WorldWideScience

Sample records for animal models predictive

  1. Underwater Sound Propagation Modeling Methods for Predicting Marine Animal Exposure.

    Science.gov (United States)

    Hamm, Craig A; McCammon, Diana F; Taillefer, Martin L

    2016-01-01

    The offshore exploration and production (E&P) industry requires comprehensive and accurate ocean acoustic models for determining the exposure of marine life to the high levels of sound used in seismic surveys and other E&P activities. This paper reviews the types of acoustic models most useful for predicting the propagation of undersea noise sources and describes current exposure models. The severe problems caused by model sensitivity to the uncertainty in the environment are highlighted to support the conclusion that it is vital that risk assessments include transmission loss estimates with statistical measures of confidence.

  2. Estimating the predictive validity of diabetic animal models in rosiglitazone studies.

    Science.gov (United States)

    Varga, O E; Zsíros, N; Olsson, I A S

    2015-06-01

    For therapeutic studies, predictive validity of animal models - arguably the most important feature of animal models in terms of human relevance - can be calculated retrospectively by obtaining data on treatment efficacy from human and animal trials. Using rosiglitazone as a case study, we aim to determine the predictive validity of animal models of diabetes, by analysing which models perform most similarly to humans during rosiglitazone treatment in terms of changes in standard diabetes diagnosis parameters (glycosylated haemoglobin [HbA1c] and fasting glucose levels). A further objective of this paper was to explore the impact of four covariates on the predictive capacity: (i) diabetes induction method; (ii) drug administration route; (iii) sex of animals and (iv) diet during the experiments. Despite the variable consistency of animal species-based models with the human reference for glucose and HbA1c treatment effects, our results show that glucose and HbA1c treatment effects in rats agreed better with the expected values based on human data than in other species. Induction method was also found to be a substantial factor affecting animal model performance. The study concluded that regular reassessment of animal models can help to identify human relevance of each model and adapt research design for actual research goals.

  3. Predictive in vivo animal models and translation to clinical trials.

    Science.gov (United States)

    Cook, Natalie; Jodrell, Duncan I; Tuveson, David A

    2012-03-01

    Vast resources are expended during the development of new cancer therapeutics, and selection of optimal in vivo models should improve this process. Genetically engineered mouse models (GEMM) of cancer have progressively improved in technical sophistication and, accurately recapitulating the human cognate condition, have had a measureable impact on our knowledge of tumourigenesis. However, the application of GEMMs to facilitate the development of innovative therapeutic and diagnostic approaches has lagged behind. GEMMs that recapitulate human cancer offer an additional opportunity to accelerate drug development, and should complement the role of the widely used engraftment tumour models.

  4. 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

    2017-03-27

    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.

  5. Animal models

    DEFF Research Database (Denmark)

    Gøtze, Jens Peter; Krentz, Andrew

    2014-01-01

    In this issue of Cardiovascular Endocrinology, we are proud to present a broad and dedicated spectrum of reviews on animal models in cardiovascular disease. The reviews cover most aspects of animal models in science from basic differences and similarities between small animals and the human...... pathology, to biomarkers in diagnosis and prognostic evaluation, to drug testing and targeted medicine....

  6. Animal models for predicting the efficacy and side effects of antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Pedro H. Gobira

    2013-01-01

    Full Text Available The use of antipsychotic drugs represents an important approach for the treatment of schizophrenia. However, their efficacy is limited to certain symptoms of this disorder, and they induce serious side effects. As a result, there is a strong demand for the development of new drugs, which depends on reliable animal models for pharmacological characterization. The present review discusses the face, construct, and predictive validity of classical animal models for studying the efficacy and side effects of compounds for the treatment of schizophrenia. These models are based on the properties of antipsychotics to impair the conditioned avoidance response and reverse certain behavioral changes induced by psychotomimetic drugs, such as stereotypies, hyperlocomotion, and deficit in prepulse inhibition of the startle response. Other tests, which are not specific to schizophrenia, may predict drug effects on negative and cognitive symptoms, such as deficits in social interaction and memory impairment. Regarding motor side effects, the catalepsy test predicts the liability of a drug to induce Parkinson-like syndrome, whereas vacuous chewing movements predict the liability to induce dyskinesia after chronic treatment. Despite certain limitations, these models may contribute to the development of more safe and efficacious antipsychotic drugs.

  7. Predicting the Response to Intravenous Immunoglobulins in an Animal Model of Chronic Neuritis

    Science.gov (United States)

    Pfaff, Johannes; Mathys, Christian; Mausberg, Anne K.; Bendszus, Martin; Pham, Mirko; Hartung, Hans-Peter; Kieseier, Bernd C.

    2016-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a disabling autoimmune disorder of the peripheral nervous system (PNS). Intravenous immunoglobulins (IVIg) are effective in CIDP, but the treatment response varies greatly between individual patients. Understanding this interindividual variability and predicting the response to IVIg constitute major clinical challenges in CIDP. We previously established intercellular adhesion molecule (ICAM)-1 deficient non-obese diabetic (NOD) mice as a novel animal model of CIDP. Here, we demonstrate that similar to human CIDP patients, ICAM-1 deficient NOD mice respond to IVIg treatment by clinical and histological measures. Nerve magnetic resonance imaging and histology demonstrated that IVIg ameliorates abnormalities preferentially in distal parts of the sciatic nerve branches. The IVIg treatment response also featured great heterogeneity allowing us to identify IVIg responders and non-responders. An increased production of interleukin (IL)-17 positively predicted IVIg treatment responses. In human sural nerve biopsy sections, high numbers of IL-17 producing cells were associated with younger age and shorter disease duration. Thus, our novel animal model can be utilized to identify prognostic markers of treatment responses in chronic inflammatory neuropathies and we identify IL-17 production as one potential such prognostic marker. PMID:27711247

  8. Phencyclidine in the social interaction test: an animal model of schizophrenia with face and predictive validity.

    Science.gov (United States)

    Sams-Dodd, F

    1999-01-01

    Phencyclidine (PCP) is a hallucinogenic drug that can mimic several aspects of the schizophrenic symptomatology in healthy volunteers. In a series of studies PCP was administered to rats to determine whether it was possible to develop an animal model of the positive and negative symptoms of schizophrenia. The rats were tested in the social interaction test and it was found that PCP dose-dependently induces stereotyped behaviour and social withdrawal, which may correspond to certain aspects of the positive and negative symptoms, respectively. The effects of PCP could be reduced selectively by antipsychotic drug treatment, whereas drugs lacking antipsychotic effects did not alleviate the PCP-induced behaviours. Together these findings indicate that PCP effects in the rat social interaction test may be a model of the positive and negative symptoms of schizophrenia with face and predictive validity and that it may be useful for the evaluation of novel antipsychotic compounds.

  9. The utility of fecal corticosterone metabolites and animal welfare assessment protocols as predictive parameters of tumor development and animal welfare in a murine xenograft model

    DEFF Research Database (Denmark)

    Jacobsen, Kirsten Rosenmaj; Jørgensen, Pernille Schønning; Pipper, Christian Bressen

    2013-01-01

    The aim of the present study was to evaluate the utility of various non-invasive parameters for the prediction of tumor development and animal welfare in a murine xenograft model in male C.B-17 SCID (C.B-Igh-1(b)/IcrTac-Prkdc(scid)) mice. The study showed that body weight, food and water consumpt......The aim of the present study was to evaluate the utility of various non-invasive parameters for the prediction of tumor development and animal welfare in a murine xenograft model in male C.B-17 SCID (C.B-Igh-1(b)/IcrTac-Prkdc(scid)) mice. The study showed that body weight, food and water...... consumption, and an animal welfare assessment (AWA) protocol revealed marked differences between control and cancer lines as the size of the tumor increased. However, only the AWA protocol was effective in predicting the tumor size and the level of fecal corticosterone metabolites (FCM). FCM levels were......, however, negatively-correlated to the AWA score, and the tumor size, both when evaluated on a given day and when accumulated over the entire period. In conclusion, the present study demonstrated that body weight and food and water consumption were negatively-affected as tumor developed but only the animal...

  10. Lack of predictability of classical animal models for hypolipidemic activity: A good time for mice?

    NARCIS (Netherlands)

    Krause, B.R.; Princen, H.M.G.

    1998-01-01

    Hypolipidemic drugs that are efficacious in man are not always active in classical animal models of dyslipidemia. Inhibitors of HMG-CoA reductase (statins) do not lower plasma cholesterol in rats, but yet this species was alone in providing activity for fibrate-type drugs. Nicotinic acid possesses m

  11. A large animal neuropathic pain model in sheep: a strategy for improving the predictability of preclinical models for therapeutic development

    Directory of Open Access Journals (Sweden)

    Wilkes D

    2012-10-01

    Full Text Available Denise Wilkes,1 Guangwen Li,2 Carmina F Angeles,3 Joel T Patterson,4 Li-Yen Mae Huang21Department of Anesthesiology, 2Department of Neuroscience and Cell Biology, 3Department of Neurosurgery University of Texas Medical Branch, Galveston, TX, USA; 4Neurospine Institute, Eugene, OR, USABackground: Evaluation of analgesics in large animals is a necessary step in the development of better pain medications or gene therapy prior to clinical trials. However, chronic neuropathic pain models in large animals are limited. To address this deficiency, we developed a neuropathic pain model in sheep, which shares many anatomical similarities in spine dimensions and cerebrospinal fluid volume as humans.Methods: A neuropathic pain state was induced in sheep by tight ligation and axotomy of the common peroneal nerve. The analgesic effect of intrathecal (IT morphine was investigated. Interspecies comparison was conducted by analyzing the ceiling doses of IT morphine for humans, sheep, and rats.Results: Peroneal nerve injury (PNI produced an 86% decrease in von-Frey filament-evoked withdrawal threshold on postsurgery day 3 and the decrease lasted for the 8-week test period. Compared to the pre-injury, sham, and contralateral hindlimb, the IT morphine dose that produces 50% of maximum analgesia (ED50 for injured PNI hindlimb was 1.8-fold larger and Emax, the dose that produces maximal analgesia, was 6.1-fold lower. The sheep model closely predicts human IT morphine ceiling dose by allometric scaling. This is in contrast to the approximately 10-fold lower morphine ceiling dose predicted by the rat spinal nerve ligated or spared nerve injury models.Conclusion: PNI sheep model has a fast onset and shows stable and long-lasting pain behavioral characteristics. Since the antinociceptive properties of IT morphine are similar to those observed in humans, the PNI sheep model will be a useful tool for the development of analgesics. Its large size and consistent chronic pain

  12. Innovative drugs to treat depression: did animal models fail to be predictive or did clinical trials fail to detect effects?

    Science.gov (United States)

    Belzung, Catherine

    2014-04-01

    Over recent decades, encouraging preclinical evidence using rodent models pointed to innovative pharmacological targets to treat major depressive disorder. However, subsequent clinical trials have failed to show convincing results. Two explanations for these rather disappointing results can be put forward, either animal models of psychiatric disorders have failed to predict the clinical effectiveness of treatments or clinical trials have failed to detect the effects of these new drugs. A careful analysis of the literature reveals that both statements are true. Indeed, in some cases, clinical efficacy has been predicted on the basis of inappropriate animal models, although the contrary is also true, as some clinical trials have not targeted the appropriate dose or clinical population. On the one hand, refinement of animal models requires using species that have better homological validity, designing models that rely on experimental manipulations inducing pathological features, and trying to model subtypes of depression. On the other hand, clinical research should consider carefully the results from preclinical studies, in order to study these compounds at the correct dose, in the appropriate psychiatric nosological entity or symptomatology, in relevant subpopulations of patients characterized by specific biomarkers. To achieve these goals, translational research has to strengthen the dialogue between basic and clinical science.

  13. Rabbit as an animal model for intravitreal pharmacokinetics: Clinical predictability and quality of the published data.

    Science.gov (United States)

    Del Amo, Eva M; Urtti, Arto

    2015-08-01

    Intravitreal administration is the method of choice in drug delivery to the retina and/or choroid. Rabbit is the most commonly used animal species in intravitreal pharmacokinetics, but it has been criticized as being a poor model of human eye. The critique is based on some anatomical differences, properties of the vitreous humor, and observed differences in drug concentrations in the anterior chamber after intravitreal injections. We have systematically analyzed all published information on intravitreal pharmacokinetics in the rabbit and human eye. The analysis revealed major problems in the design of the pharmacokinetic studies. In this review we provide advice for study design. Overall, the pharmacokinetic parameters (clearance, volume of distribution, half-life) in the human and rabbit eye have good correlation and comparable absolute values. Therefore, reliable rabbit-to-man translation of intravitreal pharmacokinetics should be feasible. The relevant anatomical and physiological parameters in rabbit and man show only small differences. Furthermore, the claimed discrepancy between drug concentrations in the human and rabbit aqueous humor is not supported by the data analysis. Based on the available and properly conducted pharmacokinetic studies, the differences in the vitreous structure in rabbits and human patients do not lead to significant pharmacokinetic differences. This review is the first step towards inter-species translation of intravitreal pharmacokinetics. More information is still needed to dissect the roles of drug delivery systems, disease states, age and ocular manipulation on the intravitreal pharmacokinetics in rabbit and man. Anyway, the published data and the derived pharmacokinetic parameters indicate that the rabbit is a useful animal model in intravitreal pharmacokinetics.

  14. In silico platform for xenobiotics ADME-T pharmacological properties modeling and prediction. Part I: Beyond the reduction of animal model use.

    NARCIS (Netherlands)

    Huynh, L.; Masereeuw, R.; Friedberg, T.; Ingelman-Sundberg, M.; Manivet, P.

    2009-01-01

    There is an urgent need for efficient in silico ADME-T prediction tools for the selection of potent therapeutic drugs as well as the elimination of toxic compounds. This is particularly important in view of the high costs and ethical issues inherent to the use of animal models for drugs filtering. T

  15. 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?...

  16. Animal models of scoliosis.

    Science.gov (United States)

    Bobyn, Justin D; Little, David G; Gray, Randolph; Schindeler, Aaron

    2015-04-01

    Multiple techniques designed to induce scoliotic deformity have been applied across many animal species. We have undertaken a review of the literature regarding experimental models of scoliosis in animals to discuss their utility in comprehending disease aetiology and treatment. Models of scoliosis in animals can be broadly divided into quadrupedal and bipedal experiments. Quadrupedal models, in the absence of axial gravitation force, depend upon development of a mechanical asymmetry along the spine to initiate a scoliotic deformity. Bipedal models more accurately mimic human posture and consequently are subject to similar forces due to gravity, which have been long appreciated to be a contributing factor to the development of scoliosis. Many effective models of scoliosis in smaller animals have not been successfully translated to primates and humans. Though these models may not clarify the aetiology of human scoliosis, by providing a reliable and reproducible deformity in the spine they are a useful means with which to test interventions designed to correct and prevent deformity.

  17. Animal models for osteoporosis

    Science.gov (United States)

    Turner, R. T.; Maran, A.; Lotinun, S.; Hefferan, T.; Evans, G. L.; Zhang, M.; Sibonga, J. D.

    2001-01-01

    Animal models will continue to be important tools in the quest to understand the contribution of specific genes to establishment of peak bone mass and optimal bone architecture, as well as the genetic basis for a predisposition toward accelerated bone loss in the presence of co-morbidity factors such as estrogen deficiency. Existing animal models will continue to be useful for modeling changes in bone metabolism and architecture induced by well-defined local and systemic factors. However, there is a critical unfulfilled need to develop and validate better animal models to allow fruitful investigation of the interaction of the multitude of factors which precipitate senile osteoporosis. Well characterized and validated animal models that can be recommended for investigation of the etiology, prevention and treatment of several forms of osteoporosis have been listed in Table 1. Also listed are models which are provisionally recommended. These latter models have potential but are inadequately characterized, deviate significantly from the human response, require careful choice of strain or age, or are not practical for most investigators to adopt. It cannot be stressed strongly enough that the enormous potential of laboratory animals as models for osteoporosis can only be realized if great care is taken in the choice of an appropriate species, age, experimental design, and measurements. Poor choices will results in misinterpretation of results which ultimately can bring harm to patients who suffer from osteoporosis by delaying advancement of knowledge.

  18. Modelling Farm Animal Welfare.

    Science.gov (United States)

    Collins, Lisa M; Part, Chérie E

    2013-05-16

    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.

  19. 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.

  20. Animal models of recurrent or bipolar depression.

    Science.gov (United States)

    Kato, T; Kasahara, T; Kubota-Sakashita, M; Kato, T M; Nakajima, K

    2016-05-03

    Animal models of mental disorders should ideally have construct, face, and predictive validity, but current animal models do not always satisfy these validity criteria. Additionally, animal models of depression rely mainly on stress-induced behavioral changes. These stress-induced models have limited validity, because stress is not a risk factor specific to depression, and the models do not recapitulate the recurrent and spontaneous nature of depressive episodes. Although animal models exhibiting recurrent depressive episodes or bipolar depression have not yet been established, several researchers are trying to generate such animals by modeling clinical risk factors as well as by manipulating a specific neural circuit using emerging techniques.

  1. e-Cow: an animal model that predicts herbage intake, milk yield and live weight change in dairy cows grazing temperate pastures, with and without supplementary feeding.

    Science.gov (United States)

    Baudracco, J; Lopez-Villalobos, N; Holmes, C W; Comeron, E A; Macdonald, K A; Barry, T N; Friggens, N C

    2012-06-01

    This animal simulation model, named e-Cow, represents a single dairy cow at grazing. The model integrates algorithms from three previously published models: a model that predicts herbage dry matter (DM) intake by grazing dairy cows, a mammary gland model that predicts potential milk yield and a body lipid model that predicts genetically driven live weight (LW) and body condition score (BCS). Both nutritional and genetic drives are accounted for in the prediction of energy intake and its partitioning. The main inputs are herbage allowance (HA; kg DM offered/cow per day), metabolisable energy and NDF concentrations in herbage and supplements, supplements offered (kg DM/cow per day), type of pasture (ryegrass or lucerne), days in milk, days pregnant, lactation number, BCS and LW at calving, breed or strain of cow and genetic merit, that is, potential yields of milk, fat and protein. Separate equations are used to predict herbage intake, depending on the cutting heights at which HA is expressed. The e-Cow model is written in Visual Basic programming language within Microsoft Excel®. The model predicts whole-lactation performance of dairy cows on a daily basis, and the main outputs are the daily and annual DM intake, milk yield and changes in BCS and LW. In the e-Cow model, neither herbage DM intake nor milk yield or LW change are needed as inputs; instead, they are predicted by the e-Cow model. The e-Cow model was validated against experimental data for Holstein-Friesian cows with both North American (NA) and New Zealand (NZ) genetics grazing ryegrass-based pastures, with or without supplementary feeding and for three complete lactations, divided into weekly periods. The model was able to predict animal performance with satisfactory accuracy, with concordance correlation coefficients of 0.81, 0.76 and 0.62 for herbage DM intake, milk yield and LW change, respectively. Simulations performed with the model showed that it is sensitive to genotype by feeding environment

  2. Animal Models of Narcolepsy

    OpenAIRE

    Chen, Lichao; Brown, Ritchie E.; McKenna, James T.; McCarley, Robert W.

    2009-01-01

    Narcolepsy is a debilitating sleep disorder with excessive daytime sleepiness and cataplexy as its two major symptoms. Although this disease was first described about one century ago, an animal model was not available until the 1970s. With the establishment of the Stanford canine narcolepsy colony, researchers were able to conduct multiple neurochemical studies to explore the pathophysiology of this disease. It was concluded that there was an imbalance between monoaminergic and cholinergic sy...

  3. Animal models of candidiasis.

    Science.gov (United States)

    Clancy, Cornelius J; Cheng, Shaoji; Nguyen, Minh Hong

    2009-01-01

    Animal models are powerful tools to study the pathogenesis of diverse types of candidiasis. Murine models are particularly attractive because of cost, ease of handling, technical feasibility, and experience with their use. In this chapter, we describe methods for two of the most popular murine models of disease caused by Candida albicans. In an intravenously disseminated candidiasis (DC) model, immunocompetent mice are infected by lateral tail vein injections of a C. albicans suspension. Endpoints include mortality, tissue burdens of infection (most importantly in the kidneys, although spleens and livers are sometimes also assessed), and histopathology of infected organs. In a model of oral/esophageal candidiasis, mice are immunosuppressed with cortisone acetate and inoculated in the oral cavities using swabs saturated with a C. albicans suspension. Since mice do not die from oral candidiasis in this model, endpoints are tissue burden of infection and histopathology. The DC and oral/esophageal models are most commonly used for studies of C. albicans virulence, in which the disease-causing ability of a mutant strain is compared with an isogenic parent strain. Nevertheless, the basic techniques we describe are also applicable to models adapted to investigate other aspects of pathogenesis, such as spatiotemporal patterns of gene expression, specific aspects of host immune response and assessment of antifungal agents, immunomodulatory strategies, and vaccines.

  4. Animal models of narcolepsy.

    Science.gov (United States)

    Chen, Lichao; Brown, Ritchie E; McKenna, James T; McCarley, Robert W

    2009-08-01

    Narcolepsy is a debilitating sleep disorder with excessive daytime sleepiness and cataplexy as its two major symptoms. Although this disease was first described about one century ago, an animal model was not available until the 1970s. With the establishment of the Stanford canine narcolepsy colony, researchers were able to conduct multiple neurochemical studies to explore the pathophysiology of this disease. It was concluded that there was an imbalance between monoaminergic and cholinergic systems in canine narcolepsy. In 1999, two independent studies revealed that orexin neurotransmission deficiency was pivotal to the development of narcolepsy with cataplexy. This scientific leap fueled the generation of several genetically engineered mouse and rat models of narcolepsy. To facilitate further research, it is imperative that researchers reach a consensus concerning the evaluation of narcoleptic behavioral and EEG phenomenology in these models.

  5. 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

    2017-01-12

    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.

  6. Predicting the Movement Speeds of Animals in Natural Environments.

    Science.gov (United States)

    Wilson, Robbie S; Husak, Jerry F; Halsey, Lewis G; Clemente, Christofer J

    2015-12-01

    An animal's movement speed affects all behaviors and underlies the intensity of an activity, the time it takes to complete it, and the probability of successfully completing it, but which factors determine how fast or slow an animal chooses to move? Despite the critical importance of an animal's choice of speed (hereafter designated as "speed-choice"), we still lack a framework for understanding and predicting how fast animals should move in nature. In this article, we develop a framework for predicting speed that is applicable to any animal-including humans-performing any behavior where choice of speed occurs. To inspire new research in this area, we (1) detail the main factors likely to affect speed-choice, including organismal constraints (i.e., energetic, physiological, and biomechanical) and environmental constraints (i.e., predation intensity and abiotic factors); (2) discuss the value of optimal foraging theory in developing models of speed-choice; and (3) describe how optimality models might be integrated with the range of potential organismal and environmental constraints to predict speed. We show that by utilizing optimality theory it is possible to provide quantitative predictions of optimal speeds across different ecological contexts. However, the usefulness of any predictive models is still entirely dependent on being able to provide relevant mathematical functions to insert into such models. We still lack basic knowledge about how an animal's speed affects its motor control, maneuverability, observational skills, and vulnerability to predators. Studies exploring these gaps in knowledge will help facilitate the field of optimal performance and allow us to adequately parameterize models predicting the speed-choice of animals, which represents one of the most basic of all behavioral decisions.

  7. Integrated in vitro-in silico models for predicting in vivo developmental toxicity : facilitating non-animal based safety assessment

    NARCIS (Netherlands)

    Louisse, J.

    2012-01-01

    In chemical safety assessment, information on adverse effects after repeated dose and chronic exposure to low levels of hazardous compounds is essential for estimating human risks. At present, this information is almost solely obtained by performing animal experiments. Therefore, suitable methods to

  8. Use of population pharmacokinetic modeling and Monte Carlo simulation to capture individual animal variability in the prediction of flunixin withdrawal times in cattle.

    Science.gov (United States)

    Wu, H; Baynes, R E; Leavens, T; Tell, L A; Riviere, J E

    2013-06-01

    The objective of this study was to develop a population pharmacokinetic (PK) model and predict tissue residues and the withdrawal interval (WDI) of flunixin in cattle. Data were pooled from published PK studies in which flunixin was administered through various dosage regimens to diverse populations of cattle. A set of liver data used to establish the regulatory label withdrawal time (WDT) also were used in this study. Compartmental models with first-order absorption and elimination were fitted to plasma and liver concentrations by a population PK modeling approach. Monte Carlo simulations were performed with the population mean and variabilities of PK parameters to predict liver concentrations of flunixin. The PK of flunixin was described best by a 3-compartment model with an extra liver compartment. The WDI estimated in this study with liver data only was the same as the label WDT. However, a longer WDI was estimated when both plasma and liver data were included in the population PK model. This study questions the use of small groups of healthy animals to determine WDTs for drugs intended for administration to large diverse populations. This may warrant a reevaluation of the current procedure for establishing WDT to prevent violative residues of flunixin.

  9. Refining Animal Models to Enhance Animal Welfare

    Institute of Scientific and Technical Information of China (English)

    Patricia V.Turner

    2012-01-01

    The use of animals in research will be necessary for scientific advances in the basic and biomedical sciences for the foreseeable future.As we learn more about the ability of animals to experience pain,suffering,and distress,and particularly for mammals,it becomes the responsibility of scientists,institutions,animal caregivers,and veterinarians to seek ways to improve the lives of research animals and refine their care and use.Refinement is one of the three R's emphasized by Russell and Burch,and refers to modification of procedures to minimise the potential for pain,suffering and distress. It may also refer to procedures used to enhance animal comfort. This paper summarizes considerations for refinements in research animal.

  10. Animal models of cerebral ischemia

    Science.gov (United States)

    Khodanovich, M. Yu.; Kisel, A. A.

