A novel animal model for hyperdynamic airway collapse.

Science.gov (United States)

Tsukada, Hisashi; O'Donnell, Carl R; Garland, Robert; Herth, Felix; Decamp, Malcolm; Ernst, Armin

2010-12-01

Tracheobronchomalacia (TBM) is increasingly recognized as a condition associated with significant pulmonary morbidity. However, treatment is invasive and complex, and because there is no appropriate animal model, novel diagnostic and treatment strategies are difficult to evaluate. We endeavored to develop a reliable airway model to simulate hyperdynamic airway collapse in humans. Seven 20-kg male sheep were enrolled in this study. Tracheomalacia was created by submucosal resection of > 50% of the circumference of 10 consecutive cervical tracheal cartilage rings through a midline cervical incision. A silicone stent was placed in the trachea to prevent airway collapse during recovery. Tracheal collapsibility was assessed at protocol-specific time points by bronchoscopy and multidetector CT imaging while temporarily removing the stent. Esophageal pressure and flow data were collected to assess flow limitation during spontaneous breathing. All animals tolerated the surgical procedure well and were stented without complications. One sheep died at 2 weeks because of respiratory failure related to stent migration. In all sheep, near-total forced inspiratory airway collapse was observed up to 3 months postprocedure. Esophageal manometry demonstrated flow limitation associated with large negative pleural pressure swings during rapid spontaneous inhalation. Hyperdynamic airway collapse can reliably be induced with this technique. It may serve as a model for evaluation of novel diagnostic and therapeutic strategies for TBM.

Inter-observer reliability of animal-based welfare indicators included in the Animal Welfare Indicators welfare assessment protocol for dairy goats.

Science.gov (United States)

Vieira, A; Battini, M; Can, E; Mattiello, S; Stilwell, G

2018-01-08

This study was conducted within the context of the Animal Welfare Indicators (AWIN) project and the underlying scientific motivation for the development of the study was the scarcity of data regarding inter-observer reliability (IOR) of welfare indicators, particularly given the importance of reliability as a further step for developing on-farm welfare assessment protocols. The objective of this study is therefore to evaluate IOR of animal-based indicators (at group and individual-level) of the AWIN welfare assessment protocol (prototype) for dairy goats. In the design of the study, two pairs of observers, one in Portugal and another in Italy, visited 10 farms each and applied the AWIN prototype protocol. Farms in both countries were visited between January and March 2014, and all the observers received the same training before the farm visits were initiated. Data collected during farm visits, and analysed in this study, include group-level and individual-level observations. The results of our study allow us to conclude that most of the group-level indicators presented the highest IOR level ('substantial', 0.85 to 0.99) in both field studies, pointing to a usable set of animal-based welfare indicators that were therefore included in the first level of the final AWIN welfare assessment protocol for dairy goats. Inter-observer reliability of individual-level indicators was lower, but the majority of them still reached 'fair to good' (0.41 to 0.75) and 'excellent' (0.76 to 1) levels. In the paper we explore reasons for the differences found in IOR between the group and individual-level indicators, including how the number of individual-level indicators to be assessed on each animal and the restraining method may have affected the results. Furthermore, we discuss the differences found in the IOR of individual-level indicators in both countries: the Portuguese pair of observers reached a higher level of IOR, when compared with the Italian observers. We argue how the

Current challenges facing the assessment of the allergenic capacity of food allergens in animal models

DEFF Research Database (Denmark)

Bøgh, Katrine Lindholm; van Bilsen, Jolanda; Głogowski, Robert

2016-01-01

of novel food proteins. There is no doubt that robust and reliable animal models for the identification and characterization of food allergens would be valuable tools for safety assessment. However, although various animal models have been proposed for this purpose, to date, none have been formally...... validated as predictive and none are currently suitable to test the allergenic potential of new foods. Here, the design of various animal models are reviewed, including among others considerations of species and strain, diet, route of administration, dose and formulation of the test protein, relevant...

A new small-animal model for the study of acquired heterotopic ossification after hip surgery.

Science.gov (United States)

Anthonissen, Joris; Ossendorf, Christian; Hock, Johanna Lisa; Ritz, Ulrike; Hofmann, Alexander; Rommens, Pol Maria

2015-01-01

Heterotopic ossification (HO)--the formation of bone in soft tissues--is a frequent problem after surgery of the hip and pelvis, but little is known about its underlying pathogenic mechanisms. It is vital to study the underlying pathogenesis in animal models to develop and evaluate new prophylactic regimens directed against HO. However, previously developed small-animal models for the study of HO imitate neither surgery nor trauma-mechanisms that potentially cause HO. Hence, the goal of this study was to develop a novel small-animal model imitating hip surgery that can reliably produce HO. Twenty male Wistar rats were subjected to surgery of the right hip during which the femoral canal was reamed in three steps up to 2 mm, and a muscle lesion was made. Twelve weeks after surgery, the amount of heterotopic bone was assessed using micro-computed tomography. Eighteen of 20 animals showed HO around the hip 12 weeks after surgery. The amount of heterotopic bone varied from very small particles up to near ankylosis. A rat model of hip/pelvic surgery that does not use exogenous osteogenic stimulus and can reliably produce HO was developed.

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.

Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis

Science.gov (United States)

Zhan, Xianbao; Wang, Fan; Bi, Yan

2016-01-01

Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mainly focus on rodent models because of their popularity. Autoimmune pancreatitis and genetically engineered animal models will be reviewed elsewhere. PMID:27418683

Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis.

Science.gov (United States)

Zhan, Xianbao; Wang, Fan; Bi, Yan; Ji, Baoan

2016-09-01

Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mainly focus on rodent models because of their popularity. Autoimmune pancreatitis and genetically engineered animal models will be reviewed elsewhere. Copyright © 2016 the American Physiological Society.

Critical overview of all available animal models for abdominal wall hernia research.

Science.gov (United States)

Vogels, R R M; Kaufmann, R; van den Hil, L C L; van Steensel, S; Schreinemacher, M H F; Lange, J F; Bouvy, N D

2017-10-01

Since the introduction of the first prosthetic mesh for abdominal hernia repair, there has been a search for the "ideal mesh." The use of preclinical or animal models for assessment of necessary characteristics of new and existing meshes is an indispensable part of hernia research. Unfortunately, in our experience there is a lack of consensus among different research groups on which model to use. Therefore, we hypothesized that there is a lack of comparability within published animal research on hernia surgery due to wide range in experimental setup among different research groups. A systematic search of the literature was performed to provide a complete overview of all animal models published between 2000 and 2014. Relevant parameters on model characteristics and outcome measurement were scored on a standardized scoring sheet. Due to the wide range in different animals used, ranging from large animal models like pigs to rodents, we decided to limit the study to 168 articles concerning rat models. Within these rat models, we found wide range of baseline animal characteristics, operation techniques, and outcome measurements. Making reliable comparison of results among these studies is impossible. There is a lack of comparability among experimental hernia research, limiting the impact of this experimental research. We therefore propose the establishment of guidelines for experimental hernia research by the EHS.

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.

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.

Are animal models predictive for human postmortem muscle protein degradation?

Science.gov (United States)

Ehrenfellner, Bianca; Zissler, Angela; Steinbacher, Peter; Monticelli, Fabio C; Pittner, Stefan

2017-11-01

A most precise determination of the postmortem interval (PMI) is a crucial aspect in forensic casework. Although there are diverse approaches available to date, the high heterogeneity of cases together with the respective postmortal changes often limit the validity and sufficiency of many methods. Recently, a novel approach for time since death estimation by the analysis of postmortal changes of muscle proteins was proposed. It is however necessary to improve the reliability and accuracy, especially by analysis of possible influencing factors on protein degradation. This is ideally investigated on standardized animal models that, however, require legitimization by a comparison of human and animal tissue, and in this specific case of protein degradation profiles. Only if protein degradation events occur in comparable fashion within different species, respective findings can sufficiently be transferred from the animal model to application in humans. Therefor samples from two frequently used animal models (mouse and pig), as well as forensic cases with representative protein profiles of highly differing PMIs were analyzed. Despite physical and physiological differences between species, western blot analysis revealed similar patterns in most of the investigated proteins. Even most degradation events occurred in comparable fashion. In some other aspects, however, human and animal profiles depicted distinct differences. The results of this experimental series clearly indicate the huge importance of comparative studies, whenever animal models are considered. Although animal models could be shown to reflect the basic principles of protein degradation processes in humans, we also gained insight in the difficulties and limitations of the applicability of the developed methodology in different mammalian species regarding protein specificity and methodic functionality.

Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis

OpenAIRE

Zhan, Xianbao; Wang, Fan; Bi, Yan; Ji, Baoan

2016-01-01

Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mai...

Animal models of dementia

DEFF Research Database (Denmark)

Olsson, I. Anna S.; Sandøe, Peter

2011-01-01

This chapter aims to encourage scientists and others interested in the use of animal models of disease – specifically, in the study of dementia – to engage in ethical reflection. It opens with a general discussion of the moral acceptability of animal use in research. Three ethical approaches...... are here distinguished. These serve as points of orientation in the following discussion of four more specific ethical questions: Does animal species matter? How effective is disease modelling in delivering the benefits claimed for it? What can be done to minimize potential harm to animals in research? Who...... bears responsibility for the use of animals in disease models?...

Modelling Farm Animal Welfare

Science.gov (United States)

Collins, Lisa M.; Part, Chérie E.

2013-01-01

Simple Summary In this review paper we discuss the different modeling techniques that have been used in animal welfare research to date. We look at what questions they have been used to answer, the advantages and pitfalls of the methods, and how future research can best use these approaches to answer some of the most important upcoming questions in farm animal welfare. Abstract The use of models in the life sciences has greatly expanded in scope and advanced in technique in recent decades. However, the range, type and complexity of models used in farm animal welfare is comparatively poor, despite the great scope for use of modeling in this field of research. In this paper, we review the different modeling approaches used in farm animal welfare science to date, discussing the types of questions they have been used to answer, the merits and problems associated with the method, and possible future applications of each technique. We find that the most frequently published types of model used in farm animal welfare are conceptual and assessment models; two types of model that are frequently (though not exclusively) based on expert opinion. Simulation, optimization, scenario, and systems modeling approaches are rarer in animal welfare, despite being commonly used in other related fields. Finally, common issues such as a lack of quantitative data to parameterize models, and model selection and validation are discussed throughout the review, with possible solutions and alternative approaches suggested. PMID:26487411

Animal welfare and use of silkworm as a model animal.

Science.gov (United States)

Sekimizu, N; Paudel, A; Hamamoto, H

2012-08-01

Sacrificing model animals is required for developing effective drugs before being used in human beings. In Japan today, at least 4,210,000 mice and other mammals are sacrificed to a total of 6,140,000 per year for the purpose of medical studies. All the animals treated in Japan, including test animals, are managed under control of "Act on Welfare and Management of Animals". Under the principle of this Act, no person shall kill, injure, or inflict cruelty on animals without due cause. "Animal" addressed in the Act can be defined as a "vertebrate animal". If we can make use of invertebrate animals in testing instead of vertebrate ones, that would be a remarkable solution for the issue of animal welfare. Furthermore, there are numerous advantages of using invertebrate animal models: less space and small equipment are enough for taking care of a large number of animals and thus are cost-effective, they can be easily handled, and many biological processes and genes are conserved between mammals and invertebrates. Today, many invertebrates have been used as animal models, but silkworms have many beneficial traits compared to mammals as well as other insects. In a Genome Pharmaceutical Institute's study, we were able to achieve a lot making use of silkworms as model animals. We would like to suggest that pharmaceutical companies and institutes consider the use of the silkworm as a model animal which is efficacious both for financial value by cost cutting and ethical aspects in animals' welfare.

Modelling Farm Animal Welfare

Directory of Open Access Journals (Sweden)

Chérie E. Part

2013-05-01

Full Text Available The use of models in the life sciences has greatly expanded in scope and advanced in technique in recent decades. However, the range, type and complexity of models used in farm animal welfare is comparatively poor, despite the great scope for use of modeling in this field of research. In this paper, we review the different modeling approaches used in farm animal welfare science to date, discussing the types of questions they have been used to answer, the merits and problems associated with the method, and possible future applications of each technique. We find that the most frequently published types of model used in farm animal welfare are conceptual and assessment models; two types of model that are frequently (though not exclusively based on expert opinion. Simulation, optimization, scenario, and systems modeling approaches are rarer in animal welfare, despite being commonly used in other related fields. Finally, common issues such as a lack of quantitative data to parameterize models, and model selection and validation are discussed throughout the review, with possible solutions and alternative approaches suggested.

Diagnosis of abdominal abscess: A large animal model

International Nuclear Information System (INIS)

Harper, R.A.; Meek, A.C.; Chidlow, A.D.; Galvin, D.A.J.; McCollum, C.N.

1988-01-01

In order to evaluate potential isotopic techniques for the diagnosis of occult sepsis an experimental model in large animals is required. Sponges placed in the abdomen of pigs were injected with mixed colonic bacteria. In 4 animals Kefzol (500 mg IV) and Metronidazole (1 g PR) were administered before the sponges were inserted and compared to 4 given no antibiotics. Finally, in 12 pigs, 20 mls autologous blood was injected into the sponge before antibiotic prophylaxis and bacterial inoculation. 111 In-leucocyte scans and post mortem were then performed 2 weeks later. Without antibiotic cover purulent peritonitis developed in all 4 pigs. Prophylactic antibiotics prevented overwhelming sepsis but at 2 weeks there was only brown fluid surrounding the sponge. Blood added to the sponge produced abscesses in every animal confirmed by leucocytosis of 25.35x10 9 cells/L, 111 In-leucocyte scanning and post mortem. Culturing the thick yellow pus showed a mixed colony of aerobes and anaerobes, similar to those cultured in clinical practice. An intra-abdominal sponge containing blood and faecal organisms in a pig on prophylactic antibiotics reliably produced a chronic abscess. This model is ideal for studies on alternative methods of abscess diagnosis and radiation dosimetry. (orig.)

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

Animal models as tools to study the pathophysiology of depression

Directory of Open Access Journals (Sweden)

Helena M. Abelaira

2013-01-01

Full Text Available The incidence of depressive illness is high worldwide, and the inadequacy of currently available drug treatments contributes to the significant health burden associated with depression. A basic understanding of the underlying disease processes in depression is lacking; therefore, recreating the disease in animal models is not possible. Popular current models of depression creatively merge ethologically valid behavioral assays with the latest technological advances in molecular biology. Within this context, this study aims to evaluate animal models of depression and determine which has the best face, construct, and predictive validity. These models differ in the degree to which they produce features that resemble a depressive-like state, and models that include stress exposure are widely used. Paradigms that employ acute or sub-chronic stress exposure include learned helplessness, the forced swimming test, the tail suspension test, maternal deprivation, chronic mild stress, and sleep deprivation, to name but a few, all of which employ relatively short-term exposure to inescapable or uncontrollable stress and can reliably detect antidepressant drug response.

A Hidden Markov Movement Model for rapidly identifying behavioral states from animal tracks

DEFF Research Database (Denmark)

Whoriskey, Kim; Auger-Méthé, Marie; Albertsen, Christoffer Moesgaard

2017-01-01

by fitting it to real tracks from a grey seal, lake trout, and blue shark, as well as to simulated data. 4. The HMMM is a fast and reliable tool for making meaningful inference from animal movement data that is ideally suited for ecologists who want to use the popular DCRWS implementation for highly accurate......1. Electronic telemetry is frequently used to document animal movement through time. Methods that can identify underlying behaviors driving specific movement patterns can help us understand how and why animals use available space, thereby aiding conservation and management efforts. For aquatic...... animal tracking data with significant measurement error, a Bayesian state-space model called the first-Difference Correlated Random Walk with Switching (DCRWS) has often been used for this purpose. However, for aquatic animals, highly accurate tracking data of animal movement are now becoming more common...

Animal models of sarcoidosis.

Science.gov (United States)

Hu, Yijie; Yibrehu, Betel; Zabini, Diana; Kuebler, Wolfgang M

2017-03-01

Sarcoidosis is a debilitating, inflammatory, multiorgan, granulomatous disease of unknown cause, commonly affecting the lung. In contrast to other chronic lung diseases such as interstitial pulmonary fibrosis or pulmonary arterial hypertension, there is so far no widely accepted or implemented animal model for this disease. This has hampered our insights into the etiology of sarcoidosis, the mechanisms of its pathogenesis, the identification of new biomarkers and diagnostic tools and, last not least, the development and implementation of novel treatment strategies. Over past years, however, a number of new animal models have been described that may provide useful tools to fill these critical knowledge gaps. In this review, we therefore outline the present status quo for animal models of sarcoidosis, comparing their pros and cons with respect to their ability to mimic the etiological, clinical and histological hallmarks of human disease and discuss their applicability for future research. Overall, the recent surge in animal models has markedly expanded our options for translational research; however, given the relative early stage of most animal models for sarcoidosis, appropriate replication of etiological and histological features of clinical disease, reproducibility and usefulness in terms of identification of new therapeutic targets and biomarkers, and testing of new treatments should be prioritized when considering the refinement of existing or the development of new models.

Quantification of intervertebral displacement with a novel MRI-based modeling technique: Assessing measurement bias and reliability with a porcine spine model.

Science.gov (United States)

Mahato, Niladri K; Montuelle, Stephane; Goubeaux, Craig; Cotton, John; Williams, Susan; Thomas, James; Clark, Brian C

2017-05-01

The purpose of this study was to develop a novel magnetic resonance imaging (MRI)-based modeling technique for measuring intervertebral displacements. Here, we present the measurement bias and reliability of the developmental work using a porcine spine model. Porcine lumbar vertebral segments were fitted in a custom-built apparatus placed within an externally calibrated imaging volume of an open-MRI scanner. The apparatus allowed movement of the vertebrae through pre-assigned magnitudes of sagittal and coronal translation and rotation. The induced displacements were imaged with static (T 1 ) and fast dynamic (2D HYCE S) pulse sequences. These images were imported into animation software, in which these images formed a background 'scene'. Three-dimensional models of vertebrae were created using static axial scans from the specimen and then transferred into the animation environment. In the animation environment, the user manually moved the models (rotoscoping) to perform model-to-'scene' matching to fit the models to their image silhouettes and assigned anatomical joint axes to the motion-segments. The animation protocol quantified the experimental translation and rotation displacements between the vertebral models. Accuracy of the technique was calculated as 'bias' using a linear mixed effects model, average percentage error and root mean square errors. Between-session reliability was examined by computing intra-class correlation coefficients (ICC) and the coefficient of variations (CV). For translation trials, a constant bias (β 0 ) of 0.35 (±0.11) mm was detected for the 2D HYCE S sequence (p=0.01). The model did not demonstrate significant additional bias with each mm increase in experimental translation (β 1 Displacement=0.01mm; p=0.69). Using the T 1 sequence for the same assessments did not significantly change the bias (p>0.05). ICC values for the T 1 and 2D HYCE S pulse sequences were 0.98 and 0.97, respectively. For rotation trials, a constant bias (�

The establishment of animal model of acute massive pulmonary embolism

International Nuclear Information System (INIS)

Lu Junliang; Yang Ning; Yang Jianping; Ma Junshan; Zhao Shijun

2008-01-01

Objective: To find a way of establishing the model of acute massive pulmonary embolism in dog. Methods: Seven dogs were selected with self-clots made outside the body transferring through a 10 F guiding catheter into the central branch of pulmonary artery via the femoral vein approach on one side and then under pressure monitor of pulmonary artery until the very branch of pulmonary artery was occluded. Blood gas and pulmonary arterial pressure were tested before and after the embolization, Pulmonary artery pressure was continuously monitored together with the examinations of angiography. The bilateral lung specimens were resected for histological examination 12 hours in average after the embolization for comparative study. Results: One animal died of cardiogenic shock after clots injection; the other one presented with tachycardia and premature ventricular beat causing partial recanalization 12 h later. The others were occluded successfully in central branch of pulmonary artery and the pulmonary arterial pressure reached above 50 mmHg after occlusion. Pathologic examination showed the formation of red and mix thrombi within the vascular lumens. Conclusions: This method for making acute massive pulmonary embolism animal model was reliable, feasible and reproducible, and could provide an animal model of acute massive pulmonary embolism for other correlative experiments. (authors)

Animal Models in Burn Research

Science.gov (United States)

Abdullahi, A.; Amini-Nik, S.; Jeschke, M.G

2014-01-01

Burn injury is a severe form of trauma affecting more than two million people in North America each year. Burn trauma is not a single pathophysiological event but a devastating injury that causes structural and functional deficits in numerous organ systems. Due to its complexity and the involvement of multiple organs, in vitro experiments cannot capture this complexity nor address the pathophysiology. In the past two decades, a number of burn animal models have been developed to replicate the various aspects of burn injury; to elucidate the pathophysiology and explore potential treatment interventions. Understanding the advantages and limitations of these animal models is essential for the design and development of treatments that are clinically relevant to humans. This review paper aims to highlight the common animal models of burn injury in order to provide investigators with a better understanding of the benefits and limitations of these models for translational applications. While many animal models of burn exist, we limit our discussion to the skin healing of mouse, rat, and pig. Additionally, we briefly explain hypermetabolic characteristics of burn injury and the animal model utilized to study this phenomena. Finally, we discuss the economic costs associated with each of these models in order to guide decisions of choosing the appropriate animal model for burn research. PMID:24714880

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)

[Animal experimentation, computer simulation and surgical research].

Science.gov (United States)

Carpentier, Alain

2009-11-01

We live in a digital world In medicine, computers are providing new tools for data collection, imaging, and treatment. During research and development of complex technologies and devices such as artificial hearts, computer simulation can provide more reliable information than experimentation on large animals. In these specific settings, animal experimentation should serve more to validate computer models of complex devices than to demonstrate their reliability.

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...

A partial hearing animal model for chronic electro-acoustic stimulation

Science.gov (United States)

Irving, S.; Wise, A. K.; Millard, R. E.; Shepherd, R. K.; Fallon, J. B.

2014-08-01

Objective. Cochlear implants (CIs) have provided some auditory function to hundreds of thousands of people around the world. Although traditionally carried out only in profoundly deaf patients, the eligibility criteria for implantation have recently been relaxed to include many partially-deaf patients with useful levels of hearing. These patients receive both electrical stimulation from their implant and acoustic stimulation via their residual hearing (electro-acoustic stimulation; EAS) and perform very well. It is unclear how EAS improves speech perception over electrical stimulation alone, and little evidence exists about the nature of the interactions between electric and acoustic stimuli. Furthermore, clinical results suggest that some patients that undergo cochlear implantation lose some, if not all, of their residual hearing, reducing the advantages of EAS over electrical stimulation alone. A reliable animal model with clinically-relevant partial deafness combined with clinical CIs is important to enable these issues to be studied. This paper outlines such a model that has been successfully used in our laboratory. Approach. This paper outlines a battery of techniques used in our laboratory to generate, validate and examine an animal model of partial deafness and chronic CI use. Main results. Ototoxic deafening produced bilaterally symmetrical hearing thresholds in neonatal and adult animals. Electrical activation of the auditory system was confirmed, and all animals were chronically stimulated via adapted clinical CIs. Acoustic compound action potentials (CAPs) were obtained from partially-hearing cochleae, using the CI amplifier. Immunohistochemical analysis allows the effects of deafness and electrical stimulation on cell survival to be studied. Significance. This animal model has applications in EAS research, including investigating the functional interactions between electric and acoustic stimulation, and the development of techniques to maintain residual

The flaws and human harms of animal experimentation.

Science.gov (United States)

Akhtar, Aysha

2015-10-01

Nonhuman animal ("animal") experimentation is typically defended by arguments that it is reliable, that animals provide sufficiently good models of human biology and diseases to yield relevant information, and that, consequently, its use provides major human health benefits. I demonstrate that a growing body of scientific literature critically assessing the validity of animal experimentation generally (and animal modeling specifically) raises important concerns about its reliability and predictive value for human outcomes and for understanding human physiology. The unreliability of animal experimentation across a wide range of areas undermines scientific arguments in favor of the practice. Additionally, I show how animal experimentation often significantly harms humans through misleading safety studies, potential abandonment of effective therapeutics, and direction of resources away from more effective testing methods. The resulting evidence suggests that the collective harms and costs to humans from animal experimentation outweigh potential benefits and that resources would be better invested in developing human-based testing methods.

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.

Overview of Animal Models of Obesity

Science.gov (United States)

Lutz, Thomas A.; Woods, Stephen C.

2012-01-01

This is a review of animal models of obesity currently used in research. We have focused upon more commonly utilized models since there are far too many newly created models to consider, especially those caused by selective molecular genetic approaches modifying one or more genes in specific populations of cells. Further, we will not discuss the generation and use of inducible transgenic animals (induced knock-out or knock-in) even though they often bear significant advantages compared to traditional transgenic animals; influences of the genetic modification during the development of the animals can be minimized. The number of these animal models is simply too large to be covered in this chapter. PMID:22948848

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)

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...

Improving the reliability of GUB-20000 gamma unit for large laboratory animals irradiation

International Nuclear Information System (INIS)

Videnskij, V.G.

1994-01-01

GUB-20000 gamma unit for large laboratory animals irradiation is described and results of investigation into its reliability improvement are considered. Cables of superstrength high-modular (SSHM) polymer fibre and capron fiber were tested to establish their applicability in the above unit. Samples were exposed to gamma-radiation and fast electrons and were tested for tensile properties. Application of SSHM-fiber cables to modernize the GUB-20000 unit was found to be perspective due to superhigh radiation strength. 5 refs., 1 tab

Animal Models for Periodontal Disease

Directory of Open Access Journals (Sweden)

Helieh S. Oz

2011-01-01

Full Text Available Animal models and cell cultures have contributed new knowledge in biological sciences, including periodontology. Although cultured cells can be used to study physiological processes that occur during the pathogenesis of periodontitis, the complex host response fundamentally responsible for this disease cannot be reproduced in vitro. Among the animal kingdom, rodents, rabbits, pigs, dogs, and nonhuman primates have been used to model human periodontitis, each with advantages and disadvantages. Periodontitis commonly has been induced by placing a bacterial plaque retentive ligature in the gingival sulcus around the molar teeth. In addition, alveolar bone loss has been induced by inoculation or injection of human oral bacteria (e.g., Porphyromonas gingivalis in different animal models. While animal models have provided a wide range of important data, it is sometimes difficult to determine whether the findings are applicable to humans. In addition, variability in host responses to bacterial infection among individuals contributes significantly to the expression of periodontal diseases. A practical and highly reproducible model that truly mimics the natural pathogenesis of human periodontal disease has yet to be developed.

Animal Models for Periodontal Disease

Science.gov (United States)

Oz, Helieh S.; Puleo, David A.

2011-01-01

Animal models and cell cultures have contributed new knowledge in biological sciences, including periodontology. Although cultured cells can be used to study physiological processes that occur during the pathogenesis of periodontitis, the complex host response fundamentally responsible for this disease cannot be reproduced in vitro. Among the animal kingdom, rodents, rabbits, pigs, dogs, and nonhuman primates have been used to model human periodontitis, each with advantages and disadvantages. Periodontitis commonly has been induced by placing a bacterial plaque retentive ligature in the gingival sulcus around the molar teeth. In addition, alveolar bone loss has been induced by inoculation or injection of human oral bacteria (e.g., Porphyromonas gingivalis) in different animal models. While animal models have provided a wide range of important data, it is sometimes difficult to determine whether the findings are applicable to humans. In addition, variability in host responses to bacterial infection among individuals contributes significantly to the expression of periodontal diseases. A practical and highly reproducible model that truly mimics the natural pathogenesis of human periodontal disease has yet to be developed. PMID:21331345

Animal models.

Science.gov (United States)

Walker, Ellen A

2010-01-01

As clinical studies reveal that chemotherapeutic agents may impair several different cognitive domains in humans, the development of preclinical animal models is critical to assess the degree of chemotherapy-induced learning and memory deficits and to understand the underlying neural mechanisms. In this chapter, the effects of various cancer chemotherapeutic agents in rodents on sensory processing, conditioned taste aversion, conditioned emotional response, passive avoidance, spatial learning, cued memory, discrimination learning, delayed-matching-to-sample, novel-object recognition, electrophysiological recordings and autoshaping is reviewed. It appears at first glance that the effects of the cancer chemotherapy agents in these many different models are inconsistent. However, a literature is emerging that reveals subtle or unique changes in sensory processing, acquisition, consolidation and retrieval that are dose- and time-dependent. As more studies examine cancer chemotherapeutic agents alone and in combination during repeated treatment regimens, the animal models will become more predictive tools for the assessment of these impairments and the underlying neural mechanisms. The eventual goal is to collect enough data to enable physicians to make informed choices about therapeutic regimens for their patients and discover new avenues of alternative or complementary therapies that reduce or eliminate chemotherapy-induced cognitive deficits.

Investigation of animal and algal bioassays for reliable saxitoxin ecotoxicity and cytotoxicity risk evaluation.

