ADAMs, Osteoclastogenesis and Bone Destruction in the Loosening of the Totally Replaced Hip

Total hip replacement is the golden standard treatment for severe osteoarthritis refractory for conservative treatment. Aseptic loosening and osteolysis are the major long-term complications after total hip replacement. Foreign body giant cells and osteoclasts are locally formed around aseptically loosening implants from precursor cells by cell fusion. When the foreign body response is fully developed, it mediates inflammatory and destructive host responses, such as collagen degradation. In the present study, it was hypothesized that the wear debris and foreign body inflammation are the forces driving local osteoclast formation, peri-implant bone resorption and enhanced tissue remodeling. Therefore the object was to characterize the eventual expression and the role of fusion molecules, ADAMs (an abbreviation for A Disintegrin And Metalloproteinase, ADAM9 and ADAM12) in the fusion of progenitor cells into multinuclear giant cells. For generation of such cells, activated macrophages trying to respond to foreign debris play an important role. Matured osteoclasts together with activated macrophages mediate bone destruction by secreting protons and proteinases, including matrix metalloproteinases (MMPs) and cathepsin K. Thus this study also assessed collagen degradation and its relationship to some of the key collagenolytic proteinases in the aggressive synovial membrane-like interface tissue around aseptically loosened hip replacement implants. ADAMs were found in the interface tissues of revision total hip replacement patients. Increased expression of ADAMs at both transcriptional and translational levels was found in synovial membrane-like interface tissue of revision total hip replacement (THR) samples compared with that in primary THR samples. These studies also demonstrate that multinucleate cell formation from monocytes by stimulation with macrophage-colony stimiulating factor (M-CSF) and receptor activator of nuclear factor kappa B ligand (RANKL) is characterized by time dependent changes of the proportion of ADAMs positive cells. This was observed both in the interface membrane in patients and in two different in vitro models. In addition to an already established MCS-F and RANKL driven model, a new virally (parainfluenza 2) driven model (of human salivary adenocarcinoma (HSY) cells or green monkey kidney (GMK) cells) was developed to study various fusion molecules and their role in cell fusion in general. In interface membranes, collagen was highly degraded and collagen degradation significantly correlated with the number of local cells containing collagenolytic enzymes, particularly cathepsin K. As a conclusion, fusion molecules ADAM9 and ADAM12 seem to be dynamically involved in cell-cell fusion processes and multinucleate cell formation. The highly significant correlation between collagen degradation and collagenolytic enzymes, particularly cathepsin K, indicates that the local acidity of the interface membrane in the pathologic bone and soft tissue destruction. This study provides profound knowledge about cell fusion and mechanism responsible for aseptic loosening as well as increases knowledge helpful for prevention and treatment.The formation of multinucleated cells such as myotubes, macrophage-derived giant cells and osteoclasts is the result of cell-cell fusion of mononuclear precursors. The ADAMs (an acronym for A Disintegrin And Metalloproteinase) is a family of multifunctional proteins that exhibit a significant similarity with snake venom metalloproteases and are involved in cell-cell fusion processes. As fusion molecules, ADAM12 and ADAM9 are involved in cell-cell fusion processes and participate in myoblast fusion and, also in osteoclast fusion. The aims of the proposed project are to characterize ADAMs expression and regulations both in the interface membrane of total hip replacement in the patients and in in vitro cell model. Further study of the relationship between the structure and function of ADAMs may provide profound knowledge of its role in cell fusion, and even one attractive therapeutic target

4-(4-Chloro­phen­yl)-5-(4-nitro­phen­yl)-3-phenyl-4H-1,2,4-triazole

The title compound, C20H13ClN4O2, was synthesized by the condensation of 4-nitro­benzohydrazide and N-(4-chlorophen­yl)­benzimidoyl chloride in N,N-dimethyl­acetamide. The asymmetric unit contains two independent mol­ecules. In one molecule, the triazole ring is oriented at dihedral angles of 23.1 (5), 85.4 (1) and 10.5 (1)° with respect to the phenyl, chlorophenyl and nitrophenyl rings, respectively. In the other molecule, the corresponding dihedral angles are 29.8 (9), 73.4 (7) and 16.4 (3)°

