56 research outputs found
Pre-Conceptual Design of a Fluoride-Salt-Cooled Small Modular Advanced High Temperature Reactor (SmAHTR)
This document presents the results of a study conducted at Oak Ridge National Laboratory during 2010 to explore the feasibility of small modular fluoride salt-cooled high temperature reactors (FHRs). A preliminary reactor system concept, SmATHR (for Small modular Advanced High Temperature Reactor) is described, along with an integrated high-temperature thermal energy storage or salt vault system. The SmAHTR is a 125 MWt, integral primary, liquid salt cooled, coated particle-graphite fueled, low-pressure system operating at 700 C. The system employs passive decay heat removal and two-out-of-three , 50% capacity, subsystem redundancy for critical functions. The reactor vessel is sufficiently small to be transportable on standard commercial tractor-trailer transport vehicles. Initial transient analyses indicated the transition from normal reactor operations to passive decay heat removal is accomplished in a manner that preserves robust safety margins at all times during the transient. Numerous trade studies and trade-space considerations are discussed, along with the resultant initial system concept. The current concept is not optimized. Work remains to more completely define the overall system with particular emphasis on refining the final fuel/core configuration, salt vault configuration, and integrated system dynamics and safety behavior
IFN-γ-Inducible Irga6 Mediates Host Resistance against Chlamydia trachomatis via Autophagy
Chlamydial infection of the host cell induces Gamma interferon (IFNγ), a central immunoprotector for humans and mice. The primary defense against Chlamydia infection in the mouse involves the IFNγ-inducible family of IRG proteins; however, the precise mechanisms mediating the pathogen's elimination are unknown. In this study, we identify Irga6 as an important resistance factor against C. trachomatis, but not C. muridarum, infection in IFNγ-stimulated mouse embryonic fibroblasts (MEFs). We show that Irga6, Irgd, Irgm2 and Irgm3 accumulate at bacterial inclusions in MEFs upon stimulation with IFNγ, whereas Irgb6 colocalized in the presence or absence of the cytokine. This accumulation triggers a rerouting of bacterial inclusions to autophagosomes that subsequently fuse to lysosomes for elimination. Autophagy-deficient Atg5−/− MEFs and lysosomal acidification impaired cells surrender to infection. Irgm2, Irgm3 and Irgd still localize to inclusions in IFNγ-induced Atg5−/− cells, but Irga6 localization is disrupted indicating its pivotal role in pathogen resistance. Irga6-deficient (Irga6−/−) MEFs, in which chlamydial growth is enhanced, do not respond to IFNγ even though Irgb6, Irgd, Irgm2 and Irgm3 still localize to inclusions. Taken together, we identify Irga6 as a necessary factor in conferring host resistance by remodelling a classically nonfusogenic intracellular pathogen to stimulate fusion with autophagosomes, thereby rerouting the intruder to the lysosomal compartment for destruction
Recommended from our members
Pre-Conceptual Design of a Fluoride-Salt-Cooled Small Modular Advanced High Temperature Reactor (SmAHTR)
This document presents the results of a study conducted at Oak Ridge National Laboratory during 2010 to explore the feasibility of small modular fluoride salt-cooled high temperature reactors (FHRs). A preliminary reactor system concept, SmATHR (for Small modular Advanced High Temperature Reactor) is described, along with an integrated high-temperature thermal energy storage or salt vault system. The SmAHTR is a 125 MWt, integral primary, liquid salt cooled, coated particle-graphite fueled, low-pressure system operating at 700 C. The system employs passive decay heat removal and two-out-of-three , 50% capacity, subsystem redundancy for critical functions. The reactor vessel is sufficiently small to be transportable on standard commercial tractor-trailer transport vehicles. Initial transient analyses indicated the transition from normal reactor operations to passive decay heat removal is accomplished in a manner that preserves robust safety margins at all times during the transient. Numerous trade studies and trade-space considerations are discussed, along with the resultant initial system concept. The current concept is not optimized. Work remains to more completely define the overall system with particular emphasis on refining the final fuel/core configuration, salt vault configuration, and integrated system dynamics and safety behavior
The ethics of ‘Trials within Cohorts’ (TwiCs): 2nd international symposium - London, UK. 7-8 November 2016
On 7-8
th
November 2016, 60 people with an interest in the
‘
Trials
within Cohorts
’
(TwiCs) approach for randomised controlled trial design
met in London. The purpose of this 2
nd
TwiCs international symposium
was to share perspectives and experiences on ethical aspects of the
TwiCs design, discuss how TwiCs relate to the current ethical frame-
work, provide a forum in which to discuss and debate ethical issues
and identify future directions for conceptual and empirical research.