Science.gov (United States)

Perreault, François; Matias, Marcelo Seleme; Melegari, Silvia Pedroso; Pinto, Catia Regina Silva de Carvalho; Creppy, Edmond Ekué; Popovic, Radovan; Matias, William Gerson

2011-05-01

Contamination of water bodies by saxitoxin can result in various toxic effects in aquatic organisms. Saxitoxin contamination has also been shown to be a threat to human health in several reported cases, even resulting in death. In this study, we evaluated the sensitivity of animal (Neuro-2A) and algal (Chlamydomonas reinhardtii) bioassays to saxitoxin effect. Neuro-2A cells were found to be sensitive to saxitoxin, as shown by a 24 h EC50 value of 1.5 nM, which was obtained using a cell viability assay. Conversely, no saxitoxin effect was found in any of the algal biomarkers evaluated, for the concentration range tested (2-128 nM). These results indicate that saxitoxin may induce toxic effects in animal and human populations at concentrations where phytoplankton communities are not affected. Therefore, when evaluating STX risk of toxicity, algal bioassays do not appear to be reliable indicators and should always be conducted in combination with animal bioassays. Copyright © 2011 Elsevier Inc. All rights reserved.

Potency of Animal Models in KANSEI Engineering

Science.gov (United States)

Ozaki, Shigeru; Hisano, Setsuji; Iwamoto, Yoshiki

Various species of animals have been used as animal models for neuroscience and provided critical information about the brain functions. Although it seems difficult to elucidate a highly advanced function of the human brain, animal models have potency to clarify the fundamental mechanisms of emotion, decision-making and social behavior. In this review, we will pick up common animal models and point to both the merits and demerits caused by the characteristics. We will also mention that wide-ranging approaches from animal models are advantageous to understand KANSEI as well as mind in humans.

An animal model for tinnitus.

Science.gov (United States)

Jastreboff, P J; Brennan, J F; Sasaki, C T

1988-03-01

Subjective tinnitus remains obscure, widespread, and without apparent cure. In the absence of a suitable animal model, past investigations took place in humans, resulting in studies that were understandably restricted by the nature of human investigation. Within this context, the development of a valid animal model would be considered a major breakthrough in this field of investigation. Our results showed changes in the spontaneous activity of single neurons in the inferior colliculus, consistent with abnormally increased neuronal activity within the auditory pathways after manipulations known to produce tinnitus in man. A procedure based on a Pavlovian conditioned suppression paradigm was recently developed that allows us to measure tinnitus behaviorally in conscious animals. Accordingly, an animal model of tinnitus is proposed that permits tests of hypotheses relating to tinnitus generation, allowing the accommodation of interventional strategies for the treatment of this widespread auditory disorder.

XX. Animal models of pneumocystosis

DEFF Research Database (Denmark)

Dei-Cas, E.; Brun-Pascaud, M.; Bille-Hansen, Vivi

1998-01-01

As in vitro culture systems allowing to isolate Pneumocystis samples from patients or other mammal hosts are still not available, animal models have critical importance in Pneumocystis research. The parasite was reported in numerous mammals but P. carinii pneumonia (PCP) experimental models were...... a source of parasites taxonomically related to P. carinii sp. f hominis. Moreover, primates might be used as experimental hosts to human Pneumocystis. A marked variability of parasite levels among corticosteroid-treated animals and the fact that the origin of the parasite strain remains unknown......, are important drawbacks of the corticosteroid-treated models. For these reasons, inoculated animal models of PCP were developed. The intratracheal inoculation of lung homogenates containing viable parasites in corticosteroid-treated non-latently infected rats resulted in extensive, reproducible Pneumocystis...

Animal models for rotator cuff repair.

Science.gov (United States)

Lebaschi, Amir; Deng, Xiang-Hua; Zong, Jianchun; Cong, Guang-Ting; Carballo, Camila B; Album, Zoe M; Camp, Christopher; Rodeo, Scott A

2016-11-01

Rotator cuff (RC) injuries represent a significant source of pain, functional impairment, and morbidity. The large disease burden of RC pathologies necessitates rapid development of research methodologies to treat these conditions. Given their ability to model anatomic, biomechanical, cellular, and molecular aspects of the human RC, animal models have played an indispensable role in reducing injury burden and advancing this field of research for many years. The development of animal models in the musculoskeletal (MSK) research arena is uniquely different from that in other fields in that the similarity of macrostructures and functions is as critical to replicate as cellular and molecular functions. Traditionally, larger animals have been used because of their anatomic similarity to humans and the ease of carrying out realistic surgical procedures. However, refinement of current molecular methods, introduction of novel research tools, and advancements in microsurgical techniques have increased the applicability of small animal models in MSK research. In this paper, we review RC animal models and emphasize a murine model that may serve as a valuable instrument for future RC tendon repair investigations. © 2016 New York Academy of Sciences.

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.

Animal Models of Hemophilia

Science.gov (United States)

Sabatino, Denise E.; Nichols, Timothy C.; Merricks, Elizabeth; Bellinger, Dwight A.; Herzog, Roland W.; Monahan, Paul E.

2013-01-01

The X-linked bleeding disorder hemophilia is caused by mutations in coagulation factor VIII (hemophilia A) or factor IX (hemophilia B). Unless prophylactic treatment is provided, patients with severe disease (less than 1% clotting activity) typically experience frequent spontaneous bleeds. Current treatment is largely based on intravenous infusion of recombinant or plasma-derived coagulation factor concentrate. More effective factor products are being developed. Moreover, gene therapies for sustained correction of hemophilia are showing much promise in pre-clinical studies and in clinical trials. These advances in molecular medicine heavily depend on availability of well-characterized small and large animal models of hemophilia, primarily hemophilia mice and dogs. Experiments in these animals represent important early and intermediate steps of translational research aimed at development of better and safer treatments for hemophilia, such a protein and gene therapies or immune tolerance protocols. While murine models are excellent for studies of large groups of animals using genetically defined strains, canine models are important for testing scale-up and for longer-term follow-up as well as for studies that require larger blood volumes. PMID:22137432

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...

Animal models of exercise and obesity.

Science.gov (United States)

Kasper, Christine E

2013-01-01

Animal models have been invaluable in the conduct of nursing research for the past 40 years. This review will focus on specific animal models that can be used in nursing research to study the physiologic phenomena of exercise and obesity when the use of human subjects is either scientifically premature or inappropriate because of the need for sampling tissue or the conduct of longitudinal studies of aging. There exists an extensive body of literature reporting the experimental use of various animal models, in both exercise science and the study of the mechanisms of obesity. Many of these studies are focused on the molecular and genetic mechanisms of organ system adaptation and plasticity in response to exercise, obesity, or both. However, this review will narrowly focus on the models useful to nursing research in the study of exercise in the clinical context of increasing performance and mobility, atrophy and bedrest, fatigue, and aging. Animal models of obesity focus on those that best approximate clinical pathology.

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.)

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.,...

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.

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.

Animal models: an important tool in mycology.

Science.gov (United States)

Capilla, Javier; Clemons, Karl V; Stevens, David A

2007-12-01

Animal models of fungal infections are, and will remain, a key tool in the advancement of the medical mycology. Many different types of animal models of fungal infection have been developed, with murine models the most frequently used, for studies of pathogenesis, virulence, immunology, diagnosis, and therapy. The ability to control numerous variables in performing the model allows us to mimic human disease states and quantitatively monitor the course of the disease. However, no single model can answer all questions and different animal species or different routes of infection can show somewhat different results. Thus, the choice of which animal model to use must be made carefully, addressing issues of the type of human disease to mimic, the parameters to follow and collection of the appropriate data to answer those questions being asked. This review addresses a variety of uses for animal models in medical mycology. It focuses on the most clinically important diseases affecting humans and cites various examples of the different types of studies that have been performed. Overall, animal models of fungal infection will continue to be valuable tools in addressing questions concerning fungal infections and contribute to our deeper understanding of how these infections occur, progress and can be controlled and eliminated.

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

Animal Models of Calcific Aortic Valve Disease

Directory of Open Access Journals (Sweden)

Krista L. Sider

2011-01-01

Full Text Available Calcific aortic valve disease (CAVD, once thought to be a degenerative disease, is now recognized to be an active pathobiological process, with chronic inflammation emerging as a predominant, and possibly driving, factor. However, many details of the pathobiological mechanisms of CAVD remain to be described, and new approaches to treat CAVD need to be identified. Animal models are emerging as vital tools to this end, facilitated by the advent of new models and improved understanding of the utility of existing models. In this paper, we summarize and critically appraise current small and large animal models of CAVD, discuss the utility of animal models for priority CAVD research areas, and provide recommendations for future animal model studies of CAVD.

Animal models of attention-deficit hyperactivity disorder

Directory of Open Access Journals (Sweden)

Sagvolden Terje

2005-07-01

Full Text Available Abstract Although animals cannot be used to study complex human behaviour such as language, they do have similar basic functions. In fact, human disorders that have animal models are better understood than disorders that do not. ADHD is a heterogeneous disorder. The relatively simple nervous systems of rodent models have enabled identification of neurobiological changes that underlie certain aspects of ADHD behaviour. Several animal models of ADHD suggest that the dopaminergic system is functionally impaired. Some animal models have decreased extracellular dopamine concentrations and upregulated postsynaptic dopamine D1 receptors (DRD1 while others have increased extracellular dopamine concentrations. In the latter case, dopamine pathways are suggested to be hyperactive. However, stimulus-evoked release of dopamine is often decreased in these models, which is consistent with impaired dopamine transmission. It is possible that the behavioural characteristics of ADHD result from impaired dopamine modulation of neurotransmission in cortico-striato-thalamo-cortical circuits. There is considerable evidence to suggest that the noradrenergic system is poorly controlled by hypofunctional α2-autoreceptors in some models, giving rise to inappropriately increased release of norepinephrine. Aspects of ADHD behaviour may result from an imbalance between increased noradrenergic and decreased dopaminergic regulation of neural circuits that involve the prefrontal cortex. Animal models of ADHD also suggest that neural circuits may be altered in the brains of children with ADHD. It is therefore of particular importance to study animal models of the disorder and not normal animals. Evidence obtained from animal models suggests that psychostimulants may not be acting on the dopamine transporter to produce the expected increase in extracellular dopamine concentration in ADHD. There is evidence to suggest that psychostimulants may decrease motor activity by

High throughput-screening of animal urine samples: It is fast but is it also reliable?

Science.gov (United States)

Kaufmann, Anton

2016-05-01

Advanced analytical technologies like ultra-high-performance liquid chromatography coupled to high resolution mass spectrometry can be used for veterinary drug screening of animal urine. The technique is sufficiently robust and reliable to detect veterinary drugs in urine samples of animals where the maximum residue limit of these compounds in organs like muscle, kidney, or liver has been exceeded. The limitations and possibilities of the technique are discussed. The most critical point is the variability of the drug concentration ratio between the tissue and urine. Ways to manage the false positive and false negatives are discussed. The capability to confirm findings and the possibility of semi-targeted analysis are also addressed. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

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...

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...

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

Bayesian inference for identifying interaction rules in moving animal groups.

Directory of Open Access Journals (Sweden)

Richard P Mann

Full Text Available The emergence of similar collective patterns from different self-propelled particle models of animal groups points to a restricted set of "universal" classes for these patterns. While universality is interesting, it is often the fine details of animal interactions that are of biological importance. Universality thus presents a challenge to inferring such interactions from macroscopic group dynamics since these can be consistent with many underlying interaction models. We present a Bayesian framework for learning animal interaction rules from fine scale recordings of animal movements in swarms. We apply these techniques to the inverse problem of inferring interaction rules from simulation models, showing that parameters can often be inferred from a small number of observations. Our methodology allows us to quantify our confidence in parameter fitting. For example, we show that attraction and alignment terms can be reliably estimated when animals are milling in a torus shape, while interaction radius cannot be reliably measured in such a situation. We assess the importance of rate of data collection and show how to test different models, such as topological and metric neighbourhood models. Taken together our results both inform the design of experiments on animal interactions and suggest how these data should be best analysed.

Modelling group dynamic animal movement

DEFF Research Database (Denmark)

Langrock, Roland; Hopcraft, J. Grant C.; Blackwell, Paul G.

2014-01-01

makes its movement decisions relative to the group centroid. The basic idea is framed within the flexible class of hidden Markov models, extending previous work on modelling animal movement by means of multi-state random walks. While in simulation experiments parameter estimators exhibit some bias......, to date, practical statistical methods which can include group dynamics in animal movement models have been lacking. We consider a flexible modelling framework that distinguishes a group-level model, describing the movement of the group's centre, and an individual-level model, such that each individual......Group dynamic movement is a fundamental aspect of many species' movements. The need to adequately model individuals' interactions with other group members has been recognised, particularly in order to differentiate the role of social forces in individual movement from environmental factors. However...

Ethical guidelines, animal profile, various animal models used in periodontal research with alternatives and future perspectives.

Science.gov (United States)

Pasupuleti, Mohan Kumar; Molahally, Subramanya Shetty; Salwaji, Supraja

2016-01-01

Laboratory animal models serve as a facilitator to investigate the etiopathogenesis of periodontal disease, are used to know the efficacy of reconstructive and regenerative procedures, and are also helpful in evaluation of newer therapeutic techniques including laser and implant therapies prior to application in the human beings. The aim of this review is to know the different animal models used in various specialties of dental research and to know the ethical guidelines prior to the usage of experimental models with main emphasis on how to refine, replace, and reduce the number of animal models usage in the laboratory. An online search for experimental animal models used in dental research was performed using MEDLINE/PubMed database. Publications from 2009 to May 2013 in the specialty of periodontics were included in writing this review. A total of 652 references were published in PubMed/MEDLINE databases based on the search terms used. Out of 245 studies, 241 were related to the periodontal research published in English from 2009 to 2013. Relevant papers were chosen according to the inclusion and exclusion criteria. After extensive electronic and hand search on animal models, it has been observed that various animal models were used in dental research. Search on animal models used for dental research purpose revealed that various animals such as rats, mice, guinea pigs, rabbit, beagle dogs, goats, and nonhuman primates were extensively used. However, with the new advancement of ex vivo animal models, it has become easy to investigate disease pathogenesis and to test the efficacy of newer therapeutic modalities with the reduced usage of animal models. This review summarized the large amount of literature on animal models used in periodontal research with main emphasis on ethical guidelines and on reducing the animal model usage in future perspective.

Ethical guidelines, animal profile, various animal models used in periodontal research with alternatives and future perspectives

Directory of Open Access Journals (Sweden)

Mohan Kumar Pasupuleti

2016-01-01

Full Text Available Laboratory animal models serve as a facilitator to investigate the etiopathogenesis of periodontal disease, are used to know the efficacy of reconstructive and regenerative procedures, and are also helpful in evaluation of newer therapeutic techniques including laser and implant therapies prior to application in the human beings. The aim of this review is to know the different animal models used in various specialties of dental research and to know the ethical guidelines prior to the usage of experimental models with main emphasis on how to refine, replace, and reduce the number of animal models usage in the laboratory. An online search for experimental animal models used in dental research was performed using MEDLINE/PubMed database. Publications from 2009 to May 2013 in the specialty of periodontics were included in writing this review. A total of 652 references were published in PubMed/MEDLINE databases based on the search terms used. Out of 245 studies, 241 were related to the periodontal research published in English from 2009 to 2013. Relevant papers were chosen according to the inclusion and exclusion criteria. After extensive electronic and hand search on animal models, it has been observed that various animal models were used in dental research. Search on animal models used for dental research purpose revealed that various animals such as rats, mice, guinea pigs, rabbit, beagle dogs, goats, and nonhuman primates were extensively used. However, with the new advancement of ex vivo animal models, it has become easy to investigate disease pathogenesis and to test the efficacy of newer therapeutic modalities with the reduced usage of animal models. This review summarized the large amount of literature on animal models used in periodontal research with main emphasis on ethical guidelines and on reducing the animal model usage in future perspective.

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

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.

Small Animal Models for Evaluating Filovirus Countermeasures.

Science.gov (United States)

Banadyga, Logan; Wong, Gary; Qiu, Xiangguo

2018-05-11

The development of novel therapeutics and vaccines to treat or prevent disease caused by filoviruses, such as Ebola and Marburg viruses, depends on the availability of animal models that faithfully recapitulate clinical hallmarks of disease as it is observed in humans. In particular, small animal models (such as mice and guinea pigs) are historically and frequently used for the primary evaluation of antiviral countermeasures, prior to testing in nonhuman primates, which represent the gold-standard filovirus animal model. In the past several years, however, the filovirus field has witnessed the continued refinement of the mouse and guinea pig models of disease, as well as the introduction of the hamster and ferret models. We now have small animal models for most human-pathogenic filoviruses, many of which are susceptible to wild type virus and demonstrate key features of disease, including robust virus replication, coagulopathy, and immune system dysfunction. Although none of these small animal model systems perfectly recapitulates Ebola virus disease or Marburg virus disease on its own, collectively they offer a nearly complete set of tools in which to carry out the preclinical development of novel antiviral drugs.

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.

Osteoarthritis: new insights in animal models.

Science.gov (United States)

Longo, Umile Giuseppe; Loppini, Mattia; Fumo, Caterina; Rizzello, Giacomo; Khan, Wasim Sardar; Maffulli, Nicola; Denaro, Vincenzo

2012-01-01

Osteoarthritis (OA) is the most frequent and symptomatic health problem in the middle-aged and elderly population, with over one-half of all people over the age of 65 showing radiographic changes in painful knees. The aim of the present study was to perform an overview on the available animal models used in the research field on the OA. Discrepancies between the animal models and the human disease are present. As regards human 'idiopathic' OA, with late onset and slow progression, it is perhaps wise not to be overly enthusiastic about animal models that show severe chondrodysplasia and very early OA. Advantage by using genetically engineered mouse models, in comparison with other surgically induced models, is that molecular etiology is known. Find potential molecular markers for the onset of the disease and pay attention to the role of gender and environmental factors should be very helpful in the study of mice that acquire premature OA. Surgically induced destabilization of joint is the most widely used induction method. These models allow the temporal control of disease induction and follow predictable progression of the disease. In animals, ACL transection and meniscectomy show a speed of onset and severity of disease higher than in humans after same injury.

Animal models of osteoporosis - necessity and limitations

Directory of Open Access Journals (Sweden)

Turner A. Simon

2001-06-01

Full Text Available There is a great need to further characterise the available animal models for postmenopausal osteoporosis, for the understanding of the pathogenesis of the disease, investigation of new therapies (e.g. selective estrogen receptor modulators (SERMs and evaluation of prosthetic devices in osteoporotic bone. Animal models that have been used in the past include non-human primates, dogs, cats, rodents, rabbits, guinea pigs and minipigs, all of which have advantages and disadvantages. Sheep are a promising model for various reasons: they are docile, easy to handle and house, relatively inexpensive, available in large numbers, spontaneously ovulate, and the sheep's bones are large enough to evaluate orthopaedic implants. Most animal models have used females and osteoporosis in the male has been largely ignored. Recently, interest in development of appropriate prosthetic devices which would stimulate osseointegration into osteoporotic, appendicular, axial and mandibular bone has intensified. Augmentation of osteopenic lumbar vertebrae with bioactive ceramics (vertebroplasty is another area that will require testing in the appropriate animal model. Using experimental animal models for the study of these different facets of osteoporosis minimizes some of the difficulties associated with studying the disease in humans, namely time and behavioral variability among test subjects. New experimental drug therapies and orthopaedic implants can potentially be tested on large numbers of animals subjected to a level of experimental control impossible in human clinical research.

Animal models for microbicide safety and efficacy testing.

Science.gov (United States)

Veazey, Ronald S

2013-07-01

Early studies have cast doubt on the utility of animal models for predicting success or failure of HIV-prevention strategies, but results of multiple human phase 3 microbicide trials, and interrogations into the discrepancies between human and animal model trials, indicate that animal models were, and are, predictive of safety and efficacy of microbicide candidates. Recent studies have shown that topically applied vaginal gels, and oral prophylaxis using single or combination antiretrovirals are indeed effective in preventing sexual HIV transmission in humans, and all of these successes were predicted in animal models. Further, prior discrepancies between animal and human results are finally being deciphered as inadequacies in study design in the model, or quite often, noncompliance in human trials, the latter being increasingly recognized as a major problem in human microbicide trials. Successful microbicide studies in humans have validated results in animal models, and several ongoing studies are further investigating questions of tissue distribution, duration of efficacy, and continued safety with repeated application of these, and other promising microbicide candidates in both murine and nonhuman primate models. Now that we finally have positive correlations with prevention strategies and protection from HIV transmission, we can retrospectively validate animal models for their ability to predict these results, and more importantly, prospectively use these models to select and advance even safer, more effective, and importantly, more durable microbicide candidates into human trials.

Animal Models of Chemotherapy-induced Mucositis

DEFF Research Database (Denmark)

Sangild, Per T; Shen, René Liang; Pontoppidan, Peter Erik Lotko

2018-01-01

constitution). Here, we briefly describe CIM pathophysiology, particularly the basic knowledge that has been obtained from CIM animal models. These model studies have indicated potential new preventive and ameliorating interventions, including supplementation with natural bioactive diets (e.g. milk fractions...... easier make clinically-relevant treatment regimens possible. In synergy, animal models improve the basic pathophysiological understanding of CIM and provide new ideas for treatment that are required to make competent decisions in clinical practice....

Animal models for dengue vaccine development and testing.

Science.gov (United States)

Na, Woonsung; Yeom, Minjoo; Choi, Il-Kyu; Yook, Heejun; Song, Daesub

2017-07-01

Dengue fever is a tropical endemic disease; however, because of climate change, it may become a problem in South Korea in the near future. Research on vaccines for dengue fever and outbreak preparedness are currently insufficient. In addition, because there are no appropriate animal models, controversial results from vaccine efficacy assessments and clinical trials have been reported. Therefore, to study the mechanism of dengue fever and test the immunogenicity of vaccines, an appropriate animal model is urgently needed. In addition to mouse models, more suitable models using animals that can be humanized will need to be constructed. In this report, we look at the current status of model animal construction and discuss which models require further development.

Animal models of pancreatic cancer for drug research.

Science.gov (United States)

Kapischke, Matthias; Pries, Alexandra

2008-10-01

The operative and conservative results of therapy in pancreatic ductal adenocarcinoma remain appallingly poor. This underlines the demand for further research for effective anticancer drugs. The various animal models remain the essential method for the determination of efficacy of substances during preclinical phase. Unfortunately, most of these tested substances showed a good efficacy in pancreatic carcinoma in the animal model but were not confirmed during the clinical phase. The available literature in PubMed, Medline, Ovid and secondary literature was searched regarding the available animal models for drug testing against pancreatic cancer. The models were analyzed regarding their pros and cons in anticancer drug testing. The different modifications of the orthotopic model (especially in mice) seem at present to be the best model for anticancer testing in pancreatic carcinoma. The value of genetically engineered animal model (GEM) and syngeneic models is on debate. A good selection of the model concerning the questions supposed to be clarified may improve the comparability of the results of animal experiments compared to clinical trials.

Interobserver reliability of the 'Welfare Quality(®) Animal Welfare Assessment Protocol for Growing Pigs'.

Science.gov (United States)

Czycholl, I; Kniese, C; Büttner, K; Beilage, E Grosse; Schrader, L; Krieter, J

2016-01-01

The present paper focuses on evaluating the interobserver reliability of the 'Welfare Quality(®) Animal Welfare Assessment Protocol for Growing Pigs'. The protocol for growing pigs mainly consists of a Qualitative Behaviour Assessment (QBA), direct behaviour observations (BO) carried out by instantaneous scan sampling and checks for different individual parameters (IP), e.g. presence of tail biting, wounds and bursitis. Three trained observers collected the data by performing 29 combined assessments, which were done at the same time and on the same animals; but they were carried out completely independent of each other. The findings were compared by the calculation of Spearman Rank Correlation Coefficients (RS), Intraclass Correlation Coefficients (ICC), Smallest Detectable Changes (SDC) and Limits of Agreements (LoA). There was no agreement found concerning the adjectives belonging to the QBA (e.g. active: RS: 0.50, ICC: 0.30, SDC: 0.38, LoA: -0.05 to 0.45; fearful: RS: 0.06, ICC: 0.0, SDC: 0.26, LoA: -0.20 to 0.30). In contrast, the BO showed good agreement (e.g. social behaviour: RS: 0.45, ICC: 0.50, SDC: 0.09, LoA: -0.09 to 0.03 use of enrichment material: RS: 0.75, ICC: 0.68, SDC: 0.06, LoA: -0.03 to 0.03). Overall, observers agreed well in the IP, e.g. tail biting (RS: 0.52, ICC: 0.88; SDC: 0.05, LoA: -0.01 to 0.02) and wounds (RS: 0.43, ICC: 0.59, SDC: 0.10, LoA: -0.09 to 0.10). The parameter bursitis showed great differences (RS: 0.10, ICC: 0.0, SDC: 0.35, LoA: -0.37 to 0.40), which can be explained by difficulties in the assessment when the animals moved around quickly or their legs were soiled. In conclusion, the interobserver reliability was good in the BO and most IP, but not for the parameter bursitis and the QBA.

Current challenges facing the assessment of the allergenic capacity of food allergens in animal models.

Science.gov (United States)

Bøgh, Katrine Lindholm; van Bilsen, Jolanda; Głogowski, Robert; López-Expósito, Iván; Bouchaud, Grégory; Blanchard, Carine; Bodinier, Marie; Smit, Joost; Pieters, Raymond; Bastiaan-Net, Shanna; de Wit, Nicole; Untersmayr, Eva; Adel-Patient, Karine; Knippels, Leon; Epstein, Michelle M; Noti, Mario; Nygaard, Unni Cecilie; Kimber, Ian; Verhoeckx, Kitty; O'Mahony, Liam

2016-01-01

Food allergy is a major health problem of increasing concern. The insufficiency of protein sources for human nutrition in a world with a growing population is also a significant problem. The introduction of new protein sources into the diet, such as newly developed innovative foods or foods produced using new technologies and production processes, insects, algae, duckweed, or agricultural products from third countries, creates the opportunity for development of new food allergies, and this in turn has driven the need to develop test methods capable of characterizing the allergenic potential of novel food proteins. There is no doubt that robust and reliable animal models for the identification and characterization of food allergens would be valuable tools for safety assessment. However, although various animal models have been proposed for this purpose, to date, none have been formally validated as predictive and none are currently suitable to test the allergenic potential of new foods. Here, the design of various animal models are reviewed, including among others considerations of species and strain, diet, route of administration, dose and formulation of the test protein, relevant controls and endpoints measured.

Latest animal models for anti-HIV drug discovery.

Science.gov (United States)

Sliva, Katja

2015-02-01

HIV research is limited by the fact that lentiviruses are highly species specific. The need for appropriate models to promote research has led to the development of many elaborate surrogate animal models. This review looks at the history of animal models for HIV research. Although natural animal lentivirus infections and chimeric viruses such as chimera between HIV and simian immunodeficiency virus and simian-tropic HIV are briefly discussed, the main focus is on small animal models, including the complex design of the 'humanized' mouse. The review also traces the historic evolution and milestones as well as depicting current models and future prospects for HIV research. HIV research is a complex and challenging task that is highly manpower-, money- and time-consuming. Besides factors such as hypervariability and latency, the lack of appropriate animal models that exhibit and recapitulate the entire infectious process of HIV, is one of the reasons behind the failure to eliminate the lentivirus from the human population. This obstacle has led to the exploitation and further development of many sophisticated surrogate animal models for HIV research. While there is no animal model that perfectly mirrors and mimics HIV infections in humans, there are a variety of host species and viruses that complement each other. Combining the insights from each model, and critically comparing the results obtained with data from human clinical trials should help expand our understanding of HIV pathogenesis and drive future drug development.

Animal models for auditory streaming

Science.gov (United States)

Itatani, Naoya

2017-01-01

Sounds in the natural environment need to be assigned to acoustic sources to evaluate complex auditory scenes. Separating sources will affect the analysis of auditory features of sounds. As the benefits of assigning sounds to specific sources accrue to all species communicating acoustically, the ability for auditory scene analysis is widespread among different animals. Animal studies allow for a deeper insight into the neuronal mechanisms underlying auditory scene analysis. Here, we will review the paradigms applied in the study of auditory scene analysis and streaming of sequential sounds in animal models. We will compare the psychophysical results from the animal studies to the evidence obtained in human psychophysics of auditory streaming, i.e. in a task commonly used for measuring the capability for auditory scene analysis. Furthermore, the neuronal correlates of auditory streaming will be reviewed in different animal models and the observations of the neurons’ response measures will be related to perception. The across-species comparison will reveal whether similar demands in the analysis of acoustic scenes have resulted in similar perceptual and neuronal processing mechanisms in the wide range of species being capable of auditory scene analysis. This article is part of the themed issue ‘Auditory and visual scene analysis’. PMID:28044022

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)

The necessity of animal models in pain research.

