80 research outputs found

    Dynamics of Vortex Dipoles in Confined Bose-Einstein Condensates

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    We present a systematic theoretical analysis of the motion of a pair of straight counter-rotating vortex lines within a trapped Bose-Einstein condensate. We introduce the dynamical equations of motion, identify the associated conserved quantities, and illustrate the integrability of the ensuing dynamics. The system possesses a stationary equilibrium as a special case in a class of exact solutions that consist of rotating guiding-center equilibria about which the vortex lines execute periodic motion; thus, the generic two-vortex motion can be classified as quasi-periodic. We conclude with an analysis of the linear and nonlinear stability of these stationary and rotating equilibria.Comment: 8 pages, 3 figures, to appear in Phys. Lett.

    HIV-Specific T Cells Generated from Naive T Cells Suppress HIV In Vitro and Recognize Wide Epitope Breadths

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    The Berlin Patient represents the first and only functional HIV cure achieved by hematopoietic stem cell transplant (HSCT). In subsequent efforts to replicate this result, HIV rebounded post-HSCT after withdrawal of antiretroviral therapy. Providing HIV-specific immunity through adoptive T cell therapy may prevent HIV rebound post-HSCT by eliminating newly infected cells before they can seed systemic infection. Adoptive T cell therapy has demonstrated success in boosting Epstein-Barr virus and cytomegalovirus-specific immunity post-HSCT, controlling viral reactivation. However, T cell immunotherapies to boost HIV-specific immunity have been limited by single-epitope specificity and minimal persistence or efficacy in vivo. To improve this strategy, we sought to generate allogeneic HIV-specific T cells from human leukocyte antigen (HLA)-A02+ HIV-negative adult or cord blood donors. We focused on HLA-A02+ donors due to well-characterized epitope restrictions observed in HIV+ populations. We show that multi-antigen HIV-specific T cells can be generated from naive T cells of both cord blood and adults using a reproducible good manufacturing practice (GMP)-grade protocol. This product lysed antigen-pulsed targets and suppressed active HIV in vitro. Interestingly, these cells displayed broad epitope recognition despite lacking recognition of the common HLA-A02-restricted HIV epitope Gag SL9. This first demonstration of functional multi-antigen HIV-specific T cells has implications for improving treatment of HIV through allogeneic HSCT. Patel et al. demonstrate the ability to generate HIV-specific T cells from HIV-seronegative adults and cord blood with a good-manufacturing-practice-compliant strategy. These immunotherapies are multi-antigen specific, display cytotoxicity, and suppress HIV in vitro, providing a promising platform for adoptive T cell therapy in a post-transplant setting

    Adverse events following infusion of T cells for adoptive immunotherapy: A 10-year experience

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    Background aims. The Food and Drug Administration (FDA) currently recommends at least 4 h of recipient monitoring after T cell infusions to detect early infusion reactions. Recent catastrophic reactions to 'first-in-man' biologic agents have emphasized the importance of this rule for initial studies of new products. The value of such monitoring for better established agents is less obvious. Methods. We reviewed infusion-related adverse events (AE) following administration of ex vivo-expanded T cell products (antigen-specific cytotoxic T lymphocytes, allodepleted T cells, and genetically modified T cells) on investigational new drug (IND) studies in our center. Results. From 1998 to 2008, we infused 381 T cell products to 180 recipients, enrolled on 18 studies, receiving T cells targeting malignancies or post-transplant viral infections. There were no grade 34 infusion reactions during initial monitoring or 24-h follow-up. Twenty-four mild (grade 12) AE occurred in 21 infusions either during or immediately following infusion (up to 6 h), most commonly nausea and vomiting (10/24, 41.6%), probably because of the dimethyl sulfoxide cryoprotectant, and hypotension (20.8%), attributable to diphenhydramine pre-medication. Twenty-two additional non-severe events were reported within 24 h of infusion, most commonly culture-negative fever, chills and nausea. An increased risk of adverse events was associated with age [incidence rate ratio (IRR) 0.98; 95% confidence interval (CI) 0.961.00, P 0.05], while an increased risk of immediate infusion-related events was higher in patients reporting allergies (IRR 2.72, 95% CI 1.007.40, P 0.05); sex, disease type and T cell source (allogeneic or autologous) had no effect on frequency of adverse events. Conclusions. Infusion of these T cell products was safe in the outpatient setting and associated with no severe reactions, so monitoring for 1 h after infusion is probably sufficient. As many of the AE were attributable to diphenhydramine premedication, a lower dose (0.25 mg/kg) should be selected

