Stimulation of the switch in myometrial activity from contractures to contractions in the pregnant sheep and nonhuman primate

The process of parturition is regulated by a set of interrelated endocrine, paracrine, and autocrine systems. Many of these systems demonstrate positive feed-forward characteristics. The sequential recruitment of signals that promote the labour process demonstrates that it is not possible to attribute the designation of the factor responsible for the 'initiation of parturition' uniquely to any one signalling mechanism. For this reason we prefer to avoid the term initiation of parturition since, mechanistically, each cellular and molecular mechanism that contributes to the process is itself initiated by an earlier process. In a very real sense, the initiation of parturition can be considered to be fertilisation. Therefore we prefer to describe the key mechanisms involved as promoting, rather than initiating, the process of labour and delivery. Despite many interspecies differences, an increase in maternal plasma oestrogen in late gestation appears to play a central role in promotion of parturition. In both sheep and monkeys signals from the fetal hypothalamo-pituitary-adrenal axis increase oestrogen production by the placenta. We propose that the key fetal adrenal product is cortisol in the sheep and androgen in the monkey. Oestrogen then recruits a range of stimulators, uterotonins, that act on the prepared myometrium to initiate the switch in myometrial activity from contractures to contractions. The various mechanisms central to the process can be considered to be either, or both, activators and/or stimulators of one or more of the key terminal steps involved.     

Full body video-based self-avatars for mixed reality: from E2E system to user study

Virtual Reality - In this work, we explore the creation of self-avatars through video pass-through in mixed reality (MR) applications. We present our end-to-end system, including custom MR video...     

Overlapping events with application to image sequences

Counting spatially and temporally overlapping events in image sequences and estimating their shape-size and duration features are important issues in some applications. We propose a stochastic model, a particular case of the nonisotropic 3D Boolean model, for performing this analysis: the temporal Boolean model. Some probabilistic properties are derived and a methodology for parameter estimation from time-lapse image sequences is proposed using an explicit treatment of the temporal dimension. We estimate the mean number of germs per unit area and time, the mean grain size and the duration distribution. A wide simulation study in order to assess the proposed estimators showed promising results. The model was applied on biological image sequences of in-vivo cells in order to estimate new parameters such as the mean number and duration distribution of endocytic events. Our results show that the proposed temporal Boolean model is effective for obtaining information about dynamic processes which exhibit short-lived, but spatially and temporally overlapping events.     

Zu einigen Anwendungen der mehrkriteriellen Entscheidungsfindung auf ingenieurwissenschaftliche Probleme

Zusammenfassung Ingenieurarbeit ist in den meisten Fällen Entwurfsarbeit im weitesten Sinne. Der Entwurf eines Systems, z. B. einer Maschine, einer Bearbeitungstechnologie oder eines Steuerungssystems, ist durchzuführen unter dem Aspekt bestimmter Zielsetzungen, die sich nicht immer auf einen einzigen 'Qualitätsparameter des zu entwerfenden Systems reduzieren lassen. Der Entwurfsingenieur sieht sich deshalb immer mit einer mehrkriteriellen Entscheidungsaufgabe konfrontiert. Die Entscheidung kann demzufolge objektiviert werden, wenn eine Analyse des 'Güteverhaltens des zu entwerfenden technischen Systems durchgeführt werden kann. Mittel und Methoden hierfür vorzustellen und an praktischen Beispielen die Zweckmäßigkeit dieser Vorgehensweise aufzuzeigen, sind die Ziele dieses Artikels.

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Summary Engineering work involves designing in the widest sense. The design of a system, e.g. a machine, a manufacturing method or a control system, must be carried out with a view to definite objectives that cannot always be reduced to a single quality parameter of the system to be designed. Therefore, the design engineer is always faced with a multi-criteria decision making problem. Thus the decision can be objectified if the analysis of the 'quality behaviour of the technical system to be designed can be made. The present paper is intended to discuss appropriate means and methods and to illustrate the potential of this approach by practical examples.

     

Development, implementation and quality assurance of biokinetic models within CONRAD

The work of the Task Group 5.2 'Research Studies on Biokinetic Models' of the CONRAD project is presented. New biokinetic models have been implemented by several European institutions. Quality assurance procedures included intercomparison of the results as well as quality assurance of model formulation. Additionally, the use of the models was examined leading to proposals of tuning parameters. Stable isotope studies were evaluated with respect to their implications to the new models, and new biokinetic models were proposed on the basis of their results. Furthermore, the development of a biokinetic model describing the effects of decorporation of actinides by diethylenetriaminepentaacetic acid treatment was initiated.     