Science.gov (United States)

Mogil, Jeffrey S; Davis, Karen D; Derbyshire, Stuart W

2010-10-01

There exists currently a fair degree of introspection in the pain research community about the value of animal research. This review represents a defense of animal research in pain. We discuss the inherent advantage of animal models over human research as well as the crucial complementary roles animal studies play vis-à-vis human imaging and genetic studies. Finally, we discuss recent developments in animal models of pain that should improve the relevance and translatability of findings using laboratory animals. We believe that pain research using animal models is a continuing necessity-to understand fundamental mechanisms, identify new analgesic targets, and inform, guide and follow up human studies-if novel analgesics are to be developed for the treatment of chronic pain. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Animal models of papillomavirus pathogenesis.

Science.gov (United States)

Campo, M Saveria

2002-11-01

Tumorigenesis due to papillomavirus (PV) infection was first demonstrated in rabbits and cattle early last century. Despite the evidence obtained in animals, the role of viruses in human cancer was dismissed as irrelevant. It took a paradigm shift in the late 1970s for some viruses to be recognised as 'tumour viruses' in humans, and in 1995, more than 60 years after Rous's first demonstration of CRPV oncogenicity, WHO officially declared that 'HPV-16 and HPV-18 are carcinogenic to humans'. Experimental studies with animal PVs have been a determining factor in this decision. Animal PVs have been studied both as agents of disease in animals and as models of human PV infection. In addition to the study of PV infection in whole animals, in vitro studies with animal PV proteins have contributed greatly to the understanding of the mechanisms of cell transformation. Animal PVs cause distressing diseases in both farm and companion animals, such as teat papillomatosis in cattle, equine sarcoids and canine oral papillomatosis and there is an urgent need to understand the pathogenesis of these problematic infections. Persistent and florid teat papillomatosis in cows can lead to mastitis, prevent the suckling of calves and make milking impossible; heavily affected animals are culled and so occasionally are whole herds. Equine sarcoids are often recurrent and untreatable and lead to loss of valuable animals. Canine oral papillomatosis can be very extensive and persistent and lead to great distress. Thus the continuing research in the biology of animal PVs is amply justified. BPVs and CRPV have been for many years the model systems with which to study the biology of HPV. Induction of papillomas and their neoplastic progression has been experimentally demonstrated and reproduced in cattle and rabbits, and virus-cofactor interactions have been elucidated in these systems. With the advancements in molecular and cell culture techniques, the direct study of HPV has become less

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…

Animal models of preeclampsia; uses and limitations.

LENUS (Irish Health Repository)

McCarthy, F P

2012-01-31

Preeclampsia remains a leading cause of maternal and fetal morbidity and mortality and has an unknown etiology. The limited progress made regarding new treatments to reduce the incidence and severity of preeclampsia has been attributed to the difficulties faced in the development of suitable animal models for the mechanistic research of this disease. In addition, animal models need hypotheses on which to be based and the slow development of testable hypotheses has also contributed to this poor progress. The past decade has seen significant advances in our understanding of preeclampsia and the development of viable reproducible animal models has contributed significantly to these advances. Although many of these models have features of preeclampsia, they are still poor overall models of the human disease and limited due to lack of reproducibility and because they do not include the complete spectrum of pathophysiological changes associated with preeclampsia. This review aims to provide a succinct and comprehensive assessment of current animal models of preeclampsia, their uses and limitations with particular attention paid to the best validated and most comprehensive models, in addition to those models which have been utilized to investigate potential therapeutic interventions for the treatment or prevention of preeclampsia.

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

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

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....

Animation of 3D Model of Human Head

Directory of Open Access Journals (Sweden)

V. Michalcin

2007-04-01

Full Text Available The paper deals with the new algorithm of animation of 3D model of the human head in combination with its global motion. The designed algorithm is very fast and with low calculation requirements, because it does not need the synthesis of the input videosequence for estimation of the animation parameters as well as the parameters of global motion. The used 3D model Candide generates different expressions using its animation units which are controlled by the animation parameters. These ones are estimated on the basis of optical flow without the need of extracting of the feature points in the frames of the input videosequence because they are given by the selected vertices of the animation units of the calibrated 3D model Candide. The established multiple iterations inside the designed animation algorithm of 3D model of the human head between two successive frames significantly improved its accuracy above all for the large motion.

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.

Animation Augmented Reality Book Model (AAR Book Model) to Enhance Teamwork

Science.gov (United States)

Chujitarom, Wannaporn; Piriyasurawong, Pallop

2017-01-01

This study aims to synthesize an Animation Augmented Reality Book Model (AAR Book Model) to enhance teamwork and to assess the AAR Book Model to enhance teamwork. Samples are five specialists that consist of one animation specialist, two communication and information technology specialists, and two teaching model design specialists, selected by…

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

Animal models of cerebral arterial gas embolism

NARCIS (Netherlands)

Weenink, Robert P.; Hollmann, Markus W.; van Hulst, Robert A.

2012-01-01

Cerebral arterial gas embolism is a dreaded complication of diving and invasive medical procedures. Many different animal models have been used in research on cerebral arterial gas embolism. This review provides an overview of the most important characteristics of these animal models. The properties

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

Large animal models for vaccine development and testing.

Science.gov (United States)

Gerdts, Volker; Wilson, Heather L; Meurens, Francois; van Drunen Littel-van den Hurk, Sylvia; Wilson, Don; Walker, Stewart; Wheler, Colette; Townsend, Hugh; Potter, Andrew A

2015-01-01

The development of human vaccines continues to rely on the use of animals for research. Regulatory authorities require novel vaccine candidates to undergo preclinical assessment in animal models before being permitted to enter the clinical phase in human subjects. Substantial progress has been made in recent years in reducing and replacing the number of animals used for preclinical vaccine research through the use of bioinformatics and computational biology to design new vaccine candidates. However, the ultimate goal of a new vaccine is to instruct the immune system to elicit an effective immune response against the pathogen of interest, and no alternatives to live animal use currently exist for evaluation of this response. Studies identifying the mechanisms of immune protection; determining the optimal route and formulation of vaccines; establishing the duration and onset of immunity, as well as the safety and efficacy of new vaccines, must be performed in a living system. Importantly, no single animal model provides all the information required for advancing a new vaccine through the preclinical stage, and research over the last two decades has highlighted that large animals more accurately predict vaccine outcome in humans than do other models. Here we review the advantages and disadvantages of large animal models for human vaccine development and demonstrate that much of the success in bringing a new vaccine to market depends on choosing the most appropriate animal model for preclinical testing. © The Author 2015. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Elements of episodic-like memory in animal models.

Science.gov (United States)

Crystal, Jonathon D

2009-03-01

Representations of unique events from one's past constitute the content of episodic memories. A number of studies with non-human animals have revealed that animals remember specific episodes from their past (referred to as episodic-like memory). The development of animal models of memory holds enormous potential for gaining insight into the biological bases of human memory. Specifically, given the extensive knowledge of the rodent brain, the development of rodent models of episodic memory would open new opportunities to explore the neuroanatomical, neurochemical, neurophysiological, and molecular mechanisms of memory. Development of such animal models holds enormous potential for studying functional changes in episodic memory in animal models of Alzheimer's disease, amnesia, and other human memory pathologies. This article reviews several approaches that have been used to assess episodic-like memory in animals. The approaches reviewed include the discrimination of what, where, and when in a radial arm maze, dissociation of recollection and familiarity, object recognition, binding, unexpected questions, and anticipation of a reproductive state. The diversity of approaches may promote the development of converging lines of evidence on the difficult problem of assessing episodic-like memory in animals.

Chimeric animal models in human stem cell biology.

Science.gov (United States)

Glover, Joel C; Boulland, Jean-Luc; Halasi, Gabor; Kasumacic, Nedim

2009-01-01

The clinical use of stem cells for regenerative medicine is critically dependent on preclinical studies in animal models. In this review we examine some of the key issues and challenges in the use of animal models to study human stem cell biology-experimental standardization, body size, immunological barriers, cell survival factors, fusion of host and donor cells, and in vivo imaging and tracking. We focus particular attention on the various imaging modalities that can be used to track cells in living animals, comparing their strengths and weaknesses and describing technical developments that are likely to lead to new opportunities for the dynamic assessment of stem cell behavior in vivo. We then provide an overview of some of the most commonly used animal models, their advantages and disadvantages, and examples of their use for xenotypic transplantation of human stem cells, with separate reviews of models involving rodents, ungulates, nonhuman primates, and the chicken embryo. As the use of human somatic, embryonic, and induced pluripotent stem cells increases, so too will the range of applications for these animal models. It is likely that increasingly sophisticated uses of human/animal chimeric models will be developed through advances in genetic manipulation, cell delivery, and in vivo imaging.

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)

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.

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

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.

Animal models of erectile dysfunction

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Snehlata V Gajbhiye

2015-01-01

Full Text Available Animal models have contributed to a great extent to understanding and advancement in the field of sexual medicine. Many current medical and surgical therapies in sexual medicine have been tried based on these animal models. Extensive literature search revealed that the compiled information is limited. In this review, we describe various experimental models of erectile dysfunction (ED encompassing their procedures, variables of assessment, advantages and disadvantages. The search strategy consisted of review of PubMed based articles. We included original research work and certain review articles available in PubMed database. The search terms used were "ED and experimental models," "ED and nervous stimulation," "ED and cavernous nerve stimulation," "ED and central stimulation," "ED and diabetes mellitus," "ED and ageing," "ED and hypercholesteremia," "ED and Peyronie′s disease," "radiation induced ED," "telemetric recording," "ED and mating test" and "ED and non-contact erection test."

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...

Animal models for Gaucher disease research

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Tamar Farfel-Becker

2011-11-01

Full Text Available Gaucher disease (GD, the most common lysosomal storage disorder (LSD, is caused by the defective activity of the lysosomal hydrolase glucocerebrosidase, which is encoded by the GBA gene. Generation of animal models that faithfully recapitulate the three clinical subtypes of GD has proved to be more of a challenge than first anticipated. The first mouse to be produced died within hours after birth owing to skin permeability problems, and mice with point mutations in Gba did not display symptoms correlating with human disease and also died soon after birth. Recently, conditional knockout mice that mimic some features of the human disease have become available. Here, we review the contribution of all currently available animal models to examining pathological pathways underlying GD and to testing the efficacy of new treatment modalities, and propose a number of criteria for the generation of more appropriate animal models of GD.

Animal models for Gaucher disease research.

Science.gov (United States)

Farfel-Becker, Tamar; Vitner, Einat B; Futerman, Anthony H

2011-11-01

Gaucher disease (GD), the most common lysosomal storage disorder (LSD), is caused by the defective activity of the lysosomal hydrolase glucocerebrosidase, which is encoded by the GBA gene. Generation of animal models that faithfully recapitulate the three clinical subtypes of GD has proved to be more of a challenge than first anticipated. The first mouse to be produced died within hours after birth owing to skin permeability problems, and mice with point mutations in Gba did not display symptoms correlating with human disease and also died soon after birth. Recently, conditional knockout mice that mimic some features of the human disease have become available. Here, we review the contribution of all currently available animal models to examining pathological pathways underlying GD and to testing the efficacy of new treatment modalities, and propose a number of criteria for the generation of more appropriate animal models of GD.

Final model of multicriterionevaluation of animal welfare

DEFF Research Database (Denmark)

Bonde, Marianne; Botreau, R; Bracke, MBM

One major objective of Welfare Quality® is to propose harmonized methods for the overall assessment of animal welfare on farm and at slaughter that are science based and meet societal concerns. Welfare is a multidimensional concept and its assessment requires measures of different aspects. Welfar......, acceptable welfare and not classified. This evaluation model is tuned according to the views of experts from animal and social sciences, and stakeholders....... Quality® proposes a formal evaluation model whereby the data on animals or their environment are transformed into value scores that reflect compliance with 12 subcriteria and 4 criteria of good welfare. Each animal unit is then allocated to one of four categories: excellent welfare, enhanced welfare...

Retinal Cell Degeneration in Animal Models

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Masayuki Niwa

2016-01-01

Full Text Available The aim of this review is to provide an overview of various retinal cell degeneration models in animal induced by chemicals (N-methyl-d-aspartate- and CoCl2-induced, autoimmune (experimental autoimmune encephalomyelitis, mechanical stress (optic nerve crush-induced, light-induced and ischemia (transient retinal ischemia-induced. The target regions, pathology and proposed mechanism of each model are described in a comparative fashion. Animal models of retinal cell degeneration provide insight into the underlying mechanisms of the disease, and will facilitate the development of novel effective therapeutic drugs to treat retinal cell damage.

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

Animal Models of Hemophilia and Related Bleeding Disorders

Science.gov (United States)

Lozier, Jay N.; Nichols, Timothy C.

2013-01-01

Animal models of hemophilia and related diseases are important for development of novel treatments and to understand the pathophysiology of bleeding disorders in humans. Testing in animals with the equivalent human disorder provides informed estimates of doses and measures of efficacy, which aids in design of human trials. Many models of hemophilia A, hemophilia B, and von Willebrand disease have been developed from animals with spontaneous mutations (hemophilia A dogs, rats, sheep; hemophilia B dogs; and von Willebrand disease pigs and dogs), or by targeted gene disruption in mice to create hemophilia A, B, or VWD models. Animal models have been used to generate new insights into the pathophysiology of each bleeding disorder and also to perform pre-clinical assessments of standard protein replacement therapies as well as novel gene transfer technology. Both the differences between species and differences in underlying causative mutations must be considered in choosing the best animal for a specific scientific study PMID:23956467

Henipavirus Infections: Lessons from Animal Models

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Kévin P. Dhondt

2013-04-01

Full Text Available The Henipavirus genus contains two highly lethal viruses, the Hendra and Nipah viruses and one, recently discovered, apparently nonpathogenic member; Cedar virus. These three, negative-sense single-stranded RNA viruses, are hosted by fruit bats and use EphrinB2 receptors for entry into cells. The Hendra and Nipah viruses are zoonotic pathogens that emerged in the middle of 90s and have caused severe, and often fatal, neurologic and/or respiratory diseases in both humans and different animals; including spillover into equine and porcine species. Development of relevant models is critical for a better understanding of viral pathogenesis, generating new diagnostic tools, and assessing anti-viral therapeutics and vaccines. This review summarizes available data on several animal models where natural and/or experimental infection has been demonstrated; including pteroid bats, horses, pigs, cats, hamsters, guinea pigs, ferrets, and nonhuman primates. It recapitulates the principal features of viral pathogenesis in these animals and current knowledge on anti-viral immune responses. Lastly it describes the recently characterized murine animal model, which provides the possibility to use numerous and powerful tools available for mice to further decipher henipaviruses immunopathogenesis, prophylaxis, and treatment. The utility of different models to analyze important aspects of henipaviruses-induced disease in humans, potential routes of transmission, and therapeutic approaches are equally discussed.

Animal models of asthma: utility and limitations

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Aun MV

2017-11-01

Full Text Available Marcelo Vivolo Aun,1,2 Rafael Bonamichi-Santos,1,2 Fernanda Magalhães Arantes-Costa,2 Jorge Kalil,1 Pedro Giavina-Bianchi1 1Clinical Immunology and Allergy Division, Department of Internal Medicine, University of São Paulo School of Medicine, São Paulo, Brazil, 2Laboratory of Experimental Therapeutics (LIM20, Department of Internal Medicine, University of Sao Paulo, Sao Paulo, Brazil Abstract: Clinical studies in asthma are not able to clear up all aspects of disease pathophysiology. Animal models have been developed to better understand these mechanisms and to evaluate both safety and efficacy of therapies before starting clinical trials. Several species of animals have been used in experimental models of asthma, such as Drosophila, rats, guinea pigs, cats, dogs, pigs, primates and equines. However, the most common species studied in the last two decades is mice, particularly BALB/c. Animal models of asthma try to mimic the pathophysiology of human disease. They classically include two phases: sensitization and challenge. Sensitization is traditionally performed by intraperitoneal and subcutaneous routes, but intranasal instillation of allergens has been increasingly used because human asthma is induced by inhalation of allergens. Challenges with allergens are performed through aerosol, intranasal or intratracheal instillation. However, few studies have compared different routes of sensitization and challenge. The causative allergen is another important issue in developing a good animal model. Despite being more traditional and leading to intense inflammation, ovalbumin has been replaced by aeroallergens, such as house dust mites, to use the allergens that cause human disease. Finally, researchers should define outcomes to be evaluated, such as serum-specific antibodies, airway hyperresponsiveness, inflammation and remodeling. The present review analyzes the animal models of asthma, assessing differences between species, allergens and routes

Maximum Entropy Discrimination Poisson Regression for Software Reliability Modeling.

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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.

Modeling individual animal histories with multistate capture–recapture models

Science.gov (United States)

Lebreton, Jean-Dominique; Nichols, James D.; Barker, Richard J.; Pradel, Roger; Spendelow, Jeffrey A.

2009-01-01

Many fields of science begin with a phase of exploration and description, followed by investigations of the processes that account for observed patterns. The science of ecology is no exception, and recent decades have seen a focus on understanding key processes underlying the dynamics of ecological systems. In population ecology, emphasis has shifted from the state variable of population size to the demographic processes responsible for changes in this state variable: birth, death, immigration, and emigration. In evolutionary ecology, some of these same demographic processes, rates of birth and death, are also the determinants of fitness. In animal population ecology, the estimation of state variables and their associated vital rates is especially problematic because of the difficulties in sampling such populations and detecting individual animals. Indeed, early capture–recapture models were developed for the purpose of estimating population size, given the reality that all animals are not caught or detected at any sampling occasion. More recently, capture–recapture models for open populations were developed to draw inferences about survival in the face of these same sampling problems. The focus of this paper is on multi‐state mark–recapture models (MSMR), which first appeared in the 1970s but have undergone substantial development in the last 15 years. These models were developed to deal explicitly with biological variation, in that animals in different “states” (classes defined by location, physiology, behavior, reproductive status, etc.) may have different probabilities of survival and detection. Animal transitions between states are also stochastic and themselves of interest. These general models have proven to be extremely useful and provide a way of thinking about a remarkably wide range of important ecological processes. These methods are now at a stage of refinement and sophistication where they can readily be used by biologists to tackle a wide

Animal model of thermal injuries

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F. Bečić

2003-11-01

Full Text Available Experimental studies of burns require the use of different animal models with the aim to imitate and reproduce pathophysiological conditions. The aim of this work was to establish experimental model of thermal injury.New Zealand rabbits, weighted from 1.8 kg to 2.3 kg, were utilised during our study. Another, also utilized, animal types were laboratory Rattus rats, species Wistar, albino type, females with body weight of about 232 g. All animals were from our own litter (Institute of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine in Sarajevo. During the experiment, animal were properly situated in adequate cages and rooms, at the controlled temperature (22 ± 2°C, and in the air with normal humidity level. All animals took food and water ad libitum.Rabbits received anesthesia - intravenous pentobarbital sodium in a dose of 60 mg/kg, and then, hair from the upper side of the each rabbit ear was removed and burns were caused by a metal seal in the same manner as in rats. Rats were primarily anesthesied by intraperitoneal pentobarbital sodium in a dose of 35 mg/kg, and then, their hair was removed from the scapula zone (5 cm x 5 cm. Burns were caused by contact with a round metal seal, heated at 80°C in a water bath, during the period of 14 seconds together with contact thermometer control. Round metal seal (radius: 2.5 cm; weight: 100 g; surface: 5 cm2 was just placed on the rat skin without any additional pressure. In order to maintain the microcirculation in the burn wound and to reduce the conversion of partial-thickness skin burns to the burns of the full-thickness skin, all burn wounds were immediately sunk in the 4°C water. Subsequent to that procedure, all animals were individually situated in the proper cages, and left to rest for 4 hours with a constant cautious monitoring of the wound development and animal general state.

Animal models for HCV and HBV studies

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Isabelle Chemin

2007-02-01

Full Text Available

The narrow host range of infection and lack of suitable tissue culture systems for the propagation of hepatitis B and C viruses are limitations that have prevented a more thorough understanding of persistent infection and the pathogenesis of chronic liver disease.

Despite decades of intensive research and significant progresses in understanding of viral hepatitis, many basic questions and clinical problems still await to be resolved. For example, the HBV cellular receptor and related mechanisms of viral entry have not yet been identified. Little is also known about the function of certain non-structural viral products, such as the hepatitis B e antigen and the X protein, or about the role of excess hepadnavirus subviral particles circulating in the blood stream during infection. Furthermore, the molecular mechanisms involved in the development of hepatocellular carcinoma and the role of the immune system in determining the fate of infection are not fully understood.

The reason for these drawbacks is essentially due to the lack of reliable cell-based in vitro infection systems and, most importantly, convenient animal models.

This lack of knowledge has been partially overcome for hepatitis B virus (HBV, by the discovery and characterization of HBV-like viruses in wild animals while for hepatitis C virus (HCV, related flaviviruses have been used as surrogate systems.

Other laboratories have developed transgenic mice that express virus gene products and/or support virus replication. Some HBV transgenic mouse models

Animal models of drug addiction.

Science.gov (United States)

García Pardo, María Pilar; Roger Sánchez, Concepción; De la Rubia Ortí, José Enrique; Aguilar Calpe, María Asunción

2017-09-29

The development of animal models of drug reward and addiction is an essential factor for progress in understanding the biological basis of this disorder and for the identification of new therapeutic targets. Depending on the component of reward to be studied, one type of animal model or another may be used. There are models of reinforcement based on the primary hedonic effect produced by the consumption of the addictive substance, such as the self-administration (SA) and intracranial self-stimulation (ICSS) paradigms, and there are models based on the component of reward related to associative learning and cognitive ability to make predictions about obtaining reward in the future, such as the conditioned place preference (CPP) paradigm. In recent years these models have incorporated methodological modifications to study extinction, reinstatement and reconsolidation processes, or to model specific aspects of addictive behavior such as motivation to consume drugs, compulsive consumption or drug seeking under punishment situations. There are also models that link different reinforcement components or model voluntary motivation to consume (two-bottle choice, or drinking in the dark tests). In short, innovations in these models allow progress in scientific knowledge regarding the different aspects that lead individuals to consume a drug and develop compulsive consumption, providing a target for future treatments of addiction.

Osteoarthritis: New Insights in Animal Models

OpenAIRE

Longo, Umile Giuseppe; Loppini, Mattia; Fumo, Caterina; Rizzello, Giacomo; Khan, Wasim Sardar; Maffulli, Nicola; Denaro, Vincenzo

2012-01-01

Osteoarthritis (OA) is the most frequent and symptomatic health problem in the middle-aged and elderly population, with over one-half of all people over the age of 65 showing radiographic changes in painful knees. The aim of the present study was to perform an overview on the available animal models used in the research field on the OA. Discrepancies between the animal models and the human disease are present. As regards human ‘idiopathic’ OA, with late onset and slow progression, it is perha...

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.

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

Basic mechanisms of MCD in animal models.

Science.gov (United States)

Battaglia, Giorgio; Becker, Albert J; LoTurco, Joseph; Represa, Alfonso; Baraban, Scott C; Roper, Steven N; Vezzani, Annamaria

2009-09-01

Epilepsy-associated glioneuronal malformations (malformations of cortical development [MCD]) include focal cortical dysplasias (FCD) and highly differentiated glioneuronal tumors, most frequently gangliogliomas. The neuropathological findings are variable but suggest aberrant proliferation, migration, and differentiation of neural precursor cells as essential pathogenetic elements. Recent advances in animal models for MCDs allow new insights in the molecular pathogenesis of these epilepsy-associated lesions. Novel approaches, presented here, comprise RNA interference strategies to generate and study experimental models of subcortical band heterotopia and study functional aspects of aberrantly shaped and positioned neurons. Exciting analyses address impaired NMDA receptor expression in FCD animal models compared to human FCDs and excitatory imbalances in MCD animal models such as lissencephaly gene ablated mice as well as in utero irradiated rats. An improved understanding of relevant pathomechanisms will advance the development of targeted treatment strategies for epilepsy-associated malformations.

Osteoporotic Animal Models of Bone Healing: Advantages and Pitfalls.

Science.gov (United States)

Calciolari, Elena; Donos, Nikolaos; Mardas, Nikos

2017-10-01

The aim of this review was to summarize the advantages and pitfalls of the available osteoporotic animal models of bone healing. A thorough literature search was performed in MEDLINE via OVID and EMBASE to identify animal studies investigating the effect of experimental osteoporosis on bone healing and bone regeneration. The osteotomy model in the proximal tibia is the most popular osseous defect model to study the bone healing process in osteoporotic-like conditions, although other well-characterized models, such as the post-extraction model, might be taken into consideration by future studies. The regenerative potential of osteoporotic bone and its response to biomaterials/regenerative techniques has not been clarified yet, and the critical size defect model might be an appropriate tool to serve this purpose. Since an ideal animal model for simulating osteoporosis does not exist, the type of bone remodeling, the animal lifespan, the age of peak bone mass, and the economic and ethical implications should be considered in our selection process. Furthermore, the influence of animal species, sex, age, and strain on the outcome measurement should be taken into account. In order to make future studies meaningful, standardized international guidelines for osteoporotic animal models of bone healing need to be set up.

RELIABILITY MODELING BASED ON INCOMPLETE DATA: OIL PUMP APPLICATION

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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.

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

What Is the Predictive Value of Animal Models for Vaccine Efficacy in Humans? Consideration of Strategies to Improve the Value of Animal Models.

Science.gov (United States)

Herati, Ramin Sedaghat; Wherry, E John

2018-04-02

Animal models are an essential feature of the vaccine design toolkit. Although animal models have been invaluable in delineating the mechanisms of immune function, their precision in predicting how well specific vaccines work in humans is often suboptimal. There are, of course, many obvious species differences that may limit animal models from predicting all details of how a vaccine works in humans. However, careful consideration of which animal models may have limitations should also allow more accurate interpretations of animal model data and more accurate predictions of what is to be expected in clinical trials. In this article, we examine some of the considerations that might be relevant to cross-species extrapolation of vaccine-related immune responses for the prediction of how vaccines will perform in humans. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Stochastic Differential Equation-Based Flexible Software Reliability Growth Model

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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.

Development of a morphology-based modeling technique for tracking solid-body displacements: examining the reliability of a potential MRI-only approach for joint kinematics assessment

International Nuclear Information System (INIS)

Mahato, Niladri K.; Montuelle, Stephane; Cotton, John; Williams, Susan; Thomas, James; Clark, Brian

2016-01-01

Single or biplanar video radiography and Roentgen stereophotogrammetry (RSA) techniques used for the assessment of in-vivo joint kinematics involves application of ionizing radiation, which is a limitation for clinical research involving human subjects. To overcome this limitation, our long-term goal is to develop a magnetic resonance imaging (MRI)-only, three dimensional (3-D) modeling technique that permits dynamic imaging of joint motion in humans. Here, we present our initial findings, as well as reliability data, for an MRI-only protocol and modeling technique. We developed a morphology-based motion-analysis technique that uses MRI of custom-built solid-body objects to animate and quantify experimental displacements between them. The technique involved four major steps. First, the imaging volume was calibrated using a custom-built grid. Second, 3-D models were segmented from axial scans of two custom-built solid-body cubes. Third, these cubes were positioned at pre-determined relative displacements (translation and rotation) in the magnetic resonance coil and scanned with a T 1 and a fast contrast-enhanced pulse sequences. The digital imaging and communications in medicine (DICOM) images were then processed for animation. The fourth step involved importing these processed images into an animation software, where they were displayed as background scenes. In the same step, 3-D models of the cubes were imported into the animation software, where the user manipulated the models to match their outlines in the scene (rotoscoping) and registered the models into an anatomical joint system. Measurements of displacements obtained from two different rotoscoping sessions were tested for reliability using coefficient of variations (CV), intraclass correlation coefficients (ICC), Bland-Altman plots, and Limits of Agreement analyses. Between-session reliability was high for both the T 1 and the contrast-enhanced sequences. Specifically, the average CVs for translation were 4

Development of a morphology-based modeling technique for tracking solid-body displacements: examining the reliability of a potential MRI-only approach for joint kinematics assessment.

Science.gov (United States)

Mahato, Niladri K; Montuelle, Stephane; Cotton, John; Williams, Susan; Thomas, James; Clark, Brian

2016-05-18

Single or biplanar video radiography and Roentgen stereophotogrammetry (RSA) techniques used for the assessment of in-vivo joint kinematics involves application of ionizing radiation, which is a limitation for clinical research involving human subjects. To overcome this limitation, our long-term goal is to develop a magnetic resonance imaging (MRI)-only, three dimensional (3-D) modeling technique that permits dynamic imaging of joint motion in humans. Here, we present our initial findings, as well as reliability data, for an MRI-only protocol and modeling technique. We developed a morphology-based motion-analysis technique that uses MRI of custom-built solid-body objects to animate and quantify experimental displacements between them. The technique involved four major steps. First, the imaging volume was calibrated using a custom-built grid. Second, 3-D models were segmented from axial scans of two custom-built solid-body cubes. Third, these cubes were positioned at pre-determined relative displacements (translation and rotation) in the magnetic resonance coil and scanned with a T1 and a fast contrast-enhanced pulse sequences. The digital imaging and communications in medicine (DICOM) images were then processed for animation. The fourth step involved importing these processed images into an animation software, where they were displayed as background scenes. In the same step, 3-D models of the cubes were imported into the animation software, where the user manipulated the models to match their outlines in the scene (rotoscoping) and registered the models into an anatomical joint system. Measurements of displacements obtained from two different rotoscoping sessions were tested for reliability using coefficient of variations (CV), intraclass correlation coefficients (ICC), Bland-Altman plots, and Limits of Agreement analyses. Between-session reliability was high for both the T1 and the contrast-enhanced sequences. Specifically, the average CVs for translation were 4

Bicistronic lentiviruses containing a viral 2A cleavage sequence reliably co-express two proteins and restore vision to an animal model of LCA1.

