405 research outputs found

    A model-based multithreshold method for subgroup identification

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    Thresholding variable plays a crucial role in subgroup identification for personalizedmedicine. Most existing partitioning methods split the sample basedon one predictor variable. In this paper, we consider setting the splitting rulefrom a combination of multivariate predictors, such as the latent factors, principlecomponents, and weighted sum of predictors. Such a subgrouping methodmay lead to more meaningful partitioning of the population than using a singlevariable. In addition, our method is based on a change point regression modeland thus yields straight forward model-based prediction results. After choosinga particular thresholding variable form, we apply a two-stage multiple changepoint detection method to determine the subgroups and estimate the regressionparameters. We show that our approach can produce two or more subgroupsfrom the multiple change points and identify the true grouping with high probability.In addition, our estimation results enjoy oracle properties. We design asimulation study to compare performances of our proposed and existing methodsand apply them to analyze data sets from a Scleroderma trial and a breastcancer study

    Technological considerations for 4D printing: an overview

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    4D printing utilizes additive manufacturing methods to produce stimulus-responsive components that can change its shape from one to another when subject to appropriate stimuli. The use of 4D printing technology is expected to significantly become more widespread with more applications across bio-medical, aerospace, and defence industries. This paper discusses emerging applications for 4D printing and suitable stimulus-responsive materials for 4D printing. In terms of designing for 4D printing, aspects of the shape memory effect (SME) including one-way SMEs, two-way SMEs and three-way SMEs are presented. Materials and structures in the form of homogenous compositions and heterogeneous compositions are discussed, as well as different types of shape-shifting behaviours such as self-folding, self-assemblies, and self-dis-assemblies. Finally, current software and examples are presented together with the existing limitations that need to be overcome to achieve widespread adoption of 4D printing

    An Overview of Material Extrusion Troubleshooting

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    © 2020 by the authors. Material extrusion (ME) systems offer end-users with a more affordable and accessible additive manufacturing (AM) technology compared to other processes in the market. ME is often used to quickly produce low-cost prototyping with the freedom of scalability where parts can be produced in different geometries, quantities and sizes. As the use of desktop ME machines has gained widespread adoption, this review paper discusses the key design strategies and considerations to produce high quality ME parts, as well as providing actional advice to aid end-users in quickly identifying and efficiently troubleshooting issues since current information is often fragmented and incomplete. The systemic issues and solutions concerning desktop ME processes discussed are not machine-specific, covering categories according to printer-associated, deposition-associated and print quality problems. The findings show that the majority of issues are associated with incorrect printer calibration and parameters, hardware, material, Computer Aided Design (CAD) model and/or slicing settings. A chart for an overview of ME troubleshooting is presented allowing designers and engineers to straightforwardly determine the possible contributing factors to a particular problem

    Complexity of the Inoculum Determines the Rate of Reversion of SIV Gag CD8 T Cell Mutant Virus and Outcome of Infection

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    Escape mutant (EM) virus that evades CD8+ T cell recognition is frequently observed following infection with HIV-1 or SIV. This EM virus is often less replicatively “fit” compared to wild-type (WT) virus, as demonstrated by reversion to WT upon transmission of HIV to a naïve host and the association of EM virus with lower viral load in vivo in HIV-1 infection. The rate and timing of reversion is, however, highly variable. We quantified reversion to WT of a series of SIV and SHIV viruses containing minor amounts of WT virus in pigtail macaques using a sensitive PCR assay. Infection with mixes of EM and WT virus containing ≥10% WT virus results in immediate and rapid outgrowth of WT virus at SIV Gag CD8 T cell epitopes within 7 days of infection of pigtail macaques with SHIV or SIV. In contrast, infection with biologically passaged SHIVmn229 viruses with much smaller proportions of WT sequence, or a molecular clone of pure EM SIVmac239, demonstrated a delayed or slow pattern of reversion. WT virus was not detectable until ≥8 days after inoculation and took ≥8 weeks to become the dominant quasispecies. A delayed pattern of reversion was associated with significantly lower viral loads. The diversity of the infecting inoculum determines the timing of reversion to WT virus, which in turn predicts the outcome of infection. The delay in reversion of fitness-reducing CD8 T cell escape mutations in some scenarios suggests opportunities to reduce the pathogenicity of HIV during very early infection
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