7,414 research outputs found

    Subsolidus Phase Relationships in Si 3 N 4 –AlN–Rare-Earth Oxide Systems

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65239/1/j.1151-2916.1986.tb07349.x.pd

    The cathepsin K inhibitor AAE581 induces morphological changes in osteoclasts of treated patients

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    Inhibitors of Cathepsin K (Cat-K) are recognized as an interesting way to inhibit osteoclast (OC) activity. OCs from patients treated with the anticathepsin-K inhibitor AAE581 (balicatib) were found enlarged. They contained numerous vacuoles filled with tartrate resistant acid phosphatase (TRAcP), an intracellular enzyme that terminates the degradation of collagen internalized in OC transcytotic vesicles. In a phase 2 clinical study, 675 patients with postmenopausal osteoporosis received the Cat-K inhibitor AAE581 at 0, 5, 10, 25, or 50 mg/D during 1 year. Eleven patients had a transiliac bone biopsy, studied undecalcified. Histoenzymatic detection of TRAcP was used to identify and count OC number. The histomorphometrist was not aware of the randomization of patients at the time of analysis. OC were unstained in one patient because of a failure in the fixation protocol, but easily observable in the 10 remaining patients. Whatever the received dose, treated patients exhibited a characteristic aspect of the OC cytoplasm which appeared filled of deeply-stained brown vacuoles, making cells looking like bunches of grape. These round vacuoles, evidenced on TRAcP-stained sections, were due to the accumulation of intracytoplasmic TRAcP. This led to a moderate enlargement of the OC size when compared to a series of control osteoporotic patients. AAE581 did not induce OC apoptosis at any dosage but it modified OC morphology. Cat-K inhibition (inhibiting the extracellular collagen breakdown) is associated with a compensatory accumulation of intracellular TRAcP that could not be used to complete protein degradation. TRAcP is also known to be degraded by Cat-K. Microsc. Res. Tech., 2010

    Quantification of Dendritic Cells and Osteoclasts in the Bone Marrow of Patients with Monoclonal Gammopathy

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    The purpose of this study was to find histological clues for reliable differentiation between monoclonal gammopathy of undetermined significance (MGUS) and myeloma when clinical parameters are controversial. Differential appearance of dendritic cells and osteoclasts, two cell types developing from the monocytic lineage upon distinct cytokine activation profile, might be a useful approach. Bone and bone-marrow biopsies performed in 105 patients were studied using histomorphometry after identification of osteoclasts (by histochemical identification of tartrate resistant acid phosphatase) and dendritic cells (by immunohistochemical detection of the S-100 protein). Patients were classified by the World Health Organization criteria but histopathological criteria were more adapted to identify MGUS (53 cases), myeloma (46), B-cell lymphoma (six) since six myeloma were not correctly classified. Histomorphometry was compared to 15 control cases. The number of marrow dendritic cell was significantly increased with B-cell lymphoma >MGUS >myeloma > controls. Dendritic cell were often mixed with lymphoma cells. Myeloma had increased bone resorption with a high osteoclast number and moderate increase in dendritic cells. B-cell lymphomas had a considerable increase in dendritic cell but presented mononucleated osteoclasts. These findings can help in the classification of MGUS in the early stages of the disease and could help to propose preventive treatments

    Computed Microtomography of Bone Specimens for Rapid Analysis of Bone Changes Associated With Malignancy

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    Breast and prostate cancers are specially metastasizing to bone. Metastases from breast cancer usually exhibit a mixed osteolytic/osteosclerotic aspect, with osteolysis predominating. Osteosclerosis is a common finding in prostatic cancer although osteolysis occurs within the sclerotic lesions. B-cell malignancies (lymphoma, myeloma) are also associated with marked osteolysis. Histopathological examination of bone biopsies was used for the diagnosis of malignancies and, prior to embedding, microcomputed tomography (microCT) was done on the bone specimens. Patients (247) who presented either a bone metastasis, an overt myeloma, a lymphoma or a monoclonal gammopathy of undetermined significance were studied. All patients had a bone biopsy studied by 2D histomorphometry for the histopathology. During the fixation time, the bone cores were analyzed by microCT. On the 3D reconstructed models provided by microCT, signs of osteolysis/osteosclerosis were searched: excess of bone resorption, focal disorganization of microarchitecture, bone metaplasia, osteosclerosis. A strong agreement was obtained between histomorphometry and microCT results using Cohen\u27s kappa test (κ = 0.713). MicroCT identified excess bone resorption on trabecular surfaces when eroded surfaces were >10.5% by histomorphometry. MicroCT failed to identify some patients with smoldering myeloma or some lymphomas with microresorption. MicroCT data are obtained within 4 hr and suggest the malignant invasion of bone marrow when excess of bone resorption/formation is obtained. MicroCT can be used in the immediate postbiopsy period making possible a fast identification of malignancy. However these signs are not specific and must be confirmed by histopathological analysis

    A computational analysis of lower bounds for big bucket production planning problems

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    In this paper, we analyze a variety of approaches to obtain lower bounds for multi-level production planning problems with big bucket capacities, i.e., problems in which multiple items compete for the same resources. We give an extensive survey of both known and new methods, and also establish relationships between some of these methods that, to our knowledge, have not been presented before. As will be highlighted, understanding the substructures of difficult problems provide crucial insights on why these problems are hard to solve, and this is addressed by a thorough analysis in the paper. We conclude with computational results on a variety of widely used test sets, and a discussion of future research

    On the distribution of high-frequency stock market traded volume: a dynamical scenario