    C9orf72 expansion differentially affects males with spinal onset amyotrophic lateral sclerosis.

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    INTRODUCTION: The C9orf72 repeat expansion has been reported as a negative prognostic factor in amyotrophic lateral sclerosis (ALS). We have examined the prognostic impact of the C9orf72 repeat expansion in European subgroups based on gender and site of onset. METHODS: C9orf72 status and demographic/clinical data from 4925 patients with ALS drawn from 3 prospective ALS registers (Ireland, Italy and the Netherlands), and clinical data sets in the UK and Belgium. Flexible parametric survival models were built including known prognostic factors (age, diagnostic delay and site of onset), gender and the presence of an expanded repeat in C9orf72. These were used to explore the effects of C9orf72 on survival by gender and site of onset. Individual patient data (IPD) meta-analysis was used to estimate HRs for results of particular importance. RESULTS: 457 (8.95%) of 4925 ALS cases carried the C9orf72 repeat expansion. A meta-analysis of C9orf72 estimated a survival HR of 1.36 (1.18 to 1.57) for those carrying the expansion. Models evaluating interaction between gender and C9orf72 repeat expansions demonstrated that the reduced survival due to C9orf72 expansion was being driven by spinal onset males (HR 1.56 (95% CI 1.25 to 1.96). CONCLUSIONS: This study represents the largest combined analysis of the prognostic characteristics of the C9orf72 expansion. We have shown for the first time that the negative prognostic implication of this variant is driven by males with spinal onset disease, indicating a hitherto unrecognised gender-mediated effect of the variant that requires further exploration

    The XMM Cluster Survey: Exploring scaling relations and completeness of the Dark Energy Survey Year 3 redMaPPer cluster catalogue

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    We cross-match and compare characteristics of galaxy clusters identified in observations from two sky surveys using two completely different techniques. One sample is optically selected from the analysis of three years of Dark Energy Survey observations using the redMaPPer cluster detection algorithm. The second is X-ray selected from XMM observations analysed by the XMM Cluster Survey. The samples comprise a total area of 57.4 deg2^2, bounded by the area of 4 contiguous XMM survey regions that overlap the DES footprint. We find that the X-ray selected sample is fully matched with entries in the redMaPPer catalogue, above λ>\lambda>20 and within 0.1<z<< z <0.9. Conversely, only 38\% of the redMaPPer catalogue is matched to an X-ray extended source. Next, using 120 optically clusters and 184 X-ray selected clusters, we investigate the form of the X-ray luminosity-temperature (LXTXL_{X}-T_{X}), luminosity-richness (LXλL_{X}-\lambda) and temperature-richness (TXλT_{X}-\lambda) scaling relations. We find that the fitted forms of the LXTXL_{X}-T_{X} relations are consistent between the two selection methods and also with other studies in the literature. However, we find tentative evidence for a steepening of the slope of the relation for low richness systems in the X-ray selected sample. When considering the scaling of richness with X-ray properties, we again find consistency in the relations (i.e., LXλL_{X}-\lambda and TXλT_{X}-\lambda) between the optical and X-ray selected samples. This is contrary to previous similar works that find a significant increase in the scatter of the luminosity scaling relation for X-ray selected samples compared to optically selected samples.Comment: Accepted for publication to MNRA

    Irish cardiac society - Proceedings of annual general meeting held 20th & 21st November 1992 in Dublin Castle

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