The role of oncostatin M in animal and human connective tissue collagen turnover and its localization within the rheumatoid joint

OBJECTIVE: To study the interaction of interleukin-1alpha (IL-1alpha) and oncostatin M (OSM) in promoting cartilage collagen destruction. METHODS: Bovine, porcine, and human cartilage and human chondrocytes were studied in culture. The levels of collagenase (matrix metalloproteinase 1 [MMP-1]) and tissue inhibitor of metalloproteinases 1 (TIMP-1) were measured by bioassay and enzyme-linked immunosorbent assay (ELISA). The levels of OSM in rheumatoid synovial fluid were measured by ELISA. RESULTS: When combined with OSM, IL-1alpha, IL-1beta, and tumor necrosis factor alpha released proteoglycan and collagen from cartilage. OSM was the only member of the IL-6 family to have this effect. Human tendon also responded to IL-1alpha and OSM. OSM increased the production of MMP-1 and TIMP-1 but when combined with IL-1alpha, synergistically promoted MMP-1 production in human chondrocytes and synovial fibroblasts. High levels of OSM were found in human rheumatoid synovial fluids, and confocal microscopy showed that OSM was produced by macrophages in rheumatoid synovial tissue. CONCLUSION: These results highlight an important new mechanism by which there is irreversible loss of collagen from cartilage.     

A Monte Carlo investigation of the dual photopeak window scattercorrection method [SPECT]

Results from a Monte Carlo investigation of the dual photopeak window (DPW) scatter correction method are presented for point and extended sources of Tc-99m in both homogeneous and nonhomogeneous attenuating media. The DPW method uses the ratio of counts in two nonoverlapping energy windows within the photopeak region as input to a regression relation. A pixel-by-pixel estimate of the scatter in the summed windows is obtained and subtracted to yield an estimate of the primary. An approximate tenfold decrease in the scatter fraction and an excellent agreement with the shape of the true scatter distribution were observed     

Development of technologies aiding large-tissue engineering

Apoptosis associated oligonucleosomal fragmentation of DNA can result from the activation of endonucleases that exhibit different pH optima and are either sensitive or insensitive to divalent cations. DNA fragmentation due to activation of cation sensitive endonucleases occurs in the absence of a change in intracellular pH whereas intracellular acidification is a feature of apoptosis characterized by activation of cation insensitive acidic endonuclease. We have reported earlier that somatostatin (SST) induced DNA fragmentation and apoptosis is signaled in a receptor subtype selective manner uniquely via human somatostatin receptor subtype 3 (hSSTR3). In the present study we investigated the pH dependence and cation sensitivity of endonuclease induced in hSSTR3 expressing CHO-K1 cells by the SST agonist octreotide (OCT) and its effect on intracellular pH. We show that OCT induced apoptosis is associated with selective stimulation of a divalent cation insensitive acidic endonuclease. The intracellular pH of of cells undergoing OCT induced apoptosis was 0.9 pH units lower than that of control cells. The effect of OCT on endonuclease and pH was inhibited by orthovanadate as well as by pretreatment with pertussis toxin, suggesting that hSSTR3 initiated cytotoxic signaling is protein tyrosine phosphatase mediated and is G protein dependent. These findings suggest that intracellular acidification and activation of acidic endonuclease mediate wild type p53 associated apoptosis signaled by hormones acting via G protein coupled receptors.     

The implementation of technical practices and human factors of the toyota production system in different industries

The Toyota Production System (TPS) can result in huge benefits for companies and has been widely implemented around the world. Nevertheless, most adopters emphasize only the technical practices of the TPS, but neglect the critical role of human factors in the implementation of the TPS. Therefore, this study aims at developing an integrated TPS model that fully integrates the technical elements and human elements of the TPS with Total Quality Management (TQM) practices. An empirical study was conducted to confirm the causal relationships among these constructs. In the empirical study, questionnaires were mailed and e‐mailed to 620 companies that had implemented the TPS, and 151 of the completed questionnaires were valid. These 151 respondents were divided into eight categories. The results revealed that the implementation level of each construct was significantly different in each industry. The automobile and motorcycle industries have put a great deal of effort into the application of Humanity, Human Resource Management (HRM), and TQM practices and obtained good results. Other industries, however, ignored the implementation of HRM practices. The results also revealed that the early adopters enjoyed significant benefits from the implementation of the TPS, which led high‐tech companies to start adopting TPS practices and become lean enterprises. © 2011 Wiley Periodicals, Inc.     

