1,228 research outputs found
Test-Retest Reliability of Diffusion Tensor Imaging in Huntington's Disease.
Diffusion tensor imaging (DTI) has shown microstructural abnormalities in patients with Huntington's Disease (HD) and work is underway to characterise how these abnormalities change with disease progression. Using methods that will be applied in longitudinal research, we sought to establish the reliability of DTI in early HD patients and controls. Test-retest reliability, quantified using the intraclass correlation coefficient (ICC), was assessed using region-of-interest (ROI)-based white matter atlas and voxelwise approaches on repeat scan data from 22 participants (10 early HD, 12 controls). T1 data was used to generate further ROIs for analysis in a reduced sample of 18 participants. The results suggest that fractional anisotropy (FA) and other diffusivity metrics are generally highly reliable, with ICCs indicating considerably lower within-subject compared to between-subject variability in both HD patients and controls. Where ICC was low, particularly for the diffusivity measures in the caudate and putamen, this was partly influenced by outliers. The analysis suggests that the specific DTI methods used here are appropriate for cross-sectional research in HD, and give confidence that they can also be applied longitudinally, although this requires further investigation. An important caveat for DTI studies is that test-retest reliability may not be evenly distributed throughout the brain whereby highly anisotropic white matter regions tended to show lower relative within-subject variability than other white or grey matter regions
A direct image of the obscuring disk surrounding an active galactic nucleus
Active galactic nuclei (AGN) are generally accepted to be powered by the
release of gravitational energy in a compact accretion disk surrounding a
massive black hole. Such disks are also necessary to collimate powerful radio
jets seen in some AGN. The unifying classification schemes for AGN further
propose that differences in their appearance can be attributed to the opacity
of the accreting material, which may obstruct our view of the central region of
some systems. The popular model for the obscuring medium is a parsec-scale disk
of dense molecular gas, although evidence for such disks has been mostly
indirect, as their angular size is much smaller than the resolution of
conventional telescopes. Here we report the first direct images of a pc-scale
disk of ionised gas within the nucleus of NGC 1068, the archetype of obscured
AGN. The disk is viewed nearly edge-on, and individual clouds within the
ionised disk are opaque to high-energy radiation, consistent with the unifying
classification scheme. In projection, the disk and AGN axes align, from which
we infer that the ionised gas disk traces the outer regions of the long-sought
inner accretion disk.Comment: 14 pages, LaTeX, PSfig, to appear in Nature. also available at
http://hethp.mpe-garching.mpg.de/Preprint
Cancer cells resist antibody-mediated destruction by neutrophils through activation of the exocyst complex
Cytotoxicity; Immunity; ImmunotherapyCitotoxicidad; Inmunidad; InmunoterapiaCitotoxicitat; Immunitat; ImmunoterĂ piaBackground Neutrophils kill antibody-opsonized tumor cells using trogocytosis, a unique mechanism of destruction of the target plasma. This previously unknown cytotoxic process of neutrophils is dependent on antibody opsonization, FcÎł receptors and CD11b/CD18 integrins. Here, we demonstrate that tumor cells can escape neutrophil-mediated cytotoxicity by calcium (Ca2+)-dependent and exocyst complex-dependent plasma membrane repair.
Methods We knocked down EXOC7 or EXOC4, two exocyst components, to evaluate their involvement in tumor cell membrane repair after neutrophil-induced trogocytosis. We used live cell microscopy and flow cytometry for visualization of the host and tumor cell interaction and tumor cell membrane repair. Last, we reported the mRNA levels of exocyst in breast cancer tumors in correlation to the response in trastuzumab-treated patients.
Results We found that tumor cells can evade neutrophil antibody-dependent cellular cytotoxicity (ADCC) by Ca2+-dependent cell membrane repair, a process induced upon neutrophil trogocytosis. Absence of exocyst components EXOC7 or EXOC4 rendered tumor cells vulnerable to neutrophil-mediated ADCC (but not natural killer cell-mediated killing), while neutrophil trogocytosis remained unaltered. Finally, mRNA levels of exocyst components in trastuzumab-treated patients were inversely correlated to complete response to therapy.
