Age-dependent Failure Research Articles

Age-dependent failure probabilities of corroding concrete sewer pipes under traffic loads

Concrete pipes are frequently used in the wastewater infrastructure. These buried structures are prone to ageing and deterioration, as well as damage under excessive stresses from traffic. This study presents the first set of temporal fragility models for underground concrete sewer pipes under the compounding effects of corrosion and truck loads. To address the high computational costs of fragility modeling, Bayesian Additive Regression Trees (BART) – a machine-learning based meta-model – are trained using a high-fidelity computational model of buried concrete pipes. The BART models are subsequently applied to develop age-dependent fragility models for serviceability and collapse of pipes conditional on truck loads. Considered uncertainties include statistically significant concrete and soil properties, truck load, and environmental factors that affect the corrosion of concrete sewer pipes. Results indicate that the direction of traffic stream, the degree of loss of wall thickness due to corrosion, and the maximum allowed truck load are critical factors that must be considered when planning inspection, rehabilitation, and retrofit of this underground infrastructure. According to the results, concrete sewer pipes buried in perpendicular to the direction of traffic flow are more vulnerable than those that are parallel to the direction of traffic flow. The results highlight that the probability of collapse is insignificant when it comes to vehicles weighing less than the design truck weight; however, the probability of collapse significantly increases for the moderate and severe corroded sewer pipes when it comes to the overweight vehicles. The age-dependent fragility models indicate that for sewer pipes buried perpendicular to the direction of traffic stream with service life of less than 25 years, the probability of the first major structural defect is less than 5%. This is also true for sewer pipes that have been in service for less than 45 years if the traffic stream is parallel to the buried pipe. The developed fragility models also constitute a key component of quantitative risk assessment of underground wastewater collection systems.

Nanoparticulate air pollution disrupts proteostasis in Caenorhabditis elegans.

The proteostasis network comprises the biochemical pathways that together maintain and regulate proper protein synthesis, transport, folding, and degradation. Many progressive neurodegenerative diseases, such as Huntington's disease (HD) and Alzheimer's disease (AD), are characterized by an age-dependent failure of the proteostasis network to sustain the health of the proteome, resulting in protein misfolding, aggregation, and, often, neurotoxicity. Although important advances have been made in recent years to identify genetic risk factors for neurodegenerative diseases, we still know relatively little about environmental risk factors such as air pollution. Exposure to nano-sized particulate air pollution, referred to herein as nanoparticulate matter (nPM), has been shown to trigger the accumulation of misfolded and oligomerized amyloid beta (Aβ) in mice. Likewise, air pollution is known to exacerbate symptoms of AD in people. We asked whether nPM contributes to the misfolded protein load, thereby overwhelming the proteostasis network and triggering proteostasis decline. To address this, we utilized C. elegans that express reporter proteins that are sensitive to changes in the protein folding environment and respond by misfolding and displaying readily scorable phenotypes, such as localized YFP fluorescence or paralysis. We found that nPM exacerbated protein aggregation in body wall muscle cells, increasing the number of large visible protein aggregates, the amount of high molecular weight protein species, and proteotoxicity. Taken together, the data point to nPM negatively impacting proteostasis. Therefore, it seems plausible that nPM exposure may exacerbate symptoms of AD and age-related dementia in a manner that is at least partially dependent on proteostasis decline.

Enhanced autophagic retrograde axonal transport by dynein intermediate chain upregulation improves Aβ clearance and cognitive function in APP/PS1 double transgenic mice.

Autophagosome accumulation is observed in the distal axons of Alzheimer disease (AD) patients and AD animal models, suggesting that deficient retrograde transport and impaired autophagic clearance of beta-amyloid (A β) contribute to AD pathogenesis. Expression of the retrograde axonal transport-related protein dynein intermediate chain (DIC) is also reduced in AD patients, but the contributions of DIC to AD pathology remain elusive. This study investigated the effects of DIC expression levels on cognitive function, autophagosome axonal transport, and A β clearance in the APP/PS1 double transgenic mouse model of AD. Autophagic activity was enhanced in the hippocampus of young (3-month-old) AD mice, as evidenced by greater expression of autophagosome markers, lysosome markers, axonal transport motors (including DIC), and dynein regulatory proteins. The expression levels of autophagosome markers remained elevated, whereas those of autophagic and axonal transport proteins decreased progressively with age, accompanied by spatial learning and memory deficits, axonal autophagosome accumulation, and A β deposition. Knockdown of DIC exacerbated while overexpression improved axonal transport, autophagosome maturation, Aβ clearance, and spatial learning and memory in aged AD mice. Our study provides evidence that age-dependent failure of axonal autophagic flux contributes to AD-associated neuropathology and cognitive deficits, suggesting DIC as a potential therapeutic target for AD.