The symposium was supported by the Wellcome Trust and the NIHR
CLAHRC Yorkshire and Humber and organised by members of the
TwiCs network led by Clare Relton and attended by people from the
UK, the Netherlands, Norway, Canada and USA. The two-day sympo-
sium enabled an international group to meet and share experiences
of the TwiCs design (also known as the
‘
cohort multiple RCT design
’
),
and to discuss plans for future research. Over the two days, invited
plenary talks were interspersed by discussions, posters and mini pre-
sentations from bioethicists, triallists and health research regulators.
Key findings of the symposium were: (1) It is possible to make a
compelling case to ethics committees that TwiCs designs are ap-
propriate and ethical; (2) The importance of wider considerations
around the ethics of inefficient trial designs; and (3) some questions
about the ethical requirements for content and timing of informed
consent for a study using the TwiCs design need to be decided on
a case-by-case basis
The first myriapod genome sequence reveals conservative arthropod gene content and genome organisation in the centipede Strigamia maritima.
Myriapods (e.g., centipedes and millipedes) display a simple homonomous body plan relative to other arthropods. All members of the class are terrestrial, but they attained terrestriality independently of insects. Myriapoda is the only arthropod class not represented by a sequenced genome. We present an analysis of the genome of the centipede Strigamia maritima. It retains a compact genome that has undergone less gene loss and shuffling than previously sequenced arthropods, and many orthologues of genes conserved from the bilaterian ancestor that have been lost in insects. Our analysis locates many genes in conserved macro-synteny contexts, and many small-scale examples of gene clustering. We describe several examples where S. maritima shows different solutions from insects to similar problems. The insect olfactory receptor gene family is absent from S. maritima, and olfaction in air is likely effected by expansion of other receptor gene families. For some genes S. maritima has evolved paralogues to generate coding sequence diversity, where insects use alternate splicing. This is most striking for the Dscam gene, which in Drosophila generates more than 100,000 alternate splice forms, but in S. maritima is encoded by over 100 paralogues. We see an intriguing linkage between the absence of any known photosensory proteins in a blind organism and the additional absence of canonical circadian clock genes. The phylogenetic position of myriapods allows us to identify where in arthropod phylogeny several particular molecular mechanisms and traits emerged. For example, we conclude that juvenile hormone signalling evolved with the emergence of the exoskeleton in the arthropods and that RR-1 containing cuticle proteins evolved in the lineage leading to Mandibulata. We also identify when various gene expansions and losses occurred. The genome of S. maritima offers us a unique glimpse into the ancestral arthropod genome, while also displaying many adaptations to its specific life history.This work was supported by the following grants: NHGRIU54HG003273 to R.A.G; EU Marie Curie ITN #215781 “Evonet” to M.A.; a Wellcome Trust Value in People (VIP) award to C.B. and Wellcome Trust graduate studentship WT089615MA to J.E.G; Marine
rhythms of Life” of the University of Vienna, an FWF (http://www.fwf.ac.at/) START award (#AY0041321) and HFSP (http://www.hfsp.org/) research grant (#RGY0082/2010) to KT-‐R; MFPL Vienna International PostDoctoral Program for Molecular Life Sciences (funded by Austrian Ministry of Science and Research and City of Vienna, Cultural Department -‐Science and Research to T.K; Direct Grant (4053034) of the Chinese University of Hong Kong to J.H.L.H.; NHGRI HG004164 to G.M.; Danish Research Agency (FNU), Carlsberg Foundation, and Lundbeck Foundation to C.J.P.G.; U.S. National Institutes of Health R01AI55624 to J.H.W.; Royal Society University Research fellowship to F.M.J.; P.D.E. was supported by the BBSRC via the Babraham Institute;This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pbio.100200
Re-visiting Meltsner: Policy Advice Systems and the Multi-Dimensional Nature of Professional Policy Analysis
10.2139/ssrn.15462511-2
Smart contracts as execution instead of expression
Analysis of the functioning of smart contracts in the framework of traditional contract performance, where the focus is no longer on the expressive function for parties, but solely on a specification of the execution
Recommended from our members