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    This manuscript reports a stochastic dynamical scenario whose associated stationary probability density function is exactly a previously proposed one to adjust high-frequency traded volume distributions. This dynamical conjecture, physically connected to superstatiscs, which is intimately related with the current nonextensive statistical mechanics framework, is based on the idea of local fluctuations in the mean traded volume associated to financial markets agents herding behaviour. The corroboration of this mesoscopic model is done by modelising NASDAQ 1 and 2 minute stock market traded volume

    A Study of the Formation of Single- and Double-Walled Carbon Nanotubes by a CVD Method

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    The reduction in H2/CH4 atmosphere of aluminum-iron oxides produces metal particles small enough to catalyze the formation of single-walled carbon nanotubes. Several experiments have been made using the same temperature profile and changing only the maximum temperature (800-1070 °C). Characterizations of the catalyst materials are performed using notably 57Fe Mo¨ssbauer spectroscopy. Electron microscopy and a macroscopical method are used to characterize the nanotubes. The nature of the iron species (Fe3+, R-Fe, ç-Fe-C, Fe3C) is correlated to their location in the material. The nature of the particles responsible for the high-temperature formation of the nanotubes is probably an Fe-C alloy which is, however, found as Fe3C by postreaction analysis. Increasing the reduction temperature increases the reduction yield and thus favors the formation of surface-metal particles, thus producing more nanotubes. The obtained carbon nanotubes are mostly single-walled and double-walled with an average diameter close to 2.5 nm. Several formation mechanisms are thought to be active. In particular, it is shown that the second wall can grow inside the first one but that subsequent ones are formed outside. It is also possible that under given experimental conditions, the smallest (<2 nm) catalyst particles preferentially produce double-walled rather than single-walled carbon nanotubes

    Toward an Anthropology of Mathematizing

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    This essay investigates the practical ways that artists and craftspeople cultivate mathematical sensibilities through their practical immersion in making and problem-solving. Mathematical sensibilities refer to skilled kinds of perception and heightened levels of attention and discernment regarding the qualitative properties of an object or composition, such as its shape, proportion, balance, symmetry, centredness, alignment or levelness. It also includes an ‘intuitive’ quantitative sense of volume, mass, weight, thickness and dimension. The objective of the investigation is not to describe the ways that a maker’s existing knowledge and training in formal mathematics is put into practice, but rather to elucidate the ways that their practices of making produce kinds of ‘non-formalised’, context-dependent mathematical understanding and knowledge. The starting point for exploring embodied mathematizing is therefore not from the cognitive or neurosciences, psychology or formal mathematics, it is argued, but rather from a phenomenological approach – ‘an opening on the world’ – that attends to person, materials, tools and other physical and qualitative features that make up the total environment in which activity unfolds

    Measurement of Strange Quark Contributions to the Nucleon's Form Factors at Q^2=0.230 (GeV/c)^2

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    We report on a measurement of the parity-violating asymmetry in the scattering of longitudinally polarized electrons on unpolarized protons at a Q2Q^2 of 0.230 (GeV/c)^2 and a scattering angle of \theta_e = 30^o - 40^o. Using a large acceptance fast PbF_2 calorimeter with a solid angle of \Delta\Omega = 0.62 sr the A4 experiment is the first parity violation experiment to count individual scattering events. The measured asymmetry is A_{phys} =(-5.44 +- 0.54_{stat} +- 0.27_{\rm sys}) 10^{-6}. The Standard Model expectation assuming no strangeness contributions to the vector form factors is A0=(6.30+0.43)106A_0=(-6.30 +- 0.43) 10^{-6}. The difference is a direct measurement of the strangeness contribution to the vector form factors of the proton. The extracted value is G^s_E + 0.225 G^s_M = 0.039 +- 0.034 or F^s_1 + 0.130 F^s_2 = 0.032 +- 0.028.Comment: 5 pages, 3 figures, submitted to Phys. Rev. Letters on Dec 11, 200

    Effects of Risedronate in Runx2 Overexpressing Mice, an Animal Model for Evaluation of Treatment Effects on Bone Quality and Fractures

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    Young mice overexpressing Runx2 specifically in cells of the osteoblastic lineage failed to gain bone mass and exhibited a dramatic increase in bone resorption, leading to severe osteopenia and spontaneous vertebral fractures. The objective of the current study was to determine whether treatment with a bisphosphonate (risedronate, Ris), which reduces fractures in postmenopausal as well as in juvenile osteoporosis, was able to improve bone quality and reduce vertebral fractures in mice overexpressing Runx2. Four-week-old female Runx2 mice received Ris at 2 and 10 μg/kg subcutaneously twice a week for 12 weeks. Runx2 and wild-type mice received vehicle (Veh) as control. We measured the number of new fractures by X-ray and bone mineral density (BMD) by DEXA. We evaluated bone quality by histomorphometry, micro-CT, and Fourier transform infrared imaging (FTIRI). Ris at 20 μg/kg weekly significantly reduced the average number of new vertebral fractures compared to controls. This was accompanied by significantly increased BMD, increased trabecular bone volume, and reduced bone remodeling (seen in indices of bone resorption and formation) in the vertebrae and femoral metaphysis compared to Runx2 Veh. At the femur, Ris also increased cortical thickness. Changes in collagen cross-linking seen on FTIRI confirmed that Runx2 mice have accelerated bone turnover and showed that Ris affects the collagen cross-link ratio at both forming and resorbing sites. In conclusion, young mice overexpressing Runx2 have high bone turnover-induced osteopenia and spontaneous fractures. Ris at 20 μg/kg weekly induced an increase in bone mass, changes in bone microarchitecture, and decreased vertebral fractures
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