    2015-11-01

    Cerebral ischemia remains one of the most frequent causes of death and disability worldwide. Animal models are necessary to understand complex molecular mechanisms of brain damage as well as for the development of new therapies for stroke. This review considers a certain range of animal models of cerebral ischemia, including several types of focal and global ischemia. Since animal models vary in specificity for the human disease which they reproduce, the complexity of surgery, infarct size, reliability of reproduction for statistical analysis, and adequate models need to be chosen according to the aim of a study. The reproduction of a particular animal model needs to be evaluated using appropriate tools, including the behavioral assessment of injury and non-invasive and post-mortem control of brain damage. These problems also have been summarized in the review.

  11. Animal models for candidiasis.

    Science.gov (United States)

    Conti, Heather R; Huppler, Anna R; Whibley, Natasha; Gaffen, Sarah L

    2014-04-02

    Multiple forms of candidiasis are clinically important in humans. Established murine models of disseminated, oropharyngeal, vaginal, and cutaneous candidiasis caused by Candida albicans are described in this unit. Detailed materials and methods for C. albicans growth and detection are also described.

  12. Animal models of portal hypertension

    Institute of Scientific and Technical Information of China (English)

    Juan G Abraldes; Marcos Pasarín; Juan Carlos; García-Pagán

    2006-01-01

    Animal models have allowed detailed study of hemodynamic alterations typical of portal hypertension and the molecular mechanisms involved in abnormalities in splanchnic and systemic circulation associated with this syndrome. Models of prehepatic portal hypertension can be used to study alterations in the splanchnic circulation and the pathophysiology of the hyperdynamic circulation. Models of cirrhosis allow study of the alterations in intrahepatic microcirculation that lead to increased resistance to portal flow. This review summarizes the currently available literature on animal models of portal hypertension and analyzes their relative utility. The criteria for choosing a particular model,depending on the specific objectives of the study, are also discussed.

  13. Impact of Relationships between Test and Reference Animals and between Reference Animals on Reliability of Genomic Prediction

    DEFF Research Database (Denmark)

    Wu, Xiaoping; Lund, Mogens Sandø; Sun, Dongxiao

    as a common test population. A GBLUP model and a Bayesian mixture model were applied to predict Genomic breeding values for bulls in the test data. Result showed that a closer relationship between test and reference animals led to a higher reliability, while a closer relationship between reference animal......This study investigated reliability of genomic prediction in various scenarios with regard to relationship between test and reference animals and between animals within the reference population. Different reference populations were generated from EuroGenomics data and 1288 Nordic Holstein bulls...... resulted in a lower reliability. Therefore, the design of reference population is important for improving the reliability of genomic prediction. With regard to model, the Bayesian mixture model in general led to slightly a higher reliability of genomic prediction than the GBLUP model....

  14. Impact of Relationships between Test and Reference Animals and between Reference Animals on Reliability of Genomic Prediction

    DEFF Research Database (Denmark)

    Wu, Xiaoping; Lund, Mogens Sandø; Sun, Dongxiao

    as a common test population. A GBLUP model and a Bayesian mixture model were applied to predict Genomic breeding values for bulls in the test data. Result showed that a closer relationship between test and reference animals led to a higher reliability, while a closer relationship between reference animal......This study investigated reliability of genomic prediction in various scenarios with regard to relationship between test and reference animals and between animals within the reference population. Different reference populations were generated from EuroGenomics data and 1288 Nordic Holstein bulls...... resulted in a lower reliability. Therefore, the design of reference population is important for improving the reliability of genomic prediction. With regard to model, the Bayesian mixture model in general led to slightly a higher reliability of genomic prediction than the GBLUP model...

  15. Evaluation of animal models of neurobehavioral disorders

    Directory of Open Access Journals (Sweden)

    Nordquist Rebecca E

    2009-02-01

    Full Text Available Abstract Animal models play a central role in all areas of biomedical research. The process of animal model building, development and evaluation has rarely been addressed systematically, despite the long history of using animal models in the investigation of neuropsychiatric disorders and behavioral dysfunctions. An iterative, multi-stage trajectory for developing animal models and assessing their quality is proposed. The process starts with defining the purpose(s of the model, preferentially based on hypotheses about brain-behavior relationships. Then, the model is developed and tested. The evaluation of the model takes scientific and ethical criteria into consideration. Model development requires a multidisciplinary approach. Preclinical and clinical experts should establish a set of scientific criteria, which a model must meet. The scientific evaluation consists of assessing the replicability/reliability, predictive, construct and external validity/generalizability, and relevance of the model. We emphasize the role of (systematic and extended replications in the course of the validation process. One may apply a multiple-tiered 'replication battery' to estimate the reliability/replicability, validity, and generalizability of result. Compromised welfare is inherent in many deficiency models in animals. Unfortunately, 'animal welfare' is a vaguely defined concept, making it difficult to establish exact evaluation criteria. Weighing the animal's welfare and considerations as to whether action is indicated to reduce the discomfort must accompany the scientific evaluation at any stage of the model building and evaluation process. Animal model building should be discontinued if the model does not meet the preset scientific criteria, or when animal welfare is severely compromised. The application of the evaluation procedure is exemplified using the rat with neonatal hippocampal lesion as a proposed model of schizophrenia. In a manner congruent to

  16. Optogenetics in psychiatric animal models.

    Science.gov (United States)

    Wentz, Christian T; Oettl, Lars-Lennart; Kelsch, Wolfgang

    2013-10-01

    Optogenetics is the optical control of neuronal excitability by genetically delivered light-activated channels and pumps and represents a promising tool to fuel the study of circuit function in psychiatric animal models. This review highlights three developments. First, we examine the application of optogenetics in one of the neuromodulators central to the pathophysiology of many psychiatric disorders, the dopaminergic system. We then discuss recent work in translating functional magnetic resonance imaging in small animals (in which optogenetics can be employed to reveal physiological mechanisms underlying disease-related alterations in brain circuits) to patients. Finally, we describe emerging technological developments for circuit manipulation in freely behaving animals.

  17. 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.

  18. 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...

  19. Predicting breeding values in animals by kalman filter

    DEFF Research Database (Denmark)

    Karacaören, Burak; Janss, Luc; Kadarmideen, Haja

    2012-01-01

    The aim of this study was to investigate usefulness of Kalman Filter (KF) Random Walk methodology (KF-RW) for prediction of breeding values in animals. We used body condition score (BCS) from dairy cattle for illustrating use of KF-RW. BCS was measured by Swiss Holstein Breeding Association during...... May 2004-March 2005 for 7 times approximately at monthly intervals from dairy cows (n=80) stationed at the Chamau research farm of Eidgenössische Technische Hochschule (ETH), Switzerland. Benefits of KF were demonstrated using random walk models via simulations. Breeding values were predicted over...... for variance components were found (with standard errors) 0.03 (0.006) for animal genetic variance 0.04 (0.007) for permanent environmental variance and 0.21 (0.02) for error variance. Since KF gives online estimation of breeding values and does not need to store or invert matrices, this methodology could...

  20. Animal Models of Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Carlos Zaragoza

    2011-01-01

    Full Text Available Cardiovascular diseases are the first leading cause of death and morbidity in developed countries. The use of animal models have contributed to increase our knowledge, providing new approaches focused to improve the diagnostic and the treatment of these pathologies. Several models have been developed to address cardiovascular complications, including atherothrombotic and cardiac diseases, and the same pathology have been successfully recreated in different species, including small and big animal models of disease. However, genetic and environmental factors play a significant role in cardiovascular pathophysiology, making difficult to match a particular disease, with a single experimental model. Therefore, no exclusive method perfectly recreates the human complication, and depending on the model, additional considerations of cost, infrastructure, and the requirement for specialized personnel, should also have in mind. Considering all these facts, and depending on the budgets available, models should be selected that best reproduce the disease being investigated. Here we will describe models of atherothrombotic diseases, including expanding and occlusive animal models, as well as models of heart failure. Given the wide range of models available, today it is possible to devise the best strategy, which may help us to find more efficient and reliable solutions against human cardiovascular diseases.

  1. 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.

  2. Animal models for auditory streaming.

    Science.gov (United States)

    Itatani, Naoya; Klump, Georg M

    2017-02-19

    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'.

  3. Animal models of neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Fabiola Mara Ribeiro

    2013-01-01

    Full Text Available The prevalence of neurodegenerative diseases, such as Alzheimer's disease (AD and Parkinson's disease (PD, increases with age, and the number of affected patients is expected to increase worldwide in the next decades. Accurately understanding the etiopathogenic mechanisms of these diseases is a crucial step for developing disease-modifying drugs able to preclude their emergence or at least slow their progression. Animal models contribute to increase the knowledge on the pathophysiology of neurodegenerative diseases. These models reproduce different aspects of a given disease, as well as the histopathological lesions and its main symptoms. The purpose of this review is to present the main animal models for AD, PD, and Huntington's disease.

  4. ANIMAL BEHAVIORAL MODELS OF TINNITUS

    Institute of Scientific and Technical Information of China (English)

    ZHANG Chao; WANG Qiuju; SUN Wei

    2014-01-01

    The pathophysiology of tinnitus is poorly understood and treatments are often unsuccessful. A number of animal models have been developed in order to gain a better understanding of tinnitus. A great deal has been learned from these models re-garding the electrophysiological and neuroanatomical correlates of tinnitus following exposure to noise or ototoxic drugs. Re-liable behavioral data is important for determining whether such electrophysiological or neuroanatomical changes are indeed related to tinnitus. Of the many documented tinnitus animal behavioral paradigms, the acoustic startle reflex had been pro-posed as a simple method to identify the presence or absence of tinnitus. Several behavioral models based on conditioned re-sponse suppression paradigms have also been developed. In addition to determining the presence or absence of tinnitus, some of the behavioral paradigms have provided signs of the onset, frequency, and intensity of tinnitus in animals. Although none of these behavioral models have been proved to be a perfect model, these studies provide useful information on understanding the neural mechanisms underlying tinnitus.

  5. Animal models of source memory.

    Science.gov (United States)

    Crystal, Jonathon D

    2016-01-01

    Source memory is the aspect of episodic memory that encodes the origin (i.e., source) of information acquired in the past. Episodic memory (i.e., our memories for unique personal past events) typically involves source memory because those memories focus on the origin of previous events. Source memory is at work when, for example, someone tells a favorite joke to a person while avoiding retelling the joke to the friend who originally shared the joke. Importantly, source memory permits differentiation of one episodic memory from another because source memory includes features that were present when the different memories were formed. This article reviews recent efforts to develop an animal model of source memory using rats. Experiments are reviewed which suggest that source memory is dissociated from other forms of memory. The review highlights strengths and weaknesses of a number of animal models of episodic memory. Animal models of source memory may be used to probe the biological bases of memory. Moreover, these models can be combined with genetic models of Alzheimer's disease to evaluate pharmacotherapies that ultimately have the potential to improve memory.

  6. Modelling group dynamic animal movement

    DEFF Research Database (Denmark)

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

    2014-01-01

    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...... 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...

  7. Animal models of eating disorders

    OpenAIRE

    Sangwon F Kim

    2012-01-01

    Feeding is a fundamental process for basic survival, and is influenced by genetics and environmental stressors. Recent advances in our understanding of behavioral genetics have provided a profound insight on several components regulating eating patterns. However, our understanding of eating disorders such as anorexia nervosa, bulimia nervosa, and binge eating is still poor. The animal model is an essential tool in the investigation of eating behaviors and their pathological forms, yet develop...

  8. Animal models of rheumatoid arthritis: How informative are they?

    Science.gov (United States)

    McNamee, Kay; Williams, Richard; Seed, Michael

    2015-07-15

    Animal models of arthritis are widely used to de-convolute disease pathways and to identify novel drug targets and therapeutic approaches. However, the high attrition rates of drugs in Phase II/III rates means that a relatively small number of drugs reach the market, despite showing efficacy in pre-clinical models. There is also increasing awareness of the ethical issues surrounding the use of animal models of disease and it is timely, therefore, to review the relevance and translatability of animal models of arthritis. In this paper we review the most commonly used animal models in terms of their pathological similarities to human rheumatoid arthritis as well as their response to drug therapy. In general, the ability of animal models to predict efficacy of biologics in man has been good. However, the predictive power of animal models for small molecules has been variable, probably because of differences in the levels of target knockdown achievable in vivo.

  9. Software Validation via Model Animation

    Science.gov (United States)

    Dutle, Aaron M.; Munoz, Cesar A.; Narkawicz, Anthony J.; Butler, Ricky W.

    2015-01-01

    This paper explores a new approach to validating software implementations that have been produced from formally-verified algorithms. Although visual inspection gives some confidence that the implementations faithfully reflect the formal models, it does not provide complete assurance that the software is correct. The proposed approach, which is based on animation of formal specifications, compares the outputs computed by the software implementations on a given suite of input values to the outputs computed by the formal models on the same inputs, and determines if they are equal up to a given tolerance. The approach is illustrated on a prototype air traffic management system that computes simple kinematic trajectories for aircraft. Proofs for the mathematical models of the system's algorithms are carried out in the Prototype Verification System (PVS). The animation tool PVSio is used to evaluate the formal models on a set of randomly generated test cases. Output values computed by PVSio are compared against output values computed by the actual software. This comparison improves the assurance that the translation from formal models to code is faithful and that, for example, floating point errors do not greatly affect correctness and safety properties.

  10. 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.

  11. Animal models of skin regeneration.

    Science.gov (United States)

    Gawronska-Kozak, Barbara; Grabowska, Anna; Kopcewicz, Marta; Kur, Anna

    2014-03-01

    Cutaneous injury in the majority of vertebrate animals results in the formation of a scar in the post-injured area. Scar tissues, although beneficial for maintaining integrity of the post-wounded region often interferes with full recovery of injured tissues. The goal of wound-healing studies is to identify mechanisms to redirect reparative pathways from debilitating scar formation to regenerative pathways that lead to normal functionality. To perform such studies models of regeneration, which are rare in mammals, are required. In this review we discussed skin regenerative capabilities present in lower vertebrates and in models of skin scar-free healing in mammals, e.g. mammalian fetuses. However, we especially focused on the attributes of two unusual models of skin scar-free healing capabilities that occur in adult mammals, that is, those associated with nude, FOXN1-deficient mice and in wild-type African spiny mice.

  12. Animal models and conserved processes

    Directory of Open Access Journals (Sweden)

    Greek Ray

    2012-09-01

    Full Text Available Abstract Background The concept of conserved processes presents unique opportunities for using nonhuman animal models in biomedical research. However, the concept must be examined in the context that humans and nonhuman animals are evolved, complex, adaptive systems. Given that nonhuman animals are examples of living systems that are differently complex from humans, what does the existence of a conserved gene or process imply for inter-species extrapolation? Methods We surveyed the literature including philosophy of science, biological complexity, conserved processes, evolutionary biology, comparative medicine, anti-neoplastic agents, inhalational anesthetics, and drug development journals in order to determine the value of nonhuman animal models when studying conserved processes. Results Evolution through natural selection has employed components and processes both to produce the same outcomes among species but also to generate different functions and traits. Many genes and processes are conserved, but new combinations of these processes or different regulation of the genes involved in these processes have resulted in unique organisms. Further, there is a hierarchy of organization in complex living systems. At some levels, the components are simple systems that can be analyzed by mathematics or the physical sciences, while at other levels the system cannot be fully analyzed by reducing it to a physical system. The study of complex living systems must alternate between focusing on the parts and examining the intact whole organism while taking into account the connections between the two. Systems biology aims for this holism. We examined the actions of inhalational anesthetic agents and anti-neoplastic agents in order to address what the characteristics of complex living systems imply for inter-species extrapolation of traits and responses related to conserved processes. Conclusion We conclude that even the presence of conserved processes is

  13. Companion animals symposium: humanized animal models of the microbiome.

    Science.gov (United States)

    Gootenberg, D B; Turnbaugh, P J

    2011-05-01

    Humans and other mammals are colonized by trillions of microorganisms, most of which reside in the gastrointestinal tract, that provide key metabolic capabilities, such as the biosynthesis of vitamins and AA, the degradation of dietary plant polysaccharides, and the metabolism of orally administered therapeutics. Although much progress has been made by studying the human microbiome directly, comparing the human microbiome with that of other animals, and constructing in vitro models of the human gut, there remains a need to develop in vivo models where host, microbial, and environmental parameters can be manipulated. Here, we discuss some of the initial results from a promising method that enables the direct manipulation of microbial community structure, environmental exposures, host genotype, and other factors: the colonization of germ-free animals with complex microbial communities, including those from humans or other animal donors. Analyses of these resulting "humanized" gut microbiomes have begun to reveal 1) that key microbial activities can be transferred from the donor to the recipient animal (e.g., microbial reduction of cholesterol and production of equol), 2) that dietary shifts can affect the composition, gene abundance, and gene expression of the gut microbiome, 3) the succession of the microbial community in infants and ex-germ-free adult animals, and 4) the biogeography of these microbes across the length of gastrointestinal tract. Continued studies of humanized and other intentionally colonized animal models stand to provide new insight into not only the human microbiome, but also the microbiomes of our animal companions.

  14. Experimental Diabetes Mellitus in Different Animal Models

    Directory of Open Access Journals (Sweden)

    Amin Al-awar

    2016-01-01

    Full Text Available Animal models have historically played a critical role in the exploration and characterization of disease pathophysiology and target identification and in the evaluation of novel therapeutic agents and treatments in vivo. Diabetes mellitus disease, commonly known as diabetes, is a group of metabolic disorders characterized by high blood glucose levels for a prolonged time. To avoid late complications of diabetes and related costs, primary prevention and early treatment are therefore necessary. Due to its chronic symptoms, new treatment strategies need to be developed, because of the limited effectiveness of the current therapies. We overviewed the pathophysiological features of diabetes in relation to its complications in type 1 and type 2 mice along with rat models, including Zucker Diabetic Fatty (ZDF rats, BB rats, LEW 1AR1/-iddm rats, Goto-Kakizaki rats, chemically induced diabetic models, and Nonobese Diabetic mouse, and Akita mice model. The advantages and disadvantages that these models comprise were also addressed in this review. This paper briefly reviews the wide pathophysiological and molecular mechanisms associated with type 1 and type 2 diabetes, particularly focusing on the challenges associated with the evaluation and predictive validation of these models as ideal animal models for preclinical assessments and discovering new drugs and therapeutic agents for translational application in humans.

  15. Translational research challenges: finding the right animal models.

    Science.gov (United States)

    Prabhakar, Sharma

    2012-12-01

    Translation of scientific discoveries into meaningful human applications, particularly novel therapies of human diseases, requires development of suitable animal models. Experimental approaches to test new drugs in preclinical phases often necessitated animal models that not only replicate human disease in etiopathogenesis and pathobiology but also biomarkers development and toxicity prediction. Whereas the transgenic and knockout techniques have revolutionized manipulation of rodents and other species to get greater insights into human disease pathogenesis, we are far from generating ideal animal models of most human disease states. The challenges in using the currently available animal models for translational research, particularly for developing potentially new drugs for human disease, coupled with the difficulties in toxicity prediction have led some researchers to develop a scoring system for translatability. These aspects and the challenges in selecting an animal model among those that are available to study human disease pathobiology and drug development are the topics covered in this detailed review.

  16. Wind power prediction models

    Science.gov (United States)

    Levy, R.; Mcginness, H.

    1976-01-01

    Investigations were performed to predict the power available from the wind at the Goldstone, California, antenna site complex. The background for power prediction was derived from a statistical evaluation of available wind speed data records at this location and at nearby locations similarly situated within the Mojave desert. In addition to a model for power prediction over relatively long periods of time, an interim simulation model that produces sample wind speeds is described. The interim model furnishes uncorrelated sample speeds at hourly intervals that reproduce the statistical wind distribution at Goldstone. A stochastic simulation model to provide speed samples representative of both the statistical speed distributions and correlations is also discussed.

  17. Animal models in drug development for MRSA.

    Science.gov (United States)

    Marra, Andrea

    2014-01-01

    One of the foremost challenges of drug discovery in any therapeutic area is that of solidifying the correlation between in vitro activity and clinical efficacy. Between these is the confirmation that affecting a particular target in vivo will lead to a therapeutic benefit. In antibacterial drug discovery, there is a key advantage from the start, since the targets are bacteria-therefore, it is simple to ascertain in vitro whether a drug has the desired effect, i.e., bacterial cell inhibition or killing, and to understand the mechanism by which that occurs. The downstream criteria, whether a compound reaches the infection site and achieves appropriately high levels to affect bacterial viability, can be evaluated in animal models of infection. In this way animal models of infection can be a highly valuable and predictive bridge between in vitro drug discovery and early clinical evaluation.The Gram-positive pathogen Staphylococcus aureus causes a wide variety of infections in humans (Archer, Clin Infect Dis 26:1179-1181, 1998) and has been said to be able to infect every tissue type. Fortunately, over the years a great deal of effort has been expended toward developing infection models in rodents using this organism, with good success. This chapter will describe the advantages, methods, and outcome measurements of the rodent models most used in drug discovery for S. aureus. Mouse models will be the focus of this chapter, as they are the most economical and thus most commonly used, but a rat infection model is included as well.

  18. AnimalTFDB 2.0: a resource for expression, prediction and functional study of animal transcription factors.

    Science.gov (United States)

    Zhang, Hong-Mei; Liu, Teng; Liu, Chun-Jie; Song, Shuangyang; Zhang, Xiantong; Liu, Wei; Jia, Haibo; Xue, Yu; Guo, An-Yuan

    2015-01-01

    Transcription factors (TFs) are key regulators for gene expression. Here we updated the animal TF database AnimalTFDB to version 2.0 (http://bioinfo.life.hust.edu.cn/AnimalTFDB/). Using the improved prediction pipeline, we identified 72 336 TF genes, 21 053 transcription co-factor genes and 6502 chromatin remodeling factor genes from 65 species covering main animal lineages. Besides the abundant annotations (basic information, gene model, protein functional domain, gene ontology, pathway, protein interaction, ortholog and paralog, etc.) in the previous version, we made several new features and functions in the updated version. These new features are: (i) gene expression from RNA-Seq for nine model species, (ii) gene phenotype information, (iii) multiple sequence alignment of TF DNA-binding domains, and the weblogo and phylogenetic tree based on the alignment, (iv) a TF prediction server to identify new TFs from input sequences and (v) a BLAST server to search against TFs in AnimalTFDB. A new nice web interface was designed for AnimalTFDB 2.0 allowing users to browse and search all data in the database. We aim to maintain the AnimalTFDB as a solid resource for TF identification and studies of transcription regulation and comparative genomics.

  19. Systematic reviews of animal models: methodology versus epistemology.

    Science.gov (United States)

    Greek, Ray; Menache, Andre

    2013-01-01

    Systematic reviews are currently favored methods of evaluating research in order to reach conclusions regarding medical practice. The need for such reviews is necessitated by the fact that no research is perfect and experts are prone to bias. By combining many studies that fulfill specific criteria, one hopes that the strengths can be multiplied and thus reliable conclusions attained. Potential flaws in this process include the assumptions that underlie the research under examination. If the assumptions, or axioms, upon which the research studies are based, are untenable either scientifically or logically, then the results must be highly suspect regardless of the otherwise high quality of the studies or the systematic reviews. We outline recent criticisms of animal-based research, namely that animal models are failing to predict human responses. It is this failure that is purportedly being corrected via systematic reviews. We then examine the assumption that animal models can predict human outcomes to perturbations such as disease or drugs, even under the best of circumstances. We examine the use of animal models in light of empirical evidence comparing human outcomes to those from animal models, complexity theory, and evolutionary biology. We conclude that even if legitimate criticisms of animal models were addressed, through standardization of protocols and systematic reviews, the animal model would still fail as a predictive modality for human response to drugs and disease. Therefore, systematic reviews and meta-analyses of animal-based research are poor tools for attempting to reach conclusions regarding human interventions.

  20. A Comparison of the Pathogenesis of Marburg Virus Disease in Humans and Nonhuman Primates and Evaluation of the Suitability of These Animal Models for Predicting Clinical Efficacy under the 'Animal Rule'.

    Science.gov (United States)

    Glaze, Elizabeth R; Roy, Michael J; Dalrymple, Lonnie W; Lanning, Lynda L

    2015-06-01

    Marburg virus outbreaks are sporadic, infrequent, brief, and relatively small in terms of numbers of subjects affected. In addition, outbreaks most likely will occur in remote regions where clinical trials are not feasible; therefore, definitive, well-controlled human efficacy studies to test the effectiveness of a drug or biologic product are not feasible. Healthy human volunteers cannot ethically be deliberately exposed to a lethal agent such as Marburg virus in order to test the efficacy of a therapy or preventive prior to licensure. When human efficacy studies are neither ethical nor feasible, the US Food and Drug Administration may grant marketing approval of a drug or biologic product under the 'Animal Rule,' through which demonstration of the efficacy of a product can be 'based on adequate and well-controlled animal efficacy studies when the results of those studies establish that the drug is reasonably likely to produce clinical benefit in humans.' This process requires that the pathogenic determinants of the disease in the animal model are similar to those that have been identified in humans. After reviewing primarily English-language, peer-reviewed journal articles, we here summarize the clinical manifestations of Marburg virus disease and the results of studies in NHP showing the characteristics and progression of the disease. We also include a detailed comparison of the characteristics of the human disease relative to those for NHP. This review reveals that the disease characteristics of Marburg virus disease are generally similar for humans and 3 NHP species: cynomolgus macaques (Macaca fascicularis), rhesus macaques (Macaca mulatta), and African green monkeys (Chlorocebus aethiops).

  1. 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.

