Bone growth and bone development in the presence of implants or after induced leg-lengthening studied using the Oxford Scanning Proton Microprobe

To respond to varying environmental demands the bone tissue in the body is under continual reconstruction throughout life. It is known that metallic elements are important for maintaining normal bone structure, but their roles are not well understood. More information about the effects of metal excess or deficiency is needed to help in the development of metallic bone implants and to improve the treatment of bone fractures and defects. The Oxford Scanning Proton Microprobe (SPM) is being applied in two studies involving metal ions in bone: (1) bone regrowth and bonding to titanium bone implants may be influenced by diffusion of Ti ions into the bone. We are using microPIXE to determine the metal ion content of bone developing in contact with implants of pure Nb, Ti and Ti alloys. (2) Bone lengthening as a surgical procedure is induced by fracturing the bone and allowing it to heal with a small gap between the fractured ends created by the use of external fixators. The gap can be slowly increased during the healing process to stimulate the production of new bone. The enzymes and other constituents of the developing bone need certain metals for their function. Using experimental animals we have studied the concentrations of the metals and whether a deficiency of trace metals limits the optimum rate of bone lengthening.     

DANGERS OF LAB-PLANT SCALEUP FOR FILTERS INVOLVING SOLIDLIQUID SYSTEMS

Many laboratory procedures have been used for predicting the size of clarifiers, thickeners, filters, and centrifuges or choosing the optimum quantity of filter-aid and flocculants. Scaleup predictions are frequently based on experiments involving small pressure and vacuum filters, compression-permeability cells, and sedimentation rates. Among major problems related to the accuracy of scaleup are: (1) unrepresentative sampling, (2) aging of suspensions with accompanying changes in properties of cakes and sediments, (3) effect of sedimentation not included in theoretical equations, (4) wall effects in small diameter filters and cells, and (5) misapplication of theory to experiment.     

Method for analysis and dynamism of factory structure in automotive manufacturing

A turbulent environment characterized by unsteady economic cycles, customized products, a growing bandwidth of products, an exploding number of variants and shorter product life cycles force manufacturers to permanent adaptation of their factories. Flexible and changeable structures will be required to enable factories dealing with the technological challenges and economic pressure of the future competitively. In order to achieve changeability objectives in manufacturing, a detailed analysis of existing structures and its representative attributes is essential. It is the basis for systematic structure planning of factories. In this paper a method for analyzing the capacitive and technological structure of a factory embedded in a network of manufacturing and its network of suppliers is presented. The synchronization of product and production development under the influence of change is intended. Therefore, the structural views of product and production are specifically in focus of the method. Based on the results of the analysis models an approach of a tool for giving product and production structure dynamism is suggested to investigate the effects and dependencies of change drivers in manufacturing.     

A strategy for allowing meaningful and comparable scores in approximate matching

Approximate data matching aims at assessing whether two distinct instances of data represent the same real-world object. The comparison between data values is usually done by applying a similarity function which returns a similarity score. If this score surpasses a given threshold, both data instances are considered as representing the same real-world object. These score values depend on the algorithm that implements the function and have no meaning to the user. In addition, score values generated by different functions are not comparable. This will potentially lead to problems when the scores returned by different similarity functions need to be combined for computing the similarity between records. In this article, we propose that thresholds should be defined in terms of the precision that is expected from the matching process rather than in terms of the raw scores returned by the similarity function. Precision is a widely known similarity metric and has a clear interpretation from the user's point of view. Our approach defines mappings from score values to precision values, which we call adjusted scores. In order to obtain such mappings, our approach requires training over a small dataset. Experiments show that training can be reused for different datasets on the same domain. Our results also demonstrate that existing methods for combining scores for computing the similarity between records may be enhanced if adjusted scores are used.     

Extracting 3D information on bone remodeling in the proximity of titanium implants in SRμCT image volumes

Bone-implant integration is measured in several ways. Traditionally and routinely, 2D histological sections of samples, containing bone and the biomaterial, are stained and analyzed using a light microscope. Such histological section provides detailed cellular information about the bone regeneration in the proximity of the implant. However, this information reflects the integration in only a very small fraction, a 10 μm thick slice, of the sample. In this study, we show that feature values quantified on 2D sections are highly dependent on the orientation and the placement of the section, suggesting that a 3D analysis of the whole sample is of importance for a more complete judgment of the bone structure in the proximity of the implant. We propose features describing the 3D data by extending the features traditionally used for 2D-analysis. We present a method for extracting these features from 3D image data and we measure them on five 3D SRμCT image volumes.We also simulate cuts through the image volume positioned at all possible section positions. These simulations show that the measurement variations due to the orientation of the section around the center line of the implant are about 30%.     

Glioblastoma Stem Cells—Useful Tools in the Battle against Cancer

Glioblastoma stem cells (GSCs) are cells with a self-renewal ability and capacity to initiate tumors upon serial transplantation that have been linked to tumor cell heterogeneity. Most standard treatments fail to completely eradicate GSCs, causing the recurrence of the disease. GSCs could represent one reason for the low efficacy of cancer therapy and for the short relapse time. Nonetheless, experimental data suggest that the presence of therapy-resistant GSCs could explain tumor recurrence. Therefore, to effectively target GSCs, a comprehensive understanding of their biology and the survival and developing mechanisms during treatment is mandatory. This review provides an overview of the molecular features, microenvironment, detection, and targeting strategies of GSCs, an essential information required for an efficient therapy. Despite the outstanding results in oncology, researchers are still developing novel strategies, of which one could be targeting the GSCs present in the hypoxic regions and invasive edge of the glioblastoma.     

Maxsim2—Real-time interactive simulations for computer-assisted teaching of pharmacokinetics and pharmacodynamics

We developed a computer program for use in undergraduate and graduate courses in pharmacology, pharmacokinetics and pharmacodynamics. This program can also be used in environmental and toxicological studies and preclinical simulation, to facilitate communication between modeling pharmacokineticists and project leaders or other decision-makers in the pharmaceutical industry. The program simulates the drug delivery and transport by means of (I) a six-compartment physiological pharmacokinetic flow model, (II) a system of traditional compartment models, or (III) a target-mediated drug disposition system. The program also can be used to simulate instantaneous equilibria between concentration and pharmacodynamic response, or as temporal delays between concentration and response. The latter is done by means of turnover models (indirect response models). Drug absorption, distribution, and elimination are represented by differential equations, which are described by organ and tissue volumes or other volumes of distribution, blood flows, clearance terms, and tissue-to-blood partition coefficients. The user can control and adjust these parameters by means of a slider in real time. By interactively changing the parameter values and simultaneously displaying the resulting concentration–time and/or response–time profiles, users can understand the major mechanisms that govern the disposition or the pharmacological response of the drug in the organism in real time. Schedule dependence is typically seen in clinical practice with a non-linear concentration–response relationship, and is difficult to communicate except via simulations. Here, we sought to illustrate the potential advantages of this approach in teaching pharmacology, pharmacokinetics, and pharmacodynamics to undergraduate pharmacy-, veterinary-, and medical students or to project teams in drug discovery/development.