Directory of Open Access Journals (Sweden)

Jonathan D Verrier

Full Text Available The disease processes underlying inherited retinal disease are complex and are not completely understood. Many of the corrective gene therapies designed to treat diseases linked to mutations in genes specifically expressed in photoreceptor cells restore function to these cells but fail to stop progression of the disease. There is growing consensus that effective treatments for these diseases will require delivery of multiple therapeutic proteins that will be selected to treat specific aspects of the disease process. The purpose of this study was to design a lentiviral transgene that reliably expresses all of the proteins it encodes and does so in a consistent manner among infected cells. We show, using both in vitro and in vivo analyses, that bicistronic lentiviral transgenes encoding two fluorescent proteins fused to a viral 2A-like cleavage peptide meet these expression criteria. To determine if this transgene design is suitable for therapeutic applications, we replaced one of the fluorescent protein genes with the gene encoding guanylate cyclase-1 (GC1 and delivered lentivirus carrying this transgene to the retinas of the GUCY1*B avian model of Leber congenital amaurosis-1 (LCA1. GUCY1*B chickens carry a null mutation in the GC1 gene that disrupts photoreceptor function and causes blindness at hatching, a phenotype that closely matches that observed in humans with LCA1. We found that treatment of these animals with the 2A lentivector encoding GC1 restored vision to these animals as evidenced by the presence of optokinetic reflexes. We conclude that 2A-like peptides, with proper optimization, can be successfully incorporated into therapeutic vectors designed to deliver multiple proteins to neural retinal. These results highlight the potential of this vector design to serve as a platform for the development of combination therapies designed to enhance or prolong the benefits of corrective gene therapies.

Reviewing model application to support animal health decision making.

Science.gov (United States)

Singer, Alexander; Salman, Mo; Thulke, Hans-Hermann

2011-04-01

Animal health is of societal importance as it affects human welfare, and anthropogenic interests shape decision making to assure animal health. Scientific advice to support decision making is manifold. Modelling, as one piece of the scientific toolbox, is appreciated for its ability to describe and structure data, to give insight in complex processes and to predict future outcome. In this paper we study the application of scientific modelling to support practical animal health decisions. We reviewed the 35 animal health related scientific opinions adopted by the Animal Health and Animal Welfare Panel of the European Food Safety Authority (EFSA). Thirteen of these documents were based on the application of models. The review took two viewpoints, the decision maker's need and the modeller's approach. In the reviewed material three types of modelling questions were addressed by four specific model types. The correspondence between tasks and models underpinned the importance of the modelling question in triggering the modelling approach. End point quantifications were the dominating request from decision makers, implying that prediction of risk is a major need. However, due to knowledge gaps corresponding modelling studies often shed away from providing exact numbers. Instead, comparative scenario analyses were performed, furthering the understanding of the decision problem and effects of alternative management options. In conclusion, the most adequate scientific support for decision making - including available modelling capacity - might be expected if the required advice is clearly stated. Copyright © 2011 Elsevier B.V. All rights reserved.

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.

Animal-based measures for welfare assessment

Directory of Open Access Journals (Sweden)

Agostino Sevi

2010-01-01

Full Text Available Animal welfare assessment can’t be irrespective of measures taken on animals. Indeed, housing parametersrelatedtostructures, designandmicro-environment, evenifreliable parameters related to structures, design and micro-environment, even if reliable and easier to take, can only identify conditions which could be detrimental to animal welfare, but can’t predict poor welfare in animals per se. Welfare assessment through animal-based measures is almost complex, given that animals’ responses to stressful conditions largely depend on the nature, length and intensity of challenges and on physiological status, age, genetic susceptibility and previous experience of animals. Welfare assessment requires a multi-disciplinary approach and the monitoring of productive, ethological, endocrine, immunological and pathological param- eters to be exhaustive and reliable. So many measures are needed, because stresses can act only on some of the mentioned parameters or on all of them but at different times and degree. Under this point of view, the main aim of research is to find feasible and most responsive indicators of poor animal welfare. In last decades, studies focused on the following parameters for animal wel- fare assessment indexes of biological efficiency, responses to behavioral tests, cortisol secretion, neutrophil to lymphocyte ratio, lymphocyte proliferation, production of antigen specific IgG and cytokine release, somatic cell count and acute phase proteins. Recently, a lot of studies have been addressed to reduce handling and constraint of animals for taking measures to be used in welfare assessment, since such procedures can induce stress in animals and undermined the reliability of measures taken for welfare assessment. Range of animal-based measures for welfare assessment is much wider under experimental condition than at on-farm level. In welfare monitoring on-farm the main aim is to find feasible measures of proved validity and reliability

Classic and New Animal Models of Parkinson's Disease

Directory of Open Access Journals (Sweden)

Javier Blesa

2012-01-01

Full Text Available Neurological disorders can be modeled in animals so as to recreate specific pathogenic events and behavioral outcomes. Parkinson’s Disease (PD is the second most common neurodegenerative disease of an aging population, and although there have been several significant findings about the PD disease process, much of this process still remains a mystery. Breakthroughs in the last two decades using animal models have offered insights into the understanding of the PD disease process, its etiology, pathology, and molecular mechanisms. Furthermore, while cellular models have helped to identify specific events, animal models, both toxic and genetic, have replicated almost all of the hallmarks of PD and are useful for testing new neuroprotective or neurorestorative strategies. Moreover, significant advances in the modeling of additional PD features have come to light in both classic and newer models. In this review, we try to provide an updated summary of the main characteristics of these models as well as the strengths and weaknesses of what we believe to be the most popular PD animal models. These models include those produced by 6-hydroxydopamine (6-OHDA, 1-methyl-1,2,3,6-tetrahydropiridine (MPTP, rotenone, and paraquat, as well as several genetic models like those related to alpha-synuclein, PINK1, Parkin and LRRK2 alterations.

Elementary of animal model for percutaneous and ocular penetration

Directory of Open Access Journals (Sweden)

Kalpesh Chhotalal Ashara

2016-12-01

Full Text Available Models of animal are the most appropriate method for assessments of human in-vivo percutaneous and ocular penetrations. Monkey and rodents are used for the same. There are several nuts and bolts of each one, so it is necessary to study each one separately. Monkey, porcine and guinea pig penetration are correlated with that of human skin. The skin of rodents, lupus, pigs, etc. has more penetration properties than human skin. Rabbit, goat and sheep eye are mostly used for ocular penetration. The researcher also used hen’s egg chorioallantoic membrane test for ocular irritation study. The other animals’ cornea, cul-de-sac, eyeballs and prepared corneal epithelial models are very less in practice. Web-based alternative non-animal models are also available instead of animal models too. This article describes characteristics of monkeys, pigs, rats, rabbits, guinea pigs and hairless rodents, HuSki model, Cellophane® membrane, egg membrane, gelatin membrane, animal models for ophthalmic delivery, hen’s egg chorioallantoic membrane test, prepared corneal epithelial models and web-based alternative non-animal database.

Animal models of 'anxiety': where next?

Science.gov (United States)

Rodgers, R J

1997-11-01

Numerous procedures have been developed to facilitate preclinical research on the behavioural pharmacology of anxiety and, as a result of this application, are often referred to as animal models of 'anxiety'. This is an unfortunate misnomer, not only because of the apparent inability of many tests to detect novel anxiolytics consistently, but also because the term implies that anxiety is a unitary emotion. Such difficulties have arisen largely as a consequence of test development strategies which, by emphasizing pharmacological (i.e. benzodiazepine) validation, have yielded models predictive of a specific type of anxiolytic activity. The present review argues that the refinement of existing tests as well as the development of new procedures requires urgent attention to the much neglected issue of behavioural validation. From an evolutionary perspective, normal human anxiety may be conceptualized as a repertoire of defence reactions tailored to meet different forms of threats, and disorders of anxiety as the inappropriate activation or exaggeration of these usually adaptive response patterns. In this context, consideration of the defensive reactions typically observed in our animal models reveals substantially greater commonality in the behavioural effects of benzodiazepine and 5-HT1A anxiolytics than would otherwise be apparent. Therefore, with the exception of the conventional plus-maze paradigm (discussed at some length), better correspondence is seen in tests involving unconditioned response to potential threat (e.g. social interaction, distress vocalizations and light/dark exploration) than in tests of conditioned fear reactions. Even within the latter grouping, however, greater commonality is seen in procedures based on reactions to proximal threat (e.g. freezing, startle, ultrasonic vocalizations, burying) than those involving reactions to distal threat (e.g. avoidance/flight). Significantly, very similar findings have been reported in tests specifically

Computer-animated model of accommodation and presbyopia.

Science.gov (United States)

Goldberg, Daniel B

2015-02-01

To understand, demonstrate, and further research the mechanisms of accommodation and presbyopia. Private practice, Little Silver, New Jersey, USA. Experimental study. The CAMA 2.0 computer-animated model of accommodation and presbyopia was produced in collaboration with an experienced medical animator using Autodesk Maya animation software and Adobe After Effects. The computer-animated model demonstrates the configuration and synchronous movements of all accommodative elements. A new classification of the zonular apparatus based on structure and function is proposed. There are 3 divisions of zonular fibers; that is, anterior, crossing, and posterior. The crossing zonular fibers form a scaffolding to support the lens; the anterior and posterior zonular fibers work reciprocally to achieve focused vision. The model demonstrates the important support function of Weiger ligament. Dynamic movement of the ora serrata demonstrates that the forces of ciliary muscle contraction store energy for disaccommodation in the elastic choroid. The flow of aqueous and vitreous provides strong evidence for our understanding of the hydrodynamic interactions during the accommodative cycle. The interaction may result from the elastic stretch in the choroid transmitted to the vitreous rather than from vitreous pressue. The model supports the concept that presbyopia results from loss of elasticity and increasing ocular rigidity in both the lenticular and extralenticular structures. The computer-animated model demonstrates the structures of accommodation moving in synchrony and might enhance understanding of the mechanisms of accommodation and presbyopia. Dr. Goldberg is a consultant to Acevision, Inc., and Bausch & Lomb. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Animal models in plastic and reconstructive surgery simulation-a review.

Science.gov (United States)

Loh, Charles Yuen Yung; Wang, Aline Yen Ling; Tiong, Vincent Tze Yang; Athanassopoulos, Thanassi; Loh, Meiling; Lim, Philip; Kao, Huang-Kai

2018-01-01

The use of live and cadaveric animal models in surgical training is well established as a means of teaching and improving surgical skill in a controlled setting. We aim to review, evaluate, and summarize the models published in the literature that are applicable to Plastic Surgery training. A PubMed search for keywords relating to animal models in Plastic Surgery and the associated procedures was conducted. Animal models that had cross over between specialties such as microsurgery with Neurosurgery and pinnaplasty with ear, nose, and throat surgery were included as they were deemed to be relevant to our training curriculum. A level of evidence and recommendation assessment was then given to each surgical model. Our review found animal models applicable to plastic surgery training in four major categories namely-microsurgery training, flap raising, facial surgery, and hand surgery. Twenty-four separate articles described various methods of practicing microsurgical techniques on different types of animals. Fourteen different articles each described various methods of conducting flap-based procedures which consisted of either local or perforator flap dissection. Eight articles described different models for practicing hand surgery techniques. Finally, eight articles described animal models that were used for head and neck procedures. A comprehensive summary of animal models related to plastic surgery training has been compiled. Cadaveric animal models provide a readily available introduction to many procedures and ought to be used instead of live models when feasible. Copyright © 2017 Elsevier Inc. All rights reserved.

Stress and adaptation : Toward ecologically relevant animal models

NARCIS (Netherlands)

Koolhaas, Jaap M.; Boer, Sietse F. de; Buwalda, Bauke

Animal models have contributed considerably to the current understanding of mechanisms underlying the role of stress in health and disease. Despite the progress made already, much more can be made by more carefully exploiting animals' and humans' shared biology, using ecologically relevant models.

[Establishment of Social Stress Induced Depression-like Animal Model in Mice of C57BL/6 Strain and Behavioral Assessments].

Science.gov (United States)

Li, Mi-hui; Wu, Xiao; Wei Ying; Dong, Jing-cheng

2016-02-01

To establish social stress induced depression-like model in mice of C57BL/6 strain, and to assess its reliability using differenf behavioral methods. Totally 20 male mice of C57BL/6 strain were divided into the normal group and the stress model group by random digit table,10 in each group. Another 10 CD1 mice were subjected to social stress. Mice in the normal control group received no stress, while those in the model group received social stress for 10 successive days. Behavioral assessment was performed using social interaction test (SIT), the elevated plus-maze (EPM) test, tail suspension test (TST), respectively. Serum cortisol level was detected by ELISA to assess the reliability of the model. In the social interaction test when the social target (CDI mice) was inexistent, mice in the normal control group spent longer time in the social interaction zone and less time in the corner zone (P stress induced depression-like animal model in mice of C57BL/6 straineasquite reliable and possibly suitable to be used in integrative medicine research of combination of disease and syndrome model.

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.

Reliability of Circumplex Axes

Directory of Open Access Journals (Sweden)

Micha Strack

2013-06-01

Full Text Available We present a confirmatory factor analysis (CFA procedure for computing the reliability of circumplex axes. The tau-equivalent CFA variance decomposition model estimates five variance components: general factor, axes, scale-specificity, block-specificity, and item-specificity. Only the axes variance component is used for reliability estimation. We apply the model to six circumplex types and 13 instruments assessing interpersonal and motivational constructs—Interpersonal Adjective List (IAL, Interpersonal Adjective Scales (revised; IAS-R, Inventory of Interpersonal Problems (IIP, Impact Messages Inventory (IMI, Circumplex Scales of Interpersonal Values (CSIV, Support Action Scale Circumplex (SAS-C, Interaction Problems With Animals (IPI-A, Team Role Circle (TRC, Competing Values Leadership Instrument (CV-LI, Love Styles, Organizational Culture Assessment Instrument (OCAI, Customer Orientation Circle (COC, and System for Multi-Level Observation of Groups (behavioral adjectives; SYMLOG—in 17 German-speaking samples (29 subsamples, grouped by self-report, other report, and metaperception assessments. The general factor accounted for a proportion ranging from 1% to 48% of the item variance, the axes component for 2% to 30%; and scale specificity for 1% to 28%, respectively. Reliability estimates varied considerably from .13 to .92. An application of the Nunnally and Bernstein formula proposed by Markey, Markey, and Tinsley overestimated axes reliabilities in cases of large-scale specificities but otherwise works effectively. Contemporary circumplex evaluations such as Tracey’s RANDALL are sensitive to the ratio of the axes and scale-specificity components. In contrast, the proposed model isolates both components.

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

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.

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

A reliability-risk modelling of nuclear rad-waste facilities

International Nuclear Information System (INIS)

Lehmann, P.H.; El-Bassioni, A.A.

1975-01-01

Rad-waste disposal systems of nuclear power sites are designed and operated to collect, delay, contain, and concentrate radioactive wastes from reactor plant processes such that on-site and off-site exposures to radiation are well below permissible limits. To assist the designer in achieving minimum release/exposure goals, a computerized reliability-risk model has been developed to simulate the rad-waste system. The objectives of the model are to furnish a practical tool for quantifying the effects of changes in system configuration, operation, and equipment, and for the identification of weak segments in the system design. Primarily, the model comprises a marriage of system analysis, reliability analysis, and release-risk assessment. Provisions have been included in the model to permit the optimization of the system design subject to constraints on cost and rad-releases. The system analysis phase involves the preparation of a physical and functional description of the rad-waste facility accompanied by the formation of a system tree diagram. The reliability analysis phase embodies the formulation of appropriate reliability models and the collection of model parameters. Release-risk assessment constitutes the analytical basis whereupon further system and reliability analyses may be warranted. Release-risk represents the potential for release of radioactivity and is defined as the product of an element's unreliability at time, t, and the radioactivity available for release in time interval, Δt. A computer code (RARISK) has been written to simulate the tree diagram of the rad-waste system. Reliability and release-risk results have been generated for cases which examined the process flow paths of typical rad-waste systems, the effects of repair and standby, the variations of equipment failure and repair rates, and changes in system configurations. The essential feature of this model is that a complex system like the rad-waste facility can be easily decomposed into its

Animal Models Used to Explore Abdominal Aortic Aneurysms

DEFF Research Database (Denmark)

Lysgaard Poulsen, J; Stubbe, J; Lindholt, J S

2016-01-01

OBJECTIVE: Experimental animal models have been used to investigate the formation, development, and progression of abdominal aortic aneurysms (AAAs) for decades. New models are constantly being developed to imitate the mechanisms of human AAAs and to identify treatments that are less risky than...... those used today. However, to the authors' knowledge, there is no model identical to the human AAA. The objective of this systematic review was to assess the different types of animal models used to investigate the development, progression, and treatment of AAA and to highlight their advantages...... and limitations. METHODS: A search protocol was used to perform a systematic literature search of PubMed and Embase. A total of 2,830 records were identified. After selection of the relevant articles, 564 papers on animal AAA models were included. RESULTS: The most common models in rodents, including elastase...

Combinations of chromosome transfer and genome editing for the development of cell/animal models of human disease and humanized animal models.

Science.gov (United States)

Uno, Narumi; Abe, Satoshi; Oshimura, Mitsuo; Kazuki, Yasuhiro

2018-02-01

Chromosome transfer technology, including chromosome modification, enables the introduction of Mb-sized or multiple genes to desired cells or animals. This technology has allowed innovative developments to be made for models of human disease and humanized animals, including Down syndrome model mice and humanized transchromosomic (Tc) immunoglobulin mice. Genome editing techniques are developing rapidly, and permit modifications such as gene knockout and knockin to be performed in various cell lines and animals. This review summarizes chromosome transfer-related technologies and the combined technologies of chromosome transfer and genome editing mainly for the production of cell/animal models of human disease and humanized animal models. Specifically, these include: (1) chromosome modification with genome editing in Chinese hamster ovary cells and mouse A9 cells for efficient transfer to desired cell types; (2) single-nucleotide polymorphism modification in humanized Tc mice with genome editing; and (3) generation of a disease model of Down syndrome-associated hematopoiesis abnormalities by the transfer of human chromosome 21 to normal human embryonic stem cells and the induction of mutation(s) in the endogenous gene(s) with genome editing. These combinations of chromosome transfer and genome editing open up new avenues for drug development and therapy as well as for basic research.

Laboratory animal models for esophageal cancer

Directory of Open Access Journals (Sweden)

Dhanya Venugopalan Nair

2016-11-01

Full Text Available The incidence of esophageal cancer is rapidly increasing especially in developing countries. The major risk factors include unhealthy lifestyle practices such as alcohol consumption, smoking, and chewing tobacco to name a few. Diagnosis at an advanced stage and poor prognosis make esophageal cancer one of the most lethal diseases. These factors have urged further research in understanding the pathophysiology of the disease. Animal models not only aid in understanding the molecular pathogenesis of esophageal cancer but also help in developing therapeutic interventions for the disease. This review throws light on the various recent laboratory animal models for esophageal cancer.

Animal Models of Allergic Diseases

Directory of Open Access Journals (Sweden)

Domenico Santoro

2014-12-01

Full Text Available Allergic diseases have great impact on the quality of life of both people and domestic animals. They are increasing in prevalence in both animals and humans, possibly due to the changed lifestyle conditions and the decreased exposure to beneficial microorganisms. Dogs, in particular, suffer from environmental skin allergies and develop a clinical presentation which is very similar to the one of children with eczema. Thus, dogs are a very useful species to improve our understanding on the mechanisms involved in people’s allergies and a natural model to study eczema. Animal models are frequently used to elucidate mechanisms of disease and to control for confounding factors which are present in studies with patients with spontaneously occurring disease and to test new therapies that can be beneficial in both species. It has been found that drugs useful in one species can also have benefits in other species highlighting the importance of a comprehensive understanding of diseases across species and the value of comparative studies. The purpose of the current article is to review allergic diseases across species and to focus on how these diseases compare to the counterpart in people.

Animal Models of Diabetic Retinopathy: Summary and Comparison

Science.gov (United States)

Lo, Amy C. Y.

2013-01-01

Diabetic retinopathy (DR) is a microvascular complication associated with chronic exposure to hyperglycemia and is a major cause of blindness worldwide. Although clinical assessment and retinal autopsy of diabetic patients provide information on the features and progression of DR, its underlying pathophysiological mechanism cannot be deduced. In order to have a better understanding of the development of DR at the molecular and cellular levels, a variety of animal models have been developed. They include pharmacological induction of hyperglycemia and spontaneous diabetic rodents as well as models of angiogenesis without diabetes (to compensate for the absence of proliferative DR symptoms). In this review, we summarize the existing protocols to induce diabetes using STZ. We also describe and compare the pathological presentations, in both morphological and functional aspects, of the currently available DR animal models. The advantages and disadvantages of using different animals, ranging from zebrafish, rodents to other higher-order mammals, are also discussed. Until now, there is no single model that displays all the clinical features of DR as seen in human. Yet, with the understanding of the pathological findings in these animal models, researchers can select the most suitable models for mechanistic studies or drug screening. PMID:24286086

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

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.

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.

The complete guide to blender graphics computer modeling and animation

CERN Document Server

Blain, John M

2014-01-01

Smoothly Leads Users into the Subject of Computer Graphics through the Blender GUIBlender, the free and open source 3D computer modeling and animation program, allows users to create and animate models and figures in scenes, compile feature movies, and interact with the models and create video games. Reflecting the latest version of Blender, The Complete Guide to Blender Graphics: Computer Modeling & Animation, 2nd Edition helps beginners learn the basics of computer animation using this versatile graphics program. This edition incorporates many new features of Blender, including developments

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.)

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...

Animal models of GM2 gangliosidosis: utility and limitations

Science.gov (United States)

Lawson, Cheryl A; Martin, Douglas R

2016-01-01

GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, β-N-acetylhexosaminidase, and includes the closely related Tay–Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay–Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described. PMID:27499644

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

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.

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

Animal models of chronic obstructive pulmonary disease.

Science.gov (United States)

Pérez-Rial, Sandra; Girón-Martínez, Álvaro; Peces-Barba, Germán

2015-03-01

Animal models of disease have always been welcomed by the scientific community because they provide an approach to the investigation of certain aspects of the disease in question. Animal models of COPD cannot reproduce the heterogeneity of the disease and usually only manage to represent the disease in its milder stages. Moreover, airflow obstruction, the variable that determines patient diagnosis, not always taken into account in the models. For this reason, models have focused on the development of emphysema, easily detectable by lung morphometry, and have disregarded other components of the disease, such as airway injury or associated vascular changes. Continuous, long-term exposure to cigarette smoke is considered the main risk factor for this disease, justifying the fact that the cigarette smoke exposure model is the most widely used. Some variations on this basic model, related to exposure time, the association of other inducers or inhibitors, exacerbations or the use of transgenic animals to facilitate the identification of pathogenic pathways have been developed. Some variations or heterogeneity of this disease, then, can be reproduced and models can be designed for resolving researchers' questions on disease identification or treatment responses. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

Comparative value of blood and skin samples for diagnosis of spotted fever group rickettsial infection in model animals.

Science.gov (United States)

Levin, Michael L; Snellgrove, Alyssa N; Zemtsova, Galina E

2016-07-01

The definitive diagnosis of spotted fever group (SFG) rickettsioses in humans is challenging due to the retrospective nature and cross reactivity of the serological methods and the absence of reliable and consistent samples for molecular diagnostics. Existing data indicate the transient character of bacteremia in experimentally infected animals. The ability of arthropod vectors to acquire rickettsial infection from the laboratory animals in the absence of systemic infection and known tropism of rickettsial agents to endothelial cells of peripheral blood vessels underline the importance of local infection and consequently the diagnostic potential of skin samples. In order to evaluate the diagnostic sensitivity of rickettsial DNA detection in blood and skin samples, we compared results of PCR testing in parallel samples collected from model laboratory animals infected with Rickettsia rickettsii, Rickettsia parkeri and Rickettsia slovaca-like agent at different time points after infection. Skin samples were collected from ears - away from the site of tick placement and without eschars. Overall, testing of skin samples resulted in a higher proportion of positive results than testing of blood samples. Presented data from model animals demonstrates that testing of skin samples from sites of rickettsial proliferation can provide definitive molecular diagnosis of up to 60-70% of tick-borne SFG rickettsial infections during the acute stage of illness. Detection of pathogen DNA in cutaneous samples is a valuable alternative to blood-PCR at least in model animals. Published by Elsevier GmbH.

Th17 in Animal Models of Rheumatoid Arthritis

Directory of Open Access Journals (Sweden)

Motomu Hashimoto

2017-07-01

Full Text Available IL-17-secreting helper CD4 T cells (Th17 cells constitute a newly identified subset of helper CD4 T cells that play a key role in the development of rheumatoid arthritis (RA in its animal models. Recently, several models of spontaneous RA, which elucidate the mechanism of RA onset, have been discovered. These animal models shed new light on the role of Th17 in the development of autoimmune arthritis. Th17 cells coordinate inflammation and promote joint destruction, acting on various cells, including neutrophils, macrophages, synovial fibroblasts, and osteoclasts. Regulatory T cells cannot control Th17 cells under conditions of inflammation. In this review, the pathogenic role of Th17 cells in arthritis development, which was revealed by the recent animal models of RA, is discussed.

Experimental animal models for COPD: a methodological review

Directory of Open Access Journals (Sweden)

Vahideh Ghorani

2017-05-01

The present review provides various methods used for induction of animal models of COPD, different animals used (mainly mice, guinea pigs and rats and measured parameters. The information provided in this review is valuable for choosing appropriate animal, method of induction and selecting parameters to be measured in studies concerning COPD.

Animal Cancer Models of Skeletal Metastasis

Directory of Open Access Journals (Sweden)

Catherine Hibberd

2013-01-01

Full Text Available The bony skeleton is one of the most common sites of metastatic spread of cancer and is a significant source of morbidity in cancer patients, causing pain and pathologic fracture, impaired ambulatory ability, and poorer quality of life. Animal cancer models of skeletal metastases are essential for better understanding of the molecular pathways behind metastatic spread and local growth and invasion of bone, to enable analysis of host-tumor cell interactions, identify barriers to the metastatic process, and to provide platforms to develop and test novel therapies prior to clinical application in human patients. Thus, the ideal model should be clinically relevant, reproducible and representative of the human condition. This review summarizes the current in vivo animal models used in the study of cancer metastases of the skeleton.

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.

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

Lanchester's attrition models and fights among social animals

OpenAIRE

Eldridge S. Adams; Michael Mesterton-Gibbons

2003-01-01

Lanchester's models of attrition during warfare have served as the basis for several predictions about conflicts between groups of animals. These models and their extensions describe rates of mortality during battles as functions of the number and fighting abilities of individuals in each group, allowing analysis of the determinants of group strength and of the cumulative numbers of casualties. We propose modifications to Lanchester's models to improve their applicability to social animals. I...

Research progress on animal models of Alzheimer's disease

Directory of Open Access Journals (Sweden)

Wen DONG

2015-08-01

Full Text Available Alzheimer's disease (AD is a degenerative disease of the central nervous system, and its pathogenesis is complex. Animal models play an important role in study on pathogenesis and treatment of AD. This paper summarized methods of building models, observation on animal models and evaluation index in recent years, so as to provide related evidence for basic and clinical research in future. DOI: 10.3969/j.issn.1672-6731.2015.08.003

Animal models of obesity and diabetes mellitus

DEFF Research Database (Denmark)

Kleinert, Maximilian; Clemmensen, Christoffer; Hofmann, Susanna M

2018-01-01

More than one-third of the worldwide population is overweight or obese and therefore at risk of developing type 2 diabetes mellitus. In order to mitigate this pandemic, safer and more potent therapeutics are urgently required. This necessitates the continued use of animal models to discover......, validate and optimize novel therapeutics for their safe use in humans. In order to improve the transition from bench to bedside, researchers must not only carefully select the appropriate model but also draw the right conclusions. In this Review, we consolidate the key information on the currently...... available animal models of obesity and diabetes and highlight the advantages, limitations and important caveats of each of these models....

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...

