Minimization of Intra-Operative Shaping of Orthopaedic Fixation Plates: A Population-Based Design

In this paper we present a new population-based method for the design of bone fixation plates. Standard pre-contoured plates are designed based on the mean shape of a certain population. We propose a computational process to design implants while reducing the amount of required intra-operative shaping, thus reducing the mechanical stresses applied to the plate. A bending and torsion model was used to measure and minimize the necessary intra-operative deformation. The method was applied and validated on a population of 200 femurs that was further augmented with a statistical shape model. The obtained results showed substantial reduction in the bending and torsion needed to shape the new design into any bone in the population when compared to the standard mean-based plates.

The GABRIEL Advanced Surveys: study design, participation and evaluation of bias

Exposure to farming environments has been shown to protect substantially against asthma and atopic disease across Europe and in other parts of the world. The GABRIEL Advanced Surveys (GABRIELA) were conducted to determine factors in farming environments which are fundamental to protecting against asthma and atopic disease. The GABRIEL Advanced Surveys have a multi-phase stratified design. In a first-screening phase, a comprehensive population-based survey was conducted to assess the prevalence of exposure to farming environments and of asthma and atopic diseases (n = 103,219). The second phase was designed to ascertain detailed exposure to farming environments and to collect biomaterial and environmental samples in a stratified random sample of phase 1 participants (n = 15,255). A third phase was carried out in a further stratified sample only in Bavaria, southern Germany, aiming at in-depth respiratory disease and exposure assessment including extensive environmental sampling (n = 895). Participation rates in phase 1 were around 60% but only about half of the participating study population consented to further study modules in phase 2. We found that consenting behaviour was related to familial allergies, high parental education, wheeze, doctor diagnosed asthma and rhinoconjunctivitis, and to a lesser extent to exposure to farming environments. The association of exposure to farm environments with asthma or rhinoconjunctivitis was not biased by participation or consenting behaviour. The GABRIEL Advanced Surveys are one of the largest studies to shed light on the protective 'farm effect' on asthma and atopic disease. Bias with regard to the main study question was able to be ruled out by representativeness and high participation rates in phases 2 and 3. The GABRIEL Advanced Surveys have created extensive collections of questionnaire data, biomaterial and environmental samples promising new insights into this area of research.

Design-based stereology to quantify structural properties of artificial and natural snow using thin sections

The quantification of the structural properties of snow is traditionally based on model-based stereology. Model-based stereology requires assumptions about the shape of the investigated structure. Here, we show how the density, specific surface area, and grain boundary area can be measured using a design-based method, where no assumptions about structural properties are necessary. The stereological results were also compared to X-ray tomography to control the accuracy of the method. The specific surface area calculated with the stereological method was 19.8 ± 12.3% smaller than with X-ray tomography. For the density, the stereological method gave results that were 11.7 ± 12.1% larger than X-ray tomography. The statistical analysis of the estimates confirmed that the stereological method and the sampling used are accurate. This stereological method was successfully tested on artificially produced ice beads but also on several snow types. Combining stereology and polarisation microscopy provides a good estimate of grain boundary areas in ice beads and in natural snow, with some limitatio

Io volcano observer (IVO) integrated approach to optimizing system design for radiation challenges

One of the major challenges for a mission to the Jovian system is the radiation tolerance of the spacecraft (S/C) and the payload. Moreover, being able to achieve science observations with high signal to noise ratios (SNR), while passing through the high flux radiation zones, requires additional ingenuity on the part of the instrument provider. Consequently, the radiation mitigation is closely intertwined with the payload, spacecraft and trajectory design, and requires a systems-level approach. This paper presents a design for the Io Volcano Observer (IVO), a Discovery mission concept that makes multiple close encounters with Io while orbiting Jupiter. The mission aims to answer key outstanding questions about Io, especially the nature of its intense active volcanism and the internal processes that drive it. The payload includes narrow-angle and wide-angle cameras (NAC and WAC), dual fluxgate magnetometers (FGM), a thermal mapper (ThM), dual ion and neutral mass spectrometers (INMS), and dual plasma ion analyzers (PIA). The radiation mitigation is implemented by drawing upon experiences from designs and studies for missions such as the Radiation Belt Storm Probes (RBSP) and Jupiter Europa Orbiter (JEO). At the core of the radiation mitigation is IVO's inclined and highly elliptical orbit, which leads to rapid passes through the most intense radiation near Io, minimizing the total ionizing dose (177 krads behind 100 mils of Aluminum with radiation design margin (RDM) of 2 after 7 encounters). The payload and the spacecraft are designed specifically to accommodate the fast flyby velocities (e.g. the spacecraft is radioisotope powered, remaining small and agile without any flexible appendages). The science instruments, which collect the majority of the high-priority data when close to Io and thus near the peak flux, also have to mitigate transient noise in their detectors. The cameras use a combination of shielding and CMOS detectors with extremely fast readout to mi- imize noise. INMS microchannel plate detectors and PIA channel electron multipliers require additional shielding. The FGM is not sensitive to noise induced by energetic particles and the ThM microbolometer detector is nearly insensitive. Detailed SNR calculations are presented. To facilitate targeting agility, all of the spacecraft components are shielded separately since this approach is more mass efficient than using a radiation vault. IVO uses proven radiation-hardened parts (rated at 100 krad behind equivalent shielding of 280 mils of Aluminum with RDM of 2) and is expected to have ample mass margin to increase shielding if needed.

