Hypertension is the most common cardiovascular disease, afflicting >30% of adults. The cause of hypertension in most individuals remains unknown, suggesting that additional contributing factors have ...yet to be discovered. Corin is a serine protease that activates the natriuretic peptides, thereby regulating blood pressure. It is synthesized as a zymogen that is activated by proteolytic cleavage. CORIN variants and mutations impairing corin activation have been identified in people with hypertension and pre-eclampsia. To date, however, the identity of the protease that activates corin remains elusive. Here we show that proprotein convertase subtilisin/kexin-6 (PCSK6, also named PACE4; ref. 10) cleaves and activates corin. In cultured cells, we found that corin activation was inhibited by inhibitors of PCSK family proteases and by small interfering RNAs blocking PCSK6 expression. Conversely, PCSK6 overexpression enhanced corin activation. In addition, purified PCSK6 cleaved wild-type corin but not the R801A variant that lacks the conserved activation site. Pcsk6-knockout mice developed salt-sensitive hypertension, and corin activation and pro-atrial natriuretic peptide processing activity were undetectable in these mice. Moreover, we found that CORIN variants in individuals with hypertension and pre-eclampsia were defective in PCSK6-mediated activation. We also identified a PCSK6 mutation that impaired corin activation activity in a hypertensive patient. Our results indicate that PCSK6 is the long-sought corin activator and is important for sodium homeostasis and normal blood pressure.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UILJ, UKNU, UL, UM, UPUK
The water-cooled lithium-lead breeding blanket is in the pre-conceptual design phase. It is a candidate option for European DEMO nuclear fusion reactor. This breeding blanket concept relies on the ...liquid lithium-lead as breeder-multiplier, pressurized water as coolant and EUROFER as structural material. Current design is based on DEMO 2017 specifications. Two separate water systems are in charge of cooling the first wall and the breeding zone: thermo-dynamic cycle is 295–328 °C at 15.5 MPa. The breeder enters and exits from the breeding zone at 330 °C. Cornerstones of the design are the single module segment approach and the water manifold between the breeding blanket box and the back supporting structure. This plate with a thickness of 100 mm supports the breeding blanket and is attached to the vacuum vessel. It is in charge to withstand the loads due to normal operation and selected postulated initiating events. Rationale and progresses of the design are presented and substantiated by engineering evaluations and analyses. Water and lithium lead manifolds are designed and integrated with the two consistent primary heat transport systems, based on a reliable pressurized water reactor operating experience, and six lithium lead systems. Open issues, areas of research and development needs are finally pointed out.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Endothelial dysfunction and impaired autophagic activity have a crucial role in aging-related diseases such as cardiovascular dysfunction and atherosclerosis. We have identified miR-216a as a ...microRNA that is induced during endothelial aging and, according to the computational analysis, among its targets includes two autophagy-related genes, Beclin1 (BECN1) and ATG5. Therefore, we have evaluated the role of miR-216a as a molecular component involved in the loss of autophagic function during endothelial aging. The inverse correlation between miR-216a and autophagic genes was conserved during human umbilical vein endothelial cells (HUVECs) aging and in vivo models of human atherosclerosis and heart failure. Luciferase experiments indicated BECN1, but not ATG5 as a direct target of miR-216a. HUVECs were transfected in order to modulate miR-216a expression and stimulated with 100 μg/ml oxidized low-density lipoprotein (ox-LDL) to induce a stress repairing autophagic process. We found that in young HUVECs, miR-216a overexpression repressed BECN1 and ATG5 expression and the ox-LDL induced autophagy, as evaluated by microtubule-associated protein 1 light chain 3 (LC3B) analysis and cytofluorimetric assay. Moreover, miR-216a stimulated ox-LDL accumulation and monocyte adhesion in HUVECs. Conversely, inhibition of miR-216a in old HUVECs rescued the ability to induce a protective autophagy in response to ox-LDL stimulus. In conclusion, mir-216a controls ox-LDL induced autophagy in HUVECs by regulating intracellular levels of BECN1 and may have a relevant role in the pathogenesis of cardiovascular disorders and atherosclerosis.