  2. Chronobiology of ethanol: animal models.

    Science.gov (United States)

    Rosenwasser, Alan M

    2015-06-01

    Clinical and epidemiological observations have revealed that alcohol abuse and alcoholism are associated with widespread disruptions in sleep and other circadian biological rhythms. As with other psychiatric disorders, animal models have been very useful in efforts to better understand the cause and effect relationships underlying the largely correlative human data. This review summarizes the experimental findings indicating bidirectional interactions between alcohol (ethanol) consumption and the circadian timing system, emphasizing behavioral studies conducted in the author's laboratory. Together with convergent evidence from multiple laboratories, the work summarized here establishes that ethanol intake (or administration) alters fundamental properties of the underlying circadian pacemaker. In turn, circadian disruption induced by either environmental or genetic manipulations can alter voluntary ethanol intake. These reciprocal interactions may create a vicious cycle that contributes to the downward spiral of alcohol and drug addiction. In the future, such studies may lead to the development of chronobiologically based interventions to prevent relapse and effectively mitigate some of the societal burden associated with such disorders.

  3. A REVIEW ON ANIMAL MODELS OF DEPRESSION

    Directory of Open Access Journals (Sweden)

    Madhu Devi* and Ramica Sharma

    2013-10-01

    Full Text Available As described by the world health organization (WHO, depression is the most common and serious disorder leading to suicide. Numbers of synthetic drugs are available for the treatment of this fatal disease, but are associated with serious complications. A wide diversity of animal models has been used to examine antidepressant activity. These range from relatively simple models sensitive to acute treatment, to highly sophisticated models. The number of validated animal models for affective disorders is large and still growing. A basic understanding of the underlying disease processes in depression is lacking, and therefore, recreating the disease in animal models is not possible. For the animal model of depression, the relevance, reliability and reproducibility in laboratories need to be focused, currently used models of depression attempt to produce quantifiable correlates of human symptoms in experimental animals and the animal modeling remains a potentially important approach towards understanding neurochemical and neurobiological mechanisms in depression. Animal models of depression attempt to represent some aspect of the etiology, symptomatology and treatment of the disorders, in order to facilitate their scientific study. Hence, this review deals with animal models that are beneficial for evaluating the potential of antidepressants. The present review further discusses the ability of currently available animal models for depression to investigate the novel hypothesis.

  4. Pain assessment in animal models of osteoarthritis.

    Science.gov (United States)

    Piel, Margaret J; Kroin, Jeffrey S; van Wijnen, Andre J; Kc, Ranjan; Im, Hee-Jeong

    2014-03-10

    Assessment of pain in animal models of osteoarthritis is integral to interpretation of a model's utility in representing the clinical condition, and enabling accurate translational medicine. Here we describe behavioral pain assessments available for small and large experimental osteoarthritic pain animal models.

  5. Predictive models in urology.

    Science.gov (United States)

    Cestari, Andrea

    2013-01-01

    Predictive modeling is emerging as an important knowledge-based technology in healthcare. The interest in the use of predictive modeling reflects advances on different fronts such as the availability of health information from increasingly complex databases and electronic health records, a better understanding of causal or statistical predictors of health, disease processes and multifactorial models of ill-health and developments in nonlinear computer models using artificial intelligence or neural networks. These new computer-based forms of modeling are increasingly able to establish technical credibility in clinical contexts. The current state of knowledge is still quite young in understanding the likely future direction of how this so-called 'machine intelligence' will evolve and therefore how current relatively sophisticated predictive models will evolve in response to improvements in technology, which is advancing along a wide front. Predictive models in urology are gaining progressive popularity not only for academic and scientific purposes but also into the clinical practice with the introduction of several nomograms dealing with the main fields of onco-urology.

  6. Towards a reliable animal model of migraine

    DEFF Research Database (Denmark)

    Olesen, Jes; Jansen-Olesen, Inger

    2012-01-01

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

  7. Experimental Animal Models in Periodontology: A Review

    OpenAIRE

    Struillou, Xavier; Boutigny, Hervé; Soueidan, Assem; Layrolle, Pierre

    2010-01-01

    In periodontal research, animal studies are complementary to in vitro experiments prior to testing new treatments. Animal models should make possible the validation of hypotheses and prove the safety and efficacy of new regenerating approaches using biomaterials, growth factors or stem cells. A review of the literature was carried out by using electronic databases (PubMed, ISI Web of Science). Numerous animal models in different species such as rats, hamsters, rabbits, ferrets, canines and pr...

  8. 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.

  9. Hyperbolic value addition and general models of animal choice.

    Science.gov (United States)

    Mazur, J E

    2001-01-01

    Three mathematical models of choice--the contextual-choice model (R. Grace, 1994), delay-reduction theory (N. Squires & E. Fantino, 1971), and a new model called the hyperbolic value-added model--were compared in their ability to predict the results from a wide variety of experiments with animal subjects. When supplied with 2 or 3 free parameters, all 3 models made fairly accurate predictions for a large set of experiments that used concurrent-chain procedures. One advantage of the hyperbolic value-added model is that it is derived from a simpler model that makes accurate predictions for many experiments using discrete-trial adjusting-delay procedures. Some results favor the hyperbolic value-added model and delay-reduction theory over the contextual-choice model, but more data are needed from choice situations for which the models make distinctly different predictions.

  10. Evaluation of spinal cord injury animal models

    Institute of Scientific and Technical Information of China (English)

    Ning Zhang; Marong Fang; Haohao Chen; Fangming Gou; Mingxing Ding

    2014-01-01

    Because there is no curative treatment for spinal cord injury, establishing an ideal animal model is important to identify injury mechanisms and develop therapies for individuals suffering from spinal cord injuries. In this article, we systematically review and analyze various kinds of animal models of spinal cord injury and assess their advantages and disadvantages for further studies.

  11. Animal model and neurobiology of suicide.

    Science.gov (United States)

    Preti, Antonio

    2011-06-01

    Animal models are formidable tools to investigate the etiology, the course and the potential treatment of an illness. No convincing animal model of suicide has been produced to date, and despite the intensive study of thousands of animal species naturalists have not identified suicide in nonhuman species in field situations. When modeling suicidal behavior in the animal, the greatest challenge is reproducing the role of will and intention in suicide mechanics. To overcome this limitation, current investigations on animals focus on every single step leading to suicide in humans. The most promising endophenotypes worth investigating in animals are the cortisol social-stress response and the aggression/impulsivity trait, involving the serotonergic system. Astroglia, neurotrophic factors and neurotrophins are implied in suicide, too. The prevention of suicide rests on the identification and treatment of every element increasing the risk.

  12. Limitations of Animal Models of Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    J. A. Potashkin

    2011-01-01

    Full Text Available Most cases of Parkinson's disease (PD are sporadic. When choosing an animal model for idiopathic PD, one must consider the extent of similarity or divergence between the physiology, anatomy, behavior, and regulation of gene expression between humans and the animal. Rodents and nonhuman primates are used most frequently in PD research because when a Parkinsonian state is induced, they mimic many aspects of idiopathic PD. These models have been useful in our understanding of the etiology of the disease and provide a means for testing new treatments. However, the current animal models often fall short in replicating the true pathophysiology occurring in idiopathic PD, and thus results from animal models often do not translate to the clinic. In this paper we will explain the limitations of animal models of PD and why their use is inappropriate for the study of some aspects of PD.

  13. A REVIEW ON ANIMAL MODELS OF DEPRESSION

    OpenAIRE

    Madhu Devi* and Ramica Sharma

    2013-01-01

    As described by the world health organization (WHO), depression is the most common and serious disorder leading to suicide. Numbers of synthetic drugs are available for the treatment of this fatal disease, but are associated with serious complications. A wide diversity of animal models has been used to examine antidepressant activity. These range from relatively simple models sensitive to acute treatment, to highly sophisticated models. The number of validated animal models for affective diso...

  14. Engineering large animal models of human disease.

    Science.gov (United States)

    Whitelaw, C Bruce A; Sheets, Timothy P; Lillico, Simon G; Telugu, Bhanu P

    2016-01-01

    The recent development of gene editing tools and methodology for use in livestock enables the production of new animal disease models. These tools facilitate site-specific mutation of the genome, allowing animals carrying known human disease mutations to be produced. In this review, we describe the various gene editing tools and how they can be used for a range of large animal models of diseases. This genomic technology is in its infancy but the expectation is that through the use of gene editing tools we will see a dramatic increase in animal model resources available for both the study of human disease and the translation of this knowledge into the clinic. Comparative pathology will be central to the productive use of these animal models and the successful translation of new therapeutic strategies.

  15. Animal models of chronic wound care

    DEFF Research Database (Denmark)

    Trostrup, Hannah; Thomsen, Kim; Calum, Henrik

    2016-01-01

    . An inhibiting effect of bacterial biofilms on wound healing is gaining significant clinical attention over the last few years. There is still a paucity of suitable animal models to recapitulate human chronic wounds. The etiology of the wound (venous insufficiency, ischemia, diabetes, pressure) has to be taken...... 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...... of establishment of the infection are well defined in suitable animal models. In addition, several endpoints can be involved for evaluation. Animals do not display chronic wounds in the way that humans do. However, in many cases, animal models can mirror the pathological conditions observed in humans, although...

  16. A Statistical Quality Model for Data-Driven Speech Animation.

    Science.gov (United States)

    Ma, Xiaohan; Deng, Zhigang

    2012-11-01

    In recent years, data-driven speech animation approaches have achieved significant successes in terms of animation quality. However, how to automatically evaluate the realism of novel synthesized speech animations has been an important yet unsolved research problem. In this paper, we propose a novel statistical model (called SAQP) to automatically predict the quality of on-the-fly synthesized speech animations by various data-driven techniques. Its essential idea is to construct a phoneme-based, Speech Animation Trajectory Fitting (SATF) metric to describe speech animation synthesis errors and then build a statistical regression model to learn the association between the obtained SATF metric and the objective speech animation synthesis quality. Through delicately designed user studies, we evaluate the effectiveness and robustness of the proposed SAQP model. To the best of our knowledge, this work is the first-of-its-kind, quantitative quality model for data-driven speech animation. We believe it is the important first step to remove a critical technical barrier for applying data-driven speech animation techniques to numerous online or interactive talking avatar applications.

  17. Animal models for simulating weightlessness

    Science.gov (United States)

    Morey-Holton, E.; Wronski, T. J.

    1982-01-01

    NASA has developed a rat model to simulate on earth some aspects of the weightlessness alterations experienced in space, i.e., unloading and fluid shifts. Comparison of data collected from space flight and from the head-down rat suspension model suggests that this model system reproduces many of the physiological alterations induced by space flight. Data from various versions of the rat model are virtually identical for the same parameters; thus, modifications of the model for acute, chronic, or metabolic studies do not alter the results as long as the critical components of the model are maintained, i.e., a cephalad shift of fluids and/or unloading of the rear limbs.

  18. Retinal Cell Degeneration in Animal Models

    OpenAIRE

    Masayuki Niwa; Hitomi Aoki; Akihiro Hirata; Hiroyuki Tomita; Green, Paul G.; Akira Hara

    2016-01-01

    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 insi...

  19. 3-D Human Modeling and Animation

    CERN Document Server

    Ratner, Peter

    2012-01-01

    3-D Human Modeling and Animation Third Edition All the tools and techniques you need to bring human figures to 3-D life Thanks to today's remarkable technology, artists can create and animate realistic, three-dimensional human figures that were not possible just a few years ago. This easy-to-follow book guides you through all the necessary steps to adapt your own artistic skill in figure drawing, painting, and sculpture to this exciting digital canvas. 3-D Human Modeling and Animation, Third Edition starts you off with simple modeling, then prepares you for more advanced techniques for crea

  20. Nominal Model Predictive Control

    OpenAIRE

    Grüne, Lars

    2014-01-01

    5 p., to appear in Encyclopedia of Systems and Control, Tariq Samad, John Baillieul (eds.); International audience; Model Predictive Control is a controller design method which synthesizes a sampled data feedback controller from the iterative solution of open loop optimal control problems.We describe the basic functionality of MPC controllers, their properties regarding feasibility, stability and performance and the assumptions needed in order to rigorously ensure these properties in a nomina...

  1. Nominal model predictive control

    OpenAIRE

    Grüne, Lars

    2013-01-01

    5 p., to appear in Encyclopedia of Systems and Control, Tariq Samad, John Baillieul (eds.); International audience; Model Predictive Control is a controller design method which synthesizes a sampled data feedback controller from the iterative solution of open loop optimal control problems.We describe the basic functionality of MPC controllers, their properties regarding feasibility, stability and performance and the assumptions needed in order to rigorously ensure these properties in a nomina...

  2. 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.

  3. 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.

  4. Animal Models of Tuberculosis: Zebrafish

    Science.gov (United States)

    van Leeuwen, Lisanne M.; van der Sar, Astrid M.; Bitter, Wilbert

    2015-01-01

    Over the past decade the zebrafish (Danio rerio) has become an attractive new vertebrate model organism for studying mycobacterial pathogenesis. The combination of medium-throughput screening and real-time in vivo visualization has allowed new ways to dissect host pathogenic interaction in a vertebrate host. Furthermore, genetic screens on the host and bacterial sides have elucidated new mechanisms involved in the initiation of granuloma formation and the importance of a balanced immune response for control of mycobacterial pathogens. This article will highlight the unique features of the zebrafish–Mycobacterium marinum infection model and its added value for tuberculosis research. PMID:25414379

  5. Predictive Surface Complexation Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Sverjensky, Dimitri A. [Johns Hopkins Univ., Baltimore, MD (United States). Dept. of Earth and Planetary Sciences

    2016-11-29

    Surface complexation plays an important role in the equilibria and kinetics of processes controlling the compositions of soilwaters and groundwaters, the fate of contaminants in groundwaters, and the subsurface storage of CO2 and nuclear waste. Over the last several decades, many dozens of individual experimental studies have addressed aspects of surface complexation that have contributed to an increased understanding of its role in natural systems. However, there has been no previous attempt to develop a model of surface complexation that can be used to link all the experimental studies in order to place them on a predictive basis. Overall, my research has successfully integrated the results of the work of many experimentalists published over several decades. For the first time in studies of the geochemistry of the mineral-water interface, a practical predictive capability for modeling has become available. The predictive correlations developed in my research now enable extrapolations of experimental studies to provide estimates of surface chemistry for systems not yet studied experimentally and for natural and anthropogenically perturbed systems.

  6. 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.

  7. A cognitive model's view of animal cognition

    Directory of Open Access Journals (Sweden)

    Sidney D'MELLO, Stan FRANKLIN

    2011-08-01

    Full Text Available Although it is a relatively new field of study, the animal cognition literature is quite extensive and difficult to synthesize. This paper explores the contributions a comprehensive, computational, cognitive model can make toward organizing and assimilating this literature, as well as toward identifying important concepts and their interrelations. Using the LIDA model as an example, a framework is described within which to integrate the diverse research in animal cognition. Such a framework can provide both an ontology of concepts and their relations, and a working model of an animal’s cognitive processes that can compliment active empirical research. In addition to helping to account for a broad range of cognitive processes, such a model can help to comparatively assess the cognitive capabilities of different animal species. After deriving an ontology for animal cognition from the LIDA model, we apply it to develop the beginnings of a database that maps the cognitive facilities of a variety of animal species. We conclude by discussing future avenues of research, particularly the use of computational models of animal cognition as valuable tools for hypotheses generation and testing [Current Zoology 57 (4: 499–513, 2011].

  8. Predicting Risk Sensitivity in Humans and Lower Animals: Risk as Variance or Coefficient of Variation

    Science.gov (United States)

    Weber, Elke U.; Shafir, Sharoni; Blais, Ann-Renee

    2004-01-01

    This article examines the statistical determinants of risk preference. In a meta-analysis of animal risk preference (foraging birds and insects), the coefficient of variation (CV), a measure of risk per unit of return, predicts choices far better than outcome variance, the risk measure of normative models. In a meta-analysis of human risk…

  9. Progress With Nonhuman Animal Models of Addiction.

    Science.gov (United States)

    Crabbe, John C

    2016-09-01

    Nonhuman animals have been major contributors to the science of the genetics of addiction. Given the explosion of interest in genetics, it is fair to ask, are we making reasonable progress toward our goals with animal models? I will argue that our goals are changing and that overall progress has been steady and seems likely to continue apace. Genetics tools have developed almost incredibly rapidly, enabling both more reductionist and more synthetic or integrative approaches. I believe that these approaches to making progress have been unbalanced in biomedical science, favoring reductionism, particularly in animal genetics. I argue that substantial, novel progress is also likely to come in the other direction, toward synthesis and abstraction. Another area in which future progress with genetic animal models seems poised to contribute more is the reconciliation of human and animal phenotypes, or consilience. The inherent power of the genetic animal models could be more profitably exploited. In the end, animal research has continued to provide novel insights about how genes influence individual differences in addiction risk and consequences. The rules of the genetics game are changing so fast that it is hard to remember how comparatively little we knew even a generation ago. Rather than worry about whether we have been wasting time and resources asking the questions we have been, we should look to the future and see if we can come up with some new ones. The valuable findings from the past will endure, and the sidetracks will be forgotten.

  10. Animal models in motion sickness research

    Science.gov (United States)

    Daunton, Nancy G.

    1990-01-01

    Practical information on candidate animal models for motion sickness research and on methods used to elicit and detect motion sickness in these models is provided. Four good potential models for use in motion sickness experiments include the dog, cat, squirrel monkey, and rat. It is concluded that the appropriate use of the animal models, combined with exploitation of state-of-the-art biomedical techniques, should generate a great step forward in the understanding of motion sickness mechanisms and in the development of efficient and effective approaches to its prevention and treatment in humans.

  11. Animal Models and Bone Histomorphometry: Translational Research for the Human Research Program

    Science.gov (United States)

    Sibonga, Jean D.

    2010-01-01

    This slide presentation reviews the use of animal models to research and inform bone morphology, in particular relating to human research in bone loss as a result of low gravity environments. Reasons for use of animal models as tools for human research programs include: time-efficient, cost-effective, invasive measures, and predictability as some model are predictive for drug effects.

  12. Candidate Prediction Models and Methods

    DEFF Research Database (Denmark)

    Nielsen, Henrik Aalborg; Nielsen, Torben Skov; Madsen, Henrik

    2005-01-01

    This document lists candidate prediction models for Work Package 3 (WP3) of the PSO-project called ``Intelligent wind power prediction systems'' (FU4101). The main focus is on the models transforming numerical weather predictions into predictions of power production. The document also outlines...

  13. 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...

  14. Current status: Animal models of nausea

    Science.gov (United States)

    Fox, Robert A.

    1991-01-01

    The advantages, and possible benefits of a valid, reliable animal model for nausea are discussed, and difficulties inherent to the development of a model are considered. A principle problem for developing models arises because nausea is a subjective sensation that can be identified only in humans. Several putative measures of nausea in animals are considered, with more detailed consideration directed to variation in cardiac rate, levels of vasopressin, and conditioned taste aversion. Demonstration that putative measures are associated with reported nausea in humans is proposed as a requirement for validating measures to be used in animal models. The necessity for a 'real-time' measure of nausea is proposed as an important factor for future research; and the need for improved understanding of the neuroanatomy underlying the emetic syndrome is discussed.

  15. 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.

  16. 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.

  17. Large animal models for stem cell therapy.

    Science.gov (United States)

    Harding, John; Roberts, R Michael; Mirochnitchenko, Oleg

    2013-03-28

    The field of regenerative medicine is approaching translation to clinical practice, and significant safety concerns and knowledge gaps have become clear as clinical practitioners are considering the potential risks and benefits of cell-based therapy. It is necessary to understand the full spectrum of stem cell actions and preclinical evidence for safety and therapeutic efficacy. The role of animal models for gaining this information has increased substantially. There is an urgent need for novel animal models to expand the range of current studies, most of which have been conducted in rodents. Extant models are providing important information but have limitations for a variety of disease categories and can have different size and physiology relative to humans. These differences can preclude the ability to reproduce the results of animal-based preclinical studies in human trials. Larger animal species, such as rabbits, dogs, pigs, sheep, goats, and non-human primates, are better predictors of responses in humans than are rodents, but in each case it will be necessary to choose the best model for a specific application. There is a wide spectrum of potential stem cell-based products that can be used for regenerative medicine, including embryonic and induced pluripotent stem cells, somatic stem cells, and differentiated cellular progeny. The state of knowledge and availability of these cells from large animals vary among species. In most cases, significant effort is required for establishing and characterizing cell lines, comparing behavior to human analogs, and testing potential applications. Stem cell-based therapies present significant safety challenges, which cannot be addressed by traditional procedures and require the development of new protocols and test systems, for which the rigorous use of larger animal species more closely resembling human behavior will be required. In this article, we discuss the current status and challenges of and several major directions

  18. Pain assessment in animal models: do we need further studies?

    Science.gov (United States)

    Gigliuto, Carmelo; De Gregori, Manuela; Malafoglia, Valentina; Raffaeli, William; Compagnone, Christian; Visai, Livia; Petrini, Paola; Avanzini, Maria Antonietta; Muscoli, Carolina; Viganò, Jacopo; Calabrese, Francesco; Dominioni, Tommaso; Allegri, Massimo; Cobianchi, Lorenzo

    2014-01-01

    In the last two decades, animal models have become important tools in understanding and treating pain, and in predicting analgesic efficacy. Although rodent models retain a dominant role in the study of pain mechanisms, large animal models may predict human biology and pharmacology in certain pain conditions more accurately. Taking into consideration the anatomical and physiological characteristics common to man and pigs (median body size, digestive apparatus, number, size, distribution and communication of vessels in dermal skin, epidermal–dermal junctions, the immunoreactivity of peptide nerve fibers, distribution of nociceptive and non-nociceptive fiber classes, and changes in axonal excitability), swines seem to provide the most suitable animal model for pain assessment. Locomotor function, clinical signs, and measurements (respiratory rate, heart rate, blood pressure, temperature, electromyography), behavior (bright/quiet, alert, responsive, depressed, unresponsive), plasma concentration of substance P and cortisol, vocalization, lameness, and axon reflex vasodilatation by laser Doppler imaging have been used to assess pain, but none of these evaluations have proved entirely satisfactory. It is necessary to identify new methods for evaluating pain in large animals (particularly pigs), because of their similarities to humans. This could lead to improved assessment of pain and improved analgesic treatment for both humans and laboratory animals. PMID:24855386

  19. Animal models for Gaucher disease research

    Directory of Open Access Journals (Sweden)

    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.

  20. Progress in animal models for predicting the results of clinical trials of cancer drugs%预测肿瘤药物临床试验效果的动物模型新进展

    Institute of Scientific and Technical Information of China (English)

    余飞; 丁慧

    2015-01-01

    基于人体试验的实际应用及伦理方面的考虑,合适的动物模型对于肿瘤药物研发至关重要。制药公司和研究机构在肿瘤治疗新药的开发过程中消耗大量资源,最佳动物体内模型的选择可以改进或缩短研发进程。在技术复杂性方面,肿瘤遗传工程小鼠模型( GEMM)已逐步完善,并且GEMM能够准确重建人类肿瘤的同源发生,为加快肿瘤药物的开发提供机遇。本文主要综合比较预测肿瘤药物临床试验效果的不同类型动物模型,探讨其优劣,并对体内模型的评估方法及与临床转化等进行简述,为肿瘤药物临床前试验提供参考。%Due to practical and ethical concerns associated with human experiments, animal models have been essential in cancer research.Vast resources are expended during the development of new cancer therapeutics, and selection of optimal in vivo models should improve this process.Genetically engineered mouse models ( GEMM) of cancer have progressively improved in technical sophistication and, accurately recapitulating the human cognate condition, have provided opportunities to accelerate the development of cancer drugs.In this article we consider the different types of animal models used for predicting the results of clinical trials of cancer drugs, and discuss the strengths and weaknesses of each in this regard.In addition, the methods of predicting in vivo models and clinical translation are discussed.

  1. 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.

  2. Animal models of anorexia and cachexia

    Science.gov (United States)

    DeBoer, Mark Daniel

    2009-01-01

    Background Cachexia is a devastating syndrome of body wasting that worsens quality of life and survival for patients suffering from diseases such as cancer, chronic kidney disease and chronic heart failure. Successful treatments have been elusive in humans, leaving a clear need for the development of new treatment compounds. Animal models of cachexia are able to recapitulate the clinical findings from human disease and have provided a much-needed means of testing the efficacy of prospective therapies. Objective This review focuses on animal models of cachexia caused by cancer, chronic heart failure and chronic kidney disease, including the features of these models, their implementation, and commonly-followed outcome measures. Conclusion Given a dire clinical need for effective treatments of cachexia, animal models will continue a vital role in assessing the efficacy and safety of potential treatments prior to testing in humans. Also important in the future will be the use of animal models to assess the durability of effect from anti-cachexia treatments and their effect on prognosis of the underlying disease states. PMID:20160874

  3. Animal models for studying penile hemodynamics

    Institute of Scientific and Technical Information of China (English)

    HiroyaMizusawa; OsamuIshizuka

    2002-01-01

    Animal models for the study of erectile function monitoring the changes in intracavernous pressure(ICP)during penile erection was reviewed.The development of new modwls using small commercially-available experimen-tal animals,rats and mice,in the last edcade facilitated in vivo investigation of erectile physiology.The technique enabled to evaluate even subtle erectile responses by analyzing ICPand systemic blood pressure,Moreover,the method has been well improved and studies using conscious animal models without the influence of any drug or anesthesia are more appropriate in exploring the precise physiological and pharmacological mechanisms in erection.Also,more natural and physiological sexual arousal instead of electrical or pharmacological stimulation is desirable in most of the studies.This article reviewed the development of ICPstudies in rats and mice.