Failure intensity of offshore power plants under varying maintenance policies

Abstract System reliability of an offshore power plant with several gas turbine engines is analyzed in this study to understand the failure intensity of a selected gas turbine engines under varying maintenance activities. A set of event data of a selected gas turbine engine is considered to identify system failure intensity levels, where unknown maintenance actions were implemented (i.e. various repairs disturb the failure rate). A non-homogeneous Poisson process (NHPP) is used to model the age dependent failure intensity of the same gas turbine engine and the maximum likelihood estimation (MLE) approach for calculating the respective model parameters is proposed. Several failure intensity rates (i.e. varying failure trends) in these models (i.e. during the system age of the gas turbine engine) are observed. Furthermore, these varying failure trend models are evaluated with actual failure events of the same gas turbine engine by considering two goodness-of-fit tests: Cramer-von Mises and Chi-square tests. Finally, system reliability of the gas turbine engine under the failure transition, failure intensity, mission reliability and mean time between failures (MTBF) is also discussed in this study.

Abstract 530: The Ufm1 Specific Ligase 1 Regulates Endoplasmic Reticulum Homeostasis and Protects Against Heart Failure

Protein modifications by ubiquitin and ubiquitin-like proteins are emerging as an important regulatory mechanism of protein function and involved in various cellular processes. Ufm1 (ubiquitin-fold modifier 1) is a novel ubiquitin-like protein that modifies protein targets in a UBA5 (E1) - Ufc1 (E2) - Ufl1 (E3) dependent manner. While defects in ubiquitin- and SUMO-modification have been shown to provoke cardiac remodeling and dysfunction, the importance of Ufm1 modification has not been explored in the normal and stressed heart. Western blotting revealed that Ufm1 specific ligase 1 (Ufl1), an enzyme essential for Ufm1 modification, was increased in hypertrophic mouse hearts but reduced in the failing hearts of patients with dilated cardiomyopathy. To determine the functional role of Ufl1 in the heart, we generated a cardiac-specific knockout mouse and showed that Ufl1-deficient mice developed age-dependent cardiomyopathy and heart failure, as indicated by elevated cardiac fetal gene expression, increased fibrosis and impaired cardiac contractility. When challenged with pressure overload, Ufl1-deficient hearts exhibited remarkably greater hypertrophy, exacerbated fibrosis and worsened cardiac contractility compared with control counterparts. Transcriptome analysis identified that genes associated with the endoplasmic reticulum (ER) function were dysregulated in Ufl1-deficient hearts. Biochemical analysis revealed that excessive ER stress preceded and deteriorated along with the development of cardiomyopathy in Ufl1-deficient hearts. Mechanistically, Ufl1 depletion impaired PERK signaling and aggravated cardiomyocyte cell death following ER stress. Administration of the chemical ER chaperone tauroursodeoxycholic acid to Ufl1-deficient mice alleviated ER stress and attenuated pressure overload-induced cardiac dysfunction. Our results advance a novel concept that the Ufm1 system is essential for cardiac homeostasis through regulation of ER function and that upregulation of myocardial Ufl1 could be protective against heart failure.

Pathways of cellular proteostasis in aging and disease.

Ensuring cellular protein homeostasis, or proteostasis, requires precise control of protein synthesis, folding, conformational maintenance, and degradation. A complex and adaptive proteostasis network coordinates these processes with molecular chaperones of different classes and their regulators functioning as major players. This network serves to ensure that cells have the proteins they need while minimizing misfolding or aggregation events that are hallmarks of age-associated proteinopathies, including neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. It is now clear that the capacity of cells to maintain proteostasis undergoes a decline during aging, rendering the organism susceptible to these pathologies. Here we discuss the major proteostasis pathways in light of recent research suggesting that their age-dependent failure can both contribute to and result from disease. We consider different strategies to modulate proteostasis capacity, which may help develop urgently needed therapies for neurodegeneration and other age-dependent pathologies.

