Development of a Continuous Segmented Flow Tubular Reactor and the “Scale‐out” Concept – In Search of Perfect Powders

The synthesis of powders with controlled shape and narrow particle size distributions is still a major challenge for many industries. A continuous Segmented Flow Tubular Reactor (SFTR) has been developed to overcome homogeneity and scale‐up problems encountered when using batch reactors. Supersaturation is created by mixing the co‐reactants in a micromixer inducing precipitation; the suspension is then segmented into identical micro‐volumes by a non‐miscible fluid and sent through a tube. These micro‐volumes are more homogeneous when compared to large batch reactors leading to narrower size distributions, better particle morphology, polymorph selectivity and stoichiometry. All these features have been demonstrated on single tube SFTR for different chemical systems. To increase productivity for commercial application the SFTR is being “scaled‐out” by multiplying the number of tubes running in parallel instead of scaling‐up by increasing their size. The versatility of the multi‐tube unit will allow changes in type of precipitate with a minimum of new investment as new chemistry can be researched, developed and optimised in a single tube SFTR and then transferred to the multi‐tube unit for powder production.     

Peak-to-average power reduction in space division multiplexing based OFDM systems through spatial shifting

A new method to reduce the peak-to-average power ratio (PAPR) in space division multiplexing systems applying orthogonal frequency division multiplexing is proposed. The method applies spatial shifting to partial transmit sequences to achieve a decreased PAPR on all transmit branches.     

Severe pulmonary hypertension reversed by antibiotics in a patient with Whipple's disease

The case is described of a 58 year old man with systemic Whipple's disease with pericardial and pleural effusions and severe pulmonary hypertension. After three months of antibiotic treatment there was a complete resolution, not only of the symptoms known to be associated with Whipple's disease (diarrhoea, arthralgia, pericardial and pleural effusions), but also of pulmonary hypertension.     

In-Situ and Real-Time Investigation of Columnar-to-Equiaxed Transition in Metallic Alloy

In this article, we present a review of observations during Al-3.5 wt pct Ni alloy solidi.cation experiments performed at the European Synchrotron Radiation Facility (ESRF) in Grenoble. These experiments provide direct access to dynamical phenomena during columnar growth (initial transient and breakdown of a planar solid-liquid interface), and for the first time to the transition from columnar-to-equiaxed microstructure (nucleation ahead of a columnar front and blocking of a columnar front by an equiaxed microstructure) and fully equiaxed growth (propagation of an effective front). Based on these experimental observations, critical parameters such as columnar growth velocity variation during the transition or equiaxed-grain diameter are measured and discussed. This article is based on a presentation made in the symposium entitled “Solidi.cation Modeling and Microstructure Formation: In Honor of Prof. John Hunt,” which occurred March 13–15, 2006, during the TMS Spring Meeting in San Antonio, Texas, under the auspices of the TMS Materials Processing and Manufacturing Division, Solidification Committee.     

3D Micro-PIXE at atmospheric pressure: A new tool for the investigation of art and archaeological objects

The paper describes a novel experiment characterized by the development of a confocal geometry in an external Micro-PIXE set-up. The position of X-ray optics in front of the X-ray detector and its proper alignment with respect to the proton micro-beam focus provided the possibility of carrying out 3D Micro-PIXE analysis. As a first application, depth intensity profiles of the major elements that compose the patina layer of a quaternary bronze alloy were measured. A simulation approach of the 3D Micro-PIXE data deduced elemental concentration profiles in rather good agreement with corresponding results obtained by electron probe micro-analysis from a cross-sectioned patina sample. With its non-destructive and depth-resolving properties, as well as its feasibility in atmospheric pressure, 3D Micro-PIXE seems especially suited for investigations in the field of cultural heritage.     

Does Physiological Blood Glucose Control Require an Adaptive Control Strategy?