Cardiac Oxidative Signaling and Physiological Hypertrophy in the Na/K-ATPase α1s/sα2s/s Mouse Model of High Affinity for Cardiotonic Steroids

The Na/K-ATPase is the specific receptor for cardiotonic steroids (CTS) such as ouabain and digoxin. At pharmacological concentrations used in the treatment of cardiac conditions, CTS inhibit the ion-pumping function of Na/K-ATPase. At much lower concentrations, in the range of those reported for endogenous CTS in the blood, they stimulate hypertrophic growth of cultured cardiac myocytes through initiation of a Na/K-ATPase-mediated and reactive oxygen species (ROS)-dependent signaling. To examine a possible effect of endogenous concentrations of CTS on cardiac structure and function in vivo, we compared mice expressing the naturally resistant Na/K-ATPase α1 and age-matched mice genetically engineered to express a mutated Na/K-ATPase α1 with high affinity for CTS. In this model, total cardiac Na/K-ATPase activity, α1, α2, and β1 protein content remained unchanged, and the cardiac Na/K-ATPase dose–response curve to ouabain shifted to the left as expected. In males aged 3–6 months, increased α1 sensitivity to CTS resulted in a significant increase in cardiac carbonylated protein content, suggesting that ROS production was elevated. A moderate but significant increase of about 15% of the heart-weight-to-tibia-length ratio accompanied by an increase in the myocyte cross-sectional area was detected. Echocardiographic analyses did not reveal any change in cardiac function, and there was no fibrosis or re-expression of the fetal gene program. RNA sequencing analysis indicated that pathways related to energy metabolism were upregulated, while those related to extracellular matrix organization were downregulated. Consistent with a functional role of the latter, an angiotensin-II challenge that triggered fibrosis in the α1^r/rα2^s/s mouse failed to do so in the α1^s/sα2^s/s. Taken together, these results are indicative of a link between circulating CTS, Na/K-ATPase α1, ROS, and physiological cardiac hypertrophy in mice under baseline laboratory conditions.     

Thermal analysis of polymer–water interactions and their relation to gas hydrate inhibition

Gas hydrates formed in oil production pipelines are crystalline solids where hydrocarbon gas molecules such as methane, propane, and their mixtures are trapped in a cagelike structure by hydrogen‐bonded water molecules to form undesirable plugs. Methanol and glycol are currently used to prevent these plugs via thermodynamic inhibition. Small amounts of water‐soluble polymers may provide an alternate approach for preventing gas hydrates. In this study, we expand the fundamental understanding of water–polymer systems with differential scanning calorimetry. Nonfreezable bound water was used to quantify polymer–water interactions and relate them to the chemical structure for a series of polymers, including acrylamides, cyclic lactams, and n‐vinyl amides. For good interactions, the water structure needs to be stabilized through hydrophobic interactions. An increased hydrophobicity of the pendant group also appears to favor polymer performance as a gas hydrate inhibitor. Good inhibitors, such as poly(diethyl acrylamide) and poly(N‐vinyl caprolactam), also show higher heat capacities, which indicate higher hydrophobicity, than poor performers such as polyzwitterions, in which hydrophilicity dominated. The phase behavior and thermodynamic properties of dilute polymer solutions were also evaluated through measurements of the heat of demixing and lower critical solution temperature. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 2642–2653, 2007     

Thermal Shock Failure in Thick Epoxy Coatings

In this paper we describe an apparatus for reproducibly measuring thermal shock resistance of thick polymer layers bonded to metals. The thermal shock behavior is discussed in terms of epoxy samples bonded to an aluminum substrate. It was found that both high resin toughness and low resin thermal expansion coefficient improved thermal shock resistance of thick coatings, but only a sample containing 60wt. % glass beads did not develop a failure crack. Effects of sample thickness, temperature gradient, and resin composition on thermal shock behavior are discussed.     

