21 research outputs found

    Neural Deformable Cone Beam CT

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    In oral and maxillofacial cone beam computed tomography (CBCT), patient motion is frequently observed and, if not accounted for, can severely affect the usability of the acquired images. We propose a highly flexible, data driven motion correction and reconstruction method which combines neural inverse rendering in a CBCT setting with a neural deformation field. We jointly optimize a lightweight coordinate based representation of the 3D volume together with a deformation network. This allows our method to generate high quality results while accurately representing occurring patient movements, such as head movements, separate jaw movements or swallowing. We evaluate our method in synthetic and clinical scenarios and are able to produce artefact-free reconstructions even in the presence of severe motion. While our approach is primarily developed for maxillofacial applications, we do not restrict the deformation field to certain kinds of motion. We demonstrate its flexibility by applying it to other scenarios, such as 4D lung scans or industrial tomography settings, achieving state-of-the art results within minutes with only minimal adjustments

    Mechanical forces couple bone matrix mineralization with inhibition of angiogenesis to limit adolescent bone growth

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    Bone growth requires a specialised, highly angiogenic blood vessel subtype, so-called type H vessels, which pave the way for osteoblasts surrounding these vessels. At the end of adolescence, type H vessels differentiate into quiescent type L endothelium lacking the capacity to promote bone growth. Until now, the signals that switch off type H vessel identity and thus limit adolescent bone growth have remained ill defined. Here we show that mechanical forces, associated with increased body weight at the end of adolescence, trigger the mechanoreceptor PIEZO1 and thereby mediate enhanced production of the kinase FAM20C in osteoblasts. FAM20C, the major kinase of the secreted phosphoproteome, phosphorylates dentin matrix protein 1, previously identified as a key factor in bone mineralization. Thereupon, dentin matrix protein 1 is secreted from osteoblasts in a burst-like manner. Extracellular dentin matrix protein 1 inhibits vascular endothelial growth factor signalling by preventing phosphorylation of vascular endothelial growth factor receptor 2. Hence, secreted dentin matrix protein 1 transforms type H vessels into type L to limit bone growth activity and enhance bone mineralization. The discovered mechanism may suggest new options for the treatment of diseases characterised by aberrant activity of bone and vessels such as osteoarthritis, osteoporosis and osteosarcoma

    Piezo1 Inactivation in Chondrocytes Impairs Trabecular Bone Formation

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    The skeleton is a dynamic tissue continuously adapting to mechanical stimuli. Although matrix‐embedded osteocytes are considered as the key mechanoresponsive bone cells, all other skeletal cell types are principally exposed to macroenvironmental and microenvironmental mechanical influences that could potentially affect their activities. It was recently reported that Piezo1, one of the two mechanically activated ion channels of the Piezo family, functions as a mechanosensor in osteoblasts and osteocytes. Here we show that Piezo1 additionally plays a critical role in the process of endochondral bone formation. More specifically, by targeted deletion of Piezo1 or Piezo2 in either osteoblast (Runx2Cre) or osteoclast lineage cells (Lyz2Cre), we observed severe osteoporosis with numerous spontaneous fractures specifically in Piezo1Runx2Cre mice. This phenotype developed at an early postnatal stage and primarily affected the formation of the secondary spongiosa. The presumptive Piezo1Runx2Cre osteoblasts in this region displayed an unusual flattened appearance and were positive for type X collagen. Moreover, transcriptome analyses of primary osteoblasts identified an unexpected induction of chondrocyte‐related genes in Piezo1Runx2Cre cultures. Because Runx2 is not only expressed in osteoblast progenitor cells, but also in prehypertrophic chondrocytes, these data suggested that Piezo1 functions in growth plate chondrocytes to ensure trabecular bone formation in the process of endochondral ossification. To confirm this hypothesis, we generated mice with Piezo1 deletion in chondrocytes (Col2a1Cre). These mice essentially recapitulated the phenotype of Piezo1Runx2Cre animals, because they displayed early‐onset osteoporosis with multiple fractures, as well as impaired formation of the secondary spongiosa with abnormal osteoblast morphology. Our data identify a previously unrecognized key function of Piezo1 in endochondral ossification, which, together with its role in bone remodeling, suggests that Piezo1 represents an attractive target for the treatment of skeletal disorders. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

    Human plasma protein N-glycosylation

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    Ion-association complexes unite classical and non-classical theories for the biomimetic nucleation of calcium phosphate

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    Despite its importance in many industrial, geological and biological processes, the mechanism of crystallization from supersaturated solutions remains a matter of debate. Recent discoveries show that in many solution systems nanometre-sized structural units are already present before nucleation. Still little is known about the structure and role of these so-called pre-nucleation clusters. Here we present a combination of in situ investigations, which show that for the crystallization of calcium phosphate these nanometre-sized units are in fact calcium triphosphate complexes. Under conditions in which apatite forms from an amorphous calcium phosphate precursor, these complexes aggregate and take up an extra calcium ion to form amorphous calcium phosphate, which is a fractal of Ca2(HPO4)32− clusters. The calcium triphosphate complex also forms the basis of the crystal structure of octacalcium phosphate and apatite. Finally, we demonstrate how the existence of these complexes lowers the energy barrier to nucleation and unites classical and non-classical nucleation theories

    How shall we all live together?: Meta-analytical review of the mutual intercultural relations in plural societies project

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    Living together in culturally plural societies poses numerous challenges for members of ethnocultural groups and for the larger society. An important goal of these societies is to achieve positive intercultural relations among all their peoples. Successful management of these relations depends on many factors including a research-based understanding of the historical, political, economic, religious and psychological features of the groups that are in contact. The core question is ‘how we shall we all live together?’ In the project reported in this paper (Mutual Intercultural Relations in Plural Societies; MIRIPS), we seek to provide such research by reviewing three core psychological hypotheses of intercultural relations (multiculturalism, contact and integration) in 21 culturally plural societies. The main goal of the project is to evaluate these hypotheses across societies within the MIRIPS project in order to identify if there are some basic psychological principles that underlie intercultural relations panculturally. If there are, the eventual goal is to employ the findings to propose some policies and programmes that may improve the quality of intercultural relationship globally. An internal meta-analysis using the MIRIPS project data showed that the empirical findings from these societies generally support the validity of the three hypotheses. Implications for the development of policies and programmes to enhance the quality of intercultural relations are discussed
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