Data Compilation for AGR-1 Pre-Production Test: NUCO350-75T-Z
This document is a compilation of characterization data for compact lot NUCO350-75T-Z. This compact lot was fabricated using particle composite NUCO350-75T, which was a composite of three batches of TRISO-coated 350 m natural uranium oxide/uranium carbide kernels (NUCO). The compacts and coated particles were produced as part of a development effort at ORNL for the Advanced Gas Reactor Fuel Development and Qualification (AGR) program. The kernels were obtained from BWXT and were identified as composite G73B-NU-69300. The BWXT kernel lot G73B-NU-69300 was riffled into sublots for characterization and coating. The ORNL identification for these kernel sublots was NUCO350-## (where ## were a series of integers beginning with 01). NUCO350-75T-Z was produced as part of the ORNL AGR development effort and is not fully representative of a final product. This compact lot was the first run through of the entire ORNL AGR-1 irradiation test fuel production process involving coating, characterization, and compacting of TRISO-coated 350 m NUCO. The results of this exercise were used to fine tune the irradiation test fuel production process and as a basis for the decision to proceed with the production of the baseline fuel for the AGR-1 irradiation test
Recommended from our members
Data Compilation for AGR-1 Variant 3 Compact Lot LEU01-49T-Z
This document is a compilation of characterization data for the AGR-1 vriant 3 fuel compact lot LEU01-49T-Z. The compacts were produced by ORNL for the Advanced Gas Reactor Fuel Development and Qualification (AGR) program for the first AGR irradiation test train (AGR-1). This compact lot was fabricated using particle composite LEU01-49T, which was a composite of three batches of TRISO-coated 350 {micro}m diameter 19.7% low enrichment uranium oxide/uranium carbide kernels (LEUCO). The AGR-1 TRISO-coated particles consist of a spherical kernel coated with an {approx} 50% dense carbon buffer layer (100 {micro}m nominal thickness), followed by a dense inner pyrocarbon layer (40 {micro}m nominal thickness), followed by a SiC layer (35 {micro}m nominal thickness), followed by another dense outer pyrocarbon layer (40 {micro}m nominal thickness). The kernels were obtained from BWXT and identified as composite G73D-20-69302. The BWXT kernel lot G73D-20-69302 was riffled into sublots for characterization and coating by ORNL and identified as LEU01-?? (where ?? is a series of integers beginning with 01). A data compilation for the AGR-1 variant 3 coated particle composite LEU01-49t CAN BE FOUND IN ornl/tm-2006/022
Recommended from our members
Data Compilation for AGR-1 Variant 2 Compact Lot LEU01-48T-Z
This document is a compilation of characterization data for the AGR-1 variant 2 compact lot LEU01-48T-Z. The compacts were produced by ORNL for the Advanced Gas Reactor Fuel Development and Qualification (AGR) program for the first AGR irradiation test train (AGR-1). This compact lot was fabricated using particle composite LEU01-48T, which was a composite of three batches of TRISO-coated 350 {micro}m diameter 19.7% low enrichment uranium oxide/uranium carbide kernels (LEUCO). The AGR-1 TRISO-coated particles consist of a spherical kernel coated with an {approx} 50% dense carbon buffer layer (100 {micro}m nominal thickness), followed by a dense inner pyrocarbon layer (40 {micro}m nominal thickness), followed by a SiC layer (35 {micro}m nominal thickness), followed by another dense outer pyrocarbon layer (40 {micro}m nominal thickness). The kernels were obtained from BWXT and identified as composite G73D-20-69302. The BWXT kernel lot G73D-20-69302 was riffled into sublots for characterization and coating by ORNL and identified as LEU01-?? (where ?? is a series of integers beginning with 01). A data compilation for the AGR-1 variant 2 coated particle composite LEU01-48T can be found in ORNL/TM-2006/021. The AGR-1 Fuel Product Specification and Characterization Guidance (INL EDF-4380) provides the requirements necessary for acceptance of the fuel manufactured for the AGR-1 irradiation test. Section 6.2 of EDF-4380 provides the property requirements for the heat treated compacts. The Statistical Sampling Plan for AGR Fuel materials (INL EDF-4542) provides additional guidance regarding statistical methods for product acceptance and recommended sample sizes. The procedures for characterizing and qualifying the compacts are outlined in ORNL product inspection plan AGR-CHAR-PIP-05. The inspection report forms generated by this product inspection plan document the product acceptance for the property requirements listed in section 6.2 of EDF-4380
- …