The in-situ extraction of bitumen from oil sands, particularly steam assisted gravity drainage, has been the fastest growing production technology in the industry. Integrated with upgrading ...operations to enhance the fuel quality, the process consumes significant amounts of energy, which are currently mostly derived from burning natural gas. On the other hand, considerable amounts of petroleum coke residues are generated in the refineries. This petcoke ends up stockpiled as a waste byproduct with associated environmental concerns. The aim of this study is to evaluate the feasibility of integrating a petroleum coke residue gasification plant to the energy infrastructure of an integrated SAGD/upgrading facility. The petcoke gasification process is specifically designed to fulfill the demands of a facility processing 112,500 barrels per day of Athabasca bitumen. Two plant configurations are compared, one without and one with CO2 capture and storage. The gasification-based polygeneration plant is modeled with the Aspen Plus flowsheeting software. Two levels of energy demands (i.e. high and low energy scenarios), reflecting the range of variability in the energy requirements of extraction and upgrading operations (e.g. steam to oil ratio), are considered. The net efficiency for polygeneration plant was determined to be in the range of 48–58%. The gasification of approximately 190 t/h of petroleum coke is required to achieve the power, thermal and hydrogen demands. The incorporation of carbon capture imposes significant energy penalties, which requires the addition of natural gas fueled gas turbines to meet the power requirements.
•A simulation-based modelling of energy demands of oil sands operations is proposed.•Aspen simulations used to simulate a petcoke polygeneration facility.•A self-sufficient power, heat and hydrogen facility with a capacity of 190 tonne/h.•The net efficiency of polygeneration is in the range of 48%–58%.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
A delayed detached eddy simulation of an overexpanded nozzle flow with shock-induced separation is carried out at a Reynolds number of
$1.7\times 10^{7}$
, based on nozzle throat diameter and ...stagnation chamber properties. In this flow, self-sustained shock oscillations induce local unsteady loads on the nozzle wall as well as global off-axis forces. Despite several studies in the last few decades, a clear physical understanding of the factors driving this unsteadiness is still lacking. The geometry under investigation is a subscale truncated ideal contour nozzle, which was experimentally tested at the University of Texas at Austin at a nozzle pressure ratio of 30. Under these conditions, the nozzle operates in a highly overexpanded state and comprises a conical separation shock that merges to form a Mach disk at the nozzle centre. The delayed detached eddy simulation model agrees well with the experimental results in terms of mean and fluctuating wall-pressure statistics. Wall-pressure spectra reveal a large bump at low frequencies associated with an axisymmetric (piston-like) motion of the shock system, followed by a broad and high-amplitude peak at higher frequencies associated with the Mach waves produced by turbulent eddies convecting through the detached shear layer. Moreover, a distinct peak at an intermediate frequency (
${\sim}1~\text{kHz}$
) persists in the wall-pressure spectra downstream of the separation shock. A Fourier-based analysis performed in both time and space (azimuthal wavenumber) reveals that this intermediate-frequency peak is associated with the
$m=1$
(non-symmetric) pressure mode and is thus related to the generation of aerodynamic side loads. It is then shown how the unsteady Mach disk motion is characterized by an intense vortex shedding activity that, together with the vortical structures of the annular shear layer, contributes to the sustainment of an aeroacoustic feedback loop occurring within the nozzle.
A calibrated delayed detached eddy simulation of a sub-scale cold-gas dual-bell nozzle flow at high Reynolds number and in sea-level mode is carried out at nozzle pressure ratio NPR = 45.7. In this ...regime the over-expanded flow exhibits a symmetric and controlled flow separation at the inflection point, that is the junction between the two bells, leading to the generation of a low content of aerodynamic side loads with respect to conventional bell nozzles. The nozzle wall-pressure signature is analyzed in the frequency domain and compared with the experimental data available in the literature for the same geometry and flow conditions. The Fourier spectra in time and space (azimuthal wavenumber) show the presence of a persistent tone associated to the symmetric shock movement. Asymmetric modes are only slightly excited by the shock and the turbulent structures. The low mean value of the side-loads magnitude is in good agreement with the experiments and confirms that the inflection point dampens the aero-acoustic interaction between the separation-shock and the detached shear layer.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•Energy and economic performance of novel IGFC plant configurations with CCS.•The role of syngas methanation in IGFC plants.•High coal-to-power efficiency (∼55%, LHV) in IGFC with CCS.•The impact of ...carbon tax on the economics of advanced integrated gasifier fuel cell plants.
This work analyzes the efficiency and economic performance of different configurations of a coal-fed integrated gasification fuel cell (IGFC) plant with CO2 capture. Our analysis evaluates novel configurations, providing a detailed economic assessment for each case.