  4. Prediction of human clearance based on animal data and molecular properties.

    Science.gov (United States)

    Huang, Wenkang; Geng, Lv; Deng, Rong; Lu, Shaoyong; Ma, Guangli; Yu, Jianxiu; Zhang, Jian; Liu, Wei; Hou, Tingjun; Lu, Xuefeng

    2015-11-01

    Human clearance is often predicted prior to clinical study from in vivo preclinical data by virtue of interspecies allometric scaling methods. The aims of this study were to determine the important molecular descriptors for the extrapolation of animal data to human clearance and further to build a model to predict human clearance by combination of animal data and the selected molecular descriptors. These important molecular descriptors selected by genetic algorithm (GA) were from five classes: quantum mechanical, shadow indices, E-state keys, molecular properties, and molecular property counts. Although the data set contained many outliers determined by the conventional Mahmood method, the variation of most outliers was reduced significantly by our final support vector machine (SVM) model. The values of cross-validated correlation coefficient and root-mean-squared error (RMSE) for leave-one-out cross-validation (LOOCV) of the final SVM model were 0.783 and 0.305, respectively. Meanwhile, the reliability and consistency of the final model were also validated by an external test set. In conclusion, the SVM model based on the molecular descriptors selected by GA and animal data achieved better prediction performance than the Mahmood method. This approach can be applied as an improved interspecies allometric scaling method in drug research and development.

  5. An animated model of reticulorumen motility.

    Science.gov (United States)

    Gookin, Jody L; Foster, Derek M; Harvey, Alice M; McWhorter, Dan

    2009-01-01

    Understanding reticulorumen motility is important to the assessment of ruminant health and optimal production, and in the recognition, diagnosis, and treatment of disease. Accordingly, the teaching of reticulorumen motility is a staple of all veterinary curricula. This teaching has historically been based on written descriptions, line drawings, or pressure tracings obtained during contraction sequences. We developed an animated model of reticulorumen motility and hypothesized that veterinary students would prefer use of the model over traditional instructional methods. First-year veterinary students were randomly allocated to one of two online learning exercises: with the animated model (Group A) or with text and line drawings (Group B) depicting reticulorumen motility. Learning was assessed with a multiple-choice quiz and feedback on the learning alternatives was obtained by survey. Seventy-four students participated in the study, including 38/42 in Group A and 36/36 in Group B. Sixty-four out of 72 students (89%) responded that they would prefer use of the animated model if only one of the two learning methods was available. A majority of students agreed or strongly agreed that the animated model was easy to understand and improved their knowledge and appreciation of the importance of reticulorumen motility, and would recommend the model to other veterinary students. Interestingly, students in Group B achieved higher scores on examination than students in Group A. This could be speculatively attributed to the inclusion of an itemized list of contraction sequences in the text provided to Group B and failure of Group A students to read the text associated with the animations.

  6. 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 differ

  7. Animal models of trauma-induced coagulopathy.

    Science.gov (United States)

    Frith, Daniel; Cohen, Mitchell J; Brohi, Karim

    2012-05-01

    Resurgent study of trauma-induced coagulopathy (TIC) has delivered considerable improvements in survival after injury. Robust, valid and clinically relevant experimental models of TIC are essential to support the evolution of our knowledge and management of this condition. The aims of this study were to identify and analyze contemporary animal models of TIC with regard to their ability to accurately characterize known mechanisms of coagulopathy and/or to test the efficacy of therapeutic agents. A literature review was performed. Structured search of the indexed online database MEDLINE/PubMed in July 2010 identified 43 relevant articles containing 23 distinct animal models of TIC. The main aim of 26 studies was to test a therapeutic and the other 17 were conducted to investigate pathophysiology. A preponderance of porcine models was identified. Three new models demonstrating an endogenous acute traumatic coagulopathy (ATC) have offered new insights into the pathophysiology of TIC. Independent or combined effects of induced hypothermia and metabolic acidosis have been extensively evaluated. Recently, a pig model of TIC has been developed that features all major etiologies of TIC, although not in correct chronological order. This review identifies a general lack of experimental research to keep pace with clinical developments. Tissue injury and hemorrhagic shock are fundamental initiating events that prime the hemostatic system for subsequent iatrogenic insults. New animal models utilizing a variety of species that accurately simulate the natural clinical trajectory of trauma are urgently needed.

  8. The modelling cycle for collective animal behaviour.

    Science.gov (United States)

    Sumpter, David J T; Mann, Richard P; Perna, Andrea

    2012-12-06

    Collective animal behaviour is the study of how interactions between individuals produce group level patterns, and why these interactions have evolved. This study has proved itself uniquely interdisciplinary, involving physicists, mathematicians, engineers as well as biologists. Almost all experimental work in this area is related directly or indirectly to mathematical models, with regular movement back and forth between models, experimental data and statistical fitting. In this paper, we describe how the modelling cycle works in the study of collective animal behaviour. We classify studies as addressing questions at different levels or linking different levels, i.e. as local, local to global, global to local or global. We also describe three distinct approaches-theory-driven, data-driven and model selection-to these questions. We show, with reference to our own research on species across different taxa, how we move between these different levels of description and how these various approaches can be applied to link levels together.

  9. Animal models of age related macular degeneration

    OpenAIRE

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

    2012-01-01

    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 ...

  10. Animal models of psoriasis and pustular psoriasis.

    Science.gov (United States)

    Mizutani, Hitoshi; Yamanaka, Keiichi; Konishi, Hiroshi; Murakami, Takaaki

    2003-04-01

    Investigation of psoriasis and pustular psoriasis is presently hampered by the lack of appropriate animal models. So far, more than ten models have been developed in mice by spontaneous gene mutations and by gene manipulation. However, none of them has satisfactorily reproduced the clinicopathological and immunopathological phenotypes of these diseases. Xenotransplantation techniques have been used for designing models of psoriasis vulgaris, in which CD4(+) T cells have been shown to play an important role. An ideal model for pustular psoriasis should have an immunological background and fulfill the diagnostic criteria of psoriasis.

  11. Large genetic animal models of Huntington's Disease.

    Science.gov (United States)

    Morton, A Jennifer; Howland, David S

    2013-01-01

    The dominant nature of the Huntington's disease gene mutation has allowed genetic models to be developed in multiple species, with the mutation causing an abnormal neurological phenotype in all animals in which it is expressed. Many different rodent models have been generated. The most widely used of these, the transgenic R6/2 mouse, carries the mutation in a fragment of the human huntingtin gene and has a rapidly progressive and fatal neurological phenotype with many relevant pathological changes. Nevertheless, their rapid decline has been frequently questioned in the context of a disease that takes years to manifest in humans, and strenuous efforts have been made to make rodent models that are genetically more 'relevant' to the human condition, including full length huntingtin gene transgenic and knock-in mice. While there is no doubt that we have learned, and continue to learn much from rodent models, their usefulness is limited by two species constraints. First, the brains of rodents differ significantly from humans in both their small size and their neuroanatomical organization. Second, rodents have much shorter lifespans than humans. Here, we review new approaches taken to these challenges in the development of models of Huntington's disease in large brained, long-lived animals. We discuss the need for such models, and how they might be used to fill specific niches in preclinical Huntington's disease research, particularly in testing gene-based therapeutics. We discuss the advantages and disadvantages of animals in which the prodromal period of disease extends over a long time span. We suggest that there is considerable 'value added' for large animal models in preclinical Huntington's disease research.

  12. [Progress in predicting animal feed intake of plant secondary compounds by spectral analysis].

    Science.gov (United States)

    Wang, Yuan-Su; Hong, Fu-Zeng; Wang, Kun

    2007-09-01

    Study on feed intake of phytophagic animals is a key issue in promoting animal productivity and conservation of wild life. However, how to accurately predict the feed intake of grazing animal and wild life is a long remaining problem. Under the mechanism of co-evolution, plant produces secondary compounds such as phenolics, terpenoids and nitrogen-containing compounds to avoid or reduce animal herbivorous damage as a defensive strategy, while animal attained detoxification capacity of biotransforming and mineralizing the compounds by microbial activities and reactions such as hydrolysis and reduction. The attributes of feedstuff and the amount of a particular feed consumed by the animal affect directly the urinary excretion of secondary metabolites. Plant secondary compounds and their metabolites can be efficiently extracted, separated and structure-identified by spectroscopic analytic method. Then the feed intake of the animal can be accurately measured or predicted by the inference model of concentration-ratio that is based on the regression of correlating the secondary metabolites to the precursors in plant. Aromatic compounds, an universal occurrence in vascular plants, play an important role in predicting feed intake of ruminants. Progresses have been made all-around about the new method. Intensive studies have found that different species and developing stage of plant have varying kinds and levels of secondary compounds, and the age, gender and type of animal have different capacity of metabolizing the compounds. Increasing concentrations of the compounds in the diet led to a dose-dependent decrease in food intake best described as an exponential decay. Animals that had not previously been exposed to the compounds ate significantly more when first offered food containing the compound than on subsequent days. Advanced spectroscopic analytic method has been developed and widely applied in extraction (e. g. microwave assisted extraction and ultrasonic extraction

  13. 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...

  14. Animal models of antimuscle specific kinase myasthenia

    Science.gov (United States)

    Richman, David P.; Nishi, Kayoko; Ferns, Michael J.; Schnier, Joachim; Pytel, Peter; Maselli, Ricardo A.; Agius, Mark A.

    2014-01-01

    Antimuscle specific kinase (anti-MuSK) myasthenia (AMM) differs from antiacetylcholine receptor myasthenia gravis in exhibiting more focal muscle involvement (neck, shoulder, facial, and bulbar muscles) with wasting of the involved, primarily axial, muscles. AMM is not associated with thymic hyperplasia and responds poorly to anticholinesterase treatment. Animal models of AMM have been induced in rabbits, mice, and rats by immunization with purified xenogeneic MuSK ectodomain, and by passive transfer of large quantities of purified serum IgG from AMM patients into mice. The models have confirmed the pathogenic role of the MuSK antibodies in AMM and have demonstrated the involvement of both the presynaptic and postsynaptic components of the neuromuscular junction. The observations in this human disease and its animal models demonstrate the role of MuSK not only in the formation of this synapse but also in its maintenance. PMID:23252909

  15. Animal models for diseases of respiratory system

    Directory of Open Access Journals (Sweden)

    R. Adil

    2012-07-01

    Full Text Available Latest trends in understanding of respiratory diseases in human beings can be derived from thorough clinical studies of these diseases occurring in man, but conducting such studies in man is difficult in terms of experimental manipulation. In the last 2 decades, various types of experimental respiratory disease models has been developed and utilized by investigators, which have contributed a lot to the understanding of respiratory diseases in man, but only little investigation has been done on the naturally occurring pulmonary diseases of animals as potential models which could have added to our knowledge. There are certain selected examples of spontaneous pulmonary disease in animals that may serve as exploitable models for human chronic bronchitis, bronchiectasis, emphysema, interstitial lung disease, hypersensitivity pneumonitis, hyaline membrane disease, and bronchial asthma.

  16. Animal models of insulin resistance: A review.

    Science.gov (United States)

    Sah, Sangeeta Pilkhwal; Singh, Barinder; Choudhary, Supriti; Kumar, Anil

    2016-12-01

    Insulin resistance can be seen as a molecular and genetic mystery, with a role in the pathophysiology of type 2 diabetes mellitus. It is a basis for a number of chronic diseases like hypertension, dyslipidemia, glucose intolerance, coronary heart disease, cerebral vascular disease along with T2DM, thus the key is to cure and prevent insulin resistance. Critical perspicacity into the etiology of insulin resistance have been gained by the use of animal models where insulin action has been modulated by various transgenic and non-transgenic models which is not possible in human studies. The following review comprises the pathophysiology involved in insulin resistance, various factors causing insulin resistance, their screening and various genetic and non-genetic animal models highlighting the pathological and metabolic characteristics of each.

  17. Animal models of anxiety disorders and stress

    Directory of Open Access Journals (Sweden)

    Alline C. Campos

    2013-01-01

    Full Text Available Anxiety and stress-related disorders are severe psychiatric conditions that affect performance in daily tasks and represent a high cost to public health. The initial observation of Charles Darwin that animals and human beings share similar characteristics in the expression of emotion raise the possibility of studying the mechanisms of psychiatric disorders in other mammals (mainly rodents. The development of animal models of anxiety and stress has helped to identify the pharmacological mechanisms and potential clinical effects of several drugs. Animal models of anxiety are based on conflict situations that can generate opposite motivational states induced by approach-avoidance situations. The present review revisited the main rodent models of anxiety and stress responses used worldwide. Here we defined as “ethological” the tests that assess unlearned/unpunished responses (such as the elevated plus maze, light-dark box, and open field, whereas models that involve learned/punished responses are referred to as “conditioned operant conflict tests” (such as the Vogel conflict test. We also discussed models that involve mainly classical conditioning tests (fear conditioning. Finally, we addressed the main protocols used to induce stress responses in rodents, including psychosocial (social defeat and neonatal isolation stress, physical (restraint stress, and chronic unpredictable stress.

  18. Towards an animal model of food addiction.

    Science.gov (United States)

    de Jong, Johannes W; Vanderschuren, Louk J M J; Adan, Roger A H

    2012-01-01

    The dramatically increasing prevalence of obesity, associated with potentially life-threatening health problems, including cardiovascular diseases and type II diabetes, poses an enormous public health problem. It has been proposed that the obesity epidemic can be explained by the concept of 'food addiction'. In this review we focus on possible similarities between binge eating disorder (BED), which is highly prevalent in the obese population, and drug addiction. Indeed, both behavioral and neural similarities between addiction and BED have been demonstrated. Behavioral similarities are reflected in the overlap in DSM-IV criteria for drug addiction with the (suggested) criteria for BED and by food addiction-like behavior in animals after prolonged intermittent access to palatable food. Neural similarities include the overlap in brain regions involved in food and drug craving. Decreased dopamine D2 receptor availability in the striatum has been found in animal models of binge eating, after cocaine self-administration in animals as well as in drug addiction and obesity in humans. To further explore the neurobiological basis of food addiction, it is essential to have an animal model to test the addictive potential of palatable food. A recently developed animal model for drug addiction involves three behavioral characteristics that are based on the DSM-IV criteria: i) extremely high motivation to obtain the drug, ii) difficulty in limiting drug seeking even in periods of explicit non-availability, iii) continuation of drug-seeking despite negative consequences. Indeed, it has been shown that a subgroup of rats, after prolonged cocaine self-administration, scores positive on these three criteria. If food possesses addictive properties, then food-addicted rats should also meet these criteria while searching for and consuming food. In this review we discuss evidence from literature regarding food addiction-like behavior. We also suggest future experiments that could

  19. Animal models of epilepsy: use and limitations

    Directory of Open Access Journals (Sweden)

    Kandratavicius L

    2014-09-01

    Full Text Available Ludmyla Kandratavicius,1 Priscila Alves Balista,1 Cleiton Lopes-Aguiar,1 Rafael Naime Ruggiero,1 Eduardo Henrique Umeoka,2 Norberto Garcia-Cairasco,2 Lezio Soares Bueno-Junior,1 Joao Pereira Leite11Department of Neurosciences and Behavior, 2Department of Physiology, Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirao Preto, BrazilAbstract: Epilepsy is a chronic neurological condition characterized by recurrent seizures that affects millions of people worldwide. Comprehension of the complex mechanisms underlying epileptogenesis and seizure generation in temporal lobe epilepsy and other forms of epilepsy cannot be fully acquired in clinical studies with humans. As a result, the use of appropriate animal models is essential. Some of these models replicate the natural history of symptomatic focal epilepsy with an initial epileptogenic insult, which is followed by an apparent latent period and by a subsequent period of chronic spontaneous seizures. Seizures are a combination of electrical and behavioral events that are able to induce chemical, molecular, and anatomic alterations. In this review, we summarize the most frequently used models of chronic epilepsy and models of acute seizures induced by chemoconvulsants, traumatic brain injury, and electrical or sound stimuli. Genetic models of absence seizures and models of seizures and status epilepticus in the immature brain were also examined. Major uses and limitations were highlighted, and neuropathological, behavioral, and neurophysiological similarities and differences between the model and the human equivalent were considered. The quest for seizure mechanisms can provide insights into overall brain functions and consciousness, and animal models of epilepsy will continue to promote the progress of both epilepsy and neurophysiology research.Keywords: epilepsy, animal model, pilocarpine, kindling, neurodevelopment

  20. 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.

  1. The pain of pain: challenges of animal behavior models.

    Science.gov (United States)

    Barrett, James E

    2015-04-15

    Berend Olivier has had a long-standing interest in the utility of animal models for a wide variety of therapeutic indications. His work has spanned multiple types of models, blending ethological, or species typical and naturalistic behaviors, along with methodologies based on learned behavior. He has consistently done so, from an analytical as well as predictive perspective, and has made multiple contributions while working in both the pharmaceutical industry and within an academic institution. Although focused primarily on psychiatric disorders, Berend has conducted research in the area of pain in humans and in animals, demonstrating an expansive appreciation for the breadth, scope and significance of the science and applications of the discipline of pharmacology to these diverse areas. This review focuses on the use of animal models in pain research from the perspective of the long-standing deficiencies in the development of therapeutics in this area and from a preclinical perspective where the translational weaknesses have been quite problematic. The challenges confronting animal models of pain, however, are not unique to this area of research, as they cut across several therapeutic areas. Despite the deficiencies, failures and concerns, existing animal models of pain continue to be of widespread use and are essential to progress in pain research as well as in other areas. Although not focusing on specific animal models of pain, this paper seeks to examine general issues facing the use of these models. It does so by exploring alternative approaches which capture recent developments, which build upon principles and concepts we have learned from Berend's contributions, and which provide the prospect of helping to address the absence of novel therapeutics in this area.

  2. 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...

  3. Animal models of alcohol and drug dependence

    Directory of Open Access Journals (Sweden)

    Cleopatra S. Planeta

    2013-01-01

    Full Text Available Drug addiction has serious health and social consequences. In the last 50 years, a wide range of techniques have been developed to model specific aspects of drug-taking behaviors and have greatly contributed to the understanding of the neurobiological basis of drug abuse and addiction. In the last two decades, new models have been proposed in an attempt to capture the more genuine aspects of addiction-like behaviors in laboratory animals. The goal of the present review is to provide an overview of the preclinical procedures used to study drug abuse and dependence and describe recent progress that has been made in studying more specific aspects of addictive behavior in animals.

  4. Animal models of age related macular degeneration.

    Science.gov (United States)

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

    2012-08-01

    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.

  5. Predictive Models for Music

    OpenAIRE

    Paiement, Jean-François; Grandvalet, Yves; Bengio, Samy

    2008-01-01

    Modeling long-term dependencies in time series has proved very difficult to achieve with traditional machine learning methods. This problem occurs when considering music data. In this paper, we introduce generative models for melodies. We decompose melodic modeling into two subtasks. We first propose a rhythm model based on the distributions of distances between subsequences. Then, we define a generative model for melodies given chords and rhythms based on modeling sequences of Narmour featur...

  6. Animal Models of Varicella Zoster Virus Infection

    Directory of Open Access Journals (Sweden)

    Ilhem Messaoudi

    2013-05-01

    Full Text Available Primary infection with varicella zoster virus (VZV results in varicella (chickenpox followed by the establishment of latency in sensory ganglia. Declining T cell immunity due to aging or immune suppressive treatments can lead to VZV reactivation and the development of herpes zoster (HZ, shingles. HZ is often associated with significant morbidity and occasionally mortality in elderly and immune compromised patients. There are currently two FDA-approved vaccines for the prevention of VZV: Varivax® (for varicella and Zostavax® (for HZ. Both vaccines contain the live-attenuated Oka strain of VZV. Although highly immunogenic, a two-dose regimen is required to achieve a 99% seroconversion rate. Zostavax vaccination reduces the incidence of HZ by 51% within a 3-year period, but a significant reduction in vaccine-induced immunity is observed within the first year after vaccination. Developing more efficacious vaccines and therapeutics requires a better understanding of the host response to VZV. These studies have been hampered by the scarcity of animal models that recapitulate all aspects of VZV infections in humans. In this review, we describe different animal models of VZV infection as well as an alternative animal model that leverages the infection of Old World macaques with the highly related simian varicella virus (SVV and discuss their contributions to our understanding of pathogenesis and immunity during VZV infection.

  7. Colon preneoplastic lesions in animal models.

    Science.gov (United States)

    Suzui, Masumi; Morioka, Takamitsu; Yoshimi, Naoki

    2013-12-01

    The animal model is a powerful and fundamental tool in the field of biochemical research including toxicology, carcinogenesis, cancer therapeutics and prevention. In the carcinogenesis animal model system, numerous examples of preneoplastic lesions have been isolated and investigated from various perspectives. This may indicate that several options of endpoints to evaluate carcinogenesis effect or therapeutic outcome are presently available; however, classification of preneoplastic lesions has become complicated. For instance, these lesions include aberrant crypt foci (ACF), dysplastic ACF, flat ACF, β-catenin accumulated crypts, and mucin-depleted foci. These lesions have been induced by commonly used chemical carcinogens such as azoxymethane (AOM), 1,2-dimethylhydrazine (DMH), methylnitrosourea (MUN), or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Investigators can choose any procedures or methods to examine colonic preneoplastic lesions according to their interests and the objectives of their experiments. Based on topographical, histopathological, and biological features of colon cancer preneoplastic lesions in the animal model, we summarize and discuss the character and implications of these lesions.

  8. Animal Models of Compulsive Eating Behavior

    Directory of Open Access Journals (Sweden)

    Matteo Di Segni

    2014-10-01

    Full Text Available Eating disorders are multifactorial conditions that can involve a combination of genetic, metabolic, environmental, and behavioral factors. Studies in humans and laboratory animals show that eating can also be regulated by factors unrelated to metabolic control. Several studies suggest a link between stress, access to highly palatable food, and eating disorders. Eating “comfort foods” in response to a negative emotional state, for example, suggests that some individuals overeat to self-medicate. Clinical data suggest that some individuals may develop addiction-like behaviors from consuming palatable foods. Based on this observation, “food addiction” has emerged as an area of intense scientific research. A growing body of evidence suggests that some aspects of food addiction, such as compulsive eating behavior, can be modeled in animals. Moreover, several areas of the brain, including various neurotransmitter systems, are involved in the reinforcement effects of both food and drugs, suggesting that natural and pharmacological stimuli activate similar neural systems. In addition, several recent studies have identified a putative connection between neural circuits activated in the seeking and intake of both palatable food and drugs. The development of well-characterized animal models will increase our understanding of the etiological factors of food addiction and will help identify the neural substrates involved in eating disorders such as compulsive overeating. Such models will facilitate the development and validation of targeted pharmacological therapies.

  9. Animal Models Utilized in HTLV-1 Research.

    Science.gov (United States)

    Panfil, Amanda R; Al-Saleem, Jacob J; Green, Patrick L

    2013-01-01

    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.

  10. Physically based modeling and animation of tornado

    Institute of Scientific and Technical Information of China (English)

    LIU Shi-guang; WANG Zhang-ye; GONG Zheng; CHEN Fei-fei; PENG Qun-sheng

    2006-01-01

    Realistic modeling and rendering of dynamic tornado scene is recognized as a challenging task for researchers of computer graphics. In this paper a new physically based method for simulating and animating tornado scene is presented. We first propose a Two-Fluid model based on the physical theory of tornado, then we simulate the flow of tornado and its interaction with surrounding objects such as debris, etc. Taking the scattering and absorption of light by the participating media into account, the illumination effects of the tornado scene can be generated realistically. With the support of graphics hardware, various kinds of dynamic tornado scenes can be rendered at interactive rates.

  11. Animal models of addiction: fat and sugar.

    Science.gov (United States)

    Morgan, Drake; Sizemore, Glen M

    2011-01-01

    The concept of "food addiction" is gaining acceptance among the scientific community, and much is known about the influence of various components of food (e.g. high-fat, sugar, carbohydrate, salt) on behavior and physiology. Most of the studies to date have studied these consequences following relatively long-term diet manipulations and/or relatively free access to the food of interest. It is suggested that these types of studies are primarily tapping into the energy regulation and homeostatic processes that govern food intake and consumption. More recently, the overlap between the neurobiology of "reward-related" or hedonic effects of food ingestion and other reinforcers such as drugs of abuse has been highlighted, contributing to the notion that "food addiction" exists and that various components of food may be the substance of abuse. Based on preclinical animal models of drug addiction, a new direction for this field is using self-administration procedures and identifying an addiction-like behavioral phenotype in animals following various environmental, genetic, pharmacological, and neurobiological manipulations. Here we provide examples from this research area, with a focus on fat and sugar self-administration, and how the sophisticated animal models of drug addiction can be used to study the determinants and consequences of food addiction.

  12. Zephyr - the prediction models

    DEFF Research Database (Denmark)

    Nielsen, Torben Skov; Madsen, Henrik; Nielsen, Henrik Aalborg

    2001-01-01

    This paper briefly describes new models and methods for predicationg the wind power output from wind farms. The system is being developed in a project which has the research organization Risø and the department of Informatics and Mathematical Modelling (IMM) as the modelling team and all the Dani...

  13. Plausible cloth animation using dynamic bending model

    Institute of Scientific and Technical Information of China (English)

    Chuan Zhou; Xiaogang Jin; Charlie C.L. Wang; Jieqing Feng

    2008-01-01

    Simulating the mechanical behavior of a cloth is a very challenging and important problem in computer animation. The models of bending in most existing cloth simulation approaches are taking the assumption that the cloth is little deformed from a plate shape.Therefore, based on the thin-plate theory, these bending models do not consider the condition that the current shape of the cloth under large deformations cannot be regarded as the approximation to that before deformation, which leads to an unreal static bending. [This paper introduces a dynamic bending model which is appropriate to describe large out-plane deformations such as cloth buckling and bending, and develops a compact implementation of the new model on spring-mass systems. Experimental results show that wrinkles and folds generated using this technique in cloth simulation, can appear and vanish in a more natural way than other approaches.