Predictive maintenance: strategic use of IT in manufacturing organizations

A combination of big data and predictive analytics orchestrated through the Internet of Things (IoT) offers many opportunities for researchers in Information Systems, Operations Management and Strategy to look at old problems in new ways, and to identify completely new research areas. While there is much hype, little research has been conducted that informs companies about how to profitably integrate the IoT with strategic or operational processes. This paper views the IoT through the lens of predictive maintenance -- the use of real-time data and predictive analytics algorithms to dynamically manage preventive maintenance policies. These are being used by numerous manufacturing organizations to transition from product-oriented to service-oriented business models. In particular, we analyze optimal preventive maintenance policies in an environment where equipment is subject to a deterioration, which shifts it from its initial, fully-productive state, having a specified, age-dependent failure rate to a less-productive or deteriorated state, having a different, presumably higher, age-dependent failure rate. The deterioration, itself, is a random process.

Cellular Aging Contributes to Failure of Cold-Induced Beige Adipocyte Formation in Old Mice and Humans

Cold temperatures induce progenitor cells within white adipose tissue to form beige adipocytes that burn energy and generate heat; this is a potential anti-diabesity therapy. However, the potential to form cold-induced beige adipocytes declines with age. This creates a clinical roadblock to potential therapeutic use in older individuals, who constitute a large percentage of the obesity epidemic. Here we show that aging murine and human beige progenitor cells display a cellular aging, senescence-like phenotype that accounts for their age-dependent failure. Activating the senescence pathway, either genetically or pharmacologically, in young beige progenitors induces premature cellular senescence and blocks their potential to form cold-induced beige adipocytes. Conversely, genetically or pharmacologically reversing cellular aging by targeting the p38/MAPK-p16Ink4a pathway in aged mouse or human beige progenitor cells rejuvenates cold-induced beiging. This in turn increases glucose sensitivity. Collectively, these data indicate that anti-aging or senescence modalities could be a strategy to induce beiging, thereby improving metabolic health in aging humans.

Long-term age-dependent failure pattern after breast-conserving therapy or mastectomy among Danish lymph-node-negative breast cancer patients

PurposeTo describe long-term failure pattern after early-stage breast cancer in relation to local treatment (breast-conserving therapy (BCT) or mastectomy) and age. Materials and methodsCohort study with balanced 5-year age groups and prospectively collected data; 813 Danish lymph-node-negative breast cancer patients diagnosed in 1989–98 and treated with mastectomy (N=515) or BCT (N=298) and no adjuvant systemic treatment. ResultsThe 20-year local recurrence (LR) risk was 20% after BCT; 8.7% after mastectomy. LR developed in mastectomy patients within the first 10years; in BCT patients throughout the entire 20-year period. Younger patients’ (⩽45years) 20-year LR risk was generally higher than older patients’ (>45years) (19% vs. 5%, p<0.001).In younger patients, LR was significantly associated with distant metastasis (DM) (hazard ratio (HR)=2.7(1.8–4.2)) and 20-year breast-cancer mortality (HR=2.7(1.7–4.4)). BCT was associated with higher 20-year breast-cancer mortality (HR=1.5(1.0–2.4)) and higher 20-year all-cause mortality (HR=1.7(1.2–2.5)) than mastectomy.In older patients, LR was not associated with DM, and breast-cancer mortality was similar for BCT and mastectomy. ConclusionBCT patients with no adjuvant systemic treatment developed LR throughout 20-year period and faced higher LR risk than mastectomy patients. LR was associated with DM among younger patients, and younger BCT patients had higher mortality than younger mastectomy patients.