Large Mammalian Animal Models of Heart Disease

Directory of Open Access Journals (Sweden)

Paula Camacho

2016-10-01

Full Text Available Due to the biological complexity of the cardiovascular system, the animal model is an urgent pre-clinical need to advance our knowledge of cardiovascular disease and to explore new drugs to repair the damaged heart. Ideally, a model system should be inexpensive, easily manipulated, reproducible, a biological representative of human disease, and ethically sound. Although a larger animal model is more expensive and difficult to manipulate, its genetic, structural, functional, and even disease similarities to humans make it an ideal model to first consider. This review presents the commonly-used large animals—dog, sheep, pig, and non-human primates—while the less-used other large animals—cows, horses—are excluded. The review attempts to introduce unique points for each species regarding its biological property, degrees of susceptibility to develop certain types of heart diseases, and methodology of induced conditions. For example, dogs barely develop myocardial infarction, while dilated cardiomyopathy is developed quite often. Based on the similarities of each species to the human, the model selection may first consider non-human primates—pig, sheep, then dog—but it also depends on other factors, for example, purposes, funding, ethics, and policy. We hope this review can serve as a basic outline of large animal models for cardiovascular researchers and clinicians.

Criticizing animal experimentation, at my peril.

Science.gov (United States)

Eisenman, Stephen F

2016-01-01

Initiatives leading to even modest reduction in animal use at major U.S. universities are likely to continue to face strong opposition. At least, that's the conclusion the author draws from his efforts at Northwestern University. In fact, despite a growing body of evidence that animal-based research is flawed at best and misleading or un-scientific at worst its use is growing at Northwestern and elsewhere. Moreover, recent discoveries concerning animal consciousness and emotion have not led to notable improvements in the conditions in which AWA protected animals live at the Chicago vivarium. There, animals languish in featureless rooms or sterile cages without access to daylight and with little opportunity to express their natural behaviors and aptitudes. The writer's public exposure of these conditions led to a fierce backlash. Unless there is a significant change in laboratory and university culture, change will only come when the marketplace and funding agencies demand better and more reliable, non-animal models for the testing of drug toxicity and effectiveness.

Animal models for evaluation of oral delivery of biopharmaceuticals

DEFF Research Database (Denmark)

Harloff-Helleberg, Stine; Nielsen, Line Hagner; Nielsen, Hanne Mørck

2017-01-01

of systems for oral delivery of biopharmaceuticals may result in new treatment modalities to increase the patient compliance and reduce product cost. In the preclinical development phase, use of experimental animal models is essential for evaluation of new formulation designs. In general, the limited oral...... bioavailability of biopharmaceuticals, of just a few percent, is expected, and therefore, the animal models and the experimental settings must be chosen with utmost care. More knowledge and focus on this topic is highly needed, despite experience from the numerous studies evaluating animal models for oral drug...... delivery of small molecule drugs. This review highlights and discusses pros and cons of the most currently used animal models and settings. Additionally, it also looks into the influence of anesthetics and sampling methods for evaluation of drug delivery systems for oral delivery of biopharmaceuticals...

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....

Animal models for HIV/AIDS research

Science.gov (United States)

Hatziioannou, Theodora; Evans, David T.

2015-01-01

The AIDS pandemic continues to present us with unique scientific and public health challenges. Although the development of effective antiretroviral therapy has been a major triumph, the emergence of drug resistance requires active management of treatment regimens and the continued development of new antiretroviral drugs. Moreover, despite nearly 30 years of intensive investigation, we still lack the basic scientific knowledge necessary to produce a safe and effective vaccine against HIV-1. Animal models offer obvious advantages in the study of HIV/AIDS, allowing for a more invasive investigation of the disease and for preclinical testing of drugs and vaccines. Advances in humanized mouse models, non-human primate immunogenetics and recombinant challenge viruses have greatly increased the number and sophistication of available mouse and simian models. Understanding the advantages and limitations of each of these models is essential for the design of animal studies to guide the development of vaccines and antiretroviral therapies for the prevention and treatment of HIV-1 infection. PMID:23154262

Animal Migraine Models for Drug Development

DEFF Research Database (Denmark)

Jansen-Olesen, Inger; Tfelt-Hansen, Peer; Olesen, Jes

2013-01-01

Migraine is number seven in WHO's list of all diseases causing disability and the third most costly neurological disorder in Europe. Acute attacks are treatable by highly selective drugs such as the triptans but there is still a huge unmet therapeutic need. Unfortunately, drug development...... for headache has almost come to a standstill partly because of a lack of valid animal models. Here we review previous models with emphasis on optimal characteristics of a future model. In addition to selection of animal species, the method of induction of migraine-like changes and the method of recording...... responses elicited by such measures are crucial. The most naturalistic way of inducing attacks is by infusion of endogenous signaling molecules that are known to cause migraine in patients. The most valid response is recording of neural activity in the trigeminal system. The most useful headache related...

Optogenetics in animal model of alcohol addiction

Science.gov (United States)

Nalberczak, Maria; Radwanska, Kasia

2014-11-01

Our understanding of the neuronal and molecular basis of alcohol addiction is still not satisfactory. As a consequence we still miss successful therapy of alcoholism. One of the reasons for such state is the lack of appropriate animal models which would allow in-depth analysis of biological basis of addiction. Here we will present our efforts to create the animal model of alcohol addiction in the automated learning device, the IntelliCage setup. Applying this model to optogenetically modified mice with remotely controlled regulation of selected neuronal populations by light may lead to very precise identification of neuronal circuits involved in coding addiction-related behaviors.

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

Animal Models of Diverticulosis: Review and Recommendations.

Science.gov (United States)

Patel, Bhavesh; Guo, Xiaomei; Noblet, Jillian; Chambers, Sean; Kassab, Ghassan S

2018-06-01

Diverticulosis is a structural alteration of the colon tissue characterized by the development of pouch-like structures called diverticula. It afflicts a significant portion of the population in Western countries, with a higher prevalence among the elderly. Diverticulosis is believed to be the result of a synergetic interaction between inherent tissue weakness, diet, colonic microstructure, motility, and genetic factors. A validated etiology has, however, not yet been established. Non-surgical treatment is currently lacking due to this poor understanding, and surgical colon resection is the only long-term solution following recurrent complications. With rising prevalence, the burden of diverticulosis on patients and hospital resources has increased over the past several years. More efficient and less invasive treatment approaches are, thus, urgently needed. Animal models of diverticulosis are crucial to enable a preclinical assessment and evaluation of such novel approaches. This review discusses the animal models of diverticulosis that have been proposed to date. The current models require either a significant amount of time to develop diverticulosis, present a relatively low success rate, or seriously deteriorate the animals' systemic health. Recommendations are thus provided to address these pitfalls through the selection of a suitable animal and the combination of multiple risk factors for diverticulosis.

Stop staring facial modeling and animation done right

CERN Document Server

Osipa, Jason

2010-01-01

The de facto official source on facial animation—now updated!. If you want to do character facial modeling and animation at the high levels achieved in today's films and games, Stop Staring: Facial Modeling and Animation Done Right, Third Edition , is for you. While thoroughly covering the basics such as squash and stretch, lip syncs, and much more, this new edition has been thoroughly updated to capture the very newest professional design techniques, as well as changes in software, including using Python to automate tasks.: Shows you how to create facial animation for movies, games, and more;

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.

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.

Predicting climate-induced range shifts: model differences and model reliability.

Science.gov (United States)

Joshua J. Lawler; Denis White; Ronald P. Neilson; Andrew R. Blaustein

2006-01-01

Predicted changes in the global climate are likely to cause large shifts in the geographic ranges of many plant and animal species. To date, predictions of future range shifts have relied on a variety of modeling approaches with different levels of model accuracy. Using a common data set, we investigated the potential implications of alternative modeling approaches for...

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)

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.

Quality assurance for animal feed analysis laboratories

NARCIS (Netherlands)

Balthrop, J.; Brand, B.; Cowie, R.A.; Danier, J.; Boever, de J.L.; Jonge, de L.H.; Jackson, F.; Makkar, H.P.S.; Piotrowski, C.

2011-01-01

Every sector of the livestock industry, the associated services and the wellbeing of both animals and humans are influenced by animal feeding. The availability of accurate, reliable and reproducible analytical data is imperative for proper feed formulation. Only reliable analysis can lead to the

Animal Models for the Study of Female Sexual Dysfunction

Science.gov (United States)

Marson, Lesley; Giamberardino, Maria Adele; Costantini, Raffaele; Czakanski, Peter; Wesselmann, Ursula

2017-01-01

Introduction Significant progress has been made in elucidating the physiological and pharmacological mechanisms of female sexual function through preclinical animal research. The continued development of animal models is vital for the understanding and treatment of the many diverse disorders that occur in women. Aim To provide an updated review of the experimental models evaluating female sexual function that may be useful for clinical translation. Methods Review of English written, peer-reviewed literature, primarily from 2000 to 2012, that described studies on female sexual behavior related to motivation, arousal, physiological monitoring of genital function and urogenital pain. Main Outcomes Measures Analysis of supporting evidence for the suitability of the animal model to provide measurable indices related to desire, arousal, reward, orgasm, and pelvic pain. Results The development of female animal models has provided important insights in the peripheral and central processes regulating sexual function. Behavioral models of sexual desire, motivation, and reward are well developed. Central arousal and orgasmic responses are less well understood, compared with the physiological changes associated with genital arousal. Models of nociception are useful for replicating symptoms and identifying the neurobiological pathways involved. While in some cases translation to women correlates with the findings in animals, the requirement of circulating hormones for sexual receptivity in rodents and the multifactorial nature of women’s sexual function requires better designed studies and careful analysis. The current models have studied sexual dysfunction or pelvic pain in isolation; combining these aspects would help to elucidate interactions of the pathophysiology of pain and sexual dysfunction. Conclusions Basic research in animals has been vital for understanding the anatomy, neurobiology, and physiological mechanisms underlying sexual function and urogenital pain

[Animal models of autoimmune prostatitis and their evaluation criteria].

Science.gov (United States)

Shen, Jia-ming; Lu, Jin-chun; Yao, Bing

2016-03-01

Chronic prostatitis is a highly prevalent disease of unclear etiology. Researches show that autoimmune reaction is one cause of the problem. An effective animal model may help a lot to understand the pathogenesis and find proper diagnostic and therapeutic strategies of the disease. Currently used autoimmune prostatitis-related animal models include those of age-dependent spontaneous prostatitis, autoimmune regulator-dependent spontaneous prostatitis, self antigen-induced prostatitis, and steroid-induced prostatitis. Whether an animal model of autoimmune prostatitis is successfully established can be evaluated mainly from the five aspects: histology, morphology, specific antigens, inflammatory factors, and pain intensity.

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.

Animal Models of Tick-Borne Hemorrhagic Fever Viruses

Directory of Open Access Journals (Sweden)

Heinz Feldmann

2013-05-01

Full Text Available Tick-borne hemorrhagic fever viruses (TBHFV are detected throughout the African and Eurasian continents and are an emerging or re-emerging threat to many nations. Due to the largely sporadic incidences of these severe diseases, information on human cases and research activities in general have been limited. In the past decade, however, novel TBHFVs have emerged and areas of endemicity have expanded. Therefore, the development of countermeasures is of utmost importance in combating TBHFV as elimination of vectors and interrupting enzootic cycles is all but impossible and ecologically questionable. As in vivo models are the only way to test efficacy and safety of countermeasures, understanding of the available animal models and the development and refinement of animal models is critical in negating the detrimental impact of TBHFVs on public and animal health.

Animal Models of Zika Virus

Science.gov (United States)

Bradley, Michael P; Nagamine, Claude M

2017-01-01

Zika virus has garnered great attention over the last several years, as outbreaks of the disease have emerged throughout the Western Hemisphere. Until quite recently Zika virus was considered a fairly benign virus, with limited clinical severity in both people and animals. The size and scope of the outbreak in the Western Hemisphere has allowed for the identification of severe clinical disease that is associated with Zika virus infection, most notably microcephaly among newborns, and an association with Guillian–Barré syndrome in adults. This recent association with severe clinical disease, of which further analysis strongly suggested causation by Zika virus, has resulted in a massive increase in the amount of both basic and applied research of this virus. Both small and large animal models are being used to uncover the pathogenesis of this emerging disease and to develop vaccine and therapeutic strategies. Here we review the animal-model–based Zika virus research that has been performed to date. PMID:28662753

STRESS RESPONSE STUDIES USING ANIMAL MODELS

Science.gov (United States)

This presentation will provide the evidence that ozone exposure in animal models induce neuroendocrine stress response and this stress response modulates lung injury and inflammation through adrenergic and glucocorticoid receptors.

Animal model of chronic abdominal hernia in rabbit Modelo animal de hérnia abdominal crônica em coelhos

Directory of Open Access Journals (Sweden)

Walter da Silva

2009-08-01

Full Text Available PURPOSE: To create a feasible animal model of hernia that should be reliable to test the different types of mesh and/or surgical technique. METHODS: Thirty six male New Zealand albino rabbits were submitted to surgical procedure to provoke a standard hole in the abdominal wall. A metallic frame measuring 3 cm length and 1 cm width was allocated longitudinally on the umbilicus scar and the comprehensive three squared centimeters area was resected. A continuous 4.0 polyamide was performed to closure the subcutaneous and skin. RESULTS: During three weeks a score of signals/symptoms was performed to evaluate the wound and clinical conditions. No death or severe complications occurred. In the 3rd week the hernia ring and visceral adhesions were evaluated. Soft omental adherences were present in the hernial sac in all animals. The area of hernia ring ranged from 32.1±5.5 to 35.6±3.1 squared centimeter and the maximum was 39 cm² and the minimum was 30 cm². The model results in protrusion which was similar to a human incisional hernia with hernia sac, visceral adhesions and fibrous healing ring. CONCLUSION: The model was more reliable to test further techniques or mesh on hernia repair.OBJETIVO: Criação de um modelo animal de hérnia que seja confiável para testar as diferentes técnicas e tipos de telas. MÉTODOS: Trinta e seis coelhos foram submetidos a procedimento operatório que provocou uma falha na parede abdominal. Uma moldura metálica com 3 cm de comprimento e 1 cm de largura foi colocada longitudinalmente sobre a cicatriz umbilical e ressecada uma área de 3cm². Uma sutura contínua de poliamida 4.0 fechou a tela subcutânea e pele. RESULTADOS: durante três semanas o escore de sinais e sintomas foi coletado para avaliar as condições clínicas e da ferida operatória. Não ocorreram óbitos ou complicações graves. Na terceira semana o anel herniário e aderências peritoneais foram avaliadas. Aderências frouxas estavam presentes

The Use of Animal Models in Behavioural Neuroscience Research

NARCIS (Netherlands)

Bovenkerk, B.; Kaldewaij, F.

2015-01-01

Animal models are used in experiments in the behavioural neurosciences that aim to contribute to the prevention and treatment of cognitive and affective disorders in human beings, such as anxiety and depression. Ironically, those animals that are likely to be the best models for psychopathology are

The Use of Animal Models in Behavioural Neuroscience Research.

NARCIS (Netherlands)

Bovenkerk, Bernice; Kaldewaij, Frederike

2015-01-01

Animal models are used in experiments in the behavioural neurosciences that aim to contribute to the prevention and treatment of cognitive and affective disorders in human beings, such as anxiety and depression. Ironically, those animals that are likely to be the best models for psychopathology are

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

Animal models of contraception: utility and limitations

Directory of Open Access Journals (Sweden)

Liechty ER

2015-04-01

Full Text Available Emma R Liechty,1 Ingrid L Bergin,1 Jason D Bell2 1Unit for Laboratory Animal Medicine, 2Program on Women's Health Care Effectiveness Research, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA Abstract: Appropriate animal modeling is vital for the successful development of novel contraceptive devices. Advances in reproductive biology have identified novel pathways for contraceptive intervention. Here we review species-specific anatomic and physiologic considerations impacting preclinical contraceptive testing, including efficacy testing, mechanistic studies, device design, and modeling off-target effects. Emphasis is placed on the use of nonhuman primate models in contraceptive device development. Keywords: nonhuman primate, preclinical, in vivo, contraceptive devices

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.

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

Animating climate model data

Science.gov (United States)

DaPonte, John S.; Sadowski, Thomas; Thomas, Paul

2006-05-01

This paper describes a collaborative project conducted by the Computer Science Department at Southern Connecticut State University and NASA's Goddard Institute for Space Science (GISS). Animations of output from a climate simulation math model used at GISS to predict rainfall and circulation have been produced for West Africa from June to September 2002. These early results have assisted scientists at GISS in evaluating the accuracy of the RM3 climate model when compared to similar results obtained from satellite imagery. The results presented below will be refined to better meet the needs of GISS scientists and will be expanded to cover other geographic regions for a variety of time frames.

Aspects of animal models for major neuropsychiatric disorders

Directory of Open Access Journals (Sweden)

Lefter Radu

2014-01-01

Full Text Available We will review the main animal models for the major neuropsychiatric disorders, focusing on schizophrenia, Alzheimer’s disease, Parkinson’s disease, depression, anxiety and autism. Although these mental disorders are specifically human pathologies and therefore impossible to perfectly replicate in animals, the use of experimental animals is based on the physiological and anatomical similarities between humans and animals such as the rat, and mouse, and on the fact that 99% of human and murine genomes are shared. Pathological conditions in animals can be assessed by manipulating the metabolism of neurotransmitters, through various behavioral tests, and by determining biochemical parameters that can serve as important markers of disorders.

Immunogenicity of therapeutic proteins: the use of animal models.

Science.gov (United States)

Brinks, Vera; Jiskoot, Wim; Schellekens, Huub

2011-10-01

Immunogenicity of therapeutic proteins lowers patient well-being and drastically increases therapeutic costs. Preventing immunogenicity is an important issue to consider when developing novel therapeutic proteins and applying them in the clinic. Animal models are increasingly used to study immunogenicity of therapeutic proteins. They are employed as predictive tools to assess different aspects of immunogenicity during drug development and have become vital in studying the mechanisms underlying immunogenicity of therapeutic proteins. However, the use of animal models needs critical evaluation. Because of species differences, predictive value of such models is limited, and mechanistic studies can be restricted. This review addresses the suitability of animal models for immunogenicity prediction and summarizes the insights in immunogenicity that they have given so far.

Cardiovascular Imaging: What Have We Learned From Animal Models?

Directory of Open Access Journals (Sweden)

Arnoldo eSantos

2015-10-01

Full Text Available Cardiovascular imaging has become an indispensable tool for patient diagnosis and follow up. Probably the wide clinical applications of imaging are due to the possibility of a detailed and high quality description and quantification of cardiovascular system structure and function. Also phenomena that involve complex physiological mechanisms and biochemical pathways, such as inflammation and ischemia, can be visualized in a nondestructive way. The widespread use and evolution of imaging would not have been possible without animal studies. Animal models have allowed for instance, i the technical development of different imaging tools, ii to test hypothesis generated from human studies and finally, iii to evaluate the translational relevance assessment of in vitro and ex-vivo results. In this review, we will critically describe the contribution of animal models to the use of biomedical imaging in cardiovascular medicine. We will discuss the characteristics of the most frequent models used in/for imaging studies. We will cover the major findings of animal studies focused in the cardiovascular use of the repeatedly used imaging techniques in clinical practice and experimental studies. We will also describe the physiological findings and/or learning processes for imaging applications coming from models of the most common cardiovascular diseases. In these diseases, imaging research using animals has allowed the study of aspects such as: ventricular size, shape, global function and wall thickening, local myocardial function, myocardial perfusion, metabolism and energetic assessment, infarct quantification, vascular lesion characterization, myocardial fiber structure, and myocardial calcium uptake. Finally we will discuss the limitations and future of imaging research with animal models.

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

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

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.

Animal models of GM2 gangliosidosis: utility and limitations

Directory of Open Access Journals (Sweden)

Lawson CA

2016-07-01

Full Text Available Cheryl A Lawson,1,2 Douglas R Martin2,3 1Department of Pathobiology, 2Scott-Ritchey Research Center, 3Department of Anatomy, Physiology and Pharmacology, Auburn University College of Veterinary Medicine, Auburn, AL, USA Abstract: GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, β-N-acetylhexosaminidase, and includes the closely related Tay–Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay–Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described. Keywords: GM2 gangliosidosis, Tay–Sachs disease, Sandhoff disease, lysosomal storage disorder, sphingolipidosis, brain disease

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...

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

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...

Experimental animal modelling for TB vaccine development

Directory of Open Access Journals (Sweden)

Pere-Joan Cardona

2017-03-01

Full Text Available Research for a novel vaccine to prevent tuberculosis is an urgent medical need. The current vaccine, BCG, has demonstrated a non-homogenous efficacy in humans, but still is the gold standard to be improved upon. In general, the main indicator for testing the potency of new candidates in animal models is the reduction of the bacillary load in the lungs at the acute phase of the infection. Usually, this reduction is similar to that induced by BCG, although in some cases a weak but significant improvement can be detected, but none of candidates are able to prevent establishment of infection. The main characteristics of several laboratory animals are reviewed, reflecting that none are able to simulate the whole characteristics of human tuberculosis. As, so far, no surrogate of protection has been found, it is important to test new candidates in several models in order to generate convincing evidence of efficacy that might be better than that of BCG in humans. It is also important to investigate the use of “in silico” and “ex vivo” models to better understand experimental data and also to try to replace, or at least reduce and refine experimental models in animals.

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.

Maynard Smith: amplifying the reasons for signal reliability.

Science.gov (United States)

Harper, D G C

2006-03-21

One of the many questions to which John Maynard Smith contributed was that of why most animal signals are reliable. He initially rejected the "handicap" argument but gradually accepted it, a process I briefly describe. This episode illustrated his preference for mathematical models over verbal ones, and the generosity with which he could change his mind. Even after accepting that some signals are reliable because of their strategic costs, he argued for a pluralistic approach to signal reliability. Signal complexity was a developing interest when he died. Signals usually involve several components, some of which appear to amplify other signal components. The terms "amplifier" and "index" require more thought to reduce the scope for semantic confusion. I conclude by describing Maynard Smith's fascination with peacocks Pavo cristatus.

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

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...

Realistic Modeling and Animation of Human Body Based on Scanned Data

Institute of Scientific and Technical Information of China (English)

Yong-You Ma; Hui Zhang; Shou-Wei Jiang

2004-01-01

In this paper we propose a novel method for building animation model of real human body from surface scanned data.The human model is represented by a triangular mesh and described as a layered geometric model.The model consists of two layers: the control skeleton generating body animation from motion capture data,and the simplified surface model providing an efficient representation of the skin surface shape.The skeleton is generated automatically from surface scanned data using the feature extraction,and thena point-to-line mapping is used to map the surface model onto the underlying skeleton.The resulting model enables real-time and smooth animation by manipulation of the skeleton while maintaining the surface detail.Compared with earlier approach,the principal advantages of our approach are the automated generation of body control skeletons from the scanned data for real-time animation,and the automatic mapping and animation of the captured human surface shape.The human model constructed in this work can be used for applications of ergonomic design,garment CAD,real-time simulating humans in virtual reality environment and so on.

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

Reflected stochastic differential equation models for constrained animal movement

Science.gov (United States)

Hanks, Ephraim M.; Johnson, Devin S.; Hooten, Mevin B.

2017-01-01

Movement for many animal species is constrained in space by barriers such as rivers, shorelines, or impassable cliffs. We develop an approach for modeling animal movement constrained in space by considering a class of constrained stochastic processes, reflected stochastic differential equations. Our approach generalizes existing methods for modeling unconstrained animal movement. We present methods for simulation and inference based on augmenting the constrained movement path with a latent unconstrained path and illustrate this augmentation with a simulation example and an analysis of telemetry data from a Steller sea lion (Eumatopias jubatus) in southeast Alaska.

Animal models of age related macular degeneration

Science.gov (United States)

Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

2013-01-01

Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444

Assessment of evidence for nanosized titanium dioxide-generated DNA strand breaks and oxidatively damaged DNA in cells and animal models

DEFF Research Database (Denmark)

Møller, Peter; Jensen, Ditte Marie; Wils, Regitze Sølling

2017-01-01

Nanosized titanium dioxide (TiO2) has been investigated in numerous studies on genotoxicity, including comet assay endpoints and oxidatively damaged DNA in cell cultures and animal models. The results have been surprisingly mixed, which might be attributed to physico-chemical differences...... culture studies also demonstrate increased levels of oxidatively damaged DNA after exposure to TiO2. There are relatively few studies on animal models where DNA strand breaks and oxidatively damaged DNA have been tested with reliable methods. Collectively, this review shows that exposure to nanosized TiO2...... of the tested TiO2. In the present review, we assess the role of certain methodological issues and publication bias. The analysis shows that studies on DNA strand breaks without proper assay controls or very low intra-group variation tend to show statistically significant effects. Levels of oxidatively damaged...

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.

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

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

Technical Note: How to use Winbugs to infer animal models

DEFF Research Database (Denmark)

Damgaard, Lars Holm

2007-01-01

This paper deals with Bayesian inferences of animal models using Gibbs sampling. First, we suggest a general and efficient method for updating additive genetic effects, in which the computational cost is independent of the pedigree depth and increases linearly only with the size of the pedigree....... Second, we show how this approach can be used to draw inferences from a wide range of animal models using the computer package Winbugs. Finally, we illustrate the approach in a simulation study, in which the data are generated and analyzed using Winbugs according to a linear model with i.i.d errors...... having Student's t distributions. In conclusion, Winbugs can be used to make inferences in small-sized, quantitative, genetic data sets applying a wide range of animal models that are not yet standard in the animal breeding literature...

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

Animal models and therapeutic molecular targets of cancer: utility and limitations

Directory of Open Access Journals (Sweden)

Cekanova M

2014-10-01

Full Text Available Maria Cekanova, Kusum Rathore Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN, USA Abstract: Cancer is the term used to describe over 100 diseases that share several common hallmarks. Despite prevention, early detection, and novel therapies, cancer is still the second leading cause of death in the USA. Successful bench-to-bedside translation of basic scientific findings about cancer into therapeutic interventions for patients depends on the selection of appropriate animal experimental models. Cancer research uses animal and human cancer cell lines in vitro to study biochemical pathways in these cancer cells. In this review, we summarize the important animal models of cancer with focus on their advantages and limitations. Mouse cancer models are well known, and are frequently used for cancer research. Rodent models have revolutionized our ability to study gene and protein functions in vivo and to better understand their molecular pathways and mechanisms. Xenograft and chemically or genetically induced mouse cancers are the most commonly used rodent cancer models. Companion animals with spontaneous neoplasms are still an underexploited tool for making rapid advances in human and veterinary cancer therapies by testing new drugs and delivery systems that have shown promise in vitro and in vivo in mouse models. Companion animals have a relatively high incidence of cancers, with biological behavior, response to therapy, and response to cytotoxic agents similar to those in humans. Shorter overall lifespan and more rapid disease progression are factors contributing to the advantages of a companion animal model. In addition, the current focus is on discovering molecular targets for new therapeutic drugs to improve survival and quality of life in cancer patients. Keywords: mouse cancer model, companion animal cancer model, dogs, cats, molecular targets

Animal models for human genetic diseases

African Journals Online (AJOL)

Sharif Sons

The study of human genetic diseases can be greatly aided by animal models because of their similarity .... and gene targeting in embryonic stem cells) has been a powerful tool in .... endonucleases that are designed to make a doublestrand.

Animal models of substance abuse and addiction: implications for science, animal welfare, and society.

Science.gov (United States)

Lynch, Wendy J; Nicholson, Katherine L; Dance, Mario E; Morgan, Richard W; Foley, Patricia L

2010-06-01

Substance abuse and addiction are well recognized public health concerns, with 2 NIH institutes (the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism) specifically targeting this societal problem. As such, this is an important area of research for which animal experiments play a critical role. This overview presents the importance of substance abuse and addiction in society; reviews the development and refinement of animal models that address crucial areas of biology, pathophysiology, clinical treatments, and drug screening for abuse liability; and discusses some of the unique veterinary, husbandry, and IACUC challenges associated with these models.

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

System Reliability Engineering

International Nuclear Information System (INIS)

Lim, Tae Jin

2005-02-01

This book tells of reliability engineering, which includes quality and reliability, reliability data, importance of reliability engineering, reliability and measure, the poisson process like goodness of fit test and the poisson arrival model, reliability estimation like exponential distribution, reliability of systems, availability, preventive maintenance such as replacement policies, minimal repair policy, shock models, spares, group maintenance and periodic inspection, analysis of common cause failure, and analysis model of repair effect.

Animal models for the study of Helicobacter pylori infection

Directory of Open Access Journals (Sweden)

Eliza Miszczyk

2014-05-01

Full Text Available The Gram-negative bacillus Helicobacter pylori is widely recognized as a major etiologic agent responsible for chronic active gastritis, peptic ulcers, the development of gastric cancer and mucosa-associated lymphoid tissue (MALT lymphoma. Still, little is known about the natural history of H. pylori infection, since patients usually after many years of not suffering from symptoms of the infection are simply asymptomatic. Since the research investigators carried out on human models has many limitations, there is an urgent need for the development of an animal model optimal and suitable for the monitoring of H. pylori infections. This review summarizes the recent findings on the suitability of animal models used in H. pylori research. Several animal models are useful for the assessment of pathological, microbiological and immunological consequences of infection, which makes it possible to monitor the natural

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.

