1,125 research outputs found

    Role of the Osteoblast Lineage in the Bone Marrow Hematopoietic Niches

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    An experimental investigation of chatter effects on tool life

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    Tool wear is one of the most important considerations in machining operations as it affects surface quality and integrity, productivity and cost. The most commonly used model for tool life analysis is the one proposed by F.W. Taylor about a century ago. Although the extended form of this equation includes the effects of important cutting conditions on tool wear, tool life studies are mostly performed under stable cutting conditions where the effect of chatter vibrations are not considered. This paper presents an empirical attempt to understand tool life under vibratory cutting conditions. Tool wear data are collected in turning and milling on different work materials under stable and chatter conditions. The effects of cutting conditions as well as severity of chatter on tool life are analyzed. The results indicate significant reduction in tool life due to chatter as expected. They also show that the severity of chatter, and thus the vibration amplitude, strongly reduces the life of cutting tools. These results can be useful in evaluating the real cost of chatter by including the reduced tool life. They can also be useful in justifying the cost of chatter suppression and more rigid machining systems

    Cross-presentation of Disialoganglioside GD3 to Natural Killer T Cells

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    GD3, a ganglioside expressed on human melanoma, can be recognized by the humoral immune system. In this paper, we demonstrate that immunizing mice with the human melanoma cell line SK-MEL-28 (GD3+ GM2− CD1−) or with syngeneic APCs loaded with GD3 can induce a GD3-reactive natural killer T (NKT) cell response. GD3-reactive NKT cells were detected among splenocytes of immunized mice at frequencies of ∼1:2,000 both by ELISPOT and GD3-loaded mouse CD1d tetramer analysis. GD3-reactive NKT cells did not react with GM2, a closely related ganglioside, and were not detectable in unimmunized mice. GD3-reactive NKT cells initially produced IL-4 and IFN-γ followed by IL-10. They were CD1d restricted in that reactivity was abrogated when APCs were blocked with anti-CD1d monoclonal antibody before being loaded with GD3 or when APCs from CD1d knockout mice were used. Because SK-MEL-28 does not express any isoform of human CD1, GD3 must be cross-presented by murine APCs in vivo. This is the first analysis of a natural ligand for mouse NKT cells and the first definitive paper of cross-presentation to NKT cells. This could be a mechanism for NKT cell recognition of tumor gangliosides in CD1− tumors

    Efficient metallic spintronic emitters of ultrabroadband terahertz radiation

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    Terahertz electromagnetic radiation is extremely useful for numerous applications such as imaging and spectroscopy. Therefore, it is highly desirable to have an efficient table-top emitter covering the 1-to-30-THz window whilst being driven by a low-cost, low-power femtosecond laser oscillator. So far, all solid-state emitters solely exploit physics related to the electron charge and deliver emission spectra with substantial gaps. Here, we take advantage of the electron spin to realize a conceptually new terahertz source which relies on tailored fundamental spintronic and photonic phenomena in magnetic metal multilayers: ultrafast photo-induced spin currents, the inverse spin-Hall effect and a broadband Fabry-P\'erot resonance. Guided by an analytical model, such spintronic route offers unique possibilities for systematic optimization. We find that a 5.8-nm-thick W/CoFeB/Pt trilayer generates ultrashort pulses fully covering the 1-to-30-THz range. Our novel source outperforms laser-oscillator-driven emitters such as ZnTe(110) crystals in terms of bandwidth, terahertz-field amplitude, flexibility, scalability and cost.Comment: 18 pages, 10 figure

    Bone CLARITY: Clearing, imaging, and computational analysis of osteoprogenitors within intact bone marrow

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    Bone tissue harbors unique and essential physiological processes, such as hematopoiesis, bone growth, and bone remodeling. To enable visualization of these processes at the cellular level in an intact environment, we developed “Bone CLARITY,” a bone tissue clearing method. We used Bone CLARITY and a custom-built light-sheet fluorescence microscope to detect the endogenous fluorescence of Sox9-tdTomato+ osteoprogenitor cells in the tibia, femur, and vertebral column of adult transgenic mice. To obtain a complete distribution map of these osteoprogenitor cells, we developed a computational pipeline that semiautomatically detects individual Sox9-tdTomato+ cells in their native three-dimensional environment. Our computational method counted all labeled osteoprogenitor cells without relying on sampling techniques and displayed increased precision when compared with traditional stereology techniques for estimating the total number of these rare cells. We demonstrate the value of the clearing-imaging pipeline by quantifying changes in the population of Sox9-tdTomato–labeled osteoprogenitor cells after sclerostin antibody treatment. Bone tissue clearing is able to provide fast and comprehensive visualization of biological processes in intact bone tissue

    Transmission Dynamics of Extended-Spectrum β-lactamase-Producing Enterobacteriaceae in the Tertiary Care Hospital and the Household Setting

