Manufacturing-oriented topology optimization has been extensively studied the past two decades, in particular for the conventional manufacturing methods, for example, machining and injection molding ...or casting. Both design and manufacturing engineers have benefited from these efforts because of the close-to-optimal and friendly-to-manufacture design solutions. Recently, additive manufacturing (AM) has received significant attention from both academia and industry. AM is characterized by producing geometrically complex components layer-by-layer, and greatly reduces the geometric complexity restrictions imposed on topology optimization by conventional manufacturing. In other words, AM can make near-full use of the freeform structural evolution of topology optimization. Even so, new rules and restrictions emerge due to the diverse and intricate AM processes, which should be carefully addressed when developing the AM-specific topology optimization algorithms. Therefore, the motivation of this perspective paper is to summarize the state-of-art topology optimization methods for a variety of AM topics. At the same time, this paper also expresses the authors’ perspectives on the challenges and opportunities in these topics. The hope is to inspire both researchers and engineers to meet these challenges with innovative solutions.
A new topology optimization method called the Proportional Topology Optimization (PTO) is presented. As a non-sensitivity method, PTO is simple to understand, easy to implement, and is also efficient ...and accurate at the same time. It is implemented into two MATLAB programs to solve the stress constrained and minimum compliance problems. Descriptions of the algorithm and computer programs are provided in detail. The method is applied to solve three numerical examples for both types of problems. The method shows comparable efficiency and accuracy with an existing optimality criteria method which computes sensitivities. Also, the PTO stress constrained algorithm and minimum compliance algorithm are compared by feeding output from one algorithm to the other in an alternative manner, where the former yields lower maximum stress and volume fraction but higher compliance compared to the latter. Advantages and disadvantages of the proposed method and future works are discussed. The computer programs are self-contained and publicly shared in the website www.ptomethod.org.
This paper presents a novel level set-based topology optimization implementation, which addresses two main problems of design-for-additive manufacturing (AM): the material anisotropy and the ...self-support manufacturability constraint. AM material anisotropy is widely recognized and taking it into account while performing structural topology optimization could more realistically evaluate the structural performance. Therefore, both build direction and in-plane raster directions are considered by the topology optimization algorithm, especially for the latter, which is calculated through deposition path planning. The self-support manufacturability constraint is addressed through a novel multi-level set modeling. The related optimization problem formulation and solution process are demonstrated in detail. It is proved by several numerical examples that the manufacturability constraints are always strictly satisfied. Marginally, the recently popular structural skeleton-based deposition paths are also employed to assist the structural topology optimization, and its characteristics are discussed.
•This paper presents a deposition path planning-integrated structural topology optimization method for 3D additive manufacturing.•Local material anisotropy is addressed by considering the build direction and the in-plane raster directions.•The support-free manufacturability constraint is addressed through a novel multi-level set modeling.•Both the contour-offset and structural skeleton-based deposition path patterns have been considered.
This paper proposed a new topology optimization method based on geometry deep learning. The density distribution in design domain is described by deep neural networks. Compared to traditional ...density-based method, using geometry deep learning method to describe the density distribution function can guarantee the smoothness of the boundary and effectively overcome the checkerboard phenomenon. The design variables can be reduced phenomenally based on deep learning representation method. The numerical results for three different kernels including the Gaussian, Tansig, and Tribas are compared. The structural complexity can be directly controlled through the architectures of the neural networks, and minimum length is also controllable for the Gaussian kernel. Several 2-D and 3-D numerical examples are demonstrated in detail to demonstrate the effectiveness of proposed method from minimum compliance to stress-constrained problems.
Objective
To study the level of anti–müllerian hormone (AMH) and its relationship to age and previous exposure to cyclophosphamide (CYC) in patients with systemic lupus erythematosus (SLE).
Methods
...Consecutive female patients ages 18–52 years who had menses at least once during the preceding 12 months and fulfilled ≥4 American College of Rheumatology criteria for SLE were recruited. AMH was determined using an enzyme‐linked immunosorbent assay (ELISA) kit. Serum AMH levels were compared in patients with and without previous use of immunosuppressive agents. The relationship of the AMH level to the patient's age and CYC exposure was studied by linear regression and receiver operating characteristic (ROC) curve analysis.
