WorldWideScience

Sample records for reliable rodent models

  1. Reliable critical sized defect rodent model for cleft palate research.

    Science.gov (United States)

    Mostafa, Nesrine Z; Doschak, Michael R; Major, Paul W; Talwar, Reena

    2014-12-01

    Suitable animal models are necessary to test the efficacy of new bone grafting therapies in cleft palate surgery. Rodent models of cleft palate are available but have limitations. This study compared and modified mid-palate cleft (MPC) and alveolar cleft (AC) models to determine the most reliable and reproducible model for bone grafting studies. Published MPC model (9 × 5 × 3 mm(3)) lacked sufficient information for tested rats. Our initial studies utilizing AC model (7 × 4 × 3 mm(3)) in 8 and 16 weeks old Sprague Dawley (SD) rats revealed injury to adjacent structures. After comparing anteroposterior and transverse maxillary dimensions in 16 weeks old SD and Wistar rats, virtual planning was performed to modify MPC and AC defects dimensions, taking the adjacent structures into consideration. Modified MPC (7 × 2.5 × 1 mm(3)) and AC (5 × 2.5 × 1 mm(3)) defects were employed in 16 weeks old Wistar rats and healing was monitored by micro-computed tomography and histology. Maxillary dimensions in SD and Wistar rats were not significantly different. Preoperative virtual planning enhanced postoperative surgical outcomes. Bone healing occurred at defect margin leaving central bone void confirming the critical size nature of the modified MPC and AC defects. Presented modifications for MPC and AC models created clinically relevant and reproducible defects. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  2. Rodent Models for Metabolic Syndrome Research

    Directory of Open Access Journals (Sweden)

    Sunil K. Panchal

    2011-01-01

    Full Text Available Rodents are widely used to mimic human diseases to improve understanding of the causes and progression of disease symptoms and to test potential therapeutic interventions. Chronic diseases such as obesity, diabetes and hypertension, together known as the metabolic syndrome, are causing increasing morbidity and mortality. To control these diseases, research in rodent models that closely mimic the changes in humans is essential. This review will examine the adequacy of the many rodent models of metabolic syndrome to mimic the causes and progression of the disease in humans. The primary criterion will be whether a rodent model initiates all of the signs, especially obesity, diabetes, hypertension and dysfunction of the heart, blood vessels, liver and kidney, primarily by diet since these are the diet-induced signs in humans with metabolic syndrome. We conclude that the model that comes closest to fulfilling this criterion is the high carbohydrate, high fat-fed male rodent.

  3. The valproic acid-induced rodent model of autism.

    Science.gov (United States)

    Nicolini, Chiara; Fahnestock, Margaret

    2018-01-01

    Autism is a lifelong neurodevelopmental disorder characterized by impairments in social communication and interaction and by repetitive patterns of behavior, interests and activities. While autism has a strong genetic component, environmental factors including toxins, pesticides, infection and drugs are known to confer autism susceptibility, likely by inducing epigenetic changes. In particular, exposure to valproic acid (VPA) during pregnancy has been demonstrated to increase the risk of autism in children. Furthermore, rodents prenatally exposed to this drug display behavioral phenotypes characteristics of the human condition. Indeed, in utero exposure of rodents to VPA represents a robust model of autism exhibiting face, construct and predictive validity. This model might better represent the many cases of idiopathic autism which are of environmental/epigenetic origins than do transgenic models carrying mutations in single autism-associated genes. The VPA model provides a valuable tool to investigate the neurobiology underlying autistic behavior and to screen for novel therapeutics. Here we review the VPA-induced rodent model of autism, highlighting its importance and reliability as an environmentally-induced animal model of autism. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Proposed reliability cost model

    Science.gov (United States)

    Delionback, L. M.

    1973-01-01

    The research investigations which were involved in the study include: cost analysis/allocation, reliability and product assurance, forecasting methodology, systems analysis, and model-building. This is a classic example of an interdisciplinary problem, since the model-building requirements include the need for understanding and communication between technical disciplines on one hand, and the financial/accounting skill categories on the other. The systems approach is utilized within this context to establish a clearer and more objective relationship between reliability assurance and the subcategories (or subelements) that provide, or reenforce, the reliability assurance for a system. Subcategories are further subdivided as illustrated by a tree diagram. The reliability assurance elements can be seen to be potential alternative strategies, or approaches, depending on the specific goals/objectives of the trade studies. The scope was limited to the establishment of a proposed reliability cost-model format. The model format/approach is dependent upon the use of a series of subsystem-oriented CER's and sometimes possible CTR's, in devising a suitable cost-effective policy.

  5. Travel time reliability modeling.

    Science.gov (United States)

    2011-07-01

    This report includes three papers as follows: : 1. Guo F., Rakha H., and Park S. (2010), "A Multi-state Travel Time Reliability Model," : Transportation Research Record: Journal of the Transportation Research Board, n 2188, : pp. 46-54. : 2. Park S.,...

  6. Reliability and Model Fit

    Science.gov (United States)

    Stanley, Leanne M.; Edwards, Michael C.

    2016-01-01

    The purpose of this article is to highlight the distinction between the reliability of test scores and the fit of psychometric measurement models, reminding readers why it is important to consider both when evaluating whether test scores are valid for a proposed interpretation and/or use. It is often the case that an investigator judges both the…

  7. Supply chain reliability modelling

    Directory of Open Access Journals (Sweden)

    Eugen Zaitsev

    2012-03-01

    Full Text Available Background: Today it is virtually impossible to operate alone on the international level in the logistics business. This promotes the establishment and development of new integrated business entities - logistic operators. However, such cooperation within a supply chain creates also many problems related to the supply chain reliability as well as the optimization of the supplies planning. The aim of this paper was to develop and formulate the mathematical model and algorithms to find the optimum plan of supplies by using economic criterion and the model for the probability evaluating of non-failure operation of supply chain. Methods: The mathematical model and algorithms to find the optimum plan of supplies were developed and formulated by using economic criterion and the model for the probability evaluating of non-failure operation of supply chain. Results and conclusions: The problem of ensuring failure-free performance of goods supply channel analyzed in the paper is characteristic of distributed network systems that make active use of business process outsourcing technologies. The complex planning problem occurring in such systems that requires taking into account the consumer's requirements for failure-free performance in terms of supply volumes and correctness can be reduced to a relatively simple linear programming problem through logical analysis of the structures. The sequence of the operations, which should be taken into account during the process of the supply planning with the supplier's functional reliability, was presented.

  8. Rodent models of adaptive decision making.

    Science.gov (United States)

    Izquierdo, Alicia; Belcher, Annabelle M

    2012-01-01

    Adaptive decision making affords the animal the ability to respond quickly to changes in a dynamic environment: one in which attentional demands, cost or effort to procure the reward, and reward contingencies change frequently. The more flexible the organism is in adapting choice behavior, the more command and success the organism has in navigating its environment. Maladaptive decision making is at the heart of much neuropsychiatric disease, including addiction. Thus, a better understanding of the mechanisms that underlie normal, adaptive decision making helps achieve a better understanding of certain diseases that incorporate maladaptive decision making as a core feature. This chapter presents three general domains of methods that the experimenter can manipulate in animal decision-making tasks: attention, effort, and reward contingency. Here, we present detailed methods of rodent tasks frequently employed within these domains: the Attentional Set-Shift Task, Effortful T-maze Task, and Visual Discrimination Reversal Learning. These tasks all recruit regions within the frontal cortex and the striatum, and performance is heavily modulated by the neurotransmitter dopamine, making these assays highly valid measures in the study of psychostimulant addiction.

  9. A rodent malarial model of Plasmodium berghei for the development ...

    African Journals Online (AJOL)

    A rodent malarial model of Plasmodium berghei for the development of pyrimethamine and sulphadoxine-pyrimethamine resistant malaria in mice. ... course approach with 125/6.25mg/kg S/P. The stability of resistance phenotypes, parasite pathogenic disposition and host leukocyte response were also investigated.

  10. Optimizing Cardiovascular Benefits of Exercise: A Review of Rodent Models

    Science.gov (United States)

    Davis, Brittany; Moriguchi, Takeshi; Sumpio, Bauer

    2013-01-01

    Although research unanimously maintains that exercise can ward off cardiovascular disease (CVD), the optimal type, duration, intensity, and combination of forms are yet not clear. In our review of existing rodent-based studies on exercise and cardiovascular health, we attempt to find the optimal forms, intensities, and durations of exercise. Using Scopus and Medline, a literature review of English language comparative journal studies of cardiovascular benefits and exercise was performed. This review examines the existing literature on rodent models of aerobic, anaerobic, and power exercise and compares the benefits of various training forms, intensities, and durations. The rodent studies reviewed in this article correlate with reports on human subjects that suggest regular aerobic exercise can improve cardiac and vascular structure and function, as well as lipid profiles, and reduce the risk of CVD. Findings demonstrate an abundance of rodent-based aerobic studies, but a lack of anaerobic and power forms of exercise, as well as comparisons of these three components of exercise. Thus, further studies must be conducted to determine a truly optimal regimen for cardiovascular health. PMID:24436579

  11. Power transformer reliability modelling

    NARCIS (Netherlands)

    Schijndel, van A.

    2010-01-01

    Problem description Electrical power grids serve to transport and distribute electrical power with high reliability and availability at acceptable costs and risks. These grids play a crucial though preferably invisible role in supplying sufficient power in a convenient form. Today’s society has

  12. Of mice and women: rodent models of placental malaria

    DEFF Research Database (Denmark)

    Hviid, Lars; Marinho, Claudio R F; Staalsoe, Trine

    2010-01-01

    Pregnant women are at increased malaria risk. The infections are characterized by placental accumulation of infected erythrocytes (IEs) with adverse consequences for mother and baby. Placental IE sequestration in the intervillous space is mediated by variant surface antigens (VSAs) selectively...... expressed in placental malaria (PM) and specific for chondroitin sulfate A (CSA). In Plasmodium falciparum, these VSA(PM) appear largely synonymous with the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family variant VAR2CSA. As rodent malaria parasites do not possess PfEMP1 homologs......, the usefulness of experimental mouse PM models remains controversial. However, many features of murine and human PM are similar, including involvement of VSAs analogous to PfEMP1. It thus appears that rodent model studies can further the understanding of VSA-dependent malaria pathogenesis and immunity....

  13. Two new rodent models for actinide toxicity studies

    International Nuclear Information System (INIS)

    Taylor, G.N.; Jones, C.W.; Gardner, P.A.; Lloyd, R.D.; Mays, C.W.; Charrier, K.E.

    1981-01-01

    Two small rodent species, the grasshopper mouse (Onychomys leucogaster) and the deer mouse (Peromyscus maniculatus), have tenacious and high retention in the liver and skeleton of plutonium and americium following intraperitoneal injection of Pu and Am in citrate solution. Liver retention of Pu and Am in the grasshopper mouse is higher than liver retention in the deer mouse. Both of these rodents are relatively long-lived, breed well in captivity, and adapt suitably to laboratory conditions. It is suggested that these two species of mice, in which plutonium retention is high and prolonged in both the skeleton and liver, as it is in man, may be useful animal models for actinide toxicity studies

  14. Rodent models of congenital and hereditary cataract in man.

    Science.gov (United States)

    Tripathi, B J; Tripathi, R C; Borisuth, N S; Dhaliwal, R; Dhaliwal, D

    1991-01-01

    Because the organogenesis and physiology of the lens are essentially similar in various mammals, an understanding of the etiology and pathogenesis of the formation of cataract in an animal model will enhance our knowledge of cataractogenesis in man. In this review, we summarize the background, etiology, and pathogenesis of cataracts that occur in rodents. The main advantages of using rodent mutants include the well-researched genetics of the animals and the comparative ease of breeding of large litters. Numerous rodent models of congenital and hereditary cataracts have been studied extensively. In mice, the models include the Cts strain, Fraser mouse, lens opacity gene (Lop) strain, Lop-2 and Lop-3 strains, Philly mouse, Nakano mouse, Nop strain, Deer mouse, Emory mouse, Swiss Webster strain, Balb/c-nct/nct mouse, and SAM-R/3 strain. The rat models include BUdR, ICR, Sprague-Dawley, and Wistar rats, the spontaneously hypertensive rat (SHR), the John Rapp inbred strain of Dahl salt-sensitive rat, as well as WBN/Kob, Royal College of Surgeons (RCS), and Brown-Norway rats. Other proposed models for the study of hereditary cataract include the degu and the guinea pig. Because of the ease of making clinical observations in vivo and the subsequent availability of the intact lens for laboratory analyses at different stages of cataract formation, these animals provide excellent models for clinicopathologic correlations, for monitoring of the natural history of the aging process and of metabolic defects, as well as for investigations on the effect of cataract-modulating agents and drugs, including the prospect of gene therapy.

  15. Models and detection of spontaneous recurrent seizures in laboratory rodents

    Directory of Open Access Journals (Sweden)

    Bin Gu

    2017-07-01

    Full Text Available Epilepsy, characterized by spontaneous recurrent seizures (SRS, is a serious and common neurological disorder afflicting an estimated 1% of the population worldwide. Animal experiments, especially those utilizing small laboratory rodents, remain essential to understanding the fundamental mechanisms underlying epilepsy and to prevent, diagnose, and treat this disease. While much attention has been focused on epileptogenesis in animal models of epilepsy, there is little discussion on SRS, the hallmark of epilepsy. This is in part due to the technical difficulties of rigorous SRS detection. In this review, we comprehensively summarize both genetic and acquired models of SRS and discuss the methodology used to monitor and detect SRS in mice and rats.

  16. Reliability analysis and operator modelling

    International Nuclear Information System (INIS)

    Hollnagel, Erik

    1996-01-01

    The paper considers the state of operator modelling in reliability analysis. Operator models are needed in reliability analysis because operators are needed in process control systems. HRA methods must therefore be able to account both for human performance variability and for the dynamics of the interaction. A selected set of first generation HRA approaches is briefly described in terms of the operator model they use, their classification principle, and the actual method they propose. In addition, two examples of second generation methods are also considered. It is concluded that first generation HRA methods generally have very simplistic operator models, either referring to the time-reliability relationship or to elementary information processing concepts. It is argued that second generation HRA methods must recognise that cognition is embedded in a context, and be able to account for that in the way human reliability is analysed and assessed

  17. Studying autism in rodent models: reconciling endophenotypes with comorbidities.

    Directory of Open Access Journals (Sweden)

    Andrew eArgyropoulos

    2013-07-01

    Full Text Available Autism spectrum disorder (ASD patients commonly exhibit a variety of comorbid traits including seizures, anxiety, aggressive behavior, gastrointestinal problems, motor deficits, abnormal sensory processing and sleep disturbances for which the cause is unknown. These features impact negatively on daily life and can exaggerate the effects of the core diagnostic traits (social communication deficits and repetitive behaviors. Studying endophenotypes relevant to both core and comorbid features of ASD in rodent models can provide insight into biological mechanisms underlying these disorders. Here we review the characterization of endophenotypes in a selection of environmental, genetic and behavioural rodent models of ASD. In addition to exhibiting core ASD-like behaviours, each of these animal models display one or more endophenotypes relevant to comorbid features including altered sensory processing, seizure susceptibility, anxiety-like behaviour and disturbed motor functions, suggesting that these traits are indicators of altered biological pathways in ASD. However, the study of behaviours paralleling comorbid traits in animal models of ASD is an emerging field and further research is needed to assess altered gastrointestinal function, aggression and disorders of sleep onset across models. Future studies should include investigation of these endophenotypes in order to advance our understanding of the etiology of this complex disorder.

  18. Reliability Overhaul Model

    Science.gov (United States)

    1989-08-01

    Random variables for the conditional exponential distribution are generated using the inverse transform method. C1) Generate U - UCO,i) (2) Set s - A ln...e - [(x+s - 7)/ n] 0 + [Cx-T)/n]0 c. Random variables from the conditional weibull distribution are generated using the inverse transform method. C1...using a standard normal transformation and the inverse transform method. B - 3 APPENDIX 3 DISTRIBUTIONS SUPPORTED BY THE MODEL (1) Generate Y - PCX S

  19. New Insights from Rodent Models of Fatty Liver Disease

    Science.gov (United States)

    2011-01-01

    Abstract Rodent models of fatty liver disease are essential research tools that provide a window into disease pathogenesis and a testing ground for prevention and treatment. Models come in many varieties involving dietary and genetic manipulations, and sometimes both. High-energy diets that induce obesity do not uniformly cause fatty liver disease; this has prompted close scrutiny of specific macronutrients and nutrient combinations to determine which have the greatest potential for hepatotoxicity. At the same time, diets that do not cause obesity or the metabolic syndrome but do cause severe steatohepatitis have been exploited to study factors important to progressive liver injury, including cell death, oxidative stress, and immune activation. Rodents with a genetic predisposition to overeating offer yet another model in which to explore the evolution of fatty liver disease. In some animals that overeat, steatohepatitis can develop even without resorting to a high-energy diet. Importantly, these models and others have been used to document that aerobic exercise can prevent or reduce fatty liver disease. This review focuses primarily on lessons learned about steatohepatitis from manipulations of diet and eating behavior. Numerous additional insights about hepatic lipid metabolism, which have been gained from genetically engineered mice, are also mentioned. Antioxid. Redox Signal. 15, 535–550. PMID:21126212

  20. Spatial memory tasks in rodents: what do they model?

    Science.gov (United States)

    Morellini, Fabio

    2013-10-01

    The analysis of spatial learning and memory in rodents is commonly used to investigate the mechanisms underlying certain forms of human cognition and to model their dysfunction in neuropsychiatric and neurodegenerative diseases. Proper interpretation of rodent behavior in terms of spatial memory and as a model of human cognitive functions is only possible if various navigation strategies and factors controlling the performance of the animal in a spatial task are taken into consideration. The aim of this review is to describe the experimental approaches that are being used for the study of spatial memory in rats and mice and the way that they can be interpreted in terms of general memory functions. After an introduction to the classification of memory into various categories and respective underlying neuroanatomical substrates, I explain the concept of spatial memory and its measurement in rats and mice by analysis of their navigation strategies. Subsequently, I describe the most common paradigms for spatial memory assessment with specific focus on methodological issues relevant for the correct interpretation of the results in terms of cognitive function. Finally, I present recent advances in the use of spatial memory tasks to investigate episodic-like memory in mice.

  1. Modelling the emergence of rodent filial huddling from physiological huddling

    Science.gov (United States)

    Wilson, Stuart P.

    2017-11-01

    Huddling behaviour in neonatal rodents reduces the metabolic costs of physiological thermoregulation. However, animals continue to huddle into adulthood, at ambient temperatures where they are able to sustain a basal metabolism in isolation from the huddle. This `filial huddling' in older animals is known to be guided by olfactory rather than thermal cues. The present study aimed to test whether thermally rewarding contacts between young mice, experienced when thermogenesis in brown adipose fat tissue (BAT) is highest, could give rise to olfactory preferences that persist as filial huddling interactions in adults. To this end, a simple model was constructed to fit existing data on the development of mouse thermal physiology and behaviour. The form of the model that emerged yields a remarkable explanation for filial huddling; associative learning maintains huddling into adulthood via processes that reduce thermodynamic entropy from BAT metabolism and increase information about social ordering among littermates.

  2. Reliability Modeling of Wind Turbines

    DEFF Research Database (Denmark)

    Kostandyan, Erik

    Cost reductions for offshore wind turbines are a substantial requirement in order to make offshore wind energy more competitive compared to other energy supply methods. During the 20 – 25 years of wind turbines useful life, Operation & Maintenance costs are typically estimated to be a quarter...... for Operation & Maintenance planning. Concentrating efforts on development of such models, this research is focused on reliability modeling of Wind Turbine critical subsystems (especially the power converter system). For reliability assessment of these components, structural reliability methods are applied...... to one third of the total cost of energy. Reduction of Operation & Maintenance costs will result in significant cost savings and result in cheaper electricity production. Operation & Maintenance processes mainly involve actions related to replacements or repair. Identifying the right times when...

  3. Osseointegration of biochemically modified implants in an osteoporosis rodent model

    Directory of Open Access Journals (Sweden)

    B Stadlinger

    2013-07-01

    Full Text Available The present study examined the impact of implant surface modifications on osseointegration in an osteoporotic rodent model. Sandblasted, acid-etched titanium implants were either used directly (control or were further modified by surface conditioning with NaOH or by coating with one of the following active agents: collagen/chondroitin sulphate, simvastatin, or zoledronic acid. Control and modified implants were inserted into the proximal tibia of aged ovariectomised (OVX osteoporotic rats (n = 32/group. In addition, aged oestrogen competent animals received either control or NaOH conditioned implants. Animals were sacrificed 2 and 4 weeks post-implantation. The excised tibiae were utilised for biomechanical and morphometric readouts (n = 8/group/readout. Biomechanical testing revealed at both time points dramatically reduced osseointegration in the tibia of oestrogen deprived osteoporotic animals compared to intact controls irrespective of NaOH exposure. Consistently, histomorphometric and microCT analyses demonstrated diminished bone-implant contact (BIC, peri-implant bone area (BA, bone volume/tissue volume (BV/TV and bone-mineral density (BMD in OVX animals. Surface coating with collagen/chondroitin sulphate had no detectable impact on osseointegration. Interestingly, statin coating resulted in a transient increase in BIC 2 weeks post-implantation; which, however, did not correspond to improvement of biomechanical readouts. Local exposure to zoledronic acid increased BIC, BA, BV/TV and BMD at 4 weeks. Yet this translated only into a non-significant improvement of biomechanical properties. In conclusion, this study presents a rodent model mimicking severely osteoporotic bone. Contrary to the other bioactive agents, locally released zoledronic acid had a positive impact on osseointegration albeit to a lesser extent than reported in less challenging models.

  4. Proposed Reliability/Cost Model

    Science.gov (United States)

    Delionback, L. M.

    1982-01-01

    New technique estimates cost of improvement in reliability for complex system. Model format/approach is dependent upon use of subsystem cost-estimating relationships (CER's) in devising cost-effective policy. Proposed methodology should have application in broad range of engineering management decisions.

  5. Reliability in the Rasch Model

    Czech Academy of Sciences Publication Activity Database

    Martinková, Patrícia; Zvára, K.

    2007-01-01

    Roč. 43, č. 3 (2007), s. 315-326 ISSN 0023-5954 R&D Projects: GA MŠk(CZ) 1M06014 Institutional research plan: CEZ:AV0Z10300504 Keywords : Cronbach's alpha * Rasch model * reliability Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 0.552, year: 2007 http://dml.cz/handle/10338.dmlcz/135776

  6. Multinomial-exponential reliability function: a software reliability model

    International Nuclear Information System (INIS)

    Saiz de Bustamante, Amalio; Saiz de Bustamante, Barbara

    2003-01-01

    The multinomial-exponential reliability function (MERF) was developed during a detailed study of the software failure/correction processes. Later on MERF was approximated by a much simpler exponential reliability function (EARF), which keeps most of MERF mathematical properties, so the two functions together makes up a single reliability model. The reliability model MERF/EARF considers the software failure process as a non-homogeneous Poisson process (NHPP), and the repair (correction) process, a multinomial distribution. The model supposes that both processes are statistically independent. The paper discusses the model's theoretical basis, its mathematical properties and its application to software reliability. Nevertheless it is foreseen model applications to inspection and maintenance of physical systems. The paper includes a complete numerical example of the model application to a software reliability analysis

  7. Odor supported place cell model and goal navigation in rodents

    DEFF Research Database (Denmark)

    Kulvicius, Tomas; Tamosiunaite, Minija; Ainge, James

    2008-01-01

    Experiments with rodents demonstrate that visual cues play an important role in the control of hippocampal place cells and spatial navigation. Nevertheless, rats may also rely on auditory, olfactory and somatosensory stimuli for orientation. It is also known that rats can track odors or self......-generated scent marks to find a food source. Here we model odor supported place cells by using a simple feed-forward network and analyze the impact of olfactory cues on place cell formation and spatial navigation. The obtained place cells are used to solve a goal navigation task by a novel mechanism based on self......-marking by odor patches combined with a Q-learning algorithm. We also analyze the impact of place cell remapping on goal directed behavior when switching between two environments. We emphasize the importance of olfactory cues in place cell formation and show that the utility of environmental and self...

  8. Use of rodents as models of human diseases

    Directory of Open Access Journals (Sweden)

    Thierry F Vandamme

    2014-01-01

    Full Text Available Advances in molecular biology have significantly increased the understanding of the biology of different diseases. However, these discoveries have not yet been fully translated into improved treatments for patients with diseases such as cancers. One of the factors limiting the translation of knowledge from preclinical studies to the clinic has been the limitations of in vivo diseases models. In this brief review, we will discuss the advantages and disadvantages of rodent models that have been developed to simulate human pathologies, focusing in models that employ xenografts and genetic modification. Within the framework of genetically engineered mouse (GEM models, we will review some of the current genetic strategies for modeling diseases in the mouse and the preclinical studies that have already been undertaken. We will also discuss how recent improvements in imaging technologies may increase the information derived from using these GEMs during early assessments of potential therapeutic pathways. Furthermore, it is interesting to note that one of the values of using a mouse model is the very rapid turnover rate of the animal, going through the process of birth to death in a very short timeframe relative to that of larger mammalian species.

  9. Behavioral testing in rodent models of orofacial neuropathic and inflammatory pain

    Science.gov (United States)

    Krzyzanowska, Agnieszka; Avendaño, Carlos

    2012-01-01

    Orofacial pain conditions are often very debilitating to the patient and difficult to treat. While clinical interest is high, the proportion of studies performed in the orofacial region in laboratory animals is relatively low, compared with other body regions. This is partly due to difficulties in testing freely moving animals and therefore lack of reliable testing methods. Here we present a comprehensive review of the currently used rodent models of inflammatory and neuropathic pain adapted to the orofacial areas, taking into account the difficulties and drawbacks of the existing approaches. We examine the available testing methods and procedures used for assessing the behavioral responses in the face in both mice and rats and provide a summary of some pharmacological agents used in these paradigms to date. The use of these agents in animal models is also compared with outcomes observed in the clinic. PMID:23139912

  10. Traumatic brain injury–Modeling neuropsychiatric symptoms in rodents

    Directory of Open Access Journals (Sweden)

    Oz eMalkesman

    2013-10-01

    Full Text Available Each year in the United States, approximately 1.5 million people sustain a traumatic brain injury (TBI. Victims of TBI can suffer from chronic post-TBI symptoms, such as sensory and motor deficits, cognitive impairments including problems with memory, learning, and attention, and neuropsychiatric symptoms such as depression, anxiety, irritability, aggression, and suicidal rumination. Although partially associated with the site and severity of injury, the biological mechanisms associated with many of these symptoms—and why some patients experience differing assortments of persistent maladies—are largely unknown. The use of animal models is a promising strategy for elucidation of the mechanisms of impairment and treatment, and learning, memory, sensory and motor tests have widespread utility in rodent models of TBI and psychopharmacology. Comparatively, behavioral tests for the evaluation of neuropsychiatric symptomatology are rarely employed in animal models of TBI and, as determined in this review, the results have been inconsistent. Animal behavioral studies contribute to the understanding of the biological mechanisms by which TBI is associated with neurobehavioral symptoms and offer a powerful means for pre-clinical treatment validation. Therefore, further exploration of the utility of animal behavioral tests for the study of injury mechanisms and therapeutic strategies for the alleviation of emotional symptoms are relevant and essential.

  11. STRESS INDUCED OBESITY: LESSONS FROM RODENT MODELS OF STRESS

    Directory of Open Access Journals (Sweden)

    Zachary Robert Patterson

    2013-07-01

    Full Text Available Stress is defined as the behavioral and physiological responses generated in the face of, or in anticipation of, a perceived threat. The stress response involves activation of the sympathetic nervous system and recruitment of the hypothalamic-pituitary-adrenal (HPA axis. When an organism encounters a stressor (social, physical, etc., these endogenous stress systems are stimulated in order to generate a fight-or-flight response, and manage the stressful situation. As such, an organism is forced to liberate energy resources in attempt to meet the energetic demands posed by the stressor. A change in the energy homeostatic balance is thus required to exploit an appropriate resource and deliver useable energy to the target muscles and tissues involved in the stress response. Acutely, this change in energy homeostasis and the liberation of energy is considered advantageous, as it is required for the survival of the organism. However, when an organism is subjected to a prolonged stressor, as is the case during chronic stress, a continuous irregularity in energy homeostasis is considered detrimental and may lead to the development of metabolic disturbances such as cardiovascular disease, type II diabetes mellitus and obesity. This concept has been studied extensively using animal models, and the neurobiological underpinnings of stress induced metabolic disorders are beginning to surface. However, different animal models of stress continue to produce divergent metabolic phenotypes wherein some animals become anorexic and loose body mass while others increase food intake and body mass and become vulnerable to the development of metabolic disturbances. It remains unclear exactly what factors associated with stress models can be used to predict the metabolic outcome of the organism. This review will explore a variety of rodent stress models and discuss the elements that influence the metabolic outcome in order to further our understanding of stress

  12. Mathematical modeling of sleep state dynamics in a rodent model of shift work

    Directory of Open Access Journals (Sweden)

    Michael J. Rempe

    2018-06-01

    Full Text Available Millions of people worldwide are required to work when their physiology is tuned for sleep. By forcing wakefulness out of the body’s normal schedule, shift workers face numerous adverse health consequences, including gastrointestinal problems, sleep problems, and higher rates of some diseases, including cancers. Recent studies have developed protocols to simulate shift work in rodents with the intention of assessing the effects of night-shift work on subsequent sleep (Grønli et al., 2017. These studies have already provided important contributions to the understanding of the metabolic consequences of shift work (Arble et al., 2015; Marti et al., 2016; Opperhuizen et al., 2015 and sleep-wake-specific impacts of night-shift work (Grønli et al., 2017. However, our understanding of the causal mechanisms underlying night-shift-related sleep disturbances is limited. In order to advance toward a mechanistic understanding of sleep disruption in shift work, we model these data with two different approaches. First we apply a simple homeostatic model to quantify differences in the rates at which sleep need, as measured by slow wave activity during slow wave sleep (SWS rises and falls. Second, we develop a simple and novel mathematical model of rodent sleep and use it to investigate the timing of sleep in a simulated shift work protocol (Grønli et al., 2017. This mathematical framework includes the circadian and homeostatic processes of the two-process model, but additionally incorporates a stochastic process to model the polyphasic nature of rodent sleep. By changing only the time at which the rodents are forced to be awake, the model reproduces some key experimental results from the previous study, including correct proportions of time spent in each stage of sleep as a function of circadian time and the differences in total wake time and SWS bout durations in the rodents representing night-shift workers and those representing day-shift workers

  13. Rodent model for assessing the long term safety and performance of peripheral nerve recording electrodes

    Science.gov (United States)

    Vasudevan, Srikanth; Patel, Kunal; Welle, Cristin

    2017-02-01

    Objective. In the US alone, there are approximately 185 000 cases of limb amputation annually, which can reduce the quality of life for those individuals. Current prosthesis technology could be improved by access to signals from the nervous system for intuitive prosthesis control. After amputation, residual peripheral nerves continue to convey motor signals and electrical stimulation of these nerves can elicit sensory percepts. However, current technology for extracting information directly from peripheral nerves has limited chronic reliability, and novel approaches must be vetted to ensure safe long-term use. The present study aims to optimize methods to establish a test platform using rodent model to assess the long term safety and performance of electrode interfaces implanted in the peripheral nerves. Approach. Floating Microelectrode Arrays (FMA, Microprobes for Life Sciences) were implanted into the rodent sciatic nerve. Weekly in vivo recordings and impedance measurements were performed in animals to assess performance and physical integrity of electrodes. Motor (walking track analysis) and sensory (Von Frey) function tests were used to assess change in nerve function due to the implant. Following the terminal recording session, the nerve was explanted and the health of axons, myelin and surrounding tissues were assessed using immunohistochemistry (IHC). The explanted electrodes were visualized under high magnification using scanning electrode microscopy (SEM) to observe any physical damage. Main results. Recordings of axonal action potentials demonstrated notable session-to-session variability. Impedance of the electrodes increased upon implantation and displayed relative stability until electrode failure. Initial deficits in motor function recovered by 2 weeks, while sensory deficits persisted through 6 weeks of assessment. The primary cause of failure was identified as lead wire breakage in all of animals. IHC indicated myelinated and unmyelinated axons

  14. Vagus nerve stimulation inhibits trigeminal nociception in a rodent model of episodic migraine

    Directory of Open Access Journals (Sweden)

    Jordan L. Hawkins

    2017-12-01

    Conclusion:. Our findings demonstrate that nVNS inhibits mechanical nociception and represses expression of proteins associated with peripheral and central sensitization of trigeminal neurons in a novel rodent model of episodic migraine.

  15. Recent advances using rodent models for predicting human allergenicity

    International Nuclear Information System (INIS)

    Knippels, Leon M.J.; Penninks, Andre H.

    2005-01-01

    The potential allergenicity of newly introduced proteins in genetically engineered foods has become an important safety evaluation issue. However, to evaluate the potential allergenicity and the potency of new proteins in our food, there are still no widely accepted and reliable test systems. The best-known allergy assessment proposal for foods derived from genetically engineered plants was the careful stepwise process presented in the so-called ILSI/IFBC decision tree. A revision of this decision tree strategy was proposed by a FAO/WHO expert consultation. As prediction of the sensitizing potential of the novel introduced protein based on animal testing was considered to be very important, animal models were introduced as one of the new test items, despite the fact that non of the currently studied models has been widely accepted and validated yet. In this paper, recent results are summarized of promising models developed in rat and mouse

  16. Large Animal Stroke Models vs. Rodent Stroke Models, Pros and Cons, and Combination?

    Science.gov (United States)

    Cai, Bin; Wang, Ning

    2016-01-01

    Stroke is a leading cause of serious long-term disability worldwide and the second leading cause of death in many countries. Long-time attempts to salvage dying neurons via various neuroprotective agents have failed in stroke translational research, owing in part to the huge gap between animal stroke models and stroke patients, which also suggests that rodent models have limited predictive value and that alternate large animal models are likely to become important in future translational research. The genetic background, physiological characteristics, behavioral characteristics, and brain structure of large animals, especially nonhuman primates, are analogous to humans, and resemble humans in stroke. Moreover, relatively new regional imaging techniques, measurements of regional cerebral blood flow, and sophisticated physiological monitoring can be more easily performed on the same animal at multiple time points. As a result, we can use large animal stroke models to decrease the gap and promote translation of basic science stroke research. At the same time, we should not neglect the disadvantages of the large animal stroke model such as the significant expense and ethical considerations, which can be overcome by rodent models. Rodents should be selected as stroke models for initial testing and primates or cats are desirable as a second species, which was recommended by the Stroke Therapy Academic Industry Roundtable (STAIR) group in 2009.

  17. Modeling Human Nonalcoholic Steatohepatitis-Associated Changes in Drug Transporter Expression Using Experimental Rodent Models

    OpenAIRE

    Canet, Mark J.; Hardwick, Rhiannon N.; Lake, April D.; Dzierlenga, Anika L.; Clarke, John D.; Cherrington, Nathan J.

    2014-01-01

    Nonalcoholic fatty liver disease is a prevalent form of chronic liver disease that can progress to the more advanced stage of nonalcoholic steatohepatitis (NASH). NASH has been shown to alter drug transporter regulation and may have implications in the development of adverse drug reactions. Several experimental rodent models have been proposed for the study of NASH, but no single model fully recapitulates all aspects of the human disease. The purpose of the current study was to determine whic...

  18. A Novel Rodent Model of Posterior Ischemic Optic Neuropathy

    Science.gov (United States)

    Wang, Yan; Brown, Dale P.; Duan, Yuanli; Kong, Wei; Watson, Brant D.; Goldberg, Jeffrey L.

    2014-01-01

    Objectives To develop a reliable, reproducible rat model of posterior ischemic optic neuropathy (PION) and study the cellular responses in the optic nerve and retina. Methods Posterior ischemic optic neuropathy was induced in adult rats by photochemically induced ischemia. Retinal and optic nerve vasculature was examined by fluorescein isothiocyanate–dextran extravasation. Tissue sectioning and immunohistochemistry were used to investigate the pathologic changes. Retinal ganglion cell survival at different times after PION induction, with or without neurotrophic application, was quantified by fluorogold retrograde labeling. Results Optic nerve injury was confirmed after PION induction, including local vascular leakage, optic nerve edema, and cavernous degeneration. Immunostaining data revealed microglial activation and focal loss of astrocytes, with adjacent astrocytic hypertrophy. Up to 23%, 50%, and 70% retinal ganglion cell loss was observed at 1 week, 2 weeks, and 3 weeks, respectively, after injury compared with a sham control group. Experimental treatment by brain-derived neurotrophic factor and ciliary neurotrophic factor remarkably prevented retinal ganglion cell loss in PION rats. At 3 weeks after injury, more than 40% of retinal ganglion cells were saved by the application of neurotrophic factors. Conclusions Rat PION created by photochemically induced ischemia is a reproducible and reliable animal model for mimicking the key features of human PION. Clinical Relevance The correspondence between the features of this rat PION model to those of human PION makes it an ideal model to study the pathophysiologic course of the disease, most of which remains to be elucidated. Furthermore, it provides an optimal model for testing therapeutic approaches for optic neuropathies. PMID:23544206

  19. Translational Rodent Models for Research on Parasitic Protozoa-A Review of Confounders and Possibilities.

    Science.gov (United States)

    Ehret, Totta; Torelli, Francesca; Klotz, Christian; Pedersen, Amy B; Seeber, Frank

    2017-01-01

    Rodents, in particular Mus musculus , have a long and invaluable history as models for human diseases in biomedical research, although their translational value has been challenged in a number of cases. We provide some examples in which rodents have been suboptimal as models for human biology and discuss confounders which influence experiments and may explain some of the misleading results. Infections of rodents with protozoan parasites are no exception in requiring close consideration upon model choice. We focus on the significant differences between inbred, outbred and wild animals, and the importance of factors such as microbiota, which are gaining attention as crucial variables in infection experiments. Frequently, mouse or rat models are chosen for convenience, e.g., availability in the institution rather than on an unbiased evaluation of whether they provide the answer to a given question. Apart from a general discussion on translational success or failure, we provide examples where infections with single-celled parasites in a chosen lab rodent gave contradictory or misleading results, and when possible discuss the reason for this. We present emerging alternatives to traditional rodent models, such as humanized mice and organoid primary cell cultures. So-called recombinant inbred strains such as the Collaborative Cross collection are also a potential solution for certain challenges. In addition, we emphasize the advantages of using wild rodents for certain immunological, ecological, and/or behavioral questions. The experimental challenges (e.g., availability of species-specific reagents) that come with the use of such non-model systems are also discussed. Our intention is to foster critical judgment of both traditional and newly available translational rodent models for research on parasitic protozoa that can complement the existing mouse and rat models.

  20. Translational Rodent Models for Research on Parasitic Protozoa—A Review of Confounders and Possibilities

    Directory of Open Access Journals (Sweden)

    Totta Ehret

    2017-06-01

    Full Text Available Rodents, in particular Mus musculus, have a long and invaluable history as models for human diseases in biomedical research, although their translational value has been challenged in a number of cases. We provide some examples in which rodents have been suboptimal as models for human biology and discuss confounders which influence experiments and may explain some of the misleading results. Infections of rodents with protozoan parasites are no exception in requiring close consideration upon model choice. We focus on the significant differences between inbred, outbred and wild animals, and the importance of factors such as microbiota, which are gaining attention as crucial variables in infection experiments. Frequently, mouse or rat models are chosen for convenience, e.g., availability in the institution rather than on an unbiased evaluation of whether they provide the answer to a given question. Apart from a general discussion on translational success or failure, we provide examples where infections with single-celled parasites in a chosen lab rodent gave contradictory or misleading results, and when possible discuss the reason for this. We present emerging alternatives to traditional rodent models, such as humanized mice and organoid primary cell cultures. So-called recombinant inbred strains such as the Collaborative Cross collection are also a potential solution for certain challenges. In addition, we emphasize the advantages of using wild rodents for certain immunological, ecological, and/or behavioral questions. The experimental challenges (e.g., availability of species-specific reagents that come with the use of such non-model systems are also discussed. Our intention is to foster critical judgment of both traditional and newly available translational rodent models for research on parasitic protozoa that can complement the existing mouse and rat models.

  1. Temporal and Spatial Characterization of Gait Pattern in Rodents as an Animal model of Cerebrovascular Lesion

    Directory of Open Access Journals (Sweden)

    Jaison D Cucarián

    2017-09-01

    Full Text Available Animal experimentation is crucial for the advance in the understanding of pathophysiological mechanisms and their application on both clinical diagnosis and neuro-rehabilitation. Particularly, rodent brain lesion is commonly used in the modeling of locomotor, somatosensory and cognitive symptoms. The automated rodent gait analysis has been proposed as a tool for studying locomotor and sensory abilities and its use includes the identification of functional alterations, structural adaptations as well as neuro-rehabilitation mechanisms. From that standpoint, the effectiveness of many therapeutic intervention (i.e. physical exercises has been documented in rodents and humans. The translation from experimental data to clinical conditions requires the continuous collaboration and feedback between researchers and health clinicians looking for the selection of the best rehabilitation protocols obtained from animal research. Here we will show some locomotor alterations, the traditional methods used to assess motor dysfunction and gait abnormalities in rodent models with stroke. The aim of this review is to show some motor deficiencies and some methods used to establish gait disturbances in rodents with cerebrovascular lesion. The review included the search of defined terms (MeSH in PychINFO, Medline and Web of Science, between January 2000 and January 2017. Qualitative and narrative reports, dissertations, end course works and conference resumes were discarded. The review focuses on some clinical signs, their effects on rodent locomotor activity, some methodologies used to create lesion and to study motor function, some assessment methods and some translational aspects.

  2. Development of reliable pavement models.

    Science.gov (United States)

    2011-05-01

    The current report proposes a framework for estimating the reliability of a given pavement structure as analyzed by : the Mechanistic-Empirical Pavement Design Guide (MEPDG). The methodology proposes using a previously fit : response surface, in plac...

  3. Software reliability models for critical applications

    Energy Technology Data Exchange (ETDEWEB)

    Pham, H.; Pham, M.

    1991-12-01

    This report presents the results of the first phase of the ongoing EG&G Idaho, Inc. Software Reliability Research Program. The program is studying the existing software reliability models and proposes a state-of-the-art software reliability model that is relevant to the nuclear reactor control environment. This report consists of three parts: (1) summaries of the literature review of existing software reliability and fault tolerant software reliability models and their related issues, (2) proposed technique for software reliability enhancement, and (3) general discussion and future research. The development of this proposed state-of-the-art software reliability model will be performed in the second place. 407 refs., 4 figs., 2 tabs.

  4. Software reliability models for critical applications

    Energy Technology Data Exchange (ETDEWEB)

    Pham, H.; Pham, M.

    1991-12-01

    This report presents the results of the first phase of the ongoing EG G Idaho, Inc. Software Reliability Research Program. The program is studying the existing software reliability models and proposes a state-of-the-art software reliability model that is relevant to the nuclear reactor control environment. This report consists of three parts: (1) summaries of the literature review of existing software reliability and fault tolerant software reliability models and their related issues, (2) proposed technique for software reliability enhancement, and (3) general discussion and future research. The development of this proposed state-of-the-art software reliability model will be performed in the second place. 407 refs., 4 figs., 2 tabs.

  5. Reliability models for Space Station power system

    Science.gov (United States)

    Singh, C.; Patton, A. D.; Kim, Y.; Wagner, H.

    1987-01-01

    This paper presents a methodology for the reliability evaluation of Space Station power system. The two options considered are the photovoltaic system and the solar dynamic system. Reliability models for both of these options are described along with the methodology for calculating the reliability indices.

  6. Reliability and continuous regeneration model

    Directory of Open Access Journals (Sweden)

    Anna Pavlisková

    2006-06-01

    Full Text Available The failure-free function of an object is very important for the service. This leads to the interest in the determination of the object reliability and failure intensity. The reliability of an element is defined by the theory of probability.The element durability T is a continuous random variate with the probability density f. The failure intensity (tλ is a very important reliability characteristics of the element. Often it is an increasing function, which corresponds to the element ageing. We disposed of the data about a belt conveyor failures recorded during the period of 90 months. The given ses behaves according to the normal distribution. By using a mathematical analysis and matematical statistics, we found the failure intensity function (tλ. The function (tλ increases almost linearly.

  7. Animal models of polycystic ovary syndrome: a focused review of rodent models in relationship to clinical phenotypes and cardiometabolic risk.

    Science.gov (United States)

    Shi, Danni; Vine, Donna F

    2012-07-01

    To review rodent animal models of polycystic ovary syndrome (PCOS), with a focus on those associated with the metabolic syndrome and cardiovascular disease risk factors. Review. Rodent models of PCOS. Description and comparison of animal models. Comparison of animal models to clinical phenotypes of PCOS. Animals used to study PCOS include rodents, mice, rhesus monkeys, and ewes. Major methods to induce PCOS in these models include subcutaneous injection or implantation of androgens, estrogens, antiprogesterone, letrozole, prenatal exposure to excess androgens, and exposure to constant light. In addition, transgenic mice models and spontaneous PCOS-like rodent models have also been developed. Rodents are the most economical and widely used animals to study PCOS and ovarian dysfunction. The model chosen to study the development of PCOS and other metabolic parameters remains dependent on the specific etiologic hypotheses being investigated. Rodent models have been shown to demonstrate changes in insulin metabolism, with or without induction of hyperandrogenemia, and limited studies have investigated cardiometabolic risk factors for type 2 diabetes and cardiovascular disease. Given the clinical heterogeneity of PCOS, the utilization of different animal models may be the best approach to further our understanding of the pathophysiologic mechanisms associated with the early etiology of PCOS and cardiometabolic risk. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  8. Rodent Models of Non-classical Progesterone Action Regulating Ovulation

    Directory of Open Access Journals (Sweden)

    Melinda A. Mittelman-Smith

    2017-07-01

    Full Text Available It is becoming clear that steroid hormones act not only by binding to nuclear receptors that associate with specific response elements in the nucleus but also by binding to receptors on the cell membrane. In this newly discovered manner, steroid hormones can initiate intracellular signaling cascades which elicit rapid effects such as release of internal calcium stores and activation of kinases. We have learned much about the translocation and signaling of steroid hormone receptors from investigations into estrogen receptor α, which can be trafficked to, and signal from, the cell membrane. It is now clear that progesterone (P4 can also elicit effects that cannot be exclusively explained by transcriptional changes. Similar to E2 and its receptors, P4 can initiate signaling at the cell membrane, both through progesterone receptor and via a host of newly discovered membrane receptors (e.g., membrane progesterone receptors, progesterone receptor membrane components. This review discusses the parallels between neurotransmitter-like E2 action and the more recently investigated non-classical P4 signaling, in the context of reproductive behaviors in the rodent.

  9. Genetic Rodent Models of Obesity-Associated Ovarian Dysfunction and Subfertility: Insights into Polycystic Ovary Syndrome

    Science.gov (United States)

    Huang-Doran, Isabel; Franks, Stephen

    2016-01-01

    Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women and a leading cause of female infertility worldwide. Defined clinically by the presence of hyperandrogenemia and oligomenorrhoea, PCOS represents a state of hormonal dysregulation, disrupted ovarian follicle dynamics, and subsequent oligo- or anovulation. The syndrome’s prevalence is attributed, at least partly, to a well-established association with obesity and insulin resistance (IR). Indeed, the presence of severe PCOS in human genetic obesity and IR syndromes supports a causal role for IR in the pathogenesis of PCOS. However, the molecular mechanisms underlying this causality, as well as the important role of hyperandrogenemia, remain poorly elucidated. As such, treatment of PCOS is necessarily empirical, focusing on symptom alleviation. The generation of knockout and transgenic rodent models of obesity and IR offers a promising platform in which to address mechanistic questions about reproductive dysfunction in the context of metabolic disease. Similarly, the impact of primary perturbations in rodent gonadotrophin or androgen signaling has been interrogated. However, the insights gained from such models have been limited by the relatively poor fidelity of rodent models to human PCOS. In this mini review, we evaluate the ovarian phenotypes associated with rodent models of obesity and IR, including the extent of endocrine disturbance, ovarian dysmorphology, and subfertility. We compare them to both human PCOS and other animal models of the syndrome (genetic and hormonal), explore reasons for their discordance, and consider the new opportunities that are emerging to better understand and treat this important condition. PMID:27375552

  10. Reliability Modeling of Double Beam Bridge Crane

    Science.gov (United States)

    Han, Zhu; Tong, Yifei; Luan, Jiahui; Xiangdong, Li

    2018-05-01

    This paper briefly described the structure of double beam bridge crane and the basic parameters of double beam bridge crane are defined. According to the structure and system division of double beam bridge crane, the reliability architecture of double beam bridge crane system is proposed, and the reliability mathematical model is constructed.

  11. Functional recovery after facial nerve cable grafting in a rodent model.

    NARCIS (Netherlands)

    Hohman, M.H.; Kleiss, I.J.; Knox, C.J.; Weinberg, J.S.; Heaton, J.T.; Hadlock, T.A.

    2014-01-01

    IMPORTANCE: Cable grafting is widely considered to be the preferred alternative to primary repair of the injured facial nerve; however, quantitative comparison of the 2 techniques has not been previously undertaken in a rodent model. OBJECTIVE: To establish functional recovery parameters after

  12. The relevance of non-human primate and rodent malaria models for humans

    OpenAIRE

    Langhorne, Jean; Buffet, Pierre; Galinski, Mary; Good, Michael; Harty, John; Leroy, Didier; Mota, Maria M; Pasini, Erica; Renia, Laurent; Riley, Eleanor; Stins, Monique; Duffy, Patrick

    2011-01-01

    Abstract At the 2010 Keystone Symposium on "Malaria: new approaches to understanding Host-Parasite interactions", an extra scientific session to discuss animal models in malaria research was convened at the request of participants. This was prompted by the concern of investigators that skepticism in the malaria community about the use and relevance of animal models, particularly rodent models of severe malaria, has impacted on funding decisions and publication of research using animal models....

  13. Development of a reliable method for determining sex for a primitive rodent, the Point Arena mountain beaver (Aplodontia rufa nigra)

    Science.gov (United States)

    Kristine L. Pilgrim; William J. Zielinski; Fredrick V. Schlexer; Michael K. Schwartz

    2012-01-01

    The mountain beaver (Aplodontia rufa) is a primitive species of rodent, often considered a living fossil. The Point Arena mountain beaver (Aplodontia rufa nigra) is an endangered subspecies that occurs in a very restricted range in northern California. Efforts to recover this taxon have been limited by the lack of knowledge on their demography, particularly sex and age...

  14. Integrative rodent models for assessing male reproductive toxicity of environmental endocrine active substances

    Directory of Open Access Journals (Sweden)

    Jacques Auger

    2014-02-01

    Full Text Available In the present review, we first summarize the main benefits, limitations and pitfalls of conventional in vivo approaches to assessing male reproductive structures and functions in rodents in cases of endocrine active substance (EAS exposure from the postulate that they may provide data that can be extrapolated to humans. Then, we briefly present some integrated approaches in rodents we have recently developed at the organism level. We particularly focus on the possible effects and modes of action (MOA of these substances at low doses and in mixtures, real-life conditions and at the organ level, deciphering the precise effects and MOA on the fetal testis. It can be considered that the in vivo experimental EAS exposure of rodents remains the first choice for studies and is a necessary tool (together with the epidemiological approach for understanding the reproductive effects and MOA of EASs, provided the pitfalls and limitations of the rodent models are known and considered. We also provide some evidence that classical rodent models may be refined for studying the multiple consequences of EAS exposure, not only on the reproductive axis but also on various hormonally regulated organs and tissues, among which several are implicated in the complex process of mammalian reproduction. Such models constitute an interesting way of approaching human exposure conditions. Finally, we show that organotypic culture models are powerful complementary tools, especially when focusing on the MOA. All these approaches have contributed in a combinatorial manner to a better understanding of the impact of EAS exposure on human reproduction.

  15. Reliability Modeling of Wind Turbines

    DEFF Research Database (Denmark)

    Kostandyan, Erik

    Cost reductions for offshore wind turbines are a substantial requirement in order to make offshore wind energy more competitive compared to other energy supply methods. During the 20 – 25 years of wind turbines useful life, Operation & Maintenance costs are typically estimated to be a quarter...... and uncertainties are quantified. Further, estimation of annual failure probability for structural components taking into account possible faults in electrical or mechanical systems is considered. For a representative structural failure mode, a probabilistic model is developed that incorporates grid loss failures...

  16. Reliability modeling of an engineered barrier system

    International Nuclear Information System (INIS)

    Ananda, M.M.A.; Singh, A.K.; Flueck, J.A.

    1993-01-01

    The Weibull distribution is widely used in reliability literature as a distribution of time to failure, as it allows for both increasing failure rate (IFR) and decreasing failure rate (DFR) models. It has also been used to develop models for an engineered barrier system (EBS), which is known to be one of the key components in a deep geological repository for high level radioactive waste (HLW). The EBS failure time can more realistically be modelled by an IFR distribution, since the failure rate for the EBS is not expected to decrease with time. In this paper, we use an IFR distribution to develop a reliability model for the EBS

  17. Reliability modeling of an engineered barrier system

    International Nuclear Information System (INIS)

    Ananda, M.M.A.; Singh, A.K.; Flueck, J.A.

    1993-01-01

    The Weibull distribution is widely used in reliability literature as a distribution of time to failure, as it allows for both increasing failure rate (IFR) and decreasing failure rate (DFR) models. It has also been used to develop models for an engineered barrier system (EBS), which is known to be one of the key components in a deep geological repository for high level radioactive waste (HLW). The EBS failure time can more realistically be modelled by an IFR distribution, since the failure rate for the EBS is not expected to decrease with time. In this paper, an IFR distribution is used to develop a reliability model for the EBS

  18. New Perspectives on Rodent Models of Advanced Paternal Age: Relevance to Autism

    Directory of Open Access Journals (Sweden)

    Claire J Foldi

    2011-06-01

    Full Text Available Offspring of older fathers have an increased risk of various adverse health outcomes, including autism and schizophrenia. With respect to biological mechanisms for this association, there are many more germline cell divisions in the life history of a sperm relative to that of an oocyte. This leads to more opportunities for copy error mutations in germ cells from older fathers. Evidence also suggests that epigenetic patterning in the sperm from older men is altered. Rodent models provide an experimental platform to examine the association between paternal age and brain development. Several rodent models of advanced paternal age (APA have been published with relevance to intermediate phenotypes related to autism. All four published APA models vary in key features creating a lack of consistency with respect to behavioural phenotypes. A consideration of common phenotypes that emerge from these APA-related mouse models may be informative in the exploration of the molecular and neurobiological correlates of APA.

  19. Towards a reliable animal model of migraine

    DEFF Research Database (Denmark)

    Olesen, Jes; Jansen-Olesen, Inger

    2012-01-01

    The pharmaceutical industry shows a decreasing interest in the development of drugs for migraine. One of the reasons for this could be the lack of reliable animal models for studying the effect of acute and prophylactic migraine drugs. The infusion of glyceryl trinitrate (GTN) is the best validated...... and most studied human migraine model. Several attempts have been made to transfer this model to animals. The different variants of this model are discussed as well as other recent models....

  20. Space Vehicle Reliability Modeling in DIORAMA

    Energy Technology Data Exchange (ETDEWEB)

    Tornga, Shawn Robert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-07-12

    When modeling system performance of space based detection systems it is important to consider spacecraft reliability. As space vehicles age the components become prone to failure for a variety of reasons such as radiation damage. Additionally, some vehicles may lose the ability to maneuver once they exhaust fuel supplies. Typically failure is divided into two categories: engineering mistakes and technology surprise. This document will report on a method of simulating space vehicle reliability in the DIORAMA framework.

  1. Models of alcoholic liver disease in rodents: a critical evaluation

    DEFF Research Database (Denmark)

    de la M. Hall, P.; Lieber, C.S.; De Carli, L.M.

    2001-01-01

    ) Lieber-DeCarli liquid diet for alcohol-induced liver injury in rats, by C. S. Lieber and L. M. DeCarli; (3) Tsukamoto-French model of alcoholic liver injury, by S. W. French; (4) Animal models to study endotoxin-ethanol interactions, by K. O. Lindros and H. Järveläinen; and (5) Jejunoileal bypass...

  2. More than two decades of Apc modeling in rodents

    Science.gov (United States)

    Zeineldin, Maged; Neufeld, Kristi L.

    2013-01-01

    Mutation of tumor suppressor gene Adenomatous polyposis coli (APC) is an initiating step in most colon cancers. This review summarizes Apc models in mice and rats, with particular concentration on those most recently developed, phenotypic variation among different models, and genotype/ phenotype correlations. PMID:23333833

  3. Post-traumatic stress disorder and beyond: an overview of rodent stress models.

    Science.gov (United States)

    Schöner, Johanna; Heinz, Andreas; Endres, Matthias; Gertz, Karen; Kronenberg, Golo

    2017-10-01

    Post-traumatic stress disorder (PTSD) is a psychiatric disorder of high prevalence and major socioeconomic impact. Patients suffering from PTSD typically present intrusion and avoidance symptoms and alterations in arousal, mood and cognition that last for more than 1 month. Animal models are an indispensable tool to investigate underlying pathophysiological pathways and, in particular, the complex interplay of neuroendocrine, genetic and environmental factors that may be responsible for PTSD induction. Since the 1960s, numerous stress paradigms in rodents have been developed, based largely on Seligman's seminal formulation of 'learned helplessness' in canines. Rodent stress models make use of physiological or psychological stressors such as foot shock, underwater trauma, social defeat, early life stress or predator-based stress. Apart from the brief exposure to an acute stressor, chronic stress models combining a succession of different stressors for a period of several weeks have also been developed. Chronic stress models in rats and mice may elicit characteristic PTSD-like symptoms alongside, more broadly, depressive-like behaviours. In this review, the major existing rodent models of PTSD are reviewed in terms of validity, advantages and limitations; moreover, significant results and implications for future research-such as the role of FKBP5, a mediator of the glucocorticoid stress response and promising target for therapeutic interventions-are discussed. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  4. Vibration acceleration promotes bone formation in rodent models.

    Directory of Open Access Journals (Sweden)

    Ryohei Uchida

    Full Text Available All living tissues and cells on Earth are subject to gravitational acceleration, but no reports have verified whether acceleration mode influences bone formation and healing. Therefore, this study was to compare the effects of two acceleration modes, vibration and constant (centrifugal accelerations, on bone formation and healing in the trunk using BMP 2-induced ectopic bone formation (EBF mouse model and a rib fracture healing (RFH rat model. Additionally, we tried to verify the difference in mechanism of effect on bone formation by accelerations between these two models. Three groups (low- and high-magnitude vibration and control-VA groups were evaluated in the vibration acceleration study, and two groups (centrifuge acceleration and control-CA groups were used in the constant acceleration study. In each model, the intervention was applied for ten minutes per day from three days after surgery for eleven days (EBF model or nine days (RFH model. All animals were sacrificed the day after the intervention ended. In the EBF model, ectopic bone was evaluated by macroscopic and histological observations, wet weight, radiography and microfocus computed tomography (micro-CT. In the RFH model, whole fracture-repaired ribs were excised with removal of soft tissue, and evaluated radiologically and histologically. Ectopic bones in the low-magnitude group (EBF model had significantly greater wet weight and were significantly larger (macroscopically and radiographically than those in the other two groups, whereas the size and wet weight of ectopic bones in the centrifuge acceleration group showed no significant difference compared those in control-CA group. All ectopic bones showed calcified trabeculae and maturated bone marrow. Micro-CT showed that bone volume (BV in the low-magnitude group of EBF model was significantly higher than those in the other two groups (3.1±1.2mm3 v.s. 1.8±1.2mm3 in high-magnitude group and 1.3±0.9mm3 in control-VA group, but

  5. Handcrafted Electrocorticography Electrodes for a Rodent Behavioral Model

    Directory of Open Access Journals (Sweden)

    Nishat Tasnim

    2016-08-01

    Full Text Available Electrocorticography (ECoG is a minimally invasive neural recording method that has been extensively used for neuroscience applications. It has proven to have the potential to ease the establishment of proper links for neural interfaces that can offer disabled patients an alternative solution for their lost sensory and motor functions through the use of brain-computer interface (BCI technology. Although many neural recording methods exist, ECoG provides a combination of stability, high spatial and temporal resolution with chronic and mobile capabilities that could make BCI systems accessible for daily applications. However, many ECoG electrodes require MEMS fabricating techniques which are accompanied by various expenses that are obstacles for research projects. For this reason, this paper presents an animal study using a low cost and simple handcrafted ECoG electrode that is made of commercially accessible materials. The study is performed on a Lewis rat implanted with a handcrafted 32-channel non-penetrative ECoG electrode covering an area of 3 × 3 mm2 on the cortical surface. The ECoG electrodes were placed on the motor and somatosensory cortex to record the signal patterns while the animal was active on a treadmill. Using a Tucker-Davis Technologies acquisition system and the software Synapse to monitor and analyze the electrophysiological signals, the electrodes obtained signals within the amplitude range of 200 µV for local field potentials with reliable spatiotemporal profiles. It was also confirmed that the handcrafted ECoG electrode has the stability and chronic features found in other commercial electrodes.

  6. From the Rodent Spinal Cord Injury Model to Human Application: Promises and Challenges.

    Science.gov (United States)

    Dietz, Volker; Schwab, Martin E

    2017-05-01

    Repair of the spinal cord and improvement of mobility after injury has been a matter of basic and clinical research for several decades. A number of repair approaches were performed in animals, mainly rodent models of spinal cord injury (SCI). Some of these experimental therapies resulted in significant regeneration of tract fibers, formation of new connections and circuits, and associated improvement of mobility. Some clinical trials aiming at translating these approaches to the human condition of an SCI are currently on-going. The present therapy, however, remains rehabiliation: Mobility of patients with an SCI can be improved to a limited extent by the exploition of neuroplasticity. In this article the present state of the art in the field of SCI research will be discussed. Studies dealing with the promotion of spinal cord repair and those directed to improve mobility by exploition of neuroplasticity will be summarized. The promises and challenges of translational basic research in rodent SCI models will be presented.

  7. A model of Leptospirosis infection in an African rodent to determine risk to humans: Seasonal fluctuations and the impact of rodent control

    DEFF Research Database (Denmark)

    Holt, J; Davis, S; Leirs, Herwig

    2006-01-01

    Human leptospirosis (Leptospira spp. infection) is aworldwide public health problem that is of greatest concern for humid tropical and subtropical regions. The magnitude of the problem in these areas is larger because of the climatic and environmental conditions the bacterium face outside...... their hosts but also because of the frequency of contacts between people and sources of infection. Rodents are thought to play the most important role in the transmission of human leptospirosis. We here model the dynamics of infection in an African rodent (Mastomys natalensis) that is thought...... to be the principal source of infection in parts of Tanzania. Our model, representing the climatic conditions in central Tanzania, suggests a strong seasonality in the force of infection on humans with a peak in the abundance of infectious mice between January and April in agricultural environments. In urban areas...

  8. Opioid Abuse after Traumatic Brain Injury: Evaluation Using Rodent Models

    Science.gov (United States)

    2015-09-01

    craniotomy was cut with a trephine by hand over the right motor cortex . An injury cannula was fashioned from the hub of a female leur-lock 20g needle...ABSTRACT This project evaluated the effect of a moderate-level brain injury on risk for opioid abuse using preclinical models in rats . We assessed the...effect of brain injury on the rewarding effects of oxycodone in three rat self-administration procedures and found significant differences in the

  9. Histaminergic activity in a rodent model of Parkinson's disease.

    Science.gov (United States)

    Nowak, Przemysław; Noras, Lukasz; Jochem, Jerzy; Szkilnik, Ryszard; Brus, Halina; Körossy, Eva; Drab, Jacek; Kostrzewa, Richard M; Brus, Ryszard

    2009-04-01

    Rats lesioned shortly after birth with 6-OHDA have been proposed to be a near-ideal model of severe Parkinson's disease, because of non-lethality of the procedure, near-total destruction of nigrostriatal dopaminergic fibers, and near-total dopamine (DA) denervation of striatum. There are scarce data that in Parkinson's disease, activity of the central histaminergic system is increased. Therefore, the aim of this study was to determine histamine content in the brain and the effect of histamine receptor antagonists on behavior of adult rats. At 3 days after birth, Wistar rats were pretreated with desipramine (20.0 mg/kg ip) 1 h before bilateral icv administration of the catecholaminergic neurotoxin 6-OHDA (67 microg base, on each side) or saline-ascorbic acid (0.1%) vehicle (control). At 8 weeks levels of DA and its metabolites L: -3,4-dihydroxyphenylalanine (DOPAC) and homovanillic acid (HVA) were estimated in the striatum and frontal cortex by HPCL/ED technique. In the hypothalamus, hippocampus, frontal cortex, and medulla oblongata, the level of histamine was analyzed by immunoenzymatic method. Behavioral observations (locomotion, exploratory-, oral-, and stereotyped-activity) were additionally made on control and 6-OHDA neonatally lesioned rats. Effects of DA receptor agonists (SKF 38393, apomorphine) and histamine receptor antagonists (e.g., S(+)chlorpheniramine, H(1); cimetidine, H(2); thioperamide, H(3) agonist) were determined. We confirmed that 6-OHDA significantly reduced contents of DA and its metabolites in the brain in adulthood. Histamine content was significantly increased in the hypothalamus, hipocampus, and medulla oblongata. Moreover, in 6-OHDA-lesioned rats behavioral response was altered mainly by thioperamide (H(3) antagonist). These findings indicate that histamine and the central histaminergic system are altered in the brain of rats lesioned to model Parkinson's disease, and that histaminergic neurons exert a modulating role in Parkinsonian 6

  10. Overcoming some limitations of imprecise reliability models

    DEFF Research Database (Denmark)

    Kozine, Igor; Krymsky, Victor

    2011-01-01

    The application of imprecise reliability models is often hindered by the rapid growth in imprecision that occurs when many components constitute a system and by the fact that time to failure is bounded from above. The latter results in the necessity to explicitly introduce an upper bound on time ...

  11. Social defeat models in animal science: What we have learned from rodent models.

    Science.gov (United States)

    Toyoda, Atsushi

    2017-07-01

    Studies on stress and its impacts on animals are very important in many fields of science, including animal science, because various stresses influence animal production and animal welfare. In particular, the social stresses within animal groups have profound impact on animals, with the potential to induce abnormal behaviors and health problems. In humans, social stress induces several health problems, including psychiatric disorders. In animal stress models, social defeat models are well characterized and used in various research fields, particularly in studies concerning mental disorders. Recently, we have focused on behavior, nutrition and metabolism in rodent models of social defeat to elucidate how social stresses affect animals. In this review, recent significant progress in studies related to animal social defeat models are described. In the field of animal science, these stress models may contribute to advances in the development of functional foods and in the management of animal welfare. © 2017 The Authors. Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.

  12. Polarization Raman spectroscopy to explain rodent models of brittle bone

    Science.gov (United States)

    Makowski, Alexander J.; Nyman, Jeffry S.; Mahadevan-Jansen, Anita

    2013-03-01

    Activation Transcription Factor 4 (Atf-4) is essential for osteoblast maturation and proper collagen synthesis. We recently found that these bones demonstrate a rare brittleness phenotype, which is independent of bone strength. We utilized a confocal Renishaw Raman microscope (50x objective; NA=.75) to evaluate embedded, polished cross-sections of mouse tibia from both wild-type and knockout mice at 8 weeks of age (24 mice, nmineral and collagen; however, compositional changes did not fully encompass biomechanical differences. To investigate the impact of material organization, we acquired colocalized spectra aligning the polarization angle parallel and perpendicular to the long bone axis from wet intact femurs. To validate our results, we used MMP9-/- mice, which have a brittleness phenotype that is not explained by compositional Raman measures. Polarization angle difference spectra show marked significant changes in orientation of these compositional differences when comparing wild type to knockout bones. Relative to wild-type, Atf4 -/- and MMP9 -/- bones show significant differences (t-test; pbones. Such findings could have alternate interpretations about net collagen orientation or the angular distribution of collagen molecules. Use of polarization specific Raman measurements has implicated a structural profile that furthers our understanding of models of bone brittleness. Polarization content of Raman spectra may prove significant in future studies of brittle fracture and human fracture risk.