  14. 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....... The discussion was divided into five areas: (1) status of commonly used rodent models of diabetes, (2) nerve structure, (3) electrophysiological assessments of nerve function, (4) behavioral assessments of nerve function, and (5) the role of biomarkers in disease phenotyping. Participants discussed the current...

  15. Animal models of anxiety: an ethological perspective

    Directory of Open Access Journals (Sweden)

    Rodgers R.J.

    1997-01-01

    Full Text Available In the field of anxiety research, animal models are used as screening tools in the search for compounds with therapeutic potential and as simulations for research on mechanisms underlying emotional behaviour. However, a solely pharmacological approach to the validation of such tests has resulted in distinct problems with their applicability to systems other than those involving the benzodiazepine/GABAA receptor complex. In this context, recent developments in our understanding of mammalian defensive behaviour have not only prompted the development of new models but also attempts to refine existing ones. The present review focuses on the application of ethological techniques to one of the most widely used animal models of anxiety, the elevated plus-maze paradigm. This fresh approach to an established test has revealed a hitherto unrecognized multidimensionality to plus-maze behaviour and, as it yields comprehensive behavioural profiles, has many advantages over conventional methodology. This assertion is supported by reference to recent work on the effects of diverse manipulations including psychosocial stress, benzodiazepines, GABA receptor ligands, neurosteroids, 5-HT1A receptor ligands, and panicolytic/panicogenic agents. On the basis of this review, it is suggested that other models of anxiety may well benefit from greater attention to behavioural detail

  16. Domestic animals as models for biomedical research.

    Science.gov (United States)

    Andersson, Leif

    2016-01-01

    Domestic animals are unique models for biomedical research due to their long history (thousands of years) of strong phenotypic selection. This process has enriched for novel mutations that have contributed to phenotype evolution in domestic animals. The characterization of such mutations provides insights in gene function and biological mechanisms. This review summarizes genetic dissection of about 50 genetic variants affecting pigmentation, behaviour, metabolic regulation, and the pattern of locomotion. The variants are controlled by mutations in about 30 different genes, and for 10 of these our group was the first to report an association between the gene and a phenotype. Almost half of the reported mutations occur in non-coding sequences, suggesting that this is the most common type of polymorphism underlying phenotypic variation since this is a biased list where the proportion of coding mutations are inflated as they are easier to find. The review documents that structural changes (duplications, deletions, and inversions) have contributed significantly to the evolution of phenotypic diversity in domestic animals. Finally, we describe five examples of evolution of alleles, which means that alleles have evolved by the accumulation of several consecutive mutations affecting the function of the same gene.

  17. Animal models of glucocorticoid-induced glaucoma.

    Science.gov (United States)

    Overby, Darryl R; Clark, Abbot F

    2015-12-01

    Glucocorticoid (GC) therapy is widely used to treat a variety of inflammatory diseases and conditions. While unmatched in their anti-inflammatory and immunosuppressive activities, GC therapy is often associated with the significant ocular side effect of GC-induced ocular hypertension (OHT) and iatrogenic open-angle glaucoma. Investigators have generated GC-induced OHT and glaucoma in at least 8 different species besides man. These models mimic many features of this condition in man and provide morphologic and molecular insights into the pathogenesis of GC-OHT. In addition, there are many clinical, morphological, and molecular similarities between GC-induced glaucoma and primary open-angle glaucoma (POAG), making animals models of GC-induced OHT and glaucoma attractive models in which to study specific aspects of POAG.

  18. Animal models of premature and retarded ejaculation.

    Science.gov (United States)

    Waldinger, Marcel D; Olivier, Berend

    2005-06-01

    Most of our current understanding of the neurobiology of sexual behavior and ejaculatory function has been derived from animal studies using rats with normal sexual behaviour. However, none of these proposed models adequately represents human ejaculatory disorders. Based on the "ejaculation distribution theory", which postulates that the intravaginal ejaculation latency time in men is represented by a biological continuum, we have developed an animal model for the research of premature and delayed ejaculation. In this model, a large number of male Wistar rats are investigated during 4-6 weekly sexual behavioural tests. Based on the number of ejaculations during 30 min tests, rapid and sluggish ejaculating rats are distinguished, each representing approximately 10% at both ends of a Gaussian distribution. Together with other parameters, such as ejaculation latency time, these rats at either side of the spectrum resemble men with premature and delayed ejaculation, respectively. Comparable to the human situation, in a normal population of rats, endophenotypes exist with regard to basal sexual (ejaculatory) performance.

  19. Macrophages and Uveitis in Experimental Animal Models

    Directory of Open Access Journals (Sweden)

    Salvador Mérida

    2015-01-01

    Full Text Available Resident and infiltrated macrophages play relevant roles in uveitis as effectors of innate immunity and inductors of acquired immunity. They are major effectors of tissue damage in uveitis and are also considered to be potent antigen-presenting cells. In the last few years, experimental animal models of uveitis have enabled us to enhance our understanding of the leading role of macrophages in eye inflammation processes, including macrophage polarization in experimental autoimmune uveoretinitis and the major role of Toll-like receptor 4 in endotoxin-induced uveitis. This improved knowledge should guide advantageous iterative research to establish mechanisms and possible therapeutic targets for human uveitis resolution.

  20. 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...... the disease mechanism and testing various therapeutic approaches and discuss the relevance of these advances for human ALS. The identification of the causative mutation linking the wobbler mutation to a vesicle transport factor and the research focussed on the cellular basis and the therapeutic treatment...

  1. Peripheral biomarkers in animal models of major depressive disorder.

    Science.gov (United States)

    Carboni, Lucia

    2013-01-01

    Investigations of preclinical biomarkers for major depressive disorder (MDD) encompass the quantification of proteins, peptides, mRNAs, or small molecules in blood or urine of animal models. Most studies aim at characterising the animal model by including the assessment of analytes or hormones affected in depressive patients. The ultimate objective is to validate the model to better understand the neurobiological basis of MDD. Stress hormones or inflammation-related analytes associated with MDD are frequently measured. In contrast, other investigators evaluate peripheral analytes in preclinical models to translate the results in clinical settings afterwards. Large-scale, hypothesis-free studies are performed in MDD models to identify candidate biomarkers. Other studies wish to propose new targets for drug discovery. Animal models endowed with predictive validity are investigated, and the assessment of peripheral analytes, such as stress hormones or immune molecules, is comprised to increase the confidence in the target. Finally, since the mechanism of action of antidepressants is incompletely understood, studies investigating molecular alterations associated with antidepressant treatment may include peripheral analyte levels. In conclusion, preclinical biomarker studies aid the identification of new candidate analytes to be tested in clinical trials. They also increase our understanding of MDD pathophysiology and help to identify new pharmacological targets.

  2. Confidence scores for prediction models

    DEFF Research Database (Denmark)

    Gerds, Thomas Alexander; van de Wiel, MA

    2011-01-01

    modelling strategy is applied to different training sets. For each modelling strategy we estimate a confidence score based on the same repeated bootstraps. A new decomposition of the expected Brier score is obtained, as well as the estimates of population average confidence scores. The latter can be used...... to distinguish rival prediction models with similar prediction performances. Furthermore, on the subject level a confidence score may provide useful supplementary information for new patients who want to base a medical decision on predicted risk. The ideas are illustrated and discussed using data from cancer...

  3. Modelling, controlling, predicting blackouts

    CERN Document Server

    Wang, Chengwei; Baptista, Murilo S

    2016-01-01

    The electric power system is one of the cornerstones of modern society. One of its most serious malfunctions is the blackout, a catastrophic event that may disrupt a substantial portion of the system, playing havoc to human life and causing great economic losses. Thus, understanding the mechanisms leading to blackouts and creating a reliable and resilient power grid has been a major issue, attracting the attention of scientists, engineers and stakeholders. In this paper, we study the blackout problem in power grids by considering a practical phase-oscillator model. This model allows one to simultaneously consider different types of power sources (e.g., traditional AC power plants and renewable power sources connected by DC/AC inverters) and different types of loads (e.g., consumers connected to distribution networks and consumers directly connected to power plants). We propose two new control strategies based on our model, one for traditional power grids, and another one for smart grids. The control strategie...

  4. Melanoma Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing melanoma cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  5. Teaching Neurophysiology, Neuropharmacology, and Experimental Design Using Animal Models of Psychiatric and Neurological Disorders

    Science.gov (United States)

    Morsink, Maarten C.; Dukers, Danny F.

    2009-01-01

    Animal models have been widely used for studying the physiology and pharmacology of psychiatric and neurological diseases. The concepts of face, construct, and predictive validity are used as indicators to estimate the extent to which the animal model mimics the disease. Currently, we used these three concepts to design a theoretical assignment to…

  6. A review of animal models used to evaluate potential allergenicity of genetically modified organisms (GMOs)

    DEFF Research Database (Denmark)

    Marsteller, Nathan; Bøgh, Katrine Lindholm; Goodman, Richard E.

    2017-01-01

    Food safety regulators request prediction of allergenicity for newly expressed proteins in genetically modified (GM) crops and in novel foods. Some have suggested using animal models to assess potential allergenicity. A variety of animal models have been used in research to evaluate sensitisation...... of genetically modified organisms (GMOs)....

  7. Mefenamic Acid Induced Nephrotoxicity: An Animal Model

    Directory of Open Access Journals (Sweden)

    Muhammad Nazrul Somchit

    2014-12-01

    Full Text Available Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs are used for the treatment of many joint disorders, inflammation and to control pain. Numerous reports have indicated that NSAIDs are capable of producing nephrotoxicity in human. Therefore, the objective of this study was to evaluate mefenamic acid, a NSAID nephrotoxicity in an animal model. Methods: Mice were dosed intraperitoneally with mefenamic acid either as a single dose (100 or 200 mg/kg in 10% Dimethyl sulfoxide/Palm oil or as single daily doses for 14 days (50 or 100 mg/kg in 10% Dimethyl sulfoxide/Palm oil per day. Venous blood samples from mice during the dosing period were taken prior to and 14 days post-dosing from cardiac puncture into heparinized vials. Plasma blood urea nitrogen (BUN and creatinine activities were measured. Results: Single dose of mefenamic acid induced mild alteration of kidney histology mainly mild glomerular necrosis and tubular atrophy. Interestingly, chronic doses induced a dose dependent glomerular necrosis, massive degeneration, inflammation and tubular atrophy. Plasma blood urea nitrogen was statistically elevated in mice treated with mefenamic acid for 14 days similar to plasma creatinine. Conclusion: Results from this study suggest that mefenamic acid as with other NSAIDs capable of producing nephrotoxicity. Therefore, the study of the exact mechanism of mefenamic acid induced severe nephrotoxicity can be done in this animal model.

  8. Animal Models of Colitis-Associated Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Manasa Kanneganti

    2011-01-01

    Full Text Available Inflammatory bowel disease (IBD is a group of chronic inflammatory disorders that affect individuals throughout life. Although the etiology and pathogenesis of IBD are largely unknown, studies with animal models of colitis indicate that dysregulation of host/microbial interactions are requisite for the development of IBD. Patients with long-standing IBD have an increased risk for developing colitis-associated cancer (CAC, especially 10 years after the initial diagnosis of colitis, although the absolute number of CAC cases is relatively small. The cancer risk seems to be not directly related to disease activity, but is related to disease duration/extent, complication of primary sclerosing cholangitis, and family history of colon cancer. In particular, high levels and continuous production of inflammatory mediators, including cytokines and chemokines, by colonic epithelial cells (CECs and immune cells in lamina propria may be strongly associated with the pathogenesis of CAC. In this article, we have summarized animal models of CAC and have reviewed the cellular and molecular mechanisms underlining the development of carcinogenic changes in CECs secondary to the chronic inflammatory conditions in the intestine. It may provide us some clues in developing a new class of therapeutic agents for the treatment of IBD and CAC in the near future.

  9. Animal Models of Parkinson's Disease: Vertebrate Genetics

    Science.gov (United States)

    Lee, Yunjong; Dawson, Valina L.; Dawson, Ted M.

    2012-01-01

    Parkinson's disease (PD) is a complex genetic disorder that is associated with environmental risk factors and aging. Vertebrate genetic models, especially mice, have aided the study of autosomal-dominant and autosomal-recessive PD. Mice are capable of showing a broad range of phenotypes and, coupled with their conserved genetic and anatomical structures, provide unparalleled molecular and pathological tools to model human disease. These models used in combination with aging and PD-associated toxins have expanded our understanding of PD pathogenesis. Attempts to refine PD animal models using conditional approaches have yielded in vivo nigrostriatal degeneration that is instructive in ordering pathogenic signaling and in developing therapeutic strategies to cure or halt the disease. Here, we provide an overview of the generation and characterization of transgenic and knockout mice used to study PD followed by a review of the molecular insights that have been gleaned from current PD mouse models. Finally, potential approaches to refine and improve current models are discussed. PMID:22960626

  10. Animal models in obesity and hypertension.

    Science.gov (United States)

    Segal-Lieberman, Gabriella; Rosenthal, Talma

    2013-06-01

    Although obesity is a well-known risk factor for hypertension, the mechanisms by which hypertension develops in obese patients are not entirely clear. Animal models of obesity and their different susceptibilities to develop hypertension have revealed some of the mechanisms linking obesity and hypertension. Adipose tissue is an endocrine organ secreting hormones that impact blood pressure, such as elements of the renin-angiotensin system whose role in hypertension have been established. In addition, the appetite-suppressing adipokine leptin activates the sympathetic nervous system via the melanocortin system, and this activation, especially in the kidney, increases blood pressure. Leptin secretion from adipocytes is increased in most models of obesity due to leptin resistance, although the resistance is often selective to the anorexigenic effect, while the susceptibility to the hypertensive effect remains intact. Understanding the pathways by which obesity contributes to increased blood pressure will hopefully pave the way to and better define the appropriate treatment for obesity-induced hypertension.

  11. Animal models for human craniofacial malformations.

    Science.gov (United States)

    Johnston, M C; Bronsky, P T

    1991-01-01

    Holoprosencephaly malformations, of which the fetal alcohol syndrome appears to be a mild form, can result from medial anterior neural plate deficiencies as demonstrated in an ethanol treated animal model. These malformations are associated with more medial positioning of the nasal placodes and resulting underdevelopment or absence of the medial nasal prominences (MNPs) and their derivatives. Malformations seen in the human retinoic acid syndrome (RAS) can be produced by administration of the drug 13-cis-retinoic acid in animals. Primary effects on neural crest cells account for most of these RAS malformations. Many of the malformations seen in the RAS are similar to those of hemifacial microsomia, suggesting similar neural crest involvement. Excessive cell death, apparently limited to trigeminal ganglion neuroblasts of placodal origin, follows 13-cis retinoic acid administration at the time of ganglion formation and leads to malformations virtually identical to those of the Treacher Collins syndrome (TCS). Secondary effects on neural crest cells in the area of the ganglion appear to be responsible for the TCS malformations. Malformations of the DiGeorge Syndrome are similar to those of the RAS and can be produced in mice by ethanol administration or by "knocking out" a homeobox gene (box 1.5). Human and animal studies indicate that cleft lips of multifactorial etiology may be generically susceptible because of small MNP)s or other MNP developmental alterations, such as those found in A/J mice, that make prominence contact more difficult. Experimental maternal hypoxia in mice indicates that cigarette smoking may increase the incidence of cleft lip by interfering with morphogenetic movements. Other human cleft lips may result from the action of a single major gene coding for TGF-alpha variants. A study with mouse palatal shelves in culture and other information suggest that a fusion problem may be involved.

  12. ANIMAL MODELS: A REVIEW FROM THREE TESTS USED IN ANXIETY

    Directory of Open Access Journals (Sweden)

    Manuel Eduardo Góngora

    2011-12-01

    Full Text Available The aim of this paper is to present a review of commonly used animal models tostudy anxiety, looking to make a presentation of three instruments used in thelaboratory. It describes the importance of using animal models for understandinghuman behavior; there are two groups of animal models and the most representativetests for each of these.

  13. Animal models for prenatal gene therapy: choosing the right model.

    Science.gov (United States)

    Mehta, Vedanta; Peebles, Donald; David, Anna L

    2012-01-01

    Testing in animal models is an essential requirement during development of prenatal gene therapy for -clinical application. Some information can be derived from cell lines or cultured fetal cells, such as the efficiency of gene transfer and the vector dose that might be required. Fetal tissues can also be maintained in culture for short periods of time and transduced ex vivo. Ultimately, however, the use of animals is unavoidable since in vivo experiments allow the length and level of transgene expression to be measured, and provide an assessment of the effect of the delivery procedure and the gene therapy on fetal and neonatal development. The choice of animal model is determined by the nature of the disease and characteristics of the animal, such as its size, lifespan, and immunology, the number of fetuses and their development, parturition, and the length of gestation and the placentation. The availability of a disease model is also critical. In this chapter, we discuss the various animal models that can be used and consider how their characteristics can affect the results obtained. The projection to human application and the regulatory hurdles are also presented.

  14. Limitations and possibilities of animal models for human allergenic risk evaluation

    DEFF Research Database (Denmark)

    Madsen, Charlotte Bernhard; Kroghsbo, Stine; Bøgh, Katrine Lindholm

    2012-01-01

    evaluation. One of the pitfalls may be the premise that an animal model needs to mimic the disease. Chemical contact sensitizers may be predicted in an animal test, the Local Lymph Node Assay (LLNA). This assay is based on detailed mechanistic knowledge of contact sensitization including knowledge on dose......-response relationship. The outcome of the test is sensitization measured as cell proliferation in the regional lymph node. Animal models in food allergy can be used to increase our understanding of food allergens and food allergy sensitization e.g. the influence of digestion or processing or to compare closely related......’t know under what circumstances oral tolerance develops. With all these unanswered questions, it is a big challenge to design an animal model that, with relatively few animals, is able to predict if a food allergen is not only a potential allergen but also predict its potency, a prerequisite for risk...

  15. 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. PMID:28298815

  16. 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.

  17. Animal models for HCV and HBV studies

    Directory of Open Access Journals (Sweden)

    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

  18. Prediction models in complex terrain

    DEFF Research Database (Denmark)

    Marti, I.; Nielsen, Torben Skov; Madsen, Henrik

    2001-01-01

    The objective of the work is to investigatethe performance of HIRLAM in complex terrain when used as input to energy production forecasting models, and to develop a statistical model to adapt HIRLAM prediction to the wind farm. The features of the terrain, specially the topography, influence...

  19. Prediction of skin sensitizers using alternative methods to animal experimentation.

    Science.gov (United States)

    Johansson, Henrik; Lindstedt, Malin

    2014-07-01

    Regulatory frameworks within the European Union demand that chemical substances are investigated for their ability to induce sensitization, an adverse health effect caused by the human immune system in response to chemical exposure. A recent ban on the use of animal tests within the cosmetics industry has led to an urgent need for alternative animal-free test methods that can be used for assessment of chemical sensitizers. To date, no such alternative assay has yet completed formal validation. However, a number of assays are in development and the understanding of the biological mechanisms of chemical sensitization has greatly increased during the last decade. In this MiniReview, we aim to summarize and give our view on the recent progress of method development for alternative assessment of chemical sensitizers. We propose that integrated testing strategies should comprise complementary assays, providing measurements of a wide range of mechanistic events, to perform well-educated risk assessments based on weight of evidence.

  20. 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.

  1. Pain assessment in animal models: do we need further studies?

    Directory of Open Access Journals (Sweden)

    Gigliuto C

    2014-05-01

    Full Text Available Carmelo Gigliuto,1 Manuela De Gregori,2 Valentina Malafoglia,3 William Raffaeli,3 Christian Compagnone,4 Livia Visai,5,6 Paola Petrini,7 Maria Antonietta Avanzini,9 Carolina Muscoli,8 Jacopo Viganò,11 Francesco Calabrese,11 Tommaso Dominioni,11 Massimo Allegri,2,10 Lorenzo Cobianchi111Anaesthesia and Intensive Care, University of Pavia, Pavia, 2Pain Therapy Service, Fondazione IRCCS Policlinico San Matteo, Pavia, 3ISAL Foundation, Institute for Research on Pain, Torre Pedrera, Rimini, 4Department of Anaesthesia, Intensive Care and Pain Therapy, Azienda Ospedaliera Universitaria Parma, University of Parma, Parma, 5Department of Molecular Medicine, Center for Tissue Engineering (CIT, INSTM UdR of Pavia, University of Pavia, Pavia, 6Department of Occupational Medicine, Ergonomy and Disability, Laboratory of Nanotechnology, Salvatore Maugeri Foundation, IRCCS, Veruno, 7Dipartimento di Chimica, Materiali e Ingegneria Chimica 'G Natta' and Unità di Ricerca Consorzio INSTM, Politecnico di Milano, Milan, 8Department of Health Science, University Magna Grecia of Catanzaro and Centro del Farmaco, IRCCS San Raffaele Pisana, Roma, 9Laboratory of Transplant Immunology/Cell Factory, Fondazione IRCCS Policlinico "San Matteo", Pavia, 10Department of Clinical, Surgical, Diagnostic and Paediatric Sciences, University of Pavia, Pavia, 11University of Pavia, Department of Surgical, Clinical, Paediatric and Diagnostic Science, General Surgery 1, IRCCS Fondazione Policlinico San Matteo, Pavia, ItalyAbstract: In the last two decades, animal models have become important tools in understanding and treating pain, and in predicting analgesic efficacy. Although rodent models retain a dominant role in the study of pain mechanisms, large animal models may predict human biology and pharmacology in certain pain conditions more accurately. Taking into consideration the anatomical and physiological characteristics common to man and pigs (median body size, digestive apparatus

  2. 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.

  3. Noninvasive Assessment of Tumor Cell Proliferation in Animal Models

    Directory of Open Access Journals (Sweden)

    Matthias Edinger

    1999-10-01

    Full Text Available Revealing the mechanisms of neoplastic disease and enhancing our ability to intervene in these processes requires an increased understanding of cellular and molecular changes as they occur in intact living animal models. We have begun to address these needs by developing a method of labeling tumor cells through constitutive expression of an optical reporter gene, noninvasively monitoring cellular proliferation in vivo using a sensitive photon detection system. A stable line of HeLa cells that expressed a modified firefly luciferase gene was generated, proliferation of these cells in irradiated severe combined immunodeficiency (SCID mice was monitored. Tumor cells were introduced into animals via subcutaneous, intraperitoneal and intravenous inoculation and whole body images, that revealed tumor location and growth kinetics, were obtained. The number of photons that were emitted from the labeled tumor cells and transmitted through murine tissues was sufficient to detect 1×103 cells in the peritoneal cavity, 1×104 cells at subcutaneous sites and 1×106 circulating cells immediately following injection. The kinetics of cell proliferation, as measured by photon emission, was exponential in the peritoneal cavity and at subcutaneous sites. Intravenous inoculation resulted in detectable colonies of tumor cells in animals receiving more than 1×103 cells. Our demonstrated ability to detect small numbers of tumor cells in living animals noninvasively suggests that therapies designed to treat minimal disease states, as occur early in the disease course and after elimination of the tumor mass, may be monitored using this approach. Moreover, it may be possible to monitor micrometastases and evaluate the molecular steps in the metastatic process. Spatiotemporal analyses of neoplasia will improve the predictability of animal models of human disease as study groups can be followed over time, this method will accelerate development of novel therapeutic

  4. RASopathies: unraveling mechanisms with animal models

    Directory of Open Access Journals (Sweden)

    Granton A. Jindal

    2015-08-01

    Full Text Available RASopathies are developmental disorders caused by germline mutations in the Ras-MAPK pathway, and are characterized by a broad spectrum of functional and morphological abnormalities. The high incidence of these disorders (∼1/1000 births motivates the development of systematic approaches for their efficient diagnosis and potential treatment. Recent advances in genome sequencing have greatly facilitated the genotyping and discovery of mutations in affected individuals, but establishing the causal relationships between molecules and disease phenotypes is non-trivial and presents both technical and conceptual challenges. Here, we discuss how these challenges could be addressed using genetically modified model organisms that have been instrumental in delineating the Ras-MAPK pathway and its roles during development. Focusing on studies in mice, zebrafish and Drosophila, we provide an up-to-date review of animal models of RASopathies at the molecular and functional level. We also discuss how increasingly sophisticated techniques of genetic engineering can be used to rigorously connect changes in specific components of the Ras-MAPK pathway with observed functional and morphological phenotypes. Establishing these connections is essential for advancing our understanding of RASopathies and for devising rational strategies for their management and treatment.

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

    OpenAIRE

    Greek Ray; Pippus Annalea; Hansen Lawrence A

    2012-01-01

    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...

  6. The maternal deprivation animal model revisited.

    Science.gov (United States)

    Marco, Eva M; Llorente, Ricardo; López-Gallardo, Meritxell; Mela, Virginia; Llorente-Berzal, Álvaro; Prada, Carmen; Viveros, María-Paz

    2015-04-01

    Early life stress, in the form of MD (24h at pnd 9), interferes with brain developmental trajectories modifying both behavioral and neurobiochemical parameters. MD has been reported to enhance neuroendocrine responses to stress, to affect emotional behavior and to impair cognitive function. More recently, changes in body weight gain, metabolic parameters and immunological responding have also been described. Present data give support to the fact that neuronal degeneration and/or astrocyte proliferation are present in specific brain regions, mainly hippocampus, prefrontal cortex and hypothalamus, which are particularly vulnerable to the effects of neonatal stress. The MD animal model arises as a valuable tool for the investigation of the brain processes occurring at the narrow time window comprised between pnd 9 and 10 that are critical for the establishment of brain circuitries critical for the regulation of behavior, metabolism and energy homeostasis. In the present review we will discuss three possible mechanisms that might be crucial for the effects of MD, namely, the rapid increase in glucocorticoids, the lack of the neonatal leptin surge, and the enhanced endocannabinoid signaling during the specific critical period of MD. A better understanding of the mechanisms underlying the detrimental consequences of MD is a concern for public health and may provide new insights into mental health prevention strategies and into novel therapeutic approaches in neuropsychiatry.

