The renewal functions (RFs) of most distribution functions do not have closed-form expressions while such expressions are desired for the optimization problems involved RF. Many efforts have been ...made to develop approximations of RF. However, it seems that no RF approximation is accurate enough in the entire time range. In this paper, we propose two RF approximations. The first approximation is obtained through smoothly connecting two limiting relations and fairly accurate in the entire time range. The second approximation has the same function form as the first part of the first approximation but the model parameter is determined in a different way so as to achieve higher accuracy for small to moderate time range. The expressions of the proposed approximations are simple and applicable for any arbitrary lifetime distribution. Their accuracy is analyzed and, the appropriateness and usefulness are illustrated by a numerical example.
•A simple two-fold sectional approximation of renewal function that is applicable for ordinary lifetime distributions is proposed.•Variance of renewals derived from the proposed approximation is ...fairly accurate.•The approximation is integrable for the Weibull distribution.•The cost rate curve of block replacement policy is usually not bathtub-shaped and the optimal solution is highly sensitive to the type of lifetime distribution.
The renewal function (RF) has many applications such as reliability analysis, maintenance policy optimization and inventory planning. The RFs of most distribution functions do not have closed-form expressions while such expressions are desired for most of applications. Several models that aim to approximate RF over the entire time range have been developed in the literature, but their accuracy is not high enough. To fill this gap, this paper proposes a two-fold sectional approximation, which is obtained through smoothly connecting two limiting relations. The proposed approximation is simple, applicable for ordinary lifetime distributions (e.g., Weibull and lognormal distributions), and accurate for the distributional parameters in the usual range. The variance of renewals derived from the approximation is fairly accuracy and the integral of the approximation has a closed-form expression for the Weibull distribution. The approximation is useful for solving the optimization problems that involve RF or/and its integral, such as optimization of block replacement policy.
The failure rate with a bathtub shape usually increases very fast in the wear-out phase. In this case, the bathtub curve model with a finite support can better adapt the sharp change in failure rate. ...There are few models with the finite support. This paper presents such a model. However, the maximum likelihood estimator of the location parameter of such models sometimes converges to the largest observation of a dataset. An extended maximum spacing method is developed to estimate the parameters for the case where the maximum likelihood method fails. Three examples are included to illustrate the appropriateness of the proposed model and estimation method.
Several attempts have been made to develop risk-sensitive cost models for the age replacement policy in order to reduce the over-budget risk in maintenance cost. Two such models are found to be ...erroneous. The purpose of this paper is threefold. We first point out and illustrate the problems of the two models. We then propose a new risk-sensitive cost model and study the performance of its solution. The results show that the solution of the proposed model is not always conservative and the cause is explained. Finally, we propose an approach to aggregate the solutions of the two expectancy-based cost models into a compromise solution and an interval solution, which provides flexibility for maintenance scheduling. The appropriateness and usefulness of the proposed approach are illustrated by a numerical example.
Advanced basal cell carcinomas (BCCs) frequently acquire resistance to Smoothened (SMO) inhibitors through unknown mechanisms. Here we identify SMO mutations in 50% (22 of 44) of resistant BCCs and ...show that these mutations maintain Hedgehog signaling in the presence of SMO inhibitors. Alterations include four ligand binding pocket mutations defining sites of inhibitor binding and four variants conferring constitutive activity and inhibitor resistance, illuminating pivotal residues that ensure receptor autoinhibition. In the presence of a SMO inhibitor, tumor cells containing either class of SMO mutants effectively outcompete cells containing the wild-type SMO. Finally, we show that both classes of SMO variants respond to aPKC-ι/λ or GLI2 inhibitors that operate downstream of SMO, setting the stage for the clinical use of GLI antagonists.
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•Functional SMO mutations are detected in the majority of SMO inhibitor-resistant BCCs•Resistance occurs by suppressing drug responsiveness and SMO autoinhibition•SMO mutants explain both intrinsic and acquired tumor resistance•Inhibition of aPKC-ι/λ or GLI2 bypasses SMO variants to suppress Hedgehog signaling
Atwood et al. identify key SMO mutations that confer resistance to SMO inhibitors in basal cell carcinomas (BCC) and show that these mutants respond to aPKC-ι/λ or GLI2 inhibitors, providing potential approaches for treating BCCs resistant to SMO inhibitors.
•Short and long FCG mechanisms in PM Ni-based superalloys are reviewed.•Effects of microstructural features on short and long FCG behaviours are evaluated.•Contribution of creep and environmental ...damage to FCG are critically assessed.•Perspectives of FCG in PM Ni-based superalloys are provided.