  13. Morphological and functional maturation of Leydig cells: from rodent models to primates.

    Science.gov (United States)

    Teerds, Katja J; Huhtaniemi, Ilpo T

    2015-01-01

    Leydig cells (LC) are the sites of testicular androgen production. Development of LC occurs in the testes of most mammalian species as two distinct growth phases, i.e. as fetal and pubertal/adult populations. In primates there are indications of a third neonatal growth phase. LC androgen production begins in embryonic life and is crucial for the intrauterine masculinization of the male fetal genital tract and brain, and continues until birth after which it rapidly declines. A short post-natal phase of LC activity in primates (including human) termed 'mini-puberty' precedes the period of juvenile quiescence. The adult population of LC evolves, depending on species, in mid- to late-prepuberty upon reawakening of the hypothalamic-pituitary-testicular axis, and these cells are responsible for testicular androgen production in adult life, which continues with a slight gradual decline until senescence. This review is an updated comparative analysis of the functional and morphological maturation of LC in model species with special reference to rodents and primates. Pubmed, Scopus, Web of Science and Google Scholar databases were searched between December 2012 and October 2014. Studies published in languages other than English or German were excluded, as were data in abstract form only. Studies available on primates were primarily examined and compared with available data from specific animal models with emphasis on rodents. Expression of different marker genes in rodents provides evidence that at least two distinct progenitor lineages give rise to the fetal LC (FLC) population, one arising from the coelomic epithelium and the other from specialized vascular-associated cells along the gonad-mesonephros border. There is general agreement that the formation and functioning of the FLC population in rodents is gonadotrophin-responsive but not gonadotrophin-dependent. In contrast, although there is in primates some controversy on the role of gonadotrophins in the formation of

  14. Reliable RANSAC Using a Novel Preprocessing Model

    Directory of Open Access Journals (Sweden)

    Xiaoyan Wang

    2013-01-01

    Full Text Available Geometric assumption and verification with RANSAC has become a crucial step for corresponding to local features due to its wide applications in biomedical feature analysis and vision computing. However, conventional RANSAC is very time-consuming due to redundant sampling times, especially dealing with the case of numerous matching pairs. This paper presents a novel preprocessing model to explore a reduced set with reliable correspondences from initial matching dataset. Both geometric model generation and verification are carried out on this reduced set, which leads to considerable speedups. Afterwards, this paper proposes a reliable RANSAC framework using preprocessing model, which was implemented and verified using Harris and SIFT features, respectively. Compared with traditional RANSAC, experimental results show that our method is more efficient.

  15. Arvicanthis ansorgei, a Novel Model for the Study of Sleep and Waking in Diurnal Rodents

    Science.gov (United States)

    Hubbard, Jeffrey; Ruppert, Elisabeth; Calvel, Laurent; Robin-Choteau, Ludivine; Gropp, Claire-Marie; Allemann, Caroline; Reibel, Sophie; Sage-Ciocca, Dominique; Bourgin, Patrice

    2015-01-01

    Study Objectives: Sleep neurobiology studies use nocturnal species, mainly rats and mice. However, because their daily sleep/wake organization is inverted as compared to humans, a diurnal model for sleep studies is needed. To fill this gap, we phenotyped sleep and waking in Arvicanthis ansorgei, a diurnal rodent widely used for the study of circadian rhythms. Design: Video-electroencephalogram (EEG), electromyogram (EMG), and electrooculogram (EOG) recordings. Setting: Rodent sleep laboratory. Participants: Fourteen male Arvicanthis ansorgei, aged 3 mo. Interventions: 12 h light (L):12 h dark (D) baseline condition, 24-h constant darkness, 6-h sleep deprivation. Measurements and Results: Wake and rapid eye movement (REM) sleep showed similar electrophysiological characteristics as nocturnal rodents. On average, animals spent 12.9 h ± 0.4 awake per 24-h cycle, of which 6.88 h ± 0.3 was during the light period. NREM sleep accounted for 9.63 h ± 0.4, which of 5.13 h ± 0.2 during dark period, and REM sleep for 89.9 min ± 6.7, which of 52.8 min ± 4.4 during dark period. The time-course of sleep and waking across the 12 h light:12 h dark was overall inverted to that observed in rats or mice, though with larger amounts of crepuscular activity at light and dark transitions. A dominant crepuscular regulation of sleep and waking persisted under constant darkness, showing the lack of a strong circadian drive in the absence of clock reinforcement by external cues, such as a running wheel. Conservation of the homeostatic regulation was confirmed with the observation of higher delta power following sustained waking periods and a 6-h sleep deprivation, with subsequent decrease during recovery sleep. Conclusions: Arvicanthis ansorgei is a valid diurnal rodent model for studying the regulatory mechanisms of sleep and so represents a valuable tool for further understanding the nocturnality/diurnality switch. Citation: Hubbard J, Ruppert E, Calvel L, Robin-Choteau L, Gropp CM

  16. The relevance of non-human primate and rodent malaria models for humans

    Directory of Open Access Journals (Sweden)

    Riley Eleanor

    2011-02-01

    Full Text Available Abstract At the 2010 Keystone Symposium on "Malaria: new approaches to understanding Host-Parasite interactions", an extra scientific session to discuss animal models in malaria research was convened at the request of participants. This was prompted by the concern of investigators that skepticism in the malaria community about the use and relevance of animal models, particularly rodent models of severe malaria, has impacted on funding decisions and publication of research using animal models. Several speakers took the opportunity to demonstrate the similarities between findings in rodent models and human severe disease, as well as points of difference. The variety of malaria presentations in the different experimental models parallels the wide diversity of human malaria disease and, therefore, might be viewed as a strength. Many of the key features of human malaria can be replicated in a variety of nonhuman primate models, which are very under-utilized. The importance of animal models in the discovery of new anti-malarial drugs was emphasized. The major conclusions of the session were that experimental and human studies should be more closely linked so that they inform each other, and that there should be wider access to relevant clinical material.

  17. Radiation-induced mammary carcinogenesis in rodent models. What's different from chemical carcinogenesis?

    International Nuclear Information System (INIS)

    Imaoka, Tatsuhiko; Nishimura, Mayumi; Iizuka, Daisuke; Daino, Kazuhiro; Takabatake, Takashi; Okamoto, Mieko; Kakinuma, Shizuko; Shimada, Yoshiya

    2009-01-01

    Ionizing radiation is one of a few well-characterized etiologic factors of human breast cancer. Laboratory rodents serve as useful experimental models for investigating dose responses and mechanisms of cancer development. Using these models, a lot of information has been accumulated about mammary gland cancer, which can be induced by both chemical carcinogens and radiation. In this review, we first list some experimental rodent models of breast cancer induction. We then focus on several topics that are important in understanding the mechanisms and risk modification of breast cancer development, and compare radiation and chemical carcinogenesis models. We will focus on the pathology and natural history of cancer development in these models, genetic changes observed in induced cancers, indirect effects of carcinogens, and finally risk modification by reproductive factors and age at exposure to the carcinogens. In addition, we summarize the knowledge available on mammary stem/progenitor cells as a potential target of carcinogens. Comparison of chemical and radiation carcinogenesis models on these topics indicates certain similarities, but it also indicates clear differences in several important aspects, such as genetic alterations of induced cancers and modification of susceptibility by age and reproductive factors. Identification of the target cell type and relevant translational research for human risk management may be among the important issues that are addressed by radiation carcinogenesis models. (author)

  18. Centralized Bayesian reliability modelling with sensor networks

    Czech Academy of Sciences Publication Activity Database

    Dedecius, Kamil; Sečkárová, Vladimíra

    2013-01-01

    Roč. 19, č. 5 (2013), s. 471-482 ISSN 1387-3954 R&D Projects: GA MŠk 7D12004 Grant - others:GA MŠk(CZ) SVV-265315 Keywords : Bayesian modelling * Sensor network * Reliability Subject RIV: BD - Theory of Information Impact factor: 0.984, year: 2013 http://library.utia.cas.cz/separaty/2013/AS/dedecius-0392551.pdf

  19. Stochastic models in reliability and maintenance

    CERN Document Server

    2002-01-01

    Our daily lives can be maintained by the high-technology systems. Computer systems are typical examples of such systems. We can enjoy our modern lives by using many computer systems. Much more importantly, we have to maintain such systems without failure, but cannot predict when such systems will fail and how to fix such systems without delay. A stochastic process is a set of outcomes of a random experiment indexed by time, and is one of the key tools needed to analyze the future behavior quantitatively. Reliability and maintainability technologies are of great interest and importance to the maintenance of such systems. Many mathematical models have been and will be proposed to describe reliability and maintainability systems by using the stochastic processes. The theme of this book is "Stochastic Models in Reliability and Main­ tainability. " This book consists of 12 chapters on the theme above from the different viewpoints of stochastic modeling. Chapter 1 is devoted to "Renewal Processes," under which cla...

  20. Measurement-based reliability/performability models

    Science.gov (United States)

    Hsueh, Mei-Chen

    1987-01-01

    Measurement-based models based on real error-data collected on a multiprocessor system are described. Model development from the raw error-data to the estimation of cumulative reward is also described. A workload/reliability model is developed based on low-level error and resource usage data collected on an IBM 3081 system during its normal operation in order to evaluate the resource usage/error/recovery process in a large mainframe system. Thus, both normal and erroneous behavior of the system are modeled. The results provide an understanding of the different types of errors and recovery processes. The measured data show that the holding times in key operational and error states are not simple exponentials and that a semi-Markov process is necessary to model the system behavior. A sensitivity analysis is performed to investigate the significance of using a semi-Markov process, as opposed to a Markov process, to model the measured system.

  1. Bayesian methodology for reliability model acceptance

    International Nuclear Information System (INIS)

    Zhang Ruoxue; Mahadevan, Sankaran

    2003-01-01

    This paper develops a methodology to assess the reliability computation model validity using the concept of Bayesian hypothesis testing, by comparing the model prediction and experimental observation, when there is only one computational model available to evaluate system behavior. Time-independent and time-dependent problems are investigated, with consideration of both cases: with and without statistical uncertainty in the model. The case of time-independent failure probability prediction with no statistical uncertainty is a straightforward application of Bayesian hypothesis testing. However, for the life prediction (time-dependent reliability) problem, a new methodology is developed in this paper to make the same Bayesian hypothesis testing concept applicable. With the existence of statistical uncertainty in the model, in addition to the application of a predictor estimator of the Bayes factor, the uncertainty in the Bayes factor is explicitly quantified through treating it as a random variable and calculating the probability that it exceeds a specified value. The developed method provides a rational criterion to decision-makers for the acceptance or rejection of the computational model

  2. Establishment of a general NAFLD scoring system for rodent models and comparison to human liver pathology.

    Directory of Open Access Journals (Sweden)

    Wen Liang

    Full Text Available The recently developed histological scoring system for non-alcoholic fatty liver disease (NAFLD by the NASH Clinical Research Network (NASH-CRN has been widely used in clinical settings, but is increasingly employed in preclinical research as well. However, it has not been systematically analyzed whether the human scoring system can directly be converted to preclinical rodent models. To analyze this, we systematically compared human NAFLD liver pathology, using human liver biopsies, with liver pathology of several NAFLD mouse models. Based upon the features pertaining to mouse NAFLD, we aimed at establishing a modified generic scoring system that is applicable to broad spectrum of rodent models.The histopathology of NAFLD was analyzed in several different mouse models of NAFLD to define generic criteria for histological assessment (preclinical scoring system. For validation of this scoring system, 36 slides of mouse livers, covering the whole spectrum of NAFLD, were blindly analyzed by ten observers. Additionally, the livers were blindly scored by one observer during two separate assessments longer than 3 months apart.The criteria macrovesicular steatosis, microvesicular steatosis, hepatocellular hypertrophy, inflammation and fibrosis were generally applicable to rodent NAFLD. The inter-observer reproducibility (evaluated using the Intraclass Correlation Coefficient between the ten observers was high for the analysis of macrovesicular steatosis and microvesicular steatosis (ICC = 0.784 and 0.776, all p<0.001, respectively and moderate for the analysis of hypertrophy and inflammation (ICC = 0.685 and 0.650, all p<0.001, respectively. The intra-observer reproducibility between the different observations of one observer was high for the analysis of macrovesicular steatosis, microvesicular steatosis and hypertrophy (ICC = 0.871, 0.871 and 0.896, all p<0.001, respectively and very high for the analysis of inflammation (ICC = 0.931, p

  3. Data Used in Quantified Reliability Models

    Science.gov (United States)

    DeMott, Diana; Kleinhammer, Roger K.; Kahn, C. J.

    2014-01-01

    Data is the crux to developing quantitative risk and reliability models, without the data there is no quantification. The means to find and identify reliability data or failure numbers to quantify fault tree models during conceptual and design phases is often the quagmire that precludes early decision makers consideration of potential risk drivers that will influence design. The analyst tasked with addressing a system or product reliability depends on the availability of data. But, where is does that data come from and what does it really apply to? Commercial industries, government agencies, and other international sources might have available data similar to what you are looking for. In general, internal and external technical reports and data based on similar and dissimilar equipment is often the first and only place checked. A common philosophy is "I have a number - that is good enough". But, is it? Have you ever considered the difference in reported data from various federal datasets and technical reports when compared to similar sources from national and/or international datasets? Just how well does your data compare? Understanding how the reported data was derived, and interpreting the information and details associated with the data is as important as the data itself.

  4. The JCR:LA-cp rat: a novel rodent model of cystic medial necrosis.

    Science.gov (United States)

    Pung, Yuh Fen; Chilian, William M; Bennett, Martin R; Figg, Nichola; Kamarulzaman, Mohd Hamzah

    2017-03-01

    Although there are multiple rodent models of the metabolic syndrome, very few develop vascular complications. In contrast, the JCR:LA-cp rat develops both metabolic syndrome and early atherosclerosis in predisposed areas. However, the pathology of the normal vessel wall has not been described. We examined JCR:LA control (+/+) or cp/cp rats fed normal chow diet for 6 or 18 mo. JCR:LA-cp rats developed multiple features of advanced cystic medial necrosis including "cysts," increased collagen formation and proteoglycan deposition around cysts, apoptosis of vascular smooth muscle cells, and spotty medial calcification. These appearances began within 6 mo and were extensive by 18 mo. JCR:LA-cp rats had reduced medial cellularity, increased medial thickness, and vessel hypoxia that was most marked in the adventitia. In conclusion, the normal chow-fed JCR:LA-cp rat represents a novel rodent model of cystic medial necrosis, associated with multiple metabolic abnormalities, vascular smooth muscle cell apoptosis, and vessel hypoxia. NEW & NOTEWORTHY Triggers for cystic medial necrosis (CMN) have been difficult to study due to lack of animal models to recapitulate the pathologies seen in humans. Our study is the first description of CMN in the rat. Thus the JCR:LA-cp rat represents a useful model to investigate the underlying molecular changes leading to the development of CMN. Copyright © 2017 the American Physiological Society.

  5. Transplacental Nutrient Transport Mechanisms of Intrauterine Growth Restriction in Rodent Models and Humans

    Directory of Open Access Journals (Sweden)

    Elke Winterhager

    2017-11-01

    Full Text Available Although the causes of intrauterine growth restriction (IUGR have been intensively investigated, important information is still lacking about the role of the placenta as a link from adverse maternal environment to adverse pregnancy outcomes of IUGR and preterm birth. IUGR is associated with an increased risk of cardiovascular, metabolic, and neurological diseases later in life. Determination of the most important pathways that regulate transplacental transport systems is necessary for identifying marker genes as diagnostic tools and for developing drugs that target the molecular pathways. Besides oxygen, the main nutrients required for appropriate fetal development and growth are glucose, amino acids, and fatty acids. Dysfunction in transplacental transport is caused by impairments in both placental morphology and blood flow, as well as by factors such as alterations in the expression of insulin-like growth factors and changes in the mTOR signaling pathway leading to a change in nutrient transport. Animal models are important tools for systematically studying such complex events. Debate centers on whether the rodent placenta is an appropriate tool for investigating the alterations in the human placenta that result in IUGR. This review provides an overview of the alterations in expression and activity of nutrient transporters and alterations in signaling associated with IUGR and compares these findings in rodents and humans. In general, the data obtained by studies of the various types of rodent and human nutrient transporters are similar. However, direct comparison is complicated by the fact that the results of such studies are controversial even within the same species, making the interpretation of the results challenging. This difficulty could be due to the absence of guidelines of the experimental design and, especially in humans, the use of trophoblast cell culture studies instead of clinical trials. Nonetheless, developing new therapy

  6. Transplacental Nutrient Transport Mechanisms of Intrauterine Growth Restriction in Rodent Models and Humans.

    Science.gov (United States)

    Winterhager, Elke; Gellhaus, Alexandra

    2017-01-01

    Although the causes of intrauterine growth restriction (IUGR) have been intensively investigated, important information is still lacking about the role of the placenta as a link from adverse maternal environment to adverse pregnancy outcomes of IUGR and preterm birth. IUGR is associated with an increased risk of cardiovascular, metabolic, and neurological diseases later in life. Determination of the most important pathways that regulate transplacental transport systems is necessary for identifying marker genes as diagnostic tools and for developing drugs that target the molecular pathways. Besides oxygen, the main nutrients required for appropriate fetal development and growth are glucose, amino acids, and fatty acids. Dysfunction in transplacental transport is caused by impairments in both placental morphology and blood flow, as well as by factors such as alterations in the expression of insulin-like growth factors and changes in the mTOR signaling pathway leading to a change in nutrient transport. Animal models are important tools for systematically studying such complex events. Debate centers on whether the rodent placenta is an appropriate tool for investigating the alterations in the human placenta that result in IUGR. This review provides an overview of the alterations in expression and activity of nutrient transporters and alterations in signaling associated with IUGR and compares these findings in rodents and humans. In general, the data obtained by studies of the various types of rodent and human nutrient transporters are similar. However, direct comparison is complicated by the fact that the results of such studies are controversial even within the same species, making the interpretation of the results challenging. This difficulty could be due to the absence of guidelines of the experimental design and, especially in humans, the use of trophoblast cell culture studies instead of clinical trials. Nonetheless, developing new therapy concepts for IUGR will

  7. Cognitive and behavioral evaluation of nutritional interventions in rodent models of brain aging and dementia

    Directory of Open Access Journals (Sweden)

    Wahl D

    2017-09-01

    Full Text Available Devin Wahl,1,2 Sean CP Coogan,1,3 Samantha M Solon-Biet,1,2 Rafael de Cabo,4 James B Haran,5 David Raubenheimer,1,6,7 Victoria C Cogger,1,2 Mark P Mattson,8 Stephen J Simpson,1,2,7 David G Le Couteur1,2 1Charles Perkins Centre, University of Sydney, Sydney, 2Aging and Alzheimers Institute, ANZAC Research Institute, Concord Clinical School/Sydney Medical School, Concord, NSW, Australia; 3Department of Renewable Resources, University of Alberta, Edmonton, AB, Canada; 4Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA; 5Philadelphia College of Osteopathic Medicine, Philadelphia, PA, USA; 6Faculty of Veterinary Science, 7School of Life and Environmental Sciences, University of Sydney, Sydney, NSW, Australia; 8Laboratory of Neurosciences, National Institute on Aging’s Intramural Research Program, National Institutes of Health, Baltimore, MD, USA Abstract: Evaluation of behavior and cognition in rodent models underpins mechanistic and interventional studies of brain aging and neurodegenerative diseases, especially ­dementia. Commonly used tests include Morris water maze, Barnes maze, object recognition, fear ­conditioning, radial arm water maze, and Y maze. Each of these tests reflects some aspects of human memory including episodic memory, recognition memory, semantic memory, spatial memory, and emotional memory. Although most interventional studies in rodent models of dementia have focused on pharmacological agents, there are an increasing number of studies that have evaluated nutritional interventions including caloric restriction, intermittent fasting, and manipulation of macronutrients. Dietary interventions have been shown to influence ­various cognitive and behavioral tests in rodents indicating that nutrition can influence brain aging and possibly neurodegeneration. Keywords: calorie restriction, intermittent fasting, aging, memory, macronutrients

  8. Barriers to developing a valid rodent model of Alzheimer's disease: from behavioural analysis to etiologicalmechanisms

    Directory of Open Access Journals (Sweden)

    Darryl Christopher Gidyk

    2015-07-01

    Full Text Available Sporadic Alzheimer's disease is the most prevalent form of age-related dementia. As such, great effort has been put forth to investigate the etiology, progression, and underlying mechanisms of the disease. Countless studies have been conducted however the details of this disease remain largely unknown. Rodent models provide opportunities to investigate certain aspects of AD that cannot be ethically studied in humans. These animal models vary from study to study and have provided some insight, but no real advancements in the prevention or treatment of the disease. In this Hypothesis and Theory paper, we discuss what we perceive as barriers to impactful discovery in rodent AD research and we offer solutions for moving forward. Although no single model of AD is capable of providing the solution to the growing epidemic of the disease, we encourage a comprehensive approach that acknowledges the complex etiology of AD with the goal of enhancing the bidirectional translatability from bench to bedside and vice versa.

  9. Animal Models for the Study of Rodent-Borne Hemorrhagic Fever Viruses: Arenaviruses and Hantaviruses

    Directory of Open Access Journals (Sweden)

    Joseph W. Golden

    2015-01-01

    Full Text Available Human pathogenic hantaviruses and arenaviruses are maintained in nature by persistent infection of rodent carrier populations. Several members of these virus groups can cause significant disease in humans that is generically termed viral hemorrhagic fever (HF and is characterized as a febrile illness with an increased propensity to cause acute inflammation. Human interaction with rodent carrier populations leads to infection. Arenaviruses are also viewed as potential biological weapons threat agents. There is an increased interest in studying these viruses in animal models to gain a deeper understating not only of viral pathogenesis, but also for the evaluation of medical countermeasures (MCM to mitigate disease threats. In this review, we examine current knowledge regarding animal models employed in the study of these viruses. We include analysis of infection models in natural reservoirs and also discuss the impact of strain heterogeneity on the susceptibility of animals to infection. This information should provide a comprehensive reference for those interested in the study of arenaviruses and hantaviruses not only for MCM development but also in the study of viral pathogenesis and the biology of these viruses in their natural reservoirs.

  10. Optical imaging of oxidative stress in retinitis pigmentosa (RP) in rodent model

    Science.gov (United States)

    Ghanian, Zahra; Maleki, Sepideh; Gopalakrishnan, Sandeep; Sepehr, Reyhaneh; Eells, Janis T.; Ranji, Mahsa

    2013-02-01

    Oxidative stress (OS), which increases during retinal degenerative disorders, contributes to photoreceptor cell loss. The objective of this study was to investigate the changes in the metabolic state of the eye tissue in rodent models of retinitis pigmentosa by using the cryofluorescence imaging technique. The mitochondrial metabolic coenzymes NADH and FADH2 are autofluorescent and can be monitored without exogenous labels using optical techniques. The NADH redox ratio (RR), which is the ratio of the fluorescence intensity of these fluorophores (NADH/FAD), was used as a quantitative diagnostic marker. The NADH RR was examined in an established rodent model of retinitis pigmentosa (RP), the P23H rat, and compared to that of control Sprague-Dawley (SD) rats and P23H NIR treated rats. Our results demonstrated 24% decrease in the mean NADH RR of the eyes from P23H transgenic rats compared to normal rats and 20% increase in the mean NADH RR of the eyes from the P23H NIR treated rats compared to P23H non-treated rats.

  11. Optical imaging of mitochondrial redox state in rodent model of retinitis pigmentosa

    Science.gov (United States)

    Maleki, Sepideh; Gopalakrishnan, Sandeep; Ghanian, Zahra; Sepehr, Reyhaneh; Schmitt, Heather; Eells, Janis; Ranji, Mahsa

    2013-01-01

    Oxidative stress (OS) and mitochondrial dysfunction contribute to photoreceptor cell loss in retinal degenerative disorders. The metabolic state of the retina in a rodent model of retinitis pigmentosa (RP) was investigated using a cryo-fluorescence imaging technique. The mitochondrial metabolic coenzymes nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) are autofluorescent and can be monitored without exogenous labels using optical techniques. The cryo-fluorescence redox imaging technique provides a quantitative assessment of the metabolism. More specifically, the ratio of the fluorescence intensity of these fluorophores (NADH/FAD), the NADH redox ratio (RR), is a marker of the metabolic state of the tissue. The NADH RR and retinal function were examined in an established rodent model of RP, the P23H rat compared to that of nondystrophic Sprague-Dawley (SD) rats. The NADH RR mean values were 1.11±0.03 in the SD normal and 0.841±0.01 in the P23H retina, indicating increased OS in the P23H retina. Electroretinographic data revealed a significant reduction in photoreceptor function in P23H animals compared to SD nozrmal rats. Thus, cryo-fluorescence redox imaging was used as a quantitative marker of OS in eyes from transgenic rats and demonstrated that alterations in the oxidative state of eyes occur during the early stages of RP.

  12. [Biological and neural bases of partner preferences in rodents: models to understand human pair bonds].

    Science.gov (United States)

    Coria-Avila, G A; Hernández-Aguilar, M E; Toledo-Cárdenas, R; García-Hernández, L I; Manzo, J; Pacheco, P; Miquel, M; Pfaus, J G

    To analyse the biological and neural bases of partner preference formation in rodents as models to understand human pair bonding. Rodents are social individuals, capable of forming short- or long-lasting partner preferences that develop slowly by stimuli like cohabitation, or rapidly by stimuli like sex and stress. Dopamine, corticosteroids, oxytocin, vasopressin, and opioids form the neurochemical substrate for pair bonding in areas like the nucleus accumbens, the prefrontal cortex, the piriform cortex, the medial preoptic area, the ventral tegmental area and the medial amygdala, among others. Additional areas may participate depending on the nature of the conditioned stimuli by which and individual recognizes a preferred partner. Animal models help us understand that the capacity of an individual to display long-lasting and selective preferences depends on neural bases, selected throughout evolution. The challenge in neuroscience is to use this knowledge to create new solutions for mental problems associated with the incapacity of an individual to display a social bond, keep one, or cope with the disruption of a consolidated one.

  13. Modeling natural photic entrainment in a subterranean rodent (Ctenomys aff. knighti, the Tuco-Tuco.

    Directory of Open Access Journals (Sweden)

    Danilo E F L Flôres

    Full Text Available Subterranean rodents spend most of the day inside underground tunnels, where there is little daily change in environmental variables. Our observations of tuco-tucos (Ctenomys aff. knighti in a field enclosure indicated that these animals perceive the aboveground light-dark cycle by several bouts of light-exposure at irregular times during the light hours of the day. To assess whether such light-dark pattern acts as an entraining agent of the circadian clock, we first constructed in laboratory the Phase Response Curve for 1 h light-pulses (1000lux. Its shape is qualitatively similar to other curves reported in the literature and to our knowledge it is the first Phase Response Curve of a subterranean rodent. Computer simulations were performed with a non-linear limit-cycle oscillator subjected to a simple model of the light regimen experienced by tuco-tucos. Results showed that synchronization is achieved even by a simple regimen of a single daily light pulse scattered uniformly along the light hours of the day. Natural entrainment studies benefit from integrated laboratory, field and computational approaches.

  14. Effects of early life adverse experiences on brain activity: Implications from maternal separation models in rodents

    Directory of Open Access Journals (Sweden)

    Mayumi eNishi

    2014-06-01

    Full Text Available During postnatal development, adverse early life experiences can affect the formation of neuronal circuits and exert long-lasting influences on neural function. Many studies have shown that daily repeated MS, an animal model of early life stress, can modulate the hypothalamic-pituitary-adrenal axis (HPA axis and can affect subsequent brain function and emotional behavior during adulthood. However, the molecular basis of the long-lasting effects of early life stress on brain function has not been completely elucidated. In this review, we introduce various cases of MS in rodents and illustrate the alterations in HPA axis activity by focusing on corticosterone (CORT, an end product of the HPA axis in rodents. We then present a characterization of the brain regions affected by various patterns of MS, including repeated MS and single time MS at various stages before weaning, by investigating c-Fos expression, a biological marker of neuronal activity. These CORT and c-Fos studies suggest that repeated early life stress may affect neuronal function in region- and temporal-specific manners, indicating a critical period for habituation to early life stress. Next, we discuss how early life stress can impact behavior, namely by inducing depression, anxiety or eating disorders. Furthermore, alterations in gene expression in adult mice exposed to MS, especially epigenetic changes of DNA methylation, are discussed.

  15. Effect of tramadol on pain-related behaviors and bladder overactivity in rodent cystitis models.

    Science.gov (United States)

    Oyama, Tatsuya; Homan, Takashi; Kyotani, Junko; Oka, Michiko

    2012-02-15

    Tramadol is a widely used analgesic that stimulates the μ opioid receptor and inhibits serotonin and noradrenalin reuptake. There have been studies on the analgesic effects of tramadol based on the tail-flick test, the formalin test, and the induction of allodynia by sciatic-nerve ligation. However, the effects of tramadol on behaviors related to bladder pain and bladder overactivity induced by cystitis have not been reported. To investigate the usefulness of tramadol for patients with cystitis, we investigated these effects of tramadol in rodent cystitis models. Intraperitoneal injection of cyclophosphamide caused bladder-specific inflammation and increases in pain-related behaviors, the number of voids and bladder weight in mice. Tramadol suppressed the cyclophosphamide-induced pain-related behaviors but did not affect the number of voids or the bladder weight. During continuous-infusion cystometrograms in anesthetized rats, cyclophosphamide shortened the intercontraction interval, indicating bladder overactivity. Tramadol significantly prolonged the intercontraction interval, and the effect was partially blocked by the opioid antagonist naloxone. This finding indicates that μ opioid receptors may be involved in the action of tramadol. In conclusion, tramadol ameliorated cyclophosphamide-induced bladder-pain-related behaviors and bladder overactivity in rodents. These findings suggest that tramadol might be a treatment option for cystitis-induced bladder pain and bladder overactivity. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. An improved cost-effective, reproducible method for evaluation of bone loss in a rodent model.

    Science.gov (United States)

    Fine, Daniel H; Schreiner, Helen; Nasri-Heir, Cibele; Greenberg, Barbara; Jiang, Shuying; Markowitz, Kenneth; Furgang, David

    2009-02-01

    This study was designed to investigate the utility of two "new" definitions for assessment of bone loss in a rodent model of periodontitis. Eighteen rats were divided into three groups. Group 1 was infected by Aggregatibacter actinomycetemcomitans (Aa), group 2 was infected with an Aa leukotoxin knock-out, and group 3 received no Aa (controls). Microbial sampling and antibody titres were determined. Initially, two examiners measured the distance from the cemento-enamel-junction to alveolar bone crest using the three following methods; (1) total area of bone loss by radiograph, (2) linear bone loss by radiograph, (3) a direct visual measurement (DVM) of horizontal bone loss. Two "new" definitions were adopted; (1) any site in infected animals showing bone loss >2 standard deviations above the mean seen at that site in control animals was recorded as bone loss, (2) any animal with two or more sites in any quadrant affected by bone loss was considered as diseased. Using the "new" definitions both evaluators independently found that infected animals had significantly more disease than controls (DVM system; p<0.05). The DVM method provides a simple, cost effective, and reproducible method for studying periodontal disease in rodents.

  17. Mathematical methods to model rodent behavior in the elevated plus-maze.

    Science.gov (United States)

    Arantes, Rafael; Tejada, Julián; Bosco, Geraldine G; Morato, Silvio; Roque, Antonio C

    2013-11-15

    The elevated plus maze is a widely used experimental test to study anxiety-like rodent behavior. It is made of four arms, two open and two closed, connected at a central area forming a plus shaped maze. The whole apparatus is elevated 50 cm from the floor. The anxiety of the animal is usually assessed by the number of entries and duration of stay in each arm type during a 5-min period. Different mathematical methods have been proposed to model the mechanisms that control the animal behavior in the maze, such as factor analysis, statistical inference on Markov chains and computational modeling. In this review we discuss these methods and propose possible extensions of them as a direction for future research. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Aberrant dopamine D2-like receptor function in a rodent model of schizophrenia.

    Science.gov (United States)

    Perez, Stephanie M; Lodge, Daniel J

    2012-11-01

    Based on the observation that antipsychotic medications display antagonist properties at dopamine D2-like receptors, aberrant dopamine signaling has been proposed to underlie psychosis in patients with schizophrenia. Thus, it is not surprising that considerable research has been devoted to understanding the mechanisms involved in the antipsychotic action of these compounds. It is important to note that the majority of these studies have been performed in "normal" experimental animals. Given that these animals do not possess the aberrant neuronal information processing typically associated with schizophrenia, the aim of the current study was to examine the dopamine D2 receptor system in a rodent model of schizophrenia. Here, we demonstrate that methylazoxymethanol acetate (MAM)-treated rats display an enhanced effect of quinpirole on dopamine neuron activity and an aberrant locomotor response to D2-like receptor activation, suggesting changes in postsynaptic D2-like receptor function. To better understand the mechanisms underlying the enhanced response to D2-like ligands in MAM-treated rats, we examined the expression of D2, D3, and dopamine transporter mRNA in the nucleus accumbens and ventral tegmental area by quantitative reverse transcription-polymerase chain reaction. MAM-treated rats displayed a significant increase in dopamine D3 receptor mRNA expression in the nucleus accumbens with no significant changes in the expression of the D2 receptor. Taken together, these data demonstrate robust alterations in dopamine D2-like receptor function in a rodent model of schizophrenia and provide evidence that preclinical studies examining the mechanisms of antipsychotic drug action should be performed in animal models that mirror aspects of the abnormal neuronal transmission thought to underlie symptoms of schizophrenia.

  19. A unique rodent model of cardiometabolic risk associated with the metabolic syndrome and polycystic ovary syndrome.

    Science.gov (United States)

    Shi, Danni; Dyck, Michael K; Uwiera, Richard R E; Russell, Jim C; Proctor, Spencer D; Vine, Donna F

    2009-09-01

    Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, oligo-/anovulation, and polycystic ovarian morphology and is a complex endocrine disorder that also presents with features of the metabolic syndrome, including obesity, insulin resistance, and dyslipidemia. These latter symptoms form cardiometabolic risk factors predisposing individuals to the development of type 2 diabetes and cardiovascular disease (CVD). To date, animal models to study PCOS in the context of the metabolic syndrome and CVD risk have been lacking. The aim of this study was to investigate the JCR:LA-cp rodent as an animal model of PCOS associated with the metabolic syndrome. Metabolic indices were measured at 6 and 12 wk, and reproductive parameters including ovarian morphology and estrous cyclicity were assessed at 12 wk or adulthood. At 6 wk of age, the cp/cp genotype of the JCR:LA-cp strain developed visceral obesity, insulin resistance, and dyslipidemia (hypertriglyceridemia and hypercholesterolemia) compared with control animals. Serum testosterone concentrations were not significantly different between groups at 6 wk of age. However, at 12 wk, the cp/cp genotype had higher serum testosterone concentrations, compared with control animals, and presented with oligoovulation, a decreased number of corpora lutea, and an increased number of total follicles, in particular atretic and cystic follicles. The cardiometabolic risk factors in the cp/cp animals were exacerbated at 12 wk including obesity, insulin resistance, and dyslipidemia. The results of this study demonstrate that the JCR:LA-cp rodent may be a useful PCOS-like model to study early mechanisms involved in the etiology of cardiometabolic risk factors in the context of both PCOS and the metabolic syndrome.

  20. Olfactory discrimination and memory deficits in the Flinders Sensitive Line rodent model of depression.

    Science.gov (United States)

    Cook, A; Pfeiffer, L-M; Thiele, S; Coenen, V A; Döbrössy, M D

    2017-10-01

    Major Depressive Disorder (MDD) is a heterogeneous psychiatric disorder with broad symptomatic manifestations. The current study examined, for the first time, olfactory memory and discrimination in the Flinders Sensitive Line (FSL) rodent model of depression. Male FSL rats and controls were trained on an Olfactory Discrimination (OD) and a Social Interaction (SI) test. On the OD test, the FSL and controls performed similarly at the shortest inter-trial interval (5min), however, with extended delay of 30min, the FSLs had a recall and odour discrimination deficit. At the longest delay (60min) both groups performed poorly. The FSL rats i.) had a deficit in olfactory discrimination suggesting impairment in olfactory memory and recall; ii.) were less likely to socialize with unfamiliar rats. The data suggests that FSL animals have an impaired olfactory information processing capacity. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Intraoperative laser speckle contrast imaging improves the stability of rodent middle cerebral artery occlusion model

    Science.gov (United States)

    Yuan, Lu; Li, Yao; Li, Hangdao; Lu, Hongyang; Tong, Shanbao

    2015-09-01

    Rodent middle cerebral artery occlusion (MCAO) model is commonly used in stroke research. Creating a stable infarct volume has always been challenging for technicians due to the variances of animal anatomy and surgical operations. The depth of filament suture advancement strongly influences the infarct volume as well. We investigated the cerebral blood flow (CBF) changes in the affected cortex using laser speckle contrast imaging when advancing suture during MCAO surgery. The relative CBF drop area (CBF50, i.e., the percentage area with CBF less than 50% of the baseline) showed an increase from 20.9% to 69.1% when the insertion depth increased from 1.6 to 1.8 cm. Using the real-time CBF50 marker to guide suture insertion during the surgery, our animal experiments showed that intraoperative CBF-guided surgery could significantly improve the stability of MCAO with a more consistent infarct volume and less mortality.

  2. Using the Activity-based Anorexia Rodent Model to Study the Neurobiological Basis of Anorexia Nervosa.

    Science.gov (United States)

    Chowdhury, Tara Gunkali; Chen, Yi-Wen; Aoki, Chiye

    2015-10-22

    Anorexia nervosa (AN) is a psychiatric illness characterized by excessively restricted caloric intake and abnormally high levels of physical activity. A challenging illness to treat, due to the lack of understanding of the underlying neurobiology, AN has the highest mortality rate among psychiatric illnesses. To address this need, neuroscientists are using an animal model to study how neural circuits may contribute toward vulnerability to AN and may be affected by AN. Activity-based anorexia (ABA) is a bio-behavioral phenomenon described in rodents that models the key symptoms of anorexia nervosa. When rodents with free access to voluntary exercise on a running wheel experience food restriction, they become hyperactive - running more than animals with free access to food. Here, we describe the procedures by which ABA is induced in adolescent female C57BL/6 mice. On postnatal day 36 (P36), the animal is housed with access to voluntary exercise on a running wheel. After 4 days of acclimation to the running wheel, on P40, all food is removed from the cage. For the next 3 days, food is returned to the cage (allowing animals free food access) for 2 hr daily. After the fourth day of food restriction, free access to food is returned and the running wheel is removed from the cage to allow the animals to recover. Continuous multi-day analysis of running wheel activity shows that mice become hyperactive within 24 hr following the onset of food restriction. The mice run even during the limited time during which they have access to food. Additionally, the circadian pattern of wheel running becomes disrupted by the experience of food restriction. We have been able to correlate neurobiological changes with various aspects of the animals' wheel running behavior to implicate particular brain regions and neurochemical changes with resilience and vulnerability to food-restriction induced hyperactivity.

  3. Modeling human reliability analysis using MIDAS

    International Nuclear Information System (INIS)

    Boring, R. L.

    2006-01-01

    This paper documents current efforts to infuse human reliability analysis (HRA) into human performance simulation. The Idaho National Laboratory is teamed with NASA Ames Research Center to bridge the SPAR-H HRA method with NASA's Man-machine Integration Design and Analysis System (MIDAS) for use in simulating and modeling the human contribution to risk in nuclear power plant control room operations. It is anticipated that the union of MIDAS and SPAR-H will pave the path for cost-effective, timely, and valid simulated control room operators for studying current and next generation control room configurations. This paper highlights considerations for creating the dynamic HRA framework necessary for simulation, including event dependency and granularity. This paper also highlights how the SPAR-H performance shaping factors can be modeled in MIDAS across static, dynamic, and initiator conditions common to control room scenarios. This paper concludes with a discussion of the relationship of the workload factors currently in MIDAS and the performance shaping factors in SPAR-H. (authors)

  4. Functional characterization and expression of thalamic GABA(B) receptors in a rodent model of Parkinson's disease

    NARCIS (Netherlands)

    de Groote, C; Wullner, U; Loschmann, PA; Luiten, PGM; Klockgether, T

    1999-01-01

    Increased GABAergic neurotransmission of the basal ganglia output nuclei projecting to the motor thalamus is thought to contribute to the pathophysiology of Parkinson's disease. We investigated the functional role of thalamic GABA(B) receptors in a rodent model of Parkinson's disease. First, we

  5. Opportunities for improving animal welfare in rodent models of epilepsy and seizures.

    Science.gov (United States)

    Lidster, Katie; Jefferys, John G; Blümcke, Ingmar; Crunelli, Vincenzo; Flecknell, Paul; Frenguelli, Bruno G; Gray, William P; Kaminski, Rafal; Pitkänen, Asla; Ragan, Ian; Shah, Mala; Simonato, Michele; Trevelyan, Andrew; Volk, Holger; Walker, Matthew; Yates, Neil; Prescott, Mark J

    2016-02-15

    Animal models of epilepsy and seizures, mostly involving mice and rats, are used to understand the pathophysiology of the different forms of epilepsy and their comorbidities, to identify biomarkers, and to discover new antiepileptic drugs and treatments for comorbidities. Such models represent an important area for application of the 3Rs (replacement, reduction and refinement of animal use). This report provides background information and recommendations aimed at minimising pain, suffering and distress in rodent models of epilepsy and seizures in order to improve animal welfare and optimise the quality of studies in this area. The report includes practical guidance on principles of choosing a model, induction procedures, in vivo recordings, perioperative care, welfare assessment, humane endpoints, social housing, environmental enrichment, reporting of studies and data sharing. In addition, some model-specific welfare considerations are discussed, and data gaps and areas for further research are identified. The guidance is based upon a systematic review of the scientific literature, survey of the international epilepsy research community, consultation with veterinarians and animal care and welfare officers, and the expert opinion and practical experience of the members of a Working Group convened by the United Kingdom's National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs). Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Human reliability data collection and modelling

    International Nuclear Information System (INIS)

    1991-09-01

    The main purpose of this document is to review and outline the current state-of-the-art of the Human Reliability Assessment (HRA) used for quantitative assessment of nuclear power plants safe and economical operation. Another objective is to consider Human Performance Indicators (HPI) which can alert plant manager and regulator to departures from states of normal and acceptable operation. These two objectives are met in the three sections of this report. The first objective has been divided into two areas, based on the location of the human actions being considered. That is, the modelling and data collection associated with control room actions are addressed first in chapter 1 while actions outside the control room (including maintenance) are addressed in chapter 2. Both chapters 1 and 2 present a brief outline of the current status of HRA for these areas, and major outstanding issues. Chapter 3 discusses HPI. Such performance indicators can signal, at various levels, changes in factors which influence human performance. The final section of this report consists of papers presented by the participants of the Technical Committee Meeting. A separate abstract was prepared for each of these papers. Refs, figs and tabs

  7. System reliability time-dependent models

    International Nuclear Information System (INIS)

    Debernardo, H.D.

    1991-06-01

    A probabilistic methodology for safety system technical specification evaluation was developed. The method for Surveillance Test Interval (S.T.I.) evaluation basically means an optimization of S.T.I. of most important system's periodically tested components. For Allowed Outage Time (A.O.T.) calculations, the method uses system reliability time-dependent models (A computer code called FRANTIC III). A new approximation, which was called Independent Minimal Cut Sets (A.C.I.), to compute system unavailability was also developed. This approximation is better than Rare Event Approximation (A.E.R.) and the extra computing cost is neglectible. A.C.I. was joined to FRANTIC III to replace A.E.R. on future applications. The case study evaluations verified that this methodology provides a useful probabilistic assessment of surveillance test intervals and allowed outage times for many plant components. The studied system is a typical configuration of nuclear power plant safety systems (two of three logic). Because of the good results, these procedures will be used by the Argentine nuclear regulatory authorities in evaluation of technical specification of Atucha I and Embalse nuclear power plant safety systems. (Author) [es

  8. Prediction of rodent carcinogenic potential of naturally occurring chemicals in the human diet using high-throughput QSAR predictive modeling

    International Nuclear Information System (INIS)

    Valerio, Luis G.; Arvidson, Kirk B.; Chanderbhan, Ronald F.; Contrera, Joseph F.

    2007-01-01

    Consistent with the U.S. Food and Drug Administration (FDA) Critical Path Initiative, predictive toxicology software programs employing quantitative structure-activity relationship (QSAR) models are currently under evaluation for regulatory risk assessment and scientific decision support for highly sensitive endpoints such as carcinogenicity, mutagenicity and reproductive toxicity. At the FDA's Center for Food Safety and Applied Nutrition's Office of Food Additive Safety and the Center for Drug Evaluation and Research's Informatics and Computational Safety Analysis Staff (ICSAS), the use of computational SAR tools for both qualitative and quantitative risk assessment applications are being developed and evaluated. One tool of current interest is MDL-QSAR predictive discriminant analysis modeling of rodent carcinogenicity, which has been previously evaluated for pharmaceutical applications by the FDA ICSAS. The study described in this paper aims to evaluate the utility of this software to estimate the carcinogenic potential of small, organic, naturally occurring chemicals found in the human diet. In addition, a group of 19 known synthetic dietary constituents that were positive in rodent carcinogenicity studies served as a control group. In the test group of naturally occurring chemicals, 101 were found to be suitable for predictive modeling using this software's discriminant analysis modeling approach. Predictions performed on these compounds were compared to published experimental evidence of each compound's carcinogenic potential. Experimental evidence included relevant toxicological studies such as rodent cancer bioassays, rodent anti-carcinogenicity studies, genotoxic studies, and the presence of chemical structural alerts. Statistical indices of predictive performance were calculated to assess the utility of the predictive modeling method. Results revealed good predictive performance using this software's rodent carcinogenicity module of over 1200 chemicals

  9. Reliability

    OpenAIRE

    Condon, David; Revelle, William

    2017-01-01

    Separating the signal in a test from the irrelevant noise is a challenge for all measurement. Low test reliability limits test validity, attenuates important relationships, and can lead to regression artifacts. Multiple approaches to the assessment and improvement of reliability are discussed. The advantages and disadvantages of several different approaches to reliability are considered. Practical advice on how to assess reliability using open source software is provided.

  10. A cell kinetic model of granulopoiesis under radiation exposure: Extension from rodents to canines and humans

    International Nuclear Information System (INIS)

    Hu, S.; Cucinotta, F. A.

    2011-01-01

    As significant ionising radiation exposure will occur during prolonged space travel in future, it is essential to understand their adverse effects on the radiosensitive organ systems that are important for immediate survival of humans, e.g. the haematopoietic system. In this paper, a bio-mathematical model of granulopoiesis is used to analyse the granulocyte changes seen in the blood of mammalians under acute and continuous radiation exposure. This is one of a set of haematopoietic models that have been successfully utilised to simulate and interpret the experimental data of acute and chronic radiation on rodents. Extension to canine and human systems indicates that the results of the model are consistent with the cumulative experimental and empirical data from various sources, implying the potential to integrate them into one united model system to monitor the haematopoietic response of various species under irradiation. The suppression of granulocytes' level of a space traveller under chronic stress of low-dose irradiation as well as the granulopoietic response when encountering a historically large solar particle event is also discussed. (authors)

  11. Using tests and models to assess antidepressant-like activity in rodents

    Directory of Open Access Journals (Sweden)

    Kedzierska Ewa

    2016-06-01

    Full Text Available In today's world, depression is one of the more prevalent forms of mental illness. According to WHO, about 10%-30% of all women and 7%-15% of all men are afflicted by depression at least once in their life-times. Today, depression is assessed to be affecting 350 million people. Regarding this issue, an important challenge for current psychopharmacology is to develop new, more effective pharmacotherapy and to understand the mechanism of action of known antidepressants. Furthermore, there is the necessity to improve the effectiveness of anti-depression treatment by way of bringing about an understanding of the neurobiology of this illness. In achieving these objectives, animal models of depression can be useful. Yet, presently, all available animal models of depression rely on two principles: the actions of known antidepressants or the responses to stress. In this paper, we present an overview of the most widely used animal tests and models that are employed in assessing antidepressant-like activity in rodents. These include amphetamine potentiation, reversal of reserpine action, the forced swimming test, the tail suspension test, learned helplessness, chronic mild stress and social defeat stress. Moreover, the advantages and major drawbacks of each model are also discussed.

  12. Gene Expression Analysis to Assess the Relevance of Rodent Models to Human Lung Injury.

    Science.gov (United States)

    Sweeney, Timothy E; Lofgren, Shane; Khatri, Purvesh; Rogers, Angela J

    2017-08-01

    The relevance of animal models to human diseases is an area of intense scientific debate. The degree to which mouse models of lung injury recapitulate human lung injury has never been assessed. Integrating data from both human and animal expression studies allows for increased statistical power and identification of conserved differential gene expression across organisms and conditions. We sought comprehensive integration of gene expression data in experimental acute lung injury (ALI) in rodents compared with humans. We performed two separate gene expression multicohort analyses to determine differential gene expression in experimental animal and human lung injury. We used correlational and pathway analyses combined with external in vitro gene expression data to identify both potential drivers of underlying inflammation and therapeutic drug candidates. We identified 21 animal lung tissue datasets and three human lung injury bronchoalveolar lavage datasets. We show that the metasignatures of animal and human experimental ALI are significantly correlated despite these widely varying experimental conditions. The gene expression changes among mice and rats across diverse injury models (ozone, ventilator-induced lung injury, LPS) are significantly correlated with human models of lung injury (Pearson r = 0.33-0.45, P human lung injury. Predicted therapeutic targets, peptide ligand signatures, and pathway analyses are also all highly overlapping. Gene expression changes are similar in animal and human experimental ALI, and provide several physiologic and therapeutic insights to the disease.

  13. Global and 3D spatial assessment of neuroinflammation in rodent models of Multiple Sclerosis.

    Directory of Open Access Journals (Sweden)

    Shashank Gupta

    Full Text Available Multiple Sclerosis (MS is a progressive autoimmune inflammatory and demyelinating disease of the central nervous system (CNS. T cells play a key role in the progression of neuroinflammation in MS and also in the experimental autoimmune encephalomyelitis (EAE animal models for the disease. A technology for quantitative and 3 dimensional (3D spatial assessment of inflammation in this and other CNS inflammatory conditions is much needed. Here we present a procedure for 3D spatial assessment and global quantification of the development of neuroinflammation based on Optical Projection Tomography (OPT. Applying this approach to the analysis of rodent models of MS, we provide global quantitative data of the major inflammatory component as a function of the clinical course. Our data demonstrates a strong correlation between the development and progression of neuroinflammation and clinical disease in several mouse and a rat model of MS refining the information regarding the spatial dynamics of the inflammatory component in EAE. This method provides a powerful tool to investigate the effect of environmental and genetic forces and for assessing the therapeutic effects of drug therapy in animal models of MS and other neuroinflammatory/neurodegenerative disorders.

  14. Rodent Models of Alcoholic Liver Disease: Role of Binge Ethanol Administration

    Directory of Open Access Journals (Sweden)

    Shubha Ghosh Dastidar

    2018-01-01

    Full Text Available Both chronic and acute (binge alcohol drinking are important health and economic concerns worldwide and prominent risk factors for the development of alcoholic liver disease (ALD. There are no FDA-approved medications to prevent or to treat any stage of ALD. Therefore, discovery of novel therapeutic strategies remains a critical need for patients with ALD. Relevant experimental animal models that simulate human drinking patterns and mimic the spectrum and severity of alcohol-induced liver pathology in humans are critical to our ability to identify new mechanisms and therapeutic targets. There are several animal models currently in use, including the most widely utilized chronic ad libitum ethanol (EtOH feeding (Lieber–DeCarli liquid diet model, chronic intragastric EtOH administration (Tsukamoto–French model, and chronic-plus-binge EtOH challenge (Bin Gao—National Institute on Alcohol Abuse and Alcoholism (NIAAA model. This review provides an overview of recent advances in rodent models of binge EtOH administration which help to recapitulate different features and etiologies of progressive ALD. These models include EtOH binge alone, and EtOH binge coupled with chronic EtOH intake, a high fat diet, or endotoxin challenge. We analyze the strengths, limitations, and translational relevance of these models, as well as summarize the liver injury outcomes and mechanistic insights. We further discuss the application(s of binge EtOH models in examining alcohol-induced multi-organ pathology, sex- and age-related differences, as well as circadian rhythm disruption.

  15. Structural hybrid reliability index and its convergent solving method based on random–fuzzy–interval reliability model

    OpenAIRE

    Hai An; Ling Zhou; Hui Sun

    2016-01-01

    Aiming to resolve the problems of a variety of uncertainty variables that coexist in the engineering structure reliability analysis, a new hybrid reliability index to evaluate structural hybrid reliability, based on the random–fuzzy–interval model, is proposed in this article. The convergent solving method is also presented. First, the truncated probability reliability model, the fuzzy random reliability model, and the non-probabilistic interval reliability model are introduced. Then, the new...

  16. Stimulant and motivational effects of alcohol: lessons from rodent and primate models.

    Science.gov (United States)

    Brabant, Christian; Guarnieri, Douglas J; Quertemont, Etienne

    2014-07-01

    In several animal species including humans, the acute administration of low doses of alcohol increases motor activity. Different theories have postulated that alcohol-induced hyperactivity is causally related to alcoholism. Moreover, a common biological mechanism in the mesolimbic dopamine system has been proposed to mediate the stimulant and motivational effects of alcohol. Numerous studies have examined whether alcohol-induced hyperactivity is related to alcoholism using a great variety of animal models and several animal species. However, there is no review that has summarized this extensive literature. In this article, we present the various experimental models that have been used to study the relationship between the stimulant and motivational effects of alcohol in rodents and primates. Furthermore, we discuss whether the theories hypothesizing a causal link between alcohol-induced hyperactivity and alcoholism are supported by published results. The reviewed findings indicate that animal species that are stimulated by alcohol also exhibit alcohol preference. Additionally, the role of dopamine in alcohol-induced hyperactivity is well established since blocking dopaminergic activity suppresses the stimulant effects of alcohol. However, dopamine transmission plays a much more complex function in the motivational properties of alcohol and the neuronal mechanisms involved in alcohol stimulation and reward are distinct. Overall, the current review provides mixed support for theories suggesting that the stimulant effects of alcohol are related to alcoholism and highlights the importance of animal models as a way to gain insight into alcoholism. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Early life stress paradigms in rodents: potential animal models of depression?

    Science.gov (United States)

    Schmidt, Mathias V; Wang, Xiao-Dong; Meijer, Onno C

    2011-03-01

    While human depressive illness is indeed uniquely human, many of its symptoms may be modeled in rodents. Based on human etiology, the assumption has been made that depression-like behavior in rats and mice can be modulated by some of the powerful early life programming effects that are known to occur after manipulations in the first weeks of life. Here we review the evidence that is available in literature for early life manipulation as risk factors for the development of depression-like symptoms such as anhedonia, passive coping strategies, and neuroendocrine changes. Early life paradigms that were evaluated include early handling, separation, and deprivation protocols, as well as enriched and impoverished environments. We have also included a small number of stress-related pharmacological models. We find that for most early life paradigms per se, the actual validity for depression is limited. A number of models have not been tested with respect to classical depression-like behaviors, while in many cases, the outcome of such experiments is variable and depends on strain and additional factors. Because programming effects confer vulnerability rather than disease, a number of paradigms hold promise for usefulness in depression research, in combination with the proper genetic background and adult life challenges.

  18. Translational rodent models of Korsakoff syndrome reveal the critical neuroanatomical substrates of memory dysfunction and recovery.

    Science.gov (United States)

    Savage, Lisa M; Hall, Joseph M; Resende, Leticia S

    2012-06-01

    Investigation of the amnesic disorder Korsakoff Syndrome (KS) has been vital in elucidating the critical brain regions involved in learning and memory. Although the thalamus and mammillary bodies are the primary sites of neuropathology in KS, functional deactivation of the hippocampus and certain cortical regions also contributes to the chronic cognitive dysfunction reported in KS. The rodent pyrithiamine-induced thiamine deficiency (PTD) model has been used to study the extent of hippocampal and cortical neuroadaptations in KS. In the PTD model, the hippocampus, frontal and retrosplenial cortical regions display loss of cholinergic innervation, decreases in behaviorally stimulated acetylcholine release and reductions in neurotrophins. While PTD treatment results in significant impairment in measures of spatial learning and memory, other cognitive processes are left intact and may be recruited to improve cognitive outcome. In addition, behavioral recovery can be stimulated in the PTD model by increasing acetylcholine levels in the medial septum, hippocampus and frontal cortex, but not in the retrosplenial cortex. These data indicate that although the hippocampus and frontal cortex are involved in the pathogenesis of KS, these regions retain neuroplasticity and may be critical targets for improving cognitive outcome in KS.

  19. Comparison of two rodent models of maternal separation on juvenile social behavior

    Directory of Open Access Journals (Sweden)

    Betty eZimmerberg

    2011-06-01

    Full Text Available Early childhood deprivation is associated with an increased risk of attachment disorders and psychopathology. The neural consequences of exposure to stress early in life have used two major rodent models to provide important tools for translational research. Although both models have been termed Maternal Separation, the paradigms differ in ways that clearly shift the focus of stress between maternal and offspring units. The first model, here called Early Deprivation (ED, isolates pups individually while the dam is left not alone, but with a subset of littermates in the home nest (Stay-at-homes. The other model, here called Maternal Separation (MS, isolates the dam in a novel cage while the pups are separated together. In this study, these two early stress models were directly compared for their effects on social behaviors in male and female juvenile offspring. Although both models altered play behavior compared to controls, patterns of prosocial behaviors versus submissive behaviors differed by model and sex. Additionally, there were main effects of sex, with female ED subjects exhibited masculinizing effects of early stress during play sessions. Maternal behavior upon reunion with the isolated subjects was significantly increased in the MS condition compared to both ED and control conditions, which also differed but by a lesser magnitude. Stay-at-homes were tested since some laboratories use them for controls rather than undisturbed litters; they displayed significantly different sex-dependent play compared to undisturbed subjects. These results indicate that early stress effects vary by paradigm of separation. We suggest that MS produces greater stress on the dam and thus greater maternal mediation, while ED causes greater stress on the neonates, resulting in different behavioral sequela that warrant attention when using these models for translational research.

  20. Building and integrating reliability models in a Reliability-Centered-Maintenance approach

    International Nuclear Information System (INIS)

    Verite, B.; Villain, B.; Venturini, V.; Hugonnard, S.; Bryla, P.

    1998-03-01

    Electricite de France (EDF) has recently developed its OMF-Structures method, designed to optimize preventive maintenance of passive structures such as pipes and support, based on risk. In particular, reliability performances of components need to be determined; it is a two-step process, consisting of a qualitative sort followed by a quantitative evaluation, involving two types of models. Initially, degradation models are widely used to exclude some components from the field of preventive maintenance. The reliability of the remaining components is then evaluated by means of quantitative reliability models. The results are then included in a risk indicator that is used to directly optimize preventive maintenance tasks. (author)

  1. Accelerated cognitive decline in a rodent model for temporal lobe epilepsy

    NARCIS (Netherlands)

    Schipper, Sandra; Aalbers, Marlien W.; Rijkers, Kim; Lagiere, Melanie; Bogaarts, Jan G.; Blokland, Arjan; Klinkenberg, Sylvia; Hoogland, Govert; Vles, Johan S. H.

    2016-01-01

    Objective: Cognitive impairment is frequently observed in patients with temporal lobe epilepsy. It is hypothesized that cumulative seizure exposure causes accelerated cognitive decline in patients with epilepsy. We investigated the influence of seizure frequency on cognitive decline in a rodent

  2. Establishment of a general NAFLD scoring system for rodent models and comparison to human liver pathology

    NARCIS (Netherlands)

    Liang, W.; Menke, A.L.; Driessen, A.; Koek, G.H.; Lindeman, J.H.; Stoop, R.; Havekes, L.M.; Kleemann., R.; Hoek, A.M. van den

    2014-01-01

    Results: The criteria macrovesicular steatosis, microvesicular steatosis, hepatocellular hypertrophy, inflammation and fibrosis were generally applicable to rodent NAFLD. The inter-observer reproducibility (evaluated using the Intraclass Correlation Coefficient) between the ten observers was high

  3. Reliability Model of Power Transformer with ONAN Cooling

    OpenAIRE

    M. Sefidgaran; M. Mirzaie; A. Ebrahimzadeh

    2010-01-01

    Reliability of a power system is considerably influenced by its equipments. Power transformers are one of the most critical and expensive equipments of a power system and their proper functions are vital for the substations and utilities. Therefore, reliability model of power transformer is very important in the risk assessment of the engineering systems. This model shows the characteristics and functions of a transformer in the power system. In this paper the reliability model...

  4. Carbamazepine potentiates the effectiveness of morphine in a rodent model of neuropathic pain.

    Directory of Open Access Journals (Sweden)

    Michael R Due

    Full Text Available Approximately 60% of morphine is glucuronidated to morphine-3-glucuronide (M3G which may aggravate preexisting pain conditions. Accumulating evidence indicates that M3G signaling through neuronal Toll-like receptor 4 (TLR4 may be central to this proalgesic signaling event. These events are known to include elevated neuronal excitability, increased voltage-gated sodium (NaV current, tactile allodynia and decreased opioid analgesic efficacy. Using an in vitro ratiometric-based calcium influx analysis of acutely dissociated small and medium-diameter neurons derived from lumbar dorsal root ganglion (DRG, we observed that M3G-sensitive neurons responded to lipopolysaccharide (LPS and over 35% of these M3G/LPS-responsive cells exhibited sensitivity to capsaicin. In addition, M3G-exposed sensory neurons significantly increased excitatory activity and potentiated NaV current as measured by current and voltage clamp, when compared to baseline level measurements. The M3G-dependent excitability and potentiation of NaV current in these sensory neurons could be reversed by the addition of carbamazepine (CBZ, a known inhibitor of several NaV currents. We then compared the efficacy between CBZ and morphine as independent agents, to the combined treatment of both drugs simultaneously, in the tibial nerve injury (TNI model of neuropathic pain. The potent anti-nociceptive effects of morphine (5 mg/kg, i.p. were observed in TNI rodents at post-injury day (PID 7-14 and absent at PID21-28, while administration of CBZ (10 mg/kg, i.p. alone failed to produce anti-nociceptive effects at any time following TNI (PID 7-28. In contrast to either drug alone at PID28, the combination of morphine and CBZ completely attenuated tactile hyperalgesia in the rodent TNI model. The basis for the potentiation of morphine in combination with CBZ may be due to the effects of a latent upregulation of NaV1.7 in the DRG following TNI. Taken together, our observations demonstrate a

  5. Preclinical Magnetic Resonance Fingerprinting (MRF) at 7 T: Effective Quantitative Imaging for Rodent Disease Models

    Science.gov (United States)

    Gao, Ying; Chen, Yong; Ma, Dan; Jiang, Yun; Herrmann, Kelsey A.; Vincent, Jason A.; Dell, Katherine M.; Drumm, Mitchell L.; Brady-Kalnay, Susann M.; Griswold, Mark A.; Flask, Chris A.; Lu, Lan

    2015-01-01

    High field, preclinical magnetic resonance imaging (MRI) scanners are now commonly used to quantitatively assess disease status and efficacy of novel therapies in a wide variety of rodent models. Unfortunately, conventional MRI methods are highly susceptible to respiratory and cardiac motion artifacts resulting in potentially inaccurate and misleading data. We have developed an initial preclinical, 7.0 T MRI implementation of the highly novel Magnetic Resonance Fingerprinting (MRF) methodology that has been previously described for clinical imaging applications. The MRF technology combines a priori variation in the MRI acquisition parameters with dictionary-based matching of acquired signal evolution profiles to simultaneously generate quantitative maps of T1 and T2 relaxation times and proton density. This preclinical MRF acquisition was constructed from a Fast Imaging with Steady-state Free Precession (FISP) MRI pulse sequence to acquire 600 MRF images with both evolving T1 and T2 weighting in approximately 30 minutes. This initial high field preclinical MRF investigation demonstrated reproducible and differentiated estimates of in vitro phantoms with different relaxation times. In vivo preclinical MRF results in mouse kidneys and brain tumor models demonstrated an inherent resistance to respiratory motion artifacts as well as sensitivity to known pathology. These results suggest that MRF methodology may offer the opportunity for quantification of numerous MRI parameters for a wide variety of preclinical imaging applications. PMID:25639694

  6. Accelerated cognitive decline in a rodent model for temporal lobe epilepsy.

    Science.gov (United States)

    Schipper, Sandra; Aalbers, Marlien W; Rijkers, Kim; Lagiere, Melanie; Bogaarts, Jan G; Blokland, Arjan; Klinkenberg, Sylvia; Hoogland, Govert; Vles, Johan S H

    2016-12-01

    Cognitive impairment is frequently observed in patients with temporal lobe epilepsy. It is hypothesized that cumulative seizure exposure causes accelerated cognitive decline in patients with epilepsy. We investigated the influence of seizure frequency on cognitive decline in a rodent model for temporal lobe epilepsy. Neurobehavioral assessment was performed before and after surgery, after the induction of self-sustaining limbic status epilepticus (SSLSE), and in the chronic phase in which rats experienced recurrent seizures. Furthermore, we assessed potential confounders of memory performance. Rats showed a deficit in spatial working memory after the induction of the SSLSE, which endured in the chronic phase. A progressive decline in recognition memory developed in SSLSE rats. Confounding factors were absent. Seizure frequency and also the severity of the status epilepticus were not correlated with the severity of cognitive deficits. The effect of the seizure frequency on cognitive comorbidity in epilepsy has long been debated, possibly because of confounders such as antiepileptic medication and the heterogeneity of epileptic etiologies. In an animal model of temporal lobe epilepsy, we showed that a decrease in spatial working memory does not relate to the seizure frequency. This suggests for other mechanisms are responsible for memory decline and potentially a common pathophysiology of cognitive deterioration and the occurrence and development of epileptic seizures. Identifying this common denominator will allow development of more targeted interventions treating cognitive decline in patients with epilepsy. The treatment of interictal symptoms will increase the quality of life of many patients with epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Classification of Multiple Seizure-Like States in Three Different Rodent Models of Epileptogenesis.

    Science.gov (United States)

    Guirgis, Mirna; Serletis, Demitre; Zhang, Jane; Florez, Carlos; Dian, Joshua A; Carlen, Peter L; Bardakjian, Berj L

    2014-01-01

    Epilepsy is a dynamical disease and its effects are evident in over fifty million people worldwide. This study focused on objective classification of the multiple states involved in the brain's epileptiform activity. Four datasets from three different rodent hippocampal preparations were explored, wherein seizure-like-events (SLE) were induced by the perfusion of a low - Mg(2+) /high-K(+) solution or 4-Aminopyridine. Local field potentials were recorded from CA3 pyramidal neurons and interneurons and modeled as Markov processes. Specifically, hidden Markov models (HMM) were used to determine the nature of the states present. Properties of the Hilbert transform were used to construct the feature spaces for HMM training. By sequentially applying the HMM training algorithm, multiple states were identified both in episodes of SLE and nonSLE activity. Specifically, preSLE and postSLE states were differentiated and multiple inner SLE states were identified. This was accomplished using features extracted from the lower frequencies (1-4 Hz, 4-8 Hz) alongside those of both the low- (40-100 Hz) and high-gamma (100-200 Hz) of the recorded electrical activity. The learning paradigm of this HMM-based system eliminates the inherent bias associated with other learning algorithms that depend on predetermined state segmentation and renders it an appropriate candidate for SLE classification.

  8. Swim stress exaggerates the hyperactive mesocortical dopamine system in a rodent model of autism.

    Science.gov (United States)

    Nakasato, Akane; Nakatani, Yasushi; Seki, Yoshinari; Tsujino, Naohisa; Umino, Masahiro; Arita, Hideho

    2008-02-08

    Several clinical reports have suggested that there is a hyperactivation of the dopaminergic system in people with autism. Using rats exposed prenatally to valproic acid (VPA) as an animal model of autism, we measured dopamine (DA) levels in samples collected from the frontal cortex (FC) using in vivo microdialysis and HPLC. The basal DA level in FC was significantly higher in VPA-exposed rats relative to controls. Since the mesocortical DA system is known to be sensitive to physical and psychological stressors, we measured DA levels in FC before, during, and after a 60-min forced swim test (FST). There were further gradual increases in FC DA levels during the FST in the VPA-exposed rats, but not in the control rats. Behavioral analysis during the last 10 min of the FST revealed a significant decrease in active, escape-oriented behavior and an increase in immobility, which is thought to reflect the development of depressive behavior that disengages the animal from active forms of coping with stressful stimuli. These results suggest that this rodent model of autism exhibits a hyperactive mesocortical DA system, which is exaggerated by swim stress. This abnormality may be responsible for depressive and withdrawal behavior observed in autism.

