130 research outputs found

    Multi-Scale Flight Path Planning for UAS Building Inspection

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    Unmanned aircraft systems (UAS) show large potential for the construction industry. Their use in condition assessment has increased significantly, due to technological and computational progress. UAS play a crucial role in developing a digital maintenance strategy for infrastructure, saving cost and effort, while increasing safety and reliability. Part of that strategy are automated visual UAS inspections of the building’s condition. The resulting images can automatically be analyzed to identify and localize damages to the structure that have to be monitored. Further interest in parts of a structure can arise from events like accidents or collisions. Areas of low interest exist, where low resolution monitoring is sufficient. From different requirements for resolution, different levels of detail can be derived. They require special image acquisition parameters that differ mainly in the distance between camera and structure. Areas with a higher level of detail require a smaller distance to the object, producing more images. This work proposes a multi-scale flight path planning procedure, enabling higher resolution requirements for areas of special interest, while reducing the number of required images to a minimum. Careful selection of the camera positions maintains the complete coverage of the structure, while achieving the required resolution in all areas. The result is an efficient UAS inspection, reducing effort for the maintenance of infrastructure

    Histone deacetylase inhibition sensitizes osteosarcoma to heavy ion radiotherapy

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    Background: Minimal improvements in treatment or survival of patients with osteosarcoma have been achieved during the last three decades. Especially in the case of incomplete tumor resection, prognosis remains poor. Heavy ion radiotherapy (HIT) and modern anticancer drugs like histone deacetylase inhibitors (HDACi) have shown promising effects in osteosarcoma in vitro. In this study, we tested the effect of HIT and the combination of HIT and the HDACi suberoylanilide hydroxamic acid (SAHA) in a xenograft mouse model. Methods: Osteosarcoma xenografts were established by subcutaneous injection of KHOS-24OS cells and treated with either vehicle (DMSO), SAHA, HIT or HIT and SAHA. Tumor growth was determined and tumor necrosis, proliferation rate, apoptotic rate as well as vessel density were evaluated. Results: Here, we show that the combination of HIT and SAHA induced a significant delay of tumor growth through increased rate of apoptosis, increased expression of p53 and p21Waf1/Cip1, inhibition of proliferation and angiogenesis compared to tumors treated with HIT only. Conclusion: HIT and in particular the combination of HIT and histone deacetylase inhibition is a promising treatment strategy in OS and may be tested in clinical trials

    Role of PP2Cα in cell growth, in radio- and chemosensitivity, and in tumorigenicity

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    <p>Abstract</p> <p>Background</p> <p>PP2Cα is the representative member of the type 2C family of protein phosphatases, and it has recently been implicated in the regulation of p53-, TGFβ-, cyclin-dependent kinase- and apoptosis-signaling. To investigate the role of PP2Cα in cell growth and in radio- and chemosensitivity, wild type and PP2Cα siRNA-expressing MCF7 cells were subjected to several different viability and cell cycle analyses, both under basal conditions and upon treatment with radio- and chemotherapy. By comparing the growth of tumors established from both types of cells, we also evaluated the involvement of PP2Cα in tumorigenesis.</p> <p>Results</p> <p>It was found that knockdown of PP2Cα did not affect the proliferation, the clonogenic survival and the membrane integrity of MCF7 cells. In addition, it did not alter their radio- and chemosensitivity. For PP2Cα siRNA-expressing MCF7 cells, the number of cells in the G0/G1 phase of the cell cycle was reduced, the induction of the G1 block was attenuated, the number of cells in G2/M was increased, and the induction of the G2 block was enhanced. The tumorigenic potential of PP2Cα siRNA-expressing MCF7 cells was found to be higher than that of wild type MCF7 cells, and the in vivo proliferation of these cells was found to be increased.</p> <p>Conclusion</p> <p>Based on these findings, we conclude that PP2Cα is not involved in controlling cell growth and radio- and chemosensitivity in vitro. It does, however, play a role in the regulation of the cell cycle, in the induction of cell cycle checkpoints and in tumorigenesis. The latter notion implies that PP2Cα may possess tumor-suppressing properties, and it thereby sets the stage for more elaborate analyses on its involvement in the development and progression of cancer.</p

    Arrhythmogenic cardiomyopathy related DSG2 mutations affect desmosomal cadherin binding kinetics