Maintaining the clinical relevance of animal models in translational studies of post-traumatic stress disorder.

Science.gov (United States)

Cohen, Hagit; Matar, Michael A; Zohar, Joseph

2014-01-01

The diagnosis of Post-Traumatic Stress Disorder (PTSD) is conditional on directly experiencing or witnessing a significantly threatening event and the presence of a certain minimal number of symptoms from each of four symptom clusters (re-experiencing, avoidance, negative cognition and mood, and hyperarousal) at least one month after the event (DSM 5) (American Psychiatric Association 2013). Only a proportion of the population exposed develops symptoms fulfilling the criteria. The individual heterogeneity in responses of stress-exposed animals suggested that adapting clearly defined and reliably reproducible "diagnostic", i.e. behavioral, criteria for animal responses would augment the clinical validity of the analysis of study data. We designed cut-off (inclusion/exclusion) behavioral criteria (CBC) which classify study subjects as being severely, minimally or partially affected by the stress paradigm, to be applied retrospectively in the analysis of behavioral data. Behavioral response classification enables the researcher to correlate (retrospectively) specific anatomic, bio-molecular and physiological parameters with the degree and pattern of the individual behavioral response, and also introduces "prevalence rates" as a valid study-parameter. The cumulative results of our studies indicate that, by classifying the data from individual subjects according to their response patterns, the animal study can more readily be translated into clinical "follow-up" studies and back again. This article will discuss the concept of the model and its background, and present a selection of studies employing and examining the model, alongside the underlying translational rationale of each. © The Author 2014. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

Sleep and Obesity: A focus on animal models

Science.gov (United States)

Mavanji, Vijayakumar; Billington, Charles J.; Kotz, Catherine M.; Teske, Jennifer A.

2012-01-01

The rapid rise in obesity prevalence in the modern world parallels a significant reduction in restorative sleep (Agras et al., 2004; Dixon et al., 2007; Dixon et al., 2001; Gangwisch and Heymsfield, 2004; Gupta et al., 2002; Sekine et al., 2002; Vioque et al., 2000; Wolk et al., 2003). Reduced sleep time and quality increases the risk for obesity, but the underlying mechanisms remain unclear (Gangwisch et al., 2005; Hicks et al., 1986; Imaki et al., 2002; Jennings et al., 2007; Moreno et al., 2006). A majority of the theories linking human sleep disturbances and obesity rely on self-reported sleep. However, studies with objective measurements of sleep/wake parameters suggest a U-shaped relationship between sleep and obesity. Studies in animal models are needed to improve our understanding of the association between sleep disturbances and obesity. Genetic and experimenter-induced models mimicking characteristics of human obesity are now available and these animal models will be useful in understanding whether sleep disturbances determine propensity for obesity, or result from obesity. These models exhibit weight gain profiles consistently different from control animals. Thus a careful evaluation of animal models will provide insight into the relationship between sleep disturbances and obesity in humans. In this review we first briefly consider the fundamentals of sleep and key sleep disturbances, such as sleep fragmentation and excessive daytime sleepiness (EDS), observed in obese individuals. Then we consider sleep deprivation studies and the role of circadian alterations in obesity. We describe sleep/wake changes in various rodent models of obesity and obesity resistance. Finally, we discuss possible mechanisms linking sleep disturbances with obesity. PMID:22266350

Animal models for Ebola and Marburg virus infections

Science.gov (United States)

Nakayama, Eri; Saijo, Masayuki

2013-01-01

Ebola and Marburg hemorrhagic fevers (EHF and MHF) are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus), respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4) pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using non-human primates (NHPs) and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics. PMID:24046765

Animal models for Ebola and Marburg virus infections

Directory of Open Access Journals (Sweden)

Eri eNakayama

2013-09-01

Full Text Available Ebola and Marburg hemorrhagic fevers (EHF and MHF are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus, respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4 pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using nonhuman primates (NHPs and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics.

An Efficient, Simple, and Noninvasive Procedure for Genotyping Aquatic and Nonaquatic Laboratory Animals.

Science.gov (United States)

Okada, Morihiro; Miller, Thomas C; Roediger, Julia; Shi, Yun-Bo; Schech, Joseph Mat

2017-09-01

Various animal models are indispensible in biomedical research. Increasing awareness and regulations have prompted the adaptation of more humane approaches in the use of laboratory animals. With the development of easier and faster methodologies to generate genetically altered animals, convenient and humane methods to genotype these animals are important for research involving such animals. Here, we report skin swabbing as a simple and noninvasive method for extracting genomic DNA from mice and frogs for genotyping. We show that this method is highly reliable and suitable for both immature and adult animals. Our approach allows a simpler and more humane approach for genotyping vertebrate animals.

Precise MRI-based stereotaxic surgery in large animal models

DEFF Research Database (Denmark)

Glud, Andreas Nørgaard; Bech, Johannes; Tvilling, Laura

BACKGROUND: Stereotaxic neurosurgery in large animals is used widely in different sophisticated models, where precision is becoming more crucial as desired anatomical target regions are becoming smaller. Individually calculated coordinates are necessary in large animal models with cortical...... and subcortical anatomical differences. NEW METHOD: We present a convenient method to make an MRI-visible skull fiducial for 3D MRI-based stereotaxic procedures in larger experimental animals. Plastic screws were filled with either copper-sulphate solution or MRI-visible paste from a commercially available...... cranial head marker. The screw fiducials were inserted in the animal skulls and T1 weighted MRI was performed allowing identification of the inserted skull marker. RESULTS: Both types of fiducial markers were clearly visible on the MRÍs. This allows high precision in the stereotaxic space. COMPARISON...

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

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.

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.

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

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.

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 ...

[RESEARCH PROGRESS OF EXPERIMENTAL ANIMAL MODELS OF AVASCULAR NECROSIS OF FEMORAL HEAD].

Science.gov (United States)

Yu, Kaifu; Tan, Hongbo; Xu, Yongqing

2015-12-01

To summarize the current researches and progress on experimental animal models of avascular necrosis of the femoral head. Domestic and internation literature concerning experimental animal models of avascular necrosis of the femoral head was reviewed and analyzed. The methods to prepare the experimental animal models of avascular necrosis of the femoral head can be mainly concluded as traumatic methods (including surgical, physical, and chemical insult), and non-traumatic methods (including steroid, lipopolysaccharide, steroid combined with lipopolysaccharide, steroid combined with horse serum, etc). Each method has both merits and demerits, yet no ideal methods have been developed. There are many methods to prepare the experimental animal models of avascular necrosis of the femoral head, but proper model should be selected based on the aim of research. The establishment of ideal experimental animal models needs further research in future.

Animal Models of Schizophrenia with a Focus on Models Targeting NMDA Receptors

Czech Academy of Sciences Publication Activity Database

Svojanovská, Markéta; Stuchlík, Aleš

2015-01-01

Roč. 4, č. 1 (2015), s. 3-18 ISSN 1805-7225 R&D Projects: GA MZd(CZ) NT13386 Institutional support: RVO:67985823 Keywords : schizophrenia * animal models * pharmacological models * genetic models * neurodevelopmental models * preclinical studies Subject RIV: FH - Neurology

Determination of processed animal proteins, including meat and bone meal, in animal feed

NARCIS (Netherlands)

Gizzi, G.; Holst, von C.; Baeten, V.; Berben, G.; Raamsdonk, van L.W.D.

2004-01-01

The presence of processed animal proteins (PAP), including meat and bone meal (MBM) from various species, in animal feed was investigated. It was demonstrated that microscopy is the most reliable method for enforcing the current total MBM ban in the European Uion (EU). It was shown that near

Kinetic parametric estimation in animal PET molecular imaging based on artificial immune network

International Nuclear Information System (INIS)

Chen Yuting; Ding Hong; Lu Rui; Huang Hongbo; Liu Li

2011-01-01

Objective: To develop an accurate,reliable method without the need of initialization in animal PET modeling for estimation of the tracer kinetic parameters based on the artificial immune network. Methods: The hepatic and left ventricular time activity curves (TACs) were obtained by drawing ROIs of liver tissue and left ventricle on dynamic 18 F-FDG PET imaging of small mice. Meanwhile, the blood TAC was analyzed by sampling the tail vein blood at different time points after injection. The artificial immune network for parametric optimization of pharmacokinetics (PKAIN) was adapted to estimate the model parameters and the metabolic rate of glucose (K i ) was calculated. Results: TACs of liver,left ventricle and tail vein blood were obtained.Based on the artificial immune network, K i in 3 mice was estimated as 0.0024, 0.0417 and 0.0047, respectively. The average weighted residual sum of squares of the output model generated by PKAIN was less than 0.0745 with a maximum standard deviation of 0.0084, which indicated that the proposed PKAIN method can provide accurate and reliable parametric estimation. Conclusion: The PKAIN method could provide accurate and reliable tracer kinetic modeling in animal PET imaging without the need of initialization of model parameters. (authors)

Behavioral impairments in animal models for zinc deficiency

Directory of Open Access Journals (Sweden)

Simone eHagmeyer

2015-01-01

Full Text Available Apart from teratogenic and pathological effects of zinc deficiency such as the occurrence of skin lesions, anorexia, growth retardation, depressed wound healing, altered immune function, impaired night vision, and alterations in taste and smell acuity, characteristic behavioral changes in animal models and human patients suffering from zinc deficiency have been observed. Given that it is estimated that about 17% of the worldwide population are at risk for zinc deficiency and that zinc deficiency is associated with a variety of brain disorders and disease states in humans, it is of major interest to investigate, how these behavioral changes will affect the individual and a putative course of a disease. Thus, here, we provide a state of the art overview about the behavioral phenotypes observed in various models of zinc deficiency, among them environmentally produced zinc deficient animals as well as animal models based on a genetic alteration of a particular zinc homeostasis gene. Finally, we compare the behavioral phenotypes to the human condition of mild to severe zinc deficiency and provide a model, how zinc deficiency that is associated with many neurodegenerative and neuropsychological disorders might modify the disease pathologies.

Animal Models Utilized in HTLV-1 Research

Directory of Open Access Journals (Sweden)

Amanda R. Panfil

2013-01-01

Full Text Available Since the isolation and discovery of human T-cell leukemia virus type 1 (HTLV-1 over 30 years ago, researchers have utilized animal models to study HTLV-1 transmission, viral persistence, virus-elicited immune responses, and HTLV-1-associated disease development (ATL, HAM/TSP. Non-human primates, rabbits, rats, and mice have all been used to help understand HTLV-1 biology and disease progression. Non-human primates offer a model system that is phylogenetically similar to humans for examining viral persistence. Viral transmission, persistence, and immune responses have been widely studied using New Zealand White rabbits. The advent of molecular clones of HTLV-1 has offered the opportunity to assess the importance of various viral genes in rabbits, non-human primates, and mice. Additionally, over-expression of viral genes using transgenic mice has helped uncover the importance of Tax and Hbz in the induction of lymphoma and other lymphocyte-mediated diseases. HTLV-1 inoculation of certain strains of rats results in histopathological features and clinical symptoms similar to that of humans with HAM/TSP. Transplantation of certain types of ATL cell lines in immunocompromised mice results in lymphoma. Recently, “humanized” mice have been used to model ATL development for the first time. Not all HTLV-1 animal models develop disease and those that do vary in consistency depending on the type of monkey, strain of rat, or even type of ATL cell line used. However, the progress made using animal models cannot be understated as it has led to insights into the mechanisms regulating viral replication, viral persistence, disease development, and, most importantly, model systems to test disease treatments.

The research methods and model of protein turnover in animal

International Nuclear Information System (INIS)

Wu Xilin; Yang Feng

2002-01-01

The author discussed the concept and research methods of protein turnover in animal body. The existing problems and the research results of animal protein turnover in recent years were presented. Meanwhile, the measures to improve the models of animal protein turnover were analyzed

A valuable animal model of spinal cord injury to study motor dysfunctions, comorbid conditions, and aging associated diseases.

Science.gov (United States)

Rouleau, Pascal; Guertin, Pierre A

2013-01-01

Most animal models of contused, compressed or transected spinal cord injury (SCI) require a laminectomy to be performed. However, despite advantages and disadvantages associated with each of these models, the laminectomy itself is generally associated with significant problems including longer surgery and anaesthesia (related post-operative complications), neuropathic pain, spinal instabilities, deformities, lordosis, and biomechanical problems, etc. This review provides an overview of findings obtained mainly from our laboratory that are associated with the development and characterization of a novel murine model of spinal cord transection that does not require a laminectomy. A number of studies successfully conducted with this model provided strong evidence that it constitutes a simple, reliable and reproducible transection model of complete paraplegia which is particularly useful for studies on large cohorts of wild-type or mutant animals - e.g., drug screening studies in vivo or studies aimed at characterizing neuronal and non-neuronal adaptive changes post-trauma. It is highly suitable also for studies aimed at identifying and developing new pharmacological treatments against aging associated comorbid problems and specific SCI-related dysfunctions (e.g., stereotyped motor behaviours such as locomotion, sexual response, defecation and micturition) largely related with 'command centers' located in lumbosacral areas of the spinal cord.

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

Animal models used for testing hydrogels in cartilage regeneration.

Science.gov (United States)

Zhu, Chuntie; Wu, Qiong; Zhang, Xu; Chen, Fubo; Liu, Xiyang; Yang, Qixiang; Zhu, Lei

2018-05-14

Focal cartilage or osteochondral lesions can be painful and detrimental. Besides pain and limited function of joints, cartilage defect is considered as one of the leading extrinsic risk factors for osteoarthritis (OA). Thus, clinicians and scientists have paid great attention to regenerative therapeutic methods for the early treatment of cartilaginous defects. Regenerative medicine, showing great hope for regenerating cartilage tissue, rely on the combination of biodegradable scaffolds and specific biological cues, such as growth factors, adhesive factors and genetic materials. Among all biomaterials, hydrogels have emerged as promising cartilage tissue engineering scaffolds for simultaneous cell growth and drug delivery. A wide range of animal models have been applied in testing repair with hydrogels in cartilage defects. This review summarized the current animal models used to test hydrogels technologies for the regeneration of cartilage. Advantages and disadvantages in the establishment of the cartilage defect animal models among different species were emphasized, as well as feasibility of replication of diseases in animals. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The Nuremberg Code subverts human health and safety by requiring animal modeling

Directory of Open Access Journals (Sweden)

Greek Ray

2012-07-01

Full Text Available Abstract Background The requirement that animals be used in research and testing in order to protect humans was formalized in the Nuremberg Code and subsequent national and international laws, codes, and declarations. Discussion We review the history of these requirements and contrast what was known via science about animal models then with what is known now. We further analyze the predictive value of animal models when used as test subjects for human response to drugs and disease. We explore the use of animals for models in toxicity testing as an example of the problem with using animal models. Summary We conclude that the requirements for animal testing found in the Nuremberg Code were based on scientifically outdated principles, compromised by people with a vested interest in animal experimentation, serve no useful function, increase the cost of drug development, and prevent otherwise safe and efficacious drugs and therapies from being implemented.

Animal models of chronic wound care

DEFF Research Database (Denmark)

Trøstrup, Hannah; Thomsen, Kim; Calum, Henrik

2016-01-01

on nonhealing wounds. Relevant hypotheses based on clinical or in vitro observations can be tested in representative animal models, which provide crucial tools to uncover the pathophysiology of cutaneous skin repair in infectious environments. Disposing factors, species of the infectious agent(s), and time...

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.

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

Advancing research on animal-transported subsidies by integrating animal movement and ecosystem modelling.

Science.gov (United States)

Earl, Julia E; Zollner, Patrick A

2017-09-01

Connections between ecosystems via animals (active subsidies) support ecosystem services and contribute to numerous ecological effects. Thus, the ability to predict the spatial distribution of active subsidies would be useful for ecology and conservation. Previous work modelling active subsidies focused on implicit space or static distributions, which treat passive and active subsidies similarly. Active subsidies are fundamentally different from passive subsidies, because animals can respond to the process of subsidy deposition and ecosystem changes caused by subsidy deposition. We propose addressing this disparity by integrating animal movement and ecosystem ecology to advance active subsidy investigations, make more accurate predictions of subsidy spatial distributions, and enable a mechanistic understanding of subsidy spatial distributions. We review selected quantitative techniques that could be used to accomplish integration and lead to novel insights. The ultimate objective for these types of studies is predictions of subsidy spatial distributions from characteristics of the subsidy and the movement strategy employed by animals that transport subsidies. These advances will be critical in informing the management of ecosystem services, species conservation and ecosystem degradation related to active subsidies. © 2017 The Authors. Journal of Animal Ecology © 2017 British Ecological Society.

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

Individual differences and the characterization of animal models of psychopathology: a strong challenge and a good opportunity.

Science.gov (United States)

Armario, Antonio; Nadal, Roser

2013-01-01

Despite the development of valuable new techniques (i.e., genetics, neuroimage) for the study of the neurobiological substrate of psychiatric diseases, there are strong limitations in the information that can be gathered from human studies. It is thus critical to develop appropriate animal models of psychiatric diseases to characterize their putative biological bases and the development of new therapeutic strategies. The present review tries to offer a general perspective and several examples of how individual differences in animals can contribute to explain differential susceptibility to develop behavioral alterations, but also emphasizes methodological problems that can lead to inappropriate or over-simplistic interpretations. A critical analysis of the approaches currently used could contribute to obtain more reliable data and allow taking full advantage of new and sophisticated technologies. The discussion is mainly focused on anxiety-like and to a lower extent on depression-like behavior in rodents.

NAFLD, Estrogens, and Physical Exercise: The Animal Model

Directory of Open Access Journals (Sweden)

Jean-Marc Lavoie

2012-01-01

Full Text Available One segment of the population that is particularly inclined to liver fat accumulation is postmenopausal women. Although nonalcoholic hepatic steatosis is more common in men than in women, after menopause there is a reversal in gender distribution. At the present time, weight loss and exercise are regarded as first line treatments for NAFLD in postmenopausal women, as it is the case for the management of metabolic syndrome. In recent years, there has been substantial evidence coming mostly from the use of the animal model, that indeed estrogens withdrawal is associated with modifications of molecular markers favouring the activity of metabolic pathways ultimately leading to liver fat accumulation. In addition, the use of the animal model has provided physiological and molecular evidence that exercise training provides estrogens-like protective effects on liver fat accumulation and its consequences. The purpose of the present paper is to present information relative to the development of a state of NAFLD resulting from the absence of estrogens and the role of exercise training, emphasizing on the contribution of the animal model on these issues.

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.

Animal models to study plaque vulnerability

NARCIS (Netherlands)

Schapira, K.; Heeneman, S.; Daemen, M. J. A. P.

2007-01-01

The need to identify and characterize vulnerable atherosclerotic lesions in humans has lead to the development of various animal models of plaque vulnerability. In this review, current concepts of the vulnerable plaque as it leads to an acute coronary event are described, such as plaque rupture,

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

Animal Models for Tuberculosis in Translational and Precision Medicine

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Lingjun Zhan

2017-05-01

Full Text Available Tuberculosis (TB is a health threat to the global population. Anti-TB drugs and vaccines are key approaches for TB prevention and control. TB animal models are basic tools for developing biomarkers of diagnosis, drugs for therapy, vaccines for prevention and researching pathogenic mechanisms for identification of targets; thus, they serve as the cornerstone of comparative medicine, translational medicine, and precision medicine. In this review, we discuss the current use of TB animal models and their problems, as well as offering perspectives on the future of these models.

Animal model for hepatitis C virus infection.

Science.gov (United States)

Tsukiyama-Kohara, Kyoko; Kohara, Michinori

2015-01-01

Hepatitis C virus (HCV) infects more than 170 million people in the world and chronic HCV infection develops into cirrhosis and hepatocellular carcinoma (HCC). Recently, the effective compounds have been approved for HCV treatment, the protease inhibitor and polymerase inhibitor (direct acting antivirals; DAA). DAA-based therapy enabled to cure from HCV infection. However, development of new drug and vaccine is still required because of the generation of HCV escape mutants from DAA, development of HCC after treatment of DAA, and the high cost of DAA. In order to develop new anti-HCV drug and vaccine, animal infection model of HCV is essential. In this manuscript, we would like to introduce the history and the current status of the development of HCV animal infection model.

Deformation Models Tracking, Animation and Applications

CERN Document Server

Torres, Arnau; Gómez, Javier

2013-01-01

The computational modelling of deformations has been actively studied for the last thirty years. This is mainly due to its large range of applications that include computer animation, medical imaging, shape estimation, face deformation as well as other parts of the human body, and object tracking. In addition, these advances have been supported by the evolution of computer processing capabilities, enabling realism in a more sophisticated way. This book encompasses relevant works of expert researchers in the field of deformation models and their applications.  The book is divided into two main parts. The first part presents recent object deformation techniques from the point of view of computer graphics and computer animation. The second part of this book presents six works that study deformations from a computer vision point of view with a common characteristic: deformations are applied in real world applications. The primary audience for this work are researchers from different multidisciplinary fields, s...

Use of the Pyrithiamine-Induced Thiamine Deficient Animal Model of Korsakoff’s Syndrome for Exploratory Research Activities in Undergraduate Physiological Psychology

Science.gov (United States)

Flint, Robert W.; Hill, Jonathan E.; Sandusky, Leslie A.; Marino, Christina L.

2007-01-01

Undergraduate neuroscience laboratory activities frequently focus on exercises that build student’s wet/dry laboratory skills, foster critical thinking, and provide opportunities for hands-on experiences. Such activities are, without a doubt, extremely important, but sometimes fall short of modeling actual research and often lack the ‘unknown’ hypothetical nature accompanying empirical studies. In this article we report a series of research activities using an animal model of Korsakoff’s syndrome in a Physiological Psychology course. The activities involve testing hypotheses regarding performance of animals with experimentally-induced Korsakoff’s syndrome and the effectiveness of glucose as a memory-enhancer in this model. Students were given a set of 24 articles for use in answering a series of laboratory report questions regarding the activities. At the conclusion of the course, students were asked to complete a questionnaire designed to assess the effectiveness of the laboratory activities. Results of the laboratory exercises indicated that locomotor activity, environmental habituation, and anxiety were unaffected in the Korsakoff condition, and glucose had no effect. Results of performance in the T-maze indicated that Korsakoff animals had significantly fewer spontaneous alternations than controls, but Korsakoff animals given glucose did not reveal this difference. Results of the student assessments indicated that the activities were considered educational, challenging, and more interesting than standard laboratory activities designed to reproduce reliable phenomena. PMID:23494173

Perinatal Hypoxia and Ischemia in Animal Models of Schizophrenia

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Dimitri Hefter

2018-03-01

Full Text Available Intrauterine or perinatal complications constitute a major risk for psychiatric diseases. Infants who suffered from hypoxia–ischemia (HI are at twofold risk to develop schizophrenia in later life. Several animal models attempt to reproduce these complications to study the yet unknown steps between an insult in early life and outbreak of the disease decades later. However, it is very challenging to find the right type and severity of insult leading to a disease-like phenotype in the animal, but not causing necrosis and focal neurological deficits. By contrast, too mild, repetitive insults may even be protective via conditioning effects. Thus, it is not surprising that animal models of hypoxia lead to mixed results. To achieve clinically translatable findings, better protocols are urgently needed. Therefore, we compare widely used models of hypoxia and HI and propose future directions for the field.

Phenotyping animal models of diabetic neuropathy

DEFF Research Database (Denmark)

Biessels, G J; Bril, V; Calcutt, N A

2014-01-01

NIDDK, JDRF, and the Diabetic Neuropathy Study Group of EASD sponsored a meeting to explore the current status of animal models of diabetic peripheral neuropathy. The goal of the workshop was to develop a set of consensus criteria for the phenotyping of rodent models of diabetic neuropathy...... with a discussion on the merits and limitations of a unified approach to phenotyping rodent models of diabetic neuropathy and a consensus formed on the definition of the minimum criteria required for establishing the presence of the disease. A neuropathy phenotype in rodents was defined as the presence...

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.

Biology of Obesity: Lessons from Animal Models of Obesity

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Keizo Kanasaki

2011-01-01

problems, including diabetes, cardiovascular disease, respiratory failure, muscle weakness, and cancer. The precise molecular mechanisms by which obesity induces these health problems are not yet clear. To better understand the pathomechanisms of human disease, good animal models are essential. In this paper, we will analyze animal models of obesity and their use in the research of obesity-associated human health conditions and diseases such as diabetes, cancer, and obstructive sleep apnea syndrome.

Animal models for bone tissue engineering and modelling disease

Science.gov (United States)

Griffin, Michelle

2018-01-01

ABSTRACT Tissue engineering and its clinical application, regenerative medicine, are instructing multiple approaches to aid in replacing bone loss after defects caused by trauma or cancer. In such cases, bone formation can be guided by engineered biodegradable and nonbiodegradable scaffolds with clearly defined architectural and mechanical properties informed by evidence-based research. With the ever-increasing expansion of bone tissue engineering and the pioneering research conducted to date, preclinical models are becoming a necessity to allow the engineered products to be translated to the clinic. In addition to creating smart bone scaffolds to mitigate bone loss, the field of tissue engineering and regenerative medicine is exploring methods to treat primary and secondary bone malignancies by creating models that mimic the clinical disease manifestation. This Review gives an overview of the preclinical testing in animal models used to evaluate bone regeneration concepts. Immunosuppressed rodent models have shown to be successful in mimicking bone malignancy via the implantation of human-derived cancer cells, whereas large animal models, including pigs, sheep and goats, are being used to provide an insight into bone formation and the effectiveness of scaffolds in induced tibial or femoral defects, providing clinically relevant similarity to human cases. Despite the recent progress, the successful translation of bone regeneration concepts from the bench to the bedside is rooted in the efforts of different research groups to standardise and validate the preclinical models for bone tissue engineering approaches. PMID:29685995

Using Computational and Mechanical Models to Study Animal Locomotion

OpenAIRE

Miller, Laura A.; Goldman, Daniel I.; Hedrick, Tyson L.; Tytell, Eric D.; Wang, Z. Jane; Yen, Jeannette; Alben, Silas

2012-01-01

Recent advances in computational methods have made realistic large-scale simulations of animal locomotion possible. This has resulted in numerous mathematical and computational studies of animal movement through fluids and over substrates with the purpose of better understanding organisms’ performance and improving the design of vehicles moving through air and water and on land. This work has also motivated the development of improved numerical methods and modeling techniques for animal locom...

Simple models for studying complex spatiotemporal patterns of animal behavior

Science.gov (United States)

Tyutyunov, Yuri V.; Titova, Lyudmila I.

2017-06-01

Minimal mathematical models able to explain complex patterns of animal behavior are essential parts of simulation systems describing large-scale spatiotemporal dynamics of trophic communities, particularly those with wide-ranging species, such as occur in pelagic environments. We present results obtained with three different modelling approaches: (i) an individual-based model of animal spatial behavior; (ii) a continuous taxis-diffusion-reaction system of partial-difference equations; (iii) a 'hybrid' approach combining the individual-based algorithm of organism movements with explicit description of decay and diffusion of the movement stimuli. Though the models are based on extremely simple rules, they all allow description of spatial movements of animals in a predator-prey system within a closed habitat, reproducing some typical patterns of the pursuit-evasion behavior observed in natural populations. In all three models, at each spatial position the animal movements are determined by local conditions only, so the pattern of collective behavior emerges due to self-organization. The movement velocities of animals are proportional to the density gradients of specific cues emitted by individuals of the antagonistic species (pheromones, exometabolites or mechanical waves of the media, e.g., sound). These cues play a role of taxis stimuli: prey attract predators, while predators repel prey. Depending on the nature and the properties of the movement stimulus we propose using either a simplified individual-based model, a continuous taxis pursuit-evasion system, or a little more detailed 'hybrid' approach that combines simulation of the individual movements with the continuous model describing diffusion and decay of the stimuli in an explicit way. These can be used to improve movement models for many species, including large marine predators.

Fuzzy Goal Programming Approach in Selective Maintenance Reliability Model

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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

Instrumental and ethical aspects of experimental research with animal models

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Mirian Watanabe

2014-02-01

Full Text Available Experimental animal models offer possibilities of physiology knowledge, pathogenesis of disease and action of drugs that are directly related to quality nursing care. This integrative review describes the current state of the instrumental and ethical aspects of experimental research with animal models, including the main recommendations of ethics committees that focus on animal welfare and raises questions about the impact of their findings in nursing care. Data show that, in Brazil, the progress in ethics for the use of animals for scientific purposes was consolidated with Law No. 11.794/2008 establishing ethical procedures, attending health, genetic and experimental parameters. The application of ethics in handling of animals for scientific and educational purposes and obtaining consistent and quality data brings unquestionable contributions to the nurse, as they offer subsidies to relate pathophysiological mechanisms and the clinical aspect on the patient.