BIM-based space management system for operation and maintenance phase in educational office buildings

Lists and floor plans have been widely adopted as space management tools for educational office buildings. However, the two-dimensional floor plans fail to present the indoor complexity, which hinders users from intuitively observing the indoor equipment arrangements and adapting to the indoor environment within a short time. Meanwhile, insufficient research has been conducted on space management tools regarding building indoor navigation. A Building Information Modeling Space Management (BIMSM) system was proposed in this study based on BIM. This system is comprised of two components, i.e. indoor space allocation management and indoor path navigation. The real-time space usage can be queried and user demands may be matched with available space by applying the Space Usage Analysis (SUA) theory. After the establishment of indoor maps, an improved A* algorithm is used to provide smooth navigation paths, and the visualization of such paths can be provided in mobile terminals. The BIMSM system was applied in an office building in a university in Shanghai, China. In this case study, the overall user satisfaction reached 91.6% by greatly reducing space arrangement failures. The time indoor navigation took outperformed that based on the traditional A* algorithm, with the search efficiency increasing 5.28%. First published online 17 December 201

Validation of a simple dynamic thermal performance characterization model based on the piston flow concept for flat-plate solar collectors

A simple dynamic characterization model of flat-plate solar collectors based on the piston flow concept is used both to identify the collector characteristic parameters and to predict the dynamic thermal performance. The heat transport time originally defined as (1 − e−1)−1τC by Amrizal et al. (2012) for the model turns out to be the collector static response time constant τC by analytical derivation. The nonlinear least squares method is applied to determine the characteristic parameters of a flat-plate solar air collector previously tested by the authors. Then the obtained parameters are used to predict the dynamic behavior of the collector outlet temperature. The model coefficients particularly c3 in the simple dynamic characterization model are examined by the collector dynamic prediction under variable meteorological conditions. Meanwhile, the prediction accuracy of the simple dynamic model based on the first-order difference method is compared to that of the numerical solution of the collector ordinary differential equation (ODE) model using the fourth-order Runge-Kutta method. The improved thermal inertia model (TIM) on the basis of closed-form solution presented by Deng et al. (2016a) is also considered. The results show that the prediction performance of the simple dynamic model is nearly as accurate as the ODE numerical solution and the TIM by Deng et al. (2016a) except some special conditions such as sharply changed solar irradiance and collector inlet temperature

Evaluating the Risk of Roof Fall in Phosphate Mines: Case Study of the Shanshuya Phosphate Mine in China

AbstractRoof fall in phosphate mines seriously endangers the safety of the mining activity. In this paper, the risk of roof fall occurring in phosphate mines is evaluated using the underground phosphate mine in Shanshuya, China, as an engineering background. The factors affecting roof fall in phosphate mines are analyzed, and an index system for evaluating the risk of roof fall in phosphate mine is established. Four evaluation models are employed to evaluate the risk of roof fall occurring: a set pair analysis model based on combination weights, a comprehensive fuzzy model based on hierarchical analysis, an approximately ideal ranking model based on entropy weight, and a gray relational analysis model. The evaluation results of the first two models are moderate risk with a bias toward intense risk. And the evaluation results of the last two models are slight risk with a bias toward moderate risk and moderate risk with a bias toward slight risk, respectively. The suitability of each of the evaluation models is analyzed which reveals that the evaluation results obtained using the different models are inconsistent. A combined evaluation method based on the four original evaluation models is subsequently proposed. Application of the combined evaluation method to the Shanshuya phosphate mine produces results that the roof fall risk is moderate with a bias toward slight risk. It is consistent with the actual situation in this phosphate mine. The results of the study can be used to provide technical support to engineers evaluating the risk of roof fall occurring in similar phosphate mines