Powder metallurgy (PM) Ni-based superalloys are widely used for aeroengine turbine disc applications due to their excellent mechanical properties and good corrosion resistance at elevated temperatures. Understanding the fatigue crack growth (FCG) mechanisms of PM Ni-based superalloys is important for both disc alloy development and life prediction of disc components in these advanced aeroengines where damage tolerance design prevails. FCG in PM Ni-based superalloys is a complicated function of microstructure, temperature, loading conditions and environment and is usually a consequence of the synergistic effects of fatigue, creep and environmental damage. In this review, the mechanisms controlled by microstructural features including grain size, grain misorientation, γ′ size and distribution on short and long FCG behaviour in PM Ni-based superalloys are discussed. The contribution of creep and environmental damage to FCG has been critically assessed. The competing effects of mechanical damage (i.e. fatigue and creep) and environmental damage at the crack tip are microstructure-sensitive, and usually results in transition between transgranular, mixed-trans-intergranular and intergranular FCG depending on the contribution of environmental damage to FCG processes.
Development of the mammalian secondary palate involves highly dynamic morphogenetic processes, including outgrowth of palatal shelves from the oral side of the embryonic maxillary prominences, ...elevation of the initially vertically oriented palatal shelves to the horizontal position above the embryonic tongue, and subsequently adhesion and fusion of the paired palatal shelves at the midline to separate the oral cavity from the nasal cavity. Perturbation of any of these processes could cause cleft palate, a common birth defect that significantly affects patients’ quality of life even after surgical treatment. In addition to identifying a large number of genes required for palate development, recent studies have begun to unravel the extensive cross-regulation of multiple signaling pathways, including Sonic hedgehog, bone morphogenetic protein, fibroblast growth factor, transforming growth factor β, and Wnt signaling, and multiple transcription factors during palatal shelf growth and patterning. Multiple studies also provide new insights into the gene regulatory networks and/or dynamic cellular processes underlying palatal shelf elevation, adhesion, and fusion. Here we summarize major recent advances and integrate the genes and molecular pathways with the cellular and morphogenetic processes of palatal shelf growth, patterning, elevation, adhesion, and fusion.
Magnetic cellulose/Fe₃O₄/activated carbon composites (m-Cell/Fe₃O₄/ACCs) were prepared successfully and characterized by X-ray diffraction (XRD), Brunauer–Emmett–Teller (BET), thermogravimetric ...analysis (TGA), scanning electron microscopy (SEM) and vibrating sample magnetometer (VSM). The adsorption of congo red onto the novel m-Cell/Fe₃O₄/ACCs was studied as a function of contact time, initial concentration of congo red, adsorbent dosage, and pH of solution. The saturated magnetization of m-Cell/Fe₃O₄/ACCs reached 48.2emug⁻¹ and the magnetic adsorbent showed characteristics of superparamagnetism, which indicated that m-Cell/Fe₃O₄/ACCs could be separated from treated solution by a magnetic process. A comparison of kinetic models showed that the overall adsorption process was best described by pseudo-second-order kinetic model. Thermodynamic analysis indicated an exothermic nature of adsorption and a spontaneous and favorable process. The m-Cell/Fe₃O₄/ACCs might be a promising candidate of high efficiency, low cost and convenient separation under magnetic field.
To evaluate the existing evidence regarding treatment regimens for
Mycobacterium avium
complex (MAC), a systematic review of the available therapeutic studies was conducted to assess treatment ...outcomes. A random-effects meta-analysis was used to assess treatment outcomes. Subgroup analyses were also conducted by separating studies based on each characteristic independently. Twenty-eight trials met the inclusion criteria. Our meta-analysis showed that the estimated pooled treatment success rate for patients with MAC disease was 39 % 95 % confidence interval (CI) 38–41 %. The rates of failure, relapse, death, and default were 27 % (95 % CI 25–29 %), 6 % (95 % CI 5–7 %), 17 % (95 % CI 15–18 %), and 12 % (95 % CI 11–13 %), respectively. The proportion of patients treated successfully did not differ significantly on the basis of the study characteristics. However, studies with treatment regimens containing macrolides had significantly higher pooled success proportions (42 %, 95 % CI 40–44 %) than that of other studies (28 %, 95 % CI 24–32 %). Substantial heterogeneity in the study characteristics prevented more conclusive determination of what factors had the greatest effect on the proportion of patients that achieve treatment success and limited the validity of this analysis. This review underscored the importance of strong patient support and treatment follow-up systems to develop successful MAC treatment programs.
An item is subject to gradual degradation. The degradation can be represented by a measurable, non-negative and non-decreasing quantity. The item can be in one of three different states: normal (when ...the degradation quantity is smaller than a threshold of alarm or potential failure), functional failure (when the degradation quantity is larger than a functional failure threshold) and in-between or potential failure (when the degradation quantity is larger than the alarm threshold and smaller than the functional failure threshold). A sequential inspection scheme is implemented to determine the state of the item so as to prevent a functional failure. The paper presents a flexible degradation model and two cost models to optimize the alarm threshold and the sequential inspection scheme. The usefulness and appropriateness of the proposed models are illustrated by examples.
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