A mitochondriotropic derivative of quercetin: a strategy to increase the effectiveness of polyphenols

Mitochondria-targeted compounds are needed to act on a variety of processes that take place in these subcellular organelles and that have great pathophysiological relevance. In particular, redox-active molecules that are capable of homing in on mitochondria provide a tool to intervene on a major cellular source of reactive oxygen species and on the processes they induce, notably the mitochondrial permeability transition and cell death. We have linked the 3-OH of quercetin (3,3',4',5,7-pentahydroxy flavone), a model polyphenol, and the triphenylphosphonium moiety, a membrane-permeant cationic group, to produce proof-of-principle mitochondriotropic quercetin derivatives. The remaining hydroxyls were sometimes acetylated to hinder metabolism and improve solubility. The new compounds accumulate in mitochondria in a transmembrane potential-driven process and are only slowly metabolised by cultured human colon cells. They inhibit mitochondrial ATPase activity much as quercetin does, and are toxic for fast-growing cells.     

Construction of Whole Genomes from Scaffolds Using Single Cell Strand-Seq Data

Accurate reference genome sequences provide the foundation for modern molecular biology and genomics as the interpretation of sequence data to study evolution, gene expression, and epigenetics depends heavily on the quality of the genome assembly used for its alignment. Correctly organising sequenced fragments such as contigs and scaffolds in relation to each other is a critical and often challenging step in the construction of robust genome references. We previously identified misoriented regions in the mouse and human reference assemblies using Strand-seq, a single cell sequencing technique that preserves DNA directionality Here we demonstrate the ability of Strand-seq to build and correct full-length chromosomes by identifying which scaffolds belong to the same chromosome and determining their correct order and orientation, without the need for overlapping sequences. We demonstrate that Strand-seq exquisitely maps assembly fragments into large related groups and chromosome-sized clusters without using new assembly data. Using template strand inheritance as a bi-allelic marker, we employ genetic mapping principles to cluster scaffolds that are derived from the same chromosome and order them within the chromosome based solely on directionality of DNA strand inheritance. We prove the utility of our approach by generating improved genome assemblies for several model organisms including the ferret, pig, Xenopus, zebrafish, Tasmanian devil and the Guinea pig.     

Human biokinetic data and a new compartmental model of zirconium--a tracer study with enriched stable isotopes

Biokinetic models describing the uptake, distribution and excretion of trace elements are an essential tool in nutrition, toxicology, or internal dosimetry of radionuclides. Zirconium, especially its radioisotope ⁹⁵Zr, is relevant to radiation protection due to its production in uranium fission and neutron activation of nuclear fuel cladding material. We present a comprehensive set of human data from a tracer study with stable isotopes of zirconium. The data are used to refine a biokinetic model of zirconium.Six female and seven male healthy adult volunteers participated in the study. It includes 16 complete double tracer investigations with oral ingestion and intravenous injection, and seven supplemental investigations. Tracer concentrations were measured in blood plasma and urine collected up to 100 d after tracer administration. The four data sets (two chemical tracer forms in plasma and urine) each encompass 105-240 measured concentration values above detection limits.Total fractional absorption of ingested zirconium was found to be 0.001 for zirconium in citrate-buffered drinking solution and 0.007 for zirconium oxalate solution.Biokinetic models were developed based on the linear first-order kinetic compartmental model approach used by the International Commission on Radiological Protection (ICRP). The main differences of the optimized systemic model of zirconium to the current ICRP model are (1) recycling into the transfer compartment made necessary by the observed tracer clearance from plasma, (2) different parameters related to fractional absorption for each form of the ingested tracer, and (3) a physiologically based excretion pathway to urine.The study considerably expands the knowledge on the biokinetics of zirconium, which was until now dominated by data from animal studies. The proposed systemic model improves the existing ICRP model, yet is based on the same principles and fits well into the ICRP radiation protection approach.     

Development of permanent magnet MnAlC/polymer composites and flexible filament for bonding and 3D-printing technologies

Searching for high-performance permanent magnets components with no limitation in shape and dimensions is highly desired to overcome the present design and manufacturing restrictions, which affect the efficiency of the final devices in energy, automotive and aerospace sectors. Advanced 3D-printing of composite materials and related technologies is an incipient route to achieve functional structures avoiding the limitations of traditional manufacturing. Gas-atomized MnAlC particles combined with polymer have been used in this work for fabricating scalable rare earth-free permanent magnet composites and extruded flexible filaments with continuous length exceeding 10 m. Solution casting has been used to synthesize homogeneous composites with tuned particles content, made of a polyethylene (PE) matrix embedding quasi-spherical particles of the ferromagnetic τ-MnAlC phase. A maximum filling factor of 86.5 and 72.3% has been obtained for the composite and the filament after extrusion, respectively. The magnetic measurements reveal no deterioration of the properties of the MnAlC particles after the composite synthesis and filament extrusion. The produced MnAlC/PE materials will serve as precursors for an efficient and scalable design and fabrication of end-products by different processing techniques (polymerized cold-compacted magnets and 3D-printing, respectively) in view of technological applications (from micro electromechanical systems to energy and transport applications).