286 research outputs found
Investigating the efficiency limitations of GaN-based emitters
In this study low temperature and high pressure techniques have been used to investigate the recombination processes taking place in InGaN-based quantum well light emitting diodes (LEDs) which have emission across the blue-green region. Despite relatively high peak efficiencies of the GaN-based emitters, there remain issues relating to the strong efficiency reduction at higher currents that are required for normal operation in most applications. It is observed that there is a relative reduction in efficiency as injection current is increased in a phenonmenon which is known as efficiency droop. There are three main arguments for the cause of efficiency droop that are discussed in the literature: non-radiative Auger recombination, carrier leakage and a defect-related loss mechanism. In spite of extensive research to date, there is little agreement on the cause of efficiency droop as most experiments can only measure the overall efficiency behaviour leading to difficulties in determining the individual contributions from the different loss mechanisms
FXR1 splicing is important for muscle development and biomolecular condensates in muscle cells
© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Smith, J. A., Curry, E. G., Blue, R. E., Roden, C., Dundon, S. E. R., RodrĂguez-Vargas, A., Jordan, D. C., Chen, X., Lyons, S. M., Crutchley, J., Anderson, P., Horb, M. E., Gladfelter, A. S., & Giudice, J. FXR1 splicing is important for muscle development and biomolecular condensates in muscle cells. Journal of Cell Biology, 219(4), (2020): e201911129, doi: 10.1083/jcb.201911129.Fragile-X mental retardation autosomal homologue-1 (FXR1) is a muscle-enriched RNA-binding protein. FXR1 depletion is perinatally lethal in mice, Xenopus, and zebrafish; however, the mechanisms driving these phenotypes remain unclear. The FXR1 gene undergoes alternative splicing, producing multiple protein isoforms and mis-splicing has been implicated in disease. Furthermore, mutations that cause frameshifts in muscle-specific isoforms result in congenital multi-minicore myopathy. We observed that FXR1 alternative splicing is pronounced in the serine- and arginine-rich intrinsically disordered domain; these domains are known to promote biomolecular condensation. Here, we show that tissue-specific splicing of fxr1 is required for Xenopus development and alters the disordered domain of FXR1. FXR1 isoforms vary in the formation of RNA-dependent biomolecular condensates in cells and in vitro. This work shows that regulation of tissue-specific splicing can influence FXR1 condensates in muscle development and how mis-splicing promotes disease.We thank the A.S. Gladfelter and J. Giudice laboratories, Nancy Kedersha, and Silvia Ramos for critical discussions; Eunice Y. Lee for technical help; Dr. Stephanie Gupton (University of North Carolina at Chapel Hill, Chapel Hill, NC) for donation of WT C57BL/6J mouse embryos; and Marcin Wlizla and National Xenopus Resource (RRID:SCR_013731) for their help in maintaining adult frogs and other important technical support.