Exploiting Batch Processing on Streaming Architectures to Solve 2D Elliptic Finite Element Problems: A Hybridized Discontinuous Galerkin (HDG) Case Study

Numerical methods for elliptic partial differential equations (PDEs) within both continuous and hybridized discontinuous Galerkin (HDG) frameworks share the same general structure: local (elemental) matrix generation followed by a global linear system assembly and solve. The lack of inter-element communication and easily parallelizable nature of the local matrix generation stage coupled with the parallelization techniques developed for the linear system solvers make a numerical scheme for elliptic PDEs a good candidate for implementation on streaming architectures such as modern graphical processing units (GPUs). We propose an algorithmic pipeline for mapping an elliptic finite element method to the GPU and perform a case study for a particular method within the HDG framework. This study provides comparison between CPU and GPU implementations of the method as well as highlights certain performance-crucial implementation details. The choice of the HDG method for the case study was dictated by the computationally-heavy local matrix generation stage as well as the reduced trace-based communication pattern, which together make the method amenable to the fine-grained parallelism of GPUs. We demonstrate that the HDG method is well-suited for GPU implementation, obtaining total speedups on the order of 30–35 times over a serial CPU implementation for moderately sized problems.     

Simulation of Climate Change Effects on Hydropower Operations in Mountain Headwater Lakes,New Zealand

Future climate change is expected to have wide ranging impacts on the hydrology of mountain rivers because of changes in the magnitudes and timing of rain and snow, as well as the significant spatial variability of topography and other catchment characteristics. In New Zealand, hydropower generation in mountain basins is the primary source of electricity and renewable energy resource in the country. The goal of this study was to simulate and evaluate the potential effects of climate change on hydropower operations in three mountain headwater lakes (lakes Pukaki, Tekapo, and Ohau) in the Upper Waitaki Basin of the central South Island. The TopNet hydrological model was used to estimate catchment runoff and lake inflows based on the 1990s (baseline), 2040s, and 2090s periods. Average temperature and precipitation results from an ensemble of 12 Global Circulation Models based on the IPCC 4th Assessment Report A1B emissions scenario were used as input to TopNet. Linked hydropower lake water balance models were developed and used to simulate hydropower operations including discharge, hydroelectric power generation, and spill based on TopNet future inflow predictions, projected electricity demand, and lake storage and outflow characteristics. Our results indicate that annual lake inflows increase under future climate scenarios, but that there are seasonal effects with increasing flows in winter and early spring, and summer flows decreasing somewhat as a result of increasing temperatures and greater winter rain with less snow. Although overall hydropower generation can increase with the increasing flows and projected electricity demand, the seasonal changes result in demand being met in winter and spring with potential shortfalls in summer and autumn. Maximum annual generation can be achieved for some generating stations, but generation will decrease at other stations and more spill will likely be required through the 2090s because of the seasonal changes. Therefore flood and drought risk could also increase for downstream areas. Results also indicate that by the 2090s electricity demand could exceed generation capacity for these headwater lakes. Copyright © 2016 John Wiley & Sons, Ltd.     

Test-data generation for control coverage by proof

Many tools can check if a test set provides control coverage; they are, however, of little or no help when coverage is not achieved and the test set needs to be completed. In this paper, we describe how a formal characterisation of a coverage criterion can be used to generate test data; we present a procedure based on traditional programming techniques like normalisation, and weakest precondition calculation. It is a basis for automation using an algebraic theorem prover. In the worst situation, if automation fails to produce a specific test, we are left with a specification of the compliant test sets. Many approaches to model-based testing rely on formal models of a system under test. Our work, on the other hand, is not concerned with the use of abstract models for testing, but with coverage based on the text of programs.