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    Transmission of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae in households outweighs nosocomial dissemination in the non-outbreak setting. Importation of ESBL producers into the hospitals is as frequent as transmission during hospital stay. ESBL-Klebsiella pneumoniae might be more efficiently transmitted within the hospital than ESBL-Escherichia col

    Re-establishing glacier monitoring in Kyrgyzstan and Uzbekistan, Central Asia

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    Glacier mass loss is among the clearest indicators of atmospheric warming. The observation of these changes is one of the major objectives of the international climate monitoring strategy developed by the Global Climate Observing System (GCOS). Long-term glacier mass balance measurements are furthermore the basis for calibrating and validating models simulating future runoff of glacierised catchments. This is essential for Central Asia, which is one of the driest continental regions of the Northern Hemisphere. In the highly populated regions, water shortage due to decreased glacierisation potentially leads to pronounced political instability, drastic ecological changes and endangered food security. As a consequence of the collapse of the former Soviet Union, however, many valuable glacier monitoring sites in the Tien Shan and Pamir Mountains were abandoned. In recent years, multinational actors have re-established a set of important in situ measuring sites to continue the invaluable long-term data series. This paper introduces the applied monitoring strategy for selected glaciers in the Kyrgyz and Uzbek Tien Shan and Pamir, highlights the existing and the new measurements on these glaciers, and presents an example for how the old and new data can be combined to establish multi-decadal mass balance time series. This is crucial for understanding the impact of climate change on glaciers in this region

    Pulse Oximetry as an Aid to Rule Out Pneumonia among Patients with a Lower Respiratory Tract Infection in Primary Care.

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    Guidelines recommend chest X-rays (CXRs) to diagnose pneumonia and guide antibiotic treatment. This study aimed to identify clinical predictors of pneumonia that are visible on a chest X-ray (CXR+) which could support ruling out pneumonia and avoiding unnecessary CXRs, including oxygen saturation. A secondary analysis was performed in a clinical trial that included patients with suspected pneumonia in Swiss primary care. CXRs were reviewed by two radiologists. We evaluated the association between clinical signs (heart rate > 100/min, respiratory rate ≥ 24/min, temperature ≥ 37.8 °C, abnormal auscultation, and oxygen saturation < 95%) and CXR+ using multivariate analysis. We also calculated the diagnostic performance of the associated clinical signs combined in a clinical decision rule (CDR), as well as a CDR derived from a large meta-analysis (at least one of the following: heart rate > 100/min, respiratory rate ≥ 24/min, temperature ≥ 37.8 °C, or abnormal auscultation). Out of 469 patients from the initial trial, 107 had a CXR and were included in this study. Of these, 26 (24%) had a CXR+. We found that temperature and oxygen saturation were associated with CXR+. A CDR based on the presence of either temperature ≥ 37.8 °C and/or an oxygen saturation level < 95% had a sensitivity of 69% and a negative likelihood ratio (LR-) of 0.45. The CDR from the meta-analysis had a sensitivity of 92% and an LR- of 0.37. The addition of saturation < 95% to this CDR increased the sensitivity (96%) and decreased the LR- (0.21). In conclusion, this study suggests that pulse oximetry could be added to a simple CDR to decrease the probability of pneumonia to an acceptable level and avoid unnecessary CXRs

    BMP signaling negatively regulates bone mass through sclerostin by inhibiting the canonical Wnt pathway

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    Bone morphogenetic proteins (BMPs) are known to induce ectopic bone. However, it is largely unknown how BMP signaling in osteoblasts directly regulates endogenous bone. This study investigated the mechanism by which BMP signaling through the type IA receptor (BMPR1A) regulates endogenous bone mass using an inducible Cre-loxP system. When BMPR1A in osteoblasts was conditionally disrupted during embryonic bone development, bone mass surprisingly was increased with upregulation of canonical Wnt signaling. Although levels of bone formation markers were modestly reduced, levels of resorption markers representing osteoclastogenesis were severely reduced, resulting in a net increase in bone mass. The reduction of osteoclastogenesis was primarily caused by Bmpr1a-deficiency in osteoblasts, at least through the RANKL-OPG pathway. Sclerostin (Sost) expression was downregulated by about 90% and SOST protein was undetectable in osteoblasts and osteocytes, whereas the Wnt signaling was upregulated. Treatment of Bmpr1a-deficient calvariae with sclerostin repressed the Wnt signaling and restored normal bone morphology. By gain of Smad-dependent BMPR1A signaling in mice, Sost expression was upregulated and osteoclastogenesis was increased. Finally, the Bmpr1a-deficient bone phenotype was rescued by enhancing BMPR1A signaling, with restoration of osteoclastogenesis. These findings demonstrate that BMPR1A signaling in osteoblasts restrain endogenous bone mass directly by upregulating osteoclastogenesis through the RANKL-OPG pathway, or indirectly by downregulating canonical Wnt signaling through sclerostin, a Wnt inhibitor and a bone mass mediator
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