Advanced operator splitting based semi-implicit spectral method to solve the binary and single component phase-field crystal model

We present extensive testing in order to find the optimum balance among errors associated with time integration, spatial discretization, and splitting for a fully spectral semi implicit scheme of the phase field crystal model. The scheme solves numerically the equations of dissipative dynamics of the binary phase field crystal model proposed by Elder et al. [Elder et al, 2007]. The fully spectral semi implicit scheme uses the operator splitting method in order to decompose the complex equations in the phase field crystal model into sub-problems that can be solved more efficiently. Using the combination of non-trivial splitting with the spectral approach, the scheme leads to a set of algebraic equations of diagonal matrix form and thus easier to solve. Using this method developed by the BCAST research team we are able to show that it speeds up the computations by orders of magnitude relative to the conventional explicit finite difference scheme, while the costs of the pointwise implicit solution per timestep remains low. Comparing both the finite difference scheme used by Elder et al [Elder et al, 2007] to the spectral semi implicit scheme, we are also able to show that the finite differencing cannot compete with the spectral differencing in regards to accuracy. This is mainly due to numerical dissipation in finite differencing. In addition the results show that this method can efficiently be parallelized for distributed memory systems, where an excellent scalability with the number of CPUs. We have applied the semi-implicit spectral scheme for binary alloys to explore polycrystalline dendritic solidification. The kinetics of transformation has been analysed in terms of Johnson-Mehl-Avrami-Kolmogorov formalism. We show that Avrami plots are not linear, and the respective Avrami-Kolmogorov exponents (PAK) vary with the transformed fraction (or time). Using the semi-implicit spectral scheme we have been able to provide extensive numerical testing of methods in solving the single component case. This has been demonstrated by using unconditional time stepping with comparable simulations using conditional time stepping. We show the accuracy of the solution for unconditional time stepping is not compromised and furthermore computational efficiency can be significantly increased with the introduction of this scheme. Finally we have investigated how the composition of the initial liquid phase influences the eutectic morphology evolving during solidification. This is the first study that addresses this question using the dynamical density functional theory.EThOS - Electronic Theses Online ServiceEPSRCGBUnited Kingdo

Repeatability of tensile properties in high pressure die-castings of an Al-Mg-Si-Mn alloy

© 2015 The Korean Institute of Metals and Materials and Springer Science+Business Media Dordrecht High pressure die-castings of an Al-Mg-Si-Mn alloy have been assessed in terms of the repeatability of the mechanical properties including yield strength, ultimate tensile strength and elongation by the normal standard deviations method and by the Weibull statistical model with three parameters. It was found that the round samples had the maximum Weibull modulus, indicating the best repeatability. The machined samples exhibited the second best of Weibull modulus. Among the square samples, the 2 mm and 5 mm thick samples had the lowest and the highest Weibull modulus respectively, indicating that the repeatability for the castings was influenced by the wall thickness. The microstructural uniformity and porosity levels are critical factors in determining the repeatability of the high pressure die-castings. A less segregation in the microstructure could uniform the stress distribution in the die-castings and a less porosity in the casting could reduce the sources for brittle fracture. These improved the repeatability in casting production.The authors acknowledge the Engineering and Physical Sciences Research Council (EPSRC), Technology Strategy Board (TSB) and Jaguar Land Rover (JLR) in United Kingdom for financial support

Influence of porosity characteristics on the variability in mechanical properties of high pressure die casting (HPDC) AlSi7MgMn alloys