Animal models of gastrointestinal and liver diseases. Animal models of infant short bowel syndrome

DEFF Research Database (Denmark)

Sangild, Per Torp; Ney, Denise M; Sigalet, David L

2014-01-01

enterocolitis, atresia, gastroschisis, volvulus and aganglionosis. Patient outcomes have improved, but there is a need to develop new therapies for SBS and to understand intestinal adaptation after different diseases, resection types, nutritional interventions and growth factor therapies. Animal studies may......, newborn pigs and weanling rats represent a translational advantage for infant SBS due to their immature intestine. A balance among practical, economical, experimental and ethical constraints determines the choice of SBS model for each clinical or basic research question....

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

Establishment of a tumor neovascularization animal model with biomaterials in rabbit corneal pouch.

Science.gov (United States)

Chu, Yu-Ping; Li, Hong-Chuan; Ma, Ling; Xia, Yang

2018-06-01

The present animal model of tumor neovascularization most often used by researchers is zebrafish. For studies on human breast cancer cell neovascularization, a new animal model was established to enable a more convenient study of tumor neovascularization. A sodium alginate-gelatin blend gel system was used to design the new animal model. The model was established using rabbit corneal pouch implantation. Then, the animal model was validated by human breast cancer cell lines MCF-7-Kindlin-2 and MCF-7-CMV. The experiment intuitively observed the relationship between tumor and neovascularization, and demonstrated the advantages of this animal model in the study of tumor neovascularization. The use of sodium alginate-gelatin blends to establish tumor neovascularization in a rabbit corneal pouch is a novel and ideal method for the study of neovascularization. It may be a better animal model for expanding the research in this area. Copyright © 2018 Elsevier Inc. All rights reserved.

Animal models of osteogenesis imperfecta: applications in clinical research

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Enderli TA

2016-09-01

Full Text Available Tanya A Enderli, Stephanie R Burtch, Jara N Templet, Alessandra Carriero Department of Biomedical Engineering, Florida Institute of Technology, Melbourne, FL, USA Abstract: Osteogenesis imperfecta (OI, commonly known as brittle bone disease, is a genetic disease characterized by extreme bone fragility and consequent skeletal deformities. This connective tissue disorder is caused by mutations in the quality and quantity of the collagen that in turn affect the overall mechanical integrity of the bone, increasing its vulnerability to fracture. Animal models of the disease have played a critical role in the understanding of the pathology and causes of OI and in the investigation of a broad range of clinical therapies for the disease. Currently, at least 20 animal models have been officially recognized to represent the phenotype and biochemistry of the 17 different types of OI in humans. These include mice, dogs, and fish. Here, we describe each of the animal models and the type of OI they represent, and present their application in clinical research for treatments of OI, such as drug therapies (ie, bisphosphonates and sclerostin and mechanical (ie, vibrational loading. In the future, different dosages and lengths of treatment need to be further investigated on different animal models of OI using potentially promising treatments, such as cellular and chaperone therapies. A combination of therapies may also offer a viable treatment regime to improve bone quality and reduce fragility in animals before being introduced into clinical trials for OI patients. Keywords: OI, brittle bone, clinical research, mouse, dog, zebrafish

Animal Models of Diabetes Mellitus for Islet Transplantation

Directory of Open Access Journals (Sweden)

Naoaki Sakata

2012-01-01

Full Text Available Due to current improvements in techniques for islet isolation and transplantation and protocols for immunosuppressants, islet transplantation has become an effective treatment for severe diabetes patients. Many diabetic animal models have contributed to such improvements. In this paper, we focus on 3 types of models with different mechanisms for inducing diabetes mellitus (DM: models induced by drugs including streptozotocin (STZ, pancreatomized models, and spontaneous models due to autoimmunity. STZ-induced diabetes is one of the most commonly used experimental diabetic models and is employed using many specimens including rodents, pigs or monkeys. The management of STZ models is well established for islet studies. Pancreatomized models reveal different aspects compared to STZ-induced models in terms of loss of function in the increase and decrease of blood glucose and therefore are useful for evaluating the condition in total pancreatomized patients. Spontaneous models are useful for preclinical studies including the assessment of immunosuppressants because such models involve the same mechanisms as type 1 DM in the clinical setting. In conclusion, islet researchers should select suitable diabetic animal models according to the aim of the study.

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...

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)

Microscopic transport model animation visualisation on KML base

Science.gov (United States)

Yatskiv, I.; Savrasovs, M.

2012-10-01

By reading classical literature devoted to the simulation theory it could be found that one of the greatest possibilities of simulation is the ability to present processes inside the system by animation. This gives to the simulation model additional value during presentation of simulation results for the public and authorities who are not familiar enough with simulation. That is why most of universal and specialised simulation tools have the ability to construct 2D and 3D representation of the model. Usually the development of such representation could take much time and there must be put a lot forces into creating an adequate 3D representation of the model. For long years such well-known microscopic traffic flow simulation software tools as VISSIM, AIMSUN and PARAMICS have had a possibility to produce 2D and 3D animation. But creation of realistic 3D model of the place where traffic flows are simulated, even in these professional software tools it is a hard and time consuming action. The goal of this paper is to describe the concepts of use the existing on-line geographical information systems for visualisation of animation produced by simulation software. For demonstration purposes the following technologies and tools have been used: PTV VISION VISSIM, KML and Google Earth.

An Overview of Animal Models for Arthropod-Borne Viruses.

Science.gov (United States)

Reynolds, Erin S; Hart, Charles E; Hermance, Meghan E; Brining, Douglas L; Thangamani, Saravanan

2017-06-01

Arthropod-borne viruses (arboviruses) have continued to emerge in recent years, posing a significant health threat to millions of people worldwide. The majority of arboviruses that are pathogenic to humans are transmitted by mosquitoes and ticks, but other types of arthropod vectors can also be involved in the transmission of these viruses. To alleviate the health burdens associated with arbovirus infections, it is necessary to focus today's research on disease control and therapeutic strategies. Animal models for arboviruses are valuable experimental tools that can shed light on the pathophysiology of infection and will enable the evaluation of future treatments and vaccine candidates. Ideally an animal model will closely mimic the disease manifestations observed in humans. In this review, we outline the currently available animal models for several viruses vectored by mosquitoes, ticks, and midges, for which there are no standardly available vaccines or therapeutics.

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...

Tissue Engineering in Animal Models for Urinary Diversion: A Systematic Review

Science.gov (United States)

Sloff, Marije; de Vries, Rob; Geutjes, Paul; IntHout, Joanna; Ritskes-Hoitinga, Merel

2014-01-01

Tissue engineering and regenerative medicine (TERM) approaches may provide alternatives for gastrointestinal tissue in urinary diversion. To continue to clinically translatable studies, TERM alternatives need to be evaluated in (large) controlled and standardized animal studies. Here, we investigated all evidence for the efficacy of tissue engineered constructs in animal models for urinary diversion. Studies investigating this subject were identified through a systematic search of three different databases (PubMed, Embase and Web of Science). From each study, animal characteristics, study characteristics and experimental outcomes for meta-analyses were tabulated. Furthermore, the reporting of items vital for study replication was assessed. The retrieved studies (8 in total) showed extreme heterogeneity in study design, including animal models, biomaterials and type of urinary diversion. All studies were feasibility studies, indicating the novelty of this field. None of the studies included appropriate control groups, i.e. a comparison with the classical treatment using GI tissue. The meta-analysis showed a trend towards successful experimentation in larger animals although no specific animal species could be identified as the most suitable model. Larger animals appear to allow a better translation to the human situation, with respect to anatomy and surgical approaches. It was unclear whether the use of cells benefits the formation of a neo urinary conduit. The reporting of the methodology and data according to standardized guidelines was insufficient and should be improved to increase the value of such publications. In conclusion, animal models in the field of TERM for urinary diversion have probably been chosen for reasons other than their predictive value. Controlled and comparative long term animal studies, with adequate methodological reporting are needed to proceed to clinical translatable studies. This will aid in good quality research with the reduction in

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

Reducing the variation in animal models by standardizing the gut microbiota

DEFF Research Database (Denmark)

Ellekilde, Merete; Hufeldt, Majbritt Ravn; Hansen, Camilla Hartmann Friis

2011-01-01

, a large proportion of laboratory animals are used to study such diseases, but inter-individual variation in these animal models leads to the need for larger group sizes to reach statistical significance and adequate power. By standardizing the microbial and immunological status of laboratory animals we...... mice changed the glucose tolerance without affecting weight or mucosal immunity. Further investigations concerning the mechanisms of how GM influences disease development is necessary, but based on these results it seems reasonable to assume that by manipulating the GM we may produce animal models...... may therefore be able to produce animals with a more standardized response and less variation. This would lead to more precise results and a reduced number of animals needed for statistical significance. Denaturing gradient gel electrophoresis (DGGE) - a culture independent approach separating PCR...

Animal models to improve our understanding and treatment of suicidal behavior

Science.gov (United States)

Gould, T D; Georgiou, P; Brenner, L A; Brundin, L; Can, A; Courtet, P; Donaldson, Z R; Dwivedi, Y; Guillaume, S; Gottesman, I I; Kanekar, S; Lowry, C A; Renshaw, P F; Rujescu, D; Smith, E G; Turecki, G; Zanos, P; Zarate, C A; Zunszain, P A; Postolache, T T

2017-01-01

Worldwide, suicide is a leading cause of death. Although a sizable proportion of deaths by suicide may be preventable, it is well documented that despite major governmental and international investments in research, education and clinical practice suicide rates have not diminished and are even increasing among several at-risk populations. Although nonhuman animals do not engage in suicidal behavior amenable to translational studies, we argue that animal model systems are necessary to investigate candidate endophenotypes of suicidal behavior and the neurobiology underlying these endophenotypes. Animal models are similarly a critical resource to help delineate treatment targets and pharmacological means to improve our ability to manage the risk of suicide. In particular, certain pathophysiological pathways to suicidal behavior, including stress and hypothalamic–pituitary–adrenal axis dysfunction, neurotransmitter system abnormalities, endocrine and neuroimmune changes, aggression, impulsivity and decision-making deficits, as well as the role of critical interactions between genetic and epigenetic factors, development and environmental risk factors can be modeled in laboratory animals. We broadly describe human biological findings, as well as protective effects of medications such as lithium, clozapine, and ketamine associated with modifying risk of engaging in suicidal behavior that are readily translatable to animal models. Endophenotypes of suicidal behavior, studied in animal models, are further useful for moving observed associations with harmful environmental factors (for example, childhood adversity, mechanical trauma aeroallergens, pathogens, inflammation triggers) from association to causation, and developing preventative strategies. Further study in animals will contribute to a more informed, comprehensive, accelerated and ultimately impactful suicide research portfolio. PMID:28398339

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...

Animal models for cancer and uses thereof

NARCIS (Netherlands)

Demaria, Marco; Campisi, Judith; van Deursen, Jan M.; Kirkland, James; Tchkonia, Tamara T.; Baker, Darren J.

2017-01-01

Non-human animal cancer models are provided herein for identifying and characterizing agents useful for therapy and prophylaxis of cancers, including agents useful for diminishing side effects related to cancer therapies and reducing metastatic disease.

Surface Simplification of 3D Animation Models Using Robust Homogeneous Coordinate Transformation

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Juin-Ling Tseng

2014-01-01

Full Text Available The goal of 3D surface simplification is to reduce the storage cost of 3D models. A 3D animation model typically consists of several 3D models. Therefore, to ensure that animation models are realistic, numerous triangles are often required. However, animation models that have a high storage cost have a substantial computational cost. Hence, surface simplification methods are adopted to reduce the number of triangles and computational cost of 3D models. Quadric error metrics (QEM has recently been identified as one of the most effective methods for simplifying static models. To simplify animation models by using QEM, Mohr and Gleicher summed the QEM of all frames. However, homogeneous coordinate problems cannot be considered completely by using QEM. To resolve this problem, this paper proposes a robust homogeneous coordinate transformation that improves the animation simplification method proposed by Mohr and Gleicher. In this study, the root mean square errors of the proposed method were compared with those of the method proposed by Mohr and Gleicher, and the experimental results indicated that the proposed approach can preserve more contour features than Mohr’s method can at the same simplification ratio.

Animal models of Duchenne muscular dystrophy: from basic mechanisms to gene therapy

Science.gov (United States)

McGreevy, Joe W.; Hakim, Chady H.; McIntosh, Mark A.; Duan, Dongsheng

2015-01-01

Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disorder. It is caused by loss-of-function mutations in the dystrophin gene. Currently, there is no cure. A highly promising therapeutic strategy is to replace or repair the defective dystrophin gene by gene therapy. Numerous animal models of DMD have been developed over the last 30 years, ranging from invertebrate to large mammalian models. mdx mice are the most commonly employed models in DMD research and have been used to lay the groundwork for DMD gene therapy. After ~30 years of development, the field has reached the stage at which the results in mdx mice can be validated and scaled-up in symptomatic large animals. The canine DMD (cDMD) model will be excellent for these studies. In this article, we review the animal models for DMD, the pros and cons of each model system, and the history and progress of preclinical DMD gene therapy research in the animal models. We also discuss the current and emerging challenges in this field and ways to address these challenges using animal models, in particular cDMD dogs. PMID:25740330

Animal models of Duchenne muscular dystrophy: from basic mechanisms to gene therapy.

Science.gov (United States)

McGreevy, Joe W; Hakim, Chady H; McIntosh, Mark A; Duan, Dongsheng

2015-03-01

Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disorder. It is caused by loss-of-function mutations in the dystrophin gene. Currently, there is no cure. A highly promising therapeutic strategy is to replace or repair the defective dystrophin gene by gene therapy. Numerous animal models of DMD have been developed over the last 30 years, ranging from invertebrate to large mammalian models. mdx mice are the most commonly employed models in DMD research and have been used to lay the groundwork for DMD gene therapy. After ~30 years of development, the field has reached the stage at which the results in mdx mice can be validated and scaled-up in symptomatic large animals. The canine DMD (cDMD) model will be excellent for these studies. In this article, we review the animal models for DMD, the pros and cons of each model system, and the history and progress of preclinical DMD gene therapy research in the animal models. We also discuss the current and emerging challenges in this field and ways to address these challenges using animal models, in particular cDMD dogs. © 2015. Published by The Company of Biologists Ltd.

Animal models of tic disorders: a translational perspective.

Science.gov (United States)

Godar, Sean C; Mosher, Laura J; Di Giovanni, Giuseppe; Bortolato, Marco

2014-12-30

Tics are repetitive, sudden movements and/or vocalizations, typically enacted as maladaptive responses to intrusive premonitory urges. The most severe tic disorder, Tourette syndrome (TS), is a childhood-onset condition featuring multiple motor and at least one phonic tic for a duration longer than 1 year. The pharmacological treatment of TS is mainly based on antipsychotic agents; while these drugs are often effective in reducing tic severity and frequency, their therapeutic compliance is limited by serious motor and cognitive side effects. The identification of novel therapeutic targets and development of better treatments for tic disorders is conditional on the development of animal models with high translational validity. In addition, these experimental tools can prove extremely useful to test hypotheses on the etiology and neurobiological bases of TS and related conditions. In recent years, the translational value of these animal models has been enhanced, thanks to a significant re-organization of our conceptual framework of neuropsychiatric disorders, with a greater focus on endophenotypes and quantitative indices, rather than qualitative descriptors. Given the complex and multifactorial nature of TS and other tic disorders, the selection of animal models that can appropriately capture specific symptomatic aspects of these conditions can pose significant theoretical and methodological challenges. In this article, we will review the state of the art on the available animal models of tic disorders, based on genetic mutations, environmental interventions as well as pharmacological manipulations. Furthermore, we will outline emerging lines of translational research showing how some of these experimental preparations have led to significant progress in the identification of novel therapeutic targets for tic disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

Animal models of tic disorders: A translational perspective

Science.gov (United States)

Godar, Sean C.; Mosher, Laura J.; Di Giovanni, Giuseppe; Bortolato, Marco

2014-01-01

Tics are repetitive, sudden movements and/or vocalizations, typically enacted as maladaptive responses to intrusive premonitory urges. The most severe tic disorder, Tourette syndrome (TS), is a childhood-onset condition featuring multiple motor and at least one phonic tic for a duration longer than 1 year. The pharmacological treatment of TS is mainly based on antipsychotic agents; while these drugs are often effective in reducing tic severity and frequency, their therapeutic compliance is limited by serious motor and cognitive side effects. The identification of novel therapeutic targets and development of better treatments for tic disorders is conditional on the development of animal models with high translational validity. In addition, these experimental tools can prove extremely useful to test hypotheses on the etiology and neurobiological bases of TS and related conditions. In recent years, the translational value of these animal models has been enhanced, thanks to a significant re-organization of our conceptual framework of neuropsychiatric disorders, with a greater focus on endophenotypes and quantitative indices, rather than qualitative descriptors. Given the complex and multifactorial nature of TS and other tic disorders, the selection of animal models that can appropriately capture specific symptomatic aspects of these conditions can pose significant theoretical and methodological challenges. In this article, we will review the state of the art on the available animal models of tic disorders, based on genetic mutations, environmental interventions as well as pharmacological manipulations. Furthermore, we will outline emerging lines of translational research showing how some of these experimental preparations have led to significant progress in the identification of novel therapeutic targets for tic disorders. PMID:25244952

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...

Models of Information Security Highly Reliable Computing Systems

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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.

Experimental Oral Candidiasis in Animal Models

Science.gov (United States)

Samaranayake, Yuthika H.; Samaranayake, Lakshman P.

2001-01-01

Oral candidiasis is as much the final outcome of the vulnerability of the host as of the virulence of the invading organism. We review here the extensive literature on animal experiments mainly appertaining to the host predisposing factors that initiate and perpetuate these infections. The monkey, rat, and mouse are the choice models for investigating oral candidiasis, but comparisons between the same or different models appear difficult, because of variables such as the study design, the number of animals used, their diet, the differences in Candida strains, and the duration of the studies. These variables notwithstanding, the following could be concluded. (i) The primate model is ideal for investigating Candida-associated denture stomatitis since both erythematous and pseudomembranous lesions have been produced in monkeys with prosthetic plates; they are, however, expensive and difficult to obtain and maintain. (ii) The rat model (both Sprague-Dawley and Wistar) is well proven for observing chronic oral candidal colonization and infection, due to the ease of breeding and handling and their ready availability. (iii) Mice are similar, but in addition there are well characterized variants simulating immunologic and genetic abnormalities (e.g., athymic, euthymic, murine-acquired immune deficiency syndrome, and severe combined immunodeficient models) and hence are used for short-term studies relating the host immune response and oral candidiasis. Nonetheless, an ideal, relatively inexpensive model representative of the human oral environment in ecological and microbiological terms is yet to be described. Until such a model is developed, researchers should pay attention to standardization of the experimental protocols described here to obtain broadly comparable and meaningful data. PMID:11292645

Current Status of Animal Models of Posttraumatic Stress Disorder: Behavioral and Biological Phenotypes, and Future Challenges in Improving Translation.

Science.gov (United States)

Deslauriers, Jessica; Toth, Mate; Der-Avakian, Andre; Risbrough, Victoria B

2018-05-15

Increasing predictability of animal models of posttraumatic stress disorder (PTSD) has required active collaboration between clinical and preclinical scientists. Modeling PTSD is challenging, as it is a heterogeneous disorder with ≥20 symptoms. Clinical research increasingly utilizes objective biological measures (e.g., imaging, peripheral biomarkers) or nonverbal behaviors and/or physiological responses to complement verbally reported symptoms. This shift toward more-objectively measurable phenotypes enables refinement of current animal models of PTSD, and it supports the incorporation of homologous measures across species. We reviewed >600 articles to examine the ability of current rodent models to probe biological phenotypes of PTSD (e.g., sleep disturbances, hippocampal and fear-circuit dysfunction, inflammation, glucocorticoid receptor hypersensitivity) in addition to behavioral phenotypes. Most models reliably produced enduring generalized anxiety-like or depression-like behaviors, as well as hyperactive fear circuits, glucocorticoid receptor hypersensitivity, and response to long-term selective serotonin reuptake inhibitors. Although a few paradigms probed fear conditioning/extinction or utilized peripheral immune, sleep, and noninvasive imaging measures, we argue that these should be incorporated more to enhance translation. Data on female subjects, on subjects at different ages across the life span, or on temporal trajectories of phenotypes after stress that can inform model validity and treatment study design are needed. Overall, preclinical (and clinical) PTSD researchers are increasingly incorporating homologous biological measures to assess markers of risk, response, and treatment outcome. This shift is exciting, as we and many others hope it not only will support translation of drug efficacy from animal models to clinical trials but also will potentially improve predictability of stage II for stage III clinical trials. Published by Elsevier Inc.

The contribution of animal models to the study of obesity.

Science.gov (United States)

Speakman, John; Hambly, Catherine; Mitchell, Sharon; Król, Elzbieta

2008-10-01

Obesity results from prolonged imbalance of energy intake and energy expenditure. Animal models have provided a fundamental contribution to the historical development of understanding the basic parameters that regulate the components of our energy balance. Five different types of animal model have been employed in the study of the physiological and genetic basis of obesity. The first models reflect single gene mutations that have arisen spontaneously in rodent colonies and have subsequently been characterized. The second approach is to speed up the random mutation rate artificially by treating rodents with mutagens or exposing them to radiation. The third type of models are mice and rats where a specific gene has been disrupted or over-expressed as a deliberate act. Such genetically-engineered disruptions may be generated through the entire body for the entire life (global transgenic manipulations) or restricted in both time and to certain tissue or cell types. In all these genetically-engineered scenarios, there are two types of situation that lead to insights: where a specific gene hypothesized to play a role in the regulation of energy balance is targeted, and where a gene is disrupted for a different purpose, but the consequence is an unexpected obese or lean phenotype. A fourth group of animal models concern experiments where selective breeding has been utilized to derive strains of rodents that differ in their degree of fatness. Finally, studies have been made of other species including non-human primates and dogs. In addition to studies of the physiological and genetic basis of obesity, studies of animal models have also informed us about the environmental aspects of the condition. Studies in this context include exploring the responses of animals to high fat or high fat/high sugar (Cafeteria) diets, investigations of the effects of dietary restriction on body mass and fat loss, and studies of the impact of candidate pharmaceuticals on components of energy

Reliability Measure Model for Assistive Care Loop Framework Using Wireless Sensor Networks

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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.

The calm mouse: an animal model of stress reduction.

Science.gov (United States)

Gurfein, Blake T; Stamm, Andrew W; Bacchetti, Peter; Dallman, Mary F; Nadkarni, Nachiket A; Milush, Jeffrey M; Touma, Chadi; Palme, Rupert; Di Borgo, Charles Pozzo; Fromentin, Gilles; Lown-Hecht, Rachel; Konsman, Jan Pieter; Acree, Michael; Premenko-Lanier, Mary; Darcel, Nicolas; Hecht, Frederick M; Nixon, Douglas F

2012-05-09

Chronic stress is associated with negative health outcomes and is linked with neuroendocrine changes, deleterious effects on innate and adaptive immunity, and central nervous system neuropathology. Although stress management is commonly advocated clinically, there is insufficient mechanistic understanding of how decreasing stress affects disease pathogenesis. Therefore, we have developed a "calm mouse model" with caging enhancements designed to reduce murine stress. Male BALB/c mice were divided into four groups: control (Cntl), standard caging; calm (Calm), large caging to reduce animal density, a cardboard nest box for shelter, paper nesting material to promote innate nesting behavior, and a polycarbonate tube to mimic tunneling; control exercise (Cntl Ex), standard caging with a running wheel, known to reduce stress; and calm exercise (Calm Ex), calm caging with a running wheel. Calm, Cntl Ex and Calm Ex animals exhibited significantly less corticosterone production than Cntl animals. We also observed changes in spleen mass, and in vitro splenocyte studies demonstrated that Calm Ex animals had innate and adaptive immune responses that were more sensitive to acute handling stress than those in Cntl. Calm animals gained greater body mass than Cntl, although they had similar food intake, and we also observed changes in body composition, using magnetic resonance imaging. Together, our results suggest that the Calm mouse model represents a promising approach to studying the biological effects of stress reduction in the context of health and in conjunction with existing disease models.

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

Steroid-associated osteonecrosis animal model in rats

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Li-Zhen Zheng

2018-04-01

Full Text Available Summary: Objective: Established preclinical disease models are essential for not only studying aetiology and/or pathophysiology of the relevant diseases but more importantly also for testing prevention and/or treatment concept(s. The present study proposed and established a detailed induction and assessment protocol for a unique and cost-effective preclinical steroid-associated osteonecrosis (SAON in rats with pulsed injections of lipopolysaccharide (LPS and methylprednisolone (MPS. Methods: Sixteen 24-week-old male Sprague–Dawley rats were used to induce SAON by one intravenous injection of LPS (0.2 mg/kg and three intraperitoneal injections of MPS (100 mg/kg with a time interval of 24 hour, and then, MPS (40 mg/kg was intraperitoneally injected three times a week from week 2 until sacrifice. Additional 12 rats were used as normal controls. Two and six weeks after induction, animals were scanned by metabolic dual energy X-ray absorptiometry for evaluation of tissue composition; serum was collected for bone turnover markers, Microfil perfusion was performed for angiography, the liver was collected for histopathology and bilateral femora and bilateral tibiae were collected for histological examination. Results: Three rats died after LPS injection, i.e., with 15.8% (3/19 mortality. Histological evaluation showed 100% incidence of SAON at week 2. Dual energy X-ray absorptiometry showed significantly higher fat percent and lower lean mass in SAON group at week 6. Micro-computed tomography (Micro-CT showed significant bone degradation at proximal tibia 6 weeks after SAON induction. Angiography illustrated significantly less blood vessels in the proximal tibia and significantly more leakage particles in the distal tibia 2 weeks after SAON induction. Serum amino-terminal propeptide of type I collagen and osteocalcin were significantly lower at both 2 and 6 weeks after SAON induction, and serum carboxy-terminal telopeptide was significantly

Collective animal behavior from Bayesian estimation and probability matching.

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Alfonso Pérez-Escudero

2011-11-01

Full Text Available Animals living in groups make movement decisions that depend, among other factors, on social interactions with other group members. Our present understanding of social rules in animal collectives is mainly based on empirical fits to observations, with less emphasis in obtaining first-principles approaches that allow their derivation. Here we show that patterns of collective decisions can be derived from the basic ability of animals to make probabilistic estimations in the presence of uncertainty. We build a decision-making model with two stages: Bayesian estimation and probabilistic matching. In the first stage, each animal makes a Bayesian estimation of which behavior is best to perform taking into account personal information about the environment and social information collected by observing the behaviors of other animals. In the probability matching stage, each animal chooses a behavior with a probability equal to the Bayesian-estimated probability that this behavior is the most appropriate one. This model derives very simple rules of interaction in animal collectives that depend only on two types of reliability parameters, one that each animal assigns to the other animals and another given by the quality of the non-social information. We test our model by obtaining theoretically a rich set of observed collective patterns of decisions in three-spined sticklebacks, Gasterosteus aculeatus, a shoaling fish species. The quantitative link shown between probabilistic estimation and collective rules of behavior allows a better contact with other fields such as foraging, mate selection, neurobiology and psychology, and gives predictions for experiments directly testing the relationship between estimation and collective behavior.

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.

Models of breast cancer: quo vadis, animal modeling?

International Nuclear Information System (INIS)

Wagner, Kay-Uwe

2004-01-01

Rodent models for breast cancer have for many decades provided unparalleled insights into cellular and molecular aspects of neoplastic transformation and tumorigenesis. Despite recent improvements in the fidelity of genetically engineered mice, rodent models are still being criticized by many colleagues for not being 'authentic' enough to the human disease. Motives for this criticism are manifold and range from a very general antipathy against the rodent model system to well-founded arguments that highlight physiological variations between species. Newly proposed differences in genetic pathways that cause cancer in humans and mice invigorated the ongoing discussion about the legitimacy of the murine system to model the human disease. The present commentary intends to stimulate a debate on this subject by providing the background about new developments in animal modeling, by disputing suggested limitations of genetically engineered mice, and by discussing improvements but also ambiguous expectations on the authenticity of xenograft models to faithfully mimic the human disease

A novel animal model of dysphagia following stroke.

Science.gov (United States)

Sugiyama, Naoto; Nishiyama, Eiji; Nishikawa, Yukitoshi; Sasamura, Takashi; Nakade, Shinji; Okawa, Katsumasa; Nagasawa, Tadashi; Yuki, Akane

2014-02-01

Patients who have an ischemic stroke are at high risk of swallowing disorders. Aspiration due to swallowing disorders, specifically delayed trigger of the pharyngeal stage of swallowing, predisposes such patients to pneumonia. In the present study, we evaluated swallowing reflex in a rat model of transient middle cerebral artery occlusion (tMCAO), which is one of the most common experimental animal models of cerebral ischemia, in order to develop a novel animal model of dysphagia following ischemic stroke. A swallowing reflex was elicited by a 10-s infusion of distilled water (DW) to the pharyngolaryngeal region in the tMCAO rat model. Swallowing reflex was estimated using the electromyographic activity of the mylohyoid muscle from 1 to 3 weeks after surgery. Two weeks after tMCAO, the number of swallows significantly decreased and the onset latency of the first swallow was prolonged compared with that of the sham group. The number of swallows in rats significantly increased by infusions of 10 mM citric acid and 0.6 μM capsaicin to the pharyngolaryngeal region compared with the number from infusion of DW. It has been reported that sensory stimulation of the pharyngolaryngeal region with citric acid, capsaicin, and L-menthol ameliorates hypofunction of pharyngeal-stage swallowing in dysphagia patients. Therefore, the tMCAO rat model may show some of the symptoms of pharyngeal-stage swallowing disorders, similar to those in patients with ischemic stroke. This rat tMCAO model has the potential to become a novel animal model of dysphagia following stroke that is useful for development of therapeutic methods and drugs.