OC-0052: Long-term age dependent failure pattern after BCT vs. mastectomy in low-risk breast cancer patients

OC-0052: Long-term age dependent failure pattern after BCT vs. mastectomy in low-risk breast cancer patients

The Dysfunction of Camp-Dependent Na+/Ca2+ Exchange in Reverse Mode as a Primary Mechanism for Age-Dependent Cardio-Muscle Failure

The Dysfunction of Camp-Dependent Na+/Ca2+ Exchange in Reverse Mode as a Primary Mechanism for Age-Dependent Cardio-Muscle Failure

A Bivariate Optimal Replacement Policy for a System With Age-dependent Minimal Repair and Cumulative Repair-cost Limit

In this article, a repairable system with age-dependent failure type and minimal repair based on a cumulative repair-cost limit policy is studied, where the information of entire repair-cost history is adopted to decide whether the system is repaired or replaced. As the failures occur, the system has two failure types: (i) a Type-I failure (minor) type that is rectified by a minimal repair, and (ii) a Type-II failure (catastrophic) type that calls for a replacement. We consider a bivariate replacement policy, denoted by (n,T), in which the system is replaced at life age T, or at the n-th Type-I failure, or at the kth Type-I failure (k < n and due to a minor failure at which the accumulated repair cost exceeds the pre-determined limit), or at the first Type-II failure, whichever occurs first. The optimal minimum-cost replacement policy (n,T)* is derived analytically in terms of its existence and uniqueness. Several classical models in maintenance literature could be regard as special cases of the presented model. Finally, a numerical example is given to illustrate the theoretical results.

Amyloid beta 25–35 impairs reconsolidation of object recognition memory in rats and this effect is prevented by lithium carbonate

Previous studies in transgenic mice models of Alzheimer's disease (AD) have demonstrated an age dependent memory reconsolidation failure, suggesting that this may be an additional mechanism that contributes to the memory impairment observed in AD. However, so far it is unknown whether this effect can be caused by exogenous administration of amyloid beta (Aβ). The purpose was to determine the effects of soluble Aβ 25–35 on reconsolidation of object recognition memory (ORM) in rats, and assess whether these effects can be prevented by lithium carbonate (LiCa). In this study, male Wistar rats were used and the following groups were formed (N=6–13): (a) control, given saline solution; (b) [NMDA antagonist] MK-801 (0.1mg/kg); (c) LiCa (350mg/kg); (d) Aβ 25–35 (100μM) injected into both hippocampi; and (e) Aβ 25–35+LiCa. In all cases, treatments were administered with or without reactivation of memory. The results showed that soluble Aβ 25–35 produces ORM impairment similar to MK-801 when given shortly after memory reactivation, and this effect is prevented by prior administration of LiCa.

Exact Results on the Statistically Expected Total Cost and Optimal Solutions for Extended Periodic Imperfect Preventive Maintenance

Sheu and Chang (IEEE Trans. Rel., vol. 58, no. 2, pp. 397-404, 2009) presented an interesting extended periodic imperfect preventive maintenance (EPIPM) model for a system with age-dependent failure type. Many cases studied previously are special cases of the EPIPM model. In the Errata (IEEE Trans. Rel., vol. 60, no. 2, 2011), Sheu and Chang showed that the proposed effective age and the proposed hazard rate function after the PM are incorrect. In this paper, based on the correct failure characteristics (effective age and hazard rate function after PM), the correct s -expected total cost per unit time for the EPIPM model is presented. By assigning three types of failure characteristics for the EPIPM model, we analyse and compare the corresponding s -expected total costs per unit time. We find that the s-expected total cost per unit time developed by Sheu and Chang (IEEE Trans. Rel., vol. 58, no. 2, pp. 397-404, 2009) is only one upper bound of the exact s-expected total cost per unit time. In addition, we also give some results on the existence of the optimal solution for the exact s -expected total cost.

Simultaneous control of maintenance and production rates of a manufacturing system with defective products

In the past three decades, studies of simultaneous maintenance and production planning have been focusing on age-dependent machine failure and inventory. This paper presents the interaction between...

Optimal replacement model with age-dependent failure type based on a cumulative repair-cost limit policy

This paper presents a replacement model with age-dependent failure type based on a cumulative repair-cost limit policy, whose concept uses the information of all repair costs to decide whether the system is repaired or replaced. As failures occur, the system experiences one of the two types of failures: a type-I failure (minor), rectified by a minimal repair; or a type-II failure (catastrophic) that calls for a replacement. A critical type-I failure means a minor failure at which the accumulated repair cost exceeds the pre-determined limit for the first time. The system is replaced at the nth type-I failure, or at a critical type-I failure, or at first type-II failure, whichever occurs first. The optimal number of minimal repairs before replacement which minimizes the mean cost rate is derived and studied in terms of its existence and uniqueness. Several classical models in maintenance literature are special cases of our model.

Can serotonin agonists unlock age-dependent failure of liver regeneration?

The function of the liver is well-preserved during the aging process, although some evidence suggests that liver regeneration might be impaired with advanced age. We observed a decreased abil- ity of the liver to restore normal volume after partial hepatectomy in elderly mice, and we identified a pathway that rescued regeneration and was triggered by serotonin. 2,5-dimethoxy-4-iodoamphetamine (DOI), a serotonin receptor agonist, reversed the age-related pseudo- capillarization of old liver and improved hepatosinusoidal blood flow. After hepatectomy, the open fenestrae were associated with a restored attachment of platelets to endothelium and the initiation of a normal regenerative response, including the up-regulation of essential growth mediators and serotonin receptors. In turn, hepato- cyte proliferation recovered along with regain of liver volume and animal survival. DOI operates through the release of VEGF, and its effects could be blocked with anti-VEGF antibodies both in vitro and in vivo. These results suggest that pseudocapillarization in the aged acts as a barrier to liver regeneration. DOI breaks this restraint through an endothelium-dependent mechanism driven by VEGF. This pathway highlights a target for reversing the age-associated decline in the capacity of the liver to regenerate. 2011 Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.

Production control in a failure-prone manufacturing network using discrete event simulation and automated response surface methodology

In this paper, a system consisting of a network of machines with random breakdown and repair times is considered. The machines in this system can be in one of four states: operational, in repair, starved, and blocked. Failure and repair times of the machines are exponentially distributed. Previous research on multi-machine failure-prone manufacturing systems (FPMS) has focused on systems consisting of machines in series or in parallel. This paper considers a network of machines with relationship constraints. Additionally, the system under study models work in process for multiple products, intermediate and final buffers and one type of final product. The demand rate for the final commodity is constant and unmet demand is either backlogged or lost. The objective of this control problem is to find the production rates and policies of the different machines so as to minimize the long run average inventory and backlog cost. The applied control policy is the hedging point policy that is determined by factors representing the level of buffer inventory for each machine. Obtaining analytical solutions is generally impossible for such complex systems. To simultaneously control the production rates of the machines we have therefore developed a method based on a combination of stochastic optimal control theory, discrete event simulation, experimental design and automated response surface methodology (RSM). The application of an automated RSM for Network FPMS is another contribution of this paper. The model can be extended easily to systems with age-dependent failure rates, a preventive repair maintenance policy and non-exponentially distributed up and down times.

Simultaneous control of maintenance and production rates of a manufacturing system with defective products

In the past three decades, studies of simultaneous maintenance and production planning have been focusing on age-dependent machine failure and inventory. This paper presents the interaction between defective products and optimal control of production rate, lead time and inventory. Our aim is to minimize the expected discounted overall cost due to maintenance activities, inventory holding and backlogs. Through Condition-Based Maintenance, we monitor in a real time the manufacturing system's health by describing N operational states. We consider two maintenance states of a machine controlled by two decision variables: production and maintenance rates. The optimal policy is characterized by the dynamic programming solution to a piecewise deterministic optimal control problem. A numerical illustration and a sensitive analysis are developed with a set of parameters calibrated on an existing manufacturing system.

An Extended Periodic Imperfect Preventive Maintenance Model With Age-Dependent Failure Type

This paper presents a generalized periodic imperfect preventive maintenance (PM) model for a system with age-dependent failure type. The imperfect PM model proposed in this study incorporates improvement factors vis-a-vis the hazard-rate function, and effective age. As failures occur, the system experiences one of the two types of failure: type-I failure (minor), and type-II failure (catastrophic). Type-I failures are rectified with minimal repair. In a PM period, the system is preventively maintained following the occurrence of a type-II failure, or at age T, whichever takes place first. At the N th PM, the system is replaced. An approach that generalizes the existing studies on the periodic PM policy is proposed. Taking age-dependent failure type into consideration, the objective consists of determining the optimal PM & replacement schedule that minimize the expected cost per unit of time, over an infinite horizon.