  9. Intestinal tumorigenesis is not affected by progesterone signaling in rodent models.

    Directory of Open Access Journals (Sweden)

    Jarom Heijmans

    Full Text Available Clinical data suggest that progestins have chemopreventive properties in the development of colorectal cancer. We set out to examine a potential protective effect of progestins and progesterone signaling on colon cancer development. In normal and neoplastic intestinal tissue, we found that the progesterone receptor (PR is not expressed. Expression was confined to sporadic mesenchymal cells. To analyze the influence of systemic progesterone receptor signaling, we crossed mice that lacked the progesterone receptor (PRKO to the Apc(Min/+ mouse, a model for spontaneous intestinal polyposis. PRKO-Apc(Min/+ mice exhibited no change in polyp number, size or localization compared to Apc(Min/+. To examine effects of progestins on the intestinal epithelium that are independent of the PR, we treated mice with MPA. We found no effects of either progesterone or MPA on gross intestinal morphology or epithelial proliferation. Also, in rats treated with MPA, injection with the carcinogen azoxymethane did not result in a difference in the number or size of aberrant crypt foci, a surrogate end-point for adenoma development. We conclude that expression of the progesterone receptor is limited to cells in the intestinal mesenchyme. We did not observe any effect of progesterone receptor signaling or of progestin treatment in rodent models of intestinal tumorigenesis.

  10. Microvascular anastomosis in rodent model evaluated by Fourier domain Doppler optical coherence tomography

    Science.gov (United States)

    Huang, Yong; Tong, Dedi; Zhu, Shan; Wu, Lehao; Ibrahim, Zuhaib; Lee, WP Andrew; Brandacher, Gerald; Kang, Jin U.

    2014-03-01

    Vascular and microvascular anastomosis are critical components of reconstructive microsurgery, vascular surgery and transplant surgery. Imaging modality that provides immediate, real-time in-depth view and 3D structure and flow information of the surgical site can be a great valuable tool for the surgeon to evaluate surgical outcome following both conventional and innovative anastomosis techniques, thus potentially increase the surgical success rate. Microvascular anastomosis for vessels with outer diameter smaller than 1.0 mm is extremely challenging and effective evaluation of the outcome is very difficult if not impossible using computed tomography (CT) angiograms, magnetic resonance (MR) angiograms and ultrasound Doppler. Optical coherence tomography (OCT) is a non-invasive high-resolution (micron level), high-speed, 3D imaging modality that has been adopted widely in biomedical and clinical applications. Phaseresolved Doppler OCT that explores the phase information of OCT signals has been shown to be capable of characterizing dynamic blood flow clinically. In this work, we explore the capability of Fourier domain Doppler OCT as an evaluation tool to detect commonly encountered post-operative complications that will cause surgical failure and to confirm positive result with surgeon's observation. Both suture and cuff based techniques were evaluated on the femoral artery and vein in the rodent model.

  11. Sorafenib prevents liver fibrosis in a non-alcoholic steatohepatitis (NASH) rodent model

    Energy Technology Data Exchange (ETDEWEB)

    Stefano, J.T.; Pereira, I.V.A.; Torres, M.M.; Bida, P.M. [Disciplina de Gastroenterologia Clínica (LIM-07), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Coelho, A.M.M. [Disciplina de Transplante de Órgãos do Aparelho Digestivo (LIM-37), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Xerfan, M.P. [Disciplina de Gastroenterologia Clínica (LIM-07), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Cogliati, B. [Departamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP (Brazil); Barbeiro, D.F. [Disciplina de Emergências Clínicas (LIM-51), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Mazo, D.F.C. [Disciplina de Gastroenterologia Clínica (LIM-07), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Kubrusly, M.S.; D' Albuquerque, L.A.C. [Disciplina de Transplante de Órgãos do Aparelho Digestivo (LIM-37), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Souza, H.P. [Disciplina de Emergências Clínicas (LIM-51), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Carrilho, F.J.; Oliveira, C.P. [Disciplina de Gastroenterologia Clínica (LIM-07), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2015-02-24

    Liver fibrosis occurring as an outcome of non-alcoholic steatohepatitis (NASH) can precede the development of cirrhosis. We investigated the effects of sorafenib in preventing liver fibrosis in a rodent model of NASH. Adult Sprague-Dawley rats were fed a choline-deficient high-fat diet and exposed to diethylnitrosamine for 6 weeks. The NASH group (n=10) received vehicle and the sorafenib group (n=10) received 2.5 mg·kg{sup -1}·day{sup -1} by gavage. A control group (n=4) received only standard diet and vehicle. Following treatment, animals were sacrificed and liver tissue was collected for histologic examination, mRNA isolation, and analysis of mitochondrial function. Genes related to fibrosis (MMP9, TIMP1, TIMP2), oxidative stress (HSP60, HSP90, GST), and mitochondrial biogenesis (PGC1α) were evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Liver mitochondrial oxidation activity was measured by a polarographic method, and cytokines by enzyme-linked immunosorbent assay (ELISA). Sorafenib treatment restored mitochondrial function and reduced collagen deposition by nearly 63% compared to the NASH group. Sorafenib upregulated PGC1α and MMP9 and reduced TIMP1 and TIMP2 mRNA and IL-6 and IL-10 protein expression. There were no differences in HSP60, HSP90 and GST expression. Sorafenib modulated PGC1α expression, improved mitochondrial respiration and prevented collagen deposition. It may, therefore, be useful in the treatment of liver fibrosis in NASH.

  12. Disruption of the Serotonergic System after Neonatal Hypoxia-Ischemia in a Rodent Model

    Directory of Open Access Journals (Sweden)

    Kathryn M. Buller

    2012-01-01

    Full Text Available Identifying which specific neuronal phenotypes are vulnerable to neonatal hypoxia-ischemia, where in the brain they are damaged, and the mechanisms that produce neuronal losses are critical to determine the anatomical substrates responsible for neurological impairments in hypoxic-ischemic brain-injured neonates. Here we describe our current work investigating how the serotonergic network in the brain is disrupted in a rodent model of preterm hypoxia-ischemia. One week after postnatal day 3 hypoxia-ischemia, losses of serotonergic raphé neurons, reductions in serotonin levels in the brain, and reduced serotonin transporter expression are evident. These changes can be prevented using two anti-inflammatory interventions; the postinsult administration of minocycline or ibuprofen. However, each drug has its own limitations and benefits for use in neonates to stem damage to the serotonergic network after hypoxia-ischemia. By understanding the fundamental mechanisms underpinning hypoxia-ischemia-induced serotonergic damage we will hopefully move closer to developing a successful clinical intervention to treat neonatal brain injury.

  13. Bipolar electrocautery: A rodent model of Sunderland third-degree nerve injury.

    Science.gov (United States)

    Moradzadeh, Arash; Brenner, Michael J; Whitlock, Elizabeth L; Tong, Alice Y; Luciano, Janina P; Hunter, Daniel A; Myckatyn, Terence M; Mackinnon, Susan E

    2010-01-01

    To determine the Sunderland classification of a bipolar electrocautery injury. Twenty-two rats received crush (a reproducible Sunderland second-degree injury) or bipolar electrocautery injury and were evaluated for functional, histomorphometric, and immunohistochemical recovery at 21 or 42 days. Animal experiments were performed between July 3 and December 12, 2007. Axonal regeneration and end plate reinnervation were evaluated in double transgenic cyan fluorescent protein-conjugated Thy1 and green fluorescent protein-conjugated S100 mice. Compared with crush injury, bipolar electrocautery injury caused greater disruption of myelin and neurofilament architecture at the injury site and decreased nerve fiber counts and percentage of neural tissue distal to the injury (P =.007). Complete functional recovery was seen after crush but not bipolar electrocautery injury. Serial live imaging demonstrated axonal regeneration at week 1 after crush and at week 3 after bipolar electrocautery injury. Qualitative assessment of motor end plate reinnervation at 42 days demonstrated complete neuromuscular end plate reinnervation in the crush group and only limited reinnervation in the bipolar electrocautery group. Bipolar electrocautery injury in a rodent model resulted in a Sunderland third-degree injury, characterized by gradual, incomplete recovery without intervention.

  14. PAIN IN A PARKINSON`S DISEASE RODENT ANIMAL MODEL INDUCED WITH 6-HYDROXYDOPAMINE

    Directory of Open Access Journals (Sweden)

    Antioch, I

    2017-06-01

    Full Text Available Pain phenomenon, the unpleasant sensory and emotional event, appears to evidently intrude in Parkinson disease (PD, a disease formally considered to be restricted only to motor deficits. Although over a half of persons with PD suffer from pain manifestations, there are very few reports targeting this issue. Considering the cases when motor symptoms of PD are eclipsed by severe pain disclosure, there is an obvious need of clarifying the intricate implications of pain in PD context. Because there are few studies researching the link between pain and PD in clinical context, but as well in animal models we chose to explore the effects of pain stimuli on a rodent model of PD. Materials and methods: We experimentally induced a PD model in Wistar rats (n=12 by injecting in the substantia nigra, a brain area known to be involved in PD occurrence, one dose of a 6-hydroxidopamine (6-OHDA solution (8µm 6-OHDA base and 4µm physiological saline, utilizing neurosurgery, while their control peers received same dose of saline solution. Two weeks after the intervention the animals were subjected to the hot-plate test, a behavioral task for acquiring pain sensitivity. Results: There was noticed a statistical significant (F(1,10 = 5.67, p=0.038 sensibility of the 6-OHDA rats to thermal pain stimuli (8.2 s ± 0.8 s in 6-OHDA group as compared to their peers (13.8 s ± 1.6 s in controls. Conclusions: The involvement of pain in PD animal models is demonstrated raising questions of how it influences PD evolution. Moreover, this result increases awareness of deficient diagnostic methods of pain in PD and as a consequence, poor treatment of pain manifestations.

  15. Neuregulin 1: a prime candidate for research into gene-environment interactions in schizophrenia? Insights from genetic rodent models

    Directory of Open Access Journals (Sweden)

    Tim eKarl

    2013-08-01

    Full Text Available Schizophrenia is a multi-factorial disease characterized by a high heritability and environmental risk factors. In recent years, an increasing number of researchers worldwide have started investigating the ‘two-hit hypothesis’ of schizophrenia predicting that genetic and environmental risk factors (GxE interactively cause the development of the disorder. This work is starting to produce valuable new animal models and reveal novel insights into the pathophysiology of schizophrenia. This mini review will focus on recent advancements in the field made by challenging mutant and transgenic rodent models for the schizophrenia candidate gene neuregulin 1 (NRG1 with particular environmental factors. It will outline results obtained from mouse and rat models for various Nrg1 isoforms/isoform types (e.g. transmembrane domain Nrg1, Type II Nrg1, which have been exposed to different forms of stress (acute versus chronic, restraint versus social and housing conditions (standard laboratory versus minimally enriched housing. These studies suggest Nrg1 as a prime candidate for GxE interactions in schizophrenia rodent models and that the use of rodent models will enable a better understanding of GxE interactions and the underlying mechanisms.

  16. Template based rodent brain extraction and atlas mapping.

    Science.gov (United States)

    Weimin Huang; Jiaqi Zhang; Zhiping Lin; Su Huang; Yuping Duan; Zhongkang Lu

    2016-08-01

    Accurate rodent brain extraction is the basic step for many translational studies using MR imaging. This paper presents a template based approach with multi-expert refinement to automatic rodent brain extraction. We first build the brain appearance model based on the learning exemplars. Together with the template matching, we encode the rodent brain position into the search space to reliably locate the rodent brain and estimate the rough segmentation. With the initial mask, a level-set segmentation and a mask-based template learning are implemented further to the brain region. The multi-expert fusion is used to generate a new mask. We finally combine the region growing based on the histogram distribution learning to delineate the final brain mask. A high-resolution rodent atlas is used to illustrate that the segmented low resolution anatomic image can be well mapped to the atlas. Tested on a public data set, all brains are located reliably and we achieve the mean Jaccard similarity score at 94.99% for brain segmentation, which is a statistically significant improvement compared to two other rodent brain extraction methods.

  17. Activity of nucleic acid polymers in rodent models of HBV infection.

    Science.gov (United States)

    Schöneweis, Katrin; Motter, Neil; Roppert, Pia L; Lu, Mengji; Wang, Baoju; Roehl, Ingo; Glebe, Dieter; Yang, Dongliang; Morrey, John D; Roggendorf, Michael; Vaillant, Andrew

    2018-01-01

    Nucleic acid polymers (NAPs) block the release of HBsAg from infected hepatocytes. These compounds have been previously shown to have the unique ability to eliminate serum surface antigen in DHBV-infected Pekin ducks and achieve multilog reduction of HBsAg or HBsAg loss in patients with chronic HBV infection and HBV/HDV coinfection. In ducks and humans, the blockage of HBsAg release by NAPs occurs by the selective targeting of the assembly and/or secretion of subviral particles (SVPs). The clinically active NAP species REP 2055 and REP 2139 were investigated in other relevant animal models of HBV infection including woodchucks chronically infected with WHV, HBV transgenic mice and HBV infected SCID-Hu mice. The liver accumulation of REP 2139 in woodchucks following subcutaneous administration was examined and was found to be similar to that observed in mice and ducks. However, in woodchucks, NAP treatment was associated with only mild (36-79% relative to baseline) reductions in WHsAg (4/10 animals) after 3-5 weeks of treatment without changes in serum WHV DNA. In HBV infected SCID-Hu mice, REP 2055 treatment was not associated with any reduction of HBsAg, HBeAg or HBV DNA in the serum after 28 days of treatment. In HBV transgenic mice, no reductions in serum HBsAg were observed with REP 2139 with up to 12 weeks of treatment. In conclusion, the antiviral effects of NAPs in DHBV infected ducks and patients with chronic HBV infection were weak or absent in woodchuck and mouse models despite similar liver accumulation of NAPs in all these species, suggesting that the mechanisms of SVP assembly and or secretion present in rodent models differs from that in DHBV and chronic HBV infections. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Frutalin reduces acute and neuropathic nociceptive behaviours in rodent models of orofacial pain.

    Science.gov (United States)

    Damasceno, Marina B M V; de Melo Júnior, José de Maria A; Santos, Sacha Aubrey A R; Melo, Luana T M; Leite, Laura Hévila I; Vieira-Neto, Antonio E; Moreira, Renato de A; Monteiro-Moreira, Ana Cristina de O; Campos, Adriana R

    2016-08-25

    Orofacial pain is a highly prevalent clinical condition, yet difficult to control effectively with available drugs. Much attention is currently focused on the anti-inflammatory and antinociceptive properties of lectins. The purpose of this study was to evaluate the antinociceptive effect of frutalin (FTL) using rodent models of inflammatory and neuropathic orofacial pain. Acute pain was induced by formalin, glutamate or capsaicin (orofacial model) and hypertonic saline (corneal model). In one experiment, animals were pretreated with l-NAME and naloxone to investigate the mechanism of antinociception. The involvement of the lectin domain in the antinociceptive effect of FTL was verified by allowing the lectin to bind to its specific ligand. In another experiment, animals pretreated with FTL or saline were submitted to the temporomandibular joint formalin test. In yet another, animals were submitted to infraorbital nerve transection to induce chronic pain, followed by induction of thermal hypersensitivity using acetone. Motor activity was evaluated with the rotarod test. A molecular docking was performed using the TRPV1 channel. Pretreatment with FTL significantly reduced nociceptive behaviour associated with acute and neuropathic pain, especially at 0.5 mg/kg. Antinociception was effectively inhibited by l-NAME and d-galactose. In line with in vivo experiments, docking studies indicated that FTL may interact with TRPV1. Our results confirm the potential pharmacological relevance of FTL as an inhibitor of orofacial nociception in acute and chronic pain mediated by TRPA1, TRPV1 and TRPM8 receptor. Copyright © 2016. Published by Elsevier Ireland Ltd.

  19. Multiparameter rodent chronic model for complex evaluation of alcoholism-mediated metabolic violations.

    Science.gov (United States)

    Shayakhmetova, Ganna M; Bondarenko, Larysa B; Kovalenko, Valentina M; Kharchenko, Olga I; Bohun, Larisa I; Omelchenko, Yuliya O

    2015-01-01

    Despite of the wide spectrum of alcoholism experimental models, the majority of them are very specialized on the short list of investigated parameters and could not provide reproduction of complex metabolic changes in the rats. The aim of the present study was to estimate whether rats selected by high alcohol preference, allowed free access to 15% alcohol for 150 days, develop simultaneous multilevel disturbances of cell macromolecules structure, metabolism and oxidative/nitrosative stress. Wistar albino male rats were divided into groups: I - rats selected by preferences to alcohol were used for chronic alcoholism modeling by replacing water with 15% ethanol (150 days), II - control. Contents of amino acids in serum, liver mRNA CYP2E1 and CYP3A2 expression, DNA fragmentation and lipid peroxidation levels, the reduced glutathione content, superoxide dismutase, catalase, iNOS and cNOS activities were evaluated. In serum of ethanol-treated rats contents of aspartic acid, serine, glycine, alanine and valine were decreased whereas contents of histidine, methionine and phenylalanine were increased. Liver CYP2E1, CYP3A2 mRNA expression, DNA fragmentation levels significantly elevated. Level of cNOS in ethanol-treated rat's hepatocytes was within the normal limits, whereas iNOS activity was raised 1.6 times. Liver pro- and anti-oxidant system alterations were shown. Rats' chronic 15% alcohol consumption (150 days) led solely to complex metabolomic changes at different levels, which simultaneously characterized cell macromolecules structure, metabolism, and oxidative/nitrosative stress. Rodent model of chronic alcoholism in the proposed modification could be an adequate and reasonably priced tool for further preclinical development and testing of pharmacotherapeutic agents.

  20. Time domain series system definition and gear set reliability modeling

    International Nuclear Information System (INIS)

    Xie, Liyang; Wu, Ningxiang; Qian, Wenxue

    2016-01-01

    Time-dependent multi-configuration is a typical feature for mechanical systems such as gear trains and chain drives. As a series system, a gear train is distinct from a traditional series system, such as a chain, in load transmission path, system-component relationship, system functioning manner, as well as time-dependent system configuration. Firstly, the present paper defines time-domain series system to which the traditional series system reliability model is not adequate. Then, system specific reliability modeling technique is proposed for gear sets, including component (tooth) and subsystem (tooth-pair) load history description, material priori/posterior strength expression, time-dependent and system specific load-strength interference analysis, as well as statistically dependent failure events treatment. Consequently, several system reliability models are developed for gear sets with different tooth numbers in the scenario of tooth root material ultimate tensile strength failure. The application of the models is discussed in the last part, and the differences between the system specific reliability model and the traditional series system reliability model are illustrated by virtue of several numerical examples. - Highlights: • A new type of series system, i.e. time-domain multi-configuration series system is defined, that is of great significance to reliability modeling. • Multi-level statistical analysis based reliability modeling method is presented for gear transmission system. • Several system specific reliability models are established for gear set reliability estimation. • The differences between the traditional series system reliability model and the new model are illustrated.

  1. Models on reliability of non-destructive testing

    International Nuclear Information System (INIS)

    Simola, K.; Pulkkinen, U.

    1998-01-01

    The reliability of ultrasonic inspections has been studied in e.g. international PISC (Programme for the Inspection of Steel Components) exercises. These exercises have produced a large amount of information on the effect of various factors on the reliability of inspections. The information obtained from reliability experiments are used to model the dependency of flaw detection probability on various factors and to evaluate the performance of inspection equipment, including the sizing accuracy. The information from experiments is utilised in a most effective way when mathematical models are applied. Here, some statistical models for reliability of non-destructive tests are introduced. In order to demonstrate the use of inspection reliability models, they have been applied to the inspection results of intergranular stress corrosion cracking (IGSCC) type flaws in PISC III exercise (PISC 1995). The models are applied to both flaw detection frequency data of all inspection teams and to flaw sizing data of one participating team. (author)

  2. Reliability modelling and simulation of switched linear system ...

    African Journals Online (AJOL)

    Reliability modelling and simulation of switched linear system control using temporal databases. ... design of fault-tolerant real-time switching systems control and modelling embedded micro-schedulers for complex systems maintenance.

  3. A possibilistic uncertainty model in classical reliability theory

    International Nuclear Information System (INIS)

    De Cooman, G.; Capelle, B.

    1994-01-01

    The authors argue that a possibilistic uncertainty model can be used to represent linguistic uncertainty about the states of a system and of its components. Furthermore, the basic properties of the application of this model to classical reliability theory are studied. The notion of the possibilistic reliability of a system or a component is defined. Based on the concept of a binary structure function, the important notion of a possibilistic function is introduced. It allows to calculate the possibilistic reliability of a system in terms of the possibilistic reliabilities of its components

  4. Investigating the Abscopal Effects of Radioablation on Shielded Bone Marrow in Rodent Models Using Multimodality Imaging.

    Science.gov (United States)

    Afshar, Solmaz F; Zawaski, Janice A; Inoue, Taeko; Rendon, David A; Zieske, Arthur W; Punia, Jyotinder N; Sabek, Omaima M; Gaber, M Waleed

    2017-07-01

    The abscopal effect is the response to radiation at sites that are distant from the irradiated site of an organism, and it is thought to play a role in bone marrow (BM) recovery by initiating responses in the unirradiated bone marrow. Understanding the mechanism of this effect has applications in treating BM failure (BMF) and BM transplantation (BMT), and improving survival of nuclear disaster victims. Here, we investigated the use of multimodality imaging as a translational tool to longitudinally assess bone marrow recovery. We used positron emission tomography/computed tomography (PET/CT), magnetic resonance imaging (MRI) and optical imaging to quantify bone marrow activity, vascular response and marrow repopulation in fully and partially irradiated rodent models. We further measured the effects of radiation on serum cytokine levels, hematopoietic cell counts and histology. PET/CT imaging revealed a radiation-induced increase in proliferation in the shielded bone marrow (SBM) compared to exposed bone marrow (EBM) and sham controls. T 2 -weighted MRI showed radiation-induced hemorrhaging in the EBM and unirradiated SBM. In the EBM and SBM groups, we found alterations in serum cytokine and hormone levels and in hematopoietic cell population proportions, and histological evidence of osteoblast activation at the bone marrow interface. Importantly, we generated a BMT mouse model using fluorescent-labeled bone marrow donor cells and performed fluorescent imaging to reveal the migration of bone marrow cells from shielded to radioablated sites. Our study validates the use of multimodality imaging to monitor bone marrow recovery and provides evidence for the abscopal response in promoting bone marrow recovery after irradiation.

  5. Human amniotic mesenchymal stromal cell transplantation improves endometrial regeneration in rodent models of intrauterine adhesions.

    Science.gov (United States)

    Gan, Lu; Duan, Hua; Xu, Qian; Tang, Yi-Qun; Li, Jin-Jiao; Sun, Fu-Qing; Wang, Sha

    2017-05-01

    Intrauterine adhesion (IUA) is a common uterine cavity disease characterized by the unsatisfactory regeneration of damaged endometria. Recently, stem cell transplantation has been proposed to promote the recovery process. Here we investigated whether human amniotic mesenchymal stromal cells (hAMSCs), a valuable resource for transplantation therapy, could improve endometrial regeneration in rodent IUA models. Forty female Sprague-Dawley rats were randomly assigned to five groups: normal, sham-operated, mechanical injury, hAMSC transplantation, and negative control group. One week after intervention and transplantation, histological analyses were performed, and immunofluorescent and immunohistochemical expression of cell-specific markers and messenger RNA expression of cytokines were measured. Thicker endometria, increased gland numbers and fewer fibrotic areas were found in the hAMSC transplantation group compared with the mechanical injury group. Engraftment of hAMSCs was detected by the presence of anti-human nuclear antigen-positive cells in the endometrial glands of the transplantation uteri. Transplantation of hAMSCs significantly decreased messenger RNA levels of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-1β), and increased those of anti-inflammatory cytokines (basic fibroblast growth factor, and interleukin-6) compared with the injured uterine horns. Immunohistochemical expression of endometrial epithelial cells was revealed in specimens after hAMSC transplantation, whereas it was absent in the mechanically injured uteri. hAMSC transplantation promotes endometrial regeneration after injury in IUA rat models, possibly due to immunomodulatory properties. These cells provide a more easily accessible source of stem cells for future research into the impact of cell transplantation on damaged endometria. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  6. Glutamate and GABA in autism spectrum disorder-a translational magnetic resonance spectroscopy study in man and rodent models.

    Science.gov (United States)

    Horder, Jamie; Petrinovic, Marija M; Mendez, Maria A; Bruns, Andreas; Takumi, Toru; Spooren, Will; Barker, Gareth J; Künnecke, Basil; Murphy, Declan G

    2018-05-25

    Autism spectrum disorder (ASD) is a pervasive neurodevelopmental syndrome with a high human and economic burden. The pathophysiology of ASD is largely unclear, thus hampering development of pharmacological treatments for the core symptoms of the disorder. Abnormalities in glutamate and GABA signaling have been hypothesized to underlie ASD symptoms, and may form a therapeutic target, but it is not known whether these abnormalities are recapitulated in humans with ASD, as well as in rodent models of the disorder. We used translational proton magnetic resonance spectroscopy ([1H]MRS) to compare glutamate and GABA levels in adult humans with ASD and in a panel of six diverse rodent ASD models, encompassing genetic and environmental etiologies. [1H]MRS was performed in the striatum and the medial prefrontal cortex, of the humans, mice, and rats in order to allow for direct cross-species comparisons in specific cortical and subcortical brain regions implicated in ASD. In humans with ASD, glutamate concentration was reduced in the striatum and this was correlated with the severity of social symptoms. GABA levels were not altered in either brain region. The reduction in striatal glutamate was recapitulated in mice prenatally exposed to valproate, and in mice and rats carrying Nlgn3 mutations, but not in rodent ASD models with other etiologies. Our findings suggest that glutamate/GABA abnormalities in the corticostriatal circuitry may be a key pathological mechanism in ASD; and may be linked to alterations in the neuroligin-neurexin signaling complex.

  7. Development of a Conservative Model Validation Approach for Reliable Analysis

    Science.gov (United States)

    2015-01-01

    CIE 2015 August 2-5, 2015, Boston, Massachusetts, USA [DRAFT] DETC2015-46982 DEVELOPMENT OF A CONSERVATIVE MODEL VALIDATION APPROACH FOR RELIABLE...obtain a conservative simulation model for reliable design even with limited experimental data. Very little research has taken into account the...3, the proposed conservative model validation is briefly compared to the conventional model validation approach. Section 4 describes how to account

  8. In vivo efficacy of acyl CoA: diacylglycerol acyltransferase (DGAT) 1 inhibition in rodent models of postprandial hyperlipidemia.

    Science.gov (United States)

    King, Andrew J; Segreti, Jason A; Larson, Kelly J; Souers, Andrew J; Kym, Philip R; Reilly, Regina M; Collins, Christine A; Voorbach, Martin J; Zhao, Gang; Mittelstadt, Scott W; Cox, Bryan F

    2010-07-10

    Postprandial serum triglyceride concentrations have recently been identified as a major, independent risk factor for future cardiovascular events. As a result, postprandial hyperlipidemia has emerged as a potential therapeutic target. The purpose of this study was two-fold. Firstly, to describe and characterize a standardized model of postprandial hyperlipidemia in multiple rodent species; and secondly, apply these rodent models to the evaluation of a novel class of pharmacologic agent; acyl CoA:diacylglycerol acyltransferase (DGAT) 1 inhibitors. Serum triglycerides were measured before and for 4h after oral administration of a standardized volume of corn oil, to fasted C57BL/6, ob/ob, apoE(-/-) and CD-1 mice; Sprague-Dawley and JCR/LA-cp rats; and normolipidemic and hyperlipidemic hamsters. Intragastric administration of corn oil increased serum triglycerides in all animals evaluated, however the magnitude and time-course of the postprandial triglyceride excursion varied. The potent and selective DGAT-1 inhibitor A-922500 (0.03, 0.3 and 3 mg/kg, p.o.), dose-dependently attenuated the maximal postprandial rise in serum triglyceride concentrations in all species tested. At the highest dose of DGAT-1 inhibitor, the postprandial triglyceride response was abolished. This study provides a comprehensive characterization of the time-course of postprandial hyperlipidemia in rodents. In addition, the ability of DGAT-1 inhibitors to attenuate postprandial hyperlipidemia in multiple rodent models, including those that feature insulin resistance, is documented. Exaggerated postprandial hyperlipidemia is inherent to insulin-resistant states in humans and contributes to the substantially elevated cardiovascular risk observed in these patients. Therefore, by attenuating postprandial hyperlipidemia, DGAT-1 inhibition may represent a novel therapeutic approach to reduce cardiovascular risk. Copyright 2010 Elsevier B.V. All rights reserved.

  9. Developing Fast and Reliable Flood Models

    DEFF Research Database (Denmark)

    Thrysøe, Cecilie; Toke, Jens; Borup, Morten

    2016-01-01

    . A surrogate model is set up for a case study area in Aarhus, Denmark, to replace a MIKE FLOOD model. The drainage surrogates are able to reproduce the MIKE URBAN results for a set of rain inputs. The coupled drainage-surface surrogate model lacks details in the surface description which reduces its overall...... accuracy. The model shows no instability, hence larger time steps can be applied, which reduces the computational time by more than a factor 1400. In conclusion, surrogate models show great potential for usage in urban water modelling....

  10. Mechanical Elongation of the Small Intestine: Evaluation of Techniques for Optimal Screw Placement in a Rodent Model

    Directory of Open Access Journals (Sweden)

    P. A. Hausbrandt

    2013-01-01

    Full Text Available Introduction. The aim of this study was to evaluate techniques and establish an optimal method for mechanical elongation of small intestine (MESI using screws in a rodent model in order to develop a potential therapy for short bowel syndrome (SBS. Material and Methods. Adult female Sprague Dawley rats (n=24 with body weight from 250 to 300 g (Σ=283 were evaluated using 5 different groups in which the basic denominator for the technique involved the fixation of a blind loop of the intestine on the abdominal wall with the placement of a screw in the lumen secured to the abdominal wall. Results. In all groups with accessible screws, the rodents removed the implants despite the use of washers or suits to prevent removal. Subcutaneous placement of the screw combined with antibiotic treatment and dietary modifications was finally successful. In two animals autologous transplantation of the lengthened intestinal segment was successful. Discussion. While the rodent model may provide useful basic information on mechanical intestinal lengthening, further investigations should be performed in larger animals to make use of the translational nature of MESI in human SBS treatment.

  11. Risk, reward, and decision-making in a rodent model of cognitive aging

    Directory of Open Access Journals (Sweden)

    Ryan J Gilbert

    2012-01-01

    Full Text Available Impaired decision-making in aging can directly impact factors (financial security, quality of healthcare that are critical to maintaining quality of life and independence at advanced ages. Naturalistic rodent models mimic human aging in other cognitive domains, and afford the opportunity to parse the effects of age on discrete aspects of decision-making in a manner relatively uncontaminated by experiential factors. Young adult (5-7 mo. and aged (23-25 mo. male F344 rats were trained on a probability discounting task in which they made discrete-trial choices between a small certain reward (1 food pellet and a large but uncertain reward (2 food pellets with varying probabilities of delivery ranging from 100% to 0%. Young rats chose the large reward when it was associated with a high probability of delivery and shifted to the smaller but certain reward as probability of the large reward decreased. As a group, aged rats performed comparably to young, but there was significantly greater variance among aged rats. One subgroup of aged rats showed strong preference for the small certain reward. This preference was maintained under conditions in which large reward delivery was certain, suggesting decreased sensitivity to reward magnitude. In contrast, another subgroup of aged rats showed strong preference for the large reward at low probabilities of delivery. Interestingly, this subgroup also showed elevated preference for probabilistic rewards when reward magnitudes were equalized. Previous findings using this same aged study population described strongly attenuated discounting of delayed rewards with age, together suggesting that a subgroup of aged rats may have deficits associated with accounting for costs (i.e., delay, probability. These deficits in cost-accounting were dissociable from the age-related differences in sensitivity to reward magnitude, suggesting that aging influences multiple, distinct neural mechanisms that can impact cost

  12. Full field optical coherence tomography can identify spermatogenesis in a rodent sertoli-cell only model.

    Science.gov (United States)

    Ramasamy, Ranjith; Sterling, Joshua; Manzoor, Maryem; Salamoon, Bekheit; Jain, Manu; Fisher, Erik; Li, Phillip S; Schlegel, Peter N; Mukherjee, Sushmita

    2012-01-01

    Microdissection testicular sperm extraction (micro-TESE) has replaced conventional testis biopsies as a method of choice for obtaining sperm for in vitro fertilization for men with nonobstructive azoospermia. A technical challenge of micro-TESE is that the low magnification inspection of the tubules with a surgical microscope is insufficient to definitively identify sperm-containing tubules, necessitating tissue removal and cytologic assessment. Full field optical coherence tomography (FFOCT) uses white light interference microscopy to generate quick high-resolution tomographic images of fresh (unprocessed and unstained) tissue. Furthermore, by using a nonlaser safe light source (150 W halogen lamp) for tissue illumination, it ensures that the sperm extracted for in vitro fertilization are not photo-damaged or mutagenized. A focal Sertoli-cell only rodent model was created with busulfan injection in adult rats. Ex vivo testicular tissues from both normal and busulfan-treated rats were imaged with a commercial modified FFOCT system, Light-CT™, and the images were correlated with gold standard hematoxylin and eosin staining. Light-CT™ identified spermatogenesis within the seminiferous tubules in freshly excised testicular tissue, without the use of exogenous contrast or fixation. Normal adult rats exhibited tubules with uniform size and shape (diameter 328 ±11 μm). The busulfan-treated animals showed marked heterogeneity in tubular size and shape (diameter 178 ± 35 μm) and only 10% contained sperm within the lumen. FFOCT has the potential to facilitate real-time visualization of spermatogenesis in humans, and aid in micro-TESE for men with infertility.

  13. Risk, reward, and decision-making in a rodent model of cognitive aging.

    Science.gov (United States)

    Gilbert, Ryan J; Mitchell, Marci R; Simon, Nicholas W; Bañuelos, Cristina; Setlow, Barry; Bizon, Jennifer L

    2011-01-01

    Impaired decision-making in aging can directly impact factors (financial security, health care) that are critical to maintaining quality of life and independence at advanced ages. Naturalistic rodent models mimic human aging in other cognitive domains, and afford the opportunity to parse the effects of age on discrete aspects of decision-making in a manner relatively uncontaminated by experiential factors. Young adult (5-7 months) and aged (23-25 months) male F344 rats were trained on a probability discounting task in which they made discrete-trial choices between a small certain reward (one food pellet) and a large but uncertain reward (two food pellets with varying probabilities of delivery ranging from 100 to 0%). Young rats chose the large reward when it was associated with a high probability of delivery and shifted to the small but certain reward as probability of the large reward decreased. As a group, aged rats performed comparably to young, but there was significantly greater variance among aged rats. One subgroup of aged rats showed strong preference for the small certain reward. This preference was maintained under conditions in which large reward delivery was also certain, suggesting decreased sensitivity to reward magnitude. In contrast, another subgroup of aged rats showed strong preference for the large reward at low probabilities of delivery. Interestingly, this subgroup also showed elevated preference for probabilistic rewards when reward magnitudes were equalized. Previous findings using this same aged study population described strongly attenuated discounting of delayed rewards with age, together suggesting that a subgroup of aged rats may have deficits associated with accounting for reward costs (i.e., delay or probability). These deficits in cost-accounting were dissociable from the age-related differences in sensitivity to reward magnitude, suggesting that aging influences multiple, distinct mechanisms that can impact cost-benefit decision-making.

  14. Characterization of the innate immune response to chronic aspiration in a novel rodent model

    Directory of Open Access Journals (Sweden)

    Lin Shu S

    2007-11-01

    Full Text Available Abstract Background Although chronic aspiration has been associated with several pulmonary diseases, the inflammatory response has not been characterized. A novel rodent model of chronic aspiration was therefore developed in order to investigate the resulting innate immune response in the lung. Methods Gastric fluid or normal saline was instilled into the left lung of rats (n = 48 weekly for 4, 8, 12, or 16 weeks (n = 6 each group. Thereafter, bronchoalveolar lavage specimens were collected and cellular phenotypes and cytokine concentrations of IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-gamma, TNF-alpha, and TGF-beta were determined. Results Following the administration of gastric fluid but not normal saline, histologic specimens exhibited prominent evidence of giant cells, fibrosis, lymphocytic bronchiolitis, and obliterative bronchiolitis. Bronchoalveolar lavage specimens from the left (treated lungs exhibited consistently higher macrophages and T cells with an increased CD4:CD8 T cell ratio after treatment with gastric fluid compared to normal saline. The concentrations of IL-1alpha, IL-1beta, IL-2, TNF-alpha and TGF-beta were increased in bronchoalveolar lavage specimens following gastric fluid aspiration compared to normal saline. Conclusion This represents the first description of the pulmonary inflammatory response that results from chronic aspiration. Repetitive aspiration events can initiate an inflammatory response consisting of macrophages and T cells that is associated with increased TGF-beta, TNF-alpha, IL-1alpha, IL-1beta, IL-2 and fibrosis in the lung. Combined with the observation of gastric fluid-induced lymphocyitic bronchiolitis and obliterative bronchiolitis, these findings further support an association between chronic aspiration and pulmonary diseases, such as obliterative bronchiolitis, pulmonary fibrosis, and asthma.

  15. Intentional weight loss reduces mortality rate in a rodent model of dietary obesity.

    Science.gov (United States)

    Vasselli, Joseph R; Weindruch, Richard; Heymsfield, Steven B; Pi-Sunyer, F Xavier; Boozer, Carol N; Yi, Nengjun; Wang, Chenxi; Pietrobelli, Angelo; Allison, David B

    2005-04-01

    We used a rodent model of dietary obesity to evaluate effects of caloric restriction-induced weight loss on mortality rate. Research Measures and Procedures: In a randomized parallel-groups design, 312 outbred Sprague-Dawley rats (one-half males) were assigned at age 10 weeks to one of three diets: low fat (LF; 18.7% calories as fat) with caloric intake adjusted to maintain body weight 10% below that for ad libitum (AL)-fed rat food, high fat (HF; 45% calories as fat) fed at the same level, or HF fed AL. At age 46 weeks, the lightest one-third of the AL group was discarded to ensure a more obese group; the remaining animals were randomly assigned to one of three diets: HF-AL, HF with energy restricted to produce body weights of animals restricted on the HF diet throughout life, or LF with energy restricted to produce the body weights of animals restricted on the LF diet throughout life. Life span, body weight, and leptin levels were measured. Animals restricted throughout life lived the longest (p < 0.001). Life span was not different among animals that had been obese and then lost weight and animals that had been nonobese throughout life (p = 0.18). Animals that were obese and lost weight lived substantially longer than animals that remained obese throughout life (p = 0.002). Diet composition had no effect on life span (p = 0.52). Weight loss after the onset of obesity during adulthood leads to a substantial increase in longevity in rats.

  16. Evaluation of mobile ad hoc network reliability using propagation-based link reliability model

    International Nuclear Information System (INIS)

    Padmavathy, N.; Chaturvedi, Sanjay K.

    2013-01-01

    A wireless mobile ad hoc network (MANET) is a collection of solely independent nodes (that can move randomly around the area of deployment) making the topology highly dynamic; nodes communicate with each other by forming a single hop/multi-hop network and maintain connectivity in decentralized manner. MANET is modelled using geometric random graphs rather than random graphs because the link existence in MANET is a function of the geometric distance between the nodes and the transmission range of the nodes. Among many factors that contribute to the MANET reliability, the reliability of these networks also depends on the robustness of the link between the mobile nodes of the network. Recently, the reliability of such networks has been evaluated for imperfect nodes (transceivers) with binary model of communication links based on the transmission range of the mobile nodes and the distance between them. However, in reality, the probability of successful communication decreases as the signal strength deteriorates due to noise, fading or interference effects even up to the nodes' transmission range. Hence, in this paper, using a propagation-based link reliability model rather than a binary-model with nodes following a known failure distribution to evaluate the network reliability (2TR m , ATR m and AoTR m ) of MANET through Monte Carlo Simulation is proposed. The method is illustrated with an application and some imperative results are also presented

  17. Long-lived cancer-resistant rodents as new model species for cancer research

    Directory of Open Access Journals (Sweden)

    Jorge eAzpurua

    2013-01-01

    Full Text Available Most rodents are small and short-lived, but several lineages have independently evolved long lifespans without a concomitant increase in body mass. Most notably, the two subterranean species naked mole rat (NMR and blind mole rat (BMR which have maximum lifespans of 32 and 21 years respectively. The longevity of these species has sparked interest in the tumor suppression strategies that may have also evolved, because for many rodent species (including mice, rats, guinea pigs, gerbils and hamsters tumors are major source of late-life mortality. Here, we review the recent literature on anticancer mechanisms in long-lived rodents. Both NMR and BMR seem to have developed tumor defenses that rely on extra-cellular signals. However, while the NMR relies on a form of contact inhibition to suppress growth, the BMR evolved a mechanism mediated by the release of interferon and rapid necrotic cell death. Although both organisms ultimately rely on canonical downstream tumor suppressors (pRB and p53 the studies reveal species can evolve different strategies to achieve tumor-resistance. Importantly, studies of these cancer-resistant rodents may benefit human health if such mechanisms can be activated in human cells.

  18. Experiment research on cognition reliability model of nuclear power plant

    International Nuclear Information System (INIS)

    Zhao Bingquan; Fang Xiang

    1999-01-01

    The objective of the paper is to improve the reliability of operation on real nuclear power plant of operators through the simulation research to the cognition reliability of nuclear power plant operators. The research method of the paper is to make use of simulator of nuclear power plant as research platform, to take present international research model of reliability of human cognition based on three-parameter Weibull distribution for reference, to develop and get the research model of Chinese nuclear power plant operators based on two-parameter Weibull distribution. By making use of two-parameter Weibull distribution research model of cognition reliability, the experiments about the cognition reliability of nuclear power plant operators have been done. Compared with the results of other countries such USA and Hungary, the same results can be obtained, which can do good to the safety operation of nuclear power plant

  19. An interval-valued reliability model with bounded failure rates

    DEFF Research Database (Denmark)

    Kozine, Igor; Krymsky, Victor

    2012-01-01

    The approach to deriving interval-valued reliability measures described in this paper is distinctive from other imprecise reliability models in that it overcomes the issue of having to impose an upper bound on time to failure. It rests on the presupposition that a constant interval-valued failure...... rate is known possibly along with other reliability measures, precise or imprecise. The Lagrange method is used to solve the constrained optimization problem to derive new reliability measures of interest. The obtained results call for an exponential-wise approximation of failure probability density...

  20. Analytical modeling of nuclear power station operator reliability

    International Nuclear Information System (INIS)

    Sabri, Z.A.; Husseiny, A.A.

    1979-01-01

    The operator-plant interface is a critical component of power stations which requires the formulation of mathematical models to be applied in plant reliability analysis. The human model introduced here is based on cybernetic interactions and allows for use of available data from psychological experiments, hot and cold training and normal operation. The operator model is identified and integrated in the control and protection systems. The availability and reliability are given for different segments of the operator task and for specific periods of the operator life: namely, training, operation and vigilance or near retirement periods. The results can be easily and directly incorporated in system reliability analysis. (author)

  1. Reliability modeling of Clinch River breeder reactor electrical shutdown systems

    International Nuclear Information System (INIS)

    Schatz, R.A.; Duetsch, K.L.

    1974-01-01

    The initial simulation of the probabilistic properties of the Clinch River Breeder Reactor Plant (CRBRP) electrical shutdown systems is described. A model of the reliability (and availability) of the systems is presented utilizing Success State and continuous-time, discrete state Markov modeling techniques as significant elements of an overall reliability assessment process capable of demonstrating the achievement of program goals. This model is examined for its sensitivity to safe/unsafe failure rates, sybsystem redundant configurations, test and repair intervals, monitoring by reactor operators; and the control exercised over system reliability by design modifications and the selection of system operating characteristics. (U.S.)

  2. Modeling and Forecasting (Un)Reliable Realized Covariances for More Reliable Financial Decisions

    DEFF Research Database (Denmark)

    Bollerslev, Tim; Patton, Andrew J.; Quaedvlieg, Rogier

    We propose a new framework for modeling and forecasting common financial risks based on (un)reliable realized covariance measures constructed from high-frequency intraday data. Our new approach explicitly incorporates the effect of measurement errors and time-varying attenuation biases into the c......We propose a new framework for modeling and forecasting common financial risks based on (un)reliable realized covariance measures constructed from high-frequency intraday data. Our new approach explicitly incorporates the effect of measurement errors and time-varying attenuation biases...

  3. Models for Battery Reliability and Lifetime

    Energy Technology Data Exchange (ETDEWEB)

    Smith, K.; Wood, E.; Santhanagopalan, S.; Kim, G. H.; Neubauer, J.; Pesaran, A.

    2014-03-01

    Models describing battery degradation physics are needed to more accurately understand how battery usage and next-generation battery designs can be optimized for performance and lifetime. Such lifetime models may also reduce the cost of battery aging experiments and shorten the time required to validate battery lifetime. Models for chemical degradation and mechanical stress are reviewed. Experimental analysis of aging data from a commercial iron-phosphate lithium-ion (Li-ion) cell elucidates the relative importance of several mechanical stress-induced degradation mechanisms.

  4. RELIABILITY MODELING BASED ON INCOMPLETE DATA: OIL PUMP APPLICATION

    Directory of Open Access Journals (Sweden)

    Ahmed HAFAIFA

    2014-07-01

    Full Text Available The reliability analysis for industrial maintenance is now increasingly demanded by the industrialists in the world. Indeed, the modern manufacturing facilities are equipped by data acquisition and monitoring system, these systems generates a large volume of data. These data can be used to infer future decisions affecting the health facilities. These data can be used to infer future decisions affecting the state of the exploited equipment. However, in most practical cases the data used in reliability modelling are incomplete or not reliable. In this context, to analyze the reliability of an oil pump, this work proposes to examine and treat the incomplete, incorrect or aberrant data to the reliability modeling of an oil pump. The objective of this paper is to propose a suitable methodology for replacing the incomplete data using a regression method.

  5. MODELING HUMAN RELIABILITY ANALYSIS USING MIDAS

    Energy Technology Data Exchange (ETDEWEB)

    Ronald L. Boring; Donald D. Dudenhoeffer; Bruce P. Hallbert; Brian F. Gore

    2006-05-01

    This paper summarizes an emerging collaboration between Idaho National Laboratory and NASA Ames Research Center regarding the utilization of high-fidelity MIDAS simulations for modeling control room crew performance at nuclear power plants. The key envisioned uses for MIDAS-based control room simulations are: (i) the estimation of human error with novel control room equipment and configurations, (ii) the investigative determination of risk significance in recreating past event scenarios involving control room operating crews, and (iii) the certification of novel staffing levels in control rooms. It is proposed that MIDAS serves as a key component for the effective modeling of risk in next generation control rooms.

  6. Modelling hemoglobin and hemoglobin:haptoglobin complex clearance in a non-rodent species– pharmacokinetic and therapeutic implications

    Directory of Open Access Journals (Sweden)

    Felicitas S Boretti

    2014-10-01

    Full Text Available Preclinical studies suggest that haptoglobin (Hp supplementation could be an effective therapeutic modality during acute or chronic hemolytic diseases. Hp prevents Hb extravasation and neutralizes Hb’s oxidative and NO scavenging activity in the vasculature. Small animal models such as mouse, rat and guinea pig appear to be valuable to provide proof-of-concept for Hb neutralization by Hp in diverse pre-clinical conditions. However, these species differ significantly from human in the clearance of Hb:Hp complexes, which leads to long persistence of circulating Hb:Hp complexes after administration of human plasma derived Hp. Alternative animal models must therefore be explored to guide pre-clinical development of these potential therapeutics. In contrast to rodents, dogs have high Hp plasma concentrations comparable to human. In this study we show that like human macrophages, dog peripheral blood monocyte derived macrophages express a glucocorticoid inducible endocytic clearance pathways with a high specificity for the Hb:Hp complex. Evaluating the Beagle dog as a non-rodent model species we provide the first pharmacokinetic parameter estimates of free Hb and Hb:Hp phenotype complexes. The data reflect a drastically reduced volume of distribution (Vc of the complex compared to free Hb, increased exposures (Cmax and AUC and significantly reduced total body clearance (CL with a terminal half-life (t1/2 of approximately 12 hours. Distribution and clearance was identical for dog and human Hb (± glucocorticoid stimulation and for dimeric and multimeric Hp preparations bound to Hb. Collectively, our study supports the dog as a non-rodent animal model to study pharmacological and pharmacokinetic aspects of Hb clearance systems and apply the model to studying Hp therapeutics.

  7. Plant and control system reliability and risk model

    International Nuclear Information System (INIS)

    Niemelae, I.M.

    1986-01-01

    A new reliability modelling technique for control systems and plants is demonstrated. It is based on modified boolean algebra and it has been automated into an efficient computer code called RELVEC. The code is useful for getting an overall view of the reliability parameters or for an in-depth reliability analysis, which is essential in risk analysis, where the model must be capable of answering to specific questions like: 'What is the probability of this temperature limiter to provide a false alarm', or 'what is the probability of air pressure in this subsystem to drop below lower limit'. (orig./DG)

  8. Quantitative metal magnetic memory reliability modeling for welded joints

    Science.gov (United States)

    Xing, Haiyan; Dang, Yongbin; Wang, Ben; Leng, Jiancheng

    2016-03-01

    Metal magnetic memory(MMM) testing has been widely used to detect welded joints. However, load levels, environmental magnetic field, and measurement noises make the MMM data dispersive and bring difficulty to quantitative evaluation. In order to promote the development of quantitative MMM reliability assessment, a new MMM model is presented for welded joints. Steel Q235 welded specimens are tested along the longitudinal and horizontal lines by TSC-2M-8 instrument in the tensile fatigue experiments. The X-ray testing is carried out synchronously to verify the MMM results. It is found that MMM testing can detect the hidden crack earlier than X-ray testing. Moreover, the MMM gradient vector sum K vs is sensitive to the damage degree, especially at early and hidden damage stages. Considering the dispersion of MMM data, the K vs statistical law is investigated, which shows that K vs obeys Gaussian distribution. So K vs is the suitable MMM parameter to establish reliability model of welded joints. At last, the original quantitative MMM reliability model is first presented based on the improved stress strength interference theory. It is shown that the reliability degree R gradually decreases with the decreasing of the residual life ratio T, and the maximal error between prediction reliability degree R 1 and verification reliability degree R 2 is 9.15%. This presented method provides a novel tool of reliability testing and evaluating in practical engineering for welded joints.

  9. An integrated approach to human reliability analysis -- decision analytic dynamic reliability model

    International Nuclear Information System (INIS)

    Holmberg, J.; Hukki, K.; Norros, L.; Pulkkinen, U.; Pyy, P.

    1999-01-01

    The reliability of human operators in process control is sensitive to the context. In many contemporary human reliability analysis (HRA) methods, this is not sufficiently taken into account. The aim of this article is that integration between probabilistic and psychological approaches in human reliability should be attempted. This is achieved first, by adopting such methods that adequately reflect the essential features of the process control activity, and secondly, by carrying out an interactive HRA process. Description of the activity context, probabilistic modeling, and psychological analysis form an iterative interdisciplinary sequence of analysis in which the results of one sub-task maybe input to another. The analysis of the context is carried out first with the help of a common set of conceptual tools. The resulting descriptions of the context promote the probabilistic modeling, through which new results regarding the probabilistic dynamics can be achieved. These can be incorporated in the context descriptions used as reference in the psychological analysis of actual performance. The results also provide new knowledge of the constraints of activity, by providing information of the premises of the operator's actions. Finally, the stochastic marked point process model gives a tool, by which psychological methodology may be interpreted and utilized for reliability analysis

  10. Software reliability growth model for safety systems of nuclear reactor

    International Nuclear Information System (INIS)

    Thirugnana Murthy, D.; Murali, N.; Sridevi, T.; Satya Murty, S.A.V.; Velusamy, K.

    2014-01-01

    The demand for complex software systems has increased more rapidly than the ability to design, implement, test, and maintain them, and the reliability of software systems has become a major concern for our, modern society.Software failures have impaired several high visibility programs in space, telecommunications, defense and health industries. Besides the costs involved, it setback the projects. The ways of quantifying it and using it for improvement and control of the software development and maintenance process. This paper discusses need for systematic approaches for measuring and assuring software reliability which is a major share of project development resources. It covers the reliability models with the concern on 'Reliability Growth'. It includes data collection on reliability, statistical estimation and prediction, metrics and attributes of product architecture, design, software development, and the operational environment. Besides its use for operational decisions like deployment, it includes guiding software architecture, development, testing and verification and validation. (author)

  11. A Reliability Based Model for Wind Turbine Selection

    Directory of Open Access Journals (Sweden)

    A.K. Rajeevan

    2013-06-01

    Full Text Available A wind turbine generator output at a specific site depends on many factors, particularly cut- in, rated and cut-out wind speed parameters. Hence power output varies from turbine to turbine. The objective of this paper is to develop a mathematical relationship between reliability and wind power generation. The analytical computation of monthly wind power is obtained from weibull statistical model using cubic mean cube root of wind speed. Reliability calculation is based on failure probability analysis. There are many different types of wind turbinescommercially available in the market. From reliability point of view, to get optimum reliability in power generation, it is desirable to select a wind turbine generator which is best suited for a site. The mathematical relationship developed in this paper can be used for site-matching turbine selection in reliability point of view.

  12. A Survey of Software Reliability Modeling and Estimation

    Science.gov (United States)

    1983-09-01

    considered include: the Jelinski-Moranda Model, the ,Geometric Model,’ and Musa’s Model. A Monte -Carlo study of the behavior of the ’V"’"*least squares...ceedings Number 261, 1979, pp. 34-1, 34-11. IoelAmrit, AGieboSSukert, Alan and Goel, Ararat , "A Guidebookfor Software Reliability Assessment, 1980

  13. Power plant reliability calculation with Markov chain models

    International Nuclear Information System (INIS)

    Senegacnik, A.; Tuma, M.

    1998-01-01

    In the paper power plant operation is modelled using continuous time Markov chains with discrete state space. The model is used to compute the power plant reliability and the importance and influence of individual states, as well as the transition probabilities between states. For comparison the model is fitted to data for coal and nuclear power plants recorded over several years. (orig.) [de

  14. System Reliability Analysis Capability and Surrogate Model Application in RAVEN

    Energy Technology Data Exchange (ETDEWEB)

    Rabiti, Cristian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Alfonsi, Andrea [Idaho National Lab. (INL), Idaho Falls, ID (United States); Huang, Dongli [Idaho National Lab. (INL), Idaho Falls, ID (United States); Gleicher, Frederick [Idaho National Lab. (INL), Idaho Falls, ID (United States); Wang, Bei [Idaho National Lab. (INL), Idaho Falls, ID (United States); Adbel-Khalik, Hany S. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Pascucci, Valerio [Idaho National Lab. (INL), Idaho Falls, ID (United States); Smith, Curtis L. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-11-01

    This report collect the effort performed to improve the reliability analysis capabilities of the RAVEN code and explore new opportunity in the usage of surrogate model by extending the current RAVEN capabilities to multi physics surrogate models and construction of surrogate models for high dimensionality fields.

  15. The effect of tear size and nerve injury on rotator cuff muscle fatty degeneration in a rodent animal model.

    Science.gov (United States)

    Kim, H Mike; Galatz, Leesa M; Lim, Chanteak; Havlioglu, Necat; Thomopoulos, Stavros

    2012-07-01

    Irreversible muscle changes after rotator cuff tears is a well-known negative prognostic factor after shoulder surgery. Currently, little is known about the pathomechanism of fatty degeneration of the rotator cuff muscles after chronic cuff tears. The purposes of this study were to (1) develop a rodent animal model of chronic rotator cuff tears that can reproduce fatty degeneration of the cuff muscles seen clinically, (2) describe the effects of tear size and concomitant nerve injury on muscle degeneration, and (3) evaluate the changes in gene expression of relevant myogenic and adipogenic factors after rotator cuff tears using the animal model. Rotator cuff tears were created in rodents with and without transection of the suprascapular nerve. The supraspinatus and infraspinatus muscles were examined at 2, 8, and 16 weeks after injury for histologic evidence of fatty degeneration and expression of myogenic and adipogenic genes. Histologic analysis revealed adipocytes, intramuscular fat globules, and intramyocellular fat droplets in the tenotomized and neurotomized supraspinatus and infraspinatus muscles. Changes increased with time and were most severe in the muscles with combined tenotomy and neurotomy. Adipogenic and myogenic transcription factors and markers were upregulated in muscles treated with tenotomy or tenotomy combined with neurotomy compared with normal muscles. The rodent animal model described in this study produces fatty degeneration of the rotator cuff muscles similar to human muscles after chronic cuff tears. The severity of changes was associated with tear size and concomitant nerve injury. Copyright © 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

  16. Maximum Entropy Discrimination Poisson Regression for Software Reliability Modeling.

    Science.gov (United States)

    Chatzis, Sotirios P; Andreou, Andreas S

    2015-11-01

    Reliably predicting software defects is one of the most significant tasks in software engineering. Two of the major components of modern software reliability modeling approaches are: 1) extraction of salient features for software system representation, based on appropriately designed software metrics and 2) development of intricate regression models for count data, to allow effective software reliability data modeling and prediction. Surprisingly, research in the latter frontier of count data regression modeling has been rather limited. More specifically, a lack of simple and efficient algorithms for posterior computation has made the Bayesian approaches appear unattractive, and thus underdeveloped in the context of software reliability modeling. In this paper, we try to address these issues by introducing a novel Bayesian regression model for count data, based on the concept of max-margin data modeling, effected in the context of a fully Bayesian model treatment with simple and efficient posterior distribution updates. Our novel approach yields a more discriminative learning technique, making more effective use of our training data during model inference. In addition, it allows of better handling uncertainty in the modeled data, which can be a significant problem when the training data are limited. We derive elegant inference algorithms for our model under the mean-field paradigm and exhibit its effectiveness using the publicly available benchmark data sets.

  17. Estimation of some stochastic models used in reliability engineering

    International Nuclear Information System (INIS)

    Huovinen, T.

    1989-04-01

    The work aims to study the estimation of some stochastic models used in reliability engineering. In reliability engineering continuous probability distributions have been used as models for the lifetime of technical components. We consider here the following distributions: exponential, 2-mixture exponential, conditional exponential, Weibull, lognormal and gamma. Maximum likelihood method is used to estimate distributions from observed data which may be either complete or censored. We consider models based on homogeneous Poisson processes such as gamma-poisson and lognormal-poisson models for analysis of failure intensity. We study also a beta-binomial model for analysis of failure probability. The estimators of the parameters for three models are estimated by the matching moments method and in the case of gamma-poisson and beta-binomial models also by maximum likelihood method. A great deal of mathematical or statistical problems that arise in reliability engineering can be solved by utilizing point processes. Here we consider the statistical analysis of non-homogeneous Poisson processes to describe the failing phenomena of a set of components with a Weibull intensity function. We use the method of maximum likelihood to estimate the parameters of the Weibull model. A common cause failure can seriously reduce the reliability of a system. We consider a binomial failure rate (BFR) model as an application of the marked point processes for modelling common cause failure in a system. The parameters of the binomial failure rate model are estimated with the maximum likelihood method

  18. Large scale serial two-photon microscopy to investigate local vascular changes in whole rodent brain models of Alzheimer's disease

    Science.gov (United States)

    Delafontaine-Martel, P.; Lefebvre, J.; Damseh, R.; Castonguay, A.; Tardif, P.; Lesage, F.

    2018-02-01

    In this study, an automated serial two-photon microscope was used to image a fluorescent gelatin filled rodent's brain in 3D. A method to compute vascular density using automatic segmentation was combined with coregistration techniques to build group-level vasculature metrics. By studying the medial prefrontal cortex and the hippocampal formation of 3 age groups (2, 4.5 and 8 months old), we compared vascular density for both WT and an Alzheimer model transgenic brain (APP/PS1). We observe a loss of vascular density caused by the ageing process and we propose further analysis to confirm our results.

  19. Systems biology integration of proteomic data in rodent models of depression reveals involvement of the immune response and glutamatergic signaling.

    Science.gov (United States)

    Carboni, Lucia; Nguyen, Thanh-Phuong; Caberlotto, Laura

    2016-12-01

    The pathophysiological basis of major depression is incompletely understood. Recently, numerous proteomic studies have been performed in rodent models of depression to investigate the molecular underpinnings of depressive-like behaviours with an unbiased approach. The objective of the study is to integrate the results of these proteomic studies in depression models to shed light on the most relevant molecular pathways involved in the disease. Network analysis is performed integrating preexisting proteomic data from rodent models of depression. The IntAct mouse and the HRPD are used as reference protein-protein interaction databases. The functionality analyses of the networks are then performed by testing overrepresented GO biological process terms and pathways. Functional enrichment analyses of the networks revealed an association with molecular processes related to depression in humans, such as those involved in the immune response. Pathways impacted by clinically effective antidepressants are modulated, including glutamatergic signaling and neurotrophic responses. Moreover, dysregulations of proteins regulating energy metabolism and circadian rhythms are implicated. The comparison with protein pathways modulated in depressive patients revealed significant overlapping. This systems biology study supports the notion that animal models can contribute to the research into the biology and therapeutics of depression. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. OBscure but not OBsolete: Perturbations of the frontal cortex in common between rodent olfactory bulbectomy model and major depression.

    Science.gov (United States)

    Rajkumar, Ramamoorthy; Dawe, Gavin S

    2018-04-07

    Olfactory bulbectomy (OBX) has been used as a model of depression over several decades. This model presupposes a mechanism that is still not proven in clinical depression. A wealth of clinical literature has focused on the derangements in frontal cortex (prefrontal, orbitofrontal and anterior cingulate cortices) associated with depression. In this comprehensive review, anatomical, electrophysiological and molecular sequelae of bulbectomy in the rodent frontal cortex are explored and compared with findings on brains of humans with major depression. Certain commonalities in neurobiological features of the perturbed frontal cortex in the bulbectomised rodent and the depressed human brain are evident. Also, meta-analysis reports on clinical studies on depressed patients provide prima facie evidence that perturbations in the frontal cortex are associated with major depression. Analysing the pattern of perturbations in the chemical neuroanatomy of the frontal cortex will contribute to understanding of the neurobiology of depression. Revisiting the OBX model of depression to examine these neurobiological changes in frontal cortex with contemporary imaging, proteomics, lipidomics, metabolomics and epigenomics technologies is proposed as an approach to enhance the translational value of this animal model to facilitate identification of targets and biomarkers for clinical depression. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. The Revised Neurobehavioral Severity Scale (NSS-R) for Rodents.

    Science.gov (United States)

    Yarnell, Angela M; Barry, Erin S; Mountney, Andrea; Shear, Deborah; Tortella, Frank; Grunberg, Neil E

    2016-04-08

    Motor and sensory deficits are common following traumatic brain injury (TBI). Although rodent models provide valuable insight into the biological and functional outcomes of TBI, the success of translational research is critically dependent upon proper selection of sensitive, reliable, and reproducible assessments. Published literature includes various observational scales designed to evaluate post-injury functionality; however, the heterogeneity in TBI location, severity, and symptomology can complicate behavioral assessments. The importance of choosing behavioral outcomes that can be reliably and objectively quantified in an efficient manner is becoming increasingly important. The Revised Neurobehavioral Severity Scale (NSS-R) is a continuous series of specific, sensitive, and standardized observational tests that evaluate balance, motor coordination, and sensorimotor reflexes in rodents. The tasks follow a specific order designed to minimize interference: balance, landing, tail raise, dragging, righting reflex, ear reflex, eye reflex, sound reflex, tail pinch, and hindpaw pinch. The NSS-R has proven to be a reliable method differentiating brain-injured rodents from non-brain-injured rodents across many brain injury models. Copyright © 2016 John Wiley & Sons, Inc.

  2. Modeling cognition dynamics and its application to human reliability analysis

    International Nuclear Information System (INIS)

    Mosleh, A.; Smidts, C.; Shen, S.H.

    1996-01-01

    For the past two decades, a number of approaches have been proposed for the identification and estimation of the likelihood of human errors, particularly for use in the risk and reliability studies of nuclear power plants. Despite the wide-spread use of the most popular among these methods, their fundamental weaknesses are widely recognized, and the treatment of human reliability has been considered as one of the soft spots of risk studies of large technological systems. To alleviate the situation, new efforts have focused on the development of human reliability models based on a more fundamental understanding of operator response and its cognitive aspects

  3. Reliability model for common mode failures in redundant safety systems

    International Nuclear Information System (INIS)

    Fleming, K.N.

    1974-12-01

    A method is presented for computing the reliability of redundant safety systems, considering both independent and common mode type failures. The model developed for the computation is a simple extension of classical reliability theory. The feasibility of the method is demonstrated with the use of an example. The probability of failure of a typical diesel-generator emergency power system is computed based on data obtained from U. S. diesel-generator operating experience. The results are compared with reliability predictions based on the assumption that all failures are independent. The comparison shows a significant increase in the probability of redundant system failure, when common failure modes are considered. (U.S.)

  4. Computer-assisted imaging algorithms facilitate histomorphometric quantification of kidney damage in rodent renal failure models

    Directory of Open Access Journals (Sweden)

    Marcin Klapczynski

    2012-01-01

    Full Text Available Introduction: Surgical 5/6 nephrectomy and adenine-induced kidney failure in rats are frequently used models of progressive renal failure. In both models, rats develop significant morphological changes in the kidneys and quantification of these changes can be used to measure the efficacy of prophylactic or therapeutic approaches. In this study, the Aperio Genie Pattern Recognition technology, along with the Positive Pixel Count, Nuclear and Rare Event algorithms were used to quantify histological changes in both rat renal failure models. Methods: Analysis was performed on digitized slides of whole kidney sagittal sections stained with either hematoxylin and eosin or immunohistochemistry with an anti-nestin antibody to identify glomeruli, regenerating tubular epithelium, and tubulointerstitial myofibroblasts. An anti-polymorphonuclear neutrophil (PMN antibody was also used to investigate neutrophil tissue infiltration. Results: Image analysis allowed for rapid and accurate quantification of relevant histopathologic changes such as increased cellularity and expansion of glomeruli, renal tubular dilatation, and degeneration, tissue inflammation, and mineral aggregation. The algorithms provided reliable and consistent results in both control and experimental groups and presented a quantifiable degree of damage associated with each model. Conclusion: These algorithms represent useful tools for the uniform and reproducible characterization of common histomorphologic features of renal injury in rats.

  5. Cardiometabolic and reproductive benefits of early dietary energy restriction and voluntary exercise in an obese PCOS-prone rodent model.

    Science.gov (United States)

    Diane, Abdoulaye; Kupreeva, Maria; Borthwick, Faye; Proctor, Spencer D; Pierce, W David; Vine, Donna F

    2015-09-01

    Polycystic ovary syndrome (PCOS) is one of the most common endocrine-metabolic disorders in women of reproductive age characterized by ovulatory dysfunction, hyperandrogenism and cardiometabolic risk. The overweight-obese PCOS phenotype appears to have exacerbated reproductive dysfunction and cardiometabolic risk. In overweight-obese adult women with PCOS, exercise and energy restricted diets have shown limited and inconsistent effects on both cardiometabolic indices and reproductive outcomes. We hypothesized that an early lifestyle intervention involving exercise and dietary energy restriction to prevent or reduce the propensity for adiposity would modulate reproductive indices and cardiometabolic risk in an obese PCOS-prone rodent model. Weanling obese PCOS-prone and Lean-Control JCR:LA-cp rodents were given a chow diet ad libitum or an energy-restricted diet combined with or without voluntary exercise (4  h/day) for 8 weeks. Dietary energy restriction and exercise lowered total body weight gain and body fat mass by 30% compared to free-fed sedentary or exercising obese PCOS-prone animals (Pexercise intensity compared to free-feeding plus exercise conditions. Energy restriction and exercise decreased fasting plasma triglycerides and apoB48 concentrations in obese PCOS-prone animals compared to free-fed and exercise or sedentary groups. The energy restriction and exercise combination in obese PCOS-prone animals significantly increased plasma sex-hormone binding globulin, hypothalamic cocaine-and amphetamine-regulated transcript (CART) and Kisspeptin mRNA expression to levels of the Lean-Control group, and this was further associated with improvements in estrous cyclicity. The combination of exercise and dietary energy restriction when initiated in early life exerts beneficial effects on cardiometabolic and reproductive indices in an obese PCOS-prone rodent model, and this may be associated with normalization of the hypothalamic neuropeptides, Kisspeptin and CART

  6. Stress in adolescence and drugs of abuse in rodent models: Role of dopamine, CRF, and HPA axis

    Science.gov (United States)

    Burke, Andrew R.; Miczek, Klaus A.

