505 research outputs found

    Tiede, Mark

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    anti-FcγRIIB (CD32) antibodies differentially modulate murine FVIII-specific recall response in vitro

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    Fc gamma receptors (FcγRs) for IgG regulate adaptive immune responses by modulating activating and inhibitory signaling pathways within immune cells. Data from a hemophilia A mouse model demonstrate that genetic deletion or blockade of the inhibitory FcγR (CD32) suppresses the formation of antibody secreting cells (ASCs) in vitro. Mechanisms preventing the FVIII-specific recall response, however, remain unclear. Here, the potential role of CD32 inhibition was studied by differentially modulating receptor activity with selected anti-CD32 monoclonal antibodies (mAbs). Splenocytes from immunized FVIII-/- mice were re-stimulated with FVIII in the absence or presence of different anti-CD32 mAbs over 6 days. At day 6, cytokine release was quantified from cell culture supernatant and the formation of FVIII-specific ASCs assessed. Binding of FVIII-containing immune complexes (F8-ICs) to bone marrow derived dendritic cells (BMdDCs) was also investigated. The antagonistic CD32 mAb AT128 suppressed the formation of FVIII-specific ASCs and reduced secretion of IFN-γ and IL-10. In contrast, the agonistic mAbs AT130-2 and AT130-5, and their F(ab')2 fragments, allowed the formation of FVIII-specific ASCs, even though the full IgG of AT130-2 reduced binding of F8-ICs to CD32. Data suggest that an inhibitory signal is transmitted when F8-ICs bind to CD32 and that this signal is required during memory B cell (MBC) activation to support formation of FVIII-specific ASCs. If the inhibitory signal is lacking due to CD32 deletion or blockade with antagonistic anti-CD32 mAbs, FVIII-specific T cell stimulation and ASC formation are suppressed, whereas agonistic stimulation of CD32 restores T cell stimulation and ASC formation

    Articulatory effects of vowel context on fricatives: an MRI study

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    Magnetic resonance imaging (MRI) is increasingly used in speech production research, particularly to obtain three-dimensional images of sustainable sounds such as fricatives or vowels. However, acoustic studies of fricatives [Shadle et al., Proc. ETRW, 193-196 (1996)] have shown that the spectral shape varies with vowel context, with the amount of variation depending on the fricative. This study, therefore, uses MRI to study the articulatory correlates of vowel context effects on fricatives. Two subjects (male French, female American English) for whom a large acoustic, aerodynamic, and articulatory database of fricatives already existed, were studied. Three different imaging methods were used that varied in acquisition time, image quality, and image extent: midsagittal turbo-flash (2 s), midsagittal spin-echo (15 s), and full coronal and axial spin-echo scans (approx. 2 min each). The subjects uttered the fricatives [f, theta, s, S] in vowel contexts [a, i, u]. Results indicate that not only are vowel context effects preserved in the longer duration images, they are often heightened. [f] showed the greatest variation in configuration with vowel context. Comparison to acoustic results and other MRI studies will be presented. [Work supported by ATR HIP Laboratories, while the first author was an invited researcher at ATR.]

    Pressure based segmentation in volumetric images

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    Analysing Roman coins found in archaeology sites has been traditionally done manually by an operator using volumetric image slices provided by a computed tomography scanner. In order to automate the counting process, a good segmentation for the coins has to be achieved to separate the touching surfaces of the coins. Separating touching surfaces in volumetric images has not yet attracted much attention. In this paper we propose a new method based on using a form of pressure to separate the intersecting surfaces. We analogise the background of the image to be filled with an ideal gas. The pressure at a point has an inverse relationship with the volume of homogeneous material surrounding it. By studying the pressure space, the locations of intersecting surfaces are highlighted and encouraging segmentation results are achieved. Our analysis concerns a selection of images, naturally demonstrating success, together with an analysis of the new technique’s sensitivity to noise
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