Conclusions Our results support that neutrophil attack towards antibody-opsonized cancer cells by trogocytosis induces an active repair process by the exocyst complex in vitro. Our findings provide insight to the possible contribution of neutrophils in current antibody therapies and the tolerance mechanism of tumor cells and support further studies for potential use of the exocyst components as clinical biomarkers.This work was supported by the Dutch Cancer Society (grant numbers 10300 and 11537, awarded to TKvdB and HLM, respectively)
A diagnostic conundrum
A 26-year-old man was referred with facial weakness, dysarthria, dysphagia, ophthalmoparesis and severely weak and wasted legs. His symptoms had begun when aged 20 with electric shock pains and paraesthesia in both feet progressing over 6 months to the lower calves. He then developed buttock numbness and occasional faecal incontinence. By age 22, he had diffuse lower limb weakness and wasting, with difficulty standing from a seated position and frequent tripping. He became wheelchair-dependent within 3 years
Apparent diffusion coefficient for molecular subtyping of non-gadolinium-enhancing WHO grade II/III glioma: volumetric segmentation versus two-dimensional region of interest analysis
OBJECTIVES: To investigate if quantitative apparent diffusion coefficient (ADC) measurements can predict genetic subtypes of non-gadolinium-enhancing gliomas, comparing whole tumour against single slice analysis. METHODS: Volumetric T2-derived masks of 44 gliomas were co-registered to ADC maps with ADC mean (ADCmean) calculated. For the slice analysis, two observers placed regions of interest in the largest tumour cross-section. The ratio (ADCratio) between ADCmeanin the tumour and normal appearing white matter was calculated for both methods. RESULTS: Isocitrate dehydrogenase (IDH) wild-type gliomas showed the lowest ADC values throughout (p < 0.001). ADCmeanin the IDH-mutant 1p19q intact group was significantly higher than in the IDH-mutant 1p19q co-deleted group (p < 0.01). A volumetric ADCmeanthreshold of 1201 × 10-6mm2/s identified IDH wild-type with a sensitivity of 83% and a specificity of 86%; a volumetric ADCratiocut-off value of 1.65 provided a sensitivity of 80% and a specificity of 92% (area under the curve (AUC) 0.9-0.94). A slice ADCratiothreshold for observer 1 (observer 2) of 1.76 (1.83) provided a sensitivity of 80% (86%), specificity of 91% (100%) and AUC of 0.95 (0.96). The intraclass correlation coefficient was excellent (0.98). CONCLUSIONS: ADC measurements can support the distinction of glioma subtypes. Volumetric and two-dimensional measurements yielded similar results in this study. KEY POINTS: • Diffusion-weighted MRI aids the identification of non-gadolinium-enhancing malignant gliomas • ADC measurements may permit non-gadolinium-enhancing glioma molecular subtyping • IDH wild-type gliomas have lower ADC values than IDH-mutant tumours • Single cross-section and volumetric ADC measurements yielded comparable results in this study
What do -ray bursts look like?
There have been great and rapid progresses in the field of -ray
bursts (denoted as GRBs) since BeppoSAX and other telescopes discovered their
afterglows in 1997. Here, we will first give a brief review on the
observational facts of GRBs and direct understanding from these facts, which
lead to the standard fireball model. The dynamical evolution of the fireball is
discussed, especially a generic model is proposed to describe the whole
dynamical evolution of GRB remnant from highly radiative to adiabatic, and from
ultra-relativistic to non-relativistic phase. Then, Various deviations from the
standard model are discussed to give new information about GRBs and their
environment. In order to relax the energy crisis, the beaming effects and their
possible observational evidences are also discussed in GRB's radiations.Comment: 10 pages, Latex. Invited talk at the Pacific Rim Conference on
Stellar Astrophysics, Hong Kong, China, Aug. 199
Schr\"odinger Deformations of AdS_3 x S^3
We study Schr\"odinger invariant deformations of the AdS_3 x S^3 x T^4 (or
K3) solution of IIB supergravity and find a large class of solutions with
integer and half-integer dynamical exponents. We analyze the supersymmetries
preserved by our solutions and find an infinite number of solutions with four
supersymmetries. We study the solutions holographically and find that the dual
D1-D5 (or F1-NS5) CFT is deformed by irrelevant operators of spin one and two.Comment: 23 page
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