    2014-01-01

    Rationale Research on adolescence and drug abuse increased substantially in the past decade. However, drug-addiction related behaviors following stressful experiences during adolescence are less studied. We focus on rodent models of adolescent stress cross-sensitization to drugs of abuse. Objectives Review the ontogeny of behavior, dopamine, corticotropin-releasing factor (CRF), and the hypothalamic pituitary adrenal (HPA) axis in adolescent rodents. We evaluate evidence that stressful experiences during adolescence engender hypersensitivity to drugs of abuse and offer potential neural mechanisms. Results and Conclusions Much evidence suggests that final maturation of behavior, dopamine systems, and HPA axis occurs during adolescence. Stress during adolescence increases amphetamine- and ethanol-stimulated locomotion, preference, and self-administration under many conditions. The influence of adolescent stress on subsequent cocaine- and nicotine-stimulated locomotion and preference is less clear. The type of adolescent stress, temporal interval between stress and testing, species, sex, and the drug tested are key methodological determinants for successful cross-sensitization procedures. The sensitization of the mesolimbic dopamine system is proposed to underlie stress cross-sensitization to drugs of abuse in both adolescents and adults through modulation by CRF. Reduced levels of mesocortical dopamine appear to be a unique consequence of social stress during adolescence. Adolescent stress may reduce the final maturation of cortical dopamine through D2 dopamine receptor regulation of dopamine synthesis or glucocorticoid-facilitated pruning of cortical dopamine fibers. Certain rodent models of adolescent adversity are useful for determining neural mechanisms underlying the cross-sensitization to drugs of abuse. PMID:24370534

  7. Modeling of system reliability Petri nets with aging tokens

    International Nuclear Information System (INIS)

    Volovoi, V.

    2004-01-01

    The paper addresses the dynamic modeling of degrading and repairable complex systems. Emphasis is placed on the convenience of modeling for the end user, with special attention being paid to the modeling part of a problem, which is considered to be decoupled from the choice of solution algorithms. Depending on the nature of the problem, these solution algorithms can include discrete event simulation or numerical solution of the differential equations that govern underlying stochastic processes. Such modularity allows a focus on the needs of system reliability modeling and tailoring of the modeling formalism accordingly. To this end, several salient features are chosen from the multitude of existing extensions of Petri nets, and a new concept of aging tokens (tokens with memory) is introduced. The resulting framework provides for flexible and transparent graphical modeling with excellent representational power that is particularly suited for system reliability modeling with non-exponentially distributed firing times. The new framework is compared with existing Petri-net approaches and other system reliability modeling techniques such as reliability block diagrams and fault trees. The relative differences are emphasized and illustrated with several examples, including modeling of load sharing, imperfect repair of pooled items, multiphase missions, and damage-tolerant maintenance. Finally, a simple implementation of the framework using discrete event simulation is described

  8. Learning reliable manipulation strategies without initial physical models

    Science.gov (United States)

    Christiansen, Alan D.; Mason, Matthew T.; Mitchell, Tom M.

    1990-01-01

    A description is given of a robot, possessing limited sensory and effectory capabilities but no initial model of the effects of its actions on the world, that acquires such a model through exploration, practice, and observation. By acquiring an increasingly correct model of its actions, it generates increasingly successful plans to achieve its goals. In an apparently nondeterministic world, achieving reliability requires the identification of reliable actions and a preference for using such actions. Furthermore, by selecting its training actions carefully, the robot can significantly improve its learning rate.

  9. Mycobacterial lesions in fish, amphibians, reptiles, rodents, lagomorphs, and ferrets with reference to animal models.

    Science.gov (United States)

    Reavill, Drury R; Schmidt, Robert E

    2012-01-01

    Mycobacteriosis is a serious disease across many animal species. Approximately more than 120 species are currently recognized in the genus Mycobacterium. This article describes the zoonotic potential of mycobacteria and mycobacteriosis in fish, amphibians, rodents, rabbits, and ferrets. It considers clinical signs; histology; molecular methods of identification, such as polymerase chain reaction and DNA sequencing; routes of infection; and disease progression. Studying the disease in animals may aid in understanding the pathogenesis of mycobacterial infections in humans and identify better therapy and preventative options such as vaccines.

  10. Using LISREL to Evaluate Measurement Models and Scale Reliability.

    Science.gov (United States)

    Fleishman, John; Benson, Jeri

    1987-01-01

    LISREL program was used to examine measurement model assumptions and to assess reliability of Coopersmith Self-Esteem Inventory for Children, Form B. Data on 722 third-sixth graders from over 70 schools in large urban school district were used. LISREL program assessed (1) nature of basic measurement model for scale, (2) scale invariance across…

  11. Travel Time Reliability for Urban Networks : Modelling and Empirics

    NARCIS (Netherlands)

    Zheng, F.; Liu, Xiaobo; van Zuylen, H.J.; Li, Jie; Lu, Chao

    2017-01-01

    The importance of travel time reliability in traffic management, control, and network design has received a lot of attention in the past decade. In this paper, a network travel time distribution model based on the Johnson curve system is proposed. The model is applied to field travel time data

  12. Reliability model of SNS linac (spallation neutron source-ORNL)

    International Nuclear Information System (INIS)

    Pitigoi, A.; Fernandez, P.

    2015-01-01

    A reliability model of SNS LINAC (Spallation Neutron Source at Oak Ridge National Laboratory) has been developed using risk spectrum reliability analysis software and the analysis of the accelerator system's reliability has been performed. The analysis results have been evaluated by comparing them with the SNS operational data. This paper presents the main results and conclusions focusing on the definition of design weaknesses and provides recommendations to improve reliability of the MYRRHA ( linear accelerator. The reliability results show that the most affected SNS LINAC parts/systems are: 1) SCL (superconducting linac), front-end systems: IS, LEBT (low-energy beam transport line), MEBT (medium-energy beam transport line), diagnostics and controls; 2) RF systems (especially the SCL RF system); 3) power supplies and PS controllers. These results are in line with the records in the SNS logbook. The reliability issue that needs to be enforced in the linac design is the redundancy of the systems, subsystems and components most affected by failures. For compensation purposes, there is a need for intelligent fail-over redundancy implementation in controllers. Enough diagnostics has to be implemented to allow reliable functioning of the redundant solutions and to ensure the compensation function

  13. Models for reliability and management of NDT data

    International Nuclear Information System (INIS)

    Simola, K.

    1997-01-01

    In this paper the reliability of NDT measurements was approached from three directions. We have modelled the flaw sizing performance, the probability of flaw detection, and developed models to update the knowledge of true flaw size based on sequential measurement results and flaw sizing reliability model. In discussed models the measured flaw characteristics (depth, length) are assumed to be simple functions of the true characteristics and random noise corresponding to measurement errors, and the models are based on logarithmic transforms. Models for Bayesian updating of the flaw size distributions were developed. Using these models, it is possible to take into account the prior information of the flaw size and combine it with the measured results. A Bayesian approach could contribute e. g. to the definition of an appropriate combination of practical assessments and technical justifications in NDT system qualifications, as expressed by the European regulatory bodies

  14. Altered Tracer Distribution and Clearance in the Extracellular Space of the Substantia Nigra in a Rodent Model of Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Yuan Fang

    2017-07-01

    Full Text Available The relationship between extracellular space (ECS diffusion parameters and brain drug clearance is not well-studied, especially in the context of Parkinson's disease (PD. Therefore, we used a rodent model of PD to explore the distribution and clearance of a magnetic resonance tracer. Forty male Sprague Dawley rats were randomized into four different groups: a PD group, a Madopar group (PD + Madopar treatment, a sham group, and a control group. All rats received an injection of the extracellular tracer gadolinium-diethylene triaminepentacetic acid (Gd-DTPA directly into the substantia nigra (SN. ECS diffusion parameters including the effective diffusion coefficient (D*, clearance coefficient (k', ratio of the maximum distribution volume of the tracer (Vd-max%, and half-life (t1/2 were measured. We found that all parameters were significantly increased in the PD group compared to the other three groups (D*: F = 5.774, p = 0.0025; k': F = 20.00, P < 0.0001; Vd-max%: F = 12.81, P < 0.0001; and t1/2: F = 23.35, P < 0.0001. In conclusion, the PD group exhibited a wider distribution and lower clearance of the tracer compared to the other groups. Moreover, k' was more sensitive than D* for monitoring morphological and functional changes in the ECS in a rodent model of PD.

  15. Transparent reliability model for fault-tolerant safety systems

    International Nuclear Information System (INIS)

    Bodsberg, Lars; Hokstad, Per

    1997-01-01

    A reliability model is presented which may serve as a tool for identification of cost-effective configurations and operating philosophies of computer-based process safety systems. The main merit of the model is the explicit relationship in the mathematical formulas between failure cause and the means used to improve system reliability such as self-test, redundancy, preventive maintenance and corrective maintenance. A component failure taxonomy has been developed which allows the analyst to treat hardware failures, human failures, and software failures of automatic systems in an integrated manner. Furthermore, the taxonomy distinguishes between failures due to excessive environmental stresses and failures initiated by humans during engineering and operation. Attention has been given to develop a transparent model which provides predictions which are in good agreement with observed system performance, and which is applicable for non-experts in the field of reliability

  16. Immune tolerance induction using fetal directed placental injection in rodent models: a murine model.

    Directory of Open Access Journals (Sweden)

    Kei Takahashi

    Full Text Available Induction of the immune response is a major problem in replacement therapies for inherited protein deficiencies. Tolerance created in utero can facilitate postnatal treatment. In this study, we aimed to induce immune tolerance towards a foreign protein with early gestational cell transplantation into the chorionic villi under ultrasound guidance in the murine model.Pregnant C57BL/6 (B6 mice on day 10 of gestation were anesthetized and imaged by high resolution ultrasound. Murine embryos and their placenta were positioned to get a clear view in B-mode with power mode of the labyrinth, which is the equivalent of chorionic villi in the human. Bone marrow cells (BMCs from B6-Green Fluorescence Protein (B6GFP transgenic mice were injected into the fetal side of the placenta which includes the labyrinth with glass microcapillary pipettes. Each fetal mouse received 2 x 105 viable GFP-BMCs. After birth, we evaluated the humoral and cell-mediated immune response against GFP.Bone marrow transfer into fetal side of placenta efficiently distributed donor cells to the fetal mice. The survival rate of this procedure was 13.5%(5 out of 37. Successful engraftment of the B6-GFP donor skin grafts was observed in all recipient (5 out of 5 mice 6 weeks after birth. Induction of anti-GFP antibodies was completely inhibited. Cytotoxic immune reactivity of thymic cells against cells harboring GFP was suppressed by ELISPOT assay.In this study, we utilized early gestational placental injection targeting the murine fetus, to transfer donor cells carrying a foreign protein into the fetal circulation. This approach is sufficient to induce both humoral and cell-mediated immune tolerance against the foreign protein.

  17. Statistical models and methods for reliability and survival analysis

    CERN Document Server

    Couallier, Vincent; Huber-Carol, Catherine; Mesbah, Mounir; Huber -Carol, Catherine; Limnios, Nikolaos; Gerville-Reache, Leo

    2013-01-01

    Statistical Models and Methods for Reliability and Survival Analysis brings together contributions by specialists in statistical theory as they discuss their applications providing up-to-date developments in methods used in survival analysis, statistical goodness of fit, stochastic processes for system reliability, amongst others. Many of these are related to the work of Professor M. Nikulin in statistics over the past 30 years. The authors gather together various contributions with a broad array of techniques and results, divided into three parts - Statistical Models and Methods, Statistical

  18. Fuse Modeling for Reliability Study of Power Electronic Circuits

    DEFF Research Database (Denmark)

    Bahman, Amir Sajjad; Iannuzzo, Francesco; Blaabjerg, Frede

    2017-01-01

    This paper describes a comprehensive modeling approach on reliability of fuses used in power electronic circuits. When fuses are subjected to current pulses, cyclic temperature stress is introduced to the fuse element and will wear out the component. Furthermore, the fuse may be used in a large......, and rated voltage/current are opposed to shift in time to effect early breaking during the normal operation of the circuit. Therefore, in such cases, a reliable protection required for the other circuit components will not be achieved. The thermo-mechanical models, fatigue analysis and thermo...

  19. Structural hybrid reliability index and its convergent solving method based on random–fuzzy–interval reliability model

    Directory of Open Access Journals (Sweden)

    Hai An

    2016-08-01

    Full Text Available Aiming to resolve the problems of a variety of uncertainty variables that coexist in the engineering structure reliability analysis, a new hybrid reliability index to evaluate structural hybrid reliability, based on the random–fuzzy–interval model, is proposed in this article. The convergent solving method is also presented. First, the truncated probability reliability model, the fuzzy random reliability model, and the non-probabilistic interval reliability model are introduced. Then, the new hybrid reliability index definition is presented based on the random–fuzzy–interval model. Furthermore, the calculation flowchart of the hybrid reliability index is presented and it is solved using the modified limit-step length iterative algorithm, which ensures convergence. And the validity of convergent algorithm for the hybrid reliability model is verified through the calculation examples in literature. In the end, a numerical example is demonstrated to show that the hybrid reliability index is applicable for the wear reliability assessment of mechanisms, where truncated random variables, fuzzy random variables, and interval variables coexist. The demonstration also shows the good convergence of the iterative algorithm proposed in this article.

  20. The brain acid-base homeostasis and serotonin: A perspective on the use of carbon dioxide as human and rodent experimental model of panic.

    Science.gov (United States)

    Leibold, N K; van den Hove, D L A; Esquivel, G; De Cort, K; Goossens, L; Strackx, E; Buchanan, G F; Steinbusch, H W M; Lesch, K P; Schruers, K R J

    2015-06-01

    Panic attacks (PAs), the core feature of panic disorder, represent a common phenomenon in the general adult population and are associated with a considerable decrease in quality of life and high health care costs. To date, the underlying pathophysiology of PAs is not well understood. A unique feature of PAs is that they represent a rare example of a psychopathological phenomenon that can be reliably modeled in the laboratory in panic disorder patients and healthy volunteers. The most effective techniques to experimentally trigger PAs are those that acutely disturb the acid-base homeostasis in the brain: inhalation of carbon dioxide (CO2), hyperventilation, and lactate infusion. This review particularly focuses on the use of CO2 inhalation in humans and rodents as an experimental model of panic. Besides highlighting the different methodological approaches, the cardio-respiratory and the endocrine responses to CO2 inhalation are summarized. In addition, the relationships between CO2 level, changes in brain pH, the serotonergic system, and adaptive physiological and behavioral responses to CO2 exposure are presented. We aim to present an integrated psychological and neurobiological perspective. Remaining gaps in the literature and future perspectives are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Average inactivity time model, associated orderings and reliability properties

    Science.gov (United States)

    Kayid, M.; Izadkhah, S.; Abouammoh, A. M.

    2018-02-01

    In this paper, we introduce and study a new model called 'average inactivity time model'. This new model is specifically applicable to handle the heterogeneity of the time of the failure of a system in which some inactive items exist. We provide some bounds for the mean average inactivity time of a lifespan unit. In addition, we discuss some dependence structures between the average variable and the mixing variable in the model when original random variable possesses some aging behaviors. Based on the conception of the new model, we introduce and study a new stochastic order. Finally, to illustrate the concept of the model, some interesting reliability problems are reserved.

  2. A model for assessing human cognitive reliability in PRA studies

    International Nuclear Information System (INIS)

    Hannaman, G.W.; Spurgin, A.J.; Lukic, Y.

    1985-01-01

    This paper summarizes the status of a research project sponsored by EPRI as part of the Probabilistic Risk Assessment (PRA) technology improvement program and conducted by NUS Corporation to develop a model of Human Cognitive Reliability (HCR). The model was synthesized from features identified in a review of existing models. The model development was based on the hypothesis that the key factors affecting crew response times are separable. The inputs to the model consist of key parameters the values of which can be determined by PRA analysts for each accident situation being assessed. The output is a set of curves which represent the probability of control room crew non-response as a function of time for different conditions affecting their performance. The non-response probability is then a contributor to the overall non-success of operating crews to achieve a functional objective identified in the PRA study. Simulator data and some small scale tests were utilized to illustrate the calibration of interim HCR model coefficients for different types of cognitive processing since the data were sparse. The model can potentially help PRA analysts make human reliability assessments more explicit. The model incorporates concepts from psychological models of human cognitive behavior, information from current collections of human reliability data sources and crew response time data from simulator training exercises

  3. The reliability of the Adelaide in-shoe foot model.

    Science.gov (United States)

    Bishop, Chris; Hillier, Susan; Thewlis, Dominic

    2017-07-01

    Understanding the biomechanics of the foot is essential for many areas of research and clinical practice such as orthotic interventions and footwear development. Despite the widespread attention paid to the biomechanics of the foot during gait, what largely remains unknown is how the foot moves inside the shoe. This study investigated the reliability of the Adelaide In-Shoe Foot Model, which was designed to quantify in-shoe foot kinematics and kinetics during walking. Intra-rater reliability was assessed in 30 participants over five walking trials whilst wearing shoes during two data collection sessions, separated by one week. Sufficient reliability for use was interpreted as a coefficient of multiple correlation and intra-class correlation coefficient of >0.61. Inter-rater reliability was investigated separately in a second sample of 10 adults by two researchers with experience in applying markers for the purpose of motion analysis. The results indicated good consistency in waveform estimation for most kinematic and kinetic data, as well as good inter-and intra-rater reliability. The exception is the peak medial ground reaction force, the minimum abduction angle and the peak abduction/adduction external hindfoot joint moments which resulted in less than acceptable repeatability. Based on our results, the Adelaide in-shoe foot model can be used with confidence for 24 commonly measured biomechanical variables during shod walking. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Modeling of humidity-related reliability in enclosures with electronics

    DEFF Research Database (Denmark)

    Hygum, Morten Arnfeldt; Popok, Vladimir

    2015-01-01

    Reliability of electronics that operate outdoor is strongly affected by environmental factors such as temperature and humidity. Fluctuations of these parameters can lead to water condensation inside enclosures. Therefore, modelling of humidity distribution in a container with air and freely exposed...

  5. Models of Information Security Highly Reliable Computing Systems

    Directory of Open Access Journals (Sweden)

    Vsevolod Ozirisovich Chukanov

    2016-03-01

    Full Text Available Methods of the combined reservation are considered. The models of reliability of systems considering parameters of restoration and prevention of blocks of system are described. Ratios for average quantity prevention and an availability quotient of blocks of system are given.

  6. Vitamin D depletion does not affect key aspects of the preeclamptic phenotype in a transgenic rodent model for preeclampsia

    DEFF Research Database (Denmark)

    Andersen, Louise Bjørkholt; Golic, Michaela; Przybyl, Lukasz

    2016-01-01

    Maternal vitamin D deficiency is proposed as a risk factor for preeclampsia in humans. We tested the hypothesis that vitamin D depletion aggravates and high supplementation ameliorates the preeclampsia phenotype in an established transgenic rat model of human renin-angiotensin system......-mediated preeclampsia. Adult rat dams, transgenic for human angiotensinogen (hAGT) and mated with male rats transgenic for human renin (hREN), were fed either vitamin D-depleted chow (VDd) or enriched chow (VDh) 2 weeks before mating and during pregnancy. Mean blood pressure was recorded by tail-cuff, and 24-hour urine...... of the preeclampsia phenotype using the transgenic rodent model of human renin-angiotensin system-mediated pre-eclampsia, plausibly due to altered vitamin D metabolism or excretion in the transgenic rats....

  7. Tissue expander stimulated lengthening of arteries (TESLA) induces early endothelial cell proliferation in a novel rodent model.

    Science.gov (United States)

    Potanos, Kristina; Fullington, Nora; Cauley, Ryan; Purcell, Patricia; Zurakowski, David; Fishman, Steven; Vakili, Khashayar; Kim, Heung Bae

    2016-04-01

    We examine the mechanism of aortic lengthening in a novel rodent model of tissue expander stimulated lengthening of arteries (TESLA). A rat model of TESLA was examined with a single stretch stimulus applied at the time of tissue expander insertion with evaluation of the aorta at 2, 4 and 7day time points. Measurements as well as histology and proliferation assays were performed and compared to sham controls. The aortic length was increased at all time points without histologic signs of tissue injury. Nuclear density remained unchanged despite the increase in length suggesting cellular hyperplasia. Cellular proliferation was confirmed in endothelial cell layer by Ki-67 stain. Aortic lengthening may be achieved using TESLA. The increase in aortic length can be achieved without tissue injury and results at least partially from cellular hyperplasia. Further studies are required to define the mechanisms involved in the growth of arteries under increased longitudinal stress. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. An architectural model for software reliability quantification: sources of data

    International Nuclear Information System (INIS)

    Smidts, C.; Sova, D.

    1999-01-01

    Software reliability assessment models in use today treat software as a monolithic block. An aversion towards 'atomic' models seems to exist. These models appear to add complexity to the modeling, to the data collection and seem intrinsically difficult to generalize. In 1997, we introduced an architecturally based software reliability model called FASRE. The model is based on an architecture derived from the requirements which captures both functional and nonfunctional requirements and on a generic classification of functions, attributes and failure modes. The model focuses on evaluation of failure mode probabilities and uses a Bayesian quantification framework. Failure mode probabilities of functions and attributes are propagated to the system level using fault trees. It can incorporate any type of prior information such as results of developers' testing, historical information on a specific functionality and its attributes, and, is ideally suited for reusable software. By building an architecture and deriving its potential failure modes, the model forces early appraisal and understanding of the weaknesses of the software, allows reliability analysis of the structure of the system, provides assessments at a functional level as well as at a systems' level. In order to quantify the probability of failure (or the probability of success) of a specific element of our architecture, data are needed. The term element of the architecture is used here in its broadest sense to mean a single failure mode or a higher level of abstraction such as a function. The paper surveys the potential sources of software reliability data available during software development. Next the mechanisms for incorporating these sources of relevant data to the FASRE model are identified

  9. Stochastic Differential Equation-Based Flexible Software Reliability Growth Model

    Directory of Open Access Journals (Sweden)

    P. K. Kapur

    2009-01-01

    Full Text Available Several software reliability growth models (SRGMs have been developed by software developers in tracking and measuring the growth of reliability. As the size of software system is large and the number of faults detected during the testing phase becomes large, so the change of the number of faults that are detected and removed through each debugging becomes sufficiently small compared with the initial fault content at the beginning of the testing phase. In such a situation, we can model the software fault detection process as a stochastic process with continuous state space. In this paper, we propose a new software reliability growth model based on Itô type of stochastic differential equation. We consider an SDE-based generalized Erlang model with logistic error detection function. The model is estimated and validated on real-life data sets cited in literature to show its flexibility. The proposed model integrated with the concept of stochastic differential equation performs comparatively better than the existing NHPP-based models.

  10. Modular reliability modeling of the TJNAF personnel safety system

    International Nuclear Information System (INIS)

    Cinnamon, J.; Mahoney, K.

    1997-01-01

    A reliability model for the Thomas Jefferson National Accelerator Facility (formerly CEBAF) personnel safety system has been developed. The model, which was implemented using an Excel spreadsheet, allows simulation of all or parts of the system. Modularity os the model's implementation allows rapid open-quotes what if open-quotes case studies to simulate change in safety system parameters such as redundancy, diversity, and failure rates. Particular emphasis is given to the prediction of failure modes which would result in the failure of both of the redundant safety interlock systems. In addition to the calculation of the predicted reliability of the safety system, the model also calculates availability of the same system. Such calculations allow the user to make tradeoff studies between reliability and availability, and to target resources to improving those parts of the system which would most benefit from redesign or upgrade. The model includes calculated, manufacturer's data, and Jefferson Lab field data. This paper describes the model, methods used, and comparison of calculated to actual data for the Jefferson Lab personnel safety system. Examples are given to illustrate the model's utility and ease of use

  11. Modeling and Analysis of Component Faults and Reliability

    DEFF Research Database (Denmark)

    Le Guilly, Thibaut; Olsen, Petur; Ravn, Anders Peter

    2016-01-01

    This chapter presents a process to design and validate models of reactive systems in the form of communicating timed automata. The models are extended with faults associated with probabilities of occurrence. This enables a fault tree analysis of the system using minimal cut sets that are automati......This chapter presents a process to design and validate models of reactive systems in the form of communicating timed automata. The models are extended with faults associated with probabilities of occurrence. This enables a fault tree analysis of the system using minimal cut sets...... that are automatically generated. The stochastic information on the faults is used to estimate the reliability of the fault affected system. The reliability is given with respect to properties of the system state space. We illustrate the process on a concrete example using the Uppaal model checker for validating...... the ideal system model and the fault modeling. Then the statistical version of the tool, UppaalSMC, is used to find reliability estimates....

  12. Reliability modeling and analysis of smart power systems

    CERN Document Server

    Karki, Rajesh; Verma, Ajit Kumar

    2014-01-01

    The volume presents the research work in understanding, modeling and quantifying the risks associated with different ways of implementing smart grid technology in power systems in order to plan and operate a modern power system with an acceptable level of reliability. Power systems throughout the world are undergoing significant changes creating new challenges to system planning and operation in order to provide reliable and efficient use of electrical energy. The appropriate use of smart grid technology is an important drive in mitigating these problems and requires considerable research acti

  13. A general graphical user interface for automatic reliability modeling

    Science.gov (United States)

    Liceaga, Carlos A.; Siewiorek, Daniel P.

    1991-01-01

    Reported here is a general Graphical User Interface (GUI) for automatic reliability modeling of Processor Memory Switch (PMS) structures using a Markov model. This GUI is based on a hierarchy of windows. One window has graphical editing capabilities for specifying the system's communication structure, hierarchy, reconfiguration capabilities, and requirements. Other windows have field texts, popup menus, and buttons for specifying parameters and selecting actions. An example application of the GUI is given.

  14. Photovoltaic Reliability Performance Model v 2.0

    Energy Technology Data Exchange (ETDEWEB)

    2016-12-16

    PV-RPM is intended to address more “real world” situations by coupling a photovoltaic system performance model with a reliability model so that inverters, modules, combiner boxes, etc. can experience failures and be repaired (or left unrepaired). The model can also include other effects, such as module output degradation over time or disruptions such as electrical grid outages. In addition, PV-RPM is a dynamic probabilistic model that can be used to run many realizations (i.e., possible future outcomes) of a system’s performance using probability distributions to represent uncertain parameter inputs.

  15. Bring Your Own Device - Providing Reliable Model of Data Access

    Directory of Open Access Journals (Sweden)

    Stąpór Paweł

    2016-10-01

    Full Text Available The article presents a model of Bring Your Own Device (BYOD as a model network, which provides the user reliable access to network resources. BYOD is a model dynamically developing, which can be applied in many areas. Research network has been launched in order to carry out the test, in which as a service of BYOD model Work Folders service was used. This service allows the user to synchronize files between the device and the server. An access to the network is completed through the wireless communication by the 802.11n standard. Obtained results are shown and analyzed in this article.

  16. NHPP-Based Software Reliability Models Using Equilibrium Distribution

    Science.gov (United States)

    Xiao, Xiao; Okamura, Hiroyuki; Dohi, Tadashi

    Non-homogeneous Poisson processes (NHPPs) have gained much popularity in actual software testing phases to estimate the software reliability, the number of remaining faults in software and the software release timing. In this paper, we propose a new modeling approach for the NHPP-based software reliability models (SRMs) to describe the stochastic behavior of software fault-detection processes. The fundamental idea is to apply the equilibrium distribution to the fault-detection time distribution in NHPP-based modeling. We also develop efficient parameter estimation procedures for the proposed NHPP-based SRMs. Through numerical experiments, it can be concluded that the proposed NHPP-based SRMs outperform the existing ones in many data sets from the perspective of goodness-of-fit and prediction performance.

  17. An in-vitro–in-vivo model for the transdermal delivery of cholecalciferol for the purposes of rodent management

    Science.gov (United States)

    Davies, J.; Ingham, A.

    2015-01-01

    The natural selection of anticoagulant resistant rats has resulted in a need for an alternative to anticoagulant rodenticides which differs in both active ingredient and in the method of dosing. Cholecalciferol toxicity to rodents using the dermal route is demonstrated using a variety of penetration enhancing formulations in two in-vitro models and finally in-vivo. A 1 ml dose of 50/50 (v/v) DMSO/ethanol containing 15% (v/v) PEG 200 and 20% (w/v) cholecalciferol was judged as ‘sufficiently effective’ in line with the European Union’s Biocidal Products Regulation (No. 528/2012) during in-vivo studies. This dose was found to cause 100% mortality in a rat population in 64.4 h (±22 h). PMID:25835266

  18. An in-vitro-in-vivo model for the transdermal delivery of cholecalciferol for the purposes of rodent management.

    Science.gov (United States)

    Davies, J; Ingham, A

    2015-06-20

    The natural selection of anticoagulant resistant rats has resulted in a need for an alternative to anticoagulant rodenticides which differs in both active ingredient and in the method of dosing. Cholecalciferol toxicity to rodents using the dermal route is demonstrated using a variety of penetration enhancing formulations in two in-vitro models and finally in-vivo. A 1 ml dose of 50/50 (v/v) DMSO/ethanol containing 15% (v/v) PEG 200 and 20% (w/v) cholecalciferol was judged as 'sufficiently effective' in line with the European Union's Biocidal Products Regulation (No. 528/2012) during in-vivo studies. This dose was found to cause 100% mortality in a rat population in 64.4h (± 22h). Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Structural reliability in context of statistical uncertainties and modelling discrepancies

    International Nuclear Information System (INIS)

    Pendola, Maurice

    2000-01-01

    Structural reliability methods have been largely improved during the last years and have showed their ability to deal with uncertainties during the design stage or to optimize the functioning and the maintenance of industrial installations. They are based on a mechanical modeling of the structural behavior according to the considered failure modes and on a probabilistic representation of input parameters of this modeling. In practice, only limited statistical information is available to build the probabilistic representation and different sophistication levels of the mechanical modeling may be introduced. Thus, besides the physical randomness, other uncertainties occur in such analyses. The aim of this work is triple: 1. at first, to propose a methodology able to characterize the statistical uncertainties due to the limited number of data in order to take them into account in the reliability analyses. The obtained reliability index measures the confidence in the structure considering the statistical information available. 2. Then, to show a methodology leading to reliability results evaluated from a particular mechanical modeling but by using a less sophisticated one. The objective is then to decrease the computational efforts required by the reference modeling. 3. Finally, to propose partial safety factors that are evolving as a function of the number of statistical data available and as a function of the sophistication level of the mechanical modeling that is used. The concepts are illustrated in the case of a welded pipe and in the case of a natural draught cooling tower. The results show the interest of the methodologies in an industrial context. [fr

  20. Inhibiting C-Reactive Protein for the Treatment of Cardiovascular Disease: Promising Evidence from Rodent Models

    Directory of Open Access Journals (Sweden)

    Alexander J. Szalai

    2014-01-01

    Full Text Available Raised blood C-reactive protein (CRP level is a predictor of cardiovascular events, but whether blood CRP is causal in the disease process is unknown. The latter would best be defined by pharmacological inhibition of the protein in the context of a randomized case-control study. However, no CRP specific drug is currently available so such a prospective study cannot be performed. Blood CRP is synthesized primarily in the liver and the liver is an organ where antisense oligonucleotide (ASO drugs accumulate. Taking advantage of this we evaluated the efficacy of CRP specific ASOs in rodents with experimentally induced cardiovascular damage. Treating rats for 4 weeks with a rat CRP-specific ASO achieved >60% reduction of blood CRP. Notably, this effect was associated with improved heart function and pathology following myocardial infarction (induced by ligation of the left anterior descending artery. Likewise in human CRP transgenic mice treated for 2 weeks with a human CRP-specific ASO, blood human CRP was reduced by >70% and carotid artery patency was improved (2 weeks after surgical ligation. CRP specific ASOs might pave the way towards a placebo-controlled trial that could clarify the role of CRP in cardiovascular disease.

  1. Reliability assessment of competing risks with generalized mixed shock models

    International Nuclear Information System (INIS)

    Rafiee, Koosha; Feng, Qianmei; Coit, David W.

    2017-01-01

    This paper investigates reliability modeling for systems subject to dependent competing risks considering the impact from a new generalized mixed shock model. Two dependent competing risks are soft failure due to a degradation process, and hard failure due to random shocks. The shock process contains fatal shocks that can cause hard failure instantaneously, and nonfatal shocks that impact the system in three different ways: 1) damaging the unit by immediately increasing the degradation level, 2) speeding up the deterioration by accelerating the degradation rate, and 3) weakening the unit strength by reducing the hard failure threshold. While the first impact from nonfatal shocks comes from each individual shock, the other two impacts are realized when the condition for a new generalized mixed shock model is satisfied. Unlike most existing mixed shock models that consider a combination of two shock patterns, our new generalized mixed shock model includes three classic shock patterns. According to the proposed generalized mixed shock model, the degradation rate and the hard failure threshold can simultaneously shift multiple times, whenever the condition for one of these three shock patterns is satisfied. An example using micro-electro-mechanical systems devices illustrates the effectiveness of the proposed approach with sensitivity analysis. - Highlights: • A rich reliability model for systems subject to dependent failures is proposed. • The degradation rate and the hard failure threshold can shift simultaneously. • The shift is triggered by a new generalized mixed shock model. • The shift can occur multiple times under the generalized mixed shock model.

  2. Testing the reliability of ice-cream cone model

    Science.gov (United States)

    Pan, Zonghao; Shen, Chenglong; Wang, Chuanbing; Liu, Kai; Xue, Xianghui; Wang, Yuming; Wang, Shui

    2015-04-01

    Coronal Mass Ejections (CME)'s properties are important to not only the physical scene itself but space-weather prediction. Several models (such as cone model, GCS model, and so on) have been raised to get rid of the projection effects within the properties observed by spacecraft. According to SOHO/ LASCO observations, we obtain the 'real' 3D parameters of all the FFHCMEs (front-side full halo Coronal Mass Ejections) within the 24th solar cycle till July 2012, by the ice-cream cone model. Considering that the method to obtain 3D parameters from the CME observations by multi-satellite and multi-angle has higher accuracy, we use the GCS model to obtain the real propagation parameters of these CMEs in 3D space and compare the results with which by ice-cream cone model. Then we could discuss the reliability of the ice-cream cone model.

  3. Creation and Reliability Analysis of Vehicle Dynamic Weighing Model

    Directory of Open Access Journals (Sweden)

    Zhi-Ling XU

    2014-08-01

    Full Text Available In this paper, it is modeled by using ADAMS to portable axle load meter of dynamic weighing system, controlling a single variable simulation weighing process, getting the simulation weighing data under the different speed and weight; simultaneously using portable weighing system with the same parameters to achieve the actual measurement, comparative analysis the simulation results under the same conditions, at 30 km/h or less, the simulation value and the measured value do not differ by more than 5 %, it is not only to verify the reliability of dynamic weighing model, but also to create possible for improving algorithm study efficiency by using dynamic weighing model simulation.

  4. Human Performance Modeling for Dynamic Human Reliability Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Boring, Ronald Laurids [Idaho National Laboratory; Joe, Jeffrey Clark [Idaho National Laboratory; Mandelli, Diego [Idaho National Laboratory

    2015-08-01

    Part of the U.S. Department of Energy’s (DOE’s) Light Water Reac- tor Sustainability (LWRS) Program, the Risk-Informed Safety Margin Charac- terization (RISMC) Pathway develops approaches to estimating and managing safety margins. RISMC simulations pair deterministic plant physics models with probabilistic risk models. As human interactions are an essential element of plant risk, it is necessary to integrate human actions into the RISMC risk framework. In this paper, we review simulation based and non simulation based human reliability analysis (HRA) methods. This paper summarizes the founda- tional information needed to develop a feasible approach to modeling human in- teractions in RISMC simulations.

  5. Imperfect Preventive Maintenance Model Study Based On Reliability Limitation

    Directory of Open Access Journals (Sweden)

    Zhou Qian

    2016-01-01

    Full Text Available Effective maintenance is crucial for equipment performance in industry. Imperfect maintenance conform to actual failure process. Taking the dynamic preventive maintenance cost into account, the preventive maintenance model was constructed by using age reduction factor. The model regards the minimization of repair cost rate as final target. It use allowed smallest reliability as the replacement condition. Equipment life was assumed to follow two parameters Weibull distribution since it was one of the most commonly adopted distributions to fit cumulative failure problems. Eventually the example verifies the rationality and benefits of the model.

  6. Modelling and estimating degradation processes with application in structural reliability

    International Nuclear Information System (INIS)

    Chiquet, J.

    2007-06-01

    The characteristic level of degradation of a given structure is modeled through a stochastic process called the degradation process. The random evolution of the degradation process is governed by a differential system with Markovian environment. We put the associated reliability framework by considering the failure of the structure once the degradation process reaches a critical threshold. A closed form solution of the reliability function is obtained thanks to Markov renewal theory. Then, we build an estimation methodology for the parameters of the stochastic processes involved. The estimation methods and the theoretical results, as well as the associated numerical algorithms, are validated on simulated data sets. Our method is applied to the modelling of a real degradation mechanism, known as crack growth, for which an experimental data set is considered. (authors)

  7. A modified beam-walking apparatus for assessment of anxiety in a rodent model of blast traumatic brain injury.

    Science.gov (United States)

    Sweis, Brian M; Bachour, Salam P; Brekke, Julia A; Gewirtz, Jonathan C; Sadeghi-Bazargani, Homayoun; Hevesi, Mario; Divani, Afshin A

    2016-01-01

    The elevated plus maze (EPM) is used to assess anxiety in rodents. Beam-walking tasks are used to assess vestibulomotor function. Brain injury in rodents can disrupt performance on both of these tasks. Developing novel paradigms that integrate tasks like these can reduce the need for multiple tests when attempting to assess multiple behaviors in the same animal. Using adult male rats, we evaluated the use of a modified beam-walking (MBW) apparatus as a surrogate indicator for anxiety. We used a model of blast-induced traumatic brain injury (bTBI). A total of 39 rats were assessed before and at 3, 6, 24, 72, and 168h either post- bTBI (n=33) or no-injury (n=6) using both EPM and MBW. A novel anxiety index was calculated that encompassed peeks and re-emergences on MBW. The proposed MBW anxiety index was compared with the standard anxiety index calculated from exploration into different sections of EPM. Post- bTBI, rats had an increased anxiety index when measured using EPM. Similarly, they peeked or fully emerged less out of the safe box on MBW. It was found that this novel MBW anxiety index captured similar aspects of behavior when compared to the standard anxiety index obtained from EPM. Further, these effects were dissociated from the effects of bTBI on motor function simultaneously measured on MBW. Over the course of 168h post-bTBI, rats gradually recovered on both EPM and MBW. The MBW apparatus succeeded at capturing and dissociating two separate facets of rat behavior, motor function and anxiety, simultaneously. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Mitogen activated protein kinase phosphatase-1 prevents the development of tactile sensitivity in a rodent model of neuropathic pain

    Directory of Open Access Journals (Sweden)

    Ndong Christian

    2012-04-01

    Full Text Available Abstract Background Neuropathic pain due to nerve injury is one of the most difficult types of pain to treat. Following peripheral nerve injury, neuronal and glial plastic changes contribute to central sensitization and perpetuation of mechanical hypersensitivity in rodents. The mitogen activated protein kinase (MAPK family is pivotal in this spinal cord plasticity. MAPK phosphatases (MKPs limit inflammatory processes by dephosphorylating MAPKs. For example, MKP-1 preferentially dephosphorylates p-p38. Since spinal p-p38 is pivotal for the development of chronic hypersensitivity in rodent models of pain, and p-p38 inhibitors have shown clinical potential in acute and chronic pain patients, we hypothesize that induction of spinal MKP-1 will prevent the development of peripheral nerve-injury-induced hypersensitivity and p-p38 overexpression. Results We cloned rat spinal cord MKP-1 and optimize MKP-1 cDNA in vitro using transfections to BV-2 cells. We observed that in vitro overexpression of MKP-1 blocked lipopolysaccharide-induced phosphorylation of p38 (and other MAPKs as well as release of pro-algesic effectors (i.e., cytokines, chemokines, nitric oxide. Using this cDNA MKP-1 and a non-viral, in vivo nanoparticle transfection approach, we found that spinal cord overexpression of MKP-1 prevented development of peripheral nerve-injury-induced tactile hypersensitivity and reduced pro-inflammatory cytokines and chemokines and the phosphorylated form of p38. Conclusions Our results indicate that MKP-1, the natural regulator of p-p38, mediates resolution of the spinal cord pro-inflammatory milieu induced by peripheral nerve injury, resulting in prevention of chronic mechanical hypersensitivity. We propose that MKP-1 is a potential therapeutic target for pain treatment or prevention.

  9. Fuzzy Goal Programming Approach in Selective Maintenance Reliability Model

    Directory of Open Access Journals (Sweden)

    Neha Gupta

    2013-12-01

    Full Text Available 800x600 In the present paper, we have considered the allocation problem of repairable components for a parallel-series system as a multi-objective optimization problem and have discussed two different models. In first model the reliability of subsystems are considered as different objectives. In second model the cost and time spent on repairing the components are considered as two different objectives. These two models is formulated as multi-objective Nonlinear Programming Problem (MONLPP and a Fuzzy goal programming method is used to work out the compromise allocation in multi-objective selective maintenance reliability model in which we define the membership functions of each objective function and then transform membership functions into equivalent linear membership functions by first order Taylor series and finally by forming a fuzzy goal programming model obtain a desired compromise allocation of maintenance components. A numerical example is also worked out to illustrate the computational details of the method.  Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4

  10. Software reliability growth models with normal failure time distributions

    International Nuclear Information System (INIS)

    Okamura, Hiroyuki; Dohi, Tadashi; Osaki, Shunji

    2013-01-01

    This paper proposes software reliability growth models (SRGM) where the software failure time follows a normal distribution. The proposed model is mathematically tractable and has sufficient ability of fitting to the software failure data. In particular, we consider the parameter estimation algorithm for the SRGM with normal distribution. The developed algorithm is based on an EM (expectation-maximization) algorithm and is quite simple for implementation as software application. Numerical experiment is devoted to investigating the fitting ability of the SRGMs with normal distribution through 16 types of failure time data collected in real software projects

  11. Reliability modelling - PETROBRAS 2010 integrated gas supply chain

    Energy Technology Data Exchange (ETDEWEB)

    Faertes, Denise; Heil, Luciana; Saker, Leonardo; Vieira, Flavia; Risi, Francisco; Domingues, Joaquim; Alvarenga, Tobias; Carvalho, Eduardo; Mussel, Patricia

    2010-09-15

    The purpose of this paper is to present the innovative reliability modeling of Petrobras 2010 integrated gas supply chain. The model represents a challenge in terms of complexity and software robustness. It was jointly developed by PETROBRAS Gas and Power Department and Det Norske Veritas. It was carried out with the objective of evaluating security of supply of 2010 gas network design that was conceived to connect Brazilian Northeast and Southeast regions. To provide best in class analysis, state of the art software was used to quantify the availability and the efficiency of the overall network and its individual components.

  12. Evaluating the reliability of predictions made using environmental transfer models

    International Nuclear Information System (INIS)

    1989-01-01

    The development and application of mathematical models for predicting the consequences of releases of radionuclides into the environment from normal operations in the nuclear fuel cycle and in hypothetical accident conditions has increased dramatically in the last two decades. This Safety Practice publication has been prepared to provide guidance on the available methods for evaluating the reliability of environmental transfer model predictions. It provides a practical introduction of the subject and a particular emphasis has been given to worked examples in the text. It is intended to supplement existing IAEA publications on environmental assessment methodology. 60 refs, 17 figs, 12 tabs

  13. Modeling specific phobias and posttraumatic stress disorder in rodents: the challenge to convey both cognitive and emotional features.

    Science.gov (United States)

    Berardi, Andrea; Trezza, Viviana; Campolongo, Campolongo

    2012-01-01

    Aberrant emotional memory processing is a core, disabling feature of both specific phobias and posttraumatic stress disorder (PTSD), two psychiatric diseases of significant prevalence and morbidity whose cognitive symptoms cannot be adequately treated by current psychopharmacological tools. Elucidating the neurobiological mechanisms involved in the etiology of these diseases is of great interest for the identification of new therapeutics that improve not only the symptomatology but also the full recovery from the pathology. To this aim, several animal models have been proposed based on substantial resemblance between the behavioral alterations seen in animals and the human pathology. The purpose of this review is to describe and comment on the most commonly used rodent models of specific phobias and PTSD. A particular focus will be reserved to the cued version of fear conditioning, as the highly specific stimulus-bound conditioned fear response seems to fit well with clinical descriptions of phobic fear.Moreover, animal models of PTSD will be evaluated by referring to three elements that are considered essential ina valid model of this disease: stressor exposure, memory for the stressor, and anxiety-related behaviors. Finally, current therapeutic directions, with a focus on cannabinoid and glucocorticoid compounds, will be briefly outlined.

  14. Reliability physics and engineering time-to-failure modeling

    CERN Document Server

    McPherson, J W

    2013-01-01

    Reliability Physics and Engineering provides critically important information that is needed for designing and building reliable cost-effective products. Key features include:  ·       Materials/Device Degradation ·       Degradation Kinetics ·       Time-To-Failure Modeling ·       Statistical Tools ·       Failure-Rate Modeling ·       Accelerated Testing ·       Ramp-To-Failure Testing ·       Important Failure Mechanisms for Integrated Circuits ·       Important Failure Mechanisms for  Mechanical Components ·       Conversion of Dynamic  Stresses into Static Equivalents ·       Small Design Changes Producing Major Reliability Improvements ·       Screening Methods ·       Heat Generation and Dissipation ·       Sampling Plans and Confidence Intervals This textbook includes numerous example problems with solutions. Also, exercise problems along with the answers are included at the end of each chapter. Relia...

  15. Power Electronic Packaging Design, Assembly Process, Reliability and Modeling

    CERN Document Server

    Liu, Yong

    2012-01-01

    Power Electronic Packaging presents an in-depth overview of power electronic packaging design, assembly,reliability and modeling. Since there is a drastic difference between IC fabrication and power electronic packaging, the book systematically introduces typical power electronic packaging design, assembly, reliability and failure analysis and material selection so readers can clearly understand each task's unique characteristics. Power electronic packaging is one of the fastest growing segments in the power electronic industry, due to the rapid growth of power integrated circuit (IC) fabrication, especially for applications like portable, consumer, home, computing and automotive electronics. This book also covers how advances in both semiconductor content and power advanced package design have helped cause advances in power device capability in recent years. The author extrapolates the most recent trends in the book's areas of focus to highlight where further improvement in materials and techniques can d...

  16. Model-based human reliability analysis: prospects and requirements

    International Nuclear Information System (INIS)

    Mosleh, A.; Chang, Y.H.

    2004-01-01

    Major limitations of the conventional methods for human reliability analysis (HRA), particularly those developed for operator response analysis in probabilistic safety assessments (PSA) of nuclear power plants, are summarized as a motivation for the need and a basis for developing requirements for the next generation HRA methods. It is argued that a model-based approach that provides explicit cognitive causal links between operator behaviors and directly or indirectly measurable causal factors should be at the core of the advanced methods. An example of such causal model is briefly reviewed, where due to the model complexity and input requirements can only be currently implemented in a dynamic PSA environment. The computer simulation code developed for this purpose is also described briefly, together with current limitations in the models, data, and the computer implementation

  17. Stochastic process corrosion growth models for pipeline reliability

    International Nuclear Information System (INIS)

    Bazán, Felipe Alexander Vargas; Beck, André Teófilo

    2013-01-01

    Highlights: •Novel non-linear stochastic process corrosion growth model is proposed. •Corrosion rate modeled as random Poisson pulses. •Time to corrosion initiation and inherent time-variability properly represented. •Continuous corrosion growth histories obtained. •Model is shown to precisely fit actual corrosion data at two time points. -- Abstract: Linear random variable corrosion models are extensively employed in reliability analysis of pipelines. However, linear models grossly neglect well-known characteristics of the corrosion process. Herein, a non-linear model is proposed, where corrosion rate is represented as a Poisson square wave process. The resulting model represents inherent time-variability of corrosion growth, produces continuous growth and leads to mean growth at less-than-one power of time. Different corrosion models are adjusted to the same set of actual corrosion data for two inspections. The proposed non-linear random process corrosion growth model leads to the best fit to the data, while better representing problem physics

  18. Do downscaled general circulation models reliably simulate historical climatic conditions?

    Science.gov (United States)

    Bock, Andrew R.; Hay, Lauren E.; McCabe, Gregory J.; Markstrom, Steven L.; Atkinson, R. Dwight

    2018-01-01

    The accuracy of statistically downscaled (SD) general circulation model (GCM) simulations of monthly surface climate for historical conditions (1950–2005) was assessed for the conterminous United States (CONUS). The SD monthly precipitation (PPT) and temperature (TAVE) from 95 GCMs from phases 3 and 5 of the Coupled Model Intercomparison Project (CMIP3 and CMIP5) were used as inputs to a monthly water balance model (MWBM). Distributions of MWBM input (PPT and TAVE) and output [runoff (RUN)] variables derived from gridded station data (GSD) and historical SD climate were compared using the Kolmogorov–Smirnov (KS) test For all three variables considered, the KS test results showed that variables simulated using CMIP5 generally are more reliable than those derived from CMIP3, likely due to improvements in PPT simulations. At most locations across the CONUS, the largest differences between GSD and SD PPT and RUN occurred in the lowest part of the distributions (i.e., low-flow RUN and low-magnitude PPT). Results indicate that for the majority of the CONUS, there are downscaled GCMs that can reliably simulate historical climatic conditions. But, in some geographic locations, none of the SD GCMs replicated historical conditions for two of the three variables (PPT and RUN) based on the KS test, with a significance level of 0.05. In these locations, improved GCM simulations of PPT are needed to more reliably estimate components of the hydrologic cycle. Simple metrics and statistical tests, such as those described here, can provide an initial set of criteria to help simplify GCM selection.

  19. Piper umbellatum L.: A medicinal plant with gastric-ulcer protective and ulcer healing effects in experimental rodent models.

    Science.gov (United States)

    da Silva Junior, Iberê Ferreira; Balogun, Sikiru Olaitan; de Oliveira, Ruberlei Godinho; Damazo, Amílcar Sabino; Martins, Domingos Tabajara de Oliveira

    2016-11-04

    Piper umbellatum L. (Piperaceae) is a shrub found in the Amazon, Savannah and Atlantic Forest region of Brazil. It is widely used in folk medicine in many countries primarily for the treatment of gastric disorders. The aim of this study was to evaluate the gastroprotective and anti-ulcer effects of hydroethanolic extract of P. umbellatum (HEPu) leaves in experimental rodents. In addition, the anti-Helicobacter pylori activity of the extract was assessed. The leaves of P. umbellatum were macerated in 75% (1:3w/v) hydroethanolic solution to obtain HEPu. The gastroprotective and ulcer healing activities of HEPu were evaluated using acidified ethanol (acute) and acetic acid (chronic) gastric ulcer models in rodents. The anti-H. pylori activity was evaluated by in vitro broth microdilution assay using H. pylori cagA + and vacA + strain. The probable mechanism of action of HEPu was evaluated by determining gastric secretory parameters, antioxidant enzyme (catalase), non-protein sulfhydryl (glutathione) and malondialdehyde levels in gastric tissue, including pro-inflammatory (IL-1β, TNF-a, IL -17, RANTES, IFN-γ and MIP-2) and anti-inflammatory (IL-10) cytokines. HEPu demonstrated potent gastroprotection against acute ulcer induced by acidified ethanol and excellent healing effect of the chronic ulcer induced by acetic acid. The gastroprotective activity in acidified ethanol is partly attributed to the antioxidant mechanisms, while anti-secretory, anti-inflammatory and regeneration of the gastric mucosa are evoked as part of its antiulcer mechanism of action. The gastric ulcer healing of HEPu also involves restoration of the altered cytokines levels to near normal. However, it has no in vitro anti-H. pylori activity. The results of this study showed that HEPu possesses preventive and curative effects in experimental models of gastric ulcers in animals. These effects are partially dependent on antioxidant, antisecretory, anti-inflammatory and mucosa regeneration. It is

  20. Plasmalemmal Vesicle Associated Protein-1 (PV-1 is a marker of blood-brain barrier disruption in rodent models

    Directory of Open Access Journals (Sweden)

    Ali Zarina S

    2008-02-01

    Full Text Available Abstract Background Plasmalemmal vesicle associated protein-1 (PV-1 is selectively expressed in human brain microvascular endothelial cells derived from clinical specimens of primary and secondary malignant brain tumors, cerebral ischemia, and other central nervous system (CNS diseases associated with blood-brain barrier breakdown. In this study, we characterize the murine CNS expression pattern of PV-1 to determine whether localized PV-1 induction is conserved across species and disease state. Results We demonstrate that PV-1 is selectively upregulated in mouse blood vessels recruited by brain tumor xenografts at the RNA and protein levels, but is not detected in non-neoplastic brain. Additionally, PV-1 is induced in a mouse model of acute ischemia. Expression is confined to the cerebovasculature within the region of infarct and is temporally regulated. Conclusion Our results confirm that PV-1 is preferentially induced in the endothelium of mouse brain tumors and acute ischemic brain tissue and corresponds to blood-brain barrier disruption in a fashion analogous to human patients. Characterization of PV-1 expression in mouse brain is the first step towards development of rodent models for testing anti-edema and anti-angiogenesis therapeutic strategies based on this molecule.

  1. Preventive effects of Flos Perariae (Gehua water extract and its active ingredient puerarin in rodent alcoholism models

    Directory of Open Access Journals (Sweden)

    Wang Yuqiang

    2010-10-01

    Full Text Available Abstract Background Radix Puerariae is used in Chinese medicine to treat alcohol addiction and intoxication. The present study investigates the effects of Flos puerariae lobatae water extract (FPE and its active ingredient puerarin on alcoholism using rodent models. Methods Alcoholic animals were given FPE or puerarin by oral intubation prior or after alcohol treatment. The loss of righting reflex (LORR assay was used to evaluate sedative/hypnotic effects. Changes of gama-aminobutyric acid type A receptor (GABAAR subunits induced by alcohol treatment in hippocampus were measured with western blot. In alcoholic mice, body weight gain was monitored throughout the experiments. Alcohol dehydrogenase (ADH levels in liver were measured. Results FPE and puerarin pretreatment significantly prolonged the time of LORR induced by diazepam in acute alcoholic rat. Puerarin increased expression of gama-aminobutyric acid type A receptor alpha1 subunit and decreased expression of alpha4 subunit. In chronic alcoholic mice, puerarin pretreatment significantly increased body weight and liver ADH activity in a dose-dependent manner. Puerarin pretreatment, but not post-treatment, can reverse the changes of gama-aminobutyric acid type A receptor subunit expression and increase ADH activity in alcoholism models. Conclusion The present study demonstrates that FPE and its active ingredient puerarin have preventive effects on alcoholism related disorders.

  2. Gastroprotective effect of the ethanolic extract of Parkia platycephala Benth. leaves against acute gastric lesion models in rodents

    Directory of Open Access Journals (Sweden)

    Hélio B Fernandes

    2010-01-01

    Full Text Available Parkia platycephala Benth. (Leguminosae - Mimosoideae, popularly known as "visgueira", fava bean tree or "fava-de-bolota", is widely found in the Northern and Northeastern regions of Brazil. Its pods are used as cattle food supplement in the drought period. Compounds with a gastroprotective activity were obtained from the genus Parkia. Therefore, this study aimed at investigating the gastroprotective effect of the ethanolic extract of Parkia platycephala Benth. leaves (Pp-EtOH, as well as evaluating its possible mechanisms of action in experimental ulcer induction models. Lesions were induced by absolute ethanol, ethanol-HCl, ischemia-reperfusion and indomethacin in rodents. Pp-EtOH showed a protective effect in the lesion models (66, 48 and 52 %, respectively, but it was not able to protect gastric mucosa against indomethacin-induced lesions. Results show a possible participation of the NO-synthase pathway in the gastroprotection and an antioxidant activity, by the increase of the catalase activity. The participation of prostaglandins and potassium channels sensitive to ATP in the gastroprotective effect of Pp-EtOH seems less likely to occur. More comprehensive studies, therefore, should be carried out to elucidate the antiulcerative effects of this promising natural product against this gastrointestinal disorder.

  3. Dietary fructose in pregnancy induces hyperglycemia, hypertension, and pathologic kidney and liver changes in a rodent model.

    Science.gov (United States)

    Shortliffe, Linda M Dairiki; Hammam, Olfat; Han, Xiaoyuan; Kouba, Erik; Tsao, Philip S; Wang, Bingyin

    2015-10-01

    The incidence of pregnancies complicated by hyperglycemia and hypertension is increasing along with associated morbidities to mother and offspring. The high fructose diet is a well-studied model that induces hyperglycemia and hypertension in male rodents, but may not affect females. We hypothesized that the physiologic stress of pregnancy may alter metabolic responses to dietary fructose. In this study female Sprague-Dawley rats were divided into two gestational dietary groups: (1) 60% carbohydrate standard rat chow (Pregnant-S-controls) and (2) 60% fructose enriched chow (Pregnant-F). Body weight, blood pressure, blood glucose, triglycerides, and insulin were measured in pregnancy and during the post-partum period. Maternal organ weight and histological changes were also assessed after delivery. By midpregnancy Pregnant-F rats had increased weight, elevated blood pressure, higher fasting glucose, and elevated triglycerides compared with Pregnant-S rats. Both groups demonstrated elevated gestational insulin levels with signs of insulin resistance (increased HOMA-IR). Pregnant-F rats showed significant histopathologic hepatic steatosis and renal tubular changes characterized by tubular dilation and glomerulosclerosis. Our study provides a model in which dietary change during pregnancy can be examined. We demonstrate, moreover, that high dietary fructose ingestion in pregnant rats may result in profound systemic and pathologic changes not appreciated during routine pregnancy. Copyright © 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

  4. Interaction of genotype and environment: Effect of strain and housing condition on cognitive behaviour in rodent models of schizophrenia

    Directory of Open Access Journals (Sweden)

    Karly M. Turner

    2013-07-01

    Full Text Available Schizophrenia is associated with many genetic and environmental risk factors and there is growing evidence that the interactions between genetic and environmental ‘hits’ are critical for disease onset. Animal models of schizophrenia have traditionally used specific strain and housing conditions to test potential risk factors. As the field moves towards testing gene (G x environment (E interactions the impact of these choices should be considered. Given the surge of research focused on cognitive deficits, we have examined studies of cognition in rodents from the perspective of GxE interactions, in which strain or housing manipulations have been varied. Behaviour is clearly altered by these factors, yet few animal models of schizophrenia have investigated cognitive deficits using different strain and housing conditions. It is important to recognise the large variation in behaviour observed when using different strain and housing combinations because GxE interactions may mask or exacerbate cognitive outcomes. Further consideration will improve our understanding of GxE interactions and the underlying neurobiology of cognitive impairments in neuropsychiatric disorders.

  5. Using the Weibull distribution reliability, modeling and inference

    CERN Document Server

    McCool, John I

    2012-01-01

    Understand and utilize the latest developments in Weibull inferential methods While the Weibull distribution is widely used in science and engineering, most engineers do not have the necessary statistical training to implement the methodology effectively. Using the Weibull Distribution: Reliability, Modeling, and Inference fills a gap in the current literature on the topic, introducing a self-contained presentation of the probabilistic basis for the methodology while providing powerful techniques for extracting information from data. The author explains the use of the Weibull distribution

  6. Understanding software faults and their role in software reliability modeling

    Science.gov (United States)

    Munson, John C.

    1994-01-01

    This study is a direct result of an on-going project to model the reliability of a large real-time control avionics system. In previous modeling efforts with this system, hardware reliability models were applied in modeling the reliability behavior of this system. In an attempt to enhance the performance of the adapted reliability models, certain software attributes were introduced in these models to control for differences between programs and also sequential executions of the same program. As the basic nature of the software attributes that affect software reliability become better understood in the modeling process, this information begins to have important implications on the software development process. A significant problem arises when raw attribute measures are to be used in statistical models as predictors, for example, of measures of software quality. This is because many of the metrics are highly correlated. Consider the two attributes: lines of code, LOC, and number of program statements, Stmts. In this case, it is quite obvious that a program with a high value of LOC probably will also have a relatively high value of Stmts. In the case of low level languages, such as assembly language programs, there might be a one-to-one relationship between the statement count and the lines of code. When there is a complete absence of linear relationship among the metrics, they are said to be orthogonal or uncorrelated. Usually the lack of orthogonality is not serious enough to affect a statistical analysis. However, for the purposes of some statistical analysis such as multiple regression, the software metrics are so strongly interrelated that the regression results may be ambiguous and possibly even misleading. Typically, it is difficult to estimate the unique effects of individual software metrics in the regression equation. The estimated values of the coefficients are very sensitive to slight changes in the data and to the addition or deletion of variables in the

  7. Reliable low precision simulations in land surface models

    Science.gov (United States)

    Dawson, Andrew; Düben, Peter D.; MacLeod, David A.; Palmer, Tim N.

    2017-12-01

    Weather and climate models must continue to increase in both resolution and complexity in order that forecasts become more accurate and reliable. Moving to lower numerical precision may be an essential tool for coping with the demand for ever increasing model complexity in addition to increasing computing resources. However, there have been some concerns in the weather and climate modelling community over the suitability of lower precision for climate models, particularly for representing processes that change very slowly over long time-scales. These processes are difficult to represent using low precision due to time increments being systematically rounded to zero. Idealised simulations are used to demonstrate that a model of deep soil heat diffusion that fails when run in single precision can be modified to work correctly using low precision, by splitting up the model into a small higher precision part and a low precision part. This strategy retains the computational benefits of reduced precision whilst preserving accuracy. This same technique is also applied to a full complexity land surface model, resulting in rounding errors that are significantly smaller than initial condition and parameter uncertainties. Although lower precision will present some problems for the weather and climate modelling community, many of the problems can likely be overcome using a straightforward and physically motivated application of reduced precision.

  8. Differential effects of subcutaneous electrical stimulation (SQS) and transcutaneous electrical nerve stimulation (TENS) in rodent models of chronic neuropathic or inflammatory pain.

    Science.gov (United States)

    Vera-Portocarrero, Louis P; Cordero, Toni; Billstrom, Tina; Swearingen, Kim; Wacnik, Paul W; Johanek, Lisa M

    2013-01-01

    Electrical stimulation has been used for many years for the treatment of pain. Present-day research demonstrates that stimulation targets and parameters impact the induction of specific pain-modulating mechanisms. New targets are increasingly being investigated clinically, but the scientific rationale for a particular target is often not well established. This present study compares the behavioral effects of targeting peripheral axons by electrode placement in the subcutaneous space vs. electrode placement on the surface of the skin in a rodent model. Rodent models of inflammatory and neuropathic pain were used to investigate subcutaneous electrical stimulation (SQS) vs. transcutaneous electrical nerve stimulation (TENS). Electrical parameters and relative location of the leads were held constant under each condition. SQS had cumulative antihypersensitivity effects in both inflammatory and neuropathic pain rodent models, with significant inhibition of mechanical hypersensitivity observed on days 3-4 of treatment. In contrast, reduction of thermal hyperalgesia in the inflammatory model was observed during the first four days of treatment with SQS, and reduction of cold allodynia in the neuropathic pain model was seen only on the first day with SQS. TENS was effective in the inflammation model, and in agreement with previous studies, tolerance developed to the antihypersensitivity effects of TENS. With the exception of a reversal of cold hypersensitivity on day 1 of testing, TENS did not reveal significant analgesic effects in the neuropathic pain rodent model. The results presented show that TENS and SQS have different effects that could point to unique biologic mechanisms underlying the analgesic effect of each therapy. Furthermore, this study is the first to demonstrate in an animal model that SQS attenuates neuropathic and inflammatory-induced pain behaviors. © 2013 Medtronic, Inc.

  9. Image-based in vivo assessment of targeting accuracy of stereotactic brain surgery in experimental rodent models

    Science.gov (United States)

    Rangarajan, Janaki Raman; Vande Velde, Greetje; van Gent, Friso; de Vloo, Philippe; Dresselaers, Tom; Depypere, Maarten; van Kuyck, Kris; Nuttin, Bart; Himmelreich, Uwe; Maes, Frederik

    2016-11-01

    Stereotactic neurosurgery is used in pre-clinical research of neurological and psychiatric disorders in experimental rat and mouse models to engraft a needle or electrode at a pre-defined location in the brain. However, inaccurate targeting may confound the results of such experiments. In contrast to the clinical practice, inaccurate targeting in rodents remains usually unnoticed until assessed by ex vivo end-point histology. We here propose a workflow for in vivo assessment of stereotactic targeting accuracy in small animal studies based on multi-modal post-operative imaging. The surgical trajectory in each individual animal is reconstructed in 3D from the physical implant imaged in post-operative CT and/or its trace as visible in post-operative MRI. By co-registering post-operative images of individual animals to a common stereotaxic template, targeting accuracy is quantified. Two commonly used neuromodulation regions were used as targets. Target localization errors showed not only variability, but also inaccuracy in targeting. Only about 30% of electrodes were within the subnucleus structure that was targeted and a-specific adverse effects were also noted. Shifting from invasive/subjective 2D histology towards objective in vivo 3D imaging-based assessment of targeting accuracy may benefit a more effective use of the experimental data by excluding off-target cases early in the study.

  10. Predictors of the nicotine reinforcement threshold, compensation, and elasticity of demand in a rodent model of nicotine reduction policy*

    Science.gov (United States)

    Grebenstein, Patricia E.; Burroughs, Danielle; Roiko, Samuel A.; Pentel, Paul R.; LeSage, Mark G.

    2015-01-01

    Background The FDA is considering reducing the nicotine content in tobacco products as a population-based strategy to reduce tobacco addiction. Research is needed to determine the threshold level of nicotine needed to maintain smoking and the extent of compensatory smoking that could occur during nicotine reduction. Sources of variability in these measures across sub-populations also need to be identified so that policies can take into account the risks and benefits of nicotine reduction in vulnerable populations. Methods The present study examined these issues in a rodent nicotine self- administration model of nicotine reduction policy to characterize individual differences in nicotine reinforcement thresholds, degree of compensation, and elasticity of demand during progressive reduction of the unit nicotine dose. The ability of individual differences in baseline nicotine intake and nicotine pharmacokinetics to predict responses to dose reduction was also examined. Results Considerable variability in the reinforcement threshold, compensation, and elasticity of demand was evident. High baseline nicotine intake was not correlated with the reinforcement threshold, but predicted less compensation and less elastic demand. Higher nicotine clearance predicted low reinforcement thresholds, greater compensation, and less elastic demand. Less elastic demand also predicted lower reinforcement thresholds. Conclusions These findings suggest that baseline nicotine intake, nicotine clearance, and the essential value of nicotine (i.e. elasticity of demand) moderate the effects of progressive nicotine reduction in rats and warrant further study in humans. They also suggest that smokers with fast nicotine metabolism may be more vulnerable to the risks of nicotine reduction. PMID:25891231

  11. Diet-induced obesity exacerbates metabolic and behavioral effects of polycystic ovary syndrome in a rodent model.

    Science.gov (United States)

    Ressler, Ilana B; Grayson, Bernadette E; Ulrich-Lai, Yvonne M; Seeley, Randy J

    2015-06-15

    Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age. Although a comorbidity of PCOS is obesity, many are lean. We hypothesized that increased saturated fat consumption and obesity would exacerbate metabolic and stress indices in a rodent model of PCOS. Female rats were implanted with the nonaromatizable androgen dihydrotestosterone (DHT) or placebo pellets prior to puberty. Half of each group was maintained ad libitum on either a high-fat diet (HFD; 40% butter fat calories) or nutrient-matched low-fat diet (LFD). Irrespective of diet, DHT-treated animals gained more body weight, had irregular cycles, and were glucose intolerant compared with controls on both diets. HFD/DHT animals had the highest levels of fat mass and insulin resistance. DHT animals demonstrated increased anxiety-related behavior in the elevated plus maze by decreased distance traveled and time in the open arms. HFD consumption increased immobility during the forced-swim test. DHT treatment suppressed diurnal corticosterone measurements in both diet groups. In parallel, DHT treatment significantly dampened stress responsivity to a mild stressor. Brains of DHT animals showed attenuated c-Fos activation in the ventromedial hypothalamus and arcuate nucleus; irrespective of DHT-treatment, however, all HFD animals had elevated hypothalamic paraventricular nucleus c-Fos activation. Whereas hyperandrogenism drives overall body weight gain, glucose intolerance, anxiety behaviors, and stress responsivity, HFD consumption exacerbates the effect of androgens on adiposity, insulin resistance, and depressive behaviors. Copyright © 2015 the American Physiological Society.

  12. Searching for the gut microbial contributing factors to social behavior in rodent models of autism spectrum disorder.