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    Dieding M, Debus JD, Kerkhoff R, et al. Arrhythmogenic cardiomyopathy related DSG2 mutations affect desmosomal cadherin binding kinetics. Scientific Reports. 2017;7(1): 13791.Cadherins are calcium dependent adhesion proteins that establish the intercellular mechanical contact by bridging the gap to adjacent cells. Desmoglein-2 (Dsg2) is a specific cadherin of the cell-cell contact in cardiac desmosomes. Mutations in the DSG2-gene are regarded to cause arrhythmogenic (right ventricular) cardiomyopathy (ARVC) which is a rare but severe heart muscle disease. The molecular pathomechanisms of the vast majority of DSG2 mutations, however, are unknown. Here, we investigated the homophilic binding of wildtype Dsg2 and two mutations which are associated with ARVC. Using single molecule force spectroscopy and applying Jarzynski's equality we determined the kinetics and thermodynamics of Dsg2 homophilic binding. Notably, the free energy landscape of Dsg2 dimerization exposes a high activation barrier which is in line with the proposed strand-swapping binding motif. Although the binding motif is not directly affected by the mutations the binding kinetics differ significantly from the wildtype. Furthermore, we applied a dispase based cell dissociation assay using HT1080 cell lines over expressing Dsg2 wildtype and mutants, respectively. Our molecular and cellular results consistently demonstrate that Dsg2 mutations can heavily affect homophilic Dsg2 interactions. Furthermore, the full thermodynamic and kinetic description of Dsg2 dimerization provides a consistent model of the so far discussed homophilic cadherin binding

    Intensity-modulated radiotherapy for the management of primary and recurrent chordomas: a retrospective long-term follow-up study

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    Background: Chordomas have a high risk of recurrence. Radiotherapy (RT) is required as adjuvant therapy after resection. Sufficient radiation doses for local control (LC) can be achieved using either particle therapy, if this technology is available and feasible, or intensity-modulated radiotherapy. Materials and methods: 57 patients (age, 11.8–81.6 years) with chordomas of the skull base, spine and pelvis who received photon radiotherapy between 1995 and 2017 were enrolled in the study. Patients were treated at the time of initial diagnosis (68.4%) or during recurrence (31.6%). 44 patients received adjuvant radiotherapy and 13 received definitive radiotherapy. The median total dose to the physical target volume was 70 Gy equivalent dose in 2 Gy fractions (EQD2) (range: 54.7–82.5) in 22–36 fractions. Results: LC was 76.4%, 58.4%, 46.7% and 39.9% and overall survival (OS) was 98.3%, 89%, 76.9% and 47.9% after 1, 3, 5 and 10 years, respectively, with a median follow-up period of 6.5 years (range, 0.5–24.3 years). Age, dose and treatment concept (post-operative or definitive) were significant prognostic factors for OS. Primary treatment, macroscopic tumour at RT and size of the irradiated volume were statistically significant prognostic factors for LC. Conclusion: Photon treatment is a safe and effective treatment for chordomas if no particle therapy is available. The best results can be achieved against primary tumours if the application of curative doses is possible due to organs at risk in direct proximity. We recommend high-dose radiotherapy, regardless of the resection status, as part of the initial treatment of chordoma, using the high conformal radiation technique if particle therapy is not feasible

    Combination of suberoylanilide hydroxamic acid with heavy ion therapy shows promising effects in infantile sarcoma cell lines

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    <p>Abstract</p> <p>Introduction</p> <p>The pan-HDAC inhibitor (HDACI) suberoylanilide hydroxamic acid (SAHA) has previously shown to be a radio-sensitizer to conventional photon radiotherapy (XRT) in pediatric sarcoma cell lines. Here, we investigate its effect on the response of two sarcoma cell lines and a normal tissue cell line to heavy ion irradiation (HIT).</p> <p>Materials and methods</p> <p>Clonogenic assays after different doses of heavy ions were performed. DNA damage and repair were evaluated by measuring γH2AX via flow-cytometry. Apoptosis and cell cycle analysis were also measured via flow cytometry. Protein expression of repair proteins, p53 and p21 were measured using immunoblot analysis. Changes of nuclear architecture after treatment with SAHA and HIT were observed in one of the sarcoma cell lines via light microscopy after staining towards chromatin and γH2AX.</p> <p>Results</p> <p>Corresponding with previously reported photon data, SAHA lead to an increase of sensitivity to heavy ions along with an increase of DSB and apoptosis in the two sarcoma cell lines. In contrast, in the osteoblast cell line (hFOB 1.19), the combination of SAHA and HIT showed a significant radio-protective effect. Laser scanning microscopy revealed no significant morphologic changes after HIT compared to the combined treatment with SAHA. Immunoblot analysis revealed no significant up or down regulation of p53. However, p21 was significantly increased by SAHA and combination treatment as compared to HIT only in the two sarcoma cell lines - again in contrast to the osteoblast cell line. Changes in the repair kinetics of DSB p53-independent apoptosis with p21 involvement may be part of the underlying mechanisms for radio-sensitization by SAHA.</p> <p>Conclusion</p> <p>Our <it>in vitro </it>data suggest an increase of the therapeutic ratio by the combination of SAHA with HIT in infantile sarcoma cell lines.</p
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