| 991. |
- Liang, Y., et al.
(author)
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Desmosomal COP9 regulates proteome degradation in arrhythmogenic right ventricular dysplasia/cardiomyopathy
- 2021
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In: Journal of Clinical Investigation. - : American Society for Clinical Investigation. - 0021-9738 .- 1558-8238. ; 131:11
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Journal article (peer-reviewed)abstract
- Dysregulated protein degradative pathways are increasingly recognized as mediators of human disease. This mechanism may have particular relevance to desmosomal proteins that play critical structural roles in both tissue architecture and cell-cell communication, as destabilization/breakdown of the desmosomal proteome is a hallmark of genetic-based desmosomal-targeted diseases, such as the cardiac disease arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). However, no information exists on whether there are resident proteins that regulate desmosomal proteome homeostasis. Here, we uncovered a cardiac constitutive photomorphogenesis 9 (COP9) desmosomal resident protein complex, composed of subunit 6 of the COP9 signalosome (CSN6), that enzymatically restricted neddylation and targeted desmosomal proteome degradation. CSN6 binding, localization, levels, and function were affected in hearts of classic mouse and human models of ARVD/C affected by desmosomal loss and mutations, respectively. Loss of desmosomal proteome degradation control due to junctional reduction/loss of CSN6 and human desmosomal mutations destabilizing junctional CSN6 were also sufficient to trigger ARVD/C in mice. We identified a desmosomal resident regulatory complex that restricted desmosomal proteome degradation and disease.
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| 992. |
- Liang, Y, et al.
(author)
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Mitigation of Type-I ELMs with n =2 Fields on JET
- 2012
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In: 24th IAEA Fusion Energy Conference, 8-13 October 2012. ; , s. EX/P4-23-
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Conference paper (peer-reviewed)abstract
- Recently, strong mitigation of Type-I Edge Localized Modes (ELMs) has been observed with application of the n = 2 field in high collisionality (nu^*_e=2.0) H-mode plasma on JET tokamak with ITER-like wall. In this experiment, the EFCC power supply system has been enhanced with a coil current up to 88kAt (twice than before). With an n = 2 field, the large type-I ELMs with frequency of ~ 45 Hz was replaced by the high frequency (few hundreds Hz) small ELMs. No density pump-out was observed during an application of the n = 2 field. The influence of the n = 2 field on the core and the pedestal electron pressure profiles is within the error bar and it can be neglected. During the normal type-I ELM H-mode phase, the maximal surface temperature (Tmax) on the outer divertor plate was overall increasing and associated with large periodical variation due to the type-I ELMs. However, during an application of the n = 2 field, Tmax was saturated and has only small variation in few degrees due to the small mitigated ELMs. Splitting of the outer strike point has been observed during the strong mitigation of the type-I ELMs.
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| 993. |
- Liang, Y., et al.
(author)
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Mitigation of type-I ELMs with n=2 fields on JET with ITER-like wall
- 2013
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In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 53:7, s. 073036-
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Journal article (peer-reviewed)abstract
- Mitigation of type-I edge-localized modes (ELMs) was observed with the application of an n = 2 field in H-mode plasmas on the JET tokamak with the ITER-like wall (ILW). Several new findings with the ILW were identified and contrasted to the previous carbon wall (C-wall) results for comparable conditions. Previous results for high collisionality plasmas (nu*(e,ped) similar to 2.0) with the C-wall saw little or no influence of either n = 1 or n = 2 fields on the ELMs. However, recent observations with the ILW show large type-I ELMs with a frequency of similar to 45 Hz were replaced by high-frequency (similar to 200 Hz) small ELMs during the application of the n = 2 field. With the ILW, splitting of the outer strike point was observed for the first time during the strong mitigation of the type-I ELMs. The maximal surface temperature (T-max) on the outer divertor plate reached a stationary state and has only small variations of a few degrees due to the small mitigated ELMs. In moderate collisionality (nu*(e,ped) similar to 0.8) H-mode plasmas, similar to previous results with the C-wall, both an increase in the ELM frequency and density pump-out were observed during the application of the n = 2 field. There are two new observations compared with the C-wall results. Firstly, the effect of ELM mitigation with the n = 2 field was seen to saturate so that the ELM frequency did not further increase above a certain level of n = 2 magnetic perturbations. Secondly splitting of the outer strike point during the ELM crash was seen, resulting in mitigation of the maximal ELM peak heat fluxes on the divertor region.
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| 994. |
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| 995. |
|
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| 996. |
|
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| 997. |
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| 998. |
|
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| 999. |
- Loh, N. D., et al.
(author)
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Cryptotomography : Reconstructing 3D Fourier Intensities from Randomly Oriented Single-Shot Diffraction Patterns
- 2010
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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 104:22, s. 225501-1-225501-5
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Journal article (peer-reviewed)abstract
- We reconstructed the 3D Fourier intensity distribution of monodisperse prolate nanoparticles using single-shot 2D coherent diffraction patterns collected at DESY's FLASH facility when a bright, coherent, ultrafast x-ray pulse intercepted individual particles of random, unmeasured orientations. This first experimental demonstration of cryptotomography extended the expansion-maximization-compression framework to accommodate unmeasured fluctuations in photon fluence and loss of data due to saturation or background scatter. This work is an important step towards realizing single-shot diffraction imaging of single biomolecules.
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| 1000. |
- Lomb, Lukas, et al.
(author)
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Radiation damage in protein serial femtosecond crystallography using an x-ray free-electron laser
- 2011
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In: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 84:21, s. 214111-1-214111-6
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Journal article (peer-reviewed)abstract
- X-ray free-electron lasers deliver intense femtosecond pulses that promise to yield high resolution diffraction data of nanocrystals before the destruction of the sample by radiation damage. Diffraction intensities of lysozyme nanocrystals collected at the Linac Coherent Light Source using 2 keV photons were used for structure determination by molecular replacement and analyzed for radiation damage as a function of pulse length and fluence. Signatures of radiation damage are observed for pulses as short as 70 fs. Parametric scaling used in conventional crystallography does not account for the observed effects.
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