    Science.gov (United States)

    Needham, Brittany D; Tang, Weiyi; Wu, Wei-Li

    2018-05-01

    Social impairment is one of the major symptoms in multiple psychiatric disorders, including autism spectrum disorder (ASD). Accumulated studies indicate a crucial role for the gut microbiota in social development, but these mechanisms remain unclear. This review focuses on two strategies adopted to elucidate the complicated relationship between gut bacteria and host social behavior. In a top-down approach, researchers have attempted to correlate behavioral abnormalities with altered gut microbial profiles in rodent models of ASD, including BTBR mice, maternal immune activation (MIA), maternal valproic acid (VPA) and maternal high-fat diet (MHFD) offspring. In a bottom-up approach, researchers use germ-free (GF) animals, antibiotics, probiotics or pathogens to manipulate the intestinal environment and ascertain effects on social behavior. The combination of both approaches will hopefully pinpoint specific bacterial communities that control host social behavior. Further discussion of how brain development and circuitry is impacted by depletion of gut microbiota is also included. The converging evidence strongly suggests that gut microbes affect host social behavior through the alteration of brain neural circuits. Investigation of intestinal microbiota and host social behavior will unveil any bidirectional communication between the gut and brain and provide alternative therapeutic targets for ASD. © 2018 Wiley Periodicals, Inc. Develop Neurobiol 78: 474-499, 2018. © 2018 Wiley Periodicals, Inc.

  13. Intermittent Hypoxia and Stem Cell Implants Preserve Breathing Capacity in a Rodent Model of Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Nichols, Nicole L.; Gowing, Genevieve; Satriotomo, Irawan; Nashold, Lisa J.; Dale, Erica A.; Suzuki, Masatoshi; Avalos, Pablo; Mulcrone, Patrick L.; McHugh, Jacalyn

    2013-01-01

    Rationale: Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease causing paralysis and death from respiratory failure. Strategies to preserve and/or restore respiratory function are critical for successful treatment. Although breathing capacity is maintained until late in disease progression in rodent models of familial ALS (SOD1G93A rats and mice), reduced numbers of phrenic motor neurons and decreased phrenic nerve activity are observed. Decreased phrenic motor output suggests imminent respiratory failure. Objectives: To preserve or restore phrenic nerve activity in SOD1G93A rats at disease end stage. Methods: SOD1G93A rats were injected with human neural progenitor cells (hNPCs) bracketing the phrenic motor nucleus before disease onset, or exposed to acute intermittent hypoxia (AIH) at disease end stage. Measurements and Main Results: The capacity to generate phrenic motor output in anesthetized rats at disease end stage was: (1) transiently restored by a single presentation of AIH; and (2) preserved ipsilateral to hNPC transplants made before disease onset. hNPC transplants improved ipsilateral phrenic motor neuron survival. Conclusions: AIH-induced respiratory plasticity and stem cell therapy have complementary translational potential to treat breathing deficits in patients with ALS. PMID:23220913

  14. Clonidine reduces norepinephrine and improves bone marrow function in a rodent model of lung contusion, hemorrhagic shock, and chronic stress.

    Science.gov (United States)

    Alamo, Ines G; Kannan, Kolenkode B; Ramos, Harry; Loftus, Tyler J; Efron, Philip A; Mohr, Alicia M

    2017-03-01

    Propranolol has been shown previously to restore bone marrow function and improve anemia after lung contusion/hemorrhagic shock. We hypothesized that daily clonidine administration would inhibit central sympathetic outflow and restore bone marrow function in our rodent model of lung contusion/hemorrhagic shock with chronic stress. Male Sprague-Dawley rats underwent 6 days of restraint stress after lung contusion/hemorrhagic shock during which the animals received clonidine (75 μg/kg) after the restraint stress. On postinjury day 7, we assessed urine norepinephrine, blood hemoglobin, plasma granulocyte colony stimulating factor, and peripheral blood mobilization of hematopoietic progenitor cells, as well as bone marrow cellularity and erythroid progenitor cell growth. The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress significantly decreased urine norepinephrine levels, improved bone marrow cellularity, restored erythroid progenitor colony growth, and improved hemoglobin (14.1 ± 0.6 vs 10.8 ± 0.6 g/dL). The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress significantly decreased hematopoietic progenitor cells mobilization and restored granulocyte colony stimulating factor levels. After lung contusion/hemorrhagic shock with chronic restraint stress, daily administration of clonidine restored bone marrow function and improved anemia. Alleviating chronic stress and decreasing norepinephrine is a key therapeutic target to improve bone marrow function after severe injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Activation of Liver AMPK with PF-06409577 Corrects NAFLD and Lowers Cholesterol in Rodent and Primate Preclinical Models.

    Science.gov (United States)

    Esquejo, Ryan M; Salatto, Christopher T; Delmore, Jake; Albuquerque, Bina; Reyes, Allan; Shi, Yuji; Moccia, Rob; Cokorinos, Emily; Peloquin, Matthew; Monetti, Mara; Barricklow, Jason; Bollinger, Eliza; Smith, Brennan K; Day, Emily A; Nguyen, Chuong; Geoghegan, Kieran F; Kreeger, John M; Opsahl, Alan; Ward, Jessica; Kalgutkar, Amit S; Tess, David; Butler, Lynne; Shirai, Norimitsu; Osborne, Timothy F; Steinberg, Gregory R; Birnbaum, Morris J; Cameron, Kimberly O; Miller, Russell A

    2018-04-08

    Dysregulation of hepatic lipid and cholesterol metabolism is a significant contributor to cardiometabolic health, resulting in excessive liver lipid accumulation and ultimately non-alcoholic steatohepatitis (NASH). Therapeutic activators of the AMP-Activated Protein Kinase (AMPK) have been proposed as a treatment for metabolic diseases; we show that the AMPK β1-biased activator PF-06409577 is capable of lowering hepatic and systemic lipid and cholesterol levels in both rodent and monkey preclinical models. PF-06409577 is able to inhibit de novo lipid and cholesterol synthesis pathways, and causes a reduction in hepatic lipids and mRNA expression of markers of hepatic fibrosis. These effects require AMPK activity in the hepatocytes. Treatment of hyperlipidemic rats or cynomolgus monkeys with PF-06409577 for 6weeks resulted in a reduction in circulating cholesterol. Together these data suggest that activation of AMPK β1 complexes with PF-06409577 is capable of impacting multiple facets of liver disease and represents a promising strategy for the treatment of NAFLD and NASH in humans. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Usage models in reliability assessment of software-based systems

    Energy Technology Data Exchange (ETDEWEB)

    Haapanen, P.; Pulkkinen, U. [VTT Automation, Espoo (Finland); Korhonen, J. [VTT Electronics, Espoo (Finland)

    1997-04-01

    This volume in the OHA-project report series deals with the statistical reliability assessment of software based systems on the basis of dynamic test results and qualitative evidence from the system design process. Other reports to be published later on in the OHA-project report series will handle the diversity requirements in safety critical software-based systems, generation of test data from operational profiles and handling of programmable automation in plant PSA-studies. In this report the issues related to the statistical testing and especially automated test case generation are considered. The goal is to find an efficient method for building usage models for the generation of statistically significant set of test cases and to gather practical experiences from this method by applying it in a case study. The scope of the study also includes the tool support for the method, as the models may grow quite large and complex. (32 refs., 30 figs.).

  17. Reliability model for offshore wind farms; Paalidelighedsmodel for havvindmoelleparker

    Energy Technology Data Exchange (ETDEWEB)

    Christensen, P.; Lundtang Paulsen, J.; Lybech Toegersen, M.; Krogh, T. [Risoe National Lab., Roskilde (Denmark); Raben, N.; Donovan, M.H.; Joergensen, L. [SEAS (Denmark); Winther-Jensen, M.

    2002-05-01

    A method for the prediction of the mean availability for an offshore windfarm has been developed. Factors comprised are the reliability of the single turbine, the strategy for preventive maintenance the climate, the number of repair teams, and the type of boats available for transport. The mean availability is defined as the sum of the fractions of time, where each turbine is available for production. The project has been carried out together with SEAS Wind Technique, and their site Roedsand has been chosen as the example of the work. A climate model has been created based on actual site measurements. The prediction of the availability is done with a Monte Carlo-simulation. Software was developed for the preparation of the climate model from weather measurements as well as for the Monte carlo-simulation. Three examples have been simulated, one with guessed parametres, and the other two with parameters more close to the Roedsand case. (au)

  18. Usage models in reliability assessment of software-based systems

    International Nuclear Information System (INIS)

    Haapanen, P.; Pulkkinen, U.; Korhonen, J.

    1997-04-01

    This volume in the OHA-project report series deals with the statistical reliability assessment of software based systems on the basis of dynamic test results and qualitative evidence from the system design process. Other reports to be published later on in the OHA-project report series will handle the diversity requirements in safety critical software-based systems, generation of test data from operational profiles and handling of programmable automation in plant PSA-studies. In this report the issues related to the statistical testing and especially automated test case generation are considered. The goal is to find an efficient method for building usage models for the generation of statistically significant set of test cases and to gather practical experiences from this method by applying it in a case study. The scope of the study also includes the tool support for the method, as the models may grow quite large and complex. (32 refs., 30 figs.)

  19. Scalable Joint Models for Reliable Uncertainty-Aware Event Prediction.

    Science.gov (United States)

    Soleimani, Hossein; Hensman, James; Saria, Suchi

    2017-08-21

    Missing data and noisy observations pose significant challenges for reliably predicting events from irregularly sampled multivariate time series (longitudinal) data. Imputation methods, which are typically used for completing the data prior to event prediction, lack a principled mechanism to account for the uncertainty due to missingness. Alternatively, state-of-the-art joint modeling techniques can be used for jointly modeling the longitudinal and event data and compute event probabilities conditioned on the longitudinal observations. These approaches, however, make strong parametric assumptions and do not easily scale to multivariate signals with many observations. Our proposed approach consists of several key innovations. First, we develop a flexible and scalable joint model based upon sparse multiple-output Gaussian processes. Unlike state-of-the-art joint models, the proposed model can explain highly challenging structure including non-Gaussian noise while scaling to large data. Second, we derive an optimal policy for predicting events using the distribution of the event occurrence estimated by the joint model. The derived policy trades-off the cost of a delayed detection versus incorrect assessments and abstains from making decisions when the estimated event probability does not satisfy the derived confidence criteria. Experiments on a large dataset show that the proposed framework significantly outperforms state-of-the-art techniques in event prediction.

  20. A review of applied aspects of dealing with gut microbiota impact on rodent models

    DEFF Research Database (Denmark)

    Hansen, Axel Kornerup; Krych, Lukasz; Nielsen, Dennis Sandris

    2015-01-01

    -negative phylum Bacteroidetes. Other important phyla are the gram-negative phyla Proteobacteria and Verrucomicrobia, and the gram-positive phylum Actinobacteria. GM members influence models for diseases, such as inflammatory bowel diseases, allergies, autoimmunity, cancer, and neuropsychiatric diseases. GM...

  1. A Physiologically Based Pharmacokinetic Model for the Oxime TMB-4: Simulation of Rodent and Human Data

    Science.gov (United States)

    2013-01-13

    later, Garrigue and other colleagues (Maurizis et al. 1992) pub- lished an in vitro binding study of TMB-4 with rabbit cartilaginous tissue cultures...as well as fat, kidney, liver, rapidly perfused tissues and slowly perfused tissues . All tissue compartments are diffusion limited. Model...pharmacokinetic data from the literature. The model was parameterized using rat plasma, tissue and urine time course data from intramuscular administration, as

  2. Self-organised criticality in the evolution of a thermodynamic model of rodent thermoregulatory huddling.

    Directory of Open Access Journals (Sweden)

    Stuart P Wilson

    2017-01-01

    Full Text Available A thermodynamic model of thermoregulatory huddling interactions between endotherms is developed. The model is presented as a Monte Carlo algorithm in which animals are iteratively exchanged between groups, with a probability of exchanging groups defined in terms of the temperature of the environment and the body temperatures of the animals. The temperature-dependent exchange of animals between groups is shown to reproduce a second-order critical phase transition, i.e., a smooth switch to huddling when the environment gets colder, as measured in recent experiments. A peak in the rate at which group sizes change, referred to as pup flow, is predicted at the critical temperature of the phase transition, consistent with a thermodynamic description of huddling, and with a description of the huddle as a self-organising system. The model was subjected to a simple evolutionary procedure, by iteratively substituting the physiologies of individuals that fail to balance the costs of thermoregulation (by huddling in groups with the costs of thermogenesis (by contributing heat. The resulting tension between cooperative and competitive interactions was found to generate a phenomenon called self-organised criticality, as evidenced by the emergence of avalanches in fitness that propagate across many generations. The emergence of avalanches reveals how huddling can introduce correlations in fitness between individuals and thereby constrain evolutionary dynamics. Finally, a full agent-based model of huddling interactions is also shown to generate criticality when subjected to the same evolutionary pressures. The agent-based model is related to the Monte Carlo model in the way that a Vicsek model is related to an Ising model in statistical physics. Huddling therefore presents an opportunity to use thermodynamic theory to study an emergent adaptive animal behaviour. In more general terms, huddling is proposed as an ideal system for investigating the interaction

  3. An assessment of the effects of serotonin 6 (5-HT6) receptor antagonists in rodent models of learning.

    Science.gov (United States)

    Lindner, Mark D; Hodges, Donald B; Hogan, John B; Orie, Anitra F; Corsa, Jason A; Barten, Donna M; Polson, Craig; Robertson, Barbara J; Guss, Valerie L; Gillman, Kevin W; Starrett, John E; Gribkoff, Valentin K

    2003-11-01

    Antagonists of serotonin 6 (5-HT6) receptors have been reported to enhance cognition in animal models of learning, although this finding has not been universal. We have assessed the therapeutic potential of the specific 5-HT6 receptor antagonists 4-amino-N-(2,6-bis-methylamino-pyrimidin-4-yl)-benzenesulfonamide (Ro 04-6790) and 5-chloro-N-(4-methoxy-3-piperazin-1-yl-phenyl)-3-methyl-2-benzothiophenesulfonamide (SB-271046) in rodent models of cognitive function. Although mice express the 5-HT6 receptor and the function of this receptor has been investigated in mice, all reports of activity with 5-HT6 receptor antagonists have used rat models. In the present study, receptor binding revealed that the pharmacological properties of the mouse receptor are different from the rat and human receptor: Ro 04-6790 does not bind to the mouse 5-HT6 receptor, so all in vivo testing included in the present report was conducted in rats. We replicated previous reports that 5-HT6 receptor antagonists produce a stretching syndrome previously shown to be mediated through cholinergic mechanisms, but Ro 04-6790 and SB-271046 failed to attenuate scopolamine-induced deficits in a test of contextual fear conditioning. We also failed to replicate the significant effects reported previously in both an autoshaping task and in a version of the Morris water maze. The results of our experiments are not consistent with previous reports that suggested that 5-HT6 antagonists might have therapeutic potential for cognitive disorders.

  4. Electroacupuncture Promotes Recovery of Motor Function and Reduces Dopaminergic Neuron Degeneration in Rodent Models of Parkinson's Disease.

    Science.gov (United States)

    Lin, Jaung-Geng; Chen, Chao-Jung; Yang, Han-Bin; Chen, Yi-Hung; Hung, Shih-Ya

    2017-08-24

    Parkinson's disease (PD) is a common neurodegenerative disease. The pathological hallmark of PD is a progressive loss of dopaminergic neurons in the substantia nigra (SN) pars compacta in the brain, ultimately resulting in severe striatal dopamine deficiency and the development of primary motor symptoms (e.g., resting tremor, bradykinesia) in PD. Acupuncture has long been used in traditional Chinese medicine to treat PD for the control of tremor and pain. Accumulating evidence has shown that using electroacupuncture (EA) as a complementary therapy ameliorates motor symptoms of PD. However, the most appropriate timing for EA intervention and its effect on dopamine neuronal protection remain unclear. Thus, this study used the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model (systemic-lesioned by intraperitoneal injection) and the 1-methyl-4-phenylpyridinium (MPP⁺)-lesioned rat model (unilateral-lesioned by intra-SN infusion) of PD, to explore the therapeutic effects and mechanisms of EA at the GB34 (Yanglingquan) and LR3 (Taichong) acupoints. We found that EA increased the latency to fall from the accelerating rotarod and improved striatal dopamine levels in the MPTP studies. In the MPP⁺ studies, EA inhibited apomorphine induced rotational behavior and locomotor activity, and demonstrated neuroprotective effects via the activation of survival pathways of Akt and brain-derived neurotrophic factor (BDNF) in the SN region. In conclusion, we observed that EA treatment reduces motor symptoms of PD and dopaminergic neurodegeneration in rodent models, whether EA is given as a pretreatment or after the initiation of disease symptoms. The results indicate that EA treatment may be an effective therapy for patients with PD.

  5. Molecular Mechanism of Gastric Carcinogenesis in Helicobacter pylori-Infected Rodent Models

    Directory of Open Access Journals (Sweden)

    Takeshi Toyoda

    2014-06-01

    Full Text Available Since the discovery of Helicobacter pylori (H. pylori, many efforts have been made to establish animal models for the investigation of the pathological features and molecular mechanisms of gastric carcinogenesis. Among the animal models, Mongolian gerbils and mice are particularly useful for the analysis of H. pylori-associated inflammatory reactions and gastric cancer development. Inhibitors of oxidative stress, cyclooxygenase-2 (COX-2 and nuclear factor-κB, exert preventive effects on chronic gastritis and the development of adenocarcinomas in H. pylori-infected gerbils. Genetically-modified mouse models, including transgenic and knockout mice, have also revealed the importance of p53, COX-2/prostaglandin, Wnt/β-catenin, proinflammatory cytokines, gastrin and type III mucin in the molecular mechanisms of gastric carcinogenesis. Microarray technology is available for comprehensive gene analysis in the gastric mucosa of mouse models, and epigenetics, such as DNA methylation, could be an alternative approach to correlate the observations in animal models with the etiology in humans.

  6. An assessment of the utilization of the preclinical rodent model literature in clinical trials of putative therapeutics for the treatment of alcohol use disorders.

    Science.gov (United States)

    Barajaz, Ashley M; Kliethermes, Christopher L

    2017-12-01

    Rodent models of Alcohol Use Disorders (AUD) are used extensively by preclinical researchers to develop new therapeutics for the treatment of AUD. Although these models play an important role in the development of novel, targeted therapeutics, their role in bringing therapeutics to clinical trials is unclear, as off-label use of existing medications not approved for the treatment of AUD is commonly seen in the clinic and clinical trials. In the current study, we used the Clinicaltrials.gov database to obtain a list of drugs that have been tested for efficacy in a clinical trial between 1997 and 2017. We then conducted a set of literature searches to determine which of the 98 unique drugs we identified had shown efficacy in a rodent model of an AUD prior to being tested in a clinical trial. We found that slightly less than half of the drugs tested in clinical trials (48%) had shown prior efficacy in any rodent model of an AUD, while the remaining 52% of drugs were used off-label, or in some cases, following non-published studies. This study raises the question of how clinical researchers incorporate results from preclinical studies in the decision to bring a drug to a clinical trial. Our results underscore the need for ongoing communication among preclinical and clinical researchers. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Application of proteomics in the study of rodent models of cancer

    DEFF Research Database (Denmark)

    Terp, Mikkel Green; Ditzel, Henrik J

    2014-01-01

    The molecular and cellular mechanisms underlying the multistage processes of cancer progression and metastasis are complex and strictly depend on the interplay between tumor cells and surrounding tissues. Identification of protein aberrations in cancer pathophysiology requires a physiologically r......, and monitoring of cancer progression and treatment response. Central to such studies is the ability to ensure at an early stage that the identified proteins are of clinical relevance by examining relevant specimens from larger cohorts of cancer patients.......The molecular and cellular mechanisms underlying the multistage processes of cancer progression and metastasis are complex and strictly depend on the interplay between tumor cells and surrounding tissues. Identification of protein aberrations in cancer pathophysiology requires a physiologically...... relevant experimental model. The mouse offers such a model to identify protein changes associated with tumor initiation and progression, metastasis development, tumor/microenvironment interplay, and treatment responses. Furthermore, the mouse model offers the ability to collect samples at any stage...

  8. Effect of the new antiepileptic drug retigabine in a rodent model of mania

    DEFF Research Database (Denmark)

    Dencker, Ditte; Dias, Rebecca; Pedersen, Mette Lund

    2008-01-01

    Bipolar spectrum disorders are severe chronic mood disorders that are characterized by episodes of mania or hypomania and depression. Because patients with manic symptoms often experience clinical benefit from treatment with anticonvulsant drugs, it was hypothesized that retigabine, a novel...... compound with anticonvulsant efficacy, may also possess antimanic activity. The amphetamine (AMPH)+chlordiazepoxide (CDP)-induced hyperactivity model has been proposed as a suitable model for studying antimanic-like activity of novel compounds in mice and rats. The aims of the present study in rats were...

  9. reliability reliability

    African Journals Online (AJOL)

    eobe

    Corresponding author, Tel: +234-703. RELIABILITY .... V , , given by the code of practice. However, checks must .... an optimization procedure over the failure domain F corresponding .... of Concrete Members based on Utility Theory,. Technical ...

  10. Reliability assessment using degradation models: bayesian and classical approaches

    Directory of Open Access Journals (Sweden)

    Marta Afonso Freitas

    2010-04-01

    Full Text Available Traditionally, reliability assessment of devices has been based on (accelerated life tests. However, for highly reliable products, little information about reliability is provided by life tests in which few or no failures are typically observed. Since most failures arise from a degradation mechanism at work for which there are characteristics that degrade over time, one alternative is monitor the device for a period of time and assess its reliability from the changes in performance (degradation observed during that period. The goal of this article is to illustrate how degradation data can be modeled and analyzed by using "classical" and Bayesian approaches. Four methods of data analysis based on classical inference are presented. Next we show how Bayesian methods can also be used to provide a natural approach to analyzing degradation data. The approaches are applied to a real data set regarding train wheels degradation.Tradicionalmente, o acesso à confiabilidade de dispositivos tem sido baseado em testes de vida (acelerados. Entretanto, para produtos altamente confiáveis, pouca informação a respeito de sua confiabilidade é fornecida por testes de vida no quais poucas ou nenhumas falhas são observadas. Uma vez que boa parte das falhas é induzida por mecanismos de degradação, uma alternativa é monitorar o dispositivo por um período de tempo e acessar sua confiabilidade através das mudanças em desempenho (degradação observadas durante aquele período. O objetivo deste artigo é ilustrar como dados de degradação podem ser modelados e analisados utilizando-se abordagens "clássicas" e Bayesiana. Quatro métodos de análise de dados baseados em inferência clássica são apresentados. A seguir, mostramos como os métodos Bayesianos podem também ser aplicados para proporcionar uma abordagem natural à análise de dados de degradação. As abordagens são aplicadas a um banco de dados real relacionado à degradação de rodas de trens.

  11. Global and 3D Spatial Assessment of Neuroinflammation in Rodent Models of Multiple Sclerosis

    DEFF Research Database (Denmark)

    Gupta, Shashank; Utoft, Regine Egeholm; Hasseldam, Henrik

    2013-01-01

    Multiple Sclerosis (MS) is a progressive autoimmune inflammatory and demyelinating disease of the central nervous system (CNS). T cells play a key role in the progression of neuroinflammation in MS and also in the experimental autoimmune encephalomyelitis (EAE) animal models for the disease. A te...

  12. "Asparagus Racemosus" Enhances Memory and Protects against Amnesia in Rodent Models

    Science.gov (United States)

    Ojha, Rakesh; Sahu, Alakh N.; Muruganandam, A. V.; Singh, Gireesh Kumar; Krishnamurthy, Sairam

    2010-01-01

    "Asparagus Racemosus" (AR) is an Ayurvedic rasayana possessing multiple neuropharmacological activities. The adpatogenic and antidepressant activity of AR is well documented. The present study was undertaken to assess nootropic and anti-amnesic activities of MAR in rats. The Morris water maze (MWM) and elevated plus maze (EPM) models were employed…

  13. Impact of the gut microbiota on rodent models of human disease.

    Science.gov (United States)

    Hansen, Axel Kornerup; Hansen, Camilla Hartmann Friis; Krych, Lukasz; Nielsen, Dennis Sandris

    2014-12-21

    Traditionally bacteria have been considered as either pathogens, commensals or symbionts. The mammal gut harbors 10(14) organisms dispersed on approximately 1000 different species. Today, diagnostics, in contrast to previous cultivation techniques, allow the identification of close to 100% of bacterial species. This has revealed that a range of animal models within different research areas, such as diabetes, obesity, cancer, allergy, behavior and colitis, are affected by their gut microbiota. Correlation studies may for some diseases show correlation between gut microbiota composition and disease parameters higher than 70%. Some disease phenotypes may be transferred when recolonizing germ free mice. The mechanistic aspects are not clear, but some examples on how gut bacteria stimulate receptors, metabolism, and immune responses are discussed. A more deeper understanding of the impact of microbiota has its origin in the overall composition of the microbiota and in some newly recognized species, such as Akkermansia muciniphila, Segmented filamentous bacteria and Faecalibacterium prausnitzii, which seem to have an impact on more or less severe disease in specific models. Thus, the impact of the microbiota on animal models is of a magnitude that cannot be ignored in future research. Therefore, either models with specific microbiota must be developed, or the microbiota must be characterized in individual studies and incorporated into data evaluation.

  14. A Dialogue about MCQs, Reliability, and Item Response Modelling

    Science.gov (United States)

    Wright, Daniel B.; Skagerberg, Elin M.

    2006-01-01

    Multiple choice questions (MCQs) are becoming more common in UK psychology departments and the need to assess their reliability is apparent. Having examined the reliability of MCQs in our department we faced many questions from colleagues about why we were examining reliability, what it was that we were doing, and what should be reported when…

  15. Ketamine is a potent antidepressant in two rodent models of depression

    DEFF Research Database (Denmark)

    Mathe, A.; Sousa, V.; Fischer, C. W.

    2013-01-01

    pathophysiological factor and converging evidence indicates that other systems, such as the glutamatergic are of paramount importance. Indeed, work at the Yale University, NIMH, and Icahn School of Medicine at Mount Sinai demonstrated the marked antidepressant effects of intravenously infused ketamine to treatment...... resistant patients diagnosed with major depressive disorder. In order to better understand the mechanisms of ketamine effects we decided to test it on animal models. Methods: All experiments were approved by the Karolinska Institutet's Committee for Animal Protection. Two rat models, bred at the Karolinska...... Institutet, the Flinders Sensitive Line (FSL) and their controls, the Flinders Resistant Line (FRL), and the SERT KO (homozygous, heterozygous, and the wild type rats) were used. Male animals were injected 10 mg ketamine/kg body weight or vehicle and the Open Field Test (OF) and Forced Swim Test (FST...

  16. Mechanisms underlying weight loss and metabolic improvements in rodent models of bariatric surgery

    Science.gov (United States)

    Arble, Deanna M.; Sandoval, Darleen A.; Seeley, Randy J.

    2014-01-01

    Obesity is a growing health risk with few successful treatment options and fewer still that target both obesity and obesity-associated comorbidities. Despite ongoing scientific efforts, the most effective treatment option to date was not developed from basic research but by surgeons observing outcomes in the clinic. Bariatric surgery is the most successful treatment for significant weight loss, resolution of type 2 diabetes and the prevention of future weight gain. Recent work with animal models has shed considerable light on the molecular underpinnings of the potent effects of these ‘metabolic’ surgical procedures. Here we review data from animal models and how these studies have evolved our understanding of the critical signalling systems that mediate the effects of bariatric surgery. These insights could lead to alternative therapies able to accomplish effects similar to bariatric surgery in a less invasive manner. PMID:25374275

  17. The fitness of drug-resistant malaria parasites in a rodent model: multiplicity of infection

    OpenAIRE

    Huijben, Silvie; Sim, Derek G.; Nelson, William, A.; Read, Andrew F.

    2011-01-01

    Malaria infections normally consist of more than one clonally-replicating lineage. Within-host interactions between sensitive and resistant parasites can have profound effects on the evolution of drug resistance. Here, using the Plasmodium chabaudi mouse malaria model, we ask whether the costs and benefits of resistance are affected by the number of co-infecting strains competing with a resistant clone. We found strong competitive suppression of resistant parasites in untreated infections and...

  18. Synergistic interactions between paracetamol and oxcarbazepine in somatic and visceral pain models in rodents.

    Science.gov (United States)

    Tomić, Maja A; Vucković, Sonja M; Stepanović-Petrović, Radica M; Ugresić, Nenad D; Prostran, Milica S; Bosković, Bogdan

    2010-04-01

    Combination therapy is a valid approach in pain treatment, in which a reduction of doses could reduce side effects and still achieve optimal analgesia. We examined the effects of coadministered paracetamol, a widely used non-opioid analgesic, and oxcarbazepine, a relatively novel anticonvulsant with analgesic properties, in a rat model of paw inflammatory hyperalgesia and in a mice model of visceral pain and determined the type of interaction between components. The effects of paracetamol, oxcarbazepine, and their combinations were examined in carrageenan-induced (0.1 mL, 1%) paw inflammatory hyperalgesia in rats and in an acetic acid-induced (10 mg/kg, 0.75%) writhing test in mice. In both models, drugs were coadministered in fixed-dose fractions of the 50% effective dose (ED(50)), and type of interaction was determined by isobolographic analysis. Paracetamol (50-200 mg/kg peroral), oxcarbazepine (40-160 mg/kg peroral), and their combination (1/8, 1/4, 1/3, and 1/2 of a single drug ED(50)) produced a significant, dose-dependent antihyperalgesia in carrageenan-injected rats. In the writhing test in mice, paracetamol (60-180 mg/kg peroral), oxcarbazepine (20-80 mg/kg peroral), and their combination (1/16, 1/8, 1/4, and 1/2 of a single drug ED(50)) significantly and dose dependently reduced the number of writhes. In both models, isobolographic analysis revealed a significant synergistic interaction between paracetamol and oxcarbazepine, with a >4-fold reduction of doses of both drugs in combination, compared with single drugs ED(50). The synergistic interaction between paracetamol and oxcarbazepine provides new information about combination pain treatment and should be explored further in patients, especially with somatic and/or visceral pain.

  19. In vivo 3-dimensional photoacoustic imaging of the renal vasculature in preclinical rodent models

    OpenAIRE

    Ogunlade, O.; Connell, J. J.; Huang, J. L.; Zhang, E.; Lythgoe, M. F.; Long, D. A.; Beard, P.

    2017-01-01

    Non-invasive imaging of the kidney vasculature in preclinical murine models is important for studying renal development, diseases and evaluating new therapies, but is challenging to achieve using existing imaging modalities. Photoacoustic imaging is a promising new technique that is particularly well suited to visualising the vasculature and could provide an alternative to existing preclinical imaging methods for studying renal vascular anatomy and function. To investigate this, an all-optica...

  20. Impaired brain glymphatic flow in a rodent model of chronic liver disease and minimal hepatic encephalopathy

    OpenAIRE

    Lythgoe, Mark; Hosford, Patrick; Arias, Natalia; Gallego-Duran, Rocio; Hadjihambi, Anna; Jalan, Rajiv; Gourine, Alexander; Habtesion, Abeba; Davies, Nathan; Harrison, Ian

    2017-01-01

    Neuronal function is exquisitely sensitive to alterations in extracellular environment. In patients with hepatic encephalopathy (HE), accumulation of metabolic waste products and noxious substances in the interstitial fluid of the brain may contribute to neuronal dysfunction and cognitive impairment. In a rat model of chronic liver disease, we used an emerging dynamic contrast-enhanced MRI technique to assess the efficacy of the glymphatic system, which facilitates clearance of solutes from t...

  1. Effects of Simulated Smog Atmospheres in Rodent Models of Metabolic and Immunologic Dysfunction.

    Science.gov (United States)

    McGee Hargrove, Marie; Snow, Samantha J; Luebke, Robert W; Wood, Charles E; Krug, Jonathan D; Krantz, Q Todd; King, Charly; Copeland, Carey B; McCullough, Shaun D; Gowdy, Kymberly M; Kodavanti, Urmila P; Gilmour, M Ian; Gavett, Stephen H

    2018-03-06

    Air pollution is a diverse and dynamic mixture of gaseous and particulate matter, limiting our understanding of associated adverse health outcomes. The biological effects of two simulated smog atmospheres (SA) with different compositions but similar air quality health indexes were compared in a nonobese diabetic rat model (Goto-Kakizaki, GK) and three mouse immune models (house dust mite (HDM) allergy, antibody response to heat-killed pneumococcus, and resistance to influenza A infection). In GK rats, both SA-PM (high particulate matter) and SA-O 3 (high ozone) decreased cholesterol levels immediately after a 4-h exposure, whereas only SA-O 3 increased airflow limitation. Airway responsiveness to methacholine was increased in HDM-allergic mice compared with nonallergic mice, but exposure to SA-PM or SA-O 3 did not significantly alter responsiveness. Exposure to SA-PM did not affect the IgM response to pneumococcus, and SA-O 3 did not affect virus titers, although inflammatory cytokine levels were decreased in mice infected at the end of a 7-day exposure. Collectively, acute SA exposures produced limited health effects in animal models of metabolic and immune diseases. Effects of SA-O 3 tended to be greater than those of SA-PM, suggesting that gas-phase components in photochemically derived multipollutant mixtures may be of greater concern than secondary organic aerosol PM.

  2. Hippocampal oscillations in the rodent model of schizophrenia induced by amygdala GABA receptor blockade

    Directory of Open Access Journals (Sweden)

    Tope eLanre-Amos

    2010-09-01

    Full Text Available Brain oscillations are critical for cognitive processes, and their alterations in schizophrenia have been proposed to contribute to cognitive impairments. Network oscillations rely upon GABAergic interneurons, which also show characteristic changes in schizophrenia. The aim of this study was to examine the capability of hippocampal networks to generate oscillations in a rat model previously shown to reproduce the stereotypic structural alterations of the hippocampal interneuron circuit seen in schizophrenic patients. This model uses injection of GABA-A receptor antagonist picrotoxin into the basolateral amygdala which causes cell-type specific disruption of interneuron signaling in the hippocampus. We found that after such treatment, hippocampal theta rhythm was still present during REM sleep, locomotion, and exploration of novel environment and could be elicited under urethane anesthesia. Subtle changes in theta and gamma parameters were observed in both preparations; specifically in the stimulus intensity—theta frequency relationship under urethane and in divergent reactions of oscillations at the two major theta dipoles in freely moving rats. Thus, theta power in the CA1 region was generally enhanced as compared with deep theta dipole which decreased or did not change. The results indicate that pathologic reorganization of interneurons that follows the over-activation of the amygdala-hippocampal pathway, as shown for this model of schizophrenia, does not lead to destruction of the oscillatory circuit but changes the normal balance of rhythmic activity in its various compartments.

  3. Diurnal rodents as animal models of human central vision: characterisation of the retina of the sand rat Psammomys obsesus.

    Science.gov (United States)

    Saïdi, Tounès; Mbarek, Sihem; Chaouacha-Chekir, Rafika Ben; Hicks, David

    2011-07-01

    Cone photoreceptor-based central vision is of paramount importance in human eyesight, and the increasing numbers of persons affected by macular degeneration emphasizes the need for relevant and amenable animal models. Although laboratory mice and rats have provided valuable information on retinal diseases, they have inherent limitations for studies on macular pathology. In the present study, we extend our recent analyses of diurnal murid rodents to demonstrate that the sand rat Psammomys obesus has a remarkably cone-rich retina, and represents a useful adjunct to available animal models of central vision. Adult P. obesus were captured and transferred to animal facilities where they were maintained under standard light/dark cycles. Animals were euthanised and their eyes enucleated. Tissue was either fixed in paraformaldehyde and prepared for immunohistochemistry, or solubilized in lysis buffer and separated by SDS-PAGE and subjected to western blot analysis. Samples were labelled with a battery of antibodies against rod and cone photoreceptors, inner retinal neurones, and glia. P. obesus showed a high percentage of cones, 41% of total photoreceptor numbers in both central and peripheral retina. They expressed multiple cone-specific proteins, including short and medium-wavelength opsin and cone transducin. A second remarkable feature of the retina concerned the horizontal cells, which expressed high levels of glial fibrillar acidic protein and occludin, two proteins which are not seen in other species. The retina of P. obesus displays high numbers of morphologically and immunologically identifiable cones which will facilitate analysis of cone pathophysiology in this species. The unusual horizontal cell phenotype may be related to the cone distribution or to an alternative facet of the animals lifestyle.

  4. Clinical correlates to assist with chronic traumatic encephalopathy diagnosis: Insights from a novel rodent repeat concussion model.

    Science.gov (United States)

    Thomsen, Gretchen M; Ko, Ara; Harada, Megan Y; Ma, Annie; Wyss, Livia; Haro, Patricia; Vit, Jean-Philippe; Avalos, Pablo; Dhillon, Navpreet K; Cho, Noell; Shelest, Oksana; Ley, Eric J

    2017-06-01

    Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repetitive head injuries. Chronic traumatic encephalopathy symptoms include changes in mood, behavior, cognition, and motor function; however, CTE is currently diagnosed only postmortem. Using a rat model of recurrent traumatic brain injury (TBI), we demonstrate rodent deficits that predict the severity of CTE-like brain pathology. Bilateral, closed-skull, mild TBI was administered once per week to 35 wild-type rats; eight rats received two injuries (2×TBI), 27 rats received five injuries (5×TBI), and 13 rats were sham controls. To determine clinical correlates for CTE diagnosis, TBI rats were separated based on the severity of rotarod deficits and classified as "mild" or "severe" and further separated into "acute," "short," and "long" based on age at euthanasia (90, 144, and 235 days, respectively). Brain atrophy, phosphorylated tau, and inflammation were assessed. All eight 2×TBI cases had mild rotarod deficiency, 11 5×TBI cases had mild deficiency, and 16 cases had severe deficiency. In one cohort of rats, tested at approximately 235 days of age, balance, rearing, and grip strength were significantly worse in the severe group relative to both sham and mild groups. At the acute time period, cortical thinning, phosphorylated tau, and inflammation were not observed in either TBI group, whereas corpus callosum thinning was observed in both TBI groups. At later time points, atrophy, tau pathology, and inflammation were increased in mild and severe TBI groups in the cortex and corpus callosum, relative to sham controls. These injury effects were exacerbated over time in the severe TBI group in the corpus callosum. Our model of repeat mild TBI suggests that permanent deficits in specific motor function tests correlate with CTE-like brain pathology. Assessing balance and motor coordination over time may predict CTE diagnosis.

  5. Numerical Model based Reliability Estimation of Selective Laser Melting Process

    DEFF Research Database (Denmark)

    Mohanty, Sankhya; Hattel, Jesper Henri

    2014-01-01

    Selective laser melting is developing into a standard manufacturing technology with applications in various sectors. However, the process is still far from being at par with conventional processes such as welding and casting, the primary reason of which is the unreliability of the process. While...... of the selective laser melting process. A validated 3D finite-volume alternating-direction-implicit numerical technique is used to model the selective laser melting process, and is calibrated against results from single track formation experiments. Correlation coefficients are determined for process input...... parameters such as laser power, speed, beam profile, etc. Subsequently, uncertainties in the processing parameters are utilized to predict a range for the various outputs, using a Monte Carlo method based uncertainty analysis methodology, and the reliability of the process is established....

  6. Development of NMR imaging using CEST agents: application to brain tumor in a rodent model

    International Nuclear Information System (INIS)

    Flament, J.

    2012-01-01

    The study aimed at developing saturation transfer imaging of lipoCEST contrast agents for the detection of angiogenesis in a U87 mouse brain tumor model. A lipoCEST with a sensitivity threshold of 100 pM in vitro was optimized in order to make it compatible with CEST imaging in vivo. Thanks to the development of an experimental setup dedicated to CEST imaging, we evaluated lipoCEST to detect specifically tumor angiogenesis. We demonstrated for the first time that lipoCEST visualization was feasible in vivo in a mouse brain after intravenous injection. Moreover, the integrin α v β 3 over expressed during tumor angiogenesis can be specifically targeted using a functionalized lipoCEST with RGD peptide. The specific association between the RGD-lipoCEST and its target α v β 3 was confirmed by immunohistochemical data and fluorescence microscopy. Finally, in order to tend to a molecular imaging protocol by CEST-MRI, we developed a quantification tool of lipoCEST contrast agents. This tool is based on modeling of proton exchange processes in vivo. By taking into account both B0 and B1 fields inhomogeneities which can dramatically alter CEST contrast, we showed that the accuracy of our quantification tool was 300 pM in vitro. The tool was applied on in vivo data acquired on the U87 mouse model and the maximum concentration of RGD-lipoCEST linked to their molecular targets was evaluated to 1.8 nM. (author) [fr

  7. Peer pressures: Social instability stress in adolescence and social deficits in adulthood in a rodent model

    Directory of Open Access Journals (Sweden)

    Cheryl M. McCormick

    2015-02-01

    Full Text Available Studies in animal models generate and test hypotheses regarding developmental stage-specific vulnerability that might inform research questions about human development. In both rats and humans, peer relationships are qualitatively different in adolescence than at other stages of development, and social experiences in adolescence are considered important determinants of adult social function. This review describes our adolescent rat social instability stress model and the long-lasting effects social instability has on social behaviour in adulthood as well as the possible neural underpinnings. Effects of other adolescent social stress experiences in rats on social behaviours in adulthood also are reviewed. We discuss the role of hypothalamic–pituitary–adrenal (HPA function and glucocorticoid release in conferring differential susceptibility to social experiences in adolescents compared to adults. We propose that although differential perception of social experiences rather than immature HPA function may underlie the heightened vulnerability of adolescents to social instability, the changes in the trajectory of brain development and resultant social deficits likely are mediated by the heightened glucocorticoid release in response to repeated social stressors in adolescence compared to in adulthood.

  8. Translational relevance of rodent models of hypothalamic-pituitary-adrenal function and stressors in adolescence

    Directory of Open Access Journals (Sweden)

    Cheryl M. McCormick

    2017-02-01

    Full Text Available Elevations in glucocorticoids that result from environmental stressors can have programming effects on brain structure and function when the exposure occurs during sensitive periods that involve heightened neural development. In recent years, adolescence has gained increasing attention as another sensitive period of development, a period in which pubertal transitions may increase the vulnerability to stressors. There are similarities in physical and behavioural development between humans and rats, and rats have been used effectively as an animal model of adolescence and the unique plasticity of this period of ontogeny. This review focuses on benefits and challenges of rats as a model for translational research on hypothalamic-pituitary-adrenal (HPA function and stressors in adolescence, highlighting important parallels and contrasts between adolescent rats and humans, and we review the main stress procedures that are used in investigating HPA stress responses and their consequences in adolescence in rats. We conclude that a greater focus on timing of puberty as a factor in research in adolescent rats may increase the translational relevance of the findings.

  9. Translational Assays for Assessment of Cognition in Rodent Models of Alzheimer's Disease and Dementia.

    Science.gov (United States)

    Shepherd, A; Tyebji, S; Hannan, A J; Burrows, E L

    2016-11-01

    Cognitive dysfunction appears as a core feature of dementia, which includes its most prevalent form, Alzheimer's disease (AD), as well as vascular dementia, frontotemporal dementia, and other brain disorders. AD alone affects more than 45 million people worldwide, with growing prevalence in aging populations. There is no cure, and therapeutic options remain limited. Gene-edited and transgenic animal models, expressing disease-specific gene mutations, illuminate pathogenic mechanisms leading to cognitive decline in AD and other forms of dementia. To date, cognitive tests in AD mouse models have not been directly relevant to the clinical presentation of AD, providing challenges for translation of findings to the clinic. Touchscreen testing in mice has enabled the assessment of specific cognitive domains in mice that are directly relevant to impairments described in human AD patients. In this review, we provide context for how cognitive decline is measured in the clinic, describe traditional methods for assessing cognition in mice, and outline novel approaches, including the use of the touchscreen platform for cognitive testing. We highlight the limitations of traditional memory-testing paradigms in mice, particularly their capacity for direct translation into cognitive testing of patients. While it is not possible to expect direct translation in testing methodologies, we can aim to develop tests that engage similar neural substrates in both humans and mice. Ultimately, that would enable us to better predict efficacy across species and therefore improve the chances that a treatment that works in mice will also work in the clinic.

  10. Treatment of amblyopia in the adult: insights from a new rodent model of visual perceptual learning.

    Science.gov (United States)

    Bonaccorsi, Joyce; Berardi, Nicoletta; Sale, Alessandro

    2014-01-01

    Amblyopia is the most common form of impairment of visual function affecting one eye, with a prevalence of about 1-5% of the total world population. Amblyopia usually derives from conditions of early functional imbalance between the two eyes, owing to anisometropia, strabismus, or congenital cataract, and results in a pronounced reduction of visual acuity and severe deficits in contrast sensitivity and stereopsis. It is widely accepted that, due to a lack of sufficient plasticity in the adult brain, amblyopia becomes untreatable after the closure of the critical period in the primary visual cortex. However, recent results obtained both in animal models and in clinical trials have challenged this view, unmasking a previously unsuspected potential for promoting recovery even in adulthood. In this context, non invasive procedures based on visual perceptual learning, i.e., the improvement in visual performance on a variety of simple visual tasks following practice, emerge as particularly promising to rescue discrimination abilities in adult amblyopic subjects. This review will survey recent work regarding the impact of visual perceptual learning on amblyopia, with a special focus on a new experimental model of perceptual learning in the amblyopic rat.

  11. Treatment of amblyopia in the adult: insights from a new rodent model of visual perceptual learning

    Science.gov (United States)

    Bonaccorsi, Joyce; Berardi, Nicoletta; Sale, Alessandro

    2014-01-01

    Amblyopia is the most common form of impairment of visual function affecting one eye, with a prevalence of about 1–5% of the total world population. Amblyopia usually derives from conditions of early functional imbalance between the two eyes, owing to anisometropia, strabismus, or congenital cataract, and results in a pronounced reduction of visual acuity and severe deficits in contrast sensitivity and stereopsis. It is widely accepted that, due to a lack of sufficient plasticity in the adult brain, amblyopia becomes untreatable after the closure of the critical period in the primary visual cortex. However, recent results obtained both in animal models and in clinical trials have challenged this view, unmasking a previously unsuspected potential for promoting recovery even in adulthood. In this context, non invasive procedures based on visual perceptual learning, i.e., the improvement in visual performance on a variety of simple visual tasks following practice, emerge as particularly promising to rescue discrimination abilities in adult amblyopic subjects. This review will survey recent work regarding the impact of visual perceptual learning on amblyopia, with a special focus on a new experimental model of perceptual learning in the amblyopic rat. PMID:25076874

  12. Optogenetic delay of status epilepticus onset in an in vivo rodent epilepsy model.

    Directory of Open Access Journals (Sweden)

    Inna Sukhotinsky

    Full Text Available Epilepsy is a devastating disease, currently treated with medications, surgery or electrical stimulation. None of these approaches is totally effective and our ability to control seizures remains limited and complicated by frequent side effects. The emerging revolutionary technique of optogenetics enables manipulation of the activity of specific neuronal populations in vivo with exquisite spatiotemporal resolution using light. We used optogenetic approaches to test the role of hippocampal excitatory neurons in the lithium-pilocarpine model of acute elicited seizures in awake behaving rats. Hippocampal pyramidal neurons were transduced in vivo with a virus carrying an enhanced halorhodopsin (eNpHR, a yellow light activated chloride pump, and acute seizure progression was then monitored behaviorally and electrophysiologically in the presence and absence of illumination delivered via an optical fiber. Inhibition of those neurons with illumination prior to seizure onset significantly delayed electrographic and behavioral initiation of status epilepticus, and altered the dynamics of ictal activity development. These results reveal an essential role of hippocampal excitatory neurons in this model of ictogenesis and illustrate the power of optogenetic approaches for elucidation of seizure mechanisms. This early success in controlling seizures also suggests future therapeutic avenues.

  13. Examination of Gelatinase Isoforms in Rodent Models of Acute Neurodegenerative Diseases Using Two-Dimensional Zymography.

    Science.gov (United States)

    Chen, Shanyan; Meng, Fanjun; Chen, Zhenzhou; Qu, Zhe; Cui, Jiankun; Gu, Zezong

    2017-01-01

    Pathological activation of gelatinases (matrix metalloproteinase-2 and -9; MMP-2/-9) has been shown to cause a number of detrimental outcomes in neurodegenerative diseases. In gel gelatin zymography is a highly sensitive methodology commonly used in revealing levels of gelatinase activity and in separating the proform and active form of gelatinases, based on their different molecular weights. However, this methodology is inadequate in resolving complex enzyme isoforms, because gelatinase expression and activity can be regulated at transcriptional and/or post-translational levels under in vivo conditions resulting in alternation of their isoelectric focusing (IEF) points. In this chapter, we describe an advanced methodology, termed two-dimensional zymography, combining IEF with zymographic electrophoresis under non-reducing conditions to achieve significant improvement in separation of the gelatinase isoforms in both cell-based and in vivo models for acute brain injuries and neuroinflammation.

  14. Abnormal stress responsivity in a rodent developmental disruption model of schizophrenia.

    Science.gov (United States)

    Zimmerman, Eric C; Bellaire, Mark; Ewing, Samuel G; Grace, Anthony A

    2013-10-01

    Although numerous studies have implicated stress in the pathophysiology of schizophrenia, less is known about how the effects of stress interact with genetic, developmental, and/or environmental determinants to promote disease progression. In particular, it has been proposed that in humans, stress exposure in adolescence could combine with a predisposition towards increased stress sensitivity, leading to prodromal symptoms and eventually psychosis. However, the neurobiological substrates for this interaction are not fully characterized. Previous work in our lab has demonstrated that rats born to dams administered with the DNA-methylating agent methylazoxymethanol acetate (MAM) at gestational day 17 exhibit as adults behavioral and anatomical abnormalities consistent with those observed in patients with schizophrenia. Here, we examined behavioral and neuroendocrine responses to stress in the MAM model of schizophrenia. MAM-treated male rats were exposed to acute and repeated footshock stress at prepubertal, peripubteral, and adult ages. Ultrasonic vocalizations (USVs), freezing, and corticosterone responses were quantified. We found that juvenile MAM-treated rats emitted significantly more calls, spent more time vocalizing, emitted calls at a higher rate, and showed more freezing in response to acute footshock stress when compared with their saline (SAL) treated counterparts, and that this difference is not present in older animals. In addition, adolescent MAM-treated animals displayed a blunted HPA axis corticosterone response to acute footshock that did not adapt after 10 days of stress exposure. These data demonstrate abnormal stress responsivity in the MAM model of schizophrenia and suggest that these animals are more sensitive to the effects of stress in youth.

  15. Kartogenin treatment prevented joint degeneration in a rodent model of osteoarthritis: A pilot study.

    Science.gov (United States)

    Mohan, Geetha; Magnitsky, Sergey; Melkus, Gerd; Subburaj, Karupppasamy; Kazakia, Galateia; Burghardt, Andrew J; Dang, Alexis; Lane, Nancy E; Majumdar, Sharmila

    2016-10-01

    Osteoarthritis (OA) is a major degenerative joint disease characterized by progressive loss of articular cartilage, synovitis, subchondral bone changes, and osteophyte formation. Currently there is no treatment for OA except temporary pain relief and end-stage joint replacement surgery. We performed a pilot study to determine the effect of kartogenin (KGN, a small molecule) on both cartilage and subchondral bone in a rat model of OA using multimodal imaging techniques. OA was induced in rats (OA and KGN treatment group) by anterior cruciate ligament transection (ACLT) surgery in the right knee joint. Sham surgery was performed on the right knee joint of control group rats. KGN group rats received weekly intra-articular injection of 125 μM KGN 1 week after surgery until week 12. All rats underwent in vivo magnetic resonance imaging (MRI) at 3, 6, and 12 weeks after surgery. Quantitative MR relaxation measures (T 1ρ and T 2 ) were determined to evaluate changes in articular cartilage. Cartilage and bone turnover markers (COMP and CTX-I) were determined at baseline, 3, 6, and 12 weeks. Animals were sacrificed at week 12 and the knee joints were removed for micro-computed tomography (micro-CT) and histology. KGN treatment significantly lowered the T 1ρ and T 2 relaxation times indicating decreased cartilage degradation. KGN treatment significantly decreased COMP and CTX-I levels indicating decreased cartilage and bone turnover rate. KGN treatment also prevented subchondral bone changes in the ACLT rat model of OA. Thus, kartogenin is a potential drug to prevent joint deterioration in post-traumatic OA. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1780-1789, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  16. Measuring Motivation and Reward-Related Decision Making in the Rodent Operant Touchscreen System.

    Science.gov (United States)

    Heath, Christopher J; Phillips, Benjamin U; Bussey, Timothy J; Saksida, Lisa M

    2016-01-04

    This unit is designed to facilitate implementation of the fixed and progressive ratio paradigms and the effort-related choice task in the rodent touchscreen apparatus to permit direct measurement of motivation and reward-related decision making in this equipment. These protocols have been optimized for use in the mouse and reliably yield stable performance levels that can be enhanced or suppressed by systemic pharmacological manipulation. Instructions are also provided for the adjustment of task parameters to permit use in mouse models of neurodegenerative disease. These tasks expand the utility of the rodent touchscreen apparatus beyond the currently available battery of cognitive assessment paradigms. Copyright © 2016 John Wiley & Sons, Inc.

  17. Altered Right Ventricular Mechanical Properties Are Afterload Dependent in a Rodent Model of Bronchopulmonary Dysplasia

    Directory of Open Access Journals (Sweden)

    Jitandrakumar R. Patel

    2017-10-01

    Full Text Available Infants born premature are at increased risk for development of bronchopulmonary dysplasia (BPD, pulmonary hypertension (PH, and ultimately right ventricular (RV dysfunction, which together carry a high risk of neonatal mortality. However, the role alveolar simplification and abnormal pulmonary microvascular development in BPD affects RV contractile properties is unknown. We used a rat model of BPD to examine the effect of hyperoxia-induced PH on RV contractile properties. We measured in vivo RV pressure as well as passive force, maximum Ca2+ activated force, calcium sensitivity of force (pCa50 and rate of force redevelopment (ktr in RV skinned trabeculae isolated from hearts of 21-and 35-day old rats pre-exposed to 21% oxygen (normoxia or 85% oxygen (hyperoxia for 14 days after birth. Systolic and diastolic RV pressure were significantly higher at day 21 in hyperoxia exposed rats compared to normoxia control rats, but normalized by 35 days of age. Passive force, maximum Ca2+ activated force, and calcium sensitivity of force were elevated and cross-bridge cycling kinetics depressed in 21-day old hyperoxic trabeculae, whereas no differences between normoxic and hyperoxic trabeculae were seen at 35 days. Myofibrillar protein analysis revealed that 21-day old hyperoxic trabeculae had increased levels of beta-myosin heavy chain (β-MHC, atrial myosin light chain 1 (aMLC1; often referred to as essential light chain, and slow skeletal troponin I (ssTnI compared to age matched normoxic trabeculae. On the other hand, 35-day old normoxic and hyperoxic trabeculae expressed similar level of α- and β-MHC, ventricular MLC1 and predominantly cTnI. These results suggest that neonatal exposure to hyperoxia increases RV afterload and affect both the steady state and dynamic contractile properties of the RV, likely as a result of hyperoxia-induced expression of β-MHC, delayed transition of slow skeletal TnI to cardiac TnI, and expression of atrial MLC1. These

  18. Adrenomedulline improves ischemic left colonic anastomotic healing in an experimental rodent model

    Directory of Open Access Journals (Sweden)

    Oguzhan Karatepe

    2011-01-01

    Full Text Available BACKGROUND: Leakage from colonic anastomosis is a major complication causing increased mortality and morbidity. Ischemia is a well-known cause of this event. This study was designed to investigate the effects of adrenomedullin on the healing of ischemic colon anastomosis in a rat model. METHODS: Standardized left colon resection 3 cm above the peritoneal reflection and colonic anastomosis were performed in 40 Wistar rats that were divided into four groups. To mimic ischemia, the mesocolon was ligated 2 cm from either side of the anastomosis in all of the groups. The control groups (1 and 2 received no further treatment. The experimental groups (3 and 4 received adrenomedullin treatment. Adrenomedullin therapy was started in the perioperative period in group 3 and 4 rats (the therapeutic groups. Group 1 and group 3 rats were sacrificed on postoperative day 3. Group 2 and group 4 rats were sacrificed on postoperative day 7. After careful relaparotomy, bursting pressure, hydroxyproline, malondialdehyde, interleukin 6, nitric oxide, vascular endothelial growth factor, and tumor necrosis factor alpha levels were measured. Histopathological characteristics of the anastomosis were analyzed. RESULTS: The group 3 animals had a significantly higher bursting pressure than group 1 (p<0.05. Hydroxyproline levels in group 1 were significantly lower than in group 3 (p<0.05. The mean bursting pressure was significantly different between group 2 and group 4 (p<0.05. Hydroxyproline levels in groups 3 and 4 were significantly increased by adrenomedullin therapy relative to the control groups (p<0.05. When all groups were compared, malondialdehyde and nitric oxide were significantly lower in the control groups (p<0.05. When vascular endothelial growth factor levels were compared, no statistically significant difference between groups was observed. Interleukin 6 and tumor necrosis factor alpha were significantly decreased by adrenomedullin therapy (p<0.05. The

  19. Modeling high-Power Accelerators Reliability-SNS LINAC (SNS-ORNL); MAX LINAC (MYRRHA)

    International Nuclear Information System (INIS)

    Pitigoi, A. E.; Fernandez Ramos, P.

    2013-01-01

    Improving reliability has recently become a very important objective in the field of particle accelerators. The particle accelerators in operation are constantly undergoing modifications, and improvements are implemented using new technologies, more reliable components or redundant schemes (to obtain more reliability, strength, more power, etc.) A reliability model of SNS (Spallation Neutron Source) LINAC has been developed within MAX project and analysis of the accelerator systems reliability has been performed within the MAX project, using the Risk Spectrum reliability analysis software. The analysis results have been evaluated by comparison with the SNS operational data. Results and conclusions are presented in this paper, oriented to identify design weaknesses and provide recommendations for improving reliability of MYRRHA linear accelerator. The SNS reliability model developed for the MAX preliminary design phase indicates possible avenues for further investigation that could be needed to improve the reliability of the high-power accelerators, in view of the future reliability targets of ADS accelerators.

  20. Evaluating North American Electric Grid Reliability Using the Barabasi-Albert Network Model

    OpenAIRE

    Chassin, David P.; Posse, Christian

    2004-01-01

    The reliability of electric transmission systems is examined using a scale-free model of network structure and failure propagation. The topologies of the North American eastern and western electric networks are analyzed to estimate their reliability based on the Barabasi-Albert network model. A commonly used power system reliability index is computed using a simple failure propagation model. The results are compared to the values of power system reliability indices previously obtained using s...

  1. Role of dopaminergic and serotonergic neurotransmitters in behavioral alterations observed in rodent model of hepatic encephalopathy.

    Science.gov (United States)

    Dhanda, Saurabh; Sandhir, Rajat

    2015-06-01

    The present study was designed to evaluate the role of biogenic amines in behavioral alterations observed in rat model of hepatic encephalopathy (HE) following bile duct ligation (BDL). Male Wistar rats subjected to BDL developed biliary fibrosis after four weeks which was supported by altered liver function tests, increased ammonia levels and histological staining (Sirius red). Animals were assessed for their behavioral performance in terms of cognitive, anxiety and motor functions. The levels of dopamine (DA), serotonin (5-HT), epinephrine and norepinephrine (NE) were estimated in different regions of brain viz. cortex, hippocampus, striatum and cerebellum using HPLC along with activity of monoamine oxidase (MAO). Cognitive assessment of BDL rats revealed a progressive decline in learning, memory formation, retrieval, exploration of novel environment and spontaneous locomotor activity along with decrease in 5-HT and NE levels. This was accompanied by an increase in MAO activity. Motor functions of BDL rats were also altered which were evident from decrease in the time spent on the rotating rod and higher foot faults assessed using narrow beam walk task. A global decrease was observed in the DA content along with an increase in MAO activity. Histopathological studies using hematoxylin-eosin (H&E) and cresyl violet exhibited marked neuronal degeneration, wherein neurons appeared more pyknotic, condensed and damaged. The results reveal that dopaminergic and serotonergic pathways are disturbed in chronic liver failure post-BDL which may be responsible for behavioral impairments observed in HE. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Consequences of adolescent use of alcohol and other drugs: Studies using rodent models

    Science.gov (United States)

    Spear, Linda Patia

    2016-01-01

    Studies using animal models of adolescent exposure to alcohol, nicotine, cannabinoids, and the stimulants cocaine, 3,4-Methylenedioxymethampethamine and methamphetamine have revealed a variety of persisting neural and behavioral consequences. Affected brain regions often include mesolimbic and prefrontal regions undergoing notable ontogenetic change during adolescence, although it is unclear whether this represents areas of specific vulnerability or particular scrutiny to date. Persisting alterations in forebrain systems critical for modulating reward, socioemotional processing and cognition have emerged, including apparent induction of a hyper-dopaminergic state with some drugs and/or attenuations in neurons expressing cholinergic markers. Disruptions in cognitive functions such as working memory, alterations in affect including increases in social anxiety, and mixed evidence for increases in later drug self-administration have also been reported. When consequences of adolescent and adult exposure were compared, adolescents were generally found to be more vulnerable to alcohol, nicotine, and cannabinoids, but generally not to stimulants. More work is needed to determine how adolescent drug exposure influences sculpting of the adolescent brain, and provide approaches to prevent/reverse these effects. PMID:27484868

  3. Kynurenine–3–monooxygenase inhibition prevents multiple organ failure in rodent models of acute pancreatitis

    Science.gov (United States)

    Mole, Damian J; Webster, Scott P; Uings, Iain; Zheng, Xiaozhong; Binnie, Margaret; Wilson, Kris; Hutchinson, Jonathan P; Mirguet, Olivier; Walker, Ann; Beaufils, Benjamin; Ancellin, Nicolas; Trottet, Lionel; Bénéton, Véronique; Mowat, Christopher G; Wilkinson, Martin; Rowland, Paul; Haslam, Carl; McBride, Andrew; Homer, Natalie ZM; Baily, James E; Sharp, Matthew GF; Garden, O James; Hughes, Jeremy; Howie, Sarah EM; Holmes, Duncan S; Liddle, John; Iredale, John P

    2015-01-01

    Acute pancreatitis (AP) is a common and devastating inflammatory condition of the pancreas that is considered to be a paradigm of sterile inflammation leading to systemic multiple organ dysfunction syndrome (MODS) and death1,2 Acute mortality from AP-MODS exceeds 20%3 and for those who survive the initial episode, their lifespan is typically shorter than the general population4. There are no specific therapies available that protect individuals against AP-MODS. Here, we show that kynurenine-3-monooxygenase (KMO), a key enzyme of tryptophan metabolism5, is central to the pathogenesis of AP-MODS. We created a mouse strain deficient for Kmo with a robust biochemical phenotype that protected against extrapancreatic tissue injury to lung, kidney and liver in experimental AP-MODS. A medicinal chemistry strategy based on modifications of the kynurenine substrate led to the discovery of GSK180 as a potent and specific inhibitor of KMO. The binding mode of the inhibitor in the active site was confirmed by X-ray co-crystallography at 3.2 Å resolution. Treatment with GSK180 resulted in rapid changes in levels of kynurenine pathway metabolites in vivo and afforded therapeutic protection against AP-MODS in a rat model of AP. Our findings establish KMO inhibition as a novel therapeutic strategy in the treatment of AP-MODS and open up a new area for drug discovery in critical illness. PMID:26752518

  4. Kynurenine-3-monooxygenase inhibition prevents multiple organ failure in rodent models of acute pancreatitis.

    Science.gov (United States)

    Mole, Damian J; Webster, Scott P; Uings, Iain; Zheng, Xiaozhong; Binnie, Margaret; Wilson, Kris; Hutchinson, Jonathan P; Mirguet, Olivier; Walker, Ann; Beaufils, Benjamin; Ancellin, Nicolas; Trottet, Lionel; Bénéton, Véronique; Mowat, Christopher G; Wilkinson, Martin; Rowland, Paul; Haslam, Carl; McBride, Andrew; Homer, Natalie Z M; Baily, James E; Sharp, Matthew G F; Garden, O James; Hughes, Jeremy; Howie, Sarah E M; Holmes, Duncan S; Liddle, John; Iredale, John P

    2016-02-01

    Acute pancreatitis (AP) is a common and devastating inflammatory condition of the pancreas that is considered to be a paradigm of sterile inflammation leading to systemic multiple organ dysfunction syndrome (MODS) and death. Acute mortality from AP-MODS exceeds 20% (ref. 3), and the lifespans of those who survive the initial episode are typically shorter than those of the general population. There are no specific therapies available to protect individuals from AP-MODS. Here we show that kynurenine-3-monooxygenase (KMO), a key enzyme of tryptophan metabolism, is central to the pathogenesis of AP-MODS. We created a mouse strain that is deficient for Kmo (encoding KMO) and that has a robust biochemical phenotype that protects against extrapancreatic tissue injury to the lung, kidney and liver in experimental AP-MODS. A medicinal chemistry strategy based on modifications of the kynurenine substrate led to the discovery of the oxazolidinone GSK180 as a potent and specific inhibitor of KMO. The binding mode of the inhibitor in the active site was confirmed by X-ray co-crystallography at 3.2 Å resolution. Treatment with GSK180 resulted in rapid changes in the levels of kynurenine pathway metabolites in vivo, and it afforded therapeutic protection against MODS in a rat model of AP. Our findings establish KMO inhibition as a novel therapeutic strategy in the treatment of AP-MODS, and they open up a new area for drug discovery in critical illness.

  5. Competitive release and facilitation of drug-resistant parasites after therapeutic chemotherapy in a rodent malaria model

    Science.gov (United States)

    Wargo, A.R.; Huijben, S.; De Roode, J. C.; Shepherd, J.; Read, A.F.

    2007-01-01

    Malaria infections frequently consist of mixtures of drug-resistant and drug-sensitive parasites. If crowding occurs, where clonal population densities are suppressed by the presence of coinfecting clones, removal of susceptible clones by drug treatment could allow resistant clones to expand into the newly vacated niche space within a host. Theoretical models show that, if such competitive release occurs, it can be a potent contributor to the strength of selection, greatly accelerating the rate at which resistance spreads in a population. A variety of correlational field data suggest that competitive release could occur in human malaria populations, but direct evidence cannot be ethically obtained from human infections. Here we show competitive release after pyrimethamine curative chemotherapy of acute infections of the rodent malaria Plasmodium chabaudi in laboratory mice. The expansion of resistant parasite numbers after treatment resulted in enhanced transmission-stage densities. After the elimination or near-elimination of sensitive parasites, the number of resistant parasites increased beyond that achieved when a competitor had never been present. Thus, a substantial competitive release occurred, markedly elevating the fitness advantages of drug resistance above those arising from survival alone. This finding may explain the rapid spread of drug resistance and the subsequently brief useful lifespans of some antimalarial drugs. In a second experiment, where subcurative chemotherapy was administered, the resistant clone was only partly released from competitive suppression and experienced a restriction in the size of its expansion after treatment. This finding raises the prospect of harnessing in-host ecology to slow the spread of drug resistance. ?? 2007 by The National Academy of Sciences of the USA.

  6. Sustained neuroprotection from a single intravitreal injection of PGJ2 in a rodent model of anterior ischemic optic neuropathy.

    Science.gov (United States)

    Touitou, Valerie; Johnson, Mary A; Guo, Yan; Miller, Neil R; Bernstein, Steven L

    2013-11-11

    Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common cause of sudden optic nerve-related vision loss in persons older than 50 in the United States. There currently is no treatment for this disorder. We previously showed that systemic administration of 15-deoxy, delta (12, 14) prostaglandin J2 (PGJ2) is neuroprotective in our rodent model of AION (rAION). In this study, we determined if a single intravitreal (IVT) injection of PGJ2 is neuroprotective after rAION, and if this method of administration is toxic to the retina, optic nerve, or both. TOXICITY was assessed after a single IVT injection of PGJ2 in one eye and PBS in the contralateral eye of normal, adult Long-Evans rats. EFFICACY was assessed by inducing rAION in one eye and injecting either PGJ2 or vehicle immediately following induction, with the fellow eye serving as naïve control. Visual evoked potentials (VEPs) and ERGs were performed before induction and at specific intervals thereafter. Animals were euthanized 30 days after induction, after which immunohistochemistry, transmission electron microscopy, and quantitative stereology of retinal ganglion cell (RGC) numbers were performed. IVT PGJ2 did not alter the VEP or ERG compared with PBS-injected control eyes, and neither IVT PGJ2 nor PBS reduced overall RGC numbers. IVT PGJ2 preserved VEP amplitude, reduced optic nerve edema, and resulted in significant preservation of RGCs and axons in eyes with rAION. A single IVT injection of PGJ2 is nontoxic to the retina and optic nerve and neuroprotective when given immediately after rAION induction.

  7. Predictors of the nicotine reinforcement threshold, compensation, and elasticity of demand in a rodent model of nicotine reduction policy.