EPSRC U

The role of stathmin, a regulator of mitosis, in hematopoiesis

Steel, JC ORCiD: 0000-0003-3608-7542Introduction Stathmin is a 17KDa cytosolic protein that plays an important role in the regulation of microtubule dynamics, mitotic spindle formation, cell cycle progression and cell differentiation. Stathmin knockout (KO) mice were initially reported to have a normal phenotype but were subsequently shown to develop an age-related neurological phenotype with axonopathy evident in both central and peripheral nervous systems. These mice were also shown to have a defect in recovery from acute ischemic renal injury. We had previously shown that stathmin plays an important role in the differentiation and proliferation of megakaryocytes (MK) and that down-regulation of stathmin is necessary for the maturation of MK and platelet production in vitro. In this study, we investigated the role of stathmin in megakaryopoiesis and hematopoiesis in vivo using the stathmin KO mouse as an experimental model. Results Stathmin KO mice had lower platelet (PLT) counts at 3 weeks of age when compared to WT mice. The WT mice had a mean PLT count of 662 ± 27 K/μL while KO mice had a mean PLT count of 543 ± 37 K/μL. This correlated with larger and fewer MK in the bone marrow of KO mice (WT: 4.2 ± 0.7 MK/40X field; KO: 3.6 ± 0.2 MK/40X field). Furthermore, in the spleen, there was a 10 fold decrease in the number of MK in KO mice compared to WT mice (6.6 ± 0.6 vs 0.7 ± 0.1 MK/40X field). By 8 weeks, PLT counts and MK size and numbers in the bone marrow and spleen were similar in WT and KO mice. Interestingly, by 16 weeks, the mean PLT of KO mice became significantly higher than that of WT and by 40 weeks, the mean PLT count of KO mice was 1379 ± 100K/μL compared to 1045 ± 120K/μL in WT mice (P<0.05). Microscopic analysis of the bone marrow at 46 weeks of age showed approximately 50% more MK in KO mice compared to WT mice. Differences in red blood cell counts (RBC) were also observed. While at 3 weeks, there were no significant differences between the 2 groups, at 8 weeks, KO mice had significantly lower RBC counts, hemoglobin levels (Hb) and hematocrit (HCT). This trend continued until the last measurement recorded at 40 weeks. Mean RBC in WT mice was 10.5 ± 0.1M/μL compared to 8.9 ± 0.2M/μL in KO mice. The mean corpuscular volume (MCV) and the red blood cell distribution width (RDW) were consistently higher in KO mice than in WT mice. No significant differences were noted in white blood cell counts. Bone marrow cell counts were significantly lower in KO mice when compared to WT mice at different ages from 3–40 weeks. Progenitor cell assays from 10–12 week old animals have shown that bone marrow from KO mice produce significantly fewer BFU-E and Pre-B colonies while no differences were observed in CFU-GMs. Conclusions The phenotypic characteristics of stathmin KO mice confirmed our prior in vitro findings that suggested a role for stathmin in megakaryopoiesis. We expected to see a decrease in the number of platelets and MK coupled with an increase in MK size. This was confirmed in stathmin KO mice at 3 weeks of age. However, we did not expect to see the marked increase in the number of platelets and MK that was observed as the mice aged. The exact mechanism for this has not been identified. Interestingly, the stathmin KO mice exhibited characteristic features of megaloblastic anemia including mild anemia and a significant increase in MCV and RDW. The megaloblastic anemia that is seen in the presence of B12 and folate deficiency results from interference with DNA synthesis resulting in asynchronous maturation of the nucleus and the cytoplasm. We believe a similar phenomenon is occurring in the stathmin KO mice. The deficiency of stathmin results in aberrant exit from mitosis, thereby delaying nuclear maturation and resulting in the megaloblastic features. Thus, the deficiency of stathmin in the KO mice results in two hematopoietic phenotypes that are seen in humans, megaloblastic anemia and thrombocytosis. It is unclear whether mutations of stathmin in humans might result in similar phenotypes. This is a question that will require further investigation. Future studies will investigate the compensatory mechanisms that result in the switch from decreased to increased platelet production as the mice age. Furthermore, examining the effects of hematopoietic stress (e.g. response to chemotherapy or bleeding) in stathmin KO mice might also elucidate a role for stathmin in the recovery from hematopoietic injury as was seen in acute ischemic renal injury

Biological and technical factors in the assessment of blood-based tumor mutational burden (bTMB) in patients with NSCLC

