This paper proposes a decoupling algorithm for reliability-based design optimization (RBDO) with high performance in terms of efficiency and convergence, which provides an effective tool for ...reliability design of many complex structures. The algorithm proceeds by performing a shifting vector calculation and then solving a deterministic design optimization in each step, and eventually converges to the optimal solution. An incremental shifting strategy is proposed to ensure stable convergence in the iteration process. In each step, the shifting vector preserves the information from the previous step, and only an adjustment is made for it through a shifting vector increment. A computation method is given for the shifting vector increment, avoiding solving an optimization problem during the reliability analysis and thus greatly reducing the computational cost of the iteration process. Six numerical examples and two engineering applications are presented to validate the effectiveness of the method proposed in this paper.
The conventional cold welding concept was extended to nanoscale, in which silver nanowires were welded together by large plastic deformation. A nanoindenter was employed as a cold welding tool to ...visualize and conduct welding. The MD simulation shows that unlike single crystal nanowire, sufficient plastic deformation is key to realize successful welding when the two nanoobjects have large orientation mismatching. The lattice orientation of joint interface is complex but no defects were found in both experimental and simulation.
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•Near fully dense TiC particles strengthened FeCrAl alloys have been fabricated by directed energy deposition.•TiC additions significantly refine the grain sizes and prompt columnar to equiaxed grain ...transition.•TiC particles strengthened FeCrAl alloys have good mechanical properties both at room temperature and high temperature of 650 ℃.
Directed energy deposition (DED) additive manufacturing process has been attractive to the fabrications of FeCrAl alloys due to the advantage of near net shaping of complex shaped components. In order to improve the strength, TiC particles strengthened FeCrAl alloys have been fabricated by DED using blended FeCrAl powder and TiC nanoparticles. The results show that the TiC particles in the DED alloys have submicron sizes, and polygonal or dendritic shapes. Most TiC particles are distributed along the dendritic/grain boundaries. The additions of TiC particles effectively refine the grain sizes, and at the same time prompt a columnar to equiaxed transition of grains. The grain sizes are reduced from 1377 μm to 47 μm, 21 μm and 22 μm when the TiC particle contents in the DED alloys increase from 0 wt% to 0.7 wt%, 2.4 wt% and 3.5 wt%, respectively. The room temperature strength of the FeCrAl alloys increase with the increase of TiC particle content. With 3.5 wt% TiC particle content, the FeCrAl alloy has good mechanical properties with yield strength of 437 MPa, ultimate tensile strength of 688 MPa, and an elongation of 19 %. The 650 ℃ high temperature strength of the FeCrAl alloys first decrease and then increase with the increase of TiC particle content. With 3.5 wt% TiC particle content, the FeCrAl alloy has excellent mechanical properties with yield strength of 208 MPa, ultimate tensile strength of 223 MPa, and an elongation of 53 %. The present study provides an important basis for fabricating high strength particle-strengthened FeCrAl alloys using the DED process.
Oncogenic NRAS and KRAS mutations are prevalent in human juvenile and chronic myelomonocytic leukemia (JMML/CMML). However, additional genetic mutations cooperating with oncogenic RAS in JMML/ CMML ...progression and/or their transformation to acute myeloid leukemia (AML) remain largely unknown. Here we tested the potential genetic interaction of DNMT3A mutations and oncogenic RAS mutations in leukemogenesis. We found that Dnmt3a-/- induces multiple hematopoietic phenotypes after a prolonged latency, including T-cell expansion in the peripheral blood, stress erythropoiesis in the spleen and myeloid malignancies in the liver. Dnmt3a-/- significantly promoted JMML/CMML progression and shortened the survival of KrasG12D/+ mice in a cell-autonomous manner. Similarly, downregulating Dnmt3a also promoted myeloid malignancies in NrasG12D/+ mice. Further studies show that Dnmt3a deficiency rescues KrasG12D/+ -mediated depletion of hematopoietic stem cells and increases self-renewal of KrasG12D/+ myeloid progenitors (MPs). Moreover, ~33% of animals developed an AML-like disease, which is driven by KrasG12D/+ ; Dnmt3a-/- MPs. Consistent with our result, COSMIC database mining demonstrates that the combination of oncogenic RAS and DNMT3A mutations exclusively occurred in patients with JMML, CMML or AML. Our results suggest that DNMT3A mutations and oncogenic RAS cooperate to regulate hematopoietic stem and progenitor cells and promote myeloid malignancies.
One of the most effective ways to improve reactive wetting of dual phase (DP) steels during galvanizing process is annealing under relatively high oxygen partial pressure. This annealing process can ...lead to internal oxide formation rather than external ones. Since these oxides are mostly observed in grain boundaries (GBs), their presence could influence GB-related phenomena such as liquid metal embrittlement (LME) cracking during further manufacturing processes such as resistance spot welding (RSW). The present work has shown that internal oxides located at GBs assisted LME crack formation during RSW of DP steel. Two types of LME cracks were observed in the shoulder and center of the weld. It has been shown that at the initial stages of welding time, LME cracks initiate in the shoulder of the nugget by the Zn diffusion into oxide-bearing GBs. As welding time continues, higher temperatures and tensile stresses are applied to the steel sheets which allow center cracks to be formed more easily due to the presence of oxides which degrade the GBs.