    Science.gov (United States)

    Grebenstein, Patricia E; Burroughs, Danielle; Roiko, Samuel A; Pentel, Paul R; LeSage, Mark G

    2015-06-01

    The FDA is considering reducing the nicotine content in tobacco products as a population-based strategy to reduce tobacco addiction. Research is needed to determine the threshold level of nicotine needed to maintain smoking and the extent of compensatory smoking that could occur during nicotine reduction. Sources of variability in these measures across sub-populations also need to be identified so that policies can take into account the risks and benefits of nicotine reduction in vulnerable populations. The present study examined these issues in a rodent nicotine self-administration model of nicotine reduction policy to characterize individual differences in nicotine reinforcement thresholds, degree of compensation, and elasticity of demand during progressive reduction of the unit nicotine dose. The ability of individual differences in baseline nicotine intake and nicotine pharmacokinetics to predict responses to dose reduction was also examined. Considerable variability in the reinforcement threshold, compensation, and elasticity of demand was evident. High baseline nicotine intake was not correlated with the reinforcement threshold, but predicted less compensation and less elastic demand. Higher nicotine clearance predicted low reinforcement thresholds, greater compensation, and less elastic demand. Less elastic demand also predicted lower reinforcement thresholds. These findings suggest that baseline nicotine intake, nicotine clearance, and the essential value of nicotine (i.e. elasticity of demand) moderate the effects of progressive nicotine reduction in rats and warrant further study in humans. They also suggest that smokers with fast nicotine metabolism may be more vulnerable to the risks of nicotine reduction. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Echinocandin treatment of pneumocystis pneumonia in rodent models depletes cysts leaving trophic burdens that cannot transmit the infection.

    Directory of Open Access Journals (Sweden)

    Melanie T Cushion

    2010-01-01

    Full Text Available Fungi in the genus Pneumocystis cause pneumonia (PCP in hosts with debilitated immune systems and are emerging as co-morbidity factors associated with chronic diseases such as COPD. Limited therapeutic choices and poor understanding of the life cycle are a result of the inability of these fungi to grow outside the mammalian lung. Within the alveolar lumen, Pneumocystis spp., appear to have a bi-phasic life cycle consisting of an asexual phase characterized by binary fission of trophic forms and a sexual cycle resulting in formation of cysts, but the life cycle stage that transmits the infection is not known. The cysts, but not the trophic forms, express beta -1,3-D-glucan synthetase and contain abundant beta -1,3-D-glucan. Here we show that therapeutic and prophylactic treatment of PCP with echinocandins, compounds which inhibit the synthesis of beta -1,3-D-glucan, depleted cysts in rodent models of PCP, while sparing the trophic forms which remained in significant numbers. Survival was enhanced in the echincandin treated mice, likely due to the decreased beta -1,3-D-glucan content in the lungs of treated mice and rats which coincided with reductions of cyst numbers, and dramatic remodeling of organism morphology. Strong evidence for the cyst as the agent of transmission was provided by the failure of anidulafungin-treated mice to transmit the infection. We show for the first time that withdrawal of anidulafungin treatment with continued immunosuppression permitted the repopulation of cyst forms. Treatment of PCP with an echinocandin alone will not likely result in eradication of infection and cessation of echinocandin treatment while the patient remains immunosuppressed could result in relapse. Importantly, the echinocandins provide novel and powerful chemical tools to probe the still poorly understood bi-phasic life cycle of this genus of fungal pathogens.

  9. Improvement of mesh recolonization in abdominal wall reconstruction with adipose vs. bone marrow mesenchymal stem cells in a rodent model.

    Science.gov (United States)

    van Steenberghe, M; Schubert, T; Guiot, Y; Goebbels, R M; Gianello, P

    2017-08-01

    Reconstruction of muscle defects remains a challenge. Our work assessed the potential of an engineered construct made of a human acellular collagen matrix (HACM) seeded with porcine mesenchymal stem cells (MSCs) to reconstruct abdominal wall muscle defects in a rodent model. This study compared 2 sources of MSCs (bone-marrow, BMSCs, and adipose, ASCs) in vitro and in vivo for parietal defect reconstruction. Cellular viability and growth factor release (VEGF, FGF-Beta, HGF, IGF-1, TGF-Beta) were investigated under normoxic/hypoxic culture conditions. Processed and recellularized HACMs were mechanically assessed. The construct was tested in vivo in full thickness abdominal wall defect treated with HACM alone vs. HACM+ASCs or BMSCs (n=14). Tissue remodeling was studied at day 30 for neo-angiogenesis and muscular reconstruction. A significantly lower secretion of IGF was observed with ASCs vs. BMSCs under hypoxic conditions (-97.6%, p<0.005) whereas significantly higher VEGF/FGF secretions were found with ASCs (+92%, p<0.001 and +72%, p<0.05, respectively). Processing and recellularization did not impair the mechanical properties of the HACM. In vivo, angiogenesis and muscle healing were significantly improved by the HACM+ASCs in comparison to BMSCs (p<0.05) at day 30. A composite graft made of an HACM seeded with ASCs can improve muscle repair by specific growth factor release in hypoxic conditions and by in vivo remodeling (neo-angiogenesis/graft integration) while maintaining mechanical properties. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Immunomodulatory and antioxidant function of albumin stabilises the endothelium and improves survival in a rodent model of chronic liver failure.

    Science.gov (United States)

    Garcia-Martinez, Rita; Andreola, Fausto; Mehta, Gautam; Poulton, Katie; Oria, Marc; Jover, Maria; Soeda, Junpei; Macnaughtan, Jane; De Chiara, Francesco; Habtesion, Abeba; Mookerjee, Rajeshwar P; Davies, Nathan; Jalan, Rajiv

    2015-04-01

    Liver failure is characterized by endothelial dysfunction, which results in hemodynamic disturbances leading to renal failure. Albumin infusion improves hemodynamics and prevents renal dysfunction in advance liver failure. These effects are only partly explained by the oncotic properties of albumin. This study was designed to test the hypothesis that albumin exerts its beneficial effects by stabilising endothelial function. In vivo: systemic hemodynamics, renal function, markers of endothelial dysfunction (ADMA) and inflammation were studied in analbuminaemic and Sprague-Dawley rats, 6-weeks after sham/bile duct ligation surgery. In vitro: human umbilical vein endothelial cells were stimulated with LPS with or without albumin. We studied protein expression and gene expression of adhesion molecules, intracellular reactive oxygen species, and cell stress markers. Compared to controls, analbuminaemic rats had significantly greater hemodynamic deterioration after bile duct ligation, resulting in worse renal function and shorter survival. This was associated with significantly greater plasma renin activity, worse endothelial function, and disturbed inflammatory response. In vitro studies showed that albumin was actively taken up by endothelial cells. Incubation of albumin pre-treated endothelial cells with LPS was associated with significantly less activation compared with untreated cells, decreased intracellular reactive oxygen species, and markers of cell stress. These results show, for the first time, that absence of albumin is characterised by worse systemic hemodynamics, renal function and higher mortality in a rodent model of chronic liver failure and illustrates the important non-oncotic properties of albumin in protecting against endothelial dysfunction. Copyright © 2015. Published by Elsevier B.V.

  11. Identification of early indicators of altered metabolism in normal development using a rodent model system

    Directory of Open Access Journals (Sweden)

    Ashok Daniel Prabakaran

    2018-03-01

    Full Text Available Although the existence of a close relationship between the early maternal developmental environment, fetal size at birth and the risk of developing disease in adulthood has been suggested, most studies, however, employed experimentally induced intrauterine growth restriction as a model to link this with later adult disease. Because embryonic size variation also occurs under normal growth and differentiation, elucidating the molecular mechanisms underlying these changes and their relevance to later adult disease risk becomes important. The birth weight of rat pups vary according to the uterine horn positions. Using birth weight as a marker, we compared two groups of rat pups – lower birth weight (LBW, 5th to 25th percentile and average birth weight (ABW, 50th to 75th percentile – using morphological, biochemical and molecular biology, and genetic techniques. Our results show that insulin metabolism, Pi3k/Akt and Pparγ signaling and the genes regulating growth and metabolism are significantly different in these groups. Methylation at the promoter of the InsII (Ins2 gene and DNA methyltransferase 1 in LBW pups are both increased. Additionally, the Dnmt1 repressor complex, which includes Hdac1, Rb (Rb1 and E2f1, was also upregulated in LBW pups. We conclude that the Dnmt1 repressor complex, which regulates the restriction point of the cell cycle, retards the rate at which cells traverse the G1 or G0 phase of the cell cycle in LBW pups, thereby slowing down growth. This regulatory mechanism mediated by Dnmt1 might contribute to the production of small-size pups and altered physiology and pathology in adult life.

  12. Effects of Vitamin D Treatment on Skeletal Muscle Histology and Ultrastructural Changes in a Rodent Model

    Directory of Open Access Journals (Sweden)

    Sobhy M. Yakout

    2012-07-01

    Full Text Available Vitamin D is well known for its role in maintaining calcium and phosphorus homeostasis and in promoting bone mineralization; however, more of its pleiotropic effects have been described recently. The aim of the present investigation was to study the effect of vitamin D treatment on skeletal muscles changes under different dietary conditions using an animal model. Four groups of C57BL/6J mice (n = 11 each were maintained on either low fat diet (LFD or high fat diet ‎‎(HFD with and without 1α,25–dihydroxyvitamin D3 (calcitriol for 16 weeks. Animal weigh was recorded at baseline and then regular intervals, and at the end of the study, skeletal muscle tissues were harvested for the evaluation of the histopathological and ultrastructural changes. When control C57BL/6J mice were fed high-fat diet for 12 weeks, body weight gain was significantly increased compared with mice fed a LFD. (30.2% vs. 8.4%, p < 0.01. There was a significant gradual decrease in the weight of HFD fed mice that were treated with vitamin D as compared with a steady increase in the weights of controls (6.8% vs. 28.7%, p < 0.01. While the LFD group showed some ultrastructural changes, HDF fed on mice showed great muscle structural abnormalities. The whole sarcosome along with its membrane and cristae were severely damaged with scattered myocytes in HFD group. Furthermore, the mitochondria appeared weak and were on the verge of degenerations. The bands were diminished with loss of connections among myofibrils. These changes were attenuated in the HFD group treated with vitamin D with tissues have regained their normal structural appearance. The current findings indicate an important effect of vitamin D on skeletal muscle histology under HFD conditions.

  13. Sexually dimorphic effects of unpredictable early life adversity on visceral pain behavior in a rodent model.

    Science.gov (United States)

    Chaloner, Aaron; Greenwood-Van Meerveld, Beverley

    2013-03-01

    Visceral pain is the hallmark feature of irritable bowel syndrome (IBS), a gastrointestinal disorder, which is more commonly diagnosed in women. Female IBS patients frequently report a history of early life adversity (ELA); however, sex differences in ELA-induced visceral pain and the role of ovarian hormones have yet to be investigated. Therefore, we tested the hypothesis that ELA induces visceral hypersensitivity through a sexually dimorphic mechanism mediated via estradiol. As a model of ELA, neonatal rats were exposed to different pairings of an odor and shock to control for trauma predictability. In adulthood, visceral sensitivity was assessed via a visceromotor response to colorectal distension. Following ovariectomy and estradiol replacement in a separate group of rats, the visceral sensitivity was quantified. We found that females that received unpredictable odor-shock developed visceral hypersensitivity in adulthood. In contrast, visceral sensitivity was not significantly different following ELA in adult males. Ovariectomy reversed visceral hypersensitivity following unpredictable ELA, whereas estradiol replacement reestablished visceral hypersensitivity in the unpredictable group. This study is the first to show sex-related differences in visceral sensitivity following unpredictable ELA. Our data highlight the activational effect of estradiol as a pivotal mechanism in maintaining visceral hypersensitivity. This article directly implicates a critical role for ovarian hormones in maintaining visceral hypersensitivity following ELA, specifically identifying the activational effect of estradiol as a key modulator of visceral sensitivity. These data suggest that ELA induces persistent functional abdominal pain in female IBS patients through an estrogen-dependent mechanism. Copyright © 2013 American Pain Society. All rights reserved.

  14. Embryonic kidney function in a chronic renal failure model in rodents.

    Science.gov (United States)

    Fujimoto, Eisuke; Yamanaka, Shuichiro; Kurihara, Sho; Tajiri, Susumu; Izuhara, Luna; Katsuoka, Yuichi; Yokote, Shinya; Matsumoto, Kei; Kobayashi, Eiji; Okano, Hirotaka James; Chikaraishi, Tatsuya; Yokoo, Takashi

    2017-08-01

    Rapid advancements have been made in alternative treatments for renal diseases. Our goal for renal regeneration is to establish a kidney graft derived from human embryonic tissues. In this study, we investigated the effects of host renal failure on the structure and activity of transplanted embryonic kidney and bladder, and found that diuretics effectively induced urine production in the transplanted kidney. Uremic conditions were reproduced using a 5/6 renal infarction rat model. An embryonic kidney plus bladder (embryonic day 15) was isolated from a pregnant Lewis rat and transplanted into the para-aortic area of a 5/6 renal-infarcted Lewis rat. Following growth, the embryonic bladder was successfully anastomosed to the host ureter. We assessed graft function in terms of survival rates and found no differences between normal (n = 5) and renal failure (n = 8) groups (median survival: 70.5 vs 74.5 h; p = 0.331) in terms of survival, indicating that the grafts prolonged rat survival, even under renal failure conditions. Furosemide (n = 9) significantly increased urine volume compared with saline-treated controls (n = 7; p < 0.05), confirming that the grafts were functional. We also demonstrated the possibilities of an in vivo imaging system for determining the viability of transplanted embryonic kidney with bladder. The results of this study demonstrate that transplanted embryonic kidney and bladder can grow and function effectively, even under uremic conditions.

  15. Glycoprotein 130 receptor signaling mediates α-cell dysfunction in a rodent model of type 2 diabetes

    DEFF Research Database (Denmark)

    Chow, Samuel Z; Speck, Madeleine; Yoganathan, Piriya

    2014-01-01

    Dysregulated glucagon secretion accompanies islet inflammation in type 2 diabetes. We recently discovered that interleukin (IL)-6 stimulates glucagon secretion from human and rodent islets. IL-6 family cytokines require the glycoprotein 130 (gp130) receptor to signal. In this study, we elucidated...

  16. Design Protocols and Analytical Strategies that Incorporate Structural Reliability Models

    Science.gov (United States)

    Duffy, Stephen F.

    1997-01-01

    Al single crystal turbine blade material; map a simplistic failure strength envelope of the material; develop a statistically based reliability computer algorithm, verify the reliability model and computer algorithm, and model stator vanes for rig tests. Thus establishing design protocols that enable the engineer to analyze and predict the mechanical behavior of ceramic composites and intermetallics would mitigate the prototype (trial and error) approach currently used by the engineering community. The primary objective of the research effort supported by this short term grant is the continued creation of enabling technologies for the macroanalysis of components fabricated from ceramic composites and intermetallic material systems. The creation of enabling technologies aids in shortening the product development cycle of components fabricated from the new high technology materials.

  17. Behavioral and histological outcomes following neonatal HI injury in a preterm (P3) and term (P7) rodent model.

    Science.gov (United States)

    Alexander, M; Garbus, H; Smith, A L; Rosenkrantz, T S; Fitch, R H

    2014-02-01

    Hypoxia-ischemia (HI) occurs when blood and/or oxygen delivery to the brain is compromised. HI injuries can occur in infants born prematurely (HI populations, brain injury is associated with subsequent behavioral deficits. Neonatal HI injury can be modeled in rodents (e.g., the Rice-Vannucci method, via cautery of right carotid followed by hypoxia). When this injury is induced early in life (between postnatal day (P)1-5), neuropathologies typical of human preterm HI are modeled. When injury is induced later (P7-12), neuropathologies typical of those seen in HI term infants are modeled. The current study sought to characterize the similarities/differences between outcomes following early (P3) and late (P7) HI injury in rats. Male rats with HI injury on P3 or P7, as well as sham controls, were tested on a variety of behavioral tasks in both juvenile and adult periods. Results showed that P7 HI rats displayed deficits on motor learning, rapid auditory processing (RAP), and other learning/memory tasks, as well as a reduction in volume in various neuroanatomical structures. P3 HI animals showed only transient deficits on RAP tasks in the juvenile period (but not in adulthood), yet robust deficits on a visual attention task in adulthood. P3 HI animals did not show any significant reductions in brain volume that we could detect. These data suggest that: (1) behavioral deficits following neonatal HI are task-specific depending on timing of injury; (2) P3 HI rats showed transient deficits on RAP tasks; (3) the more pervasive behavioral deficits seen following P7 HI injury were associated with substantial global tissue loss; and (4) persistent deficits in attention in P3 HI subjects might be linked to neural connectivity disturbances rather than a global loss of brain volume, given that no such pathology was found. These combined findings can be applied to our understanding of differing long-term outcomes following neonatal HI injury in premature versus term infants

  18. Impact of anesthesia, analgesia, and euthanasia technique on the inflammatory cytokine profile in a rodent model of severe burn injury.

    Science.gov (United States)

    Al-Mousawi, Ahmed M; Kulp, Gabriela A; Branski, Ludwik K; Kraft, Robert; Mecott, Gabriel A; Williams, Felicia N; Herndon, David N; Jeschke, Marc G

    2010-09-01

    Anesthetics used in burn and trauma animal models may be influencing results by modulating inflammatory and acute-phase responses. Accordingly, we determined the effects of various anesthetics, analgesia, and euthanasia techniques in a rodent burn model. Isoflurane (ISO), ketamine-xylazine (KX), or pentobarbital (PEN) with or without buprenorphine were administered before scald-burn in 72 rats that were euthanized without anesthesia by decapitation after 24 h and compared with unburned shams. In a second experiment, 120 rats underwent the same scald-burn injury using KX, and 24 h later were euthanized under anesthesia or carbon dioxide (CO2). In addition, we compared euthanasia by exsanguination with that of decapitation. Serum cytokine levels were determined by an enzyme-linked immunosorbent assay. In the first experiment, ISO was associated with elevation of cytokine-induced neutrophil chemoattractant 2 (CINC-2) and monocyte chemotactic protein 1 (MCP-1), and KX and PEN was associated with elevation of CINC-1,CINC-2, IL-6, and MCP-1. Pentobarbital also decreased IL-1". IL-6 increased significantly when ISO or PEN were combined with buprenorphine. In the second experiment, euthanasia performed by exsanguination under ISO was associated with reduced levels of IL-1", CINC-1, CINC-2, and MCP-1, whereas KX reduced CINC-2 and increased IL-6 levels. Meanwhile, PEN reduced levels of IL-1" and MCP-1, and CO2 reduced CINC-2 and MCP-1. In addition,decapitation after KX, PEN, or CO2 decreased IL-1" and MCP-1, although we found no significant difference between ISO and controls. Euthanasia by exsanguination compared with decapitation using the same agent also led to modulation of several cytokines. Differential expression of inflammatory markers with the use of anesthetics and analgesics should be considered when designing animal studies and interpreting results because these seem to have a significant modulating impact. Our findings indicate that brief anesthesia with ISO

  19. Approach for an integral power transformer reliability model

    NARCIS (Netherlands)

    Schijndel, van A.; Wouters, P.A.A.F.; Steennis, E.F.; Wetzer, J.M.

    2012-01-01

    In electrical power transmission and distribution networks power transformers represent a crucial group of assets both in terms of reliability and investments. In order to safeguard the required quality at acceptable costs, decisions must be based on a reliable forecast of future behaviour. The aim

  20. Wireless Channel Modeling Perspectives for Ultra-Reliable Communications

    DEFF Research Database (Denmark)

    Eggers, Patrick Claus F.; Popovski, Petar

    2018-01-01

    Ultra-Reliable Communication (URC) is one of the distinctive features of the upcoming 5G wireless communication. The level of reliability, going down to packet error rates (PER) of $10^{-9}$, should be sufficiently convincing in order to remove cables in an industrial setting or provide remote co...

  1. Reliability of multi-model and structurally different single-model ensembles

    Energy Technology Data Exchange (ETDEWEB)

    Yokohata, Tokuta [National Institute for Environmental Studies, Center for Global Environmental Research, Tsukuba, Ibaraki (Japan); Annan, James D.; Hargreaves, Julia C. [Japan Agency for Marine-Earth Science and Technology, Research Institute for Global Change, Yokohama, Kanagawa (Japan); Collins, Matthew [University of Exeter, College of Engineering, Mathematics and Physical Sciences, Exeter (United Kingdom); Jackson, Charles S.; Tobis, Michael [The University of Texas at Austin, Institute of Geophysics, 10100 Burnet Rd., ROC-196, Mail Code R2200, Austin, TX (United States); Webb, Mark J. [Met Office Hadley Centre, Exeter (United Kingdom)

    2012-08-15

    The performance of several state-of-the-art climate model ensembles, including two multi-model ensembles (MMEs) and four structurally different (perturbed parameter) single model ensembles (SMEs), are investigated for the first time using the rank histogram approach. In this method, the reliability of a model ensemble is evaluated from the point of view of whether the observations can be regarded as being sampled from the ensemble. Our analysis reveals that, in the MMEs, the climate variables we investigated are broadly reliable on the global scale, with a tendency towards overdispersion. On the other hand, in the SMEs, the reliability differs depending on the ensemble and variable field considered. In general, the mean state and historical trend of surface air temperature, and mean state of precipitation are reliable in the SMEs. However, variables such as sea level pressure or top-of-atmosphere clear-sky shortwave radiation do not cover a sufficiently wide range in some. It is not possible to assess whether this is a fundamental feature of SMEs generated with particular model, or a consequence of the algorithm used to select and perturb the values of the parameters. As under-dispersion is a potentially more serious issue when using ensembles to make projections, we recommend the application of rank histograms to assess reliability when designing and running perturbed physics SMEs. (orig.)

  2. Beneficial Effects of Caloric Restriction on Chronic Kidney Disease in Rodent Models: A Meta-Analysis and Systematic Review.

    Directory of Open Access Journals (Sweden)

    Xiao-Meng Xu

    Full Text Available Numerous studies have demonstrated the life-extending effect of caloric restriction. It is generally accepted that caloric restriction has health benefits, such as prolonging lifespan and delaying the onset and progression of CKD in various species, especially in rodent models. Although many studies have tested the efficacy of caloric restriction, no complete quantitative analysis of the potential beneficial effects of reducing caloric intake on the development and progression of CKD has been published.All studies regarding the relationship between caloric restriction and chronic kidney diseases were searched in electronic databases, including PubMed/MEDLINE, EMBASE, Science Citation Index (SCI, OVID evidence-based medicine, Chinese Bio-medical Literature and Chinese science and technology periodicals (CNKI, VIP, and Wan Fang. The pooled odds ratios (OR and 95% confidence intervals (95% CI were calculated by using fixed- or random-effects models.The data from 27 of all the studies mentioned above was used in the Meta analysis. Through the meta-analysis, we found that the parameter of blood urea nitrogen, serum creatinine and urinary protein levels of the AL group was significant higher than that of the CR group, which are 4.11 mg/dl, 0.08mg/dl and 33.20mg/kg/24h, respectively. The incidence of the nephropathy in the caloric restriction (CR group was significantly lower than that in the ad libitum-fed (AL group. We further introduced the subgroup analysis and found that the effect of caloric restriction on the occurrence of kidney disease was only significant with prolonged intervention; the beneficial effects of CR on the 60%-caloric-restriction group were greater than on the less-than-60%-caloric-restriction group, and caloric restriction did not show obvious protective effects in genetically modified strains. Moreover, survival rate of the caloric restriction group is much higher than that of the ad libitum-fed (AL group.Our findings

  3. Long Non-Coding RNA Profiling in a Non-Alcoholic Fatty Liver Disease Rodent Model: New Insight into Pathogenesis

    Directory of Open Access Journals (Sweden)

    Yi Chen

    2017-01-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is one of the most prevalent chronic liver diseases worldwide with an unclear mechanism. Long non-coding RNAs (lncRNAs have recently emerged as important regulatory molecules. To better understand NAFLD pathogenesis, lncRNA and messenger RNA (mRNA microarrays were conducted in an NAFLD rodent model. Potential target genes of significantly changed lncRNA were predicted using cis/trans-regulatory algorithms. Gene Ontology (GO analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG pathway enrichment analysis were then performed to explore their function. In the current analysis, 89 upregulated and 177 downregulated mRNAs were identified, together with 291 deregulated lncRNAs. Bioinformatic analysis of these RNAs has categorized these RNAs into pathways including arachidonic acid metabolism, circadian rhythm, linoleic acid metabolism, peroxisome proliferator-activated receptor (PPAR signaling pathway, sphingolipid metabolism, steroid biosynthesis, tryptophan metabolism and tyrosine metabolism were compromised. Quantitative polymerase chain reaction (qPCR of representative nine mRNAs and eight lncRNAs (named fatty liver-related lncRNA, FLRL was conducted and this verified previous microarray results. Several lncRNAs, such as FLRL1, FLRL6 and FLRL2 demonstrated to be involved in circadian rhythm targeting period circadian clock 3 (Per3, Per2 and aryl hydrocarbon receptor nuclear translocator-like (Arntl, respectively. While FLRL8, FLRL3 and FLRL7 showed a potential role in PPAR signaling pathway through interaction with fatty acid binding protein 5 (Fabp5, lipoprotein lipase (Lpl and fatty acid desaturase 2 (Fads2. Functional experiments showed that interfering of lncRNA FLRL2 expression affected the expression of predicted target, circadian rhythm gene Arntl. Moreover, both FLRL2 and Arntl were downregulated in the NAFLD cellular model. The current study identified lncRNA and corresponding mRNA in NAFLD

  4. Models and data requirements for human reliability analysis

    International Nuclear Information System (INIS)

    1989-03-01

    It has been widely recognised for many years that the safety of the nuclear power generation depends heavily on the human factors related to plant operation. This has been confirmed by the accidents at Three Mile Island and Chernobyl. Both these cases revealed how human actions can defeat engineered safeguards and the need for special operator training to cover the possibility of unexpected plant conditions. The importance of the human factor also stands out in the analysis of abnormal events and insights from probabilistic safety assessments (PSA's), which reveal a large proportion of cases having their origin in faulty operator performance. A consultants' meeting, organized jointly by the International Atomic Energy Agency (IAEA) and the International Institute for Applied Systems Analysis (IIASA) was held at IIASA in Laxenburg, Austria, December 7-11, 1987, with the aim of reviewing existing models used in Probabilistic Safety Assessment (PSA) for Human Reliability Analysis (HRA) and of identifying the data required. The report collects both the contributions offered by the members of the Expert Task Force and the findings of the extensive discussions that took place during the meeting. Refs, figs and tabs

  5. Integrating software reliability concepts into risk and reliability modeling of digital instrumentation and control systems used in nuclear power plants

    International Nuclear Information System (INIS)

    Arndt, S. A.

    2006-01-01

    As software-based digital systems are becoming more and more common in all aspects of industrial process control, including the nuclear power industry, it is vital that the current state of the art in quality, reliability, and safety analysis be advanced to support the quantitative review of these systems. Several research groups throughout the world are working on the development and assessment of software-based digital system reliability methods and their applications in the nuclear power, aerospace, transportation, and defense industries. However, these groups are hampered by the fact that software experts and probabilistic safety assessment experts view reliability engineering very differently. This paper discusses the characteristics of a common vocabulary and modeling framework. (authors)

  6. ℮-conome: an automated tissue counting platform of cone photoreceptors for rodent models of retinitis pigmentosa

    Directory of Open Access Journals (Sweden)

    Clérin Emmanuelle

    2011-12-01

    Full Text Available Abstract Background Retinitis pigmentosa is characterized by the sequential loss of rod and cone photoreceptors. The preservation of cones would prevent blindness due to their essential role in human vision. Rod-derived Cone Viability Factor is a thioredoxin-like protein that is secreted by rods and is involved in cone survival. To validate the activity of Rod-derived Cone Viability Factors (RdCVFs as therapeutic agents for treating retinitis Pigmentosa, we have developed e-conome, an automated cell counting platform for retinal flat mounts of rodent models of cone degeneration. This automated quantification method allows for faster data analysis thereby accelerating translational research. Methods An inverted fluorescent microscope, motorized and coupled to a CCD camera records images of cones labeled with fluorescent peanut agglutinin lectin on flat-mounted retinas. In an average of 300 fields per retina, nine Z-planes at magnification X40 are acquired after two-stage autofocus individually for each field. The projection of the stack of 9 images is subject to a threshold, filtered to exclude aberrant images based on preset variables. The cones are identified by treating the resulting image using 13 variables empirically determined. The cone density is calculated over the 300 fields. Results The method was validated by comparison to the conventional stereological counting. The decrease in cone density in rd1 mouse was found to be equivalent to the decrease determined by stereological counting. We also studied the spatiotemporal pattern of the degeneration of cones in the rd1 mouse and show that while the reduction in cone density starts in the central part of the retina, cone degeneration progresses at the same speed over the whole retinal surface. We finally show that for mice with an inactivation of the Nucleoredoxin-like genes Nxnl1 or Nxnl2 encoding RdCVFs, the loss of cones is more pronounced in the ventral retina. Conclusion The automated

  7. ℮-conome: an automated tissue counting platform of cone photoreceptors for rodent models of retinitis pigmentosa.

    Science.gov (United States)

    Clérin, Emmanuelle; Wicker, Nicolas; Mohand-Saïd, Saddek; Poch, Olivier; Sahel, José-Alain; Léveillard, Thierry

    2011-12-20

    Retinitis pigmentosa is characterized by the sequential loss of rod and cone photoreceptors. The preservation of cones would prevent blindness due to their essential role in human vision. Rod-derived Cone Viability Factor is a thioredoxin-like protein that is secreted by rods and is involved in cone survival. To validate the activity of Rod-derived Cone Viability Factors (RdCVFs) as therapeutic agents for treating retinitis Pigmentosa, we have developed e-conome, an automated cell counting platform for retinal flat mounts of rodent models of cone degeneration. This automated quantification method allows for faster data analysis thereby accelerating translational research. An inverted fluorescent microscope, motorized and coupled to a CCD camera records images of cones labeled with fluorescent peanut agglutinin lectin on flat-mounted retinas. In an average of 300 fields per retina, nine Z-planes at magnification X40 are acquired after two-stage autofocus individually for each field. The projection of the stack of 9 images is subject to a threshold, filtered to exclude aberrant images based on preset variables. The cones are identified by treating the resulting image using 13 variables empirically determined. The cone density is calculated over the 300 fields. The method was validated by comparison to the conventional stereological counting. The decrease in cone density in rd1 mouse was found to be equivalent to the decrease determined by stereological counting. We also studied the spatiotemporal pattern of the degeneration of cones in the rd1 mouse and show that while the reduction in cone density starts in the central part of the retina, cone degeneration progresses at the same speed over the whole retinal surface. We finally show that for mice with an inactivation of the Nucleoredoxin-like genes Nxnl1 or Nxnl2 encoding RdCVFs, the loss of cones is more pronounced in the ventral retina. The automated platform ℮-conome used here for retinal disease is a tool that

  8. Characterization of the early proliferative response of the rodent bladder to subtotal cystectomy: a unique model of mammalian organ regeneration.

    Directory of Open Access Journals (Sweden)

    Charles C Peyton

    previous observations and further establishes the rodent bladder as an excellent model for studying novel aspects of mammalian organ regeneration.

  9. Reliability Analysis of Wireless Sensor Networks Using Markovian Model

    Directory of Open Access Journals (Sweden)

    Jin Zhu

    2012-01-01

    Full Text Available This paper investigates reliability analysis of wireless sensor networks whose topology is switching among possible connections which are governed by a Markovian chain. We give the quantized relations between network topology, data acquisition rate, nodes' calculation ability, and network reliability. By applying Lyapunov method, sufficient conditions of network reliability are proposed for such topology switching networks with constant or varying data acquisition rate. With the conditions satisfied, the quantity of data transported over wireless network node will not exceed node capacity such that reliability is ensured. Our theoretical work helps to provide a deeper understanding of real-world wireless sensor networks, which may find its application in the fields of network design and topology control.

  10. Modeling, implementation, and validation of arterial travel time reliability : [summary].

    Science.gov (United States)

    2013-11-01

    Travel time reliability (TTR) has been proposed as : a better measure of a facilitys performance than : a statistical measure like peak hour demand. TTR : is based on more information about average traffic : flows and longer time periods, thus inc...

  11. Modeling, implementation, and validation of arterial travel time reliability.

    Science.gov (United States)

    2013-11-01

    Previous research funded by Florida Department of Transportation (FDOT) developed a method for estimating : travel time reliability for arterials. This method was not initially implemented or validated using field data. This : project evaluated and r...

  12. Wild rodents as a model to discover genes and pathways underlying natural variation in infectious disease susceptibility.

    Science.gov (United States)

    Turner, A K; Paterson, S

    2013-11-01

    Individuals vary in their susceptibility to infectious disease, and it is now well established that host genetic factors form a major component of this variation. The discovery of genes underlying susceptibility has the potential to lead to improved disease control, through the identification and management of vulnerable individuals and the discovery of novel therapeutic targets. Laboratory rodents have proved invaluable for ascertaining the function of genes involved in immunity to infection. However, these captive animals experience conditions very different to the natural environment, lacking the genetic diversity and environmental pressures characteristic of natural populations, including those of humans. It has therefore often proved difficult to translate basic laboratory research to the real world. In order to further our understanding of the genetic basis of infectious disease resistance, and the evolutionary forces that drive variation in susceptibility, we propose that genetic research traditionally conducted on laboratory animals is expanded to the more ecologically valid arena of natural populations. In this article, we highlight the potential of using wild rodents as a new resource for biomedical research, to link the functional genetic knowledge gained from laboratory rodents with the variation in infectious disease susceptibility observed in humans and other natural populations. © 2013 John Wiley & Sons Ltd.

  13. Study of redundant Models in reliability prediction of HXMT's HES

    International Nuclear Information System (INIS)

    Wang Jinming; Liu Congzhan; Zhang Zhi; Ji Jianfeng

    2010-01-01

    Two redundant equipment structures of HXMT's HES are proposed firstly, the block backup and dual system cold-redundancy. Then prediction of the reliability is made by using parts count method. Research of comparison and analysis is also performed on the two proposals. A conclusion is drawn that a higher reliability and longer service life could be offered by taking a redundant equipment structure of block backup. (authors)

  14. Parameter estimation of component reliability models in PSA model of Krsko NPP

    International Nuclear Information System (INIS)

    Jordan Cizelj, R.; Vrbanic, I.

    2001-01-01

    In the paper, the uncertainty analysis of component reliability models for independent failures is shown. The present approach for parameter estimation of component reliability models in NPP Krsko is presented. Mathematical approaches for different types of uncertainty analyses are introduced and used in accordance with some predisposed requirements. Results of the uncertainty analyses are shown in an example for time-related components. As the most appropriate uncertainty analysis proved the Bayesian estimation with the numerical estimation of a posterior, which can be approximated with some appropriate probability distribution, in this paper with lognormal distribution.(author)

  15. Reliability model analysis and primary experimental evaluation of laser triggered pulse trigger

    International Nuclear Information System (INIS)

    Chen Debiao; Yang Xinglin; Li Yuan; Li Jin

    2012-01-01

    High performance pulse trigger can enhance performance and stability of the PPS. It is necessary to evaluate the reliability of the LTGS pulse trigger, so we establish the reliability analysis model of this pulse trigger based on CARMES software, the reliability evaluation is accord with the statistical results. (authors)

  16. 78 FR 45447 - Revisions to Modeling, Data, and Analysis Reliability Standard

    Science.gov (United States)

    2013-07-29

    ...; Order No. 782] Revisions to Modeling, Data, and Analysis Reliability Standard AGENCY: Federal Energy... Analysis (MOD) Reliability Standard MOD- 028-2, submitted to the Commission for approval by the North... Organization. The Commission finds that the proposed Reliability Standard represents an improvement over the...

  17. Computer Model to Estimate Reliability Engineering for Air Conditioning Systems

    International Nuclear Information System (INIS)

    Afrah Al-Bossly, A.; El-Berry, A.; El-Berry, A.

    2012-01-01

    Reliability engineering is used to predict the performance and optimize design and maintenance of air conditioning systems. Air conditioning systems are expose to a number of failures. The failures of an air conditioner such as turn on, loss of air conditioner cooling capacity, reduced air conditioning output temperatures, loss of cool air supply and loss of air flow entirely can be due to a variety of problems with one or more components of an air conditioner or air conditioning system. Forecasting for system failure rates are very important for maintenance. This paper focused on the reliability of the air conditioning systems. Statistical distributions that were commonly applied in reliability settings: the standard (2 parameter) Weibull and Gamma distributions. After distributions parameters had been estimated, reliability estimations and predictions were used for evaluations. To evaluate good operating condition in a building, the reliability of the air conditioning system that supplies conditioned air to the several The company's departments. This air conditioning system is divided into two, namely the main chilled water system and the ten air handling systems that serves the ten departments. In a chilled-water system the air conditioner cools water down to 40-45 degree F (4-7 degree C). The chilled water is distributed throughout the building in a piping system and connected to air condition cooling units wherever needed. Data analysis has been done with support a computer aided reliability software, this is due to the Weibull and Gamma distributions indicated that the reliability for the systems equal to 86.012% and 77.7% respectively. A comparison between the two important families of distribution functions, namely, the Weibull and Gamma families was studied. It was found that Weibull method performed for decision making.

  18. Possibilities and limitations of applying software reliability growth models to safety-critical software

    International Nuclear Information System (INIS)

    Kim, Man Cheol; Jang, Seung Cheol; Ha, Jae Joo

    2007-01-01

    It is generally known that software reliability growth models such as the Jelinski-Moranda model and the Goel-Okumoto's Non-Homogeneous Poisson Process (NHPP) model cannot be applied to safety-critical software due to a lack of software failure data. In this paper, by applying two of the most widely known software reliability growth models to sample software failure data, we demonstrate the possibility of using the software reliability growth models to prove the high reliability of safety-critical software. The high sensitivity of a piece of software's reliability to software failure data, as well as a lack of sufficient software failure data, is also identified as a possible limitation when applying the software reliability growth models to safety-critical software

  19. Analgesic and Anti-Inflammatory Effects of 80% Methanol Extract of Leonotis ocymifolia (Burm.f. Iwarsson Leaves in Rodent Models

    Directory of Open Access Journals (Sweden)

    Asnakech Alemu

    2018-01-01

    Full Text Available Background. Pain and inflammation are the major health problems commonly treated with traditional remedies mainly using medicinal plants. Leonotis ocymifolia is one of such medicinal plants used in folkloric medicine of Ethiopia. However, the plant has not been scientifically evaluated. The aim of this study was to evaluate analgesic and anti-inflammatory effects of the 80% methanol leaves extract of Leonotis ocymifolia using rodent models. Method. The central and peripheral analgesic effect of the extract at 100, 200, and 400 mg/kg dose levels was evaluated using hot plate and acetic acid induced writhing rodent models, whereas carrageenan induced paw edema and cotton pellet granuloma methods were used to screen anti-inflammatory effect of the extract at the same dose levels. Acute toxicity test was also done. Data were analyzed using one-way ANOVA followed by Tukey’s post hoc test and p<0.05 was considered significant. Results. The extract did not produce mortality up to 2000 mg/kg. All tested doses of the extract showed significant analgesic effect with maximum latency response of 62.8% and inhibition of acetic acid induced writhing. Maximum anti-inflammatory effect was recorded at 6 h after induction, with 75.88% reduction in carrageenan induced paw edema. Moreover, all tested doses of extract significantly inhibited the formation of inflammatory exudates and granuloma formation (p<0.001. Conclusion. The study indicated that the extract was safe in mice and it has both analgesic and anti-inflammatory effect in rodent models.

  20. Competing risk models in reliability systems, a Weibull distribution model with Bayesian analysis approach

    International Nuclear Information System (INIS)

    Iskandar, Ismed; Gondokaryono, Yudi Satria

    2016-01-01

    In reliability theory, the most important problem is to determine the reliability of a complex system from the reliability of its components. The weakness of most reliability theories is that the systems are described and explained as simply functioning or failed. In many real situations, the failures may be from many causes depending upon the age and the environment of the system and its components. Another problem in reliability theory is one of estimating the parameters of the assumed failure models. The estimation may be based on data collected over censored or uncensored life tests. In many reliability problems, the failure data are simply quantitatively inadequate, especially in engineering design and maintenance system. The Bayesian analyses are more beneficial than the classical one in such cases. The Bayesian estimation analyses allow us to combine past knowledge or experience in the form of an apriori distribution with life test data to make inferences of the parameter of interest. In this paper, we have investigated the application of the Bayesian estimation analyses to competing risk systems. The cases are limited to the models with independent causes of failure by using the Weibull distribution as our model. A simulation is conducted for this distribution with the objectives of verifying the models and the estimators and investigating the performance of the estimators for varying sample size. The simulation data are analyzed by using Bayesian and the maximum likelihood analyses. The simulation results show that the change of the true of parameter relatively to another will change the value of standard deviation in an opposite direction. For a perfect information on the prior distribution, the estimation methods of the Bayesian analyses are better than those of the maximum likelihood. The sensitivity analyses show some amount of sensitivity over the shifts of the prior locations. They also show the robustness of the Bayesian analysis within the range

  1. Tactile learning in rodents: Neurobiology and neuropharmacology.

    Science.gov (United States)

    Roohbakhsh, Ali; Shamsizadeh, Ali; Arababadi, Mohammad Kazemi; Ayoobi, Fateme; Fatemi, Iman; Allahtavakoli, Mohammad; Mohammad-Zadeh, Mohammad

    2016-02-15

    Animal models of learning and memory have been the subject of considerable research. Rodents such as mice and rats are nocturnal animals with poor vision, and their survival depends on their sense of touch. Recent reports have shown that whisker somatosensation is the main channel through which rodents collect and process environmental information. This review describes tactile learning in rodents from a neurobiological and neuropharmacological perspective, and how this is involved in memory-related processes. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Conceptual Software Reliability Prediction Models for Nuclear Power Plant Safety Systems

    International Nuclear Information System (INIS)

    Johnson, G.; Lawrence, D.; Yu, H.

    2000-01-01

    The objective of this project is to develop a method to predict the potential reliability of software to be used in a digital system instrumentation and control system. The reliability prediction is to make use of existing measures of software reliability such as those described in IEEE Std 982 and 982.2. This prediction must be of sufficient accuracy to provide a value for uncertainty that could be used in a nuclear power plant probabilistic risk assessment (PRA). For the purposes of the project, reliability was defined to be the probability that the digital system will successfully perform its intended safety function (for the distribution of conditions under which it is expected to respond) upon demand with no unintended functions that might affect system safety. The ultimate objective is to use the identified measures to develop a method for predicting the potential quantitative reliability of a digital system. The reliability prediction models proposed in this report are conceptual in nature. That is, possible prediction techniques are proposed and trial models are built, but in order to become a useful tool for predicting reliability, the models must be tested, modified according to the results, and validated. Using methods outlined by this project, models could be constructed to develop reliability estimates for elements of software systems. This would require careful review and refinement of the models, development of model parameters from actual experience data or expert elicitation, and careful validation. By combining these reliability estimates (generated from the validated models for the constituent parts) in structural software models, the reliability of the software system could then be predicted. Modeling digital system reliability will also require that methods be developed for combining reliability estimates for hardware and software. System structural models must also be developed in order to predict system reliability based upon the reliability

  3. Adjoint sensitivity analysis of dynamic reliability models based on Markov chains - II: Application to IFMIF reliability assessment

    Energy Technology Data Exchange (ETDEWEB)

    Cacuci, D. G. [Commiss Energy Atom, Direct Energy Nucl, Saclay, (France); Cacuci, D. G.; Balan, I. [Univ Karlsruhe, Inst Nucl Technol and Reactor Safetly, Karlsruhe, (Germany); Ionescu-Bujor, M. [Forschungszentrum Karlsruhe, Fus Program, D-76021 Karlsruhe, (Germany)

    2008-07-01

    In Part II of this work, the adjoint sensitivity analysis procedure developed in Part I is applied to perform sensitivity analysis of several dynamic reliability models of systems of increasing complexity, culminating with the consideration of the International Fusion Materials Irradiation Facility (IFMIF) accelerator system. Section II presents the main steps of a procedure for the automated generation of Markov chains for reliability analysis, including the abstraction of the physical system, construction of the Markov chain, and the generation and solution of the ensuing set of differential equations; all of these steps have been implemented in a stand-alone computer code system called QUEFT/MARKOMAG-S/MCADJSEN. This code system has been applied to sensitivity analysis of dynamic reliability measures for a paradigm '2-out-of-3' system comprising five components and also to a comprehensive dynamic reliability analysis of the IFMIF accelerator system facilities for the average availability and, respectively, the system's availability at the final mission time. The QUEFT/MARKOMAG-S/MCADJSEN has been used to efficiently compute sensitivities to 186 failure and repair rates characterizing components and subsystems of the first-level fault tree of the IFMIF accelerator system. (authors)

  4. Adjoint sensitivity analysis of dynamic reliability models based on Markov chains - II: Application to IFMIF reliability assessment

    International Nuclear Information System (INIS)

    Cacuci, D. G.; Cacuci, D. G.; Balan, I.; Ionescu-Bujor, M.

    2008-01-01

    In Part II of this work, the adjoint sensitivity analysis procedure developed in Part I is applied to perform sensitivity analysis of several dynamic reliability models of systems of increasing complexity, culminating with the consideration of the International Fusion Materials Irradiation Facility (IFMIF) accelerator system. Section II presents the main steps of a procedure for the automated generation of Markov chains for reliability analysis, including the abstraction of the physical system, construction of the Markov chain, and the generation and solution of the ensuing set of differential equations; all of these steps have been implemented in a stand-alone computer code system called QUEFT/MARKOMAG-S/MCADJSEN. This code system has been applied to sensitivity analysis of dynamic reliability measures for a paradigm '2-out-of-3' system comprising five components and also to a comprehensive dynamic reliability analysis of the IFMIF accelerator system facilities for the average availability and, respectively, the system's availability at the final mission time. The QUEFT/MARKOMAG-S/MCADJSEN has been used to efficiently compute sensitivities to 186 failure and repair rates characterizing components and subsystems of the first-level fault tree of the IFMIF accelerator system. (authors)

  5. Probabilistic risk assessment for a loss of coolant accident in McMaster Nuclear Reactor and application of reliability physics model for modeling human reliability

    Science.gov (United States)

    Ha, Taesung

    A probabilistic risk assessment (PRA) was conducted for a loss of coolant accident, (LOCA) in the McMaster Nuclear Reactor (MNR). A level 1 PRA was completed including event sequence modeling, system modeling, and quantification. To support the quantification of the accident sequence identified, data analysis using the Bayesian method and human reliability analysis (HRA) using the accident sequence evaluation procedure (ASEP) approach were performed. Since human performance in research reactors is significantly different from that in power reactors, a time-oriented HRA model (reliability physics model) was applied for the human error probability (HEP) estimation of the core relocation. This model is based on two competing random variables: phenomenological time and performance time. The response surface and direct Monte Carlo simulation with Latin Hypercube sampling were applied for estimating the phenomenological time, whereas the performance time was obtained from interviews with operators. An appropriate probability distribution for the phenomenological time was assigned by statistical goodness-of-fit tests. The human error probability (HEP) for the core relocation was estimated from these two competing quantities: phenomenological time and operators' performance time. The sensitivity of each probability distribution in human reliability estimation was investigated. In order to quantify the uncertainty in the predicted HEPs, a Bayesian approach was selected due to its capability of incorporating uncertainties in model itself and the parameters in that model. The HEP from the current time-oriented model was compared with that from the ASEP approach. Both results were used to evaluate the sensitivity of alternative huinan reliability modeling for the manual core relocation in the LOCA risk model. This exercise demonstrated the applicability of a reliability physics model supplemented with a. Bayesian approach for modeling human reliability and its potential

  6. Modeling Sensor Reliability in Fault Diagnosis Based on Evidence Theory

    Directory of Open Access Journals (Sweden)

    Kaijuan Yuan

    2016-01-01

    Full Text Available Sensor data fusion plays an important role in fault diagnosis. Dempster–Shafer (D-R evidence theory is widely used in fault diagnosis, since it is efficient to combine evidence from different sensors. However, under the situation where the evidence highly conflicts, it may obtain a counterintuitive result. To address the issue, a new method is proposed in this paper. Not only the statistic sensor reliability, but also the dynamic sensor reliability are taken into consideration. The evidence distance function and the belief entropy are combined to obtain the dynamic reliability of each sensor report. A weighted averaging method is adopted to modify the conflict evidence by assigning different weights to evidence according to sensor reliability. The proposed method has better performance in conflict management and fault diagnosis due to the fact that the information volume of each sensor report is taken into consideration. An application in fault diagnosis based on sensor fusion is illustrated to show the efficiency of the proposed method. The results show that the proposed method improves the accuracy of fault diagnosis from 81.19% to 89.48% compared to the existing methods.

  7. SIERRA - A 3-D device simulator for reliability modeling

    Science.gov (United States)

    Chern, Jue-Hsien; Arledge, Lawrence A., Jr.; Yang, Ping; Maeda, John T.

    1989-05-01

    SIERRA is a three-dimensional general-purpose semiconductor-device simulation program which serves as a foundation for investigating integrated-circuit (IC) device and reliability issues. This program solves the Poisson and continuity equations in silicon under dc, transient, and small-signal conditions. Executing on a vector/parallel minisupercomputer, SIERRA utilizes a matrix solver which uses an incomplete LU (ILU) preconditioned conjugate gradient square (CGS, BCG) method. The ILU-CGS method provides a good compromise between memory size and convergence rate. The authors have observed a 5x to 7x speedup over standard direct methods in simulations of transient problems containing highly coupled Poisson and continuity equations such as those found in reliability-oriented simulations. The application of SIERRA to parasitic CMOS latchup and dynamic random-access memory single-event-upset studies is described.

  8. Modeling of seismic hazards for dynamic reliability analysis

    International Nuclear Information System (INIS)

    Mizutani, M.; Fukushima, S.; Akao, Y.; Katukura, H.

    1993-01-01

    This paper investigates the appropriate indices of seismic hazard curves (SHCs) for seismic reliability analysis. In the most seismic reliability analyses of structures, the seismic hazards are defined in the form of the SHCs of peak ground accelerations (PGAs). Usually PGAs play a significant role in characterizing ground motions. However, PGA is not always a suitable index of seismic motions. When random vibration theory developed in the frequency domain is employed to obtain statistics of responses, it is more convenient for the implementation of dynamic reliability analysis (DRA) to utilize an index which can be determined in the frequency domain. In this paper, we summarize relationships among the indices which characterize ground motions. The relationships between the indices and the magnitude M are arranged as well. In this consideration, duration time plays an important role in relating two distinct class, i.e. energy class and power class. Fourier and energy spectra are involved in the energy class, and power and response spectra and PGAs are involved in the power class. These relationships are also investigated by using ground motion records. Through these investigations, we have shown the efficiency of employing the total energy as an index of SHCs, which can be determined in the time and frequency domains and has less variance than the other indices. In addition, we have proposed the procedure of DRA based on total energy. (author)

  9. Sensitivity of Reliability Estimates in Partially Damaged RC Structures subject to Earthquakes, using Reduced Hysteretic Models

    DEFF Research Database (Denmark)

    Iwankiewicz, R.; Nielsen, Søren R. K.; Skjærbæk, P. S.

    The subject of the paper is the investigation of the sensitivity of structural reliability estimation by a reduced hysteretic model for a reinforced concrete frame under an earthquake excitation.......The subject of the paper is the investigation of the sensitivity of structural reliability estimation by a reduced hysteretic model for a reinforced concrete frame under an earthquake excitation....

  10. Possibilities and Limitations of Applying Software Reliability Growth Models to Safety- Critical Software

    International Nuclear Information System (INIS)

    Kim, Man Cheol; Jang, Seung Cheol; Ha, Jae Joo

    2006-01-01

    As digital systems are gradually introduced to nuclear power plants (NPPs), the need of quantitatively analyzing the reliability of the digital systems is also increasing. Kang and Sung identified (1) software reliability, (2) common-cause failures (CCFs), and (3) fault coverage as the three most critical factors in the reliability analysis of digital systems. For the estimation of the safety-critical software (the software that is used in safety-critical digital systems), the use of Bayesian Belief Networks (BBNs) seems to be most widely used. The use of BBNs in reliability estimation of safety-critical software is basically a process of indirectly assigning a reliability based on various observed information and experts' opinions. When software testing results or software failure histories are available, we can use a process of directly estimating the reliability of the software using various software reliability growth models such as Jelinski- Moranda model and Goel-Okumoto's nonhomogeneous Poisson process (NHPP) model. Even though it is generally known that software reliability growth models cannot be applied to safety-critical software due to small number of expected failure data from the testing of safety-critical software, we try to find possibilities and corresponding limitations of applying software reliability growth models to safety critical software

  11. Comparison of Model Reliabilities from Single-Step and Bivariate Blending Methods

    DEFF Research Database (Denmark)

    Taskinen, Matti; Mäntysaari, Esa; Lidauer, Martin

    2013-01-01

    Model based reliabilities in genetic evaluation are compared between three methods: animal model BLUP, single-step BLUP, and bivariate blending after genomic BLUP. The original bivariate blending is revised in this work to better account animal models. The study data is extracted from...... be calculated. Model reliabilities by the single-step and the bivariate blending methods were higher than by animal model due to genomic information. Compared to the single-step method, the bivariate blending method reliability estimates were, in general, lower. Computationally bivariate blending method was......, on the other hand, lighter than the single-step method....

  12. Using Model Replication to Improve the Reliability of Agent-Based Models

    Science.gov (United States)

    Zhong, Wei; Kim, Yushim

    The basic presupposition of model replication activities for a computational model such as an agent-based model (ABM) is that, as a robust and reliable tool, it must be replicable in other computing settings. This assumption has recently gained attention in the community of artificial society and simulation due to the challenges of model verification and validation. Illustrating the replication of an ABM representing fraudulent behavior in a public service delivery system originally developed in the Java-based MASON toolkit for NetLogo by a different author, this paper exemplifies how model replication exercises provide unique opportunities for model verification and validation process. At the same time, it helps accumulate best practices and patterns of model replication and contributes to the agenda of developing a standard methodological protocol for agent-based social simulation.

  13. Procedure for Application of Software Reliability Growth Models to NPP PSA

    International Nuclear Information System (INIS)

    Son, Han Seong; Kang, Hyun Gook; Chang, Seung Cheol

    2009-01-01

    As the use of software increases at nuclear power plants (NPPs), the necessity for including software reliability and/or safety into the NPP Probabilistic Safety Assessment (PSA) rises. This work proposes an application procedure of software reliability growth models (RGMs), which are most widely used to quantify software reliability, to NPP PSA. Through the proposed procedure, it can be determined if a software reliability growth model can be applied to the NPP PSA before its real application. The procedure proposed in this work is expected to be very helpful for incorporating software into NPP PSA

  14. Time-dependent reliability analysis of nuclear reactor operators using probabilistic network models

    International Nuclear Information System (INIS)

    Oka, Y.; Miyata, K.; Kodaira, H.; Murakami, S.; Kondo, S.; Togo, Y.

    1987-01-01

    Human factors are very important for the reliability of a nuclear power plant. Human behavior has essentially a time-dependent nature. The details of thinking and decision making processes are important for detailed analysis of human reliability. They have, however, not been well considered by the conventional methods of human reliability analysis. The present paper describes the models for the time-dependent and detailed human reliability analysis. Recovery by an operator is taken into account and two-operators models are also presented

  15. Dynamic reliability modeling of three-state networks

    OpenAIRE

    Ashrafi, S.; Asadi, M.

    2014-01-01

    This paper is an investigation into the reliability and stochastic properties of three-state networks. We consider a single-step network consisting of n links and we assume that the links are subject to failure. We assume that the network can be in three states, up (K = 2), partial performance (K = 1), and down (K = 0). Using the concept of the two-dimensional signature, we study the residual lifetimes of the networks under different scenarios on the states and the number of...

  16. Beneficial effects of chronic oxytocin administration and social co-housing in a rodent model of post-traumatic stress disorder.

    Science.gov (United States)

    Janezic, Eric M; Uppalapati, Swetha; Nagl, Stephanie; Contreras, Marco; French, Edward D; Fellous, Jean-Marc

    2016-12-01

    Post-traumatic stress disorder (PTSD) is in part due to a deficit in memory consolidation and extinction. Oxytocin (OXT) has anxiolytic effects and promotes prosocial behaviors in both rodents and humans, and evidence suggests that it plays a role in memory consolidation. We studied the effects of administered OXT and social co-housing in a rodent model of PTSD. Acute OXT yielded a short-term increase in the recall of the traumatic memory if administered immediately after trauma. Low doses of OXT delivered chronically had a cumulating anxiolytic effect that became apparent after 4 days and persisted. Repeated injections of OXT after short re-exposures to the trauma apparatus yielded a long-term reduction in anxiety. Co-housing with naive nonshocked animals decreased the memory of the traumatic context compared with single-housed animals. In the long term, these animals showed less thigmotaxis and increased interest in novel objects, and a low OXT plasma level. Co-housed PTSD animals showed an increase in risk-taking behavior. These results suggest beneficial effects of OXT if administered chronically through increases in memory consolidation after re-exposure to a safe trauma context. We also show differences between the benefits of social co-housing with naive rats and co-housing with other shocked animals on trauma-induced long-term anxiety.

  17. Theory model and experiment research about the cognition reliability of nuclear power plant operators

    International Nuclear Information System (INIS)

    Fang Xiang; Zhao Bingquan

    2000-01-01

    In order to improve the reliability of NPP operation, the simulation research on the reliability of nuclear power plant operators is needed. Making use of simulator of nuclear power plant as research platform, and taking the present international reliability research model-human cognition reliability for reference, the part of the model is modified according to the actual status of Chinese nuclear power plant operators and the research model of Chinese nuclear power plant operators obtained based on two-parameter Weibull distribution. Experiments about the reliability of nuclear power plant operators are carried out using the two-parameter Weibull distribution research model. Compared with those in the world, the same results are achieved. The research would be beneficial to the operation safety of nuclear power plant

  18. Stochastic modeling for reliability shocks, burn-in and heterogeneous populations

    CERN Document Server

    Finkelstein, Maxim

    2013-01-01

    Focusing on shocks modeling, burn-in and heterogeneous populations, Stochastic Modeling for Reliability naturally combines these three topics in the unified stochastic framework and presents numerous practical examples that illustrate recent theoretical findings of the authors.  The populations of manufactured items in industry are usually heterogeneous. However, the conventional reliability analysis is performed under the implicit assumption of homogeneity, which can result in distortion of the corresponding reliability indices and various misconceptions. Stochastic Modeling for Reliability fills this gap and presents the basics and further developments of reliability theory for heterogeneous populations. Specifically, the authors consider burn-in as a method of elimination of ‘weak’ items from heterogeneous populations. The real life objects are operating in a changing environment. One of the ways to model an impact of this environment is via the external shocks occurring in accordance with some stocha...

  19. Research on cognitive reliability model for main control room considering human factors in nuclear power plants

    International Nuclear Information System (INIS)

    Jiang Jianjun; Zhang Li; Wang Yiqun; Zhang Kun; Peng Yuyuan; Zhou Cheng

    2012-01-01

    Facing the shortcomings of the traditional cognitive factors and cognitive model, this paper presents a Bayesian networks cognitive reliability model by taking the main control room as a reference background and human factors as the key points. The model mainly analyzes the cognitive reliability affected by the human factors, and for the cognitive node and influence factors corresponding to cognitive node, a series of methods and function formulas to compute the node cognitive reliability is proposed. The model and corresponding methods can be applied to the evaluation of cognitive process for the nuclear power plant operators and have a certain significance for the prevention of safety accidents in nuclear power plants. (authors)

  20. SHP-1 activation inhibits vascular smooth muscle cell proliferation and intimal hyperplasia in a rodent model of insulin resistance and diabetes

    DEFF Research Database (Denmark)

    Qi, Weier; Li, Qian; Liew, Chong Wee

    2017-01-01

    . However, the role of SHP-1 in intimal hyperplasia and restenosis has not been clarified in insulin resistance and diabetes. METHODS: We used a femoral artery wire injury mouse model, rodent models with insulin resistance and diabetes, and patients with type 2 diabetes. Further, we modulated SHP-1...... expression using a transgenic mouse that overexpresses SHP-1 in VSMCs (Shp-1-Tg). SHP-1 agonists were also employed to study the molecular mechanisms underlying the regulation of SHP-1 by oxidised lipids. RESULTS: Mice fed a high-fat diet (HFD) exhibited increased femoral artery intimal hyperplasia...... and decreased arterial SHP-1 expression compared with mice fed a regular diet. Arterial SHP-1 expression was also decreased in Zucker fatty rats, Zucker diabetic fatty rats and in patients with type 2 diabetes. In primary cultured VSMCs, oxidised LDL suppressed SHP-1 expression by activating Mek-1 (also known...

  1. Model case IRS-RWE for the determination of reliability data in practical operation

    Energy Technology Data Exchange (ETDEWEB)

    Hoemke, P; Krause, H

    1975-11-01

    Reliability und availability analyses are carried out to assess the safety of nuclear power plants. The paper deals in the first part with the requirement of accuracy for the input data of such analyses and in the second part with the prototype data collection of reliability data 'Model case IRS-RWE'. The objectives and the structure of the data collection are described. The present results show that the estimation of reliability data in power plants is possible and gives reasonable results.

  2. Estimating the Parameters of Software Reliability Growth Models Using the Grey Wolf Optimization Algorithm

    OpenAIRE

    Alaa F. Sheta; Amal Abdel-Raouf

    2016-01-01

    In this age of technology, building quality software is essential to competing in the business market. One of the major principles required for any quality and business software product for value fulfillment is reliability. Estimating software reliability early during the software development life cycle saves time and money as it prevents spending larger sums fixing a defective software product after deployment. The Software Reliability Growth Model (SRGM) can be used to predict the number of...

  3. A new model for reliability optimization of series-parallel systems with non-homogeneous components

    International Nuclear Information System (INIS)

    Feizabadi, Mohammad; Jahromi, Abdolhamid Eshraghniaye

    2017-01-01

    In discussions related to reliability optimization using redundancy allocation, one of the structures that has attracted the attention of many researchers, is series-parallel structure. In models previously presented for reliability optimization of series-parallel systems, there is a restricting assumption based on which all components of a subsystem must be homogeneous. This constraint limits system designers in selecting components and prevents achieving higher levels of reliability. In this paper, a new model is proposed for reliability optimization of series-parallel systems, which makes possible the use of non-homogeneous components in each subsystem. As a result of this flexibility, the process of supplying system components will be easier. To solve the proposed model, since the redundancy allocation problem (RAP) belongs to the NP-hard class of optimization problems, a genetic algorithm (GA) is developed. The computational results of the designed GA are indicative of high performance of the proposed model in increasing system reliability and decreasing costs. - Highlights: • In this paper, a new model is proposed for reliability optimization of series-parallel systems. • In the previous models, there is a restricting assumption based on which all components of a subsystem must be homogeneous. • The presented model provides a possibility for the subsystems’ components to be non- homogeneous in the required conditions. • The computational results demonstrate the high performance of the proposed model in improving reliability and reducing costs.

  4. Reliability-cost models for the power switching devices of wind power converters

    DEFF Research Database (Denmark)

    Ma, Ke; Blaabjerg, Frede

    2012-01-01

    In order to satisfy the growing reliability requirements for the wind power converters with more cost-effective solution, the target of this paper is to establish a new reliability-cost model which can connect the relationship between reliability performances and corresponding semiconductor cost...... temperature mean value Tm and fluctuation amplitude ΔTj of power devices, are presented. With the proposed reliability-cost model, it is possible to enable future reliability-oriented design of the power switching devices for wind power converters, and also an evaluation benchmark for different wind power...... for power switching devices. First the conduction loss, switching loss as well as thermal impedance models of power switching devices (IGBT module) are related to the semiconductor chip number information respectively. Afterwards simplified analytical solutions, which can directly extract the junction...

  5. Evaluation of Validity and Reliability for Hierarchical Scales Using Latent Variable Modeling

    Science.gov (United States)

    Raykov, Tenko; Marcoulides, George A.

    2012-01-01

    A latent variable modeling method is outlined, which accomplishes estimation of criterion validity and reliability for a multicomponent measuring instrument with hierarchical structure. The approach provides point and interval estimates for the scale criterion validity and reliability coefficients, and can also be used for testing composite or…

  6. Reliability Based Optimal Design of Vertical Breakwaters Modelled as a Series System Failure

    DEFF Research Database (Denmark)

    Christiani, E.; Burcharth, H. F.; Sørensen, John Dalsgaard

    1996-01-01

    Reliability based design of monolithic vertical breakwaters is considered. Probabilistic models of important failure modes such as sliding and rupture failure in the rubble mound and the subsoil are described. Characterisation of the relevant stochastic parameters are presented, and relevant design...... variables are identified and an optimal system reliability formulation is presented. An illustrative example is given....

  7. Model correction factor method for reliability problems involving integrals of non-Gaussian random fields

    DEFF Research Database (Denmark)

    Franchin, P.; Ditlevsen, Ove Dalager; Kiureghian, Armen Der

    2002-01-01

    The model correction factor method (MCFM) is used in conjunction with the first-order reliability method (FORM) to solve structural reliability problems involving integrals of non-Gaussian random fields. The approach replaces the limit-state function with an idealized one, in which the integrals ...

  8. Reliability Models Applied to a System of Power Converters in Particle Accelerators

    OpenAIRE

    Siemaszko, D; Speiser, M; Pittet, S

    2012-01-01

    Several reliability models are studied when applied to a power system containing a large number of power converters. A methodology is proposed and illustrated in the case study of a novel linear particle accelerator designed for reaching high energies. The proposed methods result in the prediction of both reliability and availability of the considered system for optimisation purposes.

  9. Analysis of Statistical Distributions Used for Modeling Reliability and Failure Rate of Temperature Alarm Circuit

    International Nuclear Information System (INIS)

    EI-Shanshoury, G.I.

    2011-01-01

    Several statistical distributions are used to model various reliability and maintainability parameters. The applied distribution depends on the' nature of the data being analyzed. The presented paper deals with analysis of some statistical distributions used in reliability to reach the best fit of distribution analysis. The calculations rely on circuit quantity parameters obtained by using Relex 2009 computer program. The statistical analysis of ten different distributions indicated that Weibull distribution gives the best fit distribution for modeling the reliability of the data set of Temperature Alarm Circuit (TAC). However, the Exponential distribution is found to be the best fit distribution for modeling the failure rate

  10. Reliability Modeling of Electromechanical System with Meta-Action Chain Methodology

    Directory of Open Access Journals (Sweden)

    Genbao Zhang

    2018-01-01

    Full Text Available To establish a more flexible and accurate reliability model, the reliability modeling and solving algorithm based on the meta-action chain thought are used in this thesis. Instead of estimating the reliability of the whole system only in the standard operating mode, this dissertation adopts the structure chain and the operating action chain for the system reliability modeling. The failure information and structure information for each component are integrated into the model to overcome the given factors applied in the traditional modeling. In the industrial application, there may be different operating modes for a multicomponent system. The meta-action chain methodology can estimate the system reliability under different operating modes by modeling the components with varieties of failure sensitivities. This approach has been identified by computing some electromechanical system cases. The results indicate that the process could improve the system reliability estimation. It is an effective tool to solve the reliability estimation problem in the system under various operating modes.

  11. Development of an Environment for Software Reliability Model Selection

    Science.gov (United States)

    1992-09-01

    now is directed to other related problems such as tools for model selection, multiversion programming, and software fault tolerance modeling... multiversion programming, 7. Hlardware can be repaired by spare modules, which is not. the case for software, 2-6 N. Preventive maintenance is very important

  12. Fatigue reliability and effective turbulence models in wind farms

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Frandsen, Sten Tronæs; Tarp-Johansen, N.J.

    2007-01-01

    behind wind turbines can imply a significant reduction in the fatigue lifetime of wind turbines placed in wakes. In this paper the design code model in the wind turbine code IEC 61400-1 (2005) is evaluated from a probabilistic point of view, including the importance of modeling the SN-curve by linear...

  13. Powering stochastic reliability models by discrete event simulation

    DEFF Research Database (Denmark)

    Kozine, Igor; Wang, Xiaoyun

    2012-01-01

    it difficult to find a solution to the problem. The power of modern computers and recent developments in discrete-event simulation (DES) software enable to diminish some of the drawbacks of stochastic models. In this paper we describe the insights we have gained based on using both Markov and DES models...