An Instrument Design for Space-Based Optical Observation of Space Debris

Currently, observations of space debris are primarily performed with ground-based sensors. These sensors have a detection limit at some centimetres diameter for objects in Low Earth Orbit (LEO) and at about two decimetres diameter for objects in Geostationary Orbit (GEO). The few space-based debris observations stem mainly from in-situ measurements and from the analysis of returned spacecraft surfaces. Both provide information about mostly sub-millimetre-sized debris particles. As a consequence the population of centimetre- and millimetre-sized debris objects remains poorly understood. The development, validation and improvement of debris reference models drive the need for measurements covering the whole diameter range. In 2003 the European Space Agency (ESA) initiated a study entitled “Space-Based Optical Observation of Space Debris”. The first tasks of the study were to define user requirements and to develop an observation strategy for a space-based instrument capable of observing uncatalogued millimetre-sized debris objects. Only passive optical observations were considered, focussing on mission concepts for the LEO, and GEO regions respectively. Starting from the requirements and the observation strategy, an instrument system architecture and an associated operations concept have been elaborated. The instrument system architecture covers the telescope, camera and onboard processing electronics. The proposed telescope is a folded Schmidt design, characterised by a 20 cm aperture and a large field of view of 6°. The camera design is based on the use of either a frame-transfer charge coupled device (CCD), or on a cooled hybrid sensor with fast read-out. A four megapixel sensor is foreseen. For the onboard processing, a scalable architecture has been selected. Performance simulations have been executed for the system as designed, focussing on the orbit determination of observed debris particles, and on the analysis of the object detection algorithms. In this paper we present some of the main results of the study. A short overview of the user requirements and observation strategy is given. The architectural design of the instrument is discussed, and the main tradeoffs are outlined. An insight into the results of the performance simulations is provided.

Crystal structure of the Leishmania major phosphodiesterase LmjPDEB1 and insight into the design of the parasite-selective inhibitors

Human leishmaniasis is a major public health problem in many countries, but chemotherapy is in an unsatisfactory state. Leishmania major phosphodiesterases (LmjPDEs) have been shown to play important roles in cell proliferation and apoptosis of the parasite. Thus LmjPDE inhibitors may potentially represent a novel class of drugs for the treatment of leishmaniasis. Reported here are the kinetic characterization of the LmjPDEB1 catalytic domain and its crystal structure as a complex with 3-isobutyl-1-methylxanthine (IBMX) at 1.55 A resolution. The structure of LmjPDEB1 is similar to that of human PDEs. IBMX stacks against the conserved phenylalanine and forms a hydrogen bond with the invariant glutamine, in a pattern common to most inhibitors bound to human PDEs. However, an extensive structural comparison reveals subtle, but significant differences between the active sites of LmjPDEB1 and human PDEs. In addition, a pocket next to the inhibitor binding site is found to be unique to LmjPDEB1. This pocket is isolated by two gating residues in human PDE families, but constitutes a natural expansion of the inhibitor binding pocket in LmjPDEB1. The structure particularity might be useful for the development of parasite-selective inhibitors for the treatment of leishmaniasis.

Design, synthesis and pharmacological characterization of analogs of 2-aminoethyl diphenylborinate (2-APB), a known store-operated calcium channel blocker, for inhibition of TRPV6-mediated calcium transport

2-Aminoethyl diphenylborinate (2-APB) is a known modulator of the IP3 receptor, the calcium ATPase SERCA, the calcium release-activated calcium channel Orai and TRP channels. More recently, it was shown that 2-APB is an efficient inhibitor of the epithelial calcium channel TRPV6 which is overexpressed in prostate cancer. We have conducted a structure-activity relationship study of 2-APB congeners to understand their inhibitory mode of action on TRPV6. Whereas modifying the aminoethyl moiety did not significantly change TRPV6 inhibition, substitution of the phenyl rings of 2-APB did. Our data show that the diaryl borinate moiety is required for biological activity and that the substitution pattern of the aryl rings can influence TRPV6 versus SOCE inhibition. We have also discovered that 2-APB is hydrolyzed and transesterified within minutes in solution.