Abstract
Objectives
To determine whether the introduction of biological DMARDs (bDMARDs) was associated with reduced incidences of total hip and knee arthroplasty (THA/TKA) among patients with RA ...compared with OA.
Methods
Using a population-based cohort in British Columbia, Canada, RA and OA patients diagnosed between 1995 and 2007 were divided into semi-annual cohorts according to diagnosis date. For each cohort, we calculated 8-year incidence rates of THA and TKA. We compared levels and trends of THA/TKA incidence in RA/OA patients diagnosed during pre-bDMARDs (1995–2001) and post-bDMARDs (2003–2007) periods using interrupted time-series analysis, adjusting for baseline characteristics. Adjusted 8-year total joint arthroplasty incidence estimated for RA/OA cohorts diagnosed five years after bDMARDs introduction were compared with expected rates assuming no bDMARDs introduction, based on extrapolation of pre-bDMARDs trends.
Results
We identified 60 227 RA and 288 260 OA incident cases. For cohorts diagnosed pre-bDMARDs, 8-year THA/TKA incidence rates increased over time in both RA and OA. For cohorts diagnosed post-bDMARDs, these rates decreased over time in RA but continued to increase for OA. For RA, differences between the post- and pre-bDMARDs secular trends in incidence rates were −0.49 (P = 0.002) for THA and −0.36 (P = 0.003) for TKA, compared with +0.40 (P = 0.006) and +0.54 (P < 0.001), respectively, for OA. For RA cohorts diagnosed five years after bDMARDs introduction, 8-year incidences were 26.9% and 12.6% lower for THA and TKA, respectively, than expected rates. In contrast, corresponding rates in OA were higher by 11.7% and 16.6%, respectively.
Conclusion
Arthritis onset after bDMARDs introduction is associated with a significant reduction in THA/TKA incidence in RA, but not in OA. The reduction reflects a significant improvement in RA treatment during the biological era.
Vacuum brazing of C/C composite to TC4 alloy was performed using nano-Al2O3 strengthened AgCuTi composite filler. The microstructure and main properties of the composite filler were characterized. ...The typical interfacial microstructure of brazed joint is TC4/diffusion layer/Ti–Cu intermetallic layers/Ag(s,s)+Cu(s,s)+TiCu/TiC/C/C composite. The effects of brazing temperature and addition of nano-Al2O3 on microstructure of brazed joints were investigated by SEM, EDS, TEM and XRD. The diffusion layer, Ti–Cu intermetallic layers and TiC layer thicken with the increasing temperature while the thickness of brazing seam decreases. The TiCu phase in brazing seam excessively develops and almost replaces the Ag(s,s) and Cu(s,s) when brazing temperature reaches 920°C. The addition of nano-Al2O3 improves the performance of brazed joints by inhibiting the growth of Ti–Cu layers adjacent to TC4 side and offering dispersive nucleation sites for TiCu phase in brazing seam. The joint brazed at 880°C for 10min exhibits the highest shear strength of 27.8MPa. The fracture positions of brazed joints are also discussed in this paper.
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•C/C composite was successfully brazed using nano-Al2O3 strengthened AgCuTi filler.•The addition of nano-Al2O3 improves the performance of joints.•The highest shear strength of joints reached 27.8MPa.•The fracture positions are related to temperatures and orientations of carbon fiber.
Recent genome-wide association studies identified over 100 genetic loci that significantly associate with schizophrenia (SZ). A top candidate gene, ZNF804A, was robustly replicated in different ...populations. However, its neural functions are largely unknown. Here we show in mouse that ZFP804A, the homolog of ZNF804A, is required for normal progenitor proliferation and neuronal migration. Using a yeast two-hybrid genome-wide screen, we identified novel interacting proteins of ZNF804A. Rather than transcriptional factors, genes involved in mRNA translation are highly represented in our interactome result. ZNF804A co-fractionates with translational machinery and modulates the translational efficiency as well as the mTOR pathway. The ribosomal protein RPSA interacts with ZNF804A and rescues the migration and translational defects caused by ZNF804A knockdown. RNA immunoprecipitation-RNAseq (RIP-Seq) identified transcripts bound to ZFP804A. Consistently, ZFP804A associates with many short transcripts involved in translational and mitochondrial regulation. Moreover, among the transcripts associated with ZFP804A, a SZ risk gene, neurogranin (NRGN), is one of ZFP804A targets. Interestingly, downregulation of ZFP804A decreases NRGN expression and overexpression of NRGN can ameliorate ZFP804A-mediated migration defect. To verify the downstream targets of ZNF804A, a Duolink in situ interaction assay confirmed genes from our RIP-Seq data as the ZNF804A targets. Thus, our work uncovered a novel mechanistic link of a SZ risk gene to neurodevelopment and translational control. The interactome-driven approach here is an effective way for translating genome-wide association findings into novel biological insights of human diseases.
Ni–SiC nanocomposite coatings were produced by electrodeposition from a nickel sulfate bath containing SiC nanoparticles with an average particle size of 30
nm. The characteristics of the coatings ...were assessed by scanning electron microscopy and microhardness test. The friction and wear performance of Ni–SiC nanocomposite coatings and Ni film were comparatively investigated sliding against Si
3N
4 ceramic balls under non-lubricated conditions. The results indicated that compared to Ni film, Ni–SiC nanocomposite coating exhibited enhanced microhardness and wear resistance. The effect of SiC nanoparticles on the friction and wear resistance is discussed in detail.
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