To test the hypothesis that only an adaptive algorithm would guarantee optimal feedback control of glycemia in insulin-dependent diabetes, fasting chronically diabetic dogs at rest were subjected to short-term artificial beta cell treatment. Insulin was applied intravenously and an oral glucose load was given during the experiment. Employing the same dosing algorithm, three different control strategies were employed in a random order on different days: adaptive control (minimum variance controller, Test A), fixed command control using on-line parameter estimates (Test B), and fixed command control using off-line individually optimized dosage constants (Test C). Comparison was made to nondiabetic control animals. The glycemic profiles were entirely normal in Test A and C, but were distinctly elevated in Test B. The peripheral hyperinsulinaemia could, however, not be avoided by adaptive control. It is concluded that the restoration of physiological blood glucose control in insulin-dependent diabetes requires dosage parameters which are either continually adapted to the actual situation (adaptive control) or are optimized to meet the individual's needs. In the latter case, fixed command control may be employed. Peripheral hyperinsulinaemia cannot be avoided as long as insulin is administered by a posthepatic route.     

Synthesis and Pharmacological In Vitro Investigations of Novel Shikonin Derivatives with a Special Focus on Cyclopropane Bearing Derivatives

Melanoma is the deadliest form of skin cancer and accounts for about three quarters of all skin cancer deaths. Especially at an advanced stage, its treatment is challenging, and survival rates are very low. In previous studies, we showed that the constituents of the roots of Onosma paniculata as well as a synthetic derivative of the most active constituent showed promising results in metastatic melanoma cell lines. In the current study, we address the question whether we can generate further derivatives with optimized activity by synthesis. Therefore, we prepared 31, mainly novel shikonin derivatives and screened them in different melanoma cell lines (WM9, WM164, and MUG-Mel2 cells) using the XTT viability assay. We identified (R)-1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl 2-cyclopropyl-2-oxoacetate as a novel derivative with even higher activity. Furthermore, pharmacological investigations including the ApoToxGlo^TM Triplex assay, LDH assay, and cell cycle measurements revealed that this compound induced apoptosis and reduced cells in the G1 phase accompanied by an increase of cells in the G2/M phase. Moreover, it showed hardly any effects on the cell membrane integrity. However, it also exhibited cytotoxicity against non-tumorigenic cells. Nevertheless, in summary, we could show that shikonin derivatives might be promising drug leads in the treatment of melanoma.     

Coaxial Alginate Hydrogels: From Self-Assembled 3D Cellular Constructs to Long-Term Storage

Alginate as a versatile naturally occurring biomaterial has found widespread use in the biomedical field due to its unique features such as biocompatibility and biodegradability. The ability of its semipermeable hydrogels to provide a favourable microenvironment for clinically relevant cells made alginate encapsulation a leading technology for immunoisolation, 3D culture, cryopreservation as well as cell and drug delivery. The aim of this work is the evaluation of structural properties and swelling behaviour of the core-shell capsules for the encapsulation of multipotent stromal cells (MSCs), their 3D culture and cryopreservation using slow freezing. The cells were encapsulated in core-shell capsules using coaxial electrospraying, cultured for 35 days and cryopreserved. Cell viability, metabolic activity and cell–cell interactions were analysed. Cryopreservation of MSCs-laden core-shell capsules was performed according to parameters pre-selected on cell-free capsules. The results suggest that core-shell capsules produced from the low viscosity high-G alginate are superior to high-M ones in terms of stability during in vitro culture, as well as to solid beads in terms of promoting formation of viable self-assembled cellular structures and maintenance of MSCs functionality on a long-term basis. The application of 0.3 M sucrose demonstrated a beneficial effect on the integrity of capsules and viability of formed 3D cell assemblies, as compared to 10% dimethyl sulfoxide (DMSO) alone. The proposed workflow from the preparation of core-shell capsules with self-assembled cellular structures to the cryopreservation appears to be a promising strategy for their off-the-shelf availability.