innovations are necessary. Research in space under microgravity (µg) conditions is a novel approach with the potential to fight cancer and develop future cancer therapies. Space travel is accompanied by adverse effects on our health, and there is a need to counteract these health problems. On the cellular level, studies have shown that real (r-) and simulated (s-) µg impact survival, apoptosis, proliferation, migration, and adhesion as well as the cytoskeleton, the extracellular matrix, focal adhesion, and growth factors in cancer cells. Moreover, the µg-environment induces in vitro 3D tumor models (multicellular spheroids and organoids) with a high potential for preclinical drug targeting, cancer drug development, and studying the processes of cancer progression and metastasis on a molecular level. This review focuses on the effects of r- and s-µg on different types of cells deriving from thyroid, breast, lung, skin, and prostate cancer, as well as tumors of the gastrointestinal tract. In addition, we summarize the current knowledge of the impact of µg on cancerous stem cells. The information demonstrates that µg has become an important new technology for increasing current knowledge of cancer biology.     

A Petri net based design engine for manufacturing systems

Support for the efficient design and operation of complex manufacturing systems requires an integrated modelling, analysis, and control methodology as well as its implementation in a software tool. In this paper the Petri net based design engine TimeNET is presented for this task. Petri nets are able to capture the characteristic features of manufacturing systems in a concise form. A subclass of coloured Petri nets is used, which has been developed especially for the application area of manufacturing. Structure and work plans are modelled separately. Stochastic as well as deterministic and more general distributions are adopted for the firing times of transitions. Fundamental questions about system properties can be answered using qualitative analysis. For an efficient performance and dependability prediction, different evaluation techniques are proposed: direct numerical analysis, approximate analysis, and simulation. Finally, the model can be used to evaluate different control strategies and to control the manufacturing system directly. There is no need to change the modelling methodology, thus avoiding additional effort, for example for model conversion. In the paper this necessary steps are described using an application example.     

3D printing of bone substitute implants using calcium phosphate and bioactive glasses

Customized implants for bone replacement are a great help for a surgeon to remodel maxillofacial or craniofacial defects in an esthetical way, and to significantly reduce operation times. The hypothesis of this study was that a composite of β-tricalcium phosphate (β-TCP) and a bioactive glass similar to the 45S5 Henchglass^® is suitable to manufacture customized implants via 3D-printing process. The composite was chosen because of the bioresorption properties of the β-TCP, its capability to react as bone cement, and because of the adjustability of the bioactive glass from inert to bioresorbable. Customized implants were manufactured using the 3D-printing technique. The four point bending strength of the printed specimens was 14.9 MPa after sintering. XRD analysis revealed the occurrence of two other phases, CaNaPO₄ and CaSiO₃, both biocompatible and with the potential of biodegradation. We conclude that it is possible to print tailored bone substitute implants using a bioactive TCP/glass composite. The glass is not involved as reactive substance in the printing process. This offers the opportunity to alter the glass composition and therefore to vary the composition of the implant.     

Landscape visualizations: Applications and requirements of 3D visualization software for environmental planning

This paper presents the findings of an investigation into the role and use of landscape visualization software for landscape and environmental planning in Germany. It examines the challenges and requirements of 3D visualization technology and its potential for application in landscape and environmental planning. Relevant literature and comparable surveys are reviewed in order to determine the current state of affairs, and the general and international relevance of the results is assessed.In 2000, a survey of user requirements for 3D landscape simulation software, including the demand for specific features, was conducted within the framework of a feasibility study for a visualization tool. As part of the German-wide survey, comprehensive questionnaires were sent to 1044 respondents from a pool of private landscape planning consultancies, freelance landscape architects, and public planning and environmental authorities.The survey showed that 3D landscape visualization has a positive image in Germany, both among user and non-user groups of visualization tools. Twenty-eight percent of private consultancies and freelance landscape architects, as well as 7% of public authorities, stated that they already used 3D simulation software. Those respondents who did not use 3D simulation software cited insufficient computer equipment, lack of technical expertise of planners and cost-related aspects as reasons for not yet having adopted the technology. “Ease of learning” and “interoperability” are deemed to be the most important features of 3D simulation software, whereas factors such as “high interactivity”, “representability of ecological processes” and “photo-realism” are, surprisingly, regarded as much less important.Users of 3D visualization software are particularly concerned by insufficient representation of plants and habitats in simulations. Looking to the future, the vast majority of respondents (91%) expect increased benefits for landscape planning from 3D visualization software, are convinced of the advantages of the technology, and are eager to integrate 3D landscape visualizations into their working practices.     

Synthesis and conductivities of (μ-cyano)phthalocyaninatometal compounds

A review of the synthesis and characterization of a new type of stacked, bridged macrocyclic metal complexes, the (μ-cyano)phthalocyaninatometal compounds [PcMCN]_n (2) is given. By using the routes described in Fig. 3 the polymers were synthesized with M = Co³⁺, Fe²⁺, Fe³⁺, Mn³⁺ and Cr³⁺ as the central metal ion. The compounds were characterized by IR, far-IR, UV, thermal and elemental analysis, and partly by ¹H NMR and FD (field desorption) mass spectroscopy.[PcCoCN] (2a) and [PcFeCN]_n (2b) exhibit d.c. room temperature conductivities around 10^?2 S/cm without doping, thereby showing conductivities which are in the same range as the iodine-doped phthalocyaninatosiloxanes [PcSiO]_n.     

Polyplexes of polyethylenimine and per-N-methylated polyethylenimine-cytotoxicity and transfection efficiency

For non-viral gene delivery, the carriers for DNA transfer into cells must be vastly improved. The branched cationic polymer polyethylenimine has been described as an efficient gene carrier. However, polyethylenimine was demonstrated to mediate substantial cytotoxicity. Therefore, this study is aimed at investigating per-N-methylated polyethylenimine, which is thought to have a much lower cytotoxicity due to its lower charge density. Results from a gel retardation assay and laser light scattering indicated that per-N-methylated polyethylenimine condenses DNA into small and compact nanoparticles with a mean diameter <150 nm. Furthermore, polyplexes of polyethylenimine and per-N-methylated polyethylenimine with DNA had a positive zeta potential and the polymers protected DNA from nuclease-mediated digestion. The transfection efficiency of polyethylenimine and per-N-methylated polyethylenimine was tested in CHO-K1 cells. Using green fluorescent protein as reporter gene and flow cytometry analysis, we demonstrated that per-N-methylated polyethylenimine has a lower cytotoxicity, but also a significantly lower transfection efficiency. Using propidium iodide staining, we could additionally distinguish between viable and dead cells. At NP > or = 12, per-N-methylated polyethylenimine showed a much higher cell viability and the ratio of viable and transfected cells to dead and transfected cells was about 1.5 to 1.7 fold higher than for polyethylenimine. The results of cell viability from flow cytometry analysis were confirmed by the MTS assay. Using luciferase reporter gene for transfection experiments, the gene expression of per-N-methylated polyethylenimine was lower at NP 6, 12 and 18 as compared to polyethylenimine, but at NP 24 it yielded similar levels.