Results
A total of 216 patients were studied (mean ± SD age 35.1 ± 10.1 years, mean ± SD SLE duration 7.6 ± 5.9 years). The mean ± SD AMH level was significantly lower in patients previously exposed to CYC therapy than in those who had not been exposed after adjustment for age (1.58 ± 2.92 versus 1.73 ± 2.11 ng/ml; P = 0.04). The median time interval between the AMH assay and the last dose of CYC administered was 6.7 years (interquartile range 3.4–8.5). AMH levels in users versus nonusers of other immunosuppressive agents, including mycophenolate mofetil, azathioprine, and the calcineurin inhibitors, were not statistically different. Linear regression revealed increasing age (beta −0.32, P = 0.02) and each 5 gm of CYC exposure (beta −0.28, P = 0.047) were independently associated with a lower AMH level. In patients ages 30 years and younger, a cumulative CYC dose cutoff of 5.9 gm yielded a sensitivity of 0.75 and a specificity of 0.80 for the prediction of undetectable AMH level on ROC curve analysis.
Conclusion
AMH is a sensitive marker for ovarian damage due to previous CYC exposure in women with SLE.
It is challenging to predict the residual deformation in the part-scale by performing detailed process simulation for the large part. In this work, the modified inherent strain theory is proposed to ...enable efficient yet accurate prediction of the residual deformation of large components produced by the Direct Metal Laser Sintering process. The proposed theory allows for the calculation of inherent strain accurately based on a small-scale process simulation of a small representative volume. The extracted mean inherent strain vector will be applied to a part-scale model layer-by-layer in order to simulate accumulation of the residual deformation by static finite element analysis. To verify the accuracy of the proposed method, the residual deformation of the double cantilever beam and the complex canonical part after the DMLS process is investigated, and the predicted residual deformation matches well with the experimental results for both large parts while the computational efficiency is also shown.
ABSTRACT
Analyses of Type Ia supernovae (SNe Ia) have found puzzling correlations between their standardized luminosities and host galaxy properties: SNe Ia in high-mass, passive hosts appear ...brighter than those in lower mass, star-forming hosts. We examine the host galaxies of SNe Ia in the Dark Energy Survey 3-yr spectroscopically confirmed cosmological sample, obtaining photometry in a series of ‘local’ apertures centred on the SN, and for the global host galaxy. We study the differences in these host galaxy properties, such as stellar mass and rest-frame U − R colours, and their correlations with SN Ia parameters including Hubble residuals. We find all Hubble residual steps to be >3σ in significance, both for splitting at the traditional environmental property sample median and for the step of maximum significance. For stellar mass, we find a maximal local step of 0.098 ± 0.018 mag; ∼0.03 mag greater than the largest global stellar mass step in our sample (0.070 ± 0.017 mag). When splitting at the sample median, differences between local and global U − R steps are small, both ∼0.08 mag, but are more significant than the global stellar mass step (0.057 ± 0.017 mag). We split the data into sub-samples based on SN Ia light-curve parameters: stretch (x1) and colour (c), finding that redder objects (c > 0) have larger Hubble residual steps, for both stellar mass and U − R, for both local and global measurements, of ∼0.14 mag. Additionally, the bluer (star-forming) local environments host a more homogeneous SN Ia sample, with local U − R rms scatter as low as 0.084 ± 0.017 mag for blue (c < 0) SNe Ia in locally blue U − R environments.
•Immunogenicity of the quadrivalent HPV vaccine is retained in the majority of SLE patients at 5 years post-vaccination.•Patients with more SLE flares, particularly renal, and have received more ...immunosuppression are at risk of sero-reversion of anti-HPV antibodies.
To evaluate the 5-year immunogenicity of a quadrivalent human papillomavirus (HPV) vaccine (GARDASIL) in patients with systemic lupus erythematosus (SLE).