This work has been funded by a University of North Carolina at Chapel Hill Junior Faculty Development Award (to J. Giudice); a Nutrition and Obesity Research Center, University of North Carolina at Chapel Hill, Pilot & Feasibility Research grant (P30DK056350 to J. Giudice); University of North Carolina at Chapel Hill startup funds (to J. Giudice); the March of Dimes Foundation (5-FY18-36, Basil OâConnor Starter Scholar Award to J. Giudice); and NCTraCs Pilot Grant (550KR181805) from the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, through Grant Award Number UL1TR002489 (to J. Giudice), National Institutes of Health National Institute of General Medical Sciences grants (R01-GM130866 to J. Giudice, R01-GM081506 to A.S. Gladfelter, R35-GM126901 to P. Anderson, K99-GM124458 to S.M. Lyons, R25-GM089569 and 2R25-GM055336-20 to E.G. Curry); Howard Hughes Medical Institute Faculty Scholars program (A.S. Gladfelter), and National Institute of Health grants R01-HD084409 and P40-OD010997 (to M.E. Horb). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.2020-09-1
Tectonic Controls on Gas Hydrate Distribution off SW Taiwan
The northern part of the South China Sea is characterized by widespread occurrence of bottom simulating reflectors (BSR) indicating the presence of marine gas hydrate. Because the area covers both a tectonically inactive passive margin and the termination of a subduction zone, the influence of tectonism on the dynamics of gas hydrate systems can be studied in this region. Geophysical data show that there are multiple thrust faults on the active margin while much fewer and smaller faults exist in the passive margin. This tectonic difference matches with a difference in the geophysical characteristics of the gas hydrate systems. High hydrate saturation derived from ocean bottom seismometer data and controlled source electromagnetic data and conspicuous highâamplitude reflections in PâCable 3D seismic data above the BSR are found in the anticlinal ridges of the active margin. In contrast all geophysical evidence for the passive margin points to normal to low hydrate saturations. Geochemical analyses of gas samples collected at seep sites on the active margin show methane with heavy ÎŽ13C isotope composition, while gas collected at the passive margin shows light carbon isotope composition. Thus, we interpret the passive margin as a typical gas hydrate province fuelled by biogenic production of methane and the active margin gas hydrate system as a system that is fuelled not only by biogenic gas production but also by additional advection of thermogenic methane from the subduction system
Seismogenic faults, landslides, and associated tsunamis off southern Italy - Cruise No. M86/2, December 27, 2011 - January 17, 2012, Cartagena (Spain) - Brindisi (Italy)
Summary
The continental margins of southern Italy are located along converging plate boundaries, which
are affected by intense seismicity and volcanic activity. Most of the coastal areas experienced
severe earthquakes, landslides, and tsunamis in historical and/or modern times. The most
prominent example is the Messina earthquake of Dec. 28, 1908 (Ms=7.3; 80,000 casualties),
which was characterized by the worst tsunami Italy experienced in the historical time (~2000
casualties). It is, however, still unclear, whether this tsunami was triggered by a sudden vertical
movement along a major fault during the earthquake or as a result of a giant marine slide
initiated by the earthquake. The recurrence rates of major landslides and therefore the risk
associated with landslides is also unknown. Based on detailed bathymetric data sets collected by
Italian colleagues in the frame of the MaGIC Project (Marine Geohazards along the Italian
Coast), we collected seismic data (2D and 3D) and gravity cores in three working areas (The
Messina Straits, off Eastern Sicily, the Gioia Basin). A dense grid of new 2D-seismic data in the
Messina Straits will allow to map fault patterns in great detail. One interesting outcome in this
context is the identification of a set of normal faults striking in an EW-direction, which is almost
perpendicular to the previously postulated faults. This EW-striking faults seem to be active. The
area off eastern Sicily is characterized by numerous landslides and a complex deformation
pattern. A 3D-seismic data set has been collected during the cruise using the so called P-cable in
order to investigate these deformation patterns in detail. The new data will be the basis for a risk
assessment in the working areas
Hazardous explosive eruptions of a recharging multi-cyclic island arc caldera
Caldera-forming eruptions of silicic volcanic systems are among the most
devastating events on Earth. By contrast, post-collapse volcanic activity
initiating new caldera cycles is generally considered less hazardous.
