51 research outputs found
Pebble bed: reflector treatment and pressure\ud velocity coupling
In this report, we describe some models and numerical methods used to simulate the flow and temperature in a pebble bed modular nuclear reactor. The reactor core is filled with around 450000 spheres containing low enriched uranium and helium is forced through these hot pebbles to cool the system down. The group first investigated the flow model in the pebbles. Numerical aspects were then considered to tackle difficulties encountered with the flow simulation and the temperature inside the pebbles. Numerical schemes are presented that can significantly improve the accuracy of the computed results
Dp-branes, NS5-branes and U-duality from nonabelian (2,0) theory with Lie 3-algebra
We derive the super Yang-Mills action of Dp-branes on a torus T^{p-4} from
the nonabelian (2,0) theory with Lie 3-algebra. Our realization is based on Lie
3-algebra with pairs of Lorentzian metric generators. The resultant theory then
has negative norm modes, but it results in a unitary theory by setting VEV's of
these modes. This procedure corresponds to the torus compactification,
therefore by taking a transformation which is equivalent to T-duality, the
Dp-brane action is obtained. We also study type IIA/IIB NS5-brane and
Kaluza-Klein monopole systems by taking other VEV assignments. Such various
compactifications can be realized in the nonabelian (2,0) theory, since both
longitudinal and transverse directions can be compactified, which is different
from the BLG theory. We finally discuss U-duality among these branes, and show
that most of the moduli parameters in U-duality group are recovered. Especially
in D5-brane case, the whole U-duality relation is properly reproduced.Comment: 1+26 page
Aspects of U-duality in BLG models with Lorentzian metric 3-algebras
In our previous paper, it was shown that BLG model based on a Lorentzian
metric 3-algebra gives Dp-brane action whose worldvolume is compactified on
torus T^d (d=p-2). Here the 3-algebra was a generalized one with d+1 pairs of
Lorentzian metric generators and expressed in terms of a loop algebra with
central extensions. In this paper, we derive the precise relation between the
coupling constant of the super Yang-Mills, the moduli of T^d and some R-R flux
with VEV's of ghost fields associated with Lorentzian metric generators. In
particular, for d=1, we derive the Yang-Mills action with theta term and show
that SL(2,Z) Montonen-Olive duality is realized as the rotation of two VEV's.
Furthermore, some moduli parameters such as NS-NS 2-form flux are identified as
the deformation parameters of the 3-algebras. By combining them, we recover
most of the moduli parameters which are required by U-duality symmetry.Comment: 27 pages, v2: minor correction
Branes from a non-Abelian (2,0) tensor multiplet with 3-algebra
In this paper, we study the equations of motion for non-Abelian N=(2,0)
tensor multiplets in six dimensions, which were recently proposed by Lambert
and Papageorgakis. Some equations are regarded as constraint equations. We
employ a loop extension of the Lorentzian three-algebra (3-algebra) and examine
the equations of motion around various solutions of the constraint equations.
The resultant equations take forms that allow Lagrangian descriptions. We find
various (5+d)-dimensional Lagrangians and investigate the relation between them
from the viewpoint of M-theory duality.Comment: 44+1 pages, reference added, typos corrected, and several discussions
added; v3, reference added, many typos corrected, the language improved; v4,
some typos and references corrected, final version to appear in J. Phys.