Female SLE patients and controls, aged 18–35 years, who received GARDASIL in 2011 and sero-converted 12 months post-vaccination were followed for persistence of immunogenicity. Antibody measurement to HPV serotypes 6, 11, 16, 18 was repeated at 5 years. The rate of sero-reversion was compared between patients and controls, and factors associated with sero-reversion of the anti-HPV antibodies were studied.
50 SLE patients and 50 controls were vaccinated with GARDASIL. Among subjects who sero-converted at 1 year and consented for this study, antibodies to HPV serotypes 6, 11, 16 and 18 at 5 years were persistent in 24/27 (89%), 26/31 (84%), 32/34 (94%) and 24/25 (96%) of the SLE patients; and 32/33 (97%), 32/33 (97%), 32/32 (100%) and 23/24 (96%) of the controls, respectively. Antibody titers to HPV-6 and 16 were significantly lower in patients than controls. Seven (21%) SLE patients had sero-reversion of ≥1 anti-HPV antibodies. Sero-reverted patients experienced significantly more SLE flares, particularly renal, and had received significantly higher cumulative doses of prednisolone, mycophenolate mofetil and tacrolimus than those with persistent immunogenicity. The cumulative doses of prednisolone correlated inversely and significantly with the anti-HPV 6, 11, and 16 titers at 5 years.
Immunogenicity of the quadrivalent HPV vaccine was retained in a high proportion of SLE patients at 5 year. Patients with more SLE renal flares and had received more immunosuppression were more likely to have sero-reversion of the anti-HPV antibodies.
Clinical trial registration number: US ClinicalTrials.gov (NCT00911521 & NCT02477254).
Thermal residual stress and distortion inherent in metal melting and solidification process is the main cause of build failure in metal additive manufacturing (AM) techniques such as laser powder bed ...fusion and directed energy deposition. To ensure build quality against residual stress/distortion, it is desirable to tailor the scanning path for a given geometry that needs to be built. Since the local deformation introduced by the moving heat source is anisotropic due to non-uniform heat transfer and mechanical constraints, the scanning path can affect residual stress within a part significantly. Aiming at thermal residual stress/distortion mitigation, this paper presents a novel level set-based scanning path optimization method. The method is developed to enable layer-wise continuous scanning path optimization for geometrically well-defined parts. To make the optimization efficient, a fast process simulation method called the inherent strain method is employed to simulate the thermal residual strain. Full sensitivity analysis for the formulated compliance- and stress-minimization problems is provided, where a novel strategy called the adaptive level set adjustment (ALSA) is proposed to remedy the deficiency of ignoring the non-implementable sensitivity terms. The effectiveness of the proposed continuous scanning path optimization method and ALSA strategy has been proved by a few numerical examples. Finally, the concurrent design scenario for simultaneous scanning path and structural optimization is investigated to demonstrate the further residual stress reduction.
Integrin alpha 11 beta 1 is a stromal cell-specific receptor for fibrillar collagens and is overexpressed in carcinoma-associated fibroblasts (CAFs). We have investigated its direct role in cancer ...progression by generating severe combined immune deficient (SCID) mice deficient in integrin alpha 11 ( alpha 11) expression. The growth of A549 lung adenocarcinoma cells and two patient-derived non-small cell lung carcinoma (NSCLC) xenografts in these alpha 11 knockout ( alpha 11 super(-/-)) mice was significantly impeded, as compared with wild-type ( alpha 11 super(+/+)) SCID mice. Orthotopic implantation of a spontaneously metastatic NCI-H460SM cell line into the lungs of alpha 11 super(-/-) and alpha 11 super(+/+) mice showed significant reduction in the metastatic potential of these cells in the alpha 11 super(-/-) mice. We identified that collagen cross-linking is associated with stromal alpha 11 expression, and the loss of tumor stromal alpha 11 expression was correlated with decreased collagen reorganization and stiffness. This study shows the role of integrin alpha 11 beta 1, a receptor for fibrillar collagen in differentiation of fibroblasts into CAFs. Furthermore, our data support an important role for alpha 11 signaling pathway in CAFs, promoting tumor growth and metastatic potential of NSCLC cells and being closely associated with collagen cross-linking and the organization and stiffness of fibrillar collagen matrices.
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