Distinguishing Emission-Associated Ambient Air PM2.5 Concentrations and Meteorological Factor-Induced Fluctuations

Although PM2.5 (particulate matter with aerodynamic diameters less than 2.5 μm) in the air originates from emissions, its concentrations are often affected by confounding meteorological effects. Therefore, direct comparisons of PM2.5 concentrations made across two periods, which are commonly used by environmental protection administrations to measure the effectiveness of mitigation efforts, can be misleading. Here, we developed a two-step method to distinguish the significance of emissions and meteorological factors and assess the effectiveness of emission mitigation efforts. We modeled ambient PM2.5 concentrations from 1980 to 2014 based on three conditional scenarios: realistic conditions, fixed emissions, and fixed meteorology. The differences found between the model outputs were analyzed to quantify the relative contributions of emissions and meteorological factors. Emission-related gridded PM2.5 concentrations excluding the meteorological effects were predicted using multivariate regression models, whereas meteorological confounding effects on PM2.5 fluctuations were characterized by probabilistic functions. When the regression models and probabilistic functions were combined, fluctuations in the PM2.5 concentrations induced by emissions and meteorological factors were quantified for all model grid cells and regions. The method was then applied to assess the historical and future trends of PM2.5 concentrations and potential fluctuations on global, national, and city scales. The proposed method may thus be used to assess the effectiveness of mitigation actions

Animal3D: A Comprehensive Dataset of 3D Animal Pose and Shape

Accurately estimating the 3D pose and shape is an essential step towards understanding animal behavior, and can potentially benefit many downstream applications, such as wildlife conservation. However, research in this area is held back by the lack of a comprehensive and diverse dataset with high-quality 3D pose and shape annotations. In this paper, we propose Animal3D, the first comprehensive dataset for mammal animal 3D pose and shape estimation. Animal3D consists of 3379 images collected from 40 mammal species, high-quality annotations of 26 keypoints, and importantly the pose and shape parameters of the SMAL model. All annotations were labeled and checked manually in a multi-stage process to ensure highest quality results. Based on the Animal3D dataset, we benchmark representative shape and pose estimation models at: (1) supervised learning from only the Animal3D data, (2) synthetic to real transfer from synthetically generated images, and (3) fine-tuning human pose and shape estimation models. Our experimental results demonstrate that predicting the 3D shape and pose of animals across species remains a very challenging task, despite significant advances in human pose estimation. Our results further demonstrate that synthetic pre-training is a viable strategy to boost the model performance. Overall, Animal3D opens new directions for facilitating future research in animal 3D pose and shape estimation, and is publicly available.Comment: 11 pages, 5 figures, link to the dataset: https://xujiacong.github.io/Animal3D

Cytochalasin E, a potential agent for anti-glioma therapy, efficiently induces U87 human glioblastoma cell death

Glioblastoma is one of the most malignant brain tumors. Current treatments for glioblastoma usually make poor responses, and novel treatment strategies are extremely imperative. Cytochalasin E was reported to inhibit angiogenesis and tumor growth in some studies, but its effects on gliomas are still unknown. In this study, we found cytochalasin E inhibits U87 human glioblastoma cell growth in a very low concentration range of 10-8 to 10-6 M in a time and concentration dependent manner, and the IC50 were 1.17 ± 0.32 × 10-7 M for 48 h treatment, 6.65 ± 1.12 × 10-8 M for 72 h and 3.78 ± 1.30 × 10-8 M for 96 h. We also found cytochalasin E induces cell-cycle G2/M phase arrest (72 h-treatment of 10-6 M cytochalasin E caused 56.2 ± 6.1 % cells arrest in G2/M phase) and cell apoptosis (96 h-treatment of 10-6 M cytochalasin E induced 24.1 ± 4.2 % cells apoptosis). Thus, cytochalasin E is proposed as a potential agent for glioblastoma chemotherapy.Colegio de Farmacéuticos de la Provincia de Buenos Aire