  14. A Novel OBDD-Based Reliability Evaluation Algorithm for Wireless Sensor Networks on the Multicast Model

    Directory of Open Access Journals (Sweden)

    Zongshuai Yan

    2015-01-01

    Full Text Available The two-terminal reliability calculation for wireless sensor networks (WSNs is a #P-hard problem. The reliability calculation of WSNs on the multicast model provides an even worse combinatorial explosion of node states with respect to the calculation of WSNs on the unicast model; many real WSNs require the multicast model to deliver information. This research first provides a formal definition for the WSN on the multicast model. Next, a symbolic OBDD_Multicast algorithm is proposed to evaluate the reliability of WSNs on the multicast model. Furthermore, our research on OBDD_Multicast construction avoids the problem of invalid expansion, which reduces the number of subnetworks by identifying the redundant paths of two adjacent nodes and s-t unconnected paths. Experiments show that the OBDD_Multicast both reduces the complexity of the WSN reliability analysis and has a lower running time than Xing’s OBDD- (ordered binary decision diagram- based algorithm.

  15. Evaluation of molecular brain changes associated with environmental stress in rodent models compared to human major depressive disorder: A proteomic systems approach.

    Science.gov (United States)

    Cox, David Alan; Gottschalk, Michael Gerd; Stelzhammer, Viktoria; Wesseling, Hendrik; Cooper, Jason David; Bahn, Sabine

    2016-11-25

    Rodent models of major depressive disorder (MDD) are indispensable when screening for novel treatments, but assessing their translational relevance with human brain pathology has proved difficult. Using a novel systems approach, proteomics data obtained from post-mortem MDD anterior prefrontal cortex tissue (n = 12) and matched controls (n = 23) were compared with equivalent data from three commonly used preclinical models exposed to environmental stressors (chronic mild stress, prenatal stress and social defeat). Functional pathophysiological features associated with depression-like behaviour were identified in these models through enrichment of protein-protein interaction networks. A cross-species comparison evaluated which model(s) represent human MDD pathology most closely. Seven functional domains associated with MDD and represented across at least two models such as "carbohydrate metabolism and cellular respiration" were identified. Through statistical evaluation using kernel-based machine learning techniques, the social defeat model was found to represent MDD brain changes most closely for four of the seven domains. This is the first study to apply a method for directly evaluating the relevance of the molecular pathology of multiple animal models to human MDD on the functional level. The methodology and findings outlined here could help to overcome translational obstacles of preclinical psychiatric research.

  16. Preclinical Testing of Antihuman CD28 Fab' Antibody in a Novel Nonhuman Primate Small Animal Rodent Model of Xenogenic Graft-Versus-Host Disease.

    Science.gov (United States)

    Hippen, Keli L; Watkins, Benjamin; Tkachev, Victor; Lemire, Amanda M; Lehnen, Charles; Riddle, Megan J; Singh, Karnail; Panoskaltsis-Mortari, Angela; Vanhove, Bernard; Tolar, Jakub; Kean, Leslie S; Blazar, Bruce R

    2016-12-01

    Graft-versus-host disease (GVHD) is a severe complication of hematopoietic stem cell transplantation. Current therapies to prevent alloreactive T cell activation largely cause generalized immunosuppression and may result in adverse drug, antileukemia and antipathogen responses. Recently, several immunomodulatory therapeutics have been developed that show efficacy in maintaining antileukemia responses while inhibiting GVHD in murine models. To analyze efficacy and better understand immunological tolerance, escape mechanisms, and side effects of clinical reagents, testing of species cross-reactive human agents in large animal GVHD models is critical. We have previously developed and refined a nonhuman primate (NHP) large animal GVHD model. However, this model is not readily amenable to semi-high throughput screening of candidate clinical reagents. Here, we report a novel, optimized NHP xenogeneic GVHD (xeno-GVHD) small animal model that recapitulates many aspects of NHP and human GVHD. This model was validated using a clinically available blocking, monovalent anti-CD28 antibody (FR104) whose effects in a human xeno-GVHD rodent model are known. Because human-reactive reagents may not be fully cross-reactive or effective in vivo on NHP immune cells, this NHP xeno-GVHD model provides immunological insights and direct testing on NHP-induced GVHD before committing to the intensive NHP studies that are being increasingly used for detailed evaluation of new immune therapeutic strategies before human trials.

  17. Wind Farm Reliability Modelling Using Bayesian Networks and Semi-Markov Processes

    Directory of Open Access Journals (Sweden)

    Robert Adam Sobolewski

    2015-09-01

    Full Text Available Technical reliability plays an important role among factors affecting the power output of a wind farm. The reliability is determined by an internal collection grid topology and reliability of its electrical components, e.g. generators, transformers, cables, switch breakers, protective relays, and busbars. A wind farm reliability’s quantitative measure can be the probability distribution of combinations of operating and failed states of the farm’s wind turbines. The operating state of a wind turbine is its ability to generate power and to transfer it to an external power grid, which means the availability of the wind turbine and other equipment necessary for the power transfer to the external grid. This measure can be used for quantitative analysis of the impact of various wind farm topologies and the reliability of individual farm components on the farm reliability, and for determining the expected farm output power with consideration of the reliability. This knowledge may be useful in an analysis of power generation reliability in power systems. The paper presents probabilistic models that quantify the wind farm reliability taking into account the above-mentioned technical factors. To formulate the reliability models Bayesian networks and semi-Markov processes were used. Using Bayesian networks the wind farm structural reliability was mapped, as well as quantitative characteristics describing equipment reliability. To determine the characteristics semi-Markov processes were used. The paper presents an example calculation of: (i probability distribution of the combination of both operating and failed states of four wind turbines included in the wind farm, and (ii expected wind farm output power with consideration of its reliability.

  18. Cognitive modelling: a basic complement of human reliability analysis

    International Nuclear Information System (INIS)

    Bersini, U.; Cacciabue, P.C.; Mancini, G.

    1988-01-01

    In this paper the issues identified in modelling humans and machines are discussed in the perspective of the consideration of human errors managing complex plants during incidental as well as normal conditions. The dichotomy between the use of a cognitive versus a behaviouristic model approach is discussed and the complementarity aspects rather than the differences of the two methods are identified. A cognitive model based on a hierarchical goal-oriented approach and driven by fuzzy logic methodology is presented as the counterpart to the 'classical' THERP methodology for studying human errors. Such a cognitive model is discussed at length and its fundamental components, i.e. the High Level Decision Making and the Low Level Decision Making models, are reviewed. Finally, the inadequacy of the 'classical' THERP methodology to deal with cognitive errors is discussed on the basis of a simple test case. For the same case the cognitive model is then applied showing the flexibility and adequacy of the model to dynamic configuration with time-dependent failures of components and with consequent need for changing of strategy during the transient itself. (author)

  19. Construction of a reliable model pyranometer for irradiance ...

    African Journals Online (AJOL)

    USER

    2010-03-22

    Mar 22, 2010 ... hour, latitude and cloud cover are the most widely or commonly used ... models in the Nigerian environment include that of Burari and Sambo .... influence the stability of the assembly (reducing its phase ... earth's surface.

  20. Reliability Estimation of Aero-engine Based on Mixed Weibull Distribution Model

    Science.gov (United States)

    Yuan, Zhongda; Deng, Junxiang; Wang, Dawei

    2018-02-01

    Aero-engine is a complex mechanical electronic system, based on analysis of reliability of mechanical electronic system, Weibull distribution model has an irreplaceable role. Till now, only two-parameter Weibull distribution model and three-parameter Weibull distribution are widely used. Due to diversity of engine failure modes, there is a big error with single Weibull distribution model. By contrast, a variety of engine failure modes can be taken into account with mixed Weibull distribution model, so it is a good statistical analysis model. Except the concept of dynamic weight coefficient, in order to make reliability estimation result more accurately, three-parameter correlation coefficient optimization method is applied to enhance Weibull distribution model, thus precision of mixed distribution reliability model is improved greatly. All of these are advantageous to popularize Weibull distribution model in engineering applications.

  1. Software reliability

    CERN Document Server

    Bendell, A

    1986-01-01

    Software Reliability reviews some fundamental issues of software reliability as well as the techniques, models, and metrics used to predict the reliability of software. Topics covered include fault avoidance, fault removal, and fault tolerance, along with statistical methods for the objective assessment of predictive accuracy. Development cost models and life-cycle cost models are also discussed. This book is divided into eight sections and begins with a chapter on adaptive modeling used to predict software reliability, followed by a discussion on failure rate in software reliability growth mo

  2. Charge transport models for reliability engineering of semiconductor devices

    International Nuclear Information System (INIS)

    Bina, M.

    2014-01-01

    The simulation of semiconductor devices is important for the assessment of device lifetimes before production. In this context, this work investigates the influence of the charge carrier transport model on the accuracy of bias temperature instability and hot-carrier degradation models in MOS devices. For this purpose, a four-state defect model based on a non-radiative multi phonon (NMP) theory is implemented to study the bias temperature instability. However, the doping concentrations typically used in nano-scale devices correspond to only a small number of dopants in the channel, leading to fluctuations of the electrostatic potential. Thus, the granularity of the doping cannot be ignored in these devices. To study the bias temperature instability in the presence of fluctuations of the electrostatic potential, the advanced drift diffusion device simulator Minimos-NT is employed. In a first effort to understand the bias temperature instability in p-channel MOSFETs at elevated temperatures, data from direct-current-current-voltage measurements is successfully reproduced using a four-state defect model. Differences between the four-state defect model and the commonly employed trapping model from Shockley, Read and Hall (SRH) have been investigated showing that the SRH model is incapable of reproducing the measurement data. This is in good agreement with the literature, where it has been extensively shown that a model based on SRH theory cannot reproduce the characteristic time constants found in BTI recovery traces. Upon inspection of recorded recovery traces after bias temperature stress in n-channel MOSFETs it is found that the gate current is strongly correlated with the drain current (recovery trace). Using a random discrete dopant model and non-equilibrium greens functions it is shown that direct tunnelling cannot explain the magnitude of the gate current reduction. Instead it is found that trap-assisted tunnelling, modelled using NMP theory, is the cause of this

  3. Reliability modeling of digital component in plant protection system with various fault-tolerant techniques

    International Nuclear Information System (INIS)

    Kim, Bo Gyung; Kang, Hyun Gook; Kim, Hee Eun; Lee, Seung Jun; Seong, Poong Hyun

    2013-01-01

    Highlights: • Integrated fault coverage is introduced for reflecting characteristics of fault-tolerant techniques in the reliability model of digital protection system in NPPs. • The integrated fault coverage considers the process of fault-tolerant techniques from detection to fail-safe generation process. • With integrated fault coverage, the unavailability of repairable component of DPS can be estimated. • The new developed reliability model can reveal the effects of fault-tolerant techniques explicitly for risk analysis. • The reliability model makes it possible to confirm changes of unavailability according to variation of diverse factors. - Abstract: With the improvement of digital technologies, digital protection system (DPS) has more multiple sophisticated fault-tolerant techniques (FTTs), in order to increase fault detection and to help the system safely perform the required functions in spite of the possible presence of faults. Fault detection coverage is vital factor of FTT in reliability. However, the fault detection coverage is insufficient to reflect the effects of various FTTs in reliability model. To reflect characteristics of FTTs in the reliability model, integrated fault coverage is introduced. The integrated fault coverage considers the process of FTT from detection to fail-safe generation process. A model has been developed to estimate the unavailability of repairable component of DPS using the integrated fault coverage. The new developed model can quantify unavailability according to a diversity of conditions. Sensitivity studies are performed to ascertain important variables which affect the integrated fault coverage and unavailability

  4. BUILDING MODEL ANALYSIS APPLICATIONS WITH THE JOINT UNIVERSAL PARAMETER IDENTIFICATION AND EVALUATION OF RELIABILITY (JUPITER) API

    Science.gov (United States)

    The open-source, public domain JUPITER (Joint Universal Parameter IdenTification and Evaluation of Reliability) API (Application Programming Interface) provides conventions and Fortran-90 modules to develop applications (computer programs) for analyzing process models. The input ...

  5. Reliability Assessment of IGBT Modules Modeled as Systems with Correlated Components

    DEFF Research Database (Denmark)

    Kostandyan, Erik; Sørensen, John Dalsgaard

    2013-01-01

    configuration. The estimated system reliability by the proposed method is a conservative estimate. Application of the suggested method could be extended for reliability estimation of systems composing of welding joints, bolts, bearings, etc. The reliability model incorporates the correlation between...... was applied for the systems failure functions estimation. It is desired to compare the results with the true system failure function, which is possible to estimate using simulation techniques. Theoretical model development should be applied for the further research. One of the directions for it might...... be modeling the system based on the Sequential Order Statistics, by considering the failure of the minimum (weakest component) at each loading level. The proposed idea to represent the system by the independent components could also be used for modeling reliability by Sequential Order Statistics....

  6. Reliability Modeling Development and Its Applications for Ceramic Capacitors with Base-Metal Electrodes (BMEs)

    Science.gov (United States)

    Liu, Donhang

    2014-01-01

    This presentation includes a summary of NEPP-funded deliverables for the Base-Metal Electrodes (BMEs) capacitor task, development of a general reliability model for BME capacitors, and a summary and future work.

  7. Microstructural Modeling of Brittle Materials for Enhanced Performance and Reliability.

    Energy Technology Data Exchange (ETDEWEB)

    Teague, Melissa Christine [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Teague, Melissa Christine [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Rodgers, Theron [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Rodgers, Theron [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Grutzik, Scott Joseph [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Grutzik, Scott Joseph [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Meserole, Stephen [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Meserole, Stephen [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-08-01

    Brittle failure is often influenced by difficult to measure and variable microstructure-scale stresses. Recent advances in photoluminescence spectroscopy (PLS), including improved confocal laser measurement and rapid spectroscopic data collection have established the potential to map stresses with microscale spatial resolution (%3C2 microns). Advanced PLS was successfully used to investigate both residual and externally applied stresses in polycrystalline alumina at the microstructure scale. The measured average stresses matched those estimated from beam theory to within one standard deviation, validating the technique. Modeling the residual stresses within the microstructure produced general agreement in comparison with the experimentally measured results. Microstructure scale modeling is primed to take advantage of advanced PLS to enable its refinement and validation, eventually enabling microstructure modeling to become a predictive tool for brittle materials.

  8. Modeling human intention formation for human reliability assessment

    International Nuclear Information System (INIS)

    Woods, D.D.; Roth, E.M.; Pople, H. Jr.

    1988-01-01

    This paper describes a dynamic simulation capability for modeling how people form intentions to act in nuclear power plant emergency situations. This modeling tool, Cognitive Environment Simulation or CES, was developed based on techniques from artificial intelligence. It simulates the cognitive processes that determine situation assessment and intention formation. It can be used to investigate analytically what situations and factors lead to intention failures, what actions follow from intention failures (e.g. errors of omission, errors of commission, common mode errors), the ability to recover from errors or additional machine failures, and the effects of changes in the NPP person machine system. One application of the CES modeling environment is to enhance the measurement of the human contribution to risk in probabilistic risk assessment studies. (author)

  9. Uus Multiphonic Rodent

    Index Scriptorium Estoniae

    2009-01-01

    Tartus tegutsenud eksperimentaal-rock-duo Opium Flirt Eestisse jäänud liige Erki Hõbe (paarimees Ervin Trofimov tegutseb Ungaris) annab välja oma teise sooloalbumi nime all Multiphonic Rodent, heliplaadi "Astral Dance" esitluskontsert toimub 5. veebruaril Tallinnas baaris Juuksur

  10. Modelling Reliability of Supply and Infrastructural Dependency in Energy Distribution Systems

    OpenAIRE

    Helseth, Arild

    2008-01-01

    This thesis presents methods and models for assessing reliability of supply and infrastructural dependency in energy distribution systems with multiple energy carriers. The three energy carriers of electric power, natural gas and district heating are considered. Models and methods for assessing reliability of supply in electric power systems are well documented, frequently applied in the industry and continuously being subject to research and improvement. On the contrary, there are compar...

  11. An analytical model for computation of reliability of waste management facilities with intermediate storages

    International Nuclear Information System (INIS)

    Kallweit, A.; Schumacher, F.

    1977-01-01

    A high reliability is called for waste management facilities within the fuel cycle of nuclear power stations which can be fulfilled by providing intermediate storage facilities and reserve capacities. In this report a model based on the theory of Markov processes is described which allows computation of reliability characteristics of waste management facilities containing intermediate storage facilities. The application of the model is demonstrated by an example. (orig.) [de

  12. Parametric and semiparametric models with applications to reliability, survival analysis, and quality of life

    CERN Document Server

    Nikulin, M; Mesbah, M; Limnios, N

    2004-01-01

    Parametric and semiparametric models are tools with a wide range of applications to reliability, survival analysis, and quality of life. This self-contained volume examines these tools in survey articles written by experts currently working on the development and evaluation of models and methods. While a number of chapters deal with general theory, several explore more specific connections and recent results in "real-world" reliability theory, survival analysis, and related fields.

  13. Appraisal and Reliability of Variable Engagement Model Prediction ...

    African Journals Online (AJOL)

    The variable engagement model based on the stress - crack opening displacement relationship and, which describes the behaviour of randomly oriented steel fibres composite subjected to uniaxial tension has been evaluated so as to determine the safety indices associated when the fibres are subjected to pullout and with ...

  14. Multi-state reliability for coolant pump based on dependent competitive failure model

    International Nuclear Information System (INIS)

    Shang Yanlong; Cai Qi; Zhao Xinwen; Chen Ling

    2013-01-01

    By taking into account the effect of degradation due to internal vibration and external shocks. and based on service environment and degradation mechanism of nuclear power plant coolant pump, a multi-state reliability model of coolant pump was proposed for the system that involves competitive failure process between shocks and degradation. Using this model, degradation state probability and system reliability were obtained under the consideration of internal vibration and external shocks for the degraded coolant pump. It provided an effective method to reliability analysis for coolant pump in nuclear power plant based on operating environment. The results can provide a decision making basis for design changing and maintenance optimization. (authors)

  15. Reliability Evaluation for the Surface to Air Missile Weapon Based on Cloud Model

    Directory of Open Access Journals (Sweden)

    Deng Jianjun

    2015-01-01

    Full Text Available The fuzziness and randomness is integrated by using digital characteristics, such as Expected value, Entropy and Hyper entropy. The cloud model adapted to reliability evaluation is put forward based on the concept of the surface to air missile weapon. The cloud scale of the qualitative evaluation is constructed, and the quantitative variable and the qualitative variable in the system reliability evaluation are corresponded. The practical calculation result shows that it is more effective to analyze the reliability of the surface to air missile weapon by this way. The practical calculation result also reflects the model expressed by cloud theory is more consistent with the human thinking style of uncertainty.

  16. Modeling reliability measurement of interface on information system: Towards the forensic of rules

    Science.gov (United States)

    Nasution, M. K. M.; Sitompul, Darwin; Harahap, Marwan

    2018-02-01

    Today almost all machines depend on the software. As a software and hardware system depends also on the rules that are the procedures for its use. If the procedure or program can be reliably characterized by involving the concept of graph, logic, and probability, then regulatory strength can also be measured accordingly. Therefore, this paper initiates an enumeration model to measure the reliability of interfaces based on the case of information systems supported by the rules of use by the relevant agencies. An enumeration model is obtained based on software reliability calculation.

  17. Reliability prediction system based on the failure rate model for electronic components

    International Nuclear Information System (INIS)

    Lee, Seung Woo; Lee, Hwa Ki

    2008-01-01

    Although many methodologies for predicting the reliability of electronic components have been developed, their reliability might be subjective according to a particular set of circumstances, and therefore it is not easy to quantify their reliability. Among the reliability prediction methods are the statistical analysis based method, the similarity analysis method based on an external failure rate database, and the method based on the physics-of-failure model. In this study, we developed a system by which the reliability of electronic components can be predicted by creating a system for the statistical analysis method of predicting reliability most easily. The failure rate models that were applied are MILHDBK- 217F N2, PRISM, and Telcordia (Bellcore), and these were compared with the general purpose system in order to validate the effectiveness of the developed system. Being able to predict the reliability of electronic components from the stage of design, the system that we have developed is expected to contribute to enhancing the reliability of electronic components

  18. Model uncertainty and multimodel inference in reliability estimation within a longitudinal framework.

    Science.gov (United States)

    Alonso, Ariel; Laenen, Annouschka

    2013-05-01

    Laenen, Alonso, and Molenberghs (2007) and Laenen, Alonso, Molenberghs, and Vangeneugden (2009) proposed a method to assess the reliability of rating scales in a longitudinal context. The methodology is based on hierarchical linear models, and reliability coefficients are derived from the corresponding covariance matrices. However, finding a good parsimonious model to describe complex longitudinal data is a challenging task. Frequently, several models fit the data equally well, raising the problem of model selection uncertainty. When model uncertainty is high one may resort to model averaging, where inferences are based not on one but on an entire set of models. We explored the use of different model building strategies, including model averaging, in reliability estimation. We found that the approach introduced by Laenen et al. (2007, 2009) combined with some of these strategies may yield meaningful results in the presence of high model selection uncertainty and when all models are misspecified, in so far as some of them manage to capture the most salient features of the data. Nonetheless, when all models omit prominent regularities in the data, misleading results may be obtained. The main ideas are further illustrated on a case study in which the reliability of the Hamilton Anxiety Rating Scale is estimated. Importantly, the ambit of model selection uncertainty and model averaging transcends the specific setting studied in the paper and may be of interest in other areas of psychometrics. © 2012 The British Psychological Society.

  19. Quantification of Wave Model Uncertainties Used for Probabilistic Reliability Assessments of Wave Energy Converters

    DEFF Research Database (Denmark)

    Ambühl, Simon; Kofoed, Jens Peter; Sørensen, John Dalsgaard

    2015-01-01

    Wave models used for site assessments are subjected to model uncertainties, which need to be quantified when using wave model results for probabilistic reliability assessments. This paper focuses on determination of wave model uncertainties. Four different wave models are considered, and validation...... data are collected from published scientific research. The bias and the root-mean-square error, as well as the scatter index, are considered for the significant wave height as well as the mean zero-crossing wave period. Based on an illustrative generic example, this paper presents how the quantified...... uncertainties can be implemented in probabilistic reliability assessments....

  20. Determination of Wave Model Uncertainties used for Probabilistic Reliability Assessments of Wave Energy Devices

    DEFF Research Database (Denmark)

    Ambühl, Simon; Kofoed, Jens Peter; Sørensen, John Dalsgaard

    2014-01-01

    Wave models used for site assessments are subject to model uncertainties, which need to be quantified when using wave model results for probabilistic reliability assessments. This paper focuses on determination of wave model uncertainties. Considered are four different wave models and validation...... data is collected from published scientific research. The bias, the root-mean-square error as well as the scatter index are considered for the significant wave height as well as the mean zero-crossing wave period. Based on an illustrative generic example it is shown how the estimated uncertainties can...... be implemented in probabilistic reliability assessments....

  1. On new cautious structural reliability models in the framework of imprecise probabilities

    DEFF Research Database (Denmark)

    Utkin, Lev; Kozine, Igor

    2010-01-01

    measures when the number of events of interest or observations is very small. The main feature of the models is that prior ignorance is not modelled by a fixed single prior distribution, but by a class of priors which is defined by upper and lower probabilities that can converge as statistical data......New imprecise structural reliability models are described in this paper. They are developed based on the imprecise Bayesian inference and are imprecise Dirichlet, imprecise negative binomial, gamma-exponential and normal models. The models are applied to computing cautious structural reliability...

  2. Adjustment of the dynamic weight distribution as a sensitive parameter for diagnosis of postural alteration in a rodent model of vestibular deficit.

    Directory of Open Access Journals (Sweden)

    Brahim Tighilet

    Full Text Available Vestibular disorders, by inducing significant posturo-locomotor and cognitive disorders, can significantly impair the most basic tasks of everyday life. Their precise diagnosis is essential to implement appropriate therapeutic countermeasures. Monitoring their evolution is also very important to validate or, on the contrary, to adapt the undertaken therapeutic actions. To date, the diagnosis methods of posturo-locomotor impairments are restricted to examinations that most often lack sensitivity and precision. In the present work we studied the alterations of the dynamic weight distribution in a rodent model of sudden and complete unilateral vestibular loss. We used a system of force sensors connected to a data analysis system to quantify in real time and in an automated way the weight bearing of the animal on the ground. We show here that sudden, unilateral, complete and permanent loss of the vestibular inputs causes a severe alteration of the dynamic ground weight distribution of vestibulo lesioned rodents. Characteristics of alterations in the dynamic weight distribution vary over time and follow the sequence of appearance and disappearance of the various symptoms that compose the vestibular syndrome. This study reveals for the first time that dynamic weight bearing is a very sensitive parameter for evaluating posturo-locomotor function impairment. Associated with more classical vestibular examinations, this paradigm can considerably enrich the methods for assessing and monitoring vestibular disorders. Systematic application of this type of evaluation to the dizzy or unstable patient could improve the detection of vestibular deficits and allow predicting better their impact on posture and walk. Thus it could also allow a better follow-up of the therapeutic approaches for rehabilitating gait and balance.

  3. Adjustment of the dynamic weight distribution as a sensitive parameter for diagnosis of postural alteration in a rodent model of vestibular deficit.

    Science.gov (United States)

    Tighilet, Brahim; Péricat, David; Frelat, Alais; Cazals, Yves; Rastoldo, Guillaume; Boyer, Florent; Dumas, Olivier; Chabbert, Christian

    2017-01-01

    Vestibular disorders, by inducing significant posturo-locomotor and cognitive disorders, can significantly impair the most basic tasks of everyday life. Their precise diagnosis is essential to implement appropriate therapeutic countermeasures. Monitoring their evolution is also very important to validate or, on the contrary, to adapt the undertaken therapeutic actions. To date, the diagnosis methods of posturo-locomotor impairments are restricted to examinations that most often lack sensitivity and precision. In the present work we studied the alterations of the dynamic weight distribution in a rodent model of sudden and complete unilateral vestibular loss. We used a system of force sensors connected to a data analysis system to quantify in real time and in an automated way the weight bearing of the animal on the ground. We show here that sudden, unilateral, complete and permanent loss of the vestibular inputs causes a severe alteration of the dynamic ground weight distribution of vestibulo lesioned rodents. Characteristics of alterations in the dynamic weight distribution vary over time and follow the sequence of appearance and disappearance of the various symptoms that compose the vestibular syndrome. This study reveals for the first time that dynamic weight bearing is a very sensitive parameter for evaluating posturo-locomotor function impairment. Associated with more classical vestibular examinations, this paradigm can considerably enrich the methods for assessing and monitoring vestibular disorders. Systematic application of this type of evaluation to the dizzy or unstable patient could improve the detection of vestibular deficits and allow predicting better their impact on posture and walk. Thus it could also allow a better follow-up of the therapeutic approaches for rehabilitating gait and balance.

  4. A Structural Reliability Business Process Modelling with System Dynamics Simulation

    OpenAIRE

    Lam, C. Y.; Chan, S. L.; Ip, W. H.

    2010-01-01

    Business activity flow analysis enables organizations to manage structured business processes, and can thus help them to improve performance. The six types of business activities identified here (i.e., SOA, SEA, MEA, SPA, MSA and FIA) are correlated and interact with one another, and the decisions from any business activity form feedback loops with previous and succeeding activities, thus allowing the business process to be modelled and simulated. For instance, for any company that is eager t...

  5. Mapping of the brain hemodynamic responses to sensorimotor stimulation in a rodent model: A BOLD fMRI study.

    Directory of Open Access Journals (Sweden)

    Salem Boussida

    find application in fMRI studies of sensorimotor disorders within cortico-basal network in rodents.

  6. A General Reliability Model for Ni-BaTiO3-Based Multilayer Ceramic Capacitors

    Science.gov (United States)

    Liu, Donhang

    2014-01-01

    The evaluation of multilayer ceramic capacitors (MLCCs) with Ni electrode and BaTiO3 dielectric material for potential space project applications requires an in-depth understanding of their reliability. A general reliability model for Ni-BaTiO3 MLCC is developed and discussed. The model consists of three parts: a statistical distribution; an acceleration function that describes how a capacitor's reliability life responds to the external stresses, and an empirical function that defines contribution of the structural and constructional characteristics of a multilayer capacitor device, such as the number of dielectric layers N, dielectric thickness d, average grain size, and capacitor chip size A. Application examples are also discussed based on the proposed reliability model for Ni-BaTiO3 MLCCs.

  7. Tracking reliability for space cabin-borne equipment in development by Crow model.

    Science.gov (United States)

    Chen, J D; Jiao, S J; Sun, H L

    2001-12-01

    Objective. To study and track the reliability growth of manned spaceflight cabin-borne equipment in the course of its development. Method. A new technique of reliability growth estimation and prediction, which is composed of the Crow model and test data conversion (TDC) method was used. Result. The estimation and prediction value of the reliability growth conformed to its expectations. Conclusion. The method could dynamically estimate and predict the reliability of the equipment by making full use of various test information in the course of its development. It offered not only a possibility of tracking the equipment reliability growth, but also the reference for quality control in manned spaceflight cabin-borne equipment design and development process.

  8. Modeling Manufacturing Impacts on Aging and Reliability of Polyurethane Foams

    Energy Technology Data Exchange (ETDEWEB)

    Rao, Rekha R.; Roberts, Christine Cardinal; Mondy, Lisa Ann; Soehnel, Melissa Marie; Johnson, Kyle; Lorenzo, Henry T.

    2016-10-01

    Polyurethane is a complex multiphase material that evolves from a viscous liquid to a system of percolating bubbles, which are created via a CO2 generating reaction. The continuous phase polymerizes to a solid during the foaming process generating heat. Foams introduced into a mold increase their volume up to tenfold, and the dynamics of the expansion process may lead to voids and will produce gradients in density and degree of polymerization. These inhomogeneities can lead to structural stability issues upon aging. For instance, structural components in weapon systems have been shown to change shape as they age depending on their molding history, which can threaten critical tolerances. The purpose of this project is to develop a Cradle-to-Grave multiphysics model, which allows us to predict the material properties of foam from its birth through aging in the stockpile, where its dimensional stability is important.

  9. Assessing Reliability of Cellulose Hydrolysis Models to Support Biofuel Process Design – Identifiability and Uncertainty Analysis

    DEFF Research Database (Denmark)

    Sin, Gürkan; Meyer, Anne S.; Gernaey, Krist

    2010-01-01

    The reliability of cellulose hydrolysis models is studied using the NREL model. An identifiability analysis revealed that only 6 out of 26 parameters are identifiable from the available data (typical hydrolysis experiments). Attempting to identify a higher number of parameters (as done in the ori......The reliability of cellulose hydrolysis models is studied using the NREL model. An identifiability analysis revealed that only 6 out of 26 parameters are identifiable from the available data (typical hydrolysis experiments). Attempting to identify a higher number of parameters (as done...

  10. Maintenance personnel performance simulation (MAPPS): a model for predicting maintenance performance reliability in nuclear power plants

    International Nuclear Information System (INIS)

    Knee, H.E.; Krois, P.A.; Haas, P.M.; Siegel, A.I.; Ryan, T.G.

    1983-01-01

    The NRC has developed a structured, quantitative, predictive methodology in the form of a computerized simulation model for assessing maintainer task performance. Objective of the overall program is to develop, validate, and disseminate a practical, useful, and acceptable methodology for the quantitative assessment of NPP maintenance personnel reliability. The program was organized into four phases: (1) scoping study, (2) model development, (3) model evaluation, and (4) model dissemination. The program is currently nearing completion of Phase 2 - Model Development

  11. On reliability and maintenance modelling of ageing equipment in electric power systems

    International Nuclear Information System (INIS)

    Lindquist, Tommie

    2008-04-01

    Maintenance optimisation is essential to achieve cost-efficiency, availability and reliability of supply in electric power systems. The process of maintenance optimisation requires information about the costs of preventive and corrective maintenance, as well as the costs of failures borne by both electricity suppliers and customers. To calculate expected costs, information is needed about equipment reliability characteristics and the way in which maintenance affects equipment reliability. The aim of this Ph.D. work has been to develop equipment reliability models taking the effect of maintenance into account. The research has focussed on the interrelated areas of condition estimation, reliability modelling and maintenance modelling, which have been investigated in a number of case studies. In the area of condition estimation two methods to quantitatively estimate the condition of disconnector contacts have been developed, which utilise results from infrared thermography inspections and contact resistance measurements. The accuracy of these methods were investigated in two case studies. Reliability models have been developed and implemented for SF6 circuit-breakers, disconnector contacts and XLPE cables in three separate case studies. These models were formulated using both empirical and physical modelling approaches. To improve confidence in such models a Bayesian statistical method incorporating information from the equipment design process was also developed. This method was illustrated in a case study of SF6 circuit-breaker operating rods. Methods for quantifying the effect of maintenance on equipment condition and reliability have been investigated in case studies on disconnector contacts and SF6 circuit-breakers. The input required by these methods are condition measurements and historical failure and maintenance data, respectively. This research has demonstrated that the effect of maintenance on power system equipment may be quantified using available data

  12. Damage Model for Reliability Assessment of Solder Joints in Wind Turbines

    DEFF Research Database (Denmark)

    Kostandyan, Erik; Sørensen, John Dalsgaard

    2012-01-01

    environmental factors. Reliability assessment for such type of products conventionally is performed by classical reliability techniques based on test data. Usually conventional reliability approaches are time and resource consuming activities. Thus in this paper we choose a physics of failure approach to define...... damage model by Miner’s rule. Our attention is focused on crack propagation in solder joints of electrical components due to the temperature loadings. Based on the proposed method it is described how to find the damage level for a given temperature loading profile. The proposed method is discussed...

  13. The model case IRS-RWE for the determination of reliability data in practical operation

    International Nuclear Information System (INIS)

    Hoemke, P.; Krause, H.

    1975-11-01

    Reliability und availability analyses are carried out to assess the safety of nuclear power plants. This paper deals in the first part with the requirement of accuracy for the input data of such analyses and in the second part with the prototype data collection of reliability data 'Model case IRS-RWE'. The objectives and the structure of the data collection will be described. The present results show that the estimation of reliability data in power plants is possible and gives reasonable results. (orig.) [de

  14. Investigation of reliability indicators of information analysis systems based on Markov’s absorbing chain model

    Science.gov (United States)

    Gilmanshin, I. R.; Kirpichnikov, A. P.

    2017-09-01

    In the result of study of the algorithm of the functioning of the early detection module of excessive losses, it is proven the ability to model it by using absorbing Markov chains. The particular interest is in the study of probability characteristics of early detection module functioning algorithm of losses in order to identify the relationship of indicators of reliability of individual elements, or the probability of occurrence of certain events and the likelihood of transmission of reliable information. The identified relations during the analysis allow to set thresholds reliability characteristics of the system components.

  15. Maintenance overtime policies in reliability theory models with random working cycles

    CERN Document Server

    Nakagawa, Toshio

    2015-01-01

    This book introduces a new concept of replacement in maintenance and reliability theory. Replacement overtime, where replacement occurs at the first completion of a working cycle over a planned time, is a new research topic in maintenance theory and also serves to provide a fresh optimization technique in reliability engineering. In comparing replacement overtime with standard and random replacement techniques theoretically and numerically, 'Maintenance Overtime Policies in Reliability Theory' highlights the key benefits to be gained by adopting this new approach and shows how they can be applied to inspection policies, parallel systems and cumulative damage models. Utilizing the latest research in replacement overtime by internationally recognized experts, readers are introduced to new topics and methods, and learn how to practically apply this knowledge to actual reliability models. This book will serve as an essential guide to a new subject of study for graduate students and researchers and also provides a...

  16. Reliable software systems via chains of object models with provably correct behavior

    International Nuclear Information System (INIS)

    Yakhnis, A.; Yakhnis, V.

    1996-01-01

    This work addresses specification and design of reliable safety-critical systems, such as nuclear reactor control systems. Reliability concerns are addressed in complimentary fashion by different fields. Reliability engineers build software reliability models, etc. Safety engineers focus on prevention of potential harmful effects of systems on environment. Software/hardware correctness engineers focus on production of reliable systems on the basis of mathematical proofs. The authors think that correctness may be a crucial guiding issue in the development of reliable safety-critical systems. However, purely formal approaches are not adequate for the task, because they neglect the connection with the informal customer requirements. They alleviate that as follows. First, on the basis of the requirements, they build a model of the system interactions with the environment, where the system is viewed as a black box. They will provide foundations for automated tools which will (a) demonstrate to the customer that all of the scenarios of system behavior are presented in the model, (b) uncover scenarios not present in the requirements, and (c) uncover inconsistent scenarios. The developers will work with the customer until the black box model will not possess scenarios (b) and (c) above. Second, the authors will build a chain of several increasingly detailed models, where the first model is the black box model and the last model serves to automatically generated proved executable code. The behavior of each model will be proved to conform to the behavior of the previous one. They build each model as a cluster of interactive concurrent objects, thus they allow both top-down and bottom-up development

  17. Reliability analysis and prediction of mixed mode load using Markov Chain Model

    International Nuclear Information System (INIS)

    Nikabdullah, N.; Singh, S. S. K.; Alebrahim, R.; Azizi, M. A.; K, Elwaleed A.; Noorani, M. S. M.

    2014-01-01

    The aim of this paper is to present the reliability analysis and prediction of mixed mode loading by using a simple two state Markov Chain Model for an automotive crankshaft. The reliability analysis and prediction for any automotive component or structure is important for analyzing and measuring the failure to increase the design life, eliminate or reduce the likelihood of failures and safety risk. The mechanical failures of the crankshaft are due of high bending and torsion stress concentration from high cycle and low rotating bending and torsional stress. The Markov Chain was used to model the two states based on the probability of failure due to bending and torsion stress. In most investigations it revealed that bending stress is much serve than torsional stress, therefore the probability criteria for the bending state would be higher compared to the torsion state. A statistical comparison between the developed Markov Chain Model and field data was done to observe the percentage of error. The reliability analysis and prediction was derived and illustrated from the Markov Chain Model were shown in the Weibull probability and cumulative distribution function, hazard rate and reliability curve and the bathtub curve. It can be concluded that Markov Chain Model has the ability to generate near similar data with minimal percentage of error and for a practical application; the proposed model provides a good accuracy in determining the reliability for the crankshaft under mixed mode loading

  18. Alterations in endo-lysosomal function induce similar hepatic lipid profiles in rodent models of drug-induced phospholipidosis and Sandhoff disease.

    Science.gov (United States)

    Lecommandeur, Emmanuelle; Baker, David; Cox, Timothy M; Nicholls, Andrew W; Griffin, Julian L

    2017-07-01

    Drug-induced phospholipidosis (DIPL) is characterized by an increase in the phospholipid content of the cell and the accumulation of drugs and lipids inside the lysosomes of affected tissues, including in the liver. Although of uncertain pathological significance for patients, the condition remains a major impediment for the clinical development of new drugs. Human Sandhoff disease (SD) is caused by inherited defects of the β subunit of lysosomal β-hexosaminidases (Hex) A and B, leading to a large array of symptoms, including neurodegeneration and ultimately death by the age of 4 in its most common form. The substrates of Hex A and B, gangliosides GM2 and GA2, accumulate inside the lysosomes of the CNS and in peripheral organs. Given that both DIPL and SD are associated with lysosomes and lipid metabolism in general, we measured the hepatic lipid profiles in rodent models of these two conditions using untargeted LC/MS to examine potential commonalities. Both model systems shared a number of perturbed lipid pathways, notably those involving metabolism of cholesteryl esters, lysophosphatidylcholines, bis(monoacylglycero)phosphates, and ceramides. We report here profound alterations in lipid metabolism in the SD liver. In addition, DIPL induced a wide range of lipid changes not previously observed in the liver, highlighting similarities with those detected in the model of SD and raising concerns that these lipid changes may be associated with underlying pathology associated with lysosomal storage disorders. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  19. On modeling human reliability in space flights - Redundancy and recovery operations

    Science.gov (United States)

    Aarset, M.; Wright, J. F.

    The reliability of humans is of paramount importance to the safety of space flight systems. This paper describes why 'back-up' operators might not be the best solution, and in some cases, might even degrade system reliability. The problem associated with human redundancy calls for special treatment in reliability analyses. The concept of Standby Redundancy is adopted, and psychological and mathematical models are introduced to improve the way such problems can be estimated and handled. In the past, human reliability has practically been neglected in most reliability analyses, and, when included, the humans have been modeled as a component and treated numerically the way technical components are. This approach is not wrong in itself, but it may lead to systematic errors if too simple analogies from the technical domain are used in the modeling of human behavior. In this paper redundancy in a man-machine system will be addressed. It will be shown how simplification from the technical domain, when applied to human components of a system, may give non-conservative estimates of system reliability.

  20. Predicting Flow Breakdown Probability and Duration in Stochastic Network Models: Impact on Travel Time Reliability

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Jing [ORNL; Mahmassani, Hani S. [Northwestern University, Evanston

    2011-01-01

    This paper proposes a methodology to produce random flow breakdown endogenously in a mesoscopic operational model, by capturing breakdown probability and duration. Based on previous research findings that probability of flow breakdown can be represented as a function of flow rate and the duration can be characterized by a hazard model. By generating random flow breakdown at various levels and capturing the traffic characteristics at the onset of the breakdown, the stochastic network simulation model provides a tool for evaluating travel time variability. The proposed model can be used for (1) providing reliability related traveler information; (2) designing ITS (intelligent transportation systems) strategies to improve reliability; and (3) evaluating reliability-related performance measures of the system.

  1. Structural reliability analysis under evidence theory using the active learning kriging model

    Science.gov (United States)

    Yang, Xufeng; Liu, Yongshou; Ma, Panke

    2017-11-01

    Structural reliability analysis under evidence theory is investigated. It is rigorously proved that a surrogate model providing only correct sign prediction of the performance function can meet the accuracy requirement of evidence-theory-based reliability analysis. Accordingly, a method based on the active learning kriging model which only correctly predicts the sign of the performance function is proposed. Interval Monte Carlo simulation and a modified optimization method based on Karush-Kuhn-Tucker conditions are introduced to make the method more efficient in estimating the bounds of failure probability based on the kriging model. Four examples are investigated to demonstrate the efficiency and accuracy of the proposed method.

  2. Stochastic models and reliability parameter estimation applicable to nuclear power plant safety

    International Nuclear Information System (INIS)

    Mitra, S.P.

    1979-01-01

    A set of stochastic models and related estimation schemes for reliability parameters are developed. The models are applicable for evaluating reliability of nuclear power plant systems. Reliability information is extracted from model parameters which are estimated from the type and nature of failure data that is generally available or could be compiled in nuclear power plants. Principally, two aspects of nuclear power plant reliability have been investigated: (1) The statistical treatment of inplant component and system failure data; (2) The analysis and evaluation of common mode failures. The model inputs are failure data which have been classified as either the time type of failure data or the demand type of failure data. Failures of components and systems in nuclear power plant are, in general, rare events.This gives rise to sparse failure data. Estimation schemes for treating sparse data, whenever necessary, have been considered. The following five problems have been studied: 1) Distribution of sparse failure rate component data. 2) Failure rate inference and reliability prediction from time type of failure data. 3) Analyses of demand type of failure data. 4) Common mode failure model applicable to time type of failure data. 5) Estimation of common mode failures from 'near-miss' demand type of failure data

  3. Designing the database for a reliability aware Model-Based System Engineering process

    International Nuclear Information System (INIS)

    Cressent, Robin; David, Pierre; Idasiak, Vincent; Kratz, Frederic

    2013-01-01

    This article outlines the need for a reliability database to implement model-based description of components failure modes and dysfunctional behaviors. We detail the requirements such a database should honor and describe our own solution: the Dysfunctional Behavior Database (DBD). Through the description of its meta-model, the benefits of integrating the DBD in the system design process is highlighted. The main advantages depicted are the possibility to manage feedback knowledge at various granularity and semantic levels and to ease drastically the interactions between system engineering activities and reliability studies. The compliance of the DBD with other reliability database such as FIDES is presented and illustrated. - Highlights: ► Model-Based System Engineering is more and more used in the industry. ► It results in a need for a reliability database able to deal with model-based description of dysfunctional behavior. ► The Dysfunctional Behavior Database aims to fulfill that need. ► It helps dealing with feedback management thanks to its structured meta-model. ► The DBD can profit from other reliability database such as FIDES.

  4. Value-Added Models for Teacher Preparation Programs: Validity and Reliability Threats, and a Manageable Alternative

    Science.gov (United States)

    Brady, Michael P.; Heiser, Lawrence A.; McCormick, Jazarae K.; Forgan, James

    2016-01-01

    High-stakes standardized student assessments are increasingly used in value-added evaluation models to connect teacher performance to P-12 student learning. These assessments are also being used to evaluate teacher preparation programs, despite validity and reliability threats. A more rational model linking student performance to candidates who…

  5. An adaptive neuro fuzzy model for estimating the reliability of component-based software systems

    Directory of Open Access Journals (Sweden)

    Kirti Tyagi

    2014-01-01

    Full Text Available Although many algorithms and techniques have been developed for estimating the reliability of component-based software systems (CBSSs, much more research is needed. Accurate estimation of the reliability of a CBSS is difficult because it depends on two factors: component reliability and glue code reliability. Moreover, reliability is a real-world phenomenon with many associated real-time problems. Soft computing techniques can help to solve problems whose solutions are uncertain or unpredictable. A number of soft computing approaches for estimating CBSS reliability have been proposed. These techniques learn from the past and capture existing patterns in data. The two basic elements of soft computing are neural networks and fuzzy logic. In this paper, we propose a model for estimating CBSS reliability, known as an adaptive neuro fuzzy inference system (ANFIS, that is based on these two basic elements of soft computing, and we compare its performance with that of a plain FIS (fuzzy inference system for different data sets.

  6. Life cycle reliability assessment of new products—A Bayesian model updating approach

    International Nuclear Information System (INIS)

    Peng, Weiwen; Huang, Hong-Zhong; Li, Yanfeng; Zuo, Ming J.; Xie, Min

    2013-01-01

    The rapidly increasing pace and continuously evolving reliability requirements of new products have made life cycle reliability assessment of new products an imperative yet difficult work. While much work has been done to separately estimate reliability of new products in specific stages, a gap exists in carrying out life cycle reliability assessment throughout all life cycle stages. We present a Bayesian model updating approach (BMUA) for life cycle reliability assessment of new products. Novel features of this approach are the development of Bayesian information toolkits by separately including “reliability improvement factor” and “information fusion factor”, which allow the integration of subjective information in a specific life cycle stage and the transition of integrated information between adjacent life cycle stages. They lead to the unique characteristics of the BMUA in which information generated throughout life cycle stages are integrated coherently. To illustrate the approach, an application to the life cycle reliability assessment of a newly developed Gantry Machining Center is shown

  7. Lung function and airway inflammation in rats following exposure to combustion products of carbon-graphite/epoxy composite material: comparison to a rodent model of acute lung injury.

    Science.gov (United States)

    Whitehead, Gregory S; Grasman, Keith A; Kimmel, Edgar C

    2003-02-01

    Pulmonary function and inflammation in the lungs of rodents exposed by inhalation to carbon/graphite/epoxy advanced composite material (ACM) combustion products were compared to that of a rodent model of acute lung injury (ALI) produced by pneumotoxic paraquat dichloride. This investigation was undertaken to determine if short-term exposure to ACM smoke induces ALI; and to determine if smoke-related responses were similar to the pathogenic mechanisms of a model of lung vascular injury. We examined the time-course for mechanical lung function, infiltration of inflammatory cells into the lung, and the expression of three inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2) and interferon-gamma (IFN-gamma). Male Fischer-344 rats were either exposed to 26.8-29.8 g/m(3) nominal concentrations of smoke or were given i.p. injections of paraquat dichloride. Measurements were determined at 1, 2, 3, and 7 days post exposure. In the smoke-challenged rats, there were no changes in lung function indicative of ALI throughout the 7-day observation period, despite the acute lethality of the smoke atmosphere. However, the animals showed signs of pulmonary inflammation. The expression of TNF-alpha was significantly increased in the lavage fluid 1 day following exposure, which preceded the maximum leukocyte infiltration. MIP-2 levels were significantly increased in lavage fluid at days 2, 3, and 7. This followed the leukocyte infiltration. IFN-gamma was significantly increased in the lung tissue at day 7, which occurred during the resolution of the inflammatory response. The paraquat, which was also lethal to a small percentage of the animals, caused several physiologic changes characteristic of ALI, including significant decreases in lung compliance, lung volumes/capacities, distribution of ventilation, and gas exchange capacity. The expression of TNF-alpha and MIP-2 increased significantly in the lung tissue as well as in the

  8. Pig BMSCs Transfected with Human TFPI Combat Species Incompatibility and Regulate the Human TF Pathway in Vitro and in a Rodent Model

    Directory of Open Access Journals (Sweden)

    Hongchen Ji

    2015-05-01

    Full Text Available Background: The activation of tissue factor (TF is one of the major reasons for coagulation dysregulation after pig-to-primate xenotransplantation. Tissue factor pathway inhibitor (TFPI is the most important inhibitor of TF. Studies have demonstrated species incompatibility between pig TFPI and human TF. Methods: A pig-to-macaque heterotopic auxiliary liver transplantation model was established to determine the origin of activated TF. Chimeric proteins of human and pig TFPI were constructed to assess the role of Kunitz domains in species incompatibility. Immortalised pig bone marrow mesenchymal stem cells transfected with human TFPI were tested for their ability to inhibit clotting in vitro. Results: TF from recipient was activated early after liver xenotransplantation. Pig TFPI Kunitz domain 2 bound human FXa, but Kunitz domain 1 did not effectively inhibit human TF/FVIIa. Immortalised pig bone marrow mesenchymal cells (BMSCs transfected with human TFPI showed a prolonged recalcification time in vitro and in a rodent model. Conclusion: Recipient TF is relevant to dysregulated coagulation after xenotransplantation. Kunitz domain 1 plays the most important role in species incompatibility between pig TFPI and human TF, and clotting can be inhibited by human TFPI-transfected pig BMSCs. Our study shows a possible way to resolve the incompatibility of pig TFPI.

  9. Automated evaluation of liver fibrosis in thioacetamide, carbon tetrachloride, and bile duct ligation rodent models using second-harmonic generation/two-photon excited fluorescence microscopy.

    Science.gov (United States)

    Liu, Feng; Chen, Long; Rao, Hui-Ying; Teng, Xiao; Ren, Ya-Yun; Lu, Yan-Qiang; Zhang, Wei; Wu, Nan; Liu, Fang-Fang; Wei, Lai

    2017-01-01

    Animal models provide a useful platform for developing and testing new drugs to treat liver fibrosis. Accordingly, we developed a novel automated system to evaluate liver fibrosis in rodent models. This system uses second-harmonic generation (SHG)/two-photon excited fluorescence (TPEF) microscopy to assess a total of four mouse and rat models, using chemical treatment with either thioacetamide (TAA) or carbon tetrachloride (CCl 4 ), and a surgical method, bile duct ligation (BDL). The results obtained by the new technique were compared with that using Ishak fibrosis scores and two currently used quantitative methods for determining liver fibrosis: the collagen proportionate area (CPA) and measurement of hydroxyproline (HYP) content. We show that 11 shared morphological parameters faithfully recapitulate Ishak fibrosis scores in the models, with high area under the receiver operating characteristic (ROC) curve (AUC) performance. The AUC values of 11 shared parameters were greater than that of the CPA (TAA: 0.758-0.922 vs 0.752-0.908; BDL: 0.874-0.989 vs 0.678-0.966) in the TAA mice and BDL rat models and similar to that of the CPA in the TAA rat and CCl 4 mouse models. Similarly, based on the trends in these parameters at different time points, 9, 10, 7, and 2 model-specific parameters were selected for the TAA rats, TAA mice, CCl 4 mice, and BDL rats, respectively. These parameters identified differences among the time points in the four models, with high AUC accuracy, and the corresponding AUC values of these parameters were greater compared with those of the CPA in the TAA rat and mouse models (rats: 0.769-0.894 vs 0.64-0.799; mice: 0.87-0.93 vs 0.739-0.836) and similar to those of the CPA in the CCl 4 mouse and BDL rat models. Similarly, the AUC values of 11 shared parameters and model-specific parameters were greater than those of HYP in the TAA rats, TAA mice, and CCl 4 mouse models and were similar to those of HYP in the BDL rat models. The automated

  10. Business Cases for Microgrids: Modeling Interactions of Technology Choice, Reliability, Cost, and Benefit

    Science.gov (United States)

    Hanna, Ryan

    Distributed energy resources (DERs), and increasingly microgrids, are becoming an integral part of modern distribution systems. Interest in microgrids--which are insular and autonomous power networks embedded within the bulk grid--stems largely from the vast array of flexibilities and benefits they can offer stakeholders. Managed well, they can improve grid reliability and resiliency, increase end-use energy efficiency by coupling electric and thermal loads, reduce transmission losses by generating power locally, and may reduce system-wide emissions, among many others. Whether these public benefits are realized, however, depends on whether private firms see a "business case", or private value, in investing. To this end, firms need models that evaluate costs, benefits, risks, and assumptions that underlie decisions to invest. The objectives of this dissertation are to assess the business case for microgrids that provide what industry analysts forecast as two primary drivers of market growth--that of providing energy services (similar to an electric utility) as well as reliability service to customers within. Prototypical first adopters are modeled--using an existing model to analyze energy services and a new model that couples that analysis with one of reliability--to explore interactions between technology choice, reliability, costs, and benefits. The new model has a bi-level hierarchy; it uses heuristic optimization to select and size DERs and analytical optimization to schedule them. It further embeds Monte Carlo simulation to evaluate reliability as well as regression models for customer damage functions to monetize reliability. It provides least-cost microgrid configurations for utility customers who seek to reduce interruption and operating costs. Lastly, the model is used to explore the impact of such adoption on system-wide greenhouse gas emissions in California. Results indicate that there are, at present, co-benefits for emissions reductions when customers

  11. Reliability Measure Model for Assistive Care Loop Framework Using Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Venki Balasubramanian

    2010-01-01

    Full Text Available Body area wireless sensor networks (BAWSNs are time-critical systems that rely on the collective data of a group of sensor nodes. Reliable data received at the sink is based on the collective data provided by all the source sensor nodes and not on individual data. Unlike conventional reliability, the definition of retransmission is inapplicable in a BAWSN and would only lead to an elapsed data arrival that is not acceptable for time-critical application. Time-driven applications require high data reliability to maintain detection and responses. Hence, the transmission reliability for the BAWSN should be based on the critical time. In this paper, we develop a theoretical model to measure a BAWSN's transmission reliability, based on the critical time. The proposed model is evaluated through simulation and then compared with the experimental results conducted in our existing Active Care Loop Framework (ACLF. We further show the effect of the sink buffer in transmission reliability after a detailed study of various other co-existing parameters.

  12. Reliability modeling of digital RPS with consideration of undetected software faults

    Energy Technology Data Exchange (ETDEWEB)

    Khalaquzzaman, M.; Lee, Seung Jun; Jung, Won Dea [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Kim, Man Cheol [Chung Ang Univ., Seoul (Korea, Republic of)

    2013-10-15

    This paper provides overview of different software reliability methodologies and proposes a technic for estimating the reliability of RPS with consideration of undetected software faults. Software reliability analysis of safety critical software has been challenging despite spending a huge effort for developing large number of software reliability models, and no consensus yet to attain on an appropriate modeling methodology. However, it is realized that the combined application of BBN based SDLC fault prediction method and random black-box testing of software would provide better ground for reliability estimation of safety critical software. Digitalizing the reactor protection system of nuclear power plant has been initiated several decades ago and now full digitalization has been adopted in the new generation of NPPs around the world because digital I and C systems have many better technical features like easier configurability and maintainability over analog I and C systems. Digital I and C systems are also drift-free and incorporation of new features is much easier. Rules and regulation for safe operation of NPPs are established and has been being practiced by the operators as well as regulators of NPPs to ensure safety. The failure mechanism of hardware and analog systems well understood and the risk analysis methods for these components and systems are well established. However, digitalization of I and C system in NPP introduces some crisis and uncertainty in reliability analysis methods of the digital systems/components because software failure mechanisms are still unclear.

  13. A multi-state reliability evaluation model for P2P networks

    International Nuclear Information System (INIS)

    Fan Hehong; Sun Xiaohan

    2010-01-01

    The appearance of new service types and the convergence tendency of the communication networks have endowed the networks more and more P2P (peer to peer) properties. These networks can be more robust and tolerant for a series of non-perfect operational states due to the non-deterministic server-client distributions. Thus a reliability model taking into account of the multi-state and non-deterministic server-client distribution properties is needed for appropriate evaluation of the networks. In this paper, two new performance measures are defined to quantify the overall and local states of the networks. A new time-evolving state-transition Monte Carlo (TEST-MC) simulation model is presented for the reliability analysis of P2P networks in multiple states. The results show that the model is not only valid for estimating the traditional binary-state network reliability parameters, but also adequate for acquiring the parameters in a series of non-perfect operational states, with good efficiencies, especially for highly reliable networks. Furthermore, the model is versatile for the reliability and maintainability analyses in that both the links and the nodes can be failure-prone with arbitrary life distributions, and various maintainability schemes can be applied.

  14. Modelling of nuclear power plant control and instrumentation elements for automatic disturbance and reliability analysis

    International Nuclear Information System (INIS)

    Hollo, E.

    1985-08-01

    Present Final Report summarizes results of R/D work done within IAEA-VEIKI (Institute for Electrical Power Research, Budapest, Hungary) Research Contract No. 3210 during 3 years' period of 01.08.1982 - 31.08.1985. Chapter 1 lists main research objectives of the project. Main results obtained are summarized in Chapters 2 and 3. Outcomes from development of failure modelling methodologies and their application for C/I components of WWER-440 units are as follows (Chapter 2): improvement of available ''failure mode and effect analysis'' methods and mini-fault tree structures usable for automatic disturbance (DAS) and reliability (RAS) analysis; general classification and determination of functional failure modes of WWER-440 NPP C/I components; set up of logic models for motor operated control valves and rod control/drive mechanism. Results of development of methods and their application for reliability modelling of NPP components and systems cover (Chapter 3): development of an algorithm (computer code COMPREL) for component-related failure and reliability parameter calculation; reliability analysis of PAKS II NPP diesel system; definition of functional requirements for reliability data bank (RDB) in WWER-440 units. Determination of RDB input/output data structure and data manipulation services. Methods used are a-priori failure mode and effect analysis, combined fault tree/event tree modelling technique, structural computer programming, probability theory application to nuclear field

  15. Modeling Optimal Scheduling for Pumping System to Minimize Operation Cost and Enhance Operation Reliability

    Directory of Open Access Journals (Sweden)

    Yin Luo

    2012-01-01

    Full Text Available Traditional pump scheduling models neglect the operation reliability which directly relates with the unscheduled maintenance cost and the wear cost during the operation. Just for this, based on the assumption that the vibration directly relates with the operation reliability and the degree of wear, it could express the operation reliability as the normalization of the vibration level. The characteristic of the vibration with the operation point was studied, it could be concluded that idealized flow versus vibration plot should be a distinct bathtub shape. There is a narrow sweet spot (80 to 100 percent BEP to obtain low vibration levels in this shape, and the vibration also follows similar law with the square of the rotation speed without resonance phenomena. Then, the operation reliability could be modeled as the function of the capacity and rotation speed of the pump and add this function to the traditional model to form the new. And contrast with the tradition method, the result shown that the new model could fix the result produced by the traditional, make the pump operate in low vibration, then the operation reliability could increase and the maintenance cost could decrease.

  16. Reliability Analysis of Sealing Structure of Electromechanical System Based on Kriging Model

    Science.gov (United States)

    Zhang, F.; Wang, Y. M.; Chen, R. W.; Deng, W. W.; Gao, Y.

    2018-05-01

    The sealing performance of aircraft electromechanical system has a great influence on flight safety, and the reliability of its typical seal structure is analyzed by researcher. In this paper, we regard reciprocating seal structure as a research object to study structural reliability. Having been based on the finite element numerical simulation method, the contact stress between the rubber sealing ring and the cylinder wall is calculated, and the relationship between the contact stress and the pressure of the hydraulic medium is built, and the friction force on different working conditions are compared. Through the co-simulation, the adaptive Kriging model obtained by EFF learning mechanism is used to describe the failure probability of the seal ring, so as to evaluate the reliability of the sealing structure. This article proposes a new idea of numerical evaluation for the reliability analysis of sealing structure, and also provides a theoretical basis for the optimal design of sealing structure.

  17. [Reliability study in the measurement of the cusp inclination angle of a chairside digital model].

    Science.gov (United States)

    Xinggang, Liu; Xiaoxian, Chen

    2018-02-01

    This study aims to evaluate the reliability of the software Picpick in the measurement of the cusp inclination angle of a digital model. Twenty-one trimmed models were used as experimental objects. The chairside digital impression was then used for the acquisition of 3D digital models, and the software Picpick was employed for the measurement of the cusp inclination of these models. The measurements were repeated three times, and the results were compared with a gold standard, which was a manually measured experimental model cusp angle. The intraclass correlation coefficient (ICC) was calculated. The paired t test value of the two measurement methods was 0.91. The ICCs between the two measurement methods and three repeated measurements were greater than 0.9. The digital model achieved a smaller coefficient of variation (9.9%). The software Picpick is reliable in measuring the cusp inclination of a digital model.

  18. Bayesian Hierarchical Scale Mixtures of Log-Normal Models for Inference in Reliability with Stochastic Constraint

    Directory of Open Access Journals (Sweden)

    Hea-Jung Kim

    2017-06-01

    Full Text Available This paper develops Bayesian inference in reliability of a class of scale mixtures of log-normal failure time (SMLNFT models with stochastic (or uncertain constraint in their reliability measures. The class is comprehensive and includes existing failure time (FT models (such as log-normal, log-Cauchy, and log-logistic FT models as well as new models that are robust in terms of heavy-tailed FT observations. Since classical frequency approaches to reliability analysis based on the SMLNFT model with stochastic constraint are intractable, the Bayesian method is pursued utilizing a Markov chain Monte Carlo (MCMC sampling based approach. This paper introduces a two-stage maximum entropy (MaxEnt prior, which elicits a priori uncertain constraint and develops Bayesian hierarchical SMLNFT model by using the prior. The paper also proposes an MCMC method for Bayesian inference in the SMLNFT model reliability and calls attention to properties of the MaxEnt prior that are useful for method development. Finally, two data sets are used to illustrate how the proposed methodology works.

  19. Reliability modeling of degradation of products with multiple performance characteristics based on gamma processes

    International Nuclear Information System (INIS)

    Pan Zhengqiang; Balakrishnan, Narayanaswamy

    2011-01-01

    Many highly reliable products usually have complex structure, with their reliability being evaluated by two or more performance characteristics. In certain physical situations, the degradation of these performance characteristics would be always positive and strictly increasing. In such a case, the gamma process is usually considered as a degradation process due to its independent and non-negative increments properties. In this paper, we suppose that a product has two dependent performance characteristics and that their degradation can be modeled by gamma processes. For such a bivariate degradation involving two performance characteristics, we propose to use a bivariate Birnbaum-Saunders distribution and its marginal distributions to approximate the reliability function. Inferential method for the corresponding model parameters is then developed. Finally, for an illustration of the proposed model and method, a numerical example about fatigue cracks is discussed and some computational results are presented.

  20. Inter-arch digital model vs. manual cast measurements: Accuracy and reliability.

    Science.gov (United States)

    Kiviahde, Heikki; Bukovac, Lea; Jussila, Päivi; Pesonen, Paula; Sipilä, Kirsi; Raustia, Aune; Pirttiniemi, Pertti

    2017-06-28

    The purpose of this study was to evaluate the accuracy and reliability of inter-arch measurements using digital dental models and conventional dental casts. Thirty sets of dental casts with permanent dentition were examined. Manual measurements were done with a digital caliper directly on the dental casts, and digital measurements were made on 3D models by two independent examiners. Intra-class correlation coefficients (ICC), a paired sample t-test or Wilcoxon signed-rank test, and Bland-Altman plots were used to evaluate intra- and inter-examiner error and to determine the accuracy and reliability of the measurements. The ICC values were generally good for manual and excellent for digital measurements. The Bland-Altman plots of all the measurements showed good agreement between the manual and digital methods and excellent inter-examiner agreement using the digital method. Inter-arch occlusal measurements on digital models are accurate and reliable and are superior to manual measurements.

  1. Comparative analysis among deterministic and stochastic collision damage models for oil tanker and bulk carrier reliability

    Directory of Open Access Journals (Sweden)

    A. Campanile

    2018-01-01

    Full Text Available The incidence of collision damage models on oil tanker and bulk carrier reliability is investigated considering the IACS deterministic model against GOALDS/IMO database statistics for collision events, substantiating the probabilistic model. Statistical properties of hull girder residual strength are determined by Monte Carlo simulation, based on random generation of damage dimensions and a modified form of incremental-iterative method, to account for neutral axis rotation and equilibrium of horizontal bending moment, due to cross-section asymmetry after collision events. Reliability analysis is performed, to investigate the incidence of collision penetration depth and height statistical properties on hull girder sagging/hogging failure probabilities. Besides, the incidence of corrosion on hull girder residual strength and reliability is also discussed, focussing on gross, hull girder net and local net scantlings, respectively. The ISSC double hull oil tanker and single side bulk carrier, assumed as test cases in the ISSC 2012 report, are taken as reference ships.

  2. Preliminary physiologically based pharmacokinetic models for benzo[a]pyrene and dibenzo[def,p]chrysene in rodents

    International Nuclear Information System (INIS)

    Crowell, Susan Ritger; Amin, Shantu G.; Anderson, Kim A.; Krishnegowda, Gowdahalli; Sharma, Arun K.; Soelberg, Jolen J.; Williams, David E.; Corley, Richard A.

    2011-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants generated as byproducts of natural and anthropogenic combustion processes. Despite significant public health concern, physiologically based pharmacokinetic (PBPK) modeling efforts for PAHs have so far been limited to naphthalene, plus simpler PK models for pyrene, nitropyrene, and benzo[a]pyrene (B[a]P). The dearth of published models is due in part to the high lipophilicity, low volatility, and myriad metabolic pathways for PAHs, all of which present analytical and experimental challenges. Our research efforts have focused upon experimental approaches and initial development of PBPK models for the prototypic PAH, B[a]P, and the more potent, albeit less studied transplacental carcinogen, dibenzo[def,p]chrysene (DBC). For both compounds, model compartments included arterial and venous blood, flow limited lung, liver, richly perfused and poorly perfused tissues, diffusion limited fat, and a two compartment theoretical gut (for oral exposures). Hepatic and pulmonary metabolism was described for both compounds, as were fractional binding in blood and fecal clearance. Partition coefficients for parent PAH along with their diol and tetraol metabolites were estimated using published algorithms and verified experimentally for the hydroxylated metabolites. The preliminary PBPK models were able to describe many, but not all, of the available data sets, comprising multiple routes of exposure (oral, intravenous) and nominal doses spanning several orders of magnitude. Supported by Award Number P42 ES016465 from the National Institute of Environmental Health Sciences. -- Highlights: ► We present PBPK models for benzo[a]pyrene (B[a]P) and dibenzo[def,p]chrysene (DBC). ► B[a]P model accurately predicts data from multiple sources over a wide dose range. ► DBC model was based on the B[a]P model as less chemical specific data is available. ► DBC model accurately predicted preliminary

  3. Development of Markov model of emergency diesel generator for dynamic reliability analysis

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Young Ho; Choi, Sun Yeong; Yang, Joon Eon [Korea Atomic Energy Research Institute, Taejon (Korea)

    1999-02-01

    The EDG (Emergency Diesal Generator) of nuclear power plant is one of the most important equipments in mitigating accidents. The FT (Fault Tree) method is widely used to assess the reliability of safety systems like an EDG in nuclear power plant. This method, however, has limitations in modeling dynamic features of safety systems exactly. We, hence, have developed a Markov model to represent the stochastic process of dynamic systems whose states change as time moves on. The Markov model enables us to develop a dynamic reliability model of EDG. This model can represent all possible states of EDG comparing to the FRANTIC code developed by U.S. NRC for the reliability analysis of standby systems. to access the regulation policy for test interval, we performed two simulations based on the generic data and plant specific data of YGN 3, respectively by using the developed model. We also estimate the effects of various repair rates and the fractions of starting failures by demand shock to the reliability of EDG. And finally, Aging effect is analyzed. (author). 23 refs., 19 figs., 9 tabs.

  4. A discrete-time Bayesian network reliability modeling and analysis framework

    International Nuclear Information System (INIS)

    Boudali, H.; Dugan, J.B.