Efficacy and safety of acoziborole in patients with human African trypanosomiasis caused by Trypanosoma brucei gambiense: a multicentre, open-label, single-arm, phase 2/3 trial
Summary Background Human African trypanosomiasis caused by Trypanosoma brucei gambiense (gambiense HAT) in patients with late-stage disease requires hospital admission to receive nifurtimox-eflornithine combination therapy (NECT). Fexinidazole, the latest treatment that has been recommended by WHO, also requires systematic admission to hospital, which is problematic in areas with few health-care resources. We aim to assess the safety and efficacy of acoziborole in adult and adolescent patients with gambiense HAT. Methods This multicentre, prospective, open-label, single-arm, phase 2/3 study recruited patients aged 15 years or older with confirmed gambiense HAT infection from ten hospitals in the Democratic Republic of the Congo and Guinea. Inclusion criteria included a Karnofsky score less than 50, ability to swallow tablets, a permanent address or traceability, ability to comply with follow-up visits and study requirements, and agreement to hospital admission during treatment. Oral acoziborole was administered as a single 960 mg dose (3 × 320 mg tablets) to fasted patients. Patients were observed in hospital until day 15 after treatment administration then for 18 months as outpatients with visits at 3, 6, 12, and 18 months. The primary efficacy endpoint was the success rate of acoziborole treatment at 18 months in patients with late-stage gambiense HAT (modified intention-to-treat [mITT] population), based on modified WHO criteria. A complementary post-hoc analysis comparing the 18-month success rates for acoziborole and NECT (using historical data) was performed. This study is registered at ClinicalTrials.gov, NCT03087955. Findings Between Oct 11, 2016, and March 25, 2019, 260 patients were screened, of whom 52 were ineligible and 208 were enrolled (167 with late-stage and 41 with early-stage or intermediate-stage gambiense HAT; primary efficacy analysis set). All 41 (100%) patients with early-stage or intermediate-stage and 160 (96%) of 167 with late-stage disease completed the last 18-month follow-up visit. The mean age of participants was 34·0 years (SD 12·4), including 117 (56%) men and 91 (44%) women. Treatment success rate at 18 months was 95·2% (95% CI 91·2-97·7) reached in 159 of 167 patients with late-stage gambiense HAT (mITT population) and 98·1% (95·1-99·5) reached in 159 of 162 patients (evaluable population). Overall, 155 (75%) of 208 patients had 600 treatment-emergent adverse events. A total of 38 drug-related treatment-emergent adverse events occurred in 29 (14%) patients; all were mild or moderate and most common were pyrexia and asthenia. Four deaths occurred during the study; none were considered treatment related. The post-hoc analysis showed similar results to the estimated historical success rate for NECT of 94%. Interpretation Given the high efficacy and favourable safety profile, acoziborole holds promise in the efforts to reach the WHO goal of interrupting HAT transmission by 2030. Funding Bill & Melinda Gates Foundation, UK Aid, Federal Ministry of Education and Research, Swiss Agency for Development and Cooperation, Médecins Sans Frontières, Dutch Ministry of Foreign Affairs, Norwegian Agency for Development Cooperation, Norwegian Ministry of Foreign Affairs, the Stavros Niarchos Foundation, Spanish Agency for International Development Cooperation, and the Banco Bilbao Vizcaya Argentaria Foundation. Translation For the French translation of the abstract see Supplementary Materials section
The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8α+ dendritic cells
Human BDCA3+ dendritic cells (DCs) were suggested to be homologous to mouse CD8α+ DCs. We demonstrate that human BDCA3+ DCs are more efficient than their BDCA1+ counterparts or plasmacytoid DCs (pDCs) in cross-presenting antigen and activating CD8+ T cells, which is similar to mouse CD8α+ DCs as compared with CD11b+ DCs or pDCs, although with more moderate differences between human DC subsets. Yet, no specific marker was known to be shared between homologous DC subsets across species. We found that XC chemokine receptor 1 (XCR1) is specifically expressed and active in mouse CD8α+, human BDCA3+, and sheep CD26+ DCs and is conserved across species. The mRNA encoding the XCR1 ligand chemokine (C motif) ligand 1 (XCL1) is selectively expressed in natural killer (NK) and CD8+ T lymphocytes at steady-state and is enhanced upon activation. Moreover, the Xcl1 mRNA is selectively expressed at high levels in central memory compared with naive CD8+ T lymphocytes. Finally, XCR1−/− mice have decreased early CD8+ T cell responses to Listeria monocytogenes infection, which is associated with higher bacterial loads early in infection. Therefore, XCR1 constitutes the first conserved specific marker for cell subsets homologous to mouse CD8α+ DCs in higher vertebrates and promotes their ability to activate early CD8+ T cell defenses against an intracellular pathogenic bacteria
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