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Loss-of-function mutations in the Sost gene lead to high bone mass phenotypes. Pharmacological inhibition of Sost/sclerostin provides a new drug strategy for treating osteoporosis. Questions remain as to how physical activity may affect bone mass under sclerostin inhibition and if that effect differs between males and females. We previously observed in female Sost knockout (KO) mice an enhanced cortical bone formation response to a moderate level of applied loading (900 με at the tibial midshaft). The purpose of the present study was to examine cortical bone adaptation to the same strain level applied to male Sost KO mice. Strain-matched in vivo compressive loading was applied to the tibiae of 10-, 26- and 52-week-old male Sost KO and littermate control (LC) mice. The effect of tibial loading on bone (re)modeling was measured by microCT, 3D time-lapse in vivo morphometry, 2D histomorphometry and gene expression analyses. As expected, Sost deficiency led to high cortical bone mass in 10- and 26-week-old male mice as a result of increased bone formation. However, the enhanced bone formation associated with Sost deficiency did not appear to diminish with skeletal maturation. An increase in bone resorption was observed with skeletal maturation in male LC and Sost KO mice. Two weeks of in vivo loading (900 με at the tibial midshaft) induced only a mild anabolic response in 10- and 26-week-old male mice, independent of Sost deficiency. A decrease in the Wnt inhibitor Dkk1 expression was observed 3 h after loading in 52-week-old Sost KO and LC mice, and an increase in Lef1 expression was observed 8 h after loading in 10-week-old Sost KO mice. The current results suggest that long-term inhibition of sclerostin in male mice does not influence the adaptive response of cortical bone to moderate levels of loading. In contrast with our previous strain-matched study in females showing enhanced bone responses with Sost ablation, these results in males indicate that the influence of Sost deficiency on the cortical bone formation response to a moderate level of loading differs between males and females. Clinical studies examining antibodies to inhibit sclerostin may need to consider that the efficacy of additional physical activity regimens may be sex dependent.

Gerodermia osteodysplastica (GO) is a segmental progeroid disorder caused by loss-of-function mutations in the GORAB gene, associated with early onset osteoporosis and bone fragility. A conditional mouse model of GO (GorabPrx1) was generated in which the Gorab gene was deleted in long bones. We examined the biomechanical/functional relevance of the GorabPrx1 mutants as a premature aging model by characterizing bone composition, tissue-level strains, and whole-bone morphology and mechanical properties of the tibia. MicroCT imaging showed that GorabPrx1 tibiae had an increased anterior convex curvature and decreased cortical cross-sectional area, cortical thickness and moments of inertia, compared to littermate control (LC) tibiae. Fourier transform infrared (FTIR) imaging indicated a 34% decrease in mineral/matrix ratio and a 27% increase in acid phosphate content in the posterior metaphyseal cortex of the GorabPrx1 tibiae (p

We present results on trapping ensembles of cold atoms with metasurface optics for portable atomic clock application, and progress towards single atom trapping and detection in high-NA optical tweezers with dielectric metalenses.

Limiting bone resorption and regenerating bone tissue are treatment goals in myeloma bone disease (MMBD). Physical stimuli such as mechanical loading prevent bone destruction and enhance bone mass in the MOPC315.BM.Luc model of MMBD. It is unknown whether treatment with the Bruton’s tyrosine kinase inhibitor CC-292 (spebrutinib), which regulates osteoclast differentiation and function, augments the anabolic effect of mechanical loading. CC-292 was administered alone and in combination with axial compressive tibial loading in the MOPC315.BM.Luc model for three weeks. However, neither CC-292 alone nor its use in combination with mechanical loading was more effective in reducing osteolytic bone disease or rescuing bone mass than mechanical stimuli alone, as evidenced by microcomputed tomography (microCT) and histomorphometric analysis. Further studies are needed to investigate novel anti-myeloma and anti-resorptive strategies in combination with physical stimuli to improve treatment of MMBD.