  7. Animal model of Mycoplasma fermentans respiratory infection

    Directory of Open Access Journals (Sweden)

    Yáñez Antonio

    2013-01-01

    Full Text Available Abstract Background Mycoplasma fermentans has been associated with respiratory, genitourinary tract infections and rheumatoid diseases but its role as pathogen is controversial. The purpose of this study was to probe that Mycoplasma fermentans is able to produce respiratory tract infection and migrate to several organs on an experimental infection model in hamsters. One hundred and twenty six hamsters were divided in six groups (A-F of 21 hamsters each. Animals of groups A, B, C were intratracheally injected with one of the mycoplasma strains: Mycoplasma fermentans P 140 (wild strain, Mycoplasma fermentans PG 18 (type strain or Mycoplasma pneumoniae Eaton strain. Groups D, E, F were the negative, media, and sham controls. Fragments of trachea, lungs, kidney, heart, brain and spleen were cultured and used for the histopathological study. U frequency test was used to compare recovery of mycoplasmas from organs. Results Mycoplasmas were detected by culture and PCR. The three mycoplasma strains induced an interstitial pneumonia; they also migrated to several organs and persisted there for at least 50 days. Mycoplasma fermentans P 140 induced a more severe damage in lungs than Mycoplasma fermentans PG 18. Mycoplasma pneumoniae produced severe damage in lungs and renal damage. Conclusions Mycoplasma fermentans induced a respiratory tract infection and persisted in different organs for several weeks in hamsters. This finding may help to explain the ability of Mycoplasma fermentans to induce pneumonia and chronic infectious diseases in humans.

  8. Epidemiological models to support animal disease surveillance activities

    DEFF Research Database (Denmark)

    Willeberg, Preben; Paisley, Larry; Lind, Peter

    2011-01-01

    Epidemiological models have been used extensively as a tool in improving animal disease surveillance activities. A review of published papers identified three main groups of model applications: models for planning surveillance, models for evaluating the performance of surveillance systems...

  9. 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....

  10. Prediction of rumen fiber pool in cattle from dietary, fecal, and animal variables.

    Science.gov (United States)

    Huhtanen, P; Detmann, E; Krizsan, S J

    2016-07-01

    Feed intake control in ruminants is based on the integration of physical constraints and metabolic feedbacks. Physical constraints are related to the fill caused by the weight or volume of digesta in the reticulo-rumen. The amount of neutral detergent fiber (NDF) in the rumen (RNDF) may be used as an indicator of rumen fill. The objective of this study was to develop equations predicting RNDF from diet and animal characteristics using a meta-analysis technique. A treatment mean data set (n=314) was obtained from 84 studies, in which rumen pool size and diet digestibility were determined in lactating cows (n=231) or growing cattle (n=83). The data were analyzed using linear and nonlinear mixed models. Intake, rumen pool size, and fecal output of NDF were scaled to body weight (BW)(1.0). Due to the heterogeneous nature of dietary NDF, predictions of RNDF based on NDF intake were not precise. Predictions were markedly improved by dividing NDF into potentially digestible and indigestible fractions, because rumen turnover time of indigestible NDF was 2.7 times longer than that of potentially digestible NDF. At equal NDF intake, RNDF was negatively associated with dietary crude protein concentration and positively with the proportion of concentrate in the diet. Models based on fecal NDF output generally performed better than those based on NDF intake, probably because the effects of intrinsic characteristics of dietary cell walls and associative effects of dietary components collectively influence fecal NDF output. The model based on fecal NDF output was improved by including dietary concentration of forage NDF in the model, reflecting slower turnover of forage NDF compared with concentrate NDF. The curvilinear relationship between fecal NDF output and RNDF could be described by a quadratic, Mitscherlich, or power function equation, which performed better than the quadratic or Mitscherlich equation. In addition to fecal NDF output and dietary concentration of forage NDF

  11. Animal models to study gluten sensitivity.

    Science.gov (United States)

    Marietta, Eric V; Murray, Joseph A

    2012-07-01

    The initial development and maintenance of tolerance to dietary antigens is a complex process that, when prevented or interrupted, can lead to human disease. Understanding the mechanisms by which tolerance to specific dietary antigens is attained and maintained is crucial to our understanding of the pathogenesis of diseases related to intolerance of specific dietary antigens. Two diseases that are the result of intolerance to a dietary antigen are celiac disease (CD) and dermatitis herpetiformis (DH). Both of these diseases are dependent upon the ingestion of gluten (the protein fraction of wheat, rye, and barley) and manifest in the gastrointestinal tract and skin, respectively. These gluten-sensitive diseases are two examples of how devastating abnormal immune responses to a ubiquitous food can be. The well-recognized risk genotype for both is conferred by either of the HLA class II molecules DQ2 or DQ8. However, only a minority of individuals who carry these molecules will develop either disease. Also of interest is that the age at diagnosis can range from infancy to 70-80 years of age. This would indicate that intolerance to gluten may potentially be the result of two different phenomena. The first would be that, for various reasons, tolerance to gluten never developed in certain individuals, but that for other individuals, prior tolerance to gluten was lost at some point after childhood. Of recent interest is the concept of non-celiac gluten sensitivity, which manifests as chronic digestive or neurologic symptoms due to gluten, but through mechanisms that remain to be elucidated. This review will address how animal models of gluten-sensitive disorders have substantially contributed to a better understanding of how gluten intolerance can arise and cause disease.

  12. Animal Models of Gastrointestinal and Liver Diseases. The difficulty of animal modeling of pancreatic cancer for preclinical evaluation of therapeutics.

    Science.gov (United States)

    Logsdon, Craig D; Arumugam, Thiruvengadam; Ramachandran, Vijaya

    2015-09-01

    Pancreatic ductal adenocarcinoma (PDAC) is relatively rare but extremely lethal. Standard cytotoxic therapeutics provide little benefit. To date, newer targeted therapeutics have also not been highly successful. Often novel therapeutics that have appeared to perform well in preclinical models have failed in the clinic. Many factors contribute to these failures, but the one most often attributed is the shortcomings of the preclinical models. A plethora of animal models now exist for PDAC, including cell line xenografts, patient-derived xenografts, a wide variety of genetic mouse models, and syngeneic xenografts. These models have generated a tremendous amount of information useful for the understanding of PDAC. Yet none seems to well predict clinical outcomes of new treatments. This review will discuss how genetic instability and cellular heterogeneity make this disease so difficult to model accurately. We will also discuss the strengths and weaknesses of many of the popular models. Ultimately we will argue that there is no perfect model and that the best approach to understanding clinical performance is the use of multiple preclinical models with an understanding of their salient features.

  13. Intraperitoneal chemotherapy (IPC) for peritoneal carcinomatosis: review of animal models.

    Science.gov (United States)

    Gremonprez, Félix; Willaert, Wouter; Ceelen, Wim

    2014-02-01

    The development of suitable animal models is essential to experimental research on intraperitoneal chemotherapy (IPC). This review of the English literature (MEDLINE) presents a detailed analysis of current animal models and gives recommendations for future experimental research. Special consideration should be given to cytotoxic drug dose and concentration, tumor models, and outcome parameters.

  14. 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

  15. Institutional Animal Care and Use Committee Considerations for Animal Models of Peripheral Neuropathy

    Science.gov (United States)

    Brabb, Thea; Carbone, Larry; Snyder, Jessica; Phillips, Nona

    2014-01-01

    Peripheral neuropathy and neuropathic pain are debilitating, life-altering conditions that affect a significant proportion of the human population. Animal models, used to study basic disease mechanisms and treatment modalities, are diverse and provide many challenges for institutional animal care and use committee (IACUC) review and postapproval monitoring. Items to consider include regulatory and ethical imperatives in animal models that may be designed to study pain, the basic mechanism of neurodegeneration, and different disease processes for which neuropathic pain is a side effect. Neuropathic pain can be difficult to detect or quantify in many models, and pain management is often unsuccessful in both humans and animals, inspiring the need for more research. Design of humane endpoints requires clear communication of potential adverse outcomes and solutions. Communication with the IACUC, researchers, and veterinary staff is also key for successful postapproval monitoring of these challenging models. PMID:24615447

  16. Predictive In Vivo Models for Oncology.

    Science.gov (United States)

    Behrens, Diana; Rolff, Jana; Hoffmann, Jens

    2016-01-01

    Experimental oncology research and preclinical drug development both substantially require specific, clinically relevant in vitro and in vivo tumor models. The increasing knowledge about the heterogeneity of cancer requested a substantial restructuring of the test systems for the different stages of development. To be able to cope with the complexity of the disease, larger panels of patient-derived tumor models have to be implemented and extensively characterized. Together with individual genetically engineered tumor models and supported by core functions for expression profiling and data analysis, an integrated discovery process has been generated for predictive and personalized drug development.Improved “humanized” mouse models should help to overcome current limitations given by xenogeneic barrier between humans and mice. Establishment of a functional human immune system and a corresponding human microenvironment in laboratory animals will strongly support further research.Drug discovery, systems biology, and translational research are moving closer together to address all the new hallmarks of cancer, increase the success rate of drug development, and increase the predictive value of preclinical models.

  17. An Integrated Approach to Flexible Modelling and Animated Simulation

    Institute of Scientific and Technical Information of China (English)

    Li Shuliang; Wu Zhenye

    1994-01-01

    Based on the software support of SIMAN/CINEMA, this paper presents an integrated approach to flexible modelling and simulation with animation. The methodology provides a structured way of integrating mathematical and logical model, statistical experinentation, and statistical analysis with computer animation. Within this methodology, an animated simulation study is separated into six different activities: simulation objectives identification , system model development, simulation experiment specification, animation layout construction, real-time simulation and animation run, and output data analysis. These six activities are objectives driven, relatively independent, and integrate through software organization and simulation files. The key ideas behind this methodology are objectives orientation, modelling flexibility,simulation and animation integration, and application tailorability. Though the methodology is closely related to SIMAN/CINEMA, it can be extended to other software environments.

  18. 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.

  19. Hierarchical animal movement models for population-level inference

    Science.gov (United States)

    Hooten, Mevin B.; Buderman, Frances E.; Brost, Brian M.; Hanks, Ephraim M.; Ivans, Jacob S.

    2016-01-01

    New methods for modeling animal movement based on telemetry data are developed regularly. With advances in telemetry capabilities, animal movement models are becoming increasingly sophisticated. Despite a need for population-level inference, animal movement models are still predominantly developed for individual-level inference. Most efforts to upscale the inference to the population level are either post hoc or complicated enough that only the developer can implement the model. Hierarchical Bayesian models provide an ideal platform for the development of population-level animal movement models but can be challenging to fit due to computational limitations or extensive tuning required. We propose a two-stage procedure for fitting hierarchical animal movement models to telemetry data. The two-stage approach is statistically rigorous and allows one to fit individual-level movement models separately, then resample them using a secondary MCMC algorithm. The primary advantages of the two-stage approach are that the first stage is easily parallelizable and the second stage is completely unsupervised, allowing for an automated fitting procedure in many cases. We demonstrate the two-stage procedure with two applications of animal movement models. The first application involves a spatial point process approach to modeling telemetry data, and the second involves a more complicated continuous-time discrete-space animal movement model. We fit these models to simulated data and real telemetry data arising from a population of monitored Canada lynx in Colorado, USA.

  20. Rabbit as an animal model for experimental research

    OpenAIRE

    Manjeet Mapara; Betsy Sara Thomas; Bhat, K. M.

    2012-01-01

    Animal experimentation is carried out in consultation with the veterinary wing but it is essential that be familiar with experimental protocols of animal model to be able to design an approriate study. This is more so in place where the veterinary facilities are not easily available.Span Rabbits are commonly used as subjects for screening implant material. They have gained favour for their numerous advantages even though they should be ideally used prior to testing in a larger animal model. T...

  1. Application of Animal Modeling to Biodefense Research

    Institute of Scientific and Technical Information of China (English)

    Mark; A.; Suckow; ACLAM

    2005-01-01

    The use of biological agents to attack enemies has substantial historical precedent,and includes documented attempts tocontaminate the wells andreservoirs of enemies withcadavers and animal carcasses;and attemptstoinfect Native Ameri-cans with smallpox via contaminated blankets offered as gifts.Awareness and concern over biological weapons has in-creased greatly as the technological sophistication required to produce related agents has become more global.That theuse of biological agents as a means of aggres...

  2. The Various Roles of Animal Models in Understanding Human Development

    Science.gov (United States)

    Gottlieb, Gilbert; Lickliter, Robert

    2004-01-01

    In this article, the authors take a very conservative view of the contribution of animal models to an understanding of human development. We do not think that homologies can be readily documented with even our most closely related relatives' behavior and psychological functioning. The major contribution of animal models is their provision of food…

  3. 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.

  4. 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.

  5. Technical intelligence in animals: the kea model.

    Science.gov (United States)

    Huber, Ludwig; Gajdon, Gyula K

    2006-10-01

    The ability to act on information flexibly is one of the cornerstones of intelligent behavior. As particularly informative example, tool-oriented behavior has been investigated to determine to which extent nonhuman animals understand means-end relations, object affordances, and have specific motor skills. Even planning with foresight, goal-directed problem solving and immediate causal inference have been a focus of research. However, these cognitive abilities may not be restricted to tool-using animals but may be found also in animals that show high levels of curiosity, object exploration and manipulation, and extractive foraging behavior. The kea, a New Zealand parrot, is a particularly good example. We here review findings from laboratory experiments and field observations of keas revealing surprising cognitive capacities in the physical domain. In an experiment with captive keas, the success rate of individuals that were allowed to observe a trained conspecific was significantly higher than that of naive control subjects due to their acquisition of some functional understanding of the task through observation. In a further experiment using the string-pulling task, a well-probed test for means-end comprehension, we found the keas finding an immediate solution that could not be improved upon in nine further trials. We interpreted their performance as insightful in the sense of being sensitive of the relevant functional properties of the task and thereby producing a new adaptive response without trial-and-error learning. Together, these findings contribute to the ongoing debate on the distribution of higher cognitive skills in the animal kingdom by showing high levels of sensorimotor intelligence in animals that do not use tools. In conclusion, we suggest that the 'Technical intelligence hypothesis' (Byrne, Machiavellian intelligence II: extensions and evaluations, pp 289-211, 1997), which has been proposed to explain the origin of the ape/monkey grade-shift in

  6. Formal models in animal-metacognition research: the problem of interpreting animals' behavior.

    Science.gov (United States)

    Smith, J David; Zakrzewski, Alexandria C; Church, Barbara A

    2016-10-01

    Ongoing research explores whether animals have precursors to metacognition-that is, the capacity to monitor mental states or cognitive processes. Comparative psychologists have tested apes, monkeys, rats, pigeons, and a dolphin using perceptual, memory, foraging, and information-seeking paradigms. The consensus is that some species have a functional analog to human metacognition. Recently, though, associative modelers have used formal-mathematical models hoping to describe animals' "metacognitive" performances in associative-behaviorist ways. We evaluate these attempts to reify formal models as proof of particular explanations of animal cognition. These attempts misunderstand the content and proper application of models. They embody mistakes of scientific reasoning. They blur fundamental distinctions in understanding animal cognition. They impede theoretical development. In contrast, an energetic empirical enterprise is achieving strong success in describing the psychology underlying animals' metacognitive performances. We argue that this careful empirical work is the clear path to useful theoretical development. The issues raised here about formal modeling-in the domain of animal metacognition-potentially extend to biobehavioral research more broadly.

  7. A Spatio-temporal Model of African Animal Trypanosomosis Risk.

    Directory of Open Access Journals (Sweden)

    Ahmadou H Dicko

    Full Text Available African animal trypanosomosis (AAT is a major constraint to sustainable development of cattle farming in sub-Saharan Africa. The habitat of the tsetse fly vector is increasingly fragmented owing to demographic pressure and shifts in climate, which leads to heterogeneous risk of cyclical transmission both in space and time. In Burkina Faso and Ghana, the most important vectors are riverine species, namely Glossina palpalis gambiensis and G. tachinoides, which are more resilient to human-induced changes than the savannah and forest species. Although many authors studied the distribution of AAT risk both in space and time, spatio-temporal models allowing predictions of it are lacking.We used datasets generated by various projects, including two baseline surveys conducted in Burkina Faso and Ghana within PATTEC (Pan African Tsetse and Trypanosomosis Eradication Campaign national initiatives. We computed the entomological inoculation rate (EIR or tsetse challenge using a range of environmental data. The tsetse apparent density and their infection rate were separately estimated and subsequently combined to derive the EIR using a "one layer-one model" approach. The estimated EIR was then projected into suitable habitat. This risk index was finally validated against data on bovine trypanosomosis. It allowed a good prediction of the parasitological status (r2 = 67%, showed a positive correlation but less predictive power with serological status (r2 = 22% aggregated at the village level but was not related to the illness status (r2 = 2%.The presented spatio-temporal model provides a fine-scale picture of the dynamics of AAT risk in sub-humid areas of West Africa. The estimated EIR was high in the proximity of rivers during the dry season and more widespread during the rainy season. The present analysis is a first step in a broader framework for an efficient risk management of climate-sensitive vector-borne diseases.

  8. Commonly used animal models of non-alcoholic steatohepatitis

    Institute of Scientific and Technical Information of China (English)

    Jian-Gao Fan; Liang Qiao

    2009-01-01

    BACKGROUND: Animal models are an essential tool in non-alcoholic steatohepatitis (NASH) studies. Ideally, such models should relfect the etiology, disease progression, and the established pathology of human NASH. To date, no single animal model displays the range of histopathologic and pathophysiologic features associated with human NASH. The currently available models do not or only partially relfect the real picture of human NASH. In particular, insulin resistance and ifbrosing steatohepatitis are rarely reproduced by the currently available models. Consequently, it is necessary to establish NASH models that can best mimic the real etiology, disease progression, and pathogenesis of human NASH. DATA SOURCES: We reviewed the major currently available animal models published in the literature (PubMed) and brielfy commented on the pros and cons of these models. RESULT: Three major categories of animal models, genetic, dietary, and combination models, were reviewed and discussed. CONCLUSIONS: Animal models are not only useful in revealing the etiology of NASH, but also are important platforms for the assessment of therapeutic strategies. Currently available models do not relfect the full picture of NASH in patients. Better animal models are needed for a full understanding of human NASH and the development of efifcient therapies for this condition.

  9. PREDICT : model for prediction of survival in localized prostate cancer

    NARCIS (Netherlands)

    Kerkmeijer, Linda G W; Monninkhof, Evelyn M.; van Oort, Inge M.; van der Poel, Henk G.; de Meerleer, Gert; van Vulpen, Marco

    2016-01-01

    Purpose: Current models for prediction of prostate cancer-specific survival do not incorporate all present-day interventions. In the present study, a pre-treatment prediction model for patients with localized prostate cancer was developed.Methods: From 1989 to 2008, 3383 patients were treated with I

  10. Penile autotransplantation in rats: An animal model

    Directory of Open Access Journals (Sweden)

    Raouf M Seyam

    2013-01-01

    Conclusions: Penile autotransplantation in rats is feasible and provides the basis for evaluation of the corpora cavernosa in an allotransplantation model. Long-term urethral continuity and dorsal neurovascular bundle survival in this model is difficult to establish.

  11. Nephrectomized and hepatectomized animal models as tools in preclinical pharmacokinetics.

    Science.gov (United States)

    Vestergaard, Bill; Agersø, Henrik; Lykkesfeldt, Jens

    2013-08-01

    Early understanding of the pharmacokinetics and metabolic patterns of new drug candidates is essential for selection of optimal candidates to move further in to the drug development process. In vitro methodologies can be used to investigate metabolic patterns, but in general, they lack several aspects of the whole-body physiology. In contrast, the complexity of intact animals does not necessarily allow individual processes to be identified. Animal models lacking a major excretion organ can be used to investigate these individual metabolic processes. Animal models of nephrectomy and hepatectomy have considerable potential as tools in preclinical pharmacokinetics to assess organs of importance for drug clearance and thereby knowledge of potential metabolic processes to manipulate to improve pharmacokinetic properties of the molecules. Detailed knowledge of anatomy and surgical techniques is crucial to successfully establish the models, and a well-balanced anaesthesia and adequate monitoring of the animals are also of major importance. An obvious drawback of animal models lacking an organ is the disruption of normal homoeostasis and the induction of dramatic and ultimately mortal systemic changes in the animals. Refining of the surgical techniques and the post-operative supportive care of the animals can increase the value of these models by minimizing the systemic changes induced, and thorough validation of nephrectomy and hepatectomy models is needed before use of such models as a tool in preclinical pharmacokinetics. The present MiniReview discusses pros and cons of the available techniques associated with establishing nephrectomy and hepatectomy models.

  12. Predictive Validity of Some Common Animal Models of Bipolar Disorder Using Lithium and Lamotrigine Therapy: An Attempt towards a Battery-Based Approach for the Evaluation of Mood Stabilizers

    Science.gov (United States)

    Kumar, Manu; Tripathi, Chakra Dhar; Verma, Veena; Padhy, Biswa Mohan; Abhilash, B

    2016-01-01

    Objective To determine the predictive validity of some of the commonly employed models of mania and depression using standard drugs i.e. lithium (70 mg/kg) and lamotrigine (5 mg/kg) in male Wistar rats. Methods The depression facet of bipolar disorder was evaluated using forced swim test, tail suspension test, and chronic mild stress test. The models used to evaluate the mania facet of bipolar disorder were isolation-induced aggression test, saccharine preference test, and morphine-sensitized hyperlocomotion test. Results The immobility time was significantly (pforced swim test, while lithium caused significant (p<0.05) reduction only in the tail suspension test. Rats exposed to chronic mild stress showed the maximal increment of 1% sucrose consumption at the 3rd week of treatment in both the lithium (p<0.001) and lamotrigine (p<0.01) groups. In the isolation-induced aggression test, the aggressive behaviour of rats was significantly reduced by both lithium [approach (p<0.001), attack (p<0.01), and bite (p<0.01)] and lamotrigine [approach (p<0.001), and attack (p<0.05)]. Neither of the drugs were effective in the saccharine preference test. Only lithium was able to significantly (p<0.05) reduce the crossing parameter in morphine-sensitized rats. Conclusion Our study identifies the chronic mild stress test and isolation-induced aggression test of having the highest predictive validity in the depression and mania facets of bipolar disorder, respectively, and should be a part of a battery of tests used to evaluate novel mood stabilizers. PMID:27482245

  13. Animal Models of Diabetic Neuropathy: Progress Since 1960s

    Directory of Open Access Journals (Sweden)

    Md. Shahidul Islam

    2013-01-01

    Full Text Available Diabetic or peripheral diabetic neuropathy (PDN is one of the major complications among some other diabetic complications such as diabetic nephropathy, diabetic retinopathy, and diabetic cardiomyopathy. The use of animal models in the research of diabetes and diabetic complications is very common when rats and mice are most commonly used for many reasons. A numbers of animal models of diabetic and PDN have been developed in the last several decades such as streptozotocin-induced diabetic rat models, conventional or genetically modified or high-fat diet-fed C57BL/Ks (db/db mice models, streptozotocin-induced C57BL6/J and ddY mice models, Chinese hamster neuropathic model, rhesus monkey PDN model, spontaneously diabetic WBN/Kob rat model, L-fucose-induced neropathic rat model, partial sciatic nerve ligated rat model, nonobese diabetic (NOD mice model, spontaneously induced Ins2 Akita mice model, leptin-deficient (ob/ob mice model, Otsuka Long-Evans Tokushima Fatty (OLETF rat model, surgically-induced neuropathic model, and genetically modified Spontaneously Diabetic Torii (SDT rat model, none of which are without limitations. An animal model of diabetic or PDN should mimic the all major pathogeneses of human diabetic neuropathy. Hence, this review comparatively evaluates the animal models of diabetic and PDN which are developed since 1960s with their advantages and disadvantages to help diabetic research groups in order to more accurately choose an appropriate model to meet their specific research objectives.

  14. 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

  15. Animals

    Energy Technology Data Exchange (ETDEWEB)

    Skuterud, L.; Strand, P. [Norwegian Radiation Protection Authority (Norway); Howard, B.J. [Inst. of Terrestrial Ecology (United Kingdom)

    1997-10-01

    The radionuclides of most concern with respect to contamination of animals after a nuclear accident are radioiodine, radiocaesium and radiostrontium (ICRP 30, 1979). Of the other significant anthropogenic radionuclides likely to be released in most accidents, only small proportions of that ingested will be absorbed in an animals gut, and the main animal products, milk and meat, will not normally be contaminated to a significant extent. Animal products will mostly be contaminated as a result of ingestion of contaminated feed and possibly, but to a much lesser extent, from inhalation (for radioiodine only). Direct external contamination of animals is of little or no consequence in human food production. Radioiodine and radiostrontium are important with respect to contamination of milk; radiocaesium contaminates both milk and meat. The physical and chemical form of a radionuclide can influence its absorption in the animal gut. For example, following the Chernobyl accident radiocaesium incorporated into vegetation by root uptake was more readily absorbed than that associated with the original deposit. The transfer of radiocaesium and radiostrontium to animals will be presented both as transfer coefficients and aggregated transfer coefficients. For most animal meat products, only radiocaesium is important as other radionuclides do not significantly contaminate muscle. Farm animal products are the most important foodstuff determining radiocaesium intake by the average consumer in the Nordic countries. The major potential source of radioiodine and radiostrontium to humans is milk and milk products. Of the different species, the smaller animals have the highest transfer of radiocaesium from fodder to meat and milk. (EG). 68 refs.

  16. Using animal models to develop new treatments for tuberculosis.

    Science.gov (United States)

    Nuermberger, Eric

    2008-10-01

    Animal models have an important role in the preclinical evaluation of new antituberculosis drug candidates. Although it does not recapitulate the clinicopathological manifestations of tuberculosis in humans, the mouse remains the best characterized and most economical animal model for experimental chemotherapy. Provided care is taken to optimize the experimental conditions, the mouse has produced reliable data on the bactericidal and sterilizing activity of existing antituberculosis drugs and informed numerous clinical trials. Still, other animal models, especially the guinea pig, may have utility as confirmatory, or even alternative, models under certain circumstances. This chapter reviews some of the important considerations when selecting an animal model and presents a model for the sequential evaluation of a new compound with promising antituberculosis activity.

  17. Understanding animal fears: a comparison of the cognitive vulnerability and harm-looming models

    Directory of Open Access Journals (Sweden)

    Armfield Jason M

    2007-12-01

    Full Text Available Abstract Background The Cognitive Vulnerability Model holds that both clinical and sub-clinical manifestations of animal fears are a result of how an animal is perceived, and can be used to explain both individual differences in fear acquisition and the uneven distribution of fears in the population. This study looked at the association between fear of a number of animals and perceptions of the animals as uncontrollable, unpredictable, dangerous and disgusting. Also assessed were the perceived loomingness, prior familiarity, and negative evaluation of the animals as well as possible conditioning experiences. Methods 162 first-year University students rated their fear and perceptions of four high-fear and four low-fear animals. Results Perceptions of the animals as dangerous, disgusting and uncontrollable were significantly associated with fear of both high- and low-fear animals while perceptions of unpredictability were significantly associated with fear of high-fear animals. Conditioning experiences were unrelated to fear of any animals. In multiple regression analyses, loomingness did not account for a significant amount of the variance in fear beyond that accounted for by the cognitive vulnerability variables. However, the vulnerability variables accounted for between 20% and 51% of the variance in all animals fears beyond that accounted for by perceptions of the animals as looming. Perceptions of dangerousness, uncontrollability and unpredictability were highly predictive of the uneven distribution of animal fears. Conclusion This study provides support for the Cognitive Vulnerability Model of the etiology of specific fears and phobias and brings into question the utility of the harm-looming model in explaining animal fear.

  18. Mathematical forecasting methods for predicting lead contents in animal organs on the basis of the environmental conditions.

    Science.gov (United States)

    Czech, Tomasz; Gambuś, Florian; Wieczorek, Jerzy

    2014-12-01

    The main objective of this study was to determine and describe the lead transfer in the soil-plant-animal system in areas polluted with this metal at varying degrees, with the use of mathematical forecasting methods and data mining tools contained in the Statistica 9.0 software programme. The starting point for the forecasting models comprised results derived from an analysis of different features of soil and plants, collected from 139 locations in an area covering 100km(2) around a lead-zinc ore mining and processing plant ('Boleslaw'), at Bukowno in southern Poland. In addition, the lead content was determined in the tissues and organs of 110 small rodents (mainly mice) caught in the same area. The prediction models, elaborated with the use of classification algorithms, forecasted with high probability the class (range) of pollution in animal tissues and organs with lead, based on various soil and plant properties of the study area. However, prediction models which use multilayer neural networks made it possible to calculate the content of lead (predicted versus measured) in animal tissues and organs with an excellent correlation coefficient.

  19. Animal models for the study of arterial hypertension

    Indian Academy of Sciences (India)

    Waleska C Dornas; Marcelo E Silva

    2011-09-01

    Hypertension is one of the leading causes of disability or death due to stroke, heart attack and kidney failure. Because the etiology of essential hypertension is not known and may be multifactorial, the use of experimental animal models has provided valuable information regarding many aspects of the disease, which include etiology, pathophysiology, complications and treatment. The models of hypertension are various, and in this review, we provide a brief overview of the most widely used animal models, their features and their importance.

  20. 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

  1. The Use of Animal Models for Cancer Chemoprevention Drug Development

    OpenAIRE

    2010-01-01

    Animal models currently are used to assess the efficacy of potential chemopreventive agents, including synthetic chemicals, chemical agents obtained from natural products and natural product mixtures. The observations made in these models as well as other data are then used to prioritize agents to determine which are qualified to progress to clinical chemoprevention trials. Organ specific animal models are employed to determine which agents or classes of agents are likely to be the most effec...

  2. Social defeat as an animal model for depression.

    Science.gov (United States)

    Hollis, Fiona; Kabbaj, Mohamed

    2014-01-01

    Depression is one of the most disabling medical conditions in the world today, yet its etiologies remain unclear and current treatments are not wholly effective. Animal models are a powerful tool to investigate possible causes and treatments for human diseases. We describe an animal model of social defeat as a possible model for human depression. We discuss the paradigm, behavioral correlates to depression, and potential underlying neurobiological mechanisms with an eye toward possible future therapies.

  3. Animal Models of Human Placentation - A Review

    DEFF Research Database (Denmark)

    Carter, Anthony Michael

    2007-01-01

    , baboon and human. Non-human primates are therefore important models for understanding the dysfunction that has been linked to pre-eclampsia and fetal growth restriction. Models that are likely to be established in the wake of comparative genomics include the marmoset, tree shrew, hedgehog tenrec and nine...

  4. Animal models of gastrointestinal and liver diseases. Animal models of cystic fibrosis: gastrointestinal, pancreatic, and hepatobiliary disease and pathophysiology.

    Science.gov (United States)

    Olivier, Alicia K; Gibson-Corley, Katherine N; Meyerholz, David K

    2015-03-15

    Multiple organ systems, including the gastrointestinal tract, pancreas, and hepatobiliary systems, are affected by cystic fibrosis (CF). Many of these changes begin early in life and are difficult to study in young CF patients. Recent development of novel CF animal models has expanded opportunities in the field to better understand CF pathogenesis and evaluate traditional and innovative therapeutics. In this review, we discuss manifestations of CF disease in gastrointestinal, pancreatic, and hepatobiliary systems of humans and animal models. We also compare the similarities and limitations of animal models and discuss future directions for modeling CF.

  5. A systematic review of animal models for Staphylococcus aureus osteomyelitis

    Directory of Open Access Journals (Sweden)

    W Reizner

    2014-03-01

    Full Text Available Staphylococcus aureus (S. aureus osteomyelitis is a significant complication for orthopaedic patients undergoing surgery, particularly with fracture fixation and arthroplasty. Given the difficulty in studying S. aureus infections in human subjects, animal models serve an integral role in exploring the pathogenesis of osteomyelitis, and aid in determining the efficacy of prophylactic and therapeutic treatments. Animal models should mimic the clinical scenarios seen in patients as closely as possible to permit the experimental results to be translated to the corresponding clinical care. To help understand existing animal models of S. aureus, we conducted a systematic search of PubMed and Ovid MEDLINE to identify in vivo animal experiments that have investigated the management of S. aureus osteomyelitis in the context of fractures and metallic implants. In this review, experimental studies are categorised by animal species and are further classified by the setting of the infection. Study methods are summarised and the relevant advantages and disadvantages of each species and model are discussed. While no ideal animal model exists, the understanding of a model’s strengths and limitations should assist clinicians and researchers to appropriately select an animal model to translate the conclusions to the clinical setting.

  6. Predictive Modeling of Cardiac Ischemia

    Science.gov (United States)

    Anderson, Gary T.

    1996-01-01

    The goal of the Contextual Alarms Management System (CALMS) project is to develop sophisticated models to predict the onset of clinical cardiac ischemia before it occurs. The system will continuously monitor cardiac patients and set off an alarm when they appear about to suffer an ischemic episode. The models take as inputs information from patient history and combine it with continuously updated information extracted from blood pressure, oxygen saturation and ECG lines. Expert system, statistical, neural network and rough set methodologies are then used to forecast the onset of clinical ischemia before it transpires, thus allowing early intervention aimed at preventing morbid complications from occurring. The models will differ from previous attempts by including combinations of continuous and discrete inputs. A commercial medical instrumentation and software company has invested funds in the project with a goal of commercialization of the technology. The end product will be a system that analyzes physiologic parameters and produces an alarm when myocardial ischemia is present. If proven feasible, a CALMS-based system will be added to existing heart monitoring hardware.

  7. Animal models in epigenetic research: institutional animal care and use committee considerations across the lifespan.

    Science.gov (United States)

    Harris, Craig

    2012-01-01

    The rapid expansion and evolution of epigenetics as a core scientific discipline have raised new questions about how endogenous and environmental factors can inform the mechanisms through which biological form and function are regulated. Existing and proposed animal models used for epigenetic research have targeted a myriad of health and disease endpoints that may be acute, chronic, and transgenerational in nature. Initiating events and outcomes may extend across the entire lifespan to elicit unanticipated phenotypes that are of particular concern to institutional animal care and use committees (IACUCs). The dynamics and plasticity of epigenetic mechanisms produce effects and consequences that are manifest differentially within discreet spatial and temporal contexts, including prenatal development, stem cells, assisted reproductive technologies, production of sexual dimorphisms, senescence, and others. Many dietary and nutritional interventions have also been shown to have a significant impact on biological functions and disease susceptibilities through altered epigenetic programming. The environmental, chemical, toxic, therapeutic, and psychosocial stressors used in animal studies to elicit epigenetic changes can become extreme and should raise IACUC concerns for the well-being and proper care of all research animals involved. Epigenetics research is rapidly becoming an integral part of the search for mechanisms in every major area of biomedical and behavioral research and will foster the continued development of new animal models. From the IACUC perspective, care must be taken to acknowledge the particular needs and concerns created by superimposition of epigenetic mechanisms over diverse fields of investigation to ensure the proper care and use of animals without impeding scientific progress.

  8. Animal models for testing anti-prion drugs.

    Science.gov (United States)

    Fernández-Borges, Natalia; Elezgarai, Saioa R; Eraña, Hasier; Castilla, Joaquín

    2013-01-01

    Prion diseases belong to a group of fatal infectious diseases with no effective therapies available. Throughout the last 35 years, less than 50 different drugs have been tested in different experimental animal models without hopeful results. An important limitation when searching for new drugs is the existence of appropriate models of the disease. The three different possible origins of prion diseases require the existence of different animal models for testing anti-prion compounds. Wild type, over-expressing transgenic mice and other more sophisticated animal models have been used to evaluate a diversity of compounds which some of them were previously tested in different in vitro experimental models. The complexity of prion diseases will require more pre-screening studies, reliable sporadic (or spontaneous) animal models and accurate chemical modifications of the selected compounds before having an effective therapy against human prion diseases. This review is intended to put on display the more relevant animal models that have been used in the search of new antiprion therapies and describe some possible procedures when handling chemical compounds presumed to have anti-prion activity prior to testing them in animal models.

  9. Numerical weather prediction model tuning via ensemble prediction system

    Science.gov (United States)

    Jarvinen, H.; Laine, M.; Ollinaho, P.; Solonen, A.; Haario, H.

    2011-12-01

    This paper discusses a novel approach to tune predictive skill of numerical weather prediction (NWP) models. NWP models contain tunable parameters which appear in parameterizations schemes of sub-grid scale physical processes. Currently, numerical values of these parameters are specified manually. In a recent dual manuscript (QJRMS, revised) we developed a new concept and method for on-line estimation of the NWP model parameters. The EPPES ("Ensemble prediction and parameter estimation system") method requires only minimal changes to the existing operational ensemble prediction infra-structure and it seems very cost-effective because practically no new computations are introduced. The approach provides an algorithmic decision making tool for model parameter optimization in operational NWP. In EPPES, statistical inference about the NWP model tunable parameters is made by (i) generating each member of the ensemble of predictions using different model parameter values, drawn from a proposal distribution, and (ii) feeding-back the relative merits of the parameter values to the proposal distribution, based on evaluation of a suitable likelihood function against verifying observations. In the presentation, the method is first illustrated in low-order numerical tests using a stochastic version of the Lorenz-95 model which effectively emulates the principal features of ensemble prediction systems. The EPPES method correctly detects the unknown and wrongly specified parameters values, and leads to an improved forecast skill. Second, results with an atmospheric general circulation model based ensemble prediction system show that the NWP model tuning capacity of EPPES scales up to realistic models and ensemble prediction systems. Finally, a global top-end NWP model tuning exercise with preliminary results is published.

  10. Animal model: dysmorphogenesis and death in a chicken embryo model.

    Science.gov (United States)

    Fineman, R M; Schoenwolf, G C

    1987-07-01

    The chicken embryo is a useful animal model for investigating problems in developmental biology and teratology. Here we report data that further define the causes of 2 different patterns of malformation (one associated with amnion abnormalities, the other with isolated neural tube defects) and death induced by making a window in the shell and subshell membranes during the first day of incubation. The interpretation of these data suggests to us the following hypotheses. An early amnion deficit spectrum or syndrome (EADS) in chicken embryos is caused by a brief (less than 10 sec) perturbation that occurs during the windowing procedure. This perturbation results in an acute increase in mechanical tension to the developing embryo and support structures, dehydration localized to the area of the blastoderm, and/or increased friction between the blastoderm and overlying vitelline and shell membranes. Isolated neural tube defects (NTDs) are caused by a longer perturbation (greater than 3 hr) consisting of increased mechanical stress across the blastoderm. The mechanical stress is associated with the introduction of a new air space over the animal pole of the yolk during windowing. The new air space causes the shape of the yolk to change (ie, to be deformed), resulting in an increase in mechanical tension across the vitelline membrane and blastoderm. NTDs involving the head are associated with significant early embryonic mortality, whereas those involving the trunk are not. Death may also be caused by cardiovascular anomalies observed in EADS. It is concluded that disturbances in morphogenesis and death in this model are, therefore, the result of extrinsic forces (eg, mechanical stress, localized dehydration, or friction) acting on different tissue types at various critical times in development. Intensity and duration of these forces on the developing blastoderm are important variables.

  11. Medulloblastoma: Molecular Genetics and Animal Models

    Directory of Open Access Journals (Sweden)

    Corey Raffel

    2004-07-01

    Full Text Available Medulloblastoma is a primary brain tumor found in the cerebellum of children. The tumor occurs in association with two inherited cancer syndromes: Turcot syndrome and Gorlin syndrome. Insights into the molecular biology of the tumor have come from looking at alterations in the genes altered in these syndromes, PTC and APC, respectively. Murine models of medulloblastoma have been constructed based on these alterations. Additional murine models that, while mimicking the appearance of the human tumor, seem unrelated to the human tumor's molecular alterations have been made. In this review, the clinical picture, origin, molecular biology, murine models of medulloblastoma are discussed. Although a great deal has been discovered about this tumor, the genetic alterations responsible for tumor development in a majority of patients have yet to be described.

  12. Assessment of Venous Thrombosis in Animal Models.

    Science.gov (United States)

    Grover, Steven P; Evans, Colin E; Patel, Ashish S; Modarai, Bijan; Saha, Prakash; Smith, Alberto

    2016-02-01

    Deep vein thrombosis and common complications, including pulmonary embolism and post-thrombotic syndrome, represent a major source of morbidity and mortality worldwide. Experimental models of venous thrombosis have provided considerable insight into the cellular and molecular mechanisms that regulate thrombus formation and subsequent resolution. Here, we critically appraise the ex vivo and in vivo techniques used to assess venous thrombosis in these models. Particular attention is paid to imaging modalities, including magnetic resonance imaging, micro-computed tomography, and high-frequency ultrasound that facilitate longitudinal assessment of thrombus size and composition.

  13. Applications of population genetics to animal breeding, from wright, fisher and lush to genomic prediction.

    Science.gov (United States)

    Hill, William G

    2014-01-01

    Although animal breeding was practiced long before the science of genetics and the relevant disciplines of population and quantitative genetics were known, breeding programs have mainly relied on simply selecting and mating the best individuals on their own or relatives' performance. This is based on sound quantitative genetic principles, developed and expounded by Lush, who attributed much of his understanding to Wright, and formalized in Fisher's infinitesimal model. Analysis at the level of individual loci and gene frequency distributions has had relatively little impact. Now with access to genomic data, a revolution in which molecular information is being used to enhance response with "genomic selection" is occurring. The predictions of breeding value still utilize multiple loci throughout the genome and, indeed, are largely compatible with additive and specifically infinitesimal model assumptions. I discuss some of the history and genetic issues as applied to the science of livestock improvement, which has had and continues to have major spin-offs into ideas and applications in other areas.

  14. Instrumental and ethical aspects of experimental research with animal models

    Directory of Open Access Journals (Sweden)

    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.

  15. Effect of Xanthone Derivatives on Animal Models of Depression

    Directory of Open Access Journals (Sweden)

    Xu Zhao, MD

    2014-12-01

    Conclusions: Within certain dose ranges, xanthone derivatives 1101 and 1105 have similar effects to venlafaxine hydrochloride in the treatment of depression as suggested by behavioral despair animal models using rats and mice.

  16. Animal models of frailty: current applications in clinical research.

    Science.gov (United States)

    Kane, Alice E; Hilmer, Sarah N; Mach, John; Mitchell, Sarah J; de Cabo, Rafael; Howlett, Susan E

    2016-01-01

    The ethical, logistical, and biological complications of working with an older population of people inherently limits clinical studies of frailty. The recent development of animal models of frailty, and tools for assessing frailty in animal models provides an invaluable opportunity for frailty research. This review summarizes currently published animal models of frailty including the interleukin-10 knock-out mouse, the mouse frailty phenotype assessment tool, and the mouse clinical frailty index. It discusses both current and potential roles of these models in research into mechanisms of frailty, interventions to prevent/delay frailty, and the effect of frailty on outcomes. Finally, this review discusses some of the challenges and opportunities of translating research findings from animals to humans.

  17. 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...

  18. Biology of Obesity: Lessons from Animal Models of Obesity

    Directory of Open Access Journals (Sweden)

    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.

  19. Analysis of animal accelerometer data using hidden Markov models

    OpenAIRE

    2016-01-01

    Use of accelerometers is now widespread within animal biotelemetry as they provide a means of measuring an animal's activity in a meaningful and quantitative way where direct observation is not possible. In sequential acceleration data there is a natural dependence between observations of movement or behaviour, a fact that has been largely ignored in most analyses. Analyses of acceleration data where serial dependence has been explicitly modelled have largely relied on hidden Markov models (H...

  20. Animal Models of Diabetic Neuropathy: Progress Since 1960s

    OpenAIRE

    Md. Shahidul Islam

    2013-01-01

    Diabetic or peripheral diabetic neuropathy (PDN) is one of the major complications among some other diabetic complications such as diabetic nephropathy, diabetic retinopathy, and diabetic cardiomyopathy. The use of animal models in the research of diabetes and diabetic complications is very common when rats and mice are most commonly used for many reasons. A numbers of animal models of diabetic and PDN have been developed in the last several decades such as streptozotocin-induced diabetic rat...

  1. The rat as an animal model of Alzheimer's disease

    DEFF Research Database (Denmark)

    Benedikz, Eirikur; Kloskowska, Ewa; Winblad, Bengt

    2009-01-01

    As a disease model, the laboratory rat has contributed enormously to neuroscience research over the years. It has also been a popular animal model for Alzheimer's disease but its popularity has diminished during the last decade, as techniques for genetic manipulation in rats have lagged behind...... that of mice. In recent years, the rat has been making a comeback as an Alzheimer's disease model and the appearance of increasing numbers of transgenic rats will be a welcome and valuable complement to the existing mouse models. This review summarizes the contributions and current status of the rat...... as an animal model of Alzheimer's disease....

  2. 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;

  3. 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.

  4. Proteomics in farm animals models of human diseases.

    Science.gov (United States)

    Ceciliani, Fabrizio; Restelli, Laura; Lecchi, Cristina

    2014-10-01

    The need to provide in vivo complex environments to understand human diseases strongly relies on the use of animal models, which traditionally include small rodents and rabbits. It is becoming increasingly evident that the few species utilised to date cannot be regarded as universal. There is a great need for new animal species that are naturally endowed with specific features relevant to human diseases. Farm animals, including pigs, cows, sheep and horses, represent a valid alternative to commonly utilised rodent models. There is an ample scope for the application of proteomic techniques in farm animals, and the establishment of several proteomic maps of plasma and tissue has clearly demonstrated that farm animals provide a disease environment that closely resembles that of human diseases. The present review offers a snapshot of how proteomic techniques have been applied to farm animals to improve their use as biomedical models. Focus will be on specific topics of biomedical research in which farm animal models have been characterised through the application of proteomic techniques.

  5. 75 FR 54349 - Animal Models-Essential Elements To Address Efficacy Under the Animal Rule; Notice of Public...

    Science.gov (United States)

    2010-09-07

    ... HUMAN SERVICES Food and Drug Administration Animal Models--Essential Elements To Address Efficacy Under... challenges as addressed in the draft document entitled ``Guidance for ] Industry: Animal Models--Essential..., suite 200N, Rockville, MD 20852, 301-827-2000, e-mail: AnimalModelGuidance@fda.hhs.gov ; or Susie...

  6. Return Predictability, Model Uncertainty, and Robust Investment

    DEFF Research Database (Denmark)

    Lukas, Manuel

    Stock return predictability is subject to great uncertainty. In this paper we use the model confidence set approach to quantify uncertainty about expected utility from investment, accounting for potential return predictability. For monthly US data and six representative return prediction models, we...

  7. 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...

  8. Animals

    Institute of Scientific and Technical Information of China (English)

    杨光

    2000-01-01

    The largest animal ever to live on the earth is the blue whale(蓝鲸)It weighs about 80 tons--more than 24 elephants. It is more than 30 metres long. A newborn baby whale weighs as much as a big elephant.

  9. Predictive Model Assessment for Count Data

    Science.gov (United States)

    2007-09-05

    critique count regression models for patent data, and assess the predictive performance of Bayesian age-period-cohort models for larynx cancer counts...the predictive performance of Bayesian age-period-cohort models for larynx cancer counts in Germany. We consider a recent suggestion by Baker and...Figure 5. Boxplots for various scores for patent data count regressions. 11 Table 1 Four predictive models for larynx cancer counts in Germany, 1998–2002

  10. Review of Animal Models of Prostate Cancer Bone Metastasis

    Directory of Open Access Journals (Sweden)

    Jessica K. Simmons

    2014-06-01

    Full Text Available Prostate cancer bone metastases are associated with a poor prognosis and are considered incurable. Insight into the formation and growth of prostate cancer bone metastasis is required for development of new imaging and therapeutic strategies to combat this devastating disease. Animal models are indispensable in investigating cancer pathogenesis and evaluating therapeutics. Multiple animal models of prostate cancer bone metastasis have been developed, but few effectively model prostatic neoplasms and osteoblastic bone metastases as they occur in men. This review discusses the animal models that have been developed to investigate prostate cancer bone metastasis, with a focus on canine models and also includes human xenograft and rodent models. Adult dogs spontaneously develop benign prostatic hyperplasia and prostate cancer with osteoblastic bone metastases. Large animal models, such as dogs, are needed to develop new molecular imaging tools and effective focal intraprostatic therapy. None of the available models fully reflect the metastatic disease seen in men, although the various models have provided important insight into the metastatic process. As additional models are developed and knowledge from the different models is combined, the molecular mechanisms of prostate cancer bone metastasis can be deciphered and targeted for development of novel therapies and molecular diagnostic imaging.

  11. Animal models for studying dengue pathogenesis and therapy.

    Science.gov (United States)

    Chan, Kitti Wing Ki; Watanabe, Satoru; Kavishna, Ranmali; Alonso, Sylvie; Vasudevan, Subhash G

    2015-11-01

    Development of a suitable animal model for dengue virus disease is critical for understanding pathogenesis and for preclinical testing of antiviral drugs and vaccines. Many laboratory animal models of dengue virus infection have been investigated, but the challenges of recapitulating the complete disease still remain. In this review, we provide a comprehensive coverage of existing models, from man to mouse, with a specific focus on recent advances in mouse models for addressing the mechanistic aspects of severe dengue in humans. This article forms part of a symposium in Antiviral Research on flavivirus drug discovery.

  12. Animal models of heart failure recent developments and perspectives.

    Science.gov (United States)

    Hongo, M; Ryoke, T; Ross, J

    1997-07-01

    Heart failure is a complex syndrome characterized by inability of the heart to supply sufficient cardiac output to meet the metabolic needs of the body. Over the past few decades, a number of animal models of heart failure have been developed to study questions that cannot be readily studied in the clinical setting. Because the syndrome of heart failure in humans has many underlying causes, ranging from primary myocardial disease (often of unknown etiology) to myocardial failure consequent to ventricular overload with secondary cardiac hypertrophy (as in hypertension, valvular heart disease, or myocardial infarction), no single animal model can successfully mimic the pathophysiology of these clinical settings. Regardless of the original cardiac abnormality, however, the end-stage heart failure syndrome generally presents a picture of cardiac dilation and circulatory congestion associated with maladaptive neurohumoral responses affecting the heart and peripheral circulation, which provide prime targets for new treatment strategies. An ideal animal model of heart failure should mimic the clinical setting as closely as possible, be accessible and reproducible, relatively stable under chronic conditions, and sufficiently economical to permit experiments in a large number of animals. In this review, we discuss the advantages and disadvantages of naturally occurring models of heart failure and models in which heart failure is induced in normal animals, focusing in particular on models that are useful for exploring disease mechanisms and interventions to prevent or treat heart failure. Much is being learned from large animals such as the dog and pig, although small animal models (rat and hamster) have many favorable features, and as genetic methods and miniaturized physiologic techniques mature, the mouse is beginning to provide gene-based models of cardiac failure aimed at better understanding of molecular mechanisms. (Trends Cardiovasc Med 1997;7:161-167). © 1997

  13. Hypoxic preconditioning in an autohypoxic animal model

    Institute of Scientific and Technical Information of China (English)

    Guo Shao; Guo-Wei Lu

    2012-01-01

    Hypoxic preconditioning refers to the exposure of organisms,systems,organs,tissues or cells to moderate hypoxia/ischemia that [Results]in increased resistance to a subsequent episode of severe hypoxia/ischemia.In this article,we review recent research based on a mouse model of repeated exposure to autohypoxia.Pre-exposure markedly increases the tolerance to or protection against hypoxic insult,and preserves the cellular structure of the brain.Furthermore,the hippocampal activity amplitude and frequency of electroencephalogram,latency of cortical somatosensory-evoked potential and spinal somatosensory-evoked potential progressively decrease,while spatial learning and memory improve.In the brain,detrimental neurochemicals such as free radicals are down-regulated,while beneficial ones such as adenosine are upregulated.Also,antihypoxia factor(s) and gene(s) are activated.We propose that the tolerance and protective effects depend on energy conservation and plasticity triggered by exposure to hypoxia via oxygen-sensing transduction pathways and hypoxia-inducible factor-initiated cascades.A potential path for further research is the development of devices and pharmaceuticals acting on antihypoxia factor(s) and gene(s) for the prevention and treatment of hypoxia and related syndromes.

  14. Modeling Leadership Hierarchy in Multilevel Animal Societies

    CERN Document Server

    Ozogány, Katalin

    2014-01-01

    A typical feature of many natural and social networks is the presence of communities giving rise to multiple levels of organization. We investigate the decision-making process of a group combining self organization and social dynamics, and reproduce the simultaneous emergence of a hierarchical and modular leadership network. All individuals in the model try, with varying degrees of ability, to find a direction of movement, with the result that leader-follower relationships evolve between them, since they tend to follow the more successful ones. The harem-forming ambitions of male individuals inspired by an observed Przewalski horse herd (Hortob\\'agy, Hungary) leads to modular structure. In this approach we find that the harem-leader to harem-member ratio observed in horses corresponds to an optimal network regarding common success, and that modularly structured hierarchy is more benefical than a non-modular one, in the sense that common success is higher, and the underlying network is more hierarchical. We al...

  15. Dive characteristics can predict foraging success in Australian fur seals (Arctocephalus pusillus doriferus as validated by animal-borne video

    Directory of Open Access Journals (Sweden)

    Beth L. Volpov

    2016-03-01

    Full Text Available Dive characteristics and dive shape are often used to infer foraging success in pinnipeds. However, these inferences have not been directly validated in the field with video, and it remains unclear if this method can be applied to benthic foraging animals. This study assessed the ability of dive characteristics from time-depth recorders (TDR to predict attempted prey capture events (APC that were directly observed on animal-borne video in Australian fur seals (Arctocephalus pusillus doriferus, n=11. The most parsimonious model predicting the probability of a dive with ≥1 APC on video included only descent rate as a predictor variable. The majority (94% of the 389 total APC were successful, and the majority of the dives (68% contained at least one successful APC. The best model predicting these successful dives included descent rate as a predictor. Comparisons of the TDR model predictions to video yielded a maximum accuracy of 77.5% in classifying dives as either APC or non-APC or 77.1% in classifying dives as successful verses unsuccessful. Foraging intensity, measured as either total APC per dive or total successful APC per dive, was best predicted by bottom duration and ascent rate. The accuracy in predicting total APC per dive varied based on the number of APC per dive with maximum accuracy occurring at 1 APC for both total (54% and only successful APC (52%. Results from this study linking verified foraging dives to dive characteristics potentially opens the door to decades of historical TDR datasets across several otariid species.

  16. Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

    Institute of Scientific and Technical Information of China (English)

    Yoshihisa Takahashi; Yurie Soejima; Toshio Fukusato

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse.Nonalcoholic steatohepatitis (NASH),a severe form of NAFLD,can progress to liver cirrhosis and hepatocellular carcinoma.NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity,type 2 diabetes,and hyperlipemia.Animal models of NAFLD/NASH give crucial information,not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents.An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH.Animal models of NAFLD/NASH are divided into genetic,dietary,and combination models.In this paper,we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages.

  17. Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

    Science.gov (United States)

    Takahashi, Yoshihisa; Soejima, Yurie; Fukusato, Toshio

    2012-05-21

    Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma. NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity, type 2 diabetes, and hyperlipemia. Animal models of NAFLD/NASH give crucial information, not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents. An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH. Animal models of NAFLD/NASH are divided into genetic, dietary, and combination models. In this paper, we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages.

  18. Animal models of suicide-trait-related behaviors.

    Science.gov (United States)

    Malkesman, Oz; Pine, Daniel S; Tragon, Tyson; Austin, Daniel R; Henter, Ioline D; Chen, Guang; Manji, Husseini K

    2009-04-01

    Although antidepressants are moderately effective in treating major depressive disorder (MDD), concerns have arisen that selective serotonin-reuptake inhibitors (SSRIs) are associated with suicidal thinking and behavior, especially in children, adolescents and young adults. Almost no experimental research in model systems has considered the mechanisms by which SSRIs might be associated with this potential side effect in some susceptible individuals. Suicide is a complex behavior and impossible to fully reproduce in an animal model. However, by investigating traits that show strong cross-species parallels in addition to associations with suicide in humans, animal models might elucidate the mechanisms by which SSRIs are associated with suicidal thinking and behavior. Traits linked with suicide in humans that can be successfully modeled in rodents include aggression, impulsivity, irritability and hopelessness/helplessness. Modeling these relevant traits in animals can help to clarify the impact of SSRIs on these traits, suggesting avenues for reducing suicide risk in this vulnerable population.

  19. Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

    Science.gov (United States)

    Takahashi, Yoshihisa; Soejima, Yurie; Fukusato, Toshio

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma. NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity, type 2 diabetes, and hyperlipemia. Animal models of NAFLD/NASH give crucial information, not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents. An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH. Animal models of NAFLD/NASH are divided into genetic, dietary, and combination models. In this paper, we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages. PMID:22654421

  20. Models of 'obesity' in large animals and birds.

    Science.gov (United States)

    Clarke, Iain J

    2008-01-01

    Most laboratory-based research on obesity is carried out in rodents, but there are a number of other interesting models in the animal kingdom that are instructive. This includes domesticated animal species such as pigs and sheep, as well as wild, migrating and hibernating species. Larger animals allow particular experimental manipulations that are not possible in smaller animals and especially useful models have been developed to address issues such as manipulation of fetal development. Although some of the most well-studied models are ruminants, with metabolic control that differs from monogastrics, the general principles of metabolic regulation still pertain. It is possible to obtain much more accurate endocrine profiles in larger animals and this has provided important data in relation to leptin and ghrelin physiology. Genetic models have been created in domesticated animals through selection and these complement those of the laboratory rodent. This short review highlights particular areas of research in domesticated and wild species that expand our knowledge of systems that are important for our understanding of obesity and metabolism.

  1. ANIMALS

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Mammals(哺乳动物)Mammals are the world's most dominant(最占优势的)animal.They are extremely(非常)diverse(多种多样的)creatures(生物,动物)that include(包括)the biggest ever animal (the blue whale鲸,which eats up to 6 tons every day),the smallest(leaf-nosed bat小蹄蝠) and the laziest(sloth树獭,who spends 80% of their time sleeping).There are over 4,600 kinds of mammals and they live in very different environments(环境)—oceans(海洋),rivers,the jungle(丛林),deserts,and plains(平原).

  2. OBESITY AND CRITICAL ILLNESS: INSIGHTS FROM ANIMAL MODELS.

    Science.gov (United States)

    Mittwede, Peter N; Clemmer, John S; Bergin, Patrick F; Xiang, Lusha

    2016-04-01

    Critical illness is a major cause of morbidity and mortality around the world. While obesity is often detrimental in the context of trauma, it is paradoxically associated with improved outcomes in some septic patients. The reasons for these disparate outcomes are not well understood. A number of animal models have been used to study the obese response to various forms of critical illness. Just as there have been many animal models that have attempted to mimic clinical conditions, there are many clinical scenarios that can occur in the highly heterogeneous critically ill patient population that occupies hospitals and intensive care units. This poses a formidable challenge for clinicians and researchers attempting to understand the mechanisms of disease and develop appropriate therapies and treatment algorithms for specific subsets of patients, including the obese. The development of new, and the modification of existing animal models, is important in order to bring effective treatments to a wide range of patients. Not only do experimental variables need to be matched as closely as possible to clinical scenarios, but animal models with pre-existing comorbid conditions need to be studied. This review briefly summarizes animal models of hemorrhage, blunt trauma, traumatic brain injury, and sepsis. It also discusses what has been learned through the use of obese models to study the pathophysiology of critical illness in light of what has been demonstrated in the clinical literature.

  3. Animal models of Parkinson's disease and their applications

    Directory of Open Access Journals (Sweden)

    Park HJ

    2016-07-01

    Full Text Available Hyun Jin Park, Ting Ting Zhao, Myung Koo LeeDepartment of Pharmacy, Research Center for Bioresource and Health, College of Pharmacy, Chungbuk National University, Cheongju, Republic of Korea Abstract: Parkinson's disease (PD is a progressive neurodegenerative disorder that occurs mainly due to the degeneration of dopaminergic neuronal cells in the substantia nigra. l-3,4-Dihydroxyphenylalanine (L-DOPA is the most effective known therapy for PD. However, chronic L-DOPA administration results in a loss of drug efficacy and irreversible adverse effects, including L-DOPA-induced dyskinesia, affective disorders, and cognitive function disorders. To study the motor and non-motor symptomatic dysfunctions in PD, neurotoxin and genetic animal models of PD have been widely applied. However, these animal models do not exhibit all of the pathophysiological symptoms of PD. Regardless, neurotoxin rat and mouse models of PD have been commonly used in the development of bioactive components from natural herbal medicines. Here, the main animal models of PD and their applications have been introduced in order to aid the development of therapeutic and adjuvant agents. Keywords: Parkinson's disease, neurotoxin animal models, genetic animal models, adjuvant therapeutics

  4. Animal models of COPD: What do they tell us?

    Science.gov (United States)

    Jones, Bernadette; Donovan, Chantal; Liu, Gang; Gomez, Henry M; Chimankar, Vrushali; Harrison, Celeste L; Wiegman, Cornelis H; Adcock, Ian M; Knight, Darryl A; Hirota, Jeremy A; Hansbro, Philip M

    2017-01-01

    COPD is a major cause of global mortality and morbidity but current treatments are poorly effective. This is because the underlying mechanisms that drive the development and progression of COPD are incompletely understood. Animal models of disease provide a valuable, ethically and economically viable experimental platform to examine these mechanisms and identify biomarkers that may be therapeutic targets that would facilitate the development of improved standard of care. Here, we review the different established animal models of COPD and the various aspects of disease pathophysiology that have been successfully recapitulated in these models including chronic lung inflammation, airway remodelling, emphysema and impaired lung function. Furthermore, some of the mechanistic features, and thus biomarkers and therapeutic targets of COPD identified in animal models are outlined. Some of the existing therapies that suppress some disease symptoms that were identified in animal models and are progressing towards therapeutic development have been outlined. Further studies of representative animal models of human COPD have the strong potential to identify new and effective therapeutic approaches for COPD.

  5. Life sciences research in space: The requirement for animal models

    Science.gov (United States)

    Fuller, C. A.; Philips, R. W.; Ballard, R. W.

    1987-01-01

    Use of animals in NASA space programs is reviewed. Animals are needed because life science experimentation frequently requires long-term controlled exposure to environments, statistical validation, invasive instrumentation or biological tissue sampling, tissue destruction, exposure to dangerous or unknown agents, or sacrifice of the subject. The availability and use of human subjects inflight is complicated by the multiple needs and demands upon crew time. Because only living organisms can sense, integrate and respond to the environment around them, the sole use of tissue culture and computer models is insufficient for understanding the influence of the space environment on intact organisms. Equipment for spaceborne experiments with animals is described.

  6. Modeling sleep alterations in Parkinson's disease: How close are we to valid translational animal models?

    Science.gov (United States)

    Fifel, Karim; Piggins, Hugh; Deboer, Tom

    2016-02-01

    Parkinson disease is one of the neurodegenerative diseases that benefited the most from the use of non-human models. Consequently, significant advances have been made in the symptomatic treatments of the motor aspects of the disease. Unfortunately, this translational success has been tempered by the recognition of the debilitating aspect of multiple non-motor symptoms of the illness. Alterations of the sleep/wakefulness behavior experienced as insomnia, excessive daytime sleepiness, sleep/wake cycle fragmentation and REM sleep behavior disorder are among the non-motor symptoms that predate motor alterations and inevitably worsen over disease progression. The absence of adequate humanized animal models with the perfect phenocopy of these sleep alterations contribute undoubtedly to the lack of efficient therapies for these non-motor complications. In the context of developing efficient translational therapies, we provide an overview of the strengths and limitations of the various currently available models to replicate sleep alterations of Parkinson's disease. Our investigation reveals that although these models replicate dopaminergic deficiency and related parkinsonism, they rarely display a combination of sleep fragmentation and excessive daytime sleepiness and never REM sleep behavior disorder. In this light, we critically discuss the construct, face and predictive validities of both rodent and non-human primate animals to model the main sleep abnormalities experienced by patients with PD. We conclude by highlighting the need of integrating a network-based perspective in our modeling approach of such complex syndrome in order to celebrate valid translational models.

  7. Animal model integration to AutDB, a genetic database for autism

    Directory of Open Access Journals (Sweden)

    Kollu Ravi

    2011-01-01

    Full Text Available Abstract Background In the post-genomic era, multi-faceted research on complex disorders such as autism has generated diverse types of molecular information related to its pathogenesis. The rapid accumulation of putative candidate genes/loci for Autism Spectrum Disorders (ASD and ASD-related animal models poses a major challenge for systematic analysis of their content. We previously created the Autism Database (AutDB to provide a publicly available web portal for ongoing collection, manual annotation, and visualization of genes linked to ASD. Here, we describe the design, development, and integration of a new module within AutDB for ongoing collection and comprehensive cataloguing of ASD-related animal models. Description As with the original AutDB, all data is extracted from published, peer-reviewed scientific literature. Animal models are annotated with a new standardized vocabulary of phenotypic terms developed by our researchers which is designed to reflect the diverse clinical manifestations of ASD. The new Animal Model module is seamlessly integrated to AutDB for dissemination of diverse information related to ASD. Animal model entries within the new module are linked to corresponding candidate genes in the original "Human Gene" module of the resource, thereby allowing for cross-modal navigation between gene models and human gene studies. Although the current release of the Animal Model module is restricted to mouse models, it was designed with an expandable framework which can easily incorporate additional species and non-genetic etiological models of autism in the future. Conclusions Importantly, this modular ASD database provides a platform from which data mining, bioinformatics, and/or computational biology strategies may be adopted to develop predictive disease models that may offer further insights into the molecular underpinnings of this disorder. It also serves as a general model for disease-driven databases curating phenotypic

  8. An Experimental Animal Model for Abdominal Fascia Healing after Surgery

    DEFF Research Database (Denmark)

    Burcharth, J; Pommergaard, H-C; Klein, M

    2013-01-01

    Background: Incisional hernia (IH) is a well-known complication after abdominal surgical procedures. The exact etiology of IH is still unknown even though many risk factors have been suggested. The aim of this study was to create an animal model of a weakly healed abdominal fascia that could...... be used to evaluate the actively healing fascia. Such an animal model may promote future research in the prevention of IH. Methods: 86 male Sprague-Dawley rats were used to establish a model involving six experiments (experiments A-F). Mechanical testing of the breaking strength of the healed fascia...... of mechanical breaking strength. This new animal model employed myofascial closing after a full thickness abdominal incision using a running suture with fast-absorbable suture material. This technique produced a weak myofascial layer compared with the control tissue measured in terms of breaking strength after...

  9. Immunology of fungal infections: lessons learned from animal models.

    Science.gov (United States)

    Steele, Chad; Wormley, Floyd L

    2012-08-01

    The continuing AIDS epidemic coupled with increased usage of immunosuppressive drugs to prevent organ rejection or treat autoimmune diseases has resulted in an increase in individuals at risk for acquiring fungal diseases. These concerns highlight the need to elucidate mechanisms of inducing protective immune responses against fungal pathogens. Consequently, several experimental models of human mycoses have been developed to study these diseases. The availability of transgenic animal models allows for in-depth analysis of specific components, receptors, and signaling pathways that elicit protection against fungal diseases. This review focuses on recent advances in our understanding of immune responses to fungal infections gained using animal models.

  10. Animal models of fear and anxiety: neurobehavioral descriptions

    OpenAIRE

    Mora Gallegos, Andrea; Salas Castillo, Sofia

    2014-01-01

    Animal models of fear and anxiety have been widely used for the comprehension of anxiety disorders in humans, however, it has not been easy to distinguish between both concepts at physiological and behavioral levels. One way to model anxiety disorders is through behavioral tests of anxiety, (such as the elevated plus maze and the open field test), and fear (using the fear conditioning paradigm and active avoidance). Furthermore, animal models are relevant to study the involvement of different...

  11. ANIMAL MODELS OF POST-TRAUMATIC STRESS DISORDER: FACE VALIDITY

    Directory of Open Access Journals (Sweden)

    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.

  12. EFFICIENT PREDICTIVE MODELLING FOR ARCHAEOLOGICAL RESEARCH

    OpenAIRE

    Balla, A.; Pavlogeorgatos, G.; Tsiafakis, D.; Pavlidis, G.

    2014-01-01

    The study presents a general methodology for designing, developing and implementing predictive modelling for identifying areas of archaeological interest. The methodology is based on documented archaeological data and geographical factors, geospatial analysis and predictive modelling, and has been applied to the identification of possible Macedonian tombs’ locations in Northern Greece. The model was tested extensively and the results were validated using a commonly used predictive gain,...

  13. Disease spread models in wild and feral animal populations: application of artificial life models.

    Science.gov (United States)

    Ward, M P; Laffan, S W; Highfield, L D

    2011-08-01

    The role that wild and feral animal populations might play in the incursion and spread of important transboundary animal diseases, such as foot and mouth disease (FMD), has received less attention than is warranted by the potential impacts. An artificial life model (Sirca) has been used to investigate this issue in studies based on spatially referenced data sets from southern Texas. An incursion of FMD in which either feral pig or deer populations were infected could result in between 698 and 1557 infected cattle and affect an area of between 166 km2 and 455 km2 after a 100-day period. Although outbreak size in deer populations can be predicted bythe size of the local deer population initially infected, the resulting outbreaks in feral pig populations are less predictable. Also, in the case of deer, the size of potential outbreaks might depend on the season when the incursion occurs. The impact of various mitigation strategies on disease spread has also been investigated. The approach used in the studies reviewed here explicitly incorporates the spatial distribution and relationships between animal populations, providing a new framework to explore potential impacts, costs, and control strategies.

  14. A novel animal model for skin flap prelamination with biomaterials

    Science.gov (United States)

    Zhou, Xianyu; Luo, Xusong; Liu, Fei; Gu, Chuan; Wang, Xi; Yang, Qun; Qian, Yunliang; Yang, Jun

    2016-09-01

    Several animal models of skin flap construction were reported using biomaterials in a way similar to prefabrication. However, there are few animal model using biomaterials similar to prelamination, another main way of clinical skin flap construction that has been proved to be reliable. Can biomaterials be added in skin flap prelamination to reduce the use of autogenous tissues? Beside individual clinical attempts, animal model is needed for randomized controlled trial to objectively evaluate the feasibility and further investigation. Combining human Acellular Dermal Matrix (hADM) and autologous skin graft, we prelaminated flaps based on inguinal fascia. One, two, three and four weeks later, hADM exhibited a sound revascularization and host cell infiltration. Prelaminated skin flaps were then raised and microsurgically transplanted back to groin region. Except for flaps after one week of prelamination, flaps from other subgroups successfully reconstructed defects. After six to sixteen weeks of transplantation, hADM was proved to being able to maintain its original structure, having a wealth of host tissue cells and achieving full revascularization.To our knowledge, this is the first animal model of prelaminating skin flap with biomaterials. Success of this animal model indicates that novel flap prelamination with biomaterials is feasible.

  15. A novel animal model for skin flap prelamination with biomaterials

    Science.gov (United States)

    Zhou, Xianyu; Luo, Xusong; Liu, Fei; Gu, Chuan; Wang, Xi; Yang, Qun; Qian, Yunliang; Yang, Jun

    2016-01-01

    Several animal models of skin flap construction were reported using biomaterials in a way similar to prefabrication. However, there are few animal model using biomaterials similar to prelamination, another main way of clinical skin flap construction that has been proved to be reliable. Can biomaterials be added in skin flap prelamination to reduce the use of autogenous tissues? Beside individual clinical attempts, animal model is needed for randomized controlled trial to objectively evaluate the feasibility and further investigation. Combining human Acellular Dermal Matrix (hADM) and autologous skin graft, we prelaminated flaps based on inguinal fascia. One, two, three and four weeks later, hADM exhibited a sound revascularization and host cell infiltration. Prelaminated skin flaps were then raised and microsurgically transplanted back to groin region. Except for flaps after one week of prelamination, flaps from other subgroups successfully reconstructed defects. After six to sixteen weeks of transplantation, hADM was proved to being able to maintain its original structure, having a wealth of host tissue cells and achieving full revascularization.To our knowledge, this is the first animal model of prelaminating skin flap with biomaterials. Success of this animal model indicates that novel flap prelamination with biomaterials is feasible. PMID:27659066

  16. Food allergy: What do we learn from animal models?

    NARCIS (Netherlands)

    Knippels, L.M.J.; Wijk, F. van; Penninks, A.H.

    2004-01-01

    Purpose of review This review summarizes selected articles on animal models of food allergy published in 2003. The research areas that are covered include mechanistic studies, the search for new therapies, as well as screening models for hazard identification of potential allergens. Recent findings

  17. How to Establish Clinical Prediction Models

    Directory of Open Access Journals (Sweden)

    Yong-ho Lee

    2016-03-01

    Full Text Available A clinical prediction model can be applied to several challenging clinical scenarios: screening high-risk individuals for asymptomatic disease, predicting future events such as disease or death, and assisting medical decision-making and health education. Despite the impact of clinical prediction models on practice, prediction modeling is a complex process requiring careful statistical analyses and sound clinical judgement. Although there is no definite consensus on the best methodology for model development and validation, a few recommendations and checklists have been proposed. In this review, we summarize five steps for developing and validating a clinical prediction model: preparation for establishing clinical prediction models; dataset selection; handling variables; model generation; and model evaluation and validation. We also review several studies that detail methods for developing clinical prediction models with comparable examples from real practice. After model development and vigorous validation in relevant settings, possibly with evaluation of utility/usability and fine-tuning, good models can be ready for the use in practice. We anticipate that this framework will revitalize the use of predictive or prognostic research in endocrinology, leading to active applications in real clinical practice.

  18. The use of animal models in behavioural neuroscience research.

    Science.gov (United States)

    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 also likely to be considered the ones that are most morally problematic to use, if it seems probable that (and if indeed they are initially selected as models because) they have experiences that are similar to human experiences that we have strong reasons to avoid causing, and indeed aim to alleviate (such as pain, anxiety or sadness). In this paper, against the background of contemporary discussions in animal ethics and the philosophy of animal minds, we discuss the views that it is morally permissible to use animals in these kinds of experiments, and that it is better to use less cognitively complex animals (such as zebrafish) than more complex animals (such as dogs). First, we criticise some justifications for the claim that human beings and more complex animals have higher moral status. We argue that contemporary approaches that attribute equal moral status to all beings that are capable of conscious strivings strivings (e.g. avoiding pain and anxiety; aiming to eat and play) are based on more plausible assumptions. Second, we argue that it is problematic to assume that less cognitively complex animals have a lesser sensory and emotional experience than more complex beings across the board. In specific cases, there might be good reasons to assume that more complex beings would be harmed more by a specific physical or environmental intervention, but it might also be that they sometimes are harmed less because of a better ability to cope. Determining whether a specific experiment is justified is therefore a complex issue. Our aim in this chapter is to stimulate further reflection on these common assumptions behind the use of animal models for psychopathologies. In

  19. Colorado animal-based plague surveillance systems: relationships between targeted animal species and prediction efficacy of areas at risk for humans.

    Science.gov (United States)

    Lowell, Jennifer L; Eisen, Rebecca J; Schotthoefer, Anna M; Xiaocheng, Liang; Montenieri, John A; Tanda, Dale; Pape, John; Schriefer, Martin E; Antolin, Michael F; Gage, Kenneth L

    2009-06-01

    Human plague risks (Yersinia pestis infection) are greatest when epizootics cause high mortality among this bacterium's natural rodent hosts. Therefore, health departments in plague-endemic areas commonly establish animal-based surveillance programs to monitor Y. pestis infection among plague hosts and vectors. The primary objectives of our study were to determine whether passive animal-based plague surveillance samples collected in Colorado from 1991 to 2005 were sampled from high human plague risk areas and whether these samples provided information useful for predicting human plague case locations. By comparing locations of plague-positive animal samples with a previously constructed GIS-based plague risk model, we determined that the majority of plague-positive Gunnison's prairie dogs (100%) and non-prairie dog sciurids (85.82%), and moderately high percentages of sigmodontine rodents (71.4%), domestic cats (69.3%), coyotes (62.9%), and domestic dogs (62.5%) were recovered within 1 km of the nearest area posing high peridomestic risk to humans. In contrast, the majority of white-tailed prairie dog (66.7%), leporid (cottontailed and jack rabbits) (71.4%), and black-tailed prairie dog (93.0%) samples originated more than 1 km from the nearest human risk habitat. Plague-positive animals or their fleas were rarely (one of 19 cases) collected within 2 km of a case exposure site during the 24 months preceding the dates of illness onset for these cases. Low spatial accuracy for identifying epizootic activity prior to human plague cases suggested that other mammalian species or their fleas are likely more important sources of human infection in high plