| 1. |
- Liu, Z. G., et al.
(author)
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Hemizygous variants in protein phosphatase 1 regulatory subunit 3F (PPP1R3F) are associated with a neurodevelopmental disorder characterized by developmental delay, intellectual disability and autistic features
- 2023
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In: Human Molecular Genetics. - 0964-6906 .- 1460-2083. ; 32:20, s. 2981-2995
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Journal article (peer-reviewed)abstract
- Protein phosphatase 1 regulatory subunit 3F (PPP1R3F) is a member of the glycogen targeting subunits (GTSs), which belong to the large group of regulatory subunits of protein phosphatase 1 (PP1), a major eukaryotic serine/threonine protein phosphatase that regulates diverse cellular processes. Here, we describe the identification of hemizygous variants in PPP1R3F associated with a novel X-linked recessive neurodevelopmental disorder in 13 unrelated individuals. This disorder is characterized by developmental delay, mild intellectual disability, neurobehavioral issues such as autism spectrum disorder, seizures and other neurological findings including tone, gait and cerebellar abnormalities. PPP1R3F variants segregated with disease in affected hemizygous males that inherited the variants from their heterozygous carrier mothers. We show that PPP1R3F is predominantly expressed in brain astrocytes and localizes to the endoplasmic reticulum in cells. Glycogen content in PPP1R3F knockout astrocytoma cells appears to be more sensitive to fluxes in extracellular glucose levels than in wild-type cells, suggesting that PPP1R3F functions in maintaining steady brain glycogen levels under changing glucose conditions. We performed functional studies on nine of the identified variants and observed defects in PP1 binding, protein stability, subcellular localization and regulation of glycogen metabolism in most of them. Collectively, the genetic and molecular data indicate that deleterious variants in PPP1R3F are associated with a new X-linked disorder of glycogen metabolism, highlighting the critical role of GTSs in neurological development. This research expands our understanding of neurodevelopmental disorders and the role of PP1 in brain development and proper function.
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| 2. |
- McKenna, P., et al.
(author)
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Effect of Lattice Structure on Energetic Electron Transport in Solids Irradiated by Ultraintense Laser Pulses
- 2011
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In: Physical Review Letters. - 1079-7114. ; 106:18
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Journal article (peer-reviewed)abstract
- The effect of lattice structure on the transport of energetic (MeV) electrons in solids irradiated by ultraintense laser pulses is investigated using various allotropes of carbon. We observe smooth electron transport in diamond, whereas beam filamentation is observed with less ordered forms of carbon. The highly ordered lattice structure of diamond is shown to result in a transient state of warm dense carbon with metalliclike conductivity, at temperatures of the order of 1-100 eV, leading to suppression of electron beam filamentation.
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| 3. |
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| 4. |
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| 5. |
- Coury, M., et al.
(author)
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Influence of laser irradiated spot size on energetic electron injection and proton acceleration in foil targets
- 2012
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In: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 100:7
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Journal article (peer-reviewed)abstract
- The influence of irradiated spot size on laser energy coupling to electrons, and subsequently to protons, in the interaction of intense laser pulses with foil targets is investigated experimentally. Proton acceleration is characterized for laser intensities ranging from 2 x 10(18) - 6 x 10(20) W/cm(2), by (1) variation of the laser energy for a fixed irradiated spot size, and (2) by variation of the spot size for a fixed energy. At a given laser pulse intensity, the maximum proton energy is higher under defocus illumination compared to tight focus and the results are explained in terms of geometrical changes to the hot electron injection. (C) 2012 American Institute of Physics. [doi:10.1063/1.3685615]
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| 6. |
- Coury, M., et al.
(author)
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Injection and transport properties of fast electrons in ultraintense laser-solid interactions
- 2013
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In: Physics of Plasmas. - : AIP Publishing. - 1070-664X .- 1089-7674. ; 20:4
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Journal article (peer-reviewed)abstract
- Fast electron injection and transport in solid foils irradiated by sub-picosecond-duration laser pulses with peak intensity equal to 4 x 10(20)W/cm(2) is investigated experimentally and via 3D simulations. The simulations are performed using a hybrid-particle-in-cell (PIC) code for a range of fast electron beam injection conditions, with and without inclusion of self-generated resistive magnetic fields. The resulting fast electron beam transport properties are used in rear-surface plasma expansion calculations to compare with measurements of proton acceleration, as a function of target thickness. An injection half-angle of similar to 50 degrees - 70 degrees is inferred, which is significantly larger than that derived from previous experiments under similar conditions. (C) 2013 American Institute of Physics. [http://dx.doi.org/10.1063/1.4799726]
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| 7. |
- Gray, R. J., et al.
(author)
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Laser pulse propagation and enhanced energy coupling to fast electrons in dense plasma gradients
- 2014
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In: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 16
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Journal article (peer-reviewed)abstract
- Laser energy absorption to fast electrons during the interaction of an ultra-intense (10(20) Wcm(-2)), picosecond laser pulse with a solid is investigated, experimentally and numerically, as a function of the plasma density scale length at the irradiated surface. It is shown that there is an optimum density gradient for efficient energy coupling to electrons and that this arises due to strong self-focusing and channeling driving energy absorption over an extended length in the preformed plasma. At longer density gradients the laser filaments, resulting in significantly lower overall energy coupling. As the scale length is further increased, a transition to a second laser energy absorption process is observed experimentally via multiple diagnostics. The results demonstrate that it is possible to significantly enhance laser energy absorption and coupling to fast electrons by dynamically controlling the plasma density gradient.
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