BACKGROUND: Patients treated with immunotherapy are at risk of considerable adverse events, and the ongoing struggle is to accurately identify the subset of patients who will benefit. Tumor mutational burden (TMB) has emerged as a promising predictive biomarker but requires tumor tissue which is not always available. Blood-based TMB (bTMB) may provide a minimally invasive assessment of mutational load. However, because of the required sequencing depth, bTMB analysis is costly and prone to false negative results. This study attempted to design a minimally sized bTMB panel, examined a counting-based method for bTMB in patients with stage I to IV non-small cell lung cancer (NSCLC) and evaluated both technical factors such as bTMB and tissue-based TMB (tTMB) cut-off, as well as sample-related factors such as cell-free DNA input mass which influence the correlation between bTMB and tTMB. METHODS: Tissue, plasma, and whole blood samples collected as part of the LEMA trial (NCT02894853) were used in this study. Samples of 185 treatment naïve patients with stage I to IV NSCLC were sequenced at the Roche Sequencing Solutions with a custom panel designed for TMB, using reagents and workflows derived from the AVENIO Tumor Tissue and circulating tumor DNA Analysis Kits. RESULTS: A TMB panel of 1.1 Mb demonstrated highly accurate TMB high calls with a positive predictive value of 95% when using a tTMB cut-off of 16 mut/Mb, corresponding with 42 mut/Mb for bTMB. The positive per cent agreement (PPA) of bTMB was relatively low at 32%. In stage IV samples with at least 20 ng of cfDNA input, PPA of bTMB improved to 63% and minimizing the panel to a subset of 577 kb was possible while maintaining 63% PPA. CONCLUSION: Plasma samples with high bTMB values are highly correspondent with tTMB, whereas bTMB low results may also be the result of low tumor burden at earlier stages of disease as well as poorly shedding tumors. For advanced stages of disease, PPA (sensitivity) of bTMB is satisfactory in comparison to tTMB, even when using a panel of less than 600 kb, warranting consideration of bTMB as a predictive biomarker for patients with NSCLC eligible for immunotherapy in the future

OECD/NEA PKL-4 benchmark activity. Code assessment of the relevant phenomena associated to a blind IBLOCA experiment

International audienceCode assessment and validation is one of the most relevant research lines in thermal hydraulics and best estimatecodes. During the last decades, the Nuclear Energy Agency (NEA) and the Organization for Economic Cooperation and Development (OECD) have sponsored dozens of experimental projects in this field. Most ofthem were compiled in the CSNI Code Validation Matrix in 1996. Several projects have been promoted in thenew century as the SETH, PKL, PKL-2, PKL-3 and PKL-4 at the PKL test facility. In 2017 a benchmark activity waslaunched within the framework of the OECD/NEA PKL-4 project with the aim of assessing the capabilities ofsystem codes to reproduce the relevant phenomena associated to the IBLOCA scenario. 16 participant organizations from 9 different countries simulated the i2.2 (run 3) experiment in semi-blind conditions. A large varietyof system codes were used in the activity: ATHLET, CATHARE, KORSAR, LOCUST, RELAP5, RELAPSCDASIM,SPACE and TRACE. This paper presents the main outcomes for the code assessment of such codes. The first partdescribes the main features of the experiment and the selection of the key phenomena for code validation. Inaddition, the paper intoduces a detailed description of each phenomena and the comparison between theexperimental data and the blind simulations of the participants. Finally, in the last part of the paper the mainsources of uncertainty associated to the codes and the modelling are listed as well as the code assessmentconclusions of the benchmark activity. In general, the results obtained by all participants showed a good performance and satisfactory agreement with experimental data, which increases the confidence in current TH codetechnologies. The overall quality of the contributions was partly a consequence of the excellent documentationand information provided by the PKL team

The eigen-structures of real (skew) circulant matrices with some applications

The circulant matrices and skew-circulant matrices are two special classes of Toeplitz matrices and play vital roles in the computation of Toeplitz matrices. In this paper, we focus on real circulant and skew-circulant matrices. We first investigate their real Schur forms, which are closely related to the family of discrete cosine transform (DCT) and discrete sine transform (DST). Using those real Schur forms, we then develop some fast algorithms for computing real circulant, skew-circulant and Toeplitz matrix-real vector multiplications. Also, we develop a DCT-DST version of circulant and skew-circulant splitting (CSCS) iteration for real positive definite Toeplitz systems. Compared with the fast Fourier transform (FFT) version of CSCS iteration, the DCT-DST version is more efficient and saves a half storage. Numerical experiments are presented to illustrate the effectiveness of our method.The authors would like to thank the supports of the National Natural Science Foundationof China under Grant No. 11371075, the Hunan Key Laboratory of Mathematical Modeling and Analysis inEngineering, and the Portuguese Funds through FCT-Fundação para a Ciência, within the Project UID/ MAT/00013/2013