We show that with a purely blue-detuned cooling mechanism we can densely load single neutral atoms into large arrays of shallow optical tweezers. With this ability, more efficient assembly of larger ordered arrays will be possible - hence expanding the number of particles available for bottom-up quantum simulation and computation with atoms. Using Lambda-enhanced grey molasses on the D1 line of 87Rb, we achieve loading into a single 0.63 mK trap with 89% probability, and we further extend this loading to 100 atoms at 80% probability. The loading behavior agrees with a model of consecutive light-assisted collisions in repulsive molecular states. With simple rearrangement that only moves rows and columns of a 2D array, we demonstrate one example of the power of enhanced loading in large arrays., 6 pages, 3 figures

Atomic magnetometry is one of the most sensitive ways to measure magnetic fields. We present a method for converting a naturally scalar atomic magnetometer into a vector magnetometer by exploiting the polarization dependence of hyperfine transitions in rubidium atoms. First, we fully determine the polarization ellipse of an applied microwave field using a self-calibrating method, i.e. a method in which the light-atom interaction provides everything required to know the field in an orthogonal laboratory frame. We then measure the direction of an applied static field using the polarization ellipse as a three-dimensional reference defined by Maxwell's equations. Although demonstrated with trapped atoms, this technique could be applied to atomic vapors, or a variety of atom-like systems., 5 pages, 3 figures + supplementary 11 pages, 5 figure

During bone healing, tissue formation processes are governed by mechanical strain. Sost/sclerostin, a key Wnt signaling inhibitor and mechano-sensitive pathway, is downregulated in response to mechanical loading. Sclerostin neutralizing antibody (SclAb) increases bone formation. Nevertheless, it remains unclear whether sclerostin inhibition can rescue bone healing in situations of mechanical instability, which otherwise delay healing. We investigated SclAb's influence on tissue formation in a mouse femoral osteotomy, stabilized with rigid or semirigid external fixation. The different fixations allowed different magnitudes of interfragmentary movement during weight bearing, thereby influencing healing outcome. SclAb or vehicle (veh) was administeredand bone healing was assessed at multiple time points up to day 21 postoperatively by in vivo micro-computed tomography, histomorphometry, biomechanical testing, immunohistochemistry, and gene expression. Our results show that SclAb treatment caused a greater bone volume than veh. However, SclAb could not overcome the characteristic delayed healing of semirigid fixation. Indeed, semirigid fixation resulted in delayed healing with a prolonged endochondral ossification phase characterized by increased cartilage, lower bone volume fraction, and less bony bridging across the osteotomy gap than rigid fixation. In a control setting, SclAb negatively affected later stages of healing under rigid fixation, evidenced by the high degree of endosteal bridging at 21 days in the rigid-SclAb group compared with rigid-veh, indicating delayed fracture callus remodeling and bone marrow reconstitution. Under rigid fixation, Sost and sclerostin expression at the gene and protein level, respectively, were increased in SclAb compared with veh-treated bones, suggesting a negative feedback mechanism. Our results suggest that SclAb could be used to enhance overall bone mass but should be carefully considered in bone healing. SclAb may help to increase bone formation early in the healing process but not during advanced stages of fracture callus remodeling and not to overcome delayed healing in semirigid fixation. © 2018 American Society for Bone and Mineral Research.

