23 research outputs found

    Microstructural evolution in materials during thermal processing

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    Copyright © 2012 Joseph K. L. Lai et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.This article is made available through the Brunel Open Access Publishing Fund

    Correction of Hirschsprung-Associated Mutations in Human Induced Pluripotent Stem Cells Via Clustered Regularly Interspaced Short Palindromic Repeats/Cas9, Restores Neural Crest Cell Function

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    ACKGROUND & AIMS: Hirschsprung disease is caused by failure of enteric neural crest cells (ENCCs) to fully colonize the bowel, leading to bowel obstruction and megacolon. Heterozygous mutations in the coding region of the RET gene cause a severe form of Hirschsprung disease (total colonic aganglionosis). However, 80% of HSCR patients have short-segment Hirschsprung disease (S-HSCR), which has not been associated with genetic factors. We sought to identify mutations associated with S-HSCR, and used the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing system to determine how mutations affect ENCC function. METHODS: We created induced pluripotent stem cell (iPSC) lines from 1 patient with total colonic aganglionosis (with the G731del mutation in RET) and from 2 patients with S-HSCR (without a RET mutation), as well as RET+/- and RET-/- iPSCs. IMR90-iPSC cells were used as the control cell line. Migration and differentiation capacities of iPSC-derived ENCCs were analyzed in differentiation and migration assays. We searched for mutation(s) associated with S-HSCR by combining genetic and transcriptome data from patient blood- and iPSC-derived ENCCs, respectively. Mutations in the iPSCs were corrected using the CRISPR/Cas9 system. RESULTS: ENCCs derived from all iPSC lines, but not control iPSCs, had defects in migration and neuronal lineage differentiation. RET mutations were associated with differentiation and migration defects of ENCCs in vitro. Genetic and transcriptome analyses associated a mutation in the vinculin gene (VCL M209L) with S-HSCR. CRISPR/Cas9 correction of the RET G731del and VCL M209L mutations in iPSCs restored the differentiation and migration capacities of ENCCs. CONCLUSIONS: We identified mutations in VCL associated with S-HSCR. Correction of this mutation in iPSC using CRISPR/Cas9 editing, as well as the RET G731del mutation that causes Hirschsprung disease with total colonic aganglionosis, restored ENCC function. Our study demonstrates how human iPSCs can be used to identify disease-associated mutations and determine how they affect cell functions and contribute to pathogenesis.postprin

    BSM W W production with a jet veto

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    We consider the impact on W W production of the unique dimension-six operator coupling gluons to the Higgs field. In order to study this process, we have to appropriately model the effect of a veto on additional jets. This requires the resummation of large logarithms of the ratio of the maximum jet transverse momentum and the invariant mass of the W boson pair. We have performed such resummation at the appropriate accuracy for the Standard Model (SM) background and for a signal beyond the SM (BSM), and devised a simple method to interface jet-veto resummations with fixed-order event generators. This resulted in the fast numerical code MCFM-RE, the Resummation Edition of the fixed-order code MCFM. We compared our resummed predictions with parton-shower event generators and assessed the size of effects, such as limited detector acceptances, hadronisation and the underlying event, that were not included in our resummation. We have then used the code to compare the sensitivity of W W and Z Z production at the HL-LHC to the considered higher-dimension operator. We have found that W W can provide complementary sensitivity with respect to Z Z, provided one is able to control theory uncertainties at the percent-level. Our method is general and can be applied to the production of any colour singlet, both within and beyond the SM

    Development of a novel temperature indicator

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    The δ-ferrite transformation characteristics of a series of specially made experimental duplex stainless steels have been studied. The ferrite content of these steels changes with time and temperature and this special property is used to develop an effective temperature indicator, i.e. if the time of exposure is known the change in ferrite content in these steels can be used to indicate the average temperature over this period. A Feritscope is used to measure the ferrite content, a measurement which can be performed on site in a matter of seconds. Further advantages of using stainless steel are that it is corrosion resistant, tough, ductile and only a small sample (e.g. 6 mm diameter × 2 mm thick) is required for reproducible measurement.link_to_subscribed_fulltex

    Texture and microstructure development in a cold-rolled duplex stainless steel annealed at 800 °C

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    A cast of austenitic-ferritic duplex stainless steel was rolled 85% and then annealed at 800 °C to study the microstructural and texture changes in the material caused by these mechanical and thermal treatments. The austenite in the duplex alloy behaves as typical low SFE materials when rolled as well as annealed but larger spreads in orientation were observed, compared with rolled and annealed brass. The cold-rolled ferrite mainly consists of long microbands and has texture similar to cold-rolled carbon steel. Upon annealing, the ferrite undergoes recovery only and the rolling texture is thus retained.link_to_subscribed_fulltex

    Knowledge Building and Conceptual Change

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    Since the early research on naive Physics that started in the 1970s, there has been growing recognition of the need for education to take account of learners intuitive ideas, many of which have been found to be robust to change, and the challenge that such ideas pose for education, within the science disciplines and beyond. Some theories have pointed to metaconceptual aspects of understanding as pivotal to conceptual change and that intentional learning would possibly prove to be an effective education approach to change. Knowledge building is a form of intentional learning that promotes epistemic agency at an individual as well as community level. Can we find evidence that knowledge building discourse lead to conceptual change and hence more effective learning of correct concepts in science? A study was designed and conducted on the possible impact of knowledge building activities on conceptual change in mechanics concepts in conjunction with the Go Up, Stay High! Science Design Competition . This contribution reports on the preliminary findings from this study

    Early stages of decomposition of ferrite in duplex stainless steel

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    The decomposition of a duplex stainless steel during aging at 600°C has been investigated using analytical transmission electron microscopy with the intention of elucidating the nucleation sites of the new phases arising from ferrite decomposition. The first transformation product to be formed is M 23 C 6 This carbide, having a cube-cube orientation relationship with the parent y grain, isfound only on certain y/a boundaries and its nucleation is shown to be strongly dependent on the y boundary plane of the y/a interface. Chromium depletion in the vicinity of γ/α boundaries caused by M 23C 6 precipitation initiates the α -→ γ transformation by migration of existing γ/ α boundaries. Another mechanism for this bcc -→ fcc phase change is observed through the growth of Widmanstatten y plates into α. Precipitation of σ begins after M 23 C 6 formation has stopped. The existence of M 23C 6 on γ/α boundaries is crucial to σ formation because the majority of σ particles are found to nucleate on nodes in migrating Y new/α boundaries caused by M 23 C 6 particle pinning. Another less common nucleation site for σ is migrating Y new/α boundaries. The σ particles nucleated on either of the sites have the Nenno orientation relationship with the parent y. In the latter stages, the σ and new γ consume the a grains via a cellular growth mechanism. © 1994 The Institute of Materials.link_to_subscribed_fulltex

    Magnetic properties of thermal-aged 316 stainless steel ands its precipitated phases

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    The magnetic properties of thermally aged bulk 316 stainless steel and the electrolytically extracted precipitates were measured in a wide temperature range from 5 to 375 K with a magnetic field up to 70 kOe using vibrating sample magnetometer. A substantial increase of the Neel temperature of the Fe-Cr-Ni-Mo alloys to approximately 80-100 K arising from long-term aging was observed. The magnetic transition features of the samples corresponding to zero-field cooling and field cooling were also investigated. The magnetizations in the samples for the two cooling conditions were identical above the transition temperature. However, below that temperature the characteristics exhibited obvious discrepancy between the two samples. (C) 2004 Elsevier B.V. All rights reserved
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