The plants studied here are based on a pressurized solid oxide fuel cell (SOFC) based power cycle integrated with a Shell coal gasifier. The design variations focus on syngas cleaning and pre-processing upstream of the SOFC power island. In particular, we have designed, simulated and optimized three main system configurations; two with a partial methanation process upstream of the SOFC (‘TREMP’ and ‘HICOM’ cases, respectively) and one without (‘DIRECT’ case). Depending on the specific plant layout, carbon capture is accomplished either before or after the SOFC power island, or both.
The best performance, both thermodynamic and economic, was achieved by the HICOM case, whose coal-to-electricity conversion efficiency is ∼55% (lower heating value, LHV, basis). Note that this paper is meant to supplant the preliminary results presented in Lanzini et al. (2012).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The LHC Optical Private Network (LHCOPN), linking CERN and the Tier 1s, and the LHC Open Network Environment (LHCONE) which links these to the Tier 2 community both successfully supported the data ...transfer needs of the LHC community during Run 1 and have now evolved to serve the networking requirements of the new computing models for Run 2. We present here the current status and the key changes, notably the delivered and planned bandwidth increases, the ongoing work to better address the needs of the Asia-Pacific region, developments to improve redundancy and progress made for provisioning point-to-point links.
The European Research Roadmap to the Realisation of Fusion Energy foresees that the DEMO reactor is going to succeed ITER in the pathway towards the exploitation of nuclear fusion, achieving long ...plasma operation time, demonstrating tritium self-sufficiency and producing net electric output on an industrial scale. Therefore, its design must be more oriented towards the Balance of Plant (BoP) than it is in ITER.
Since the early pre-conceptual phase of the DEMO project, emphasis has been laid on identifying the main requirements affecting the overall architecture of the BoP. For instance, specific efforts and proper solutions have been envisaged to cope with the pulsed nature of the heat source. Furthermore, the current development of two blanket concepts calls for two separate BoP options to be conceived.
This paper summarizes the main alternatives outlined at the end of DEMO pre-conceptual design phase for the BoP concepts based on both the Helium-Cooled Pebble Bed (HCPB) and Water-Cooled Lithium Lead (WCLL) Breeding Blanket (BB) technologies. Then, the assumed reference configurations of both the BoP concepts are described in detail, highlighting the main features and the most relevant engineering aspects. Attention will be focussed on technological challenges, integration constraints and other open issues, highlighting pros and cons of the chosen BoP options to be further investigated in the next design phase.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary
The water‐cooled lithium–lead breeding blanket is a candidate option for the European Demonstration Power Plant (DEMO) nuclear fusion reactor. This breeding blanket concept relies on the ...liquid lithium–lead as breeder–multiplier, pressurized water as coolant, and EUROFER as structural material. The current design is based on DEMO 2015 specifications and represents the follow‐up of the design developed in 2015. The single‐module‐segment approach is employed. This is constituted by a basic geometry repeated along the poloidal direction. The power is removed by means of radial–toroidal (i.e., horizontal) water cooling tubes in the breeding zone. The lithium–lead flows in a radial–poloidal direction. On the back of the segment, a 100‐mm‐thick plate is in charge of withstanding the loads due to normal operation and selected postulated initiating events. Water and lithium–lead manifolds are designed and integrated with a consistent primary heat transport system, based on a reliable pressurized water reactor operating experience, and the lithium–lead system. Rationale and features of the single‐module‐segment water‐cooled lithium–lead breeding blanket design are discussed and supported by thermo‐mechanic, thermo‐hydraulic, and neutronic analyses. Preliminary integration with the primary heat transfer system, the energy storage system, and the balance of plant is briefly discussed. Open issues, areas of research, and development needs are finally pointed out. @EUROfusion Consortium*, 2017. *For more details see http://www.euro‐fusionscipub.org/disclaimer‐copyright
The paper concerns the new design of the water‐cooled lithium–lead breeding blanket, which is one of the candidate options for the European Demonstration Power Plant fusion reactor. The new design consists of a single‐module blanket segment concept and presents horizontal (i.e., radial–toroidal) water‐cooling tubes in the breeding zone, and lithium–lead flowing in the radial–poloidal direction. The paper presents the rationale and features of the water‐cooled lithium–lead breeding blanket design, supported by thermo‐mechanic, thermo‐hydraulic, magneto‐hydrodynamic, and neutronic analyses.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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