Physical Review A, 95 (5), ISSN:1094-1622, ISSN:0556-2791, ISSN:1050-2947

Das Ingenieurburo Leonhardt, Andra und Partner konnte in den letzten Jahren weitreichende Erfahrungen mit der Anwendung von Building Information Modeling (BIM) sammeln. Dabei wurde nicht nur in der Praxis BIM der ersten und zweiten Stufe angewandt, sondern auch im Zuge von Forschungsprojekten an der Weiterentwicklung der Methode auf hoheren Ebenen gearbeitet. Bei der praktischen Anwendung kommen zurzeit hauptsachlich geschlossene Methoden, also mit einer speziellen Software bzw. Partnersoftware und deren spezifischer Schnittstelle zum Einsatz. Bereits bei dieser sog. ersten Stufe von BIM ergeben sich auch schon in fruhen Projektphasen zahlreiche Vorteile, die dessen Einsatz lohnenswert machen. Bei der Anwendung der offenen Methode mit Datenaustausch via IFC wurde wiederholt deutlich, dass die Funktionalitaten der beteiligten Software dadurch eingeschrankt werden, dass bestimmte Modellparameter nicht ausgetauscht werden konnen oder die Schnittstellen noch fehlerbehaftet sind. Bei der Beteiligung an Forschungsprojekten wird ersichtlich, welche weitreichenden Chancen open BIM bietet, aber auch welche technischen Hurden zu uberwinden sind. Durch die Weiterentwicklung der Schnittstellen sowie die Verwendung von Cloud bzw. Grid Computing werden hochkomplexe und rechenaufwandige Analysen der Bauwerke ermoglicht. Webbasierte Plattformen erlauben effizientes Zusammenarbeiten verschiedener Fachdisziplinen sowie ein optimiertes Zusammenspiel unterschiedlichster Analysesoftware. BIM – Experiences of the application of a new method in an engineering company Consulting engineers Leonhardt Andra and Partners were able to gather extensive experiences in the application of BIM. Not only first and second level BIM was used in practice, but also by contributing to research projects, the method was developed on higher levels. At daily practice, mainly closed BIMs are worked on by using proprietary software with a specific interface. Already on this first level BIM, many advantages are becoming obvious that also pay off on early project stages. It became apparent, that the application of open BIM with data exchange via IFC limits the functionalities of the participating software, as some model parameters can't be exchanged, or interfaces are defective. The participation in research projects shows on the one hand the chances of open BIM, on the other hand what problems have to be resolved. By developing the interfaces and Cloud/Grid computing, highly complex and computing time consuming analyses are made feasible. Web-based platforms allow efficient co-working of different disciplines and an optimized cooperation of different tools.

Bone loss occurs during adulthood in both women and men and affects trabecular bone more than cortical bone. The mechanism responsible for trabecular bone loss during adulthood remains unexplained, but may be due at least in part to a reduced mechanoresponsiveness. We hypothesized that trabecular and cortical bone would respond anabolically to loading and that the bone response to mechanical loading would be reduced and the onset delayed in adult compared to postpubescent mice. We evaluated the longitudinal adaptive response of trabecular and cortical bone in postpubescent, young (10 week old) and adult (26 week old) female C57Bl/6J mice to axial tibial compression using in vivo microCT (days 0, 5, 10, and 15) and dynamic histomorphometry (day 15). Loading elicited an anabolic response in both trabecular and cortical bone in young and adult mice. As hypothesized, trabecular bone in adult mice exhibited a reduced and delayed response to loading compared to the young mice, apparent in trabecular bone volume fraction and architecture after 10 days. No difference in mechanoresponsiveness of the cortical bone was observed between young and adult mice. Finite element analysis showed that load-induced strain was reduced with age. Our results suggest that trabecular bone loss that occurs in adulthood may in part be due to a reduced mechanoresponsiveness in this tissue and/or a reduction in the induced tissue deformation which occurs during habitual loading. Therapeutic approaches that address the mechanoresponsiveness of the bone tissue may be a promising and alternate strategy to maintain trabecular bone mass during aging.

Gerodermia osteodysplastica (GO) is a segmental progeroid disorder caused by loss-of-function mutations in the GORAB gene, associated with early onset osteoporosis and bone fragility. A conditional mouse model of GO (GorabPrx1) was generated in which the Gorab gene was deleted in long bones. We examined the biomechanical/functional relevance of the GorabPrx1 mutants as a premature aging model by characterizing bone composition, tissue-level strains, and whole-bone morphology and mechanical properties of the tibia. MicroCT imaging showed that GorabPrx1 tibiae had an increased anterior convex curvature and decreased cortical cross-sectional area, cortical thickness and moments of inertia, compared to littermate control (LC) tibiae. Fourier transform infrared imaging (FTIRI) indicated a 34% decrease in mineral/matrix ratio and a 27% increase in acid phosphate content in the posterior metaphyseal cortex of the GorabPrx1 tibiae (p