    2005-01-01

    Dependability tools are becoming an indispensable tool for modeling and analyzing (critical) systems. However the growing complexity of such systems calls for increasing sophistication of these tools. Dependability tools need to not only capture the complex dynamic behavior of the system components, but they must be also easy to use, intuitive, and computationally efficient. In general, current tools have a number of shortcomings including lack of modeling power, incapacity to efficiently handle general component failure distributions, and ineffectiveness in solving large models that exhibit complex dependencies between their components. We propose a novel reliability modeling and analysis framework based on the Bayesian network (BN) formalism. The overall approach is to investigate timed Bayesian networks and to find a suitable reliability framework for dynamic systems. We have applied our methodology to two example systems and preliminary results are promising. We have defined a discrete-time BN reliability formalism and demonstrated its capabilities from a modeling and analysis point of view. This research shows that a BN based reliability formalism is a powerful potential solution to modeling and analyzing various kinds of system components behaviors and interactions. Moreover, being based on the BN formalism, the framework is easy to use and intuitive for non-experts, and provides a basis for more advanced and useful analyses such as system diagnosis

  5. Linear and evolutionary polynomial regression models to forecast coastal dynamics: Comparison and reliability assessment

    Science.gov (United States)

    Bruno, Delia Evelina; Barca, Emanuele; Goncalves, Rodrigo Mikosz; de Araujo Queiroz, Heithor Alexandre; Berardi, Luigi; Passarella, Giuseppe

    2018-01-01

    In this paper, the Evolutionary Polynomial Regression data modelling strategy has been applied to study small scale, short-term coastal morphodynamics, given its capability for treating a wide database of known information, non-linearly. Simple linear and multilinear regression models were also applied to achieve a balance between the computational load and reliability of estimations of the three models. In fact, even though it is easy to imagine that the more complex the model, the more the prediction improves, sometimes a "slight" worsening of estimations can be accepted in exchange for the time saved in data organization and computational load. The models' outcomes were validated through a detailed statistical, error analysis, which revealed a slightly better estimation of the polynomial model with respect to the multilinear model, as expected. On the other hand, even though the data organization was identical for the two models, the multilinear one required a simpler simulation setting and a faster run time. Finally, the most reliable evolutionary polynomial regression model was used in order to make some conjecture about the uncertainty increase with the extension of extrapolation time of the estimation. The overlapping rate between the confidence band of the mean of the known coast position and the prediction band of the estimated position can be a good index of the weakness in producing reliable estimations when the extrapolation time increases too much. The proposed models and tests have been applied to a coastal sector located nearby Torre Colimena in the Apulia region, south Italy.

  6. ARA and ARI imperfect repair models: Estimation, goodness-of-fit and reliability prediction

    International Nuclear Information System (INIS)

    Toledo, Maria Luíza Guerra de; Freitas, Marta A.; Colosimo, Enrico A.; Gilardoni, Gustavo L.

    2015-01-01

    An appropriate maintenance policy is essential to reduce expenses and risks related to equipment failures. A fundamental aspect to be considered when specifying such policies is to be able to predict the reliability of the systems under study, based on a well fitted model. In this paper, the classes of models Arithmetic Reduction of Age and Arithmetic Reduction of Intensity are explored. Likelihood functions for such models are derived, and a graphical method is proposed for model selection. A real data set involving failures in trucks used by a Brazilian mining is analyzed considering models with different memories. Parameters, namely, shape and scale for Power Law Process, and the efficiency of repair were estimated for the best fitted model. Estimation of model parameters allowed us to derive reliability estimators to predict the behavior of the failure process. These results are a valuable information for the mining company and can be used to support decision making regarding preventive maintenance policy. - Highlights: • Likelihood functions for imperfect repair models are derived. • A goodness-of-fit technique is proposed as a tool for model selection. • Failures in trucks owned by a Brazilian mining are modeled. • Estimation allowed deriving reliability predictors to forecast the future failure process of the trucks

  7. An overview of erosion corrosion models and reliability assessment for corrosion defects in piping system

    International Nuclear Information System (INIS)

    Srividya, A.; Suresh, H.N.; Verma, A.K.; Gopika, V.; Santosh

    2006-01-01

    Piping systems are part of passive structural elements in power plants. The analysis of the piping systems and their quantification in terms of failure probability is of utmost importance. The piping systems may fail due to various degradation mechanisms like thermal fatigue, erosion-corrosion, stress corrosion cracking and vibration fatigue. On examination of previous results, erosion corrosion was more prevalent and wall thinning is a time dependent phenomenon. The paper is intended to consolidate the work done by various investigators on erosion corrosion in estimating the erosion corrosion rate and reliability predictions. A comparison of various erosion corrosion models is made. The reliability predictions based on remaining strength of corroded pipelines by wall thinning is also attempted. Variables in the limit state functions are modelled using normal distributions and Reliability assessment is carried out using some of the existing failure pressure models. A steady state corrosion rate is assumed to estimate the corrosion defect and First Order Reliability Method (FORM) is used to find the probability of failure associated with corrosion defects over time using the software for Component Reliability evaluation (COMREL). (author)

  8. Efficient surrogate models for reliability analysis of systems with multiple failure modes

    International Nuclear Information System (INIS)

    Bichon, Barron J.; McFarland, John M.; Mahadevan, Sankaran

    2011-01-01

    Despite many advances in the field of computational reliability analysis, the efficient estimation of the reliability of a system with multiple failure modes remains a persistent challenge. Various sampling and analytical methods are available, but they typically require accepting a tradeoff between accuracy and computational efficiency. In this work, a surrogate-based approach is presented that simultaneously addresses the issues of accuracy, efficiency, and unimportant failure modes. The method is based on the creation of Gaussian process surrogate models that are required to be locally accurate only in the regions of the component limit states that contribute to system failure. This approach to constructing surrogate models is demonstrated to be both an efficient and accurate method for system-level reliability analysis. - Highlights: → Extends efficient global reliability analysis to systems with multiple failure modes. → Constructs locally accurate Gaussian process models of each response. → Highly efficient and accurate method for assessing system reliability. → Effectiveness is demonstrated on several test problems from the literature.

  9. Intra-observer reliability and agreement of manual and digital orthodontic model analysis.

    Science.gov (United States)

    Koretsi, Vasiliki; Tingelhoff, Linda; Proff, Peter; Kirschneck, Christian

    2018-01-23

    Digital orthodontic model analysis is gaining acceptance in orthodontics, but its reliability is dependent on the digitalisation hardware and software used. We thus investigated intra-observer reliability and agreement / conformity of a particular digital model analysis work-flow in relation to traditional manual plaster model analysis. Forty-eight plaster casts of the upper/lower dentition were collected. Virtual models were obtained with orthoX®scan (Dentaurum) and analysed with ivoris®analyze3D (Computer konkret). Manual model analyses were done with a dial caliper (0.1 mm). Common parameters were measured on each plaster cast and its virtual counterpart five times each by an experienced observer. We assessed intra-observer reliability within method (ICC), agreement/conformity between methods (Bland-Altman analyses and Lin's concordance correlation), and changing bias (regression analyses). Intra-observer reliability was substantial within each method (ICC ≥ 0.7), except for five manual outcomes (12.8 per cent). Bias between methods was statistically significant, but less than 0.5 mm for 87.2 per cent of the outcomes. In general, larger tooth sizes were measured digitally. Total difference maxilla and mandible had wide limits of agreement (-3.25/6.15 and -2.31/4.57 mm), but bias between methods was mostly smaller than intra-observer variation within each method with substantial conformity of manual and digital measurements in general. No changing bias was detected. Although both work-flows were reliable, the investigated digital work-flow proved to be more reliable and yielded on average larger tooth sizes. Averaged differences between methods were within 0.5 mm for directly measured outcomes but wide ranges are expected for some computed space parameters due to cumulative error. © The Author 2017. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com

  10. Dual action of high estradiol doses on MNU-induced prostate neoplasms in a rodent model with high serum testosterone: Protective effect and emergence of unstable epithelial microenvironment.

    Science.gov (United States)

    Gonçalves, Bianca F; de Campos, Silvana G P; Góes, Rejane M; Scarano, Wellerson R; Taboga, Sebastião R; Vilamaior, Patricia S L

    2017-06-01

    Estrogens are critical players in prostate growth and disease. Estrogen therapy has been the standard treatment for advanced prostate cancer for several decades; however, it has currently been replaced by alternative anti-androgenic therapies. Additionally, studies of its action on prostate biology, resulting from an association between carcinogens and estrogen, at different stages of life are scarce or inconclusive about its protective and beneficial role on induced-carcinogenesis. Thus, the aim of this study was to determine whether estradiol exerts a protective and/or stimulatory role on N-methyl-N-nitrosurea-induced prostate neoplasms. We adopted a rodent model that has been used to study induced-prostate carcinogenesis: the Mongolian gerbil. We investigated the occurrence of neoplasms, karyometric patterns, androgen and estrogen receptors, basal cells, and global methylation status in ventral and dorsolateral prostate tissues. Histopathological analysis showed that estrogen was able to slow tumor growth in both lobes after prolonged treatment. However, a true neoplastic regression was observed only in the dorsolateral prostate. In addition to the protective effects against neoplastic progression, estrogen treatment resulted in an epithelium that exhibited features distinctive from a normal prostate, including increased androgen-insensitive basal cells, high androgens and estrogen receptor positivity, and changes in DNA methylation patterns. Estrogen was able to slow tumor growth, but the epithelium exhibited features distinct from a normal prostatic epithelium, and this unstable microenvironment could trigger lesion recurrence over time. © 2017 Wiley Periodicals, Inc.

  11. Effects of L-arginine on anatomical and electrophysiological deterioration of the eye in a rodent model of nonarteritic ischemic optic neuropathy.

    Science.gov (United States)

    Chuman, Hideki; Maekubo, Tomoyuki; Osako, Takako; Ishiai, Michitaka; Kawano, Naoko; Nao-I, Nobuhisa

    2013-07-01

    The aims of this study were to clarify the effectiveness of L-arginine (1) for reducing the severity of anatomical changes in the eye and improving visual function in the acute stage of a rodent model of nonarteritic ischemic optic neuropathy (rNAION) and (2) in preventing those changes in anatomy and visual function. For the first aim, L-arginine was intravenously injected into rats 3 h after rNAION induction; for the second aim, rNAION was induced after the oral administration of L-arginine for 7 days. The inner retinal thickness was determined over time by optical coherence tomography, and the amplitude of the scotopic threshold response (STR) and the number of surviving retinal ganglion cells (RGCs) were measured. These data were compared with the baseline data from the control group. Both intravenous infusion of L-arginine after rNAION induction and oral pretreatment with L-arginine significantly decreased optic disc edema in the acute stage and thinning of the inner retina, reduced the decrease in STR amplitude, and reduced the decrease in the number of RGCs during rNAION. Based on these results, we conclude that L-arginine treatment is effective for reducing anatomical changes in the eye and improving visual function in the acute stage of rNAION and that pretreatment with L-arginine is an effective therapy to reduce the severity of the condition during recurrence in the other eye.

  12. Traumatic stress causes distinctive effects on fear circuit catecholamines and the fear extinction profile in a rodent model of posttraumatic stress disorder.

    Science.gov (United States)

    Lin, Chen-Cheng; Tung, Che-Se; Lin, Pin-Hsuan; Huang, Chuen-Lin; Liu, Yia-Ping

    2016-09-01

    Central catecholamines regulate fear memory across the medial prefrontal cortex (mPFC), amygdala (AMYG), and hippocampus (HPC). However, inadequate evidence exists to address the relationships among these fear circuit areas in terms of the fear symptoms of posttraumatic stress disorder (PTSD). By examining the behavioral profile in a Pavlovian fear conditioning paradigm together with tissue/efflux levels of dopamine (DA) and norepinephrine (NE) and their reuptake abilities across the fear circuit areas in rats that experienced single prolonged stress (SPS, a rodent model of PTSD), we demonstrated that SPS-impaired extinction retrieval was concomitant with the changes of central DA/NE in a dissociable manner. For tissue levels, diminished DA and increased NE were both observed in the mPFC and AMYG. DA efflux and synaptosomal DA transporter were consistently reduced in the AMYG/vHPC, whereas SPS reduced NE efflux in the infralimbic cortex and synaptosomal NE transporter in the mPFC. Furthermore, a lower expression of synaptosomal VMAT2 was observed in the mPFC, AMYG, and vHPC after SPS. Finally, negative correlations were observed between retrieval freezing and DA in the mPFC/AMYG; nevertheless, the phenomena became invalid after SPS. Our results suggest that central catecholamines are crucially involved in the retrieval of fear extinction in which DA and NE play distinctive roles across the fear circuit areas. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  13. Deep brain stimulation of the ventral hippocampus restores deficits in processing of auditory evoked potentials in a rodent developmental disruption model of schizophrenia.

    Science.gov (United States)

    Ewing, Samuel G; Grace, Anthony A

    2013-02-01

    Existing antipsychotic drugs are most effective at treating the positive symptoms of schizophrenia but their relative efficacy is low and they are associated with considerable side effects. In this study deep brain stimulation of the ventral hippocampus was performed in a rodent model of schizophrenia (MAM-E17) in an attempt to alleviate one set of neurophysiological alterations observed in this disorder. Bipolar stimulating electrodes were fabricated and implanted, bilaterally, into the ventral hippocampus of rats. High frequency stimulation was delivered bilaterally via a custom-made stimulation device and both spectral analysis (power and coherence) of resting state local field potentials and amplitude of auditory evoked potential components during a standard inhibitory gating paradigm were examined. MAM rats exhibited alterations in specific components of the auditory evoked potential in the infralimbic cortex, the core of the nucleus accumbens, mediodorsal thalamic nucleus, and ventral hippocampus in the left hemisphere only. DBS was effective in reversing these evoked deficits in the infralimbic cortex and the mediodorsal thalamic nucleus of MAM-treated rats to levels similar to those observed in control animals. In contrast stimulation did not alter evoked potentials in control rats. No deficits or stimulation-induced alterations were observed in the prelimbic and orbitofrontal cortices, the shell of the nucleus accumbens or ventral tegmental area. These data indicate a normalization of deficits in generating auditory evoked potentials induced by a developmental disruption by acute high frequency, electrical stimulation of the ventral hippocampus. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Amyloid beta and the longest-lived rodent: the naked mole-rat as a model for natural protection from Alzheimer's disease.

    Science.gov (United States)

    Edrey, Yael H; Medina, David X; Gaczynska, Maria; Osmulski, Pawel A; Oddo, Salvatore; Caccamo, Antonella; Buffenstein, Rochelle

    2013-10-01

    Amyloid beta (Aβ) is implicated in Alzheimer's disease (AD) as an integral component of both neural toxicity and plaque formation. Brains of the longest-lived rodents, naked mole-rats (NMRs) approximately 32 years of age, had levels of Aβ similar to those of the 3xTg-AD mouse model of AD. Interestingly, there was no evidence of extracellular plaques, nor was there an age-related increase in Aβ levels in the individuals examined (2-20+ years). The NMR Aβ peptide showed greater homology to the human sequence than to the mouse sequence, differing by only 1 amino acid from the former. This subtle difference led to interspecies differences in aggregation propensity but not neurotoxicity; NMR Aβ was less prone to aggregation than human Aβ. Nevertheless, both NMR and human Aβ were equally toxic to mouse hippocampal neurons, suggesting that Aβ neurotoxicity and aggregation properties were not coupled. Understanding how NMRs acquire and tolerate high levels of Aβ with no plaque formation could provide useful insights into AD, and may elucidate protective mechanisms that delay AD progression. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Robot-Applied Resistance Augments the Effects of Body Weight-Supported Treadmill Training on Stepping and Synaptic Plasticity in a Rodent Model of Spinal Cord Injury.

    Science.gov (United States)

    Hinahon, Erika; Estrada, Christina; Tong, Lin; Won, Deborah S; de Leon, Ray D

    2017-08-01

    The application of resistive forces has been used during body weight-supported treadmill training (BWSTT) to improve walking function after spinal cord injury (SCI). Whether this form of training actually augments the effects of BWSTT is not yet known. To determine if robotic-applied resistance augments the effects of BWSTT using a controlled experimental design in a rodent model of SCI. Spinally contused rats were treadmill trained using robotic resistance against horizontal (n = 9) or vertical (n = 8) hind limb movements. Hind limb stepping was tested before and after 6 weeks of training. Two control groups, one receiving standard training (ie, without resistance; n = 9) and one untrained (n = 8), were also tested. At the terminal experiment, the spinal cords were prepared for immunohistochemical analysis of synaptophysin. Six weeks of training with horizontal resistance increased step length, whereas training with vertical resistance enhanced step height and movement velocity. None of these changes occurred in the group that received standard (ie, no resistance) training or in the untrained group. Only standard training increased the number of step cycles and shortened cycle period toward normal values. Synaptophysin expression in the ventral horn was highest in rats trained with horizontal resistance and in untrained rats and was positively correlated with step length. Adding robotic-applied resistance to BWSTT produced gains in locomotor function over BWSTT alone. The impact of resistive forces on spinal connections may depend on the nature of the resistive forces and the synaptic milieu that is present after SCI.

  16. A simulation model for reliability evaluation of Space Station power systems

    Science.gov (United States)

    Singh, C.; Patton, A. D.; Kumar, Mudit; Wagner, H.

    1988-01-01

    A detailed simulation model for the hybrid Space Station power system is presented which allows photovoltaic and solar dynamic power sources to be mixed in varying proportions. The model considers the dependence of reliability and storage characteristics during the sun and eclipse periods, and makes it possible to model the charging and discharging of the energy storage modules in a relatively accurate manner on a continuous basis.

  17. A Mathematical Model of the Olfactory Bulb for the Selective Adaptation Mechanism in the Rodent Olfactory System.

    Science.gov (United States)

    Soh, Zu; Nishikawa, Shinya; Kurita, Yuichi; Takiguchi, Noboru; Tsuji, Toshio

    2016-01-01

    To predict the odor quality of an odorant mixture, the interaction between odorants must be taken into account. Previously, an experiment in which mice discriminated between odorant mixtures identified a selective adaptation mechanism in the olfactory system. This paper proposes an olfactory model for odorant mixtures that can account for selective adaptation in terms of neural activity. The proposed model uses the spatial activity pattern of the mitral layer obtained from model simulations to predict the perceptual similarity between odors. Measured glomerular activity patterns are used as input to the model. The neural interaction between mitral cells and granular cells is then simulated, and a dissimilarity index between odors is defined using the activity patterns of the mitral layer. An odor set composed of three odorants is used to test the ability of the model. Simulations are performed based on the odor discrimination experiment on mice. As a result, we observe that part of the neural activity in the glomerular layer is enhanced in the mitral layer, whereas another part is suppressed. We find that the dissimilarity index strongly correlates with the odor discrimination rate of mice: r = 0.88 (p = 0.019). We conclude that our model has the ability to predict the perceptual similarity of odorant mixtures. In addition, the model also accounts for selective adaptation via the odor discrimination rate, and the enhancement and inhibition in the mitral layer may be related to this selective adaptation.

  18. Modeling reliability of power systems substations by using stochastic automata networks

    International Nuclear Information System (INIS)

    Šnipas, Mindaugas; Radziukynas, Virginijus; Valakevičius, Eimutis

    2017-01-01

    In this paper, stochastic automata networks (SANs) formalism to model reliability of power systems substations is applied. The proposed strategy allows reducing the size of state space of Markov chain model and simplifying system specification. Two case studies of standard configurations of substations are considered in detail. SAN models with different assumptions were created. SAN approach is compared with exact reliability calculation by using a minimal path set method. Modeling results showed that total independence of automata can be assumed for relatively small power systems substations with reliable equipment. In this case, the implementation of Markov chain model by a using SAN method is a relatively easy task. - Highlights: • We present the methodology to apply stochastic automata network formalism to create Markov chain models of power systems. • The stochastic automata network approach is combined with minimal path sets and structural functions. • Two models of substation configurations with different model assumptions are presented to illustrate the proposed methodology. • Modeling results of system with independent automata and functional transition rates are similar. • The conditions when total independence of automata can be assumed are addressed.

  19. Reliable gain-scheduled control of discrete-time systems and its application to CSTR model

    Science.gov (United States)

    Sakthivel, R.; Selvi, S.; Mathiyalagan, K.; Shi, Y.

    2016-10-01

    This paper is focused on reliable gain-scheduled controller design for a class of discrete-time systems with randomly occurring nonlinearities and actuator fault. Further, the nonlinearity in the system model is assumed to occur randomly according to a Bernoulli distribution with measurable time-varying probability in real time. The main purpose of this paper is to design a gain-scheduled controller by implementing a probability-dependent Lyapunov function and linear matrix inequality (LMI) approach such that the closed-loop discrete-time system is stochastically stable for all admissible randomly occurring nonlinearities. The existence conditions for the reliable controller is formulated in terms of LMI constraints. Finally, the proposed reliable gain-scheduled control scheme is applied on continuously stirred tank reactor model to demonstrate the effectiveness and applicability of the proposed design technique.

  20. Study on reliability analysis based on multilevel flow models and fault tree method

    International Nuclear Information System (INIS)

    Chen Qiang; Yang Ming

    2014-01-01

    Multilevel flow models (MFM) and fault tree method describe the system knowledge in different forms, so the two methods express an equivalent logic of the system reliability under the same boundary conditions and assumptions. Based on this and combined with the characteristics of MFM, a method mapping MFM to fault tree was put forward, thus providing a way to establish fault tree rapidly and realizing qualitative reliability analysis based on MFM. Taking the safety injection system of pressurized water reactor nuclear power plant as an example, its MFM was established and its reliability was analyzed qualitatively. The analysis result shows that the logic of mapping MFM to fault tree is correct. The MFM is easily understood, created and modified. Compared with the traditional fault tree analysis, the workload is greatly reduced and the modeling time is saved. (authors)

  1. Estimation of placental and lactational transfer and tissue distribution of atrazine and its main metabolites in rodent dams, fetuses, and neonates with physiologically based pharmacokinetic modeling

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Zhoumeng [Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602 (United States); Interdisciplinary Toxicology Program, University of Georgia, Athens, GA 30602 (United States); Fisher, Jeffrey W. [Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States); Wang, Ran [Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762 (United States); Institute of Food Safety, Jiangsu Academy of Agricultural Sciences, Nanjing 210014 (China); Ross, Matthew K. [Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762 (United States); Filipov, Nikolay M., E-mail: filipov@uga.edu [Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602 (United States); Interdisciplinary Toxicology Program, University of Georgia, Athens, GA 30602 (United States)

    2013-11-15

    Atrazine (ATR) is a widely used chlorotriazine herbicide, a ubiquitous environmental contaminant, and a potential developmental toxicant. To quantitatively evaluate placental/lactational transfer and fetal/neonatal tissue dosimetry of ATR and its major metabolites, physiologically based pharmacokinetic models were developed for rat dams, fetuses and neonates. These models were calibrated using pharmacokinetic data from rat dams repeatedly exposed (oral gavage; 5 mg/kg) to ATR followed by model evaluation against other available rat data. Model simulations corresponded well to the majority of available experimental data and suggest that: (1) the fetus is exposed to both ATR and its major metabolite didealkylatrazine (DACT) at levels similar to maternal plasma levels, (2) the neonate is exposed mostly to DACT at levels two-thirds lower than maternal plasma or fetal levels, while lactational exposure to ATR is minimal, and (3) gestational carryover of DACT greatly affects its neonatal dosimetry up until mid-lactation. To test the model's cross-species extrapolation capability, a pharmacokinetic study was conducted with pregnant C57BL/6 mice exposed (oral gavage; 5 mg/kg) to ATR from gestational day 12 to 18. By using mouse-specific parameters, the model predictions fitted well with the measured data, including placental ATR/DACT levels. However, fetal concentrations of DACT were overestimated by the model (10-fold). This overestimation suggests that only around 10% of the DACT that reaches the fetus is tissue-bound. These rodent models could be used in fetal/neonatal tissue dosimetry predictions to help design/interpret early life toxicity/pharmacokinetic studies with ATR and as a foundation for scaling to humans. - Highlights: • We developed PBPK models for atrazine in rat dams, fetuses, and neonates. • We conducted pharmacokinetic (PK) study with atrazine in pregnant mice. • Model predictions were in good agreement with experimental rat and mouse PK data

  2. Estimation of placental and lactational transfer and tissue distribution of atrazine and its main metabolites in rodent dams, fetuses, and neonates with physiologically based pharmacokinetic modeling

    International Nuclear Information System (INIS)

    Lin, Zhoumeng; Fisher, Jeffrey W.; Wang, Ran; Ross, Matthew K.; Filipov, Nikolay M.

    2013-01-01

    Atrazine (ATR) is a widely used chlorotriazine herbicide, a ubiquitous environmental contaminant, and a potential developmental toxicant. To quantitatively evaluate placental/lactational transfer and fetal/neonatal tissue dosimetry of ATR and its major metabolites, physiologically based pharmacokinetic models were developed for rat dams, fetuses and neonates. These models were calibrated using pharmacokinetic data from rat dams repeatedly exposed (oral gavage; 5 mg/kg) to ATR followed by model evaluation against other available rat data. Model simulations corresponded well to the majority of available experimental data and suggest that: (1) the fetus is exposed to both ATR and its major metabolite didealkylatrazine (DACT) at levels similar to maternal plasma levels, (2) the neonate is exposed mostly to DACT at levels two-thirds lower than maternal plasma or fetal levels, while lactational exposure to ATR is minimal, and (3) gestational carryover of DACT greatly affects its neonatal dosimetry up until mid-lactation. To test the model's cross-species extrapolation capability, a pharmacokinetic study was conducted with pregnant C57BL/6 mice exposed (oral gavage; 5 mg/kg) to ATR from gestational day 12 to 18. By using mouse-specific parameters, the model predictions fitted well with the measured data, including placental ATR/DACT levels. However, fetal concentrations of DACT were overestimated by the model (10-fold). This overestimation suggests that only around 10% of the DACT that reaches the fetus is tissue-bound. These rodent models could be used in fetal/neonatal tissue dosimetry predictions to help design/interpret early life toxicity/pharmacokinetic studies with ATR and as a foundation for scaling to humans. - Highlights: • We developed PBPK models for atrazine in rat dams, fetuses, and neonates. • We conducted pharmacokinetic (PK) study with atrazine in pregnant mice. • Model predictions were in good agreement with experimental rat and mouse PK data.

  3. Human psychophysics and rodent spinal neurones exhibit peripheral and central mechanisms of inflammatory pain in the UVB and UVB heat rekindling models.

    Science.gov (United States)

    O'Neill, Jessica; Sikandar, Shafaq; McMahon, Stephen B; Dickenson, Anthony H

    2015-09-01

    Translational research is key to bridging the gaps between preclinical findings and the patients, and a translational model of inflammatory pain will ideally induce both peripheral and central sensitisation, more effectively mimicking clinical pathophysiology in some chronic inflammatory conditions. We conducted a parallel investigation of two models of inflammatory pain, using ultraviolet B (UVB) irradiation alone and UVB irradiation with heat rekindling. We used rodent electrophysiology and human quantitative sensory testing to characterise nociceptive processing in the peripheral and central nervous systems in both models. In both species, UVB irradiation produces peripheral sensitisation measured as augmented evoked activity of rat dorsal horn neurones and increased perceptual responses of human subjects to mechanical and thermal stimuli. In both species, UVB with heat rekindling produces central sensitisation. UVB irradiation alone and UVB with heat rekindling are translational models of inflammation that produce peripheral and central sensitisation, respectively. The predictive value of laboratory models for human pain processing is crucial for improving translational research. The discrepancy between peripheral and central mechanisms of pain is an important consideration for drug targets, and here we describe two models of inflammatory pain that involve ultraviolet B (UVB) irradiation, which can employ peripheral and central sensitisation to produce mechanical and thermal hyperalgesia in rats and humans. We use electrophysiology in rats to measure the mechanically- and thermally-evoked activity of rat spinal neurones and quantitative sensory testing to assess human psychophysical responses to mechanical and thermal stimulation in a model of UVB irradiation and in a model of UVB irradiation with heat rekindling. Our results demonstrate peripheral sensitisation in both species driven by UVB irradiation, with a clear mechanical and thermal hypersensitivity of

  4. Reliability of Coulomb stress changes inferred from correlated uncertainties of finite-fault source models

    KAUST Repository

    Woessner, J.

    2012-07-14

    Static stress transfer is one physical mechanism to explain triggered seismicity. Coseismic stress-change calculations strongly depend on the parameterization of the causative finite-fault source model. These models are uncertain due to uncertainties in input data, model assumptions, and modeling procedures. However, fault model uncertainties have usually been ignored in stress-triggering studies and have not been propagated to assess the reliability of Coulomb failure stress change (ΔCFS) calculations. We show how these uncertainties can be used to provide confidence intervals for co-seismic ΔCFS-values. We demonstrate this for the MW = 5.9 June 2000 Kleifarvatn earthquake in southwest Iceland and systematically map these uncertainties. A set of 2500 candidate source models from the full posterior fault-parameter distribution was used to compute 2500 ΔCFS maps. We assess the reliability of the ΔCFS-values from the coefficient of variation (CV) and deem ΔCFS-values to be reliable where they are at least twice as large as the standard deviation (CV ≤ 0.5). Unreliable ΔCFS-values are found near the causative fault and between lobes of positive and negative stress change, where a small change in fault strike causes ΔCFS-values to change sign. The most reliable ΔCFS-values are found away from the source fault in the middle of positive and negative ΔCFS-lobes, a likely general pattern. Using the reliability criterion, our results support the static stress-triggering hypothesis. Nevertheless, our analysis also suggests that results from previous stress-triggering studies not considering source model uncertainties may have lead to a biased interpretation of the importance of static stress-triggering.

  5. The application of cognitive models to the evaluation and prediction of human reliability

    International Nuclear Information System (INIS)

    Embrey, D.E.; Reason, J.T.

    1986-01-01

    The first section of the paper provides a brief overview of a number of important principles relevant to human reliability modeling that have emerged from cognitive models, and presents a synthesis of these approaches in the form of a Generic Error Modeling System (GEMS). The next section illustrates the application of GEMS to some well known nuclear power plant (NPP) incidents in which human error was a major contributor. The way in which design recommendations can emerge from analyses of this type is illustrated. The third section describes the use of cognitive models in the classification of human errors for prediction and data collection purposes. The final section addresses the predictive modeling of human error as part of human reliability assessment in Probabilistic Risk Assessment

  6. A hybrid reliability algorithm using PSO-optimized Kriging model and adaptive importance sampling

    Science.gov (United States)

    Tong, Cao; Gong, Haili

    2018-03-01

    This paper aims to reduce the computational cost of reliability analysis. A new hybrid algorithm is proposed based on PSO-optimized Kriging model and adaptive importance sampling method. Firstly, the particle swarm optimization algorithm (PSO) is used to optimize the parameters of Kriging model. A typical function is fitted to validate improvement by comparing results of PSO-optimized Kriging model with those of the original Kriging model. Secondly, a hybrid algorithm for reliability analysis combined optimized Kriging model and adaptive importance sampling is proposed. Two cases from literatures are given to validate the efficiency and correctness. The proposed method is proved to be more efficient due to its application of small number of sample points according to comparison results.

  7. The hippocampus, medial prefrontal cortex, and selective memory retrieval: evidence from a rodent model of the retrieval-induced forgetting effect.

    Science.gov (United States)

    Wu, Jade Q; Peters, Greg J; Rittner, Pedro; Cleland, Thomas A; Smith, David M

    2014-09-01

    Inhibition is an important component of many cognitive functions, including memory. For example, the retrieval-induced forgetting (RIF) effect occurs when extra practice with some items from a study list inhibits the retrieval of the nonpracticed items relative to a baseline condition that does not involve extra practice. Although counterintuitive, the RIF phenomenon may be important for resolving interference by inhibiting potentially competing retrieval targets. Neuroimaging studies suggest that the hippocampus and prefrontal cortex are involved in the RIF effect, but controlled lesion studies have not yet been performed. We developed a rodent model of the RIF training procedure and trained control rats and rats with temporary inactivation of the hippocampus or medial prefrontal cortex (mPFC). Rats were trained on a list of odor cues, presented in cups of digging medium with a buried reward, followed by additional practice trials with a subset of the cues. We then tested the rats' memories for the cues and their association with reward by presenting them with unbaited cups containing the test odorants and measuring how long they persisted in digging. Control rats exhibited a robust RIF effect in which memory for the nonpracticed odors was significantly inhibited. Thus, extra practice with some odor cues inhibited memory for the others, relative to a baseline condition that involved an identical amount of training. Inactivation of either the hippocampus or the mPFC blocked the RIF effect. We also constructed a computational model of a representational learning circuit to simulate the RIF effect. We show in this model that "sideband suppression" of similar memory representations can reproduce the RIF effect and that alteration of the suppression parameters and learning rate can reproduce the lesion effects seen in our rats. Our results suggest that the RIF effect is widespread and that inhibitory processes are an important feature of memory function. © 2014 Wiley

  8. Dysregulated neuronal activity patterns implicate corticostriatal circuit dysfunction in multiple rodent models of Huntington’s disease

    Directory of Open Access Journals (Sweden)

    Benjamin R. Miller

    2011-05-01

    Full Text Available Huntington’s disease (HD is an autosomal dominant neurodegenerative disorder that targets the corticostriatal system and results in progressive deterioration of cognitive, emotional, and motor skills. Although cortical and striatal neurons are widely studied in animal models of HD, there is little information on neuronal function during expression of the HD behavioral phenotype. To address this knowledge gap, we used chronically implanted micro-wire bundles to record extracellular spikes and local field potentials (LFPs in truncated (R6/1 and R6/2 and full-length (knock-in, KI mouse models as well as in tgHD rats behaving in an open-field arena. Spike activity was recorded in the striatum of all models and in prefrontal cortex (PFC of R6/2 and KI mice, and in primary motor cortex (M1 of R6/2 mice. We also recorded LFP activity in R6/2 striatum. All HD models exhibited altered neuronal activity relative to wild-type (WT controls. Although there was no consistent effect on firing rate across models and brain areas, burst firing was reduced in striatum, PFC, and M1 of R6/2 mice, and in striatum of KI mice. Consistent with a decline in bursting, the interspike-interval coefficient of variation was reduced in all regions of all models, except PFC of KI mice and striatum of tgHD rats. Among simultaneously recorded neuron pairs, correlated firing was reduced in all brain regions of all models, while coincident bursting, which measures the temporal overlap between bursting pairs, was reduced in striatum of all models as well as in M1 of R6/2's. Preliminary analysis of striatal LFPs revealed aberrant behavior-related oscillations in the delta to theta range and in gamma activity. Collectively, our results indicate that disrupted corticostriatal processing occurs across multiple HD models despite differences in the severity of the behavioral phenotype. Efforts aimed at normalizing corticostriatal activity may hold the key to developing new HD

  9. Development of web-based reliability data analysis algorithm model and its application

    International Nuclear Information System (INIS)

    Hwang, Seok-Won; Oh, Ji-Yong; Moosung-Jae

    2010-01-01

    For this study, a database model of plant reliability was developed for the effective acquisition and management of plant-specific data that can be used in various applications of plant programs as well as in Probabilistic Safety Assessment (PSA). Through the development of a web-based reliability data analysis algorithm, this approach systematically gathers specific plant data such as component failure history, maintenance history, and shift diary. First, for the application of the developed algorithm, this study reestablished the raw data types, data deposition procedures and features of the Enterprise Resource Planning (ERP) system process. The component codes and system codes were standardized to make statistical analysis between different types of plants possible. This standardization contributes to the establishment of a flexible database model that allows the customization of reliability data for the various applications depending on component types and systems. In addition, this approach makes it possible for users to perform trend analyses and data comparisons for the significant plant components and systems. The validation of the algorithm is performed through a comparison of the importance measure value (Fussel-Vesely) of the mathematical calculation and that of the algorithm application. The development of a reliability database algorithm is one of the best approaches for providing systemic management of plant-specific reliability data with transparency and continuity. This proposed algorithm reinforces the relationships between raw data and application results so that it can provide a comprehensive database that offers everything from basic plant-related data to final customized data.

  10. A Review of the Progress with Statistical Models of Passive Component Reliability

    Directory of Open Access Journals (Sweden)

    Bengt O.Y. Lydell

    2017-03-01

    Full Text Available During the past 25 years, in the context of probabilistic safety assessment, efforts have been directed towards establishment of comprehensive pipe failure event databases as a foundation for exploratory research to better understand how to effectively organize a piping reliability analysis task. The focused pipe failure database development efforts have progressed well with the development of piping reliability analysis frameworks that utilize the full body of service experience data, fracture mechanics analysis insights, expert elicitation results that are rolled into an integrated and risk-informed approach to the estimation of piping reliability parameters with full recognition of the embedded uncertainties. The discussion in this paper builds on a major collection of operating experience data (more than 11,000 pipe failure records and the associated lessons learned from data analysis and data applications spanning three decades. The piping reliability analysis lessons learned have been obtained from the derivation of pipe leak and rupture frequencies for corrosion resistant piping in a raw water environment, loss-of-coolant-accident frequencies given degradation mitigation, high-energy pipe break analysis, moderate-energy pipe break analysis, and numerous plant-specific applications of a statistical piping reliability model framework. Conclusions are presented regarding the feasibility of determining and incorporating aging effects into probabilistic safety assessment models.

  11. A review of the progress with statistical models of passive component reliability

    Energy Technology Data Exchange (ETDEWEB)

    Lydell, Bengt O. Y. [Sigma-Phase Inc., Vail (United States)

    2017-03-15

    During the past 25 years, in the context of probabilistic safety assessment, efforts have been directed towards establishment of comprehensive pipe failure event databases as a foundation for exploratory research to better understand how to effectively organize a piping reliability analysis task. The focused pipe failure database development efforts have progressed well with the development of piping reliability analysis frameworks that utilize the full body of service experience data, fracture mechanics analysis insights, expert elicitation results that are rolled into an integrated and risk-informed approach to the estimation of piping reliability parameters with full recognition of the embedded uncertainties. The discussion in this paper builds on a major collection of operating experience data (more than 11,000 pipe failure records) and the associated lessons learned from data analysis and data applications spanning three decades. The piping reliability analysis lessons learned have been obtained from the derivation of pipe leak and rupture frequencies for corrosion resistant piping in a raw water environment, loss-of-coolant-accident frequencies given degradation mitigation, high-energy pipe break analysis, moderate-energy pipe break analysis, and numerous plant-specific applications of a statistical piping reliability model framework. Conclusions are presented regarding the feasibility of determining and incorporating aging effects into probabilistic safety assessment models.

  12. Development of web-based reliability data analysis algorithm model and its application

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Seok-Won, E-mail: swhwang@khnp.co.k [Korea Hydro and Nuclear Power Co. Ltd., Jang-Dong 25-1, Yuseong-Gu, 305-343 Daejeon (Korea, Republic of); Oh, Ji-Yong [Korea Hydro and Nuclear Power Co. Ltd., Jang-Dong 25-1, Yuseong-Gu, 305-343 Daejeon (Korea, Republic of); Moosung-Jae [Department of Nuclear Engineering Hanyang University 17 Haengdang, Sungdong, Seoul (Korea, Republic of)

    2010-02-15

    For this study, a database model of plant reliability was developed for the effective acquisition and management of plant-specific data that can be used in various applications of plant programs as well as in Probabilistic Safety Assessment (PSA). Through the development of a web-based reliability data analysis algorithm, this approach systematically gathers specific plant data such as component failure history, maintenance history, and shift diary. First, for the application of the developed algorithm, this study reestablished the raw data types, data deposition procedures and features of the Enterprise Resource Planning (ERP) system process. The component codes and system codes were standardized to make statistical analysis between different types of plants possible. This standardization contributes to the establishment of a flexible database model that allows the customization of reliability data for the various applications depending on component types and systems. In addition, this approach makes it possible for users to perform trend analyses and data comparisons for the significant plant components and systems. The validation of the algorithm is performed through a comparison of the importance measure value (Fussel-Vesely) of the mathematical calculation and that of the algorithm application. The development of a reliability database algorithm is one of the best approaches for providing systemic management of plant-specific reliability data with transparency and continuity. This proposed algorithm reinforces the relationships between raw data and application results so that it can provide a comprehensive database that offers everything from basic plant-related data to final customized data.

  13. Reliability model for helicopter main gearbox lubrication system using influence diagrams

    International Nuclear Information System (INIS)

    Rashid, H.S.J.; Place, C.S.; Mba, D.; Keong, R.L.C.; Healey, A.; Kleine-Beek, W.; Romano, M.

    2015-01-01

    The loss of oil from a helicopter main gearbox (MGB) leads to increased friction between components, a rise in component surface temperatures, and subsequent mechanical failure of gearbox components. A number of significant helicopter accidents have been caused due to such loss of lubrication. This paper presents a model to assess the reliability of helicopter MGB lubricating systems. Safety risk modeling was conducted for MGB oil system related accidents in order to analyse key failure mechanisms and the contributory factors. Thus, the dominant failure modes for lubrication systems and key contributing components were identified. The Influence Diagram (ID) approach was then employed to investigate reliability issues of the MGB lubrication systems at the level of primary causal factors, thus systematically investigating a complex context of events, conditions, and influences that are direct triggers of the helicopter MGB lubrication system failures. The interrelationships between MGB lubrication system failure types were thus identified, and the influence of each of these factors on the overall MGB lubrication system reliability was assessed. This paper highlights parts of the HELMGOP project, sponsored by the European Aviation Safety Agency to improve helicopter main gearbox reliability. - Highlights: • We investigated methods to optimize helicopter MGB oil system run-dry capability. • Used Influence Diagram to assess design and maintenance factors of MGB oil system. • Factors influencing overall MGB lubrication system reliability were identified. • This globally influences current and future helicopter MGB designs

  14. A review of the progress with statistical models of passive component reliability

    International Nuclear Information System (INIS)

    Lydell, Bengt O. Y.

    2017-01-01

    During the past 25 years, in the context of probabilistic safety assessment, efforts have been directed towards establishment of comprehensive pipe failure event databases as a foundation for exploratory research to better understand how to effectively organize a piping reliability analysis task. The focused pipe failure database development efforts have progressed well with the development of piping reliability analysis frameworks that utilize the full body of service experience data, fracture mechanics analysis insights, expert elicitation results that are rolled into an integrated and risk-informed approach to the estimation of piping reliability parameters with full recognition of the embedded uncertainties. The discussion in this paper builds on a major collection of operating experience data (more than 11,000 pipe failure records) and the associated lessons learned from data analysis and data applications spanning three decades. The piping reliability analysis lessons learned have been obtained from the derivation of pipe leak and rupture frequencies for corrosion resistant piping in a raw water environment, loss-of-coolant-accident frequencies given degradation mitigation, high-energy pipe break analysis, moderate-energy pipe break analysis, and numerous plant-specific applications of a statistical piping reliability model framework. Conclusions are presented regarding the feasibility of determining and incorporating aging effects into probabilistic safety assessment models

  15. A focus on reward in anorexia nervosa through the lens of the activity-based anorexia rodent model.

    Science.gov (United States)

    Foldi, C J; Milton, L K; Oldfield, B J

    2017-10-01

    Patients suffering anorexia nervosa (AN) become anhedonic, unable or unwilling to derive normal pleasures and tend to avoid rewarding outcomes, most profoundly in food intake. The activity-based anorexia model recapitulates many of the pathophysiological and behavioural hallmarks of the human condition, including a reduction in food intake, excessive exercise, dramatic weight loss, loss of reproductive cycles, hypothermia and anhedonia, and therefore it allows investigation into the underlying neurobiology of anorexia nervosa. The use of this model has directed attention to disruptions in central reward neurocircuitry, which may contribute to disease susceptibility. The purpose of this review is to demonstrate the utility of this unique model to provide insight into the mechanisms of reward relevant to feeding and weight loss, which may ultimately help to unravel the neurobiology of anorexia nervosa and, in a broader sense, the foundation of reward-based feeding. © 2017 British Society for Neuroendocrinology.

  16. Improved radiograph measurement inter-observer reliability by use of statistical shape models

    Energy Technology Data Exchange (ETDEWEB)

    Pegg, E.C., E-mail: elise.pegg@ndorms.ox.ac.uk [University of Oxford, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Nuffield Orthopaedic Centre, Windmill Road, Oxford OX3 7LD (United Kingdom); Mellon, S.J., E-mail: stephen.mellon@ndorms.ox.ac.uk [University of Oxford, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Nuffield Orthopaedic Centre, Windmill Road, Oxford OX3 7LD (United Kingdom); Salmon, G. [University of Oxford, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Nuffield Orthopaedic Centre, Windmill Road, Oxford OX3 7LD (United Kingdom); Alvand, A., E-mail: abtin.alvand@ndorms.ox.ac.uk [University of Oxford, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Nuffield Orthopaedic Centre, Windmill Road, Oxford OX3 7LD (United Kingdom); Pandit, H., E-mail: hemant.pandit@ndorms.ox.ac.uk [University of Oxford, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Nuffield Orthopaedic Centre, Windmill Road, Oxford OX3 7LD (United Kingdom); Murray, D.W., E-mail: david.murray@ndorms.ox.ac.uk [University of Oxford, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Nuffield Orthopaedic Centre, Windmill Road, Oxford OX3 7LD (United Kingdom); Gill, H.S., E-mail: richie.gill@ndorms.ox.ac.uk [University of Oxford, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Nuffield Orthopaedic Centre, Windmill Road, Oxford OX3 7LD (United Kingdom)

    2012-10-15

    Pre- and post-operative radiographs of patients undergoing joint arthroplasty are often examined for a variety of purposes including preoperative planning and patient assessment. This work examines the feasibility of using active shape models (ASM) to semi-automate measurements from post-operative radiographs for the specific case of the Oxford™ Unicompartmental Knee. Measurements of the proximal tibia and the position of the tibial tray were made using the ASM model and manually. Data were obtained by four observers and one observer took four sets of measurements to allow assessment of the inter- and intra-observer reliability, respectively. The parameters measured were the tibial tray angle, the tray overhang, the tray size, the sagittal cut position, the resection level and the tibial width. Results demonstrated improved reliability (average of 27% and 11.2% increase for intra- and inter-reliability, respectively) and equivalent accuracy (p > 0.05 for compared data values) for all of the measurements using the ASM model, with the exception of the tray overhang (p = 0.0001). Less time (15 s) was required to take measurements using the ASM model compared with manual measurements, which was significant. These encouraging results indicate that semi-automated measurement techniques could improve the reliability of radiographic measurements.

  17. Improved radiograph measurement inter-observer reliability by use of statistical shape models

    International Nuclear Information System (INIS)

    Pegg, E.C.; Mellon, S.J.; Salmon, G.; Alvand, A.; Pandit, H.; Murray, D.W.; Gill, H.S.

    2012-01-01

    Pre- and post-operative radiographs of patients undergoing joint arthroplasty are often examined for a variety of purposes including preoperative planning and patient assessment. This work examines the feasibility of using active shape models (ASM) to semi-automate measurements from post-operative radiographs for the specific case of the Oxford™ Unicompartmental Knee. Measurements of the proximal tibia and the position of the tibial tray were made using the ASM model and manually. Data were obtained by four observers and one observer took four sets of measurements to allow assessment of the inter- and intra-observer reliability, respectively. The parameters measured were the tibial tray angle, the tray overhang, the tray size, the sagittal cut position, the resection level and the tibial width. Results demonstrated improved reliability (average of 27% and 11.2% increase for intra- and inter-reliability, respectively) and equivalent accuracy (p > 0.05 for compared data values) for all of the measurements using the ASM model, with the exception of the tray overhang (p = 0.0001). Less time (15 s) was required to take measurements using the ASM model compared with manual measurements, which was significant. These encouraging results indicate that semi-automated measurement techniques could improve the reliability of radiographic measurements

  18. Reliability Analysis of an Extended Shock Model and Its Optimization Application in a Production Line

    Directory of Open Access Journals (Sweden)

    Renbin Liu

    2014-01-01

    some important reliability indices are derived, such as availability, failure frequency, mean vacation period, mean renewal cycle, mean startup period, and replacement frequency. Finally, a production line controlled by two cold-standby computers is modeled to present numerical illustration and its optimal part-time job policy at a maximum profit.

  19. Role of frameworks, models, data, and judgment in human reliability analysis

    Energy Technology Data Exchange (ETDEWEB)

    Hannaman, G W

    1986-05-01

    Many advancements in the methods for treating human interactions in PRA studies have occurred in the last decade. These advancements appear to increase the capability of PRAs to extend beyond just the assessment of the human's importance to safety. However, variations in the application of these advanced models, data, and judgements in recent PRAs make quantitative comparisons among studies extremely difficult. This uncertainty in the analysis diminishes the usefulness of the PRA study for upgrading procedures, enhancing traning, simulator design, technical specification guidance, and for aid in designing the man-machine interface. Hence, there is a need for a framework to guide analysts in incorporating human interactions into the PRA systems analyses so that future users of a PRA study will have a clear understanding of the approaches, models, data, and assumptions which were employed in the initial study. This paper describes the role of the systematic human action reliability procedure (SHARP) in providing a road map through the complex terrain of human reliability that promises to improve the reproducibility of such analysis in the areas of selecting the models, data, representations, and assumptions. Also described is the role that a human cognitive reliability model can have in collecting data from simulators and helping analysts assign human reliability parameters in a PRA study. Use of these systematic approaches to perform or upgrade existing PRAs promises to make PRA studies more useful as risk management tools.

  20. Assessing the Reliability of Curriculum-Based Measurement: An Application of Latent Growth Modeling

    Science.gov (United States)

    Yeo, Seungsoo; Kim, Dong-Il; Branum-Martin, Lee; Wayman, Miya Miura; Espin, Christine A.

    2012-01-01

    The purpose of this study was to demonstrate the use of Latent Growth Modeling (LGM) as a method for estimating reliability of Curriculum-Based Measurement (CBM) progress-monitoring data. The LGM approach permits the error associated with each measure to differ at each time point, thus providing an alternative method for examining of the…

  1. A reliability model for interlayer dielectric cracking during fast thermal cycling

    NARCIS (Netherlands)

    Nguyen, Van Hieu; Salm, Cora; Krabbenborg, B.H.; Krabbenborg, B.H.; Bisschop, J.; Mouthaan, A.J.; Kuper, F.G.; Ray, Gary W.; Smy, Tom; Ohta, Tomohiro; Tsujimura, Manabu

    2003-01-01

    Interlayer dielectric (ILD) cracking can result in short circuits of multilevel interconnects. This paper presents a reliability model for ILD cracking induced by fast thermal cycling (FTC) stress. FTC tests have been performed under different temperature ranges (∆T) and minimum temperatures (Tmin).

  2. Positive end-expiratory pressure improves survival in a rodent model of cardiopulmonary resuscitation using high-dose epinephrine.

    LENUS (Irish Health Repository)

    McCaul, Conán

    2009-10-01

    Multiple interventions have been tested in models of cardiopulmonary resuscitation (CPR) to optimize drug use, chest compressions, and ventilation. None has studied the effects of positive end-expiratory pressure (PEEP) on outcome. We hypothesized that because PEEP can reverse pulmonary atelectasis, lower pulmonary vascular resistance, and potentially improve cardiac output, its use during CPR would increase survival.

  3. Protective Effects of Sodium (±-5-Bromo-2-(α-Hydroxypentyl Benzoate in a Rodent Model of Global Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Yuan Gao

    2017-09-01

    Full Text Available The aim of the current study was to explore the protective effects of sodium (±-5-bromo-2-(α-hydroxypentyl benzoate (brand name: brozopine, BZP in a rat model of global cerebral ischemia. The rat model was established using a modified Winocur’s method; close postoperative observation was conducted at all times. Neurological function was detected through prehensile traction and beam-walking test. BZP reduced mortality and prolonged the survival time of rats with global cerebral ischemia, within 24 h. There was a decreased survival rate (60% in the Model group, while the survival rate of the BZP (3 and 12 mg/kg remarkably increased the survival rate (to 80 and 90%, respectively, in a dose-dependent manner. Compared with the Model group (survival time: 18.50 h, the administration of BZP (0.75, 3, and 12 mg/kg prolonged the survival time (to 20.38, 21.85, and 23.90 h, respectively, particularly in BZP 12 mg/kg group (P < 0.05. Additionally, the BZP (12 mg/kg group exhibited an improvement in their motor function (P < 0.05. The BZP groups (0.75, 3, and 12 mg/kg displayed significantly reduced necrosis and the percentage of apoptotic cells (P < 0.05 and P < 0.01, respectively. Compared with Model group, BZP (0.75, 3, and 12 mg/kg increased the NeuN optical density values (P < 0.01. Rats with global ischemia had a high expression of Cyt-c, caspase-3, and the Bax/Bcl-2 ratio compared with sham group (P < 0.01. BZP (0.75, 3, and 12 mg/kg, however, reduced the expression of Cyt-c, caspase-3, and the Bax/Bcl-2 ratio, in a dose-dependent manner (P < 0.01. There was low expression of p-Akt and PI3K in Model group, compared with the sham group (P < 0.01. Meanwhile, BZP (0.75, 3, and 12 mg/kg increased the expression of p-Akt and PI3K in a dose-dependent manner (P < 0.01. We also found the expression of Cyt-c, caspase-3, Bax/Bcl-2 ratio, PI3K, p-Akt, and comprehensive score were directly related. In conclusion, BZP had therapeutic potential and prevented

  4. A systems biology approach reveals a link between systemic cytokines and skeletal muscle energy metabolism in a rodent smoking model and human COPD.

    Science.gov (United States)

    Davidsen, Peter K; Herbert, John M; Antczak, Philipp; Clarke, Kim; Ferrer, Elisabet; Peinado, Victor I; Gonzalez, Constancio; Roca, Josep; Egginton, Stuart; Barberá, Joan A; Falciani, Francesco

    2014-01-01

    A relatively large percentage of patients with chronic obstructive pulmonary disease (COPD) develop systemic co-morbidities that affect prognosis, among which muscle wasting is particularly debilitating. Despite significant research effort, the pathophysiology of this important extrapulmonary manifestation is still unclear. A key question that remains unanswered is to what extent systemic inflammatory mediators might play a role in this pathology. Cigarette smoke (CS) is the main risk factor for developing COPD and therefore animal models chronically exposed to CS have been proposed for mechanistic studies and biomarker discovery. Although mice have been successfully used as a pre-clinical in vivo model to study the pulmonary effects of acute and chronic CS exposure, data suggest that they may be inadequate models for studying the effects of CS on peripheral muscle function. In contrast, recent findings indicate that the guinea pig model (Cavia porcellus) may better mimic muscle wasting. We have used a systems biology approach to compare the transcriptional profile of hindlimb skeletal muscles from a Guinea pig rodent model exposed to CS and/or chronic hypoxia to COPD patients with muscle wasting. We show that guinea pigs exposed to long-term CS accurately reflect most of the transcriptional changes observed in dysfunctional limb muscle of severe COPD patients when compared to matched controls. Using network inference, we could then show that the expression profile in whole lung of genes encoding for soluble inflammatory mediators is informative of the molecular state of skeletal muscles in the guinea pig smoking model. Finally, we show that CXCL10 and CXCL9, two of the candidate systemic cytokines identified using this pre-clinical model, are indeed detected at significantly higher levels in serum of COPD patients, and that their serum protein level is inversely correlated with the expression of aerobic energy metabolism genes in skeletal muscle. We conclude that

  5. Machine Learning Approach for Software Reliability Growth Modeling with Infinite Testing Effort Function

    Directory of Open Access Journals (Sweden)

    Subburaj Ramasamy

    2017-01-01

    Full Text Available Reliability is one of the quantifiable software quality attributes. Software Reliability Growth Models (SRGMs are used to assess the reliability achieved at different times of testing. Traditional time-based SRGMs may not be accurate enough in all situations where test effort varies with time. To overcome this lacuna, test effort was used instead of time in SRGMs. In the past, finite test effort functions were proposed, which may not be realistic as, at infinite testing time, test effort will be infinite. Hence in this paper, we propose an infinite test effort function in conjunction with a classical Nonhomogeneous Poisson Process (NHPP model. We use Artificial Neural Network (ANN for training the proposed model with software failure data. Here it is possible to get a large set of weights for the same model to describe the past failure data equally well. We use machine learning approach to select the appropriate set of weights for the model which will describe both the past and the future data well. We compare the performance of the proposed model with existing model using practical software failure data sets. The proposed log-power TEF based SRGM describes all types of failure data equally well and also improves the accuracy of parameter estimation more than existing TEF and can be used for software release time determination as well.

  6. Reliability analysis of nuclear component cooling water system using semi-Markov process model

    International Nuclear Information System (INIS)

    Veeramany, Arun; Pandey, Mahesh D.

    2011-01-01

    Research highlights: → Semi-Markov process (SMP) model is used to evaluate system failure probability of the nuclear component cooling water (NCCW) system. → SMP is used because it can solve reliability block diagram with a mixture of redundant repairable and non-repairable components. → The primary objective is to demonstrate that SMP can consider Weibull failure time distribution for components while a Markov model cannot → Result: the variability in component failure time is directly proportional to the NCCW system failure probability. → The result can be utilized as an initiating event probability in probabilistic safety assessment projects. - Abstract: A reliability analysis of nuclear component cooling water (NCCW) system is carried out. Semi-Markov process model is used in the analysis because it has potential to solve a reliability block diagram with a mixture of repairable and non-repairable components. With Markov models it is only possible to assume an exponential profile for component failure times. An advantage of the proposed model is the ability to assume Weibull distribution for the failure time of components. In an attempt to reduce the number of states in the model, it is shown that usage of poly-Weibull distribution arises. The objective of the paper is to determine system failure probability under these assumptions. Monte Carlo simulation is used to validate the model result. This result can be utilized as an initiating event probability in probabilistic safety assessment projects.

  7. The bioeconomics of controlling an African rodent pest species

    DEFF Research Database (Denmark)

    Skonhoft, Anders; Leirs, Herwig; Andreassen, Harry P

    2006-01-01

    The paper treats the economy of controlling an African pest rodent, the multimammate rat, causing major damage in maize production. An ecological population model is presented and used as a basis for the economic analyses carried out at the village level using data from Tanzania. This model...... incorporates both density-dependent and density-independent (stochastic) factors. Rodents are controlled by applying poison, and the costs are made up of the cost of poison plus the damage to maize production. We analyse how the present-value costs of maize production are affected by various rodent control...

  8. Human reliability

    International Nuclear Information System (INIS)

    Embrey, D.E.

    1987-01-01

    Concepts and techniques of human reliability have been developed and are used mostly in probabilistic risk assessment. For this, the major application of human reliability assessment has been to identify the human errors which have a significant effect on the overall safety of the system and to quantify the probability of their occurrence. Some of the major issues within human reliability studies are reviewed and it is shown how these are applied to the assessment of human failures in systems. This is done under the following headings; models of human performance used in human reliability assessment, the nature of human error, classification of errors in man-machine systems, practical aspects, human reliability modelling in complex situations, quantification and examination of human reliability, judgement based approaches, holistic techniques and decision analytic approaches. (UK)

  9. Novel Therapeutic Approaches for the Treatment of Depression and Cognitive Deficits in a Rodent Model of Gulf War Veterans Illness

    Science.gov (United States)

    2015-10-01

    forced swim test. No two tests were carried out on the same day. Depression is a complex psychological phenomenon and as such is difficult to analyze...grant has also given both of us professional development opportunities. Our abstract has been accepted for presentation at American Epilepsy ...and neurologists at the 2015 American Epilepsy Society annual meeting. Our work on model development is currently under-review at “Neurotoxicology

  10. Anti-anxiety activity of hydro alcoholic extract of Scoparia dulcis Linn. assessed using different experimental anxiety models In rodents

    OpenAIRE

    Arasan Elayaraja; S. A. Rahaman; Prem kumar P.; Phani Kumar K.

    2015-01-01

    Scoparia dulcis belonging to the family Scrophulariaceae is an valuable medicinal herb, had showed antiviral, antimalarial, anticancer and antidiabetic activities. The present study was aimed to investigate the anti-anxiety activity of crude ethanolic extract of S.dulcis L by various behavioural models. Preliminary phytochemical investigation revealed the presence of  phenols and flavonoids. The extract at 100mg/kg and 200mg/kg was evaluated for anti anxiety activity by  Open-field test [OFT]...

  11. Modeling hemoglobin and hemoglobin:haptoglobin complex clearance in a non-rodent species–pharmacokinetic and therapeutic implications

    OpenAIRE

    Boretti, Felicitas S.; Baek, Jin Hyen; Palmer, Andre F.; Schaer, Dominik J.; Buehler, Paul W.

    2014-01-01

    Background: Haptoglobin (Hp) prevents hemoglobin (Hb) extravasation and attenuates Hb induced tissue oxidation and vasoconstriction. Small animal models such as mouse, rat and guinea pig appear to demonstrate proof-of-concept for Hb neutralization by Hp in diverse pre-clinical conditions. However, these species differ significantly from humans in the clearance of Hb:Hp and demonstrate long persistence of circulating Hb:Hp complexes. Objective: The focus of this study is to understand Hb:Hp...

  12. Translation of Novel Serotonin 5-HT7 Agonist Drug Candidates in Rodent Models of Fragile X Syndrome

    Science.gov (United States)

    2016-09-01

    HT1A partial agonist for autism . 6th Cisbio HTRF symposium (Brewster, MA), September 14-17, 2015. Acknowledged DOD funding. Teaching Lectures . 10...grant is to synthesize 5-PAT-type 5HT7 receptor agonists and assess their effectiveness to correct FXS phenotypes in Fmr1-KO mice and other mouse models...President of DELSIA (Delivering Science Innovation for Autism ) and Vice President, Innovative Technologies at Autism Speaks, Daniel Smith, who

  13. Reliability of a new biokinetic model of zirconium in internal dosimetry: part I, parameter uncertainty analysis.

    Science.gov (United States)

    Li, Wei Bo; Greiter, Matthias; Oeh, Uwe; Hoeschen, Christoph

    2011-12-01

    The reliability of biokinetic models is essential in internal dose assessments and radiation risk analysis for the public, occupational workers, and patients exposed to radionuclides. In this paper, a method for assessing the reliability of biokinetic models by means of uncertainty and sensitivity analysis was developed. The paper is divided into two parts. In the first part of the study published here, the uncertainty sources of the model parameters for zirconium (Zr), developed by the International Commission on Radiological Protection (ICRP), were identified and analyzed. Furthermore, the uncertainty of the biokinetic experimental measurement performed at the Helmholtz Zentrum München-German Research Center for Environmental Health (HMGU) for developing a new biokinetic model of Zr was analyzed according to the Guide to the Expression of Uncertainty in Measurement, published by the International Organization for Standardization. The confidence interval and distribution of model parameters of the ICRP and HMGU Zr biokinetic models were evaluated. As a result of computer biokinetic modelings, the mean, standard uncertainty, and confidence interval of model prediction calculated based on the model parameter uncertainty were presented and compared to the plasma clearance and urinary excretion measured after intravenous administration. It was shown that for the most important compartment, the plasma, the uncertainty evaluated for the HMGU model was much smaller than that for the ICRP model; that phenomenon was observed for other organs and tissues as well. The uncertainty of the integral of the radioactivity of Zr up to 50 y calculated by the HMGU model after ingestion by adult members of the public was shown to be smaller by a factor of two than that of the ICRP model. It was also shown that the distribution type of the model parameter strongly influences the model prediction, and the correlation of the model input parameters affects the model prediction to a

  14. A Combined Reliability Model of VSC-HVDC Connected Offshore Wind Farms Considering Wind Speed Correlation

    DEFF Research Database (Denmark)

    Guo, Yifei; Gao, Houlei; Wu, Qiuwei

    2017-01-01

    and WTGs outage. The wind speed correlation between different WFs is included in the two-dimensional multistate WF model by using an improved k-means clustering method. Then, the entire system with two WFs and a threeterminal VSC-HVDC system is modeled as a multi-state generation unit. The proposed model...... is applied to the Roy Billinton test system (RBTS) for adequacy studies. Both the probability and frequency indices are calculated. The effectiveness and accuracy of the combined model is validated by comparing results with the sequential Monte Carlo simulation (MCS) method. The effects of the outage of VSC-HVDC...... system and wind speed correlation on the system reliability were analyzed. Sensitivity analyses were conducted to investigate the impact of repair time of the offshore VSC-HVDC system on system reliability....

  15. Reliability modelling of repairable systems using Petri nets and fuzzy Lambda-Tau methodology

    International Nuclear Information System (INIS)

    Knezevic, J.; Odoom, E.R.

    2001-01-01

    A methodology is developed which uses Petri nets instead of the fault tree methodology and solves for reliability indices utilising fuzzy Lambda-Tau method. Fuzzy set theory is used for representing the failure rate and repair time instead of the classical (crisp) set theory because fuzzy numbers allow expert opinions, linguistic variables, operating conditions, uncertainty and imprecision in reliability information to be incorporated into the system model. Petri nets are used because unlike the fault tree methodology, the use of Petri nets allows efficient simultaneous generation of minimal cut and path sets

  16. Model reliability and software quality assurance in simulation of nuclear fuel waste management systems

    International Nuclear Information System (INIS)

    Oeren, T.I.; Elzas, M.S.; Sheng, G.; Wageningen Agricultural Univ., Netherlands; McMaster Univ., Hamilton, Ontario)

    1985-01-01

    As is the case with all scientific simulation studies, computerized simulation of nuclear fuel waste management systems can introduce and hide various types of errors. Frameworks to clarify issues of model reliability and software quality assurance are offered. Potential problems with reference to the main areas of concern for reliability and quality are discussed; e.g., experimental issues, decomposition, scope, fidelity, verification, requirements, testing, correctness, robustness are treated with reference to the experience gained in the past. A list comprising over 80 most common computerization errors is provided. Software tools and techniques used to detect and to correct computerization errors are discussed

  17. Meeting Human Reliability Requirements through Human Factors Design, Testing, and Modeling

    Energy Technology Data Exchange (ETDEWEB)

    R. L. Boring

    2007-06-01

    In the design of novel systems, it is important for the human factors engineer to work in parallel with the human reliability analyst to arrive at the safest achievable design that meets design team safety goals and certification or regulatory requirements. This paper introduces the System Development Safety Triptych, a checklist of considerations for the interplay of human factors and human reliability through design, testing, and modeling in product development. This paper also explores three phases of safe system development, corresponding to the conception, design, and implementation of a system.

  18. Phd study of reliability and validity: One step closer to a standardized music therapy assessment model

    DEFF Research Database (Denmark)

    Jacobsen, Stine Lindahl

    The paper will present a phd study concerning reliability and validity of music therapy assessment model “Assessment of Parenting Competences” (APC) in the area of families with emotionally neglected children. This study had a multiple strategy design with a philosophical base of critical realism...... and pragmatism. The fixed design for this study was a between and within groups design in testing the APCs reliability and validity. The two different groups were parents with neglected children and parents with non-neglected children. The flexible design had a multiple case study strategy specifically...

  19. Assessment of Electronic Circuits Reliability Using Boolean Truth Table Modeling Method

    International Nuclear Information System (INIS)

    EI-Shanshoury, A.I.

    2011-01-01

    This paper explores the use of Boolean Truth Table modeling Method (BTTM) in the analysis of qualitative data. It is widely used in certain fields especially in the fields of electrical and electronic engineering. Our work focuses on the evaluation of power supply circuit reliability using (BTTM) which involves systematic attempts to falsify and identify hypotheses on the basis of truth tables constructed from qualitative data. Reliability parameters such as the system's failure rates for the power supply case study are estimated. All possible state combinations (operating and failed states) of the major components in the circuit were listed and their effects on overall system were studied

  20. Oligodendrocyte death, neuroinflammation, and the effects of minocycline in a rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION).

    Science.gov (United States)

    Mehrabian, Zara; Guo, Yan; Weinreich, Daniel; Bernstein, Steven L

    2017-01-01

    Optic nerve (ON) damage following nonarteritic anterior ischemic optic neuropathy (NAION) and its models is associated with neurodegenerative inflammation. Minocycline is a tetracycline derivative antibiotic believed to exert a neuroprotective effect by selective alteration and activation of the neuroinflammatory response. We evaluated minocycline's post-induction ability to modify early and late post-ischemic inflammatory responses and its retinal ganglion cell (RGC)-neuroprotective ability. We used the rodent NAION (rNAION) model in male Sprague-Dawley rats. Animals received either vehicle or minocycline (33 mg/kg) daily intraperitoneally for 28 days. Early (3 days) ON-cytokine responses were evaluated, and oligodendrocyte death was temporally evaluated using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis. Cellular inflammation was evaluated with immunohistochemistry, and RGC preservation was compared with stereology of Brn3a-positive cells in flat mounted retinas. Post-rNAION, oligodendrocytes exhibit a delayed pattern of apoptosis extending over a month, with extrinsic monocyte infiltration occurring only in the primary rNAION lesion and progressive distal microglial activation. Post-induction minocycline failed to improve retinal ganglion cell survival compared with the vehicle treated (893.14 vs. 920.72; p>0.9). Cytokine analysis of the rNAION lesion 3 days post-induction revealed that minocycline exert general inflammatory suppression without selective upregulation of cytokines associated with the proposed alternative or neuroprotective M2 inflammatory pathway. The pattern of cytokine release, extended temporal window of oligodendrocyte death, and progressive microglial activation suggests that selective neuroimmunomodulation, rather than general inflammatory suppression, may be required for effective repair strategies in ischemic optic neuropathies.