921 research outputs found

    Length functions on currents and applications to dynamics and counting

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    The aim of this (mostly expository) article is twofold. We first explore a variety of length functions on the space of currents, and we survey recent work regarding applications of length functions to counting problems. Secondly, we use length functions to provide a proof of a folklore theorem which states that pseudo-Anosov homeomorphisms of closed hyperbolic surfaces act on the space of projective geodesic currents with uniform north-south dynamics.Comment: 35pp, 2 figures, comments welcome! Second version: minor corrections. To appear as a chapter in the forthcoming book "In the tradition of Thurston" edited by V. Alberge, K. Ohshika and A. Papadopoulo

    High-mobility group box protein 1 (HMGB1): an alarmin mediating the pathogenesis of rheumatic disease

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    High-mobility group box protein 1 (HMGB1) is a non-histone nuclear protein that has a dual function. Inside the cell, HMGB1 binds DNA, regulating transcription and determining chromosomal architecture. Outside the cell, HMGB1 can serve as an alarmin to activate the innate system and mediate a wide range of physiological and pathological responses. To function as an alarmin, HMGB1 translocates from the nucleus of the cell to the extra-cellular milieu, a process that can take place with cell activation as well as cell death. HMGB1 can interact with receptors that include RAGE (receptor for advanced glycation endproducts) as well as Toll-like receptor-2 (TLR-2) and TLR-4 and function in a synergistic fashion with other proinflammatory mediators to induce responses. As shown in studies on patients as well as animal models, HMGB1 can play an important role in the pathogenesis of rheumatic disease, including rheumatoid arthritis, systemic lupus erythematosus, and polymyositis among others. New approaches to therapy for these diseases may involve strategies to inhibit HMGB1 release from cells, its interaction with receptors, and downstream signaling

    Estimation of an image derived input function with MR-defined carotid arteries in FDG-PET human studies using a novel partial volume correction method

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    Kinetic analysis of (18)F-fluorodeoxyglucose positron emission tomography data requires an accurate knowledge the arterial input function. The gold standard method to measure the arterial input function requires collection of arterial blood samples and is an invasive method. Measuring an image derived input function is a non-invasive alternative but is challenging due to partial volume effects caused by the limited spatial resolution of the positron emission tomography scanners. In this work, a practical image derived input function extraction method is presented, which only requires segmentation of the carotid arteries from MR images. The simulation study results showed that at least 92% of the true intensity could be recovered after the partial volume correction. Results from 19 subjects showed that the mean cerebral metabolic rate of glucose calculated using arterial samples and partial volume corrected image derived input function were 26.9 and 25.4 mg/min/100 g, respectively, for the grey matter and 7.2 and 6.7 mg/min/100 g for the white matter. No significant difference in the estimated cerebral metabolic rate of glucose values was observed between arterial samples and corrected image derived input function (p > 0.12 for grey matter and white matter). Hence, the presented image derived input function extraction method can be a practical alternative to noninvasively analyze dynamic (18)F-fluorodeoxyglucose data without the need for blood sampling

    Towards Accurate Partial Volume Correction - Perturbation for SPECT Resolution Estimation

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    The accuracy of quantitative SPECT imaging is limited by the Partial Volume Effect as a result of the relatively poor spatial resolution. There is currently no consensus on the optimal Partial Volume Correction (PVC) algorithm in the application of SPECT oncology imaging. Several promising candidates require information on the reconstructed resolution - usually in the form of the Point Spread Function (PSF). A particular challenge that SPECT poses for PVC is that the resolution is known to vary with position in the field-of-view, as well as with activity distribution and reconstruction method. In this work, we assessed the potential benefit of using perturbation to measure case-specific resolution for PVC. A small point source was used to measure the resolution in phantoms designed to replicate the issues encountered in oncology imaging, including anthropomorphic phantoms which had not previously been examined in perturbation applications. Results demonstrate that, provided that a sufficient number of iterations is used for image reconstruction, perturbation can be used to measure a case-specific PSF. When PVC is applied with this case-specific PSF, quantitative accuracy is improved compared with no correction or applying PVC with an inappropriate PSF

    Citrullinated proteins in arthritis: presence in joints and effects on immunogenicity

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    Contains fulltext : 60098.pdf (publisher's version ) (Open Access

    Moral preferences in helping dilemmas expressed by matching and forced choice

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    This paper asks whether moral preferences in eight medical dilemmas change as a function of how preferences are expressed, and how people choose when they are faced with two equally attractive help projects. In two large-scale studies, participants first read dilemmas where they “matched” two suggested helping projects (which varied on a single attribute) so that they became equally attractive. They did this by filling in a missing number (e.g., how many male patients must Project M save in order to be equally attractive as Project F which can save 100 female patients). Later, the same participants were asked to choose between the two equally attractive projects. We found robust evidence that people do not choose randomly, but instead tend to choose projects that help female (vs. male), children (vs. adult), innocent (vs. non-innocent), ingroup (vs. outgroup) and existing (vs. future) patients, and imply no (vs. some) risk of a harmful side-effect, even when these projects have been matched as equally attractive as, and save fewer patients than the contrasting project. We also found that some moral preferences are hidden when expressed with matching but apparent when expressed with forced choice. For example, 88–95% of the participants expressed that female and male patients are equally valuable when doing the matching task, but over 80% of them helped female patients in the choice task

    Parallel cyclin E and cyclin A expression in neoplastic lesions of the uterine cervix

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    Cyclin E levels are high during late G1 and early S-phase in normal cells. The cyclin E expression over the cell cycle in tumours is not fully known. The impact on patient outcome by high cyclin E levels during other parts of the cell cycle than late G1- and early S-phase is unknown. We set out to study the expression of cyclin E over the cell cycle in cervical carcinomas. Using immunofluorescence staining of cyclin A, digital microscopy, and digital image analysis, we determined which cells in a tissue section that were in S- or G2-phase. M-phase cells were detected by morphology. By simultaneously staining for cyclin E, we investigated the variation in cyclin E levels over the cell cycle in cervical carcinoma lesions. In a case–control study, in which each deceased patient was matched with a patient still alive and well after >5 years of follow-up, we found that the deceased patients had a considerably higher fraction of cyclin A-positive cells staining for cyclin E than the survivors (n=36). We conclude that parallel cyclin E and cyclin A expression is an indicator for poor outcome in cervical carcinomas. In addition, we investigated the expression pattern of cyclin E and cyclin A in consecutive biopsy samples from cervical carcinomas at different stages, as well as in human papillomavirus positive or negative adenocarcinomas in order to further study the cyclin E and cyclin A expression pattern in neoplastic lesions of the uterine cervix
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