Bone adaptation optimizes mass and structure, but the mechano-response is already reduced at maturation. Downregulation of sclerostin was believed to be a mandatory step in mechano-adaptation, but in young mice it was shown that load-induced formation can occur independent of sclerostin, a product of the Sost gene. We hypothesized that the bone formation and resorption response to loading is not affected by Sost deficiency, but is age-specific. Our findings indicate that the anabolic response to in vivo tibial loading was reduced at maturation in Sost Knockout (KO) and littermate control (LC) mice. Age affected all anabolic and catabolic parameters and altered Sost and Wnt target gene expression. While load-induced cortical resorption was similar between genotypes, loading-induced gains in mineralizing surface was enhanced in Sost KO compared to LC mice. Loading led to a downregulation in expression of the Wnt inhibitor Dkk1. Expression of Dkk1 was greater in both control and loaded limbs of Sost KO compared to LC mice suggesting a compensatory role in the absence of Sost. These data suggest physical activity could enhance bone mass concurrently with sclerostin-neutralizing antibodies, but treatment strategies should consider the influence of age on ultimate load-induced bone mass gains.

We propose a versatile arrangement for the trapping and manipulation of single atoms in optical tweezers formed by the direct image of a spatial light modulator (SLM). The scheme incorporates a high numerical aperture microscope to map the intensity distribution of a SLM onto a cloud of cold atoms. The regions of high intensity act as optical dipole-force traps. With a SLM fast enough to modify the trapping potential in real time, this technique is well suited for the controlled addressing and manipulation of arbitrarily selected atoms., SCOPUS: ar.j, info:eu-repo/semantics/published

Physical Review A, 92 (6), ISSN:1094-1622, ISSN:0556-2791, ISSN:1050-2947

Physical Review A, 90 (1), ISSN:1094-1622, ISSN:0556-2791, ISSN:1050-2947

We investigate the properties of a laser-plasma electron accelerator as a bright source of keV x-ray radiation. During the interaction, the electrons undergo betatron oscillations and from the carefully measured x-ray spectrum the oscillation amplitude of the electrons can be deduced which decreases with increasing electron energies. From the oscillation amplitude and the independently measured x-ray source size of $(1.8\ifmmode\pm\else\textpm\fi{}0.3)\text{ }\text{ }\ensuremath{\mu}\mathrm{m}$ we are able to estimate the electron bunch diameter to be $(1.6\ifmmode\pm\else\textpm\fi{}0.3)\text{ }\text{ }\ensuremath{\mu}\mathrm{m}$.

We present a spatial and spectral characterization of a laser-plasma based betatron source which allows us to determine the betatron oscillation amplitude of the electrons which decreases with increasing electron energies. Due to the observed oscillation amplitude and the independently measured x-ray source size of (1.8±0.3)μm we are able to estimate the electron bunch diameter to be (1.6±0.3)μm.

Physical Review Letters, 108 (6), ISSN:0031-9007, ISSN:1079-7114

Considerable effort is being made to realize all the elements required for a distributed quantum network [1]. Ideally such a network would be composed of individual nodes acting as quantum gates/memories, connected together by optical links. Recent work in cavity-QED has shown that it is possible to deterministically create single photons. The narrow bandwidth (MHz) and coherence properties of these photons can be controlled to create atom-photon, as well as photon-photon entanglement [2]. The goals of our work are to build on photon sources for implementing the quantum memories and state mapping schemes required in a quantum network.

Through the application of a solid-phase dynamic extraction (SPDE) method for the determination of volatile substances, different parameters may influence the extraction and desorption process and are, therefore, vital for the determination of the extracted substances via gas chromatography (GC). In this study, the influence of extraction und desorption parameters of an SPDE-GC method for the determination of the d-limonene degradation products, namely, -terpineol, (-)-carveol, and (S)-carvone, in an aqueous model system was evaluated using a factorial fractional design. The aim was to reduce the number of factors that should be considered for the optimization of an SPDE procedure for different applications. It could be shown that the extraction efficiency of -terpineol, (-)-carveol, and (S)-carvone is significantly influenced by the extraction parameters incubation temperature, number of extraction strokes, and amount of added NaCl. All 3 parameters have a positive effect on the extraction and determination of the examined d-limonene degradation products. Due to the identification of significant factors on the basis of an experimental design, the results of this study can be very useful for further development of SPDE methods for different applications.