A TIME-HONORED system of recording medical histories and the data obtained on physical and laboratory examination has been that of writing the information on record sheets that go into a folder for each patient. In order to have information which would be more readily retrieved, 'a program was initiated in 1952 by the U. S. Naval School of Aviation Medicine in connection with their "Care of the Flyer" study to place this information on machine record cards. In 1958, a machine record card method was developed for recording medical data in connection with the astronaut selection program. Machine record cards were also developed by the Aero Medical Laboratory, Wright-Patterson AFB, Ohio, and the Aviation Medical Acceleration Laboratory, Naval Air Development Center, Johnsville, Pennsylvania, for use in connection with a variety of tests including acceleration stress.1 Therefore, a variety of systems resulted in which data of a medical nature could easily be recalled. During the NASA, Ames Research Center centrifuge studies/'S the pilot subjects were interviewed after each centrifuge run, or series of runs, and subjective information was recorded in a log book by the usual history taking methods referred to above. After the methods Were reviewed, it' was recognized that a card system would be very useful in recording data from our pilots after they had been exposed to acceleration stress. Since the acceleration stress cards already developed did not meet our requirements, it was decided a different card was needed.
The SAT protein (SATp) of porcine parvovirus (PPV) accumulates in the endoplasmic reticulum (ER), and SAT deletion induces the slow-spreading phenotype. The in vitro comparison of the wild-type Kresse strain and its SAT knockout (SAT - ) mutant revealed that prolonged cell integrity and late viral release are responsible for the slower spreading of the SAT - virus. During PPV infection, regardless of the presence or absence of SATp, the expression of downstream ER stress response proteins (Xbp1 and CHOP) was induced. However, in the absence of SATp, significant differences in the quantity and the localization of CHOP were detected, suggesting a role of SATp in the induction of irreversible ER stress in infected cells. The involvement of the induction of irreversible ER stress in porcine testis (PT) cell necrosis and viral egress was confirmed by treatment of infected cells by ER stress-inducing chemicals (MG132, dithiothreitol, and thapsigargin), which accelerated the egress and spreading of both the wild-type and the SAT - viruses. UV stress induction had no beneficial effect on PPV infection, underscoring the specificity of ER stress pathways in the process. However, induction of CHOP and its nuclear translocation cannot alone be responsible for the biological effect of SAT, since nuclear CHOP could not complement the lack of SAT in a coexpression experiment. IMPORTANCE SATp is encoded by an alternative open reading frame of the PPV genome. Earlier we showed that SATp of the attenuated PPV NADL-2 strain accumulates in the ER and accelerates virus release and spreading. Our present work revealed that slow spreading is a general feature of SAT - PPVs and is the consequence of prolonged cell integrity. PPV infection induced ER stress in infected cells regardless of the presence of SATp, as demonstrated by the morphological changes of the ER and expression of the stress response proteins Xbp1 and CHOP. However, the presence of SATp made the ER stress more severe and
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This research is to illustrate the use of statistical inference techniques in order to quantify the uncertainty surrounding reliability estimates in a step-stress accelerated degradation testing (SSADT) scenario. SSADT can be used when a researcher is faced with a resource-constrained environment, e.g., limits on chamber time or on the number of units to test. We apply the SSADT methodology to a degradation experiment involving concentrated solar power (CSP) mirrors and compare the results to a more traditional multiple accelerated testing paradigm. Specifically, our work includes: (1) designing a durability testing plan for solar mirrors (3M's new improved silvered acrylic "Solarmore Reflector Film (SFM) 1100") through the ultra-accelerated weathering system (UAWS), (2) defining degradation paths of optical performance based on the SSADT model which is accelerated by high UV-radiant exposure, and (3) developing service lifetime prediction models for solar mirrors using advanced statistical inference. We use the method of least squares to estimate the model parameters and this serves as the basis for the statistical inference in SSADT. Several quantities of interest can be estimated from this procedure, e.g., mean-time-to-failure (MTTF) and warranty time. The methods allow for the estimation of quantities that may be of interest to the domain scientists. less