ANIMAL MODELS OF POST-TRAUMATIC STRESS DISORDER: FACE VALIDITY

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SONAL eGOSWAMI

2013-05-01

Full Text Available Post-traumatic stress disorder (PTSD is a debilitating condition that develops in a proportion of individuals following a traumatic event. Despite recent advances, ethical limitations associated with human research impede progress in understanding PTSD. Fortunately, much effort has focused on developing animal models to help study the pathophysiology of PTSD. Here, we provide an overview of animal PTSD models where a variety of stressors (physical, psychosocial, or psychogenic are used to examine the long-term effects of severe trauma. We emphasize models involving predator threat because they reproduce human individual differences in susceptibility to, and in the long-term consequences of, psychological trauma.

The Animal Model of Spinal Cord Injury as an Experimental Pain Model

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Aya Nakae

2011-01-01

Full Text Available Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of pathology. However, results can be easily misunderstood and falsely interpreted. Therefore, it is important to fully understand the symptoms of human spinal cord injury, as well as the various spinal cord injury models and the possible pathologies. The present paper summarizes results from animal models of spinal cord injury, as well as the most effective use of these models.

The Animal Model of Spinal Cord Injury as an Experimental Pain Model

Science.gov (United States)

Nakae, Aya; Nakai, Kunihiro; Yano, Kenji; Hosokawa, Ko; Shibata, Masahiko; Mashimo, Takashi

2011-01-01

Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of pathology. However, results can be easily misunderstood and falsely interpreted. Therefore, it is important to fully understand the symptoms of human spinal cord injury, as well as the various spinal cord injury models and the possible pathologies. The present paper summarizes results from animal models of spinal cord injury, as well as the most effective use of these models. PMID:21436995

Dynamic Variables Fail to Predict Fluid Responsiveness in an Animal Model With Pericardial Effusion.

Science.gov (United States)

Broch, Ole; Renner, Jochen; Meybohm, Patrick; Albrecht, Martin; Höcker, Jan; Haneya, Assad; Steinfath, Markus; Bein, Berthold; Gruenewald, Matthias

2016-10-01

The reliability of dynamic and volumetric variables of fluid responsiveness in the presence of pericardial effusion is still elusive. The aim of the present study was to investigate their predictive power in a porcine model with hemodynamic relevant pericardial effusion. A single-center animal investigation. Twelve German domestic pigs. Pigs were studied before and during pericardial effusion. Instrumentation included a pulmonary artery catheter and a transpulmonary thermodilution catheter in the femoral artery. Hemodynamic variables like cardiac output (COPAC) and stroke volume (SVPAC) derived from pulmonary artery catheter, global end-diastolic volume (GEDV), stroke volume variation (SVV), and pulse-pressure variation (PPV) were obtained. At baseline, SVV, PPV, GEDV, COPAC, and SVPAC reliably predicted fluid responsiveness (area under the curve 0.81 [p = 0.02], 0.82 [p = 0.02], 0.74 [p = 0.07], 0.74 [p = 0.07], 0.82 [p = 0.02]). After establishment of pericardial effusion the predictive power of dynamic variables was impaired and only COPAC and SVPAC and GEDV allowed significant prediction of fluid responsiveness (area under the curve 0.77 [p = 0.04], 0.76 [p = 0.05], 0.83 [p = 0.01]) with clinically relevant changes in threshold values. In this porcine model, hemodynamic relevant pericardial effusion abolished the ability of dynamic variables to predict fluid responsiveness. COPAC, SVPAC, and GEDV enabled prediction, but their threshold values were significantly changed. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Animal models in fetal medicine and obstetrics

DEFF Research Database (Denmark)

Dahl Andersen, Maria; Alstrup, Aage Kristian Olsen; Duvald, Christina Søndergaard

2018-01-01

Animal models remain essential to understand the fundamental mechanisms occurring in fetal medicine and obstetric diseases, such as intrauterine growth restriction, preeclampsia and gestational diabetes. These vary regarding the employed method used for induction of the disease, and vary regardin...

Age-dependent reliability model considering effects of maintenance and working conditions

International Nuclear Information System (INIS)

Martorell, Sebastian; Sanchez, Ana; Serradell, Vicente

1999-01-01

Nowadays, there is some doubt about building new nuclear power plants (NPPs). Instead, there is a growing interest in analyzing the possibility to extend current NPP operation, where life management programs play an important role. The evolution of the NPP safety depends on the evolution of the reliability of its safety components, which, in turn, is a function of their age along the NPP operational life. In this paper, a new age-dependent reliability model is presented, which includes parameters related to surveillance and maintenance effectiveness and working conditions of the equipment, both environmental and operational. This model may be used to support NPP life management and life extension programs, by improving or optimizing surveillance and maintenance tasks using risk and cost models based on such an age-dependent reliability model. The results of the sensitivity study in the example application show that the selection of the most appropriate maintenance strategy would directly depend on the previous parameters. Then, very important differences are expected to appear under certain circumstances, particularly, in comparison with other models that do not consider maintenance effectiveness and working conditions simultaneously

Animal models got you puzzled?: think pig.

Science.gov (United States)

Walters, Eric M; Agca, Yuksel; Ganjam, Venkataseshu; Evans, Tim

2011-12-01

Swine are an excellent large animal model for human health and disease because their size and physiology are similar to humans, in particular, with respect to the skin, heart, gastrointestinal tract, and kidneys. In addition, the pig has many emerging technologies that will only enhance the development of the pig as the nonrodent biomedical model of choice. © 2011 New York Academy of Sciences.

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)

Effects of Caffeine and Warrior Stress on Behavioral : An Animal Model

Science.gov (United States)

2016-03-14

typically in the form of food (e.g., chocolate ) and drinks (e.g., coffee, tea, energy drinks, and soft drinks), improves attention and performance...administration in an animal model of neuroleptic therapy . Journal of neuroscience methods 146:159-64 81. Schmidt MV, Muller MB. 2006. Animal models of anxiety

The safety, efficacy and regulatory triangle in drug development: Impact for animal models and the use of animals.

Science.gov (United States)

van Meer, Peter J K; Graham, Melanie L; Schuurman, Henk-Jan

2015-07-15

Nonclinical studies in animals are conducted to demonstrate proof-of-concept, mechanism of action and safety of new drugs. For a large part, in particular safety assessment, studies are done in compliance with international regulatory guidance. However, animal models supporting the initiation of clinical trials have their limitations, related to uncertainty regarding the predictive value for a clinical condition. The 3Rs principles (refinement, reduction and replacement) are better applied nowadays, with a more comprehensive application with respect to the original definition. This regards also regulatory guidance, so that opportunities exist to revise or reduce regulatory guidance with the perspective that the optimal balance between scientifically relevant data and animal wellbeing or a reduction in animal use can be achieved. In this manuscript we review the connections in the triangle between nonclinical efficacy/safety studies and regulatory aspects, with focus on in vivo testing of drugs. These connections differ for different drugs (chemistry-based low molecular weight compounds, recombinant proteins, cell therapy or gene therapy products). Regarding animal models and their translational value we focus on regulatory aspects and indications where scientific outcomes warrant changes, reduction or replacement, like for, e.g., biosimilar evaluation and safety testing of monoclonal antibodies. On the other hand, we present applications where translational value has been clearly demonstrated, e.g., immunosuppressives in transplantation. Especially for drugs of more recent date like recombinant proteins, cell therapy products and gene therapy products, a regulatory approach that allows the possibility to conduct combined efficacy/safety testing in validated animal models should strengthen scientific outcomes and improve translational value, while reducing the numbers of animals necessary. Copyright © 2015 Elsevier B.V. All rights reserved.

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…

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

Cardiovascular Changes in Animal Models of Metabolic Syndrome

Directory of Open Access Journals (Sweden)

Alexandre M. Lehnen

2013-01-01

Full Text Available Metabolic syndrome has been defined as a group of risk factors that directly contribute to the development of cardiovascular disease and/or type 2 diabetes. Insulin resistance seems to have a fundamental role in the genesis of this syndrome. Over the past years to the present day, basic and translational research has used small animal models to explore the pathophysiology of metabolic syndrome and to develop novel therapies that might slow the progression of this prevalent condition. In this paper we discuss the animal models used for the study of metabolic syndrome, with particular focus on cardiovascular changes, since they are the main cause of death associated with the condition in humans.

Modelling animal waste pathogen transport from agricultural land to streams

International Nuclear Information System (INIS)

Pandey, Pramod K; Soupir, Michelle L; Ikenberry, Charles

2014-01-01

The transport of animal waste pathogens from crop land to streams can potentially elevate pathogen levels in stream water. Applying animal manure into crop land as fertilizers is a common practice in developing as well as in developed countries. Manure application into the crop land, however, can cause potential human health. To control pathogen levels in ambient water bodies such as streams, improving our understanding of pathogen transport at farm scale as well as at watershed scale is required. To understand the impacts of crop land receiving animal waste as fertilizers on stream's pathogen levels, here we investigate pathogen indicator transport at watershed scale. We exploited watershed scale hydrological model to estimate the transport of pathogens from the crop land to streams. Pathogen indicator levels (i.e., E. coli levels) in the stream water were predicted. With certain assumptions, model results are reasonable. This study can be used as guidelines for developing the models for calculating the impacts of crop land's animal manure on stream water

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.

Validating Animal Models

Directory of Open Access Journals (Sweden)

Nina Atanasova

2015-06-01

Full Text Available In this paper, I respond to the challenge raised against contemporary experimental neurobiology according to which the field is in a state of crisis because of the multiple experimental protocols employed in different laboratories and strengthening their reliability that presumably preclude the validity of neurobiological knowledge. I provide an alternative account of experimentation in neurobiology which makes sense of its experimental practices. I argue that maintaining a multiplicity of experimental protocols and strengthening their reliability are well justified and they foster rather than preclude the validity of neurobiological knowledge. Thus, their presence indicates thriving rather than crisis of experimental neurobiology.

Animal model of neuropathic tachycardia syndrome

Science.gov (United States)

Carson, R. P.; Appalsamy, M.; Diedrich, A.; Davis, T. L.; Robertson, D.

2001-01-01

Clinically relevant autonomic dysfunction can result from either complete or partial loss of sympathetic outflow to effector organs. Reported animal models of autonomic neuropathy have aimed to achieve complete lesions of sympathetic nerves, but incomplete lesions might be more relevant to certain clinical entities. We hypothesized that loss of sympathetic innervation would result in a predicted decrease in arterial pressure and a compensatory increase in heart rate. Increased heart rate due to loss of sympathetic innervation is seemingly paradoxical, but it provides a mechanistic explanation for clinical autonomic syndromes such as neuropathic postural tachycardia syndrome. Partially dysautonomic animals were generated by selectively lesioning postganglionic sympathetic neurons with 150 mg/kg 6-hydroxydopamine hydrobromide in male Sprague-Dawley rats. Blood pressure and heart rate were monitored using radiotelemetry. Systolic blood pressure decreased within hours postlesion (Delta>20 mm Hg). Within 4 days postlesion, heart rate rose and remained elevated above control levels. The severity of the lesion was determined functionally and pharmacologically by spectral analysis and responsiveness to tyramine. Low-frequency spectral power of systolic blood pressure was reduced postlesion and correlated with the diminished tyramine responsiveness (r=0.9572, P=0.0053). The tachycardia was abolished by treatment with the beta-antagonist propranolol, demonstrating that it was mediated by catecholamines acting on cardiac beta-receptors. Partial lesions of the autonomic nervous system have been hypothesized to underlie many disorders, including neuropathic postural tachycardia syndrome. This animal model may help us better understand the pathophysiology of autonomic dysfunction and lead to development of therapeutic interventions.

Practical applications of age-dependent reliability models and analysis of operational data

Energy Technology Data Exchange (ETDEWEB)

Lannoy, A.; Nitoi, M.; Backstrom, O.; Burgazzi, L.; Couallier, V.; Nikulin, M.; Derode, A.; Rodionov, A.; Atwood, C.; Fradet, F.; Antonov, A.; Berezhnoy, A.; Choi, S.Y.; Starr, F.; Dawson, J.; Palmen, H.; Clerjaud, L

2005-07-01

The purpose of the workshop was to present the experience of practical application of time-dependent reliability models. The program of the workshop comprises the following sessions: -) aging management and aging PSA (Probabilistic Safety Assessment), -) modeling, -) operation experience, and -) accelerating aging tests. In order to introduce time aging effect of particular component to the PSA model, it has been proposed to use the constant unavailability values on the short period of time (one year for example) calculated on the basis of age-dependent reliability models. As for modeling, it appears that the problem of too detailed statistical models for application is the lack of data for required parameters. As for operating experience, several methods of operating experience analysis have been presented (algorithms for reliability data elaboration and statistical identification of aging trend). As for accelerated aging tests, it is demonstrated that a combination of operating experience analysis with the results of accelerated aging tests of naturally aged equipment could provide a good basis for continuous operation of instrumentation and control systems.

Practical applications of age-dependent reliability models and analysis of operational data

International Nuclear Information System (INIS)

Lannoy, A.; Nitoi, M.; Backstrom, O.; Burgazzi, L.; Couallier, V.; Nikulin, M.; Derode, A.; Rodionov, A.; Atwood, C.; Fradet, F.; Antonov, A.; Berezhnoy, A.; Choi, S.Y.; Starr, F.; Dawson, J.; Palmen, H.; Clerjaud, L.

2005-01-01

The purpose of the workshop was to present the experience of practical application of time-dependent reliability models. The program of the workshop comprises the following sessions: -) aging management and aging PSA (Probabilistic Safety Assessment), -) modeling, -) operation experience, and -) accelerating aging tests. In order to introduce time aging effect of particular component to the PSA model, it has been proposed to use the constant unavailability values on the short period of time (one year for example) calculated on the basis of age-dependent reliability models. As for modeling, it appears that the problem of too detailed statistical models for application is the lack of data for required parameters. As for operating experience, several methods of operating experience analysis have been presented (algorithms for reliability data elaboration and statistical identification of aging trend). As for accelerated aging tests, it is demonstrated that a combination of operating experience analysis with the results of accelerated aging tests of naturally aged equipment could provide a good basis for continuous operation of instrumentation and control systems

The wobbler mouse, an ALS animal model

DEFF Research Database (Denmark)

Moser, Jakob Maximilian; Bigini, Paolo; Schmitt-John, Thomas

2013-01-01

This review article is focused on the research progress made utilizing the wobbler mouse as animal model for human motor neuron diseases, especially the amyotrophic lateral sclerosis (ALS). The wobbler mouse develops progressive degeneration of upper and lower motor neurons and shows striking...

Antimyeloperoxidase-associated proliferative glomerulonephritis: an animal model

NARCIS (Netherlands)

Brouwer, E.; Huitema, M. G.; Klok, P. A.; de Weerd, H.; Tervaert, J. W.; Weening, J. J.; Kallenberg, C. G.

1993-01-01

To develop an animal model for antimyeloperoxidase (MPO)-associated necrotizing crescentic glomerulonephritis (NCGN), we immunized Brown Norway rats with MPO and localized a neutrophil lysosomal enzyme extract, primarily consisting of MPO and elastinolytic enzymes, plus H2O2, the substrate of MPO,

ANTIMYELOPEROXIDASE-ASSOCIATED PROLIFERATIVE GLOMERULONEPHRITIS - AN ANIMAL-MODEL

NARCIS (Netherlands)

BROUWER, E; HUITEMA, MG; KLOK, PA; DEWEERD, H; TERVAERT, JWC; WEENING, JJ; KALLENBERG, CGM

1993-01-01

To develop an animal model for antimyeloperoxidase (MPO)-associated necrotizing crescentic glomerulonephritis (NCGN), we immunized Brown Norway rats with MPO and localized a neutrophil lysosomal enzyme extract, primarily consisting of MPO and elastinolytic enzymes, plus H2O2, the substrate of MPO,

Animal model of human disease. Multiple myeloma

NARCIS (Netherlands)

Radl, J.; Croese, J.W.; Zurcher, C.; Enden-Vieveen, M.H.M. van den; Leeuw, A.M. de

1988-01-01

Animal models of spontaneous and induced plasmacytomas in some inbred strains of mice have proven to be useful tools for different studies on tumorigenesis and immunoregulation. Their wide applicability and the fact that after their intravenous transplantation, the recipient mice developed bone

Reducing the number of laboratory animals used in tissue engineering research by restricting the variety of animal models. Articular cartilage tissue engineering as a case study.

Science.gov (United States)

de Vries, Rob B M; Buma, Pieter; Leenaars, Marlies; Ritskes-Hoitinga, Merel; Gordijn, Bert

2012-12-01

The use of laboratory animals in tissue engineering research is an important underexposed ethical issue. Several ethical questions may be raised about this use of animals. This article focuses on the possibilities of reducing the number of animals used. Given that there is considerable debate about the adequacy of the current animal models in tissue engineering research, we investigate whether it is possible to reduce the number of laboratory animals by selecting and using only those models that have greatest predictive value for future clinical application of the tissue engineered product. The field of articular cartilage tissue engineering is used as a case study. Based on a study of the scientific literature and interviews with leading experts in the field, an overview is provided of the animal models used and the advantages and disadvantages of each model, particularly in terms of extrapolation to the human situation. Starting from this overview, it is shown that, by skipping the small models and using only one large preclinical model, it is indeed possible to restrict the number of animal models, thereby reducing the number of laboratory animals used. Moreover, it is argued that the selection of animal models should become more evidence based and that researchers should seize more opportunities to choose or create characteristics in the animal models that increase their predictive value.

Research advances in animal models of nonalcoholic fatty liver disease

Directory of Open Access Journals (Sweden)

HUANG Haiyan

2014-09-01

Full Text Available In recent years, the incidence of nonalcoholic fatty liver disease (NAFLD has increased gradually along with the rising prevalence of obesity, type 2 diabetes, and hyperlipidemia, and NAFLD has become one of the most common chronic liver diseases in the world and the second major liver disease after chronic viral hepatitis in China. However, its pathogenesis has not yet been clarified. Animal models are playing an important role in researches on NAFLD due to the facts that the development and progression of NAFLD require a long period of time, and ethical limitations exist in conducting drug trials in patients or collecting liver tissues from patients. The animal models with histopathology similar to that of NAFLD patients are reviewed, and their modeling principle, as well as the advantages and disadvantages, are compared. Animal models provide a powerful tool for further studies of NAFLD pathogenesis and drug screening for prevention and treatment of NAFLD.

Current Animal Models of Postoperative Spine Infection and Potential Future Advances

Directory of Open Access Journals (Sweden)

Alexandra eStavrakis

2015-05-01

Full Text Available Implant related infection following spine surgery is a devastating complication for patients and can potentially lead to significant neurological compromise, disability, morbidity, and even mortality. This paper provides an overview of the existing animal models of postoperative spine infection and highlights the strengths and weaknesses of each model. In addition there is discussion regarding potential modifications to these animal models to better evaluate preventative and treatment strategies for this challenging complication. Current models are effective in simulating surgical procedures but fail to evaluate infection longitudinally using multiple techniques. Potential future modifications to these models include using advanced imaging technologies to evaluate infection, use of bioluminescent bacterial species, and testing of novel treatment strategies against multiple bacterial strains. There is potential to establish a postoperative spine infection model using smaller animals, such as mice, as these would be a more cost-effective screening tool for potential therapeutic interventions.

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

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.)

Dependent systems reliability estimation by structural reliability approach

DEFF Research Database (Denmark)

Kostandyan, Erik; Sørensen, John Dalsgaard

2014-01-01

Estimation of system reliability by classical system reliability methods generally assumes that the components are statistically independent, thus limiting its applicability in many practical situations. A method is proposed for estimation of the system reliability with dependent components, where...... the leading failure mechanism(s) is described by physics of failure model(s). The proposed method is based on structural reliability techniques and accounts for both statistical and failure effect correlations. It is assumed that failure of any component is due to increasing damage (fatigue phenomena...... identification. Application of the proposed method can be found in many real world systems....

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)

Cluster-based upper body marker models for three-dimensional kinematic analysis: Comparison with an anatomical model and reliability analysis.

Science.gov (United States)

Boser, Quinn A; Valevicius, Aïda M; Lavoie, Ewen B; Chapman, Craig S; Pilarski, Patrick M; Hebert, Jacqueline S; Vette, Albert H

2018-04-27

Quantifying angular joint kinematics of the upper body is a useful method for assessing upper limb function. Joint angles are commonly obtained via motion capture, tracking markers placed on anatomical landmarks. This method is associated with limitations including administrative burden, soft tissue artifacts, and intra- and inter-tester variability. An alternative method involves the tracking of rigid marker clusters affixed to body segments, calibrated relative to anatomical landmarks or known joint angles. The accuracy and reliability of applying this cluster method to the upper body has, however, not been comprehensively explored. Our objective was to compare three different upper body cluster models with an anatomical model, with respect to joint angles and reliability. Non-disabled participants performed two standardized functional upper limb tasks with anatomical and cluster markers applied concurrently. Joint angle curves obtained via the marker clusters with three different calibration methods were compared to those from an anatomical model, and between-session reliability was assessed for all models. The cluster models produced joint angle curves which were comparable to and highly correlated with those from the anatomical model, but exhibited notable offsets and differences in sensitivity for some degrees of freedom. Between-session reliability was comparable between all models, and good for most degrees of freedom. Overall, the cluster models produced reliable joint angles that, however, cannot be used interchangeably with anatomical model outputs to calculate kinematic metrics. Cluster models appear to be an adequate, and possibly advantageous alternative to anatomical models when the objective is to assess trends in movement behavior. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

Geospatial forecast model for tsetse-transmitted animal ...

African Journals Online (AJOL)

Results indicate that GIS model developed for parasitic diseases based on growing degree day (GDD) concept can be applied to tsetse-transmitted trypanosomosis. GIS for animal trypanosomosis was created using Food and Agriculture Organization – Crop Production System Zones (FAO-CPSZ) database and Normalized ...

Cancer immunotherapy : insights from transgenic animal models

NARCIS (Netherlands)

McLaughlin, PMJ; Kroesen, BJ; Harmsen, MC; de Leij, LFMH

2001-01-01

A wide range of strategies in cancer immunotherapy has been developed in the last decade, some of which are currently being used in clinical settings. The development of these immunotherapeutical strategies has been facilitated by the generation of relevant transgenic animal models. Since the

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.

Non-Invasive in vivo Imaging in Small Animal Research

Directory of Open Access Journals (Sweden)

V. Koo

2006-01-01

Full Text Available Non-invasive real time in vivo molecular imaging in small animal models has become the essential bridge between in vitro data and their translation into clinical applications. The tremendous development and technological progress, such as tumour modelling, monitoring of tumour growth and detection of metastasis, has facilitated translational drug development. This has added to our knowledge on carcinogenesis. The modalities that are commonly used include Magnetic Resonance Imaging (MRI, Computed Tomography (CT, Positron Emission Tomography (PET, bioluminescence imaging, fluorescence imaging and multi-modality imaging systems. The ability to obtain multiple images longitudinally provides reliable information whilst reducing animal numbers. As yet there is no one modality that is ideal for all experimental studies. This review outlines the instrumentation available together with corresponding applications reported in the literature with particular emphasis on cancer research. Advantages and limitations to current imaging technology are discussed and the issues concerning small animal care during imaging are highlighted.

Estimates of Genetic Parameters of Production Traits for Khuzestan Buffaloes of Iran using Repeated-Records Animal Model

Directory of Open Access Journals (Sweden)

Maryam Baharizadeh

2012-10-01

Full Text Available Buffalo milk yield records were obtained from monthly records of the Animal Breeding Organization of Iran from 1992 to 2009 in 33 herds raised in the Khuzestan province. Variance components, heritability and repeatability were estimated for milk yield, fat yield, fat percentage, protein yield and protein percentage. These estimates were carried out through single trait animal model using DFREML program. Herd-year-season was considered as fixed effect in the model. For milk production traits, age at calving was fitted as a covariate. The additive genetic and permanent environmental effects were also included in the model. The mean values (±SD for milk yield, fat yield, fat percentage, protein yield and protein percentage were 2285.08±762.47 kg, 144.35±54.86 kg, 6.25±0.90%, 97.30±26.73 kg and 4.19±0.27%, respectively. The heritability (±SE of milk yield, fat yield, fat percentage, protein yield and protein percentage were 0.093±0.08, 0.054±0.06, 0.043±0.05, 0.093±0.16 and zero, respectively. These estimates for repeatability were 0.272, 0.132, 0.043, 0.674 and 0.0002, respectively. Lower values of genetic parameter estimates require more data and reliable pedigree records.

Small Animal [18F]FDG PET Imaging for Tumor Model Study

International Nuclear Information System (INIS)

Woo, Sang Keun; Kim, Kyeong Min; Cheon, Gi Jeong

2008-01-01

PET allows non-invasive, quantitative and repetitive imaging of biological function in living animals. Small animal PET imaging with [ 18 F]FDG has been successfully applied to investigation of metabolism, receptor, ligand interactions, gene expression, adoptive cell therapy and somatic gene therapy. Experimental condition of animal handling impacts on the biodistribution of [ 18 F]FDG in small animal study. The small animal PET and CT images were registered using the hardware fiducial markers and small animal contour point. Tumor imaging in small animal with small animal [ 18 F]FDG PET should be considered fasting, warming, and isoflurane anesthesia level. Registered imaging with small animal PET and CT image could be useful for the detection of tumor. Small animal experimental condition of animal handling and registration method will be of most importance for small lesion detection of metastases tumor model

A proposed model for the transfer of environmental tritium to man and tritium metabolism in model animals

International Nuclear Information System (INIS)

Saito, Masahiro; Ishida, M.R.

1987-01-01

To evaluate the accumulated dose in human bodies due to the environmental tritium, it is of required to establish an adequate model for the tritium transfer from the environment to man and to obtain enough information on the metabolic behaviour of tritium in animal bodies using model animal system. In this report, first we describe about a proposed model for the transfer of environmental tritium to man and secondly mention briefly about the recent works on the tritium metabolism in newborn animals which have been treated as a model system of tritium intake through food chain. (author)

Systems reliability/structural reliability

International Nuclear Information System (INIS)

Green, A.E.

1980-01-01

The question of reliability technology using quantified techniques is considered for systems and structures. Systems reliability analysis has progressed to a viable and proven methodology whereas this has yet to be fully achieved for large scale structures. Structural loading variants over the half-time of the plant are considered to be more difficult to analyse than for systems, even though a relatively crude model may be a necessary starting point. Various reliability characteristics and environmental conditions are considered which enter this problem. The rare event situation is briefly mentioned together with aspects of proof testing and normal and upset loading conditions. (orig.)

Translational neuropharmacology and the appropriate and effective use of animal models.

Science.gov (United States)

Green, A R; Gabrielsson, J; Fone, K C F

2011-10-01

This issue of the British Journal of Pharmacology is dedicated to reviews of the major animal models used in neuropharmacology to examine drugs for both neurological and psychiatric conditions. Almost all major conditions are reviewed. In general, regulatory authorities require evidence for the efficacy of novel compounds in appropriate animal models. However, the failure of many compounds in clinical trials following clear demonstration of efficacy in animal models has called into question both the value of the models and the discovery process in general. These matters are expertly reviewed in this issue and proposals for better models outlined. In this editorial, we further suggest that more attention be made to incorporate pharmacokinetic knowledge into the studies (quantitative pharmacology). We also suggest that more attention be made to ensure that full methodological details are published and recommend that journals should be more amenable to publishing negative data. Finally, we propose that new approaches must be used in drug discovery so that preclinical studies become more reflective of the clinical situation, and studies using animal models mimic the anticipated design of studies to be performed in humans, as closely as possible. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

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.

OSS reliability measurement and assessment

CERN Document Server

Yamada, Shigeru

2016-01-01

This book analyses quantitative open source software (OSS) reliability assessment and its applications, focusing on three major topic areas: the Fundamentals of OSS Quality/Reliability Measurement and Assessment; the Practical Applications of OSS Reliability Modelling; and Recent Developments in OSS Reliability Modelling. Offering an ideal reference guide for graduate students and researchers in reliability for open source software (OSS) and modelling, the book introduces several methods of reliability assessment for OSS including component-oriented reliability analysis based on analytic hierarchy process (AHP), analytic network process (ANP), and non-homogeneous Poisson process (NHPP) models, the stochastic differential equation models and hazard rate models. These measurement and management technologies are essential to producing and maintaining quality/reliable systems using OSS.

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.