Formed after Santoriniâs latest caldera-forming eruption of ~1600âbce, the
Kameni Volcano in the southern Aegean Sea enables the eruptive evolution
of a recharging multi-cyclic caldera to be reconstructed. Santoriniâs
eruptive record has been documented by onshore products and historical
descriptions of mainly effusive eruptions dating back to 197âbce. Here we
combine high-resolution seismic reflection data with cored lithologies
from International Ocean Discovery Program Expedition 398 at four sites to
determine the submarine architecture and volcanic history of intra-caldera
deposits from Kameni. Our shore-crossing analysis reveals the deposits
of a submarine explosive eruption that produced up to 3.1âkm3
of pumice
and ash, which we relate to a historical eruption in 726âce. The estimated
volcanic explosivity index of magnitude 5 exceeds previously considered
worst-case eruptive scenarios for Santorini. Our finding that the Santorini
caldera is capable of producing large explosive eruptions at an early stage
in the caldera cycle implies an elevated hazard potential for the eastern
Mediterranean region, and potentially for other recharging silicic calderas
Submarine record of volcanic island construction and collapse in the Lesser Antilles arc: First scientific drilling of submarine volcanic island landslides by IODP Expedition 340
IODP Expedition 340 successfully drilled a series of sites offshore Montserrat, Martinique and Dominica in the Lesser Antilles from March to April 2012. These are among the few drill sites gathered around volcanic islands, and the first scientific drilling of large and likely tsunamigenic volcanic island-arc landslide deposits. These cores provide evidence and tests of previous hypotheses for the composition and origin of those deposits. Sites U1394, U1399, and U1400 that penetrated landslide deposits recovered exclusively seafloor-sediment, comprising mainly turbidites and hemipelagic deposits, and lacked debris avalanche deposits. This supports the concepts that i/ volcanic debris avalanches tend to stop at the slope break, and ii/ widespread and voluminous failures of pre-existing low-gradient seafloor sediment can be triggered by initial emplacement of material from the volcano. Offshore Martinique (U1399 and 1400), the landslide deposits comprised blocks of parallel strata that were tilted or micro-faulted, sometimes separated by intervals of homogenized sediment (intense shearing), while Site U1394 offshore Montserrat penetrated a flat-lying block of intact strata. The most likely mechanism for generating these large-scale seafloor-sediment failures appears to be propagation of a decollement from proximal areas loaded and incised by a volcanic debris avalanche. These results have implications for the magnitude of tsunami generation. Under some conditions, volcanic island landslide deposits comprised of mainly seafloor sediment will tend to form smaller magnitude tsunamis than equivalent volumes of subaerial block-rich mass flows rapidly entering water. Expedition 340 also successfully drilled sites to access the undisturbed record of eruption fallout layers intercalated with marine sediment which provide an outstanding high-resolution dataset to analyze eruption and landslides cycles, improve understanding of magmatic evolution as well as offshore sedimentation processes. This article is protected by copyright. All rights reserved
Identification of Novel Therapeutic Targets in Microdissected Clear Cell Ovarian Cancers
Clear cell ovarian cancer is an epithelial ovarian cancer histotype that is less responsive to chemotherapy and carries poorer prognosis than serous and endometrioid histotypes. Despite this, patients with these tumors are treated in a similar fashion as all other ovarian cancers. Previous genomic analysis has suggested that clear cell cancers represent a unique tumor subtype. Here we generated the first whole genomic expression profiling using epithelial component of clear cell ovarian cancers and normal ovarian surface specimens isolated by laser capture microdissection. All the arrays were analyzed using BRB ArrayTools and PathwayStudio software to identify the signaling pathways. Identified pathways validated using serous, clear cell cancer cell lines and RNAi technology. In vivo validations carried out using an orthotopic mouse model and liposomal encapsulated siRNA. Patient-derived clear cell and serous ovarian tumors were grafted under the renal capsule of NOD-SCID mice to evaluate the therapeutic potential of the identified pathway. We identified major activated pathways in clear cells involving in hypoxic cell growth, angiogenesis, and glucose metabolism not seen in other histotypes. Knockdown of key genes in these pathways sensitized clear cell ovarian cancer cell lines to hypoxia/glucose deprivation. In vivo experiments using patient derived tumors demonstrate that clear cell tumors are exquisitely sensitive to antiangiogenesis therapy (i.e. sunitinib) compared with serous tumors. We generated a histotype specific, gene signature associated with clear cell ovarian cancer which identifies important activated pathways critical for their clinicopathologic characteristics. These results provide a rational basis for a radically different treatment for ovarian clear cell patients
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