Highly accelerated life testing has been heavily promoted at Sandia (and elsewhere) as a means to rapidly identify product weaknesses caused by flaws in the product's design or manufacturing process. During product development, a small number of units are forced to fail at high stress. The failed units are then examined to determine the root causes of failure. The identification of the root causes of product failures exposed by highly accelerated life testing can instigate changes to the product's design and/or manufacturing process that result in a product with increased reliability. It is widely viewed that this qualitative use ofmore highly accelerated life testing (often associated with the acronym HALT) can be useful. However, highly accelerated life testing has also been proposed as a quantitative means for "demonstrating" the reliability of a product where unreliability is associated with loss of margin via an identified and dominating failure mechanism. It is assumed that the dominant failure mechanism can be accelerated by changing the level of a stress factor that is assumed to be related to the dominant failure mode. In extreme cases, a minimal number of units (often from a pre-production lot) are subjected to a single highly accelerated stress relative to normal use. If no (or, sufficiently few) units fail at this high stress level, some might claim that a certain level of reliability has been demonstrated (relative to normal use conditions). Underlying this claim are assumptions regarding the level of knowledge associated with the relationship between the stress level and the probability of failure. The primary purpose of this document is to discuss (from a statistical perspective) the efficacy of using accelerated life testing protocols (and, in particular, "highly accelerated" protocols) to make quantitative inferences concerning the performance of a product (e.g., reliability) when in fact there is lack-of-knowledge and uncertainty concerning
Early life stress (ELS) increases the risk for later cognitive and emotional dysfunction. ELS is known to truncate neural development through effects on suppressing cell birth, increasing cell death, and altering neuronal morphology, effects that have been associated with behavioral profiles indicative of precocious maturation. However, how earlier silencing of growth drives accelerated behavioral maturation has remained puzzling. Here, we test the novel hypothesis that, ELS drives a switch from growth to maturation to accelerate neural and behavioral development. To test this, we used a mouse model of ELS, fragmented maternal care, and a cross-sectional dense sampling approach focusing on hippocampus and measured effects of ELS on the ontogeny of behavioral development and biomarkers of neural maturation. Consistent with previous work, ELS was associated with an earlier developmental decline in expression of markers of cell proliferation (Ki-67) and differentiation (doublecortin). However, ELS also led to a precocious arrival of Parvalbumin-positive cells, led to an earlier switch in NMDA receptor subunit expression (marker of synaptic maturity), and was associated with an earlier rise in myelin basic protein expression (key component of the myelin sheath). In addition, in a contextual fear-conditioning task, ELS accelerated the timed developmental suppression of contextual fear. Together, these data provide support for the hypothesis that ELS serves to switch neurodevelopment from processes of growth to maturation and promotes accelerated development of some forms of emotional learning. Copyright 2016 Elsevier Inc. All rights reserved.
Accelerated degradation testing (ADT) is an efficient tool to conduct material service reliability and safety evaluations by analyzing performance degradation data. Traditional stochastic process models are mainly for linear or linearization degradation paths. However, those methods are not applicable for the situations where the degradation processes cannot be linearized. Hence, in this paper, a general ADT model based on the Wiener process is proposed to solve the problem for accelerated degradation data analysis. The general model can consider the unit-to-unit variation and temporal variation of the degradation process, and is suitable for both linear and nonlinear ADT analyses with single or multiple acceleration variables. The statistical inference is given to estimate the unknown parameters in both constant stress and step stress ADT. The simulation example and two real applications demonstrate that the proposed method can yield reliable lifetime evaluation results compared with the existing linear and time-scale transformation Wiener processes in both linear and nonlinear ADT analyses.
Accelerated degradation testing (ADT) is an efficient tool to conduct material service reliability and safety evaluations by analyzing performance degradation data. Traditional stochastic process models are mainly for linear or linearization degradation paths. However, those methods are not applicable for the situations where the degradation processes cannot be linearized. Hence, in this paper, a general ADT model based on the Wiener process is proposed to solve the problem for accelerated degradation data analysis. The general model can consider the unit-to-unit variation and temporal variation of the degradation process, and is suitable for both linear and nonlinear ADT analyses with single or multiple acceleration variables. The statistical inference is given to estimate the unknown parameters in both constant stress and step stress ADT. The simulation example and two real applications demonstrate that the proposed method can yield reliable lifetime evaluation results compared with the existing linear and time-scale transformation Wiener processes in both linear and nonlinear ADT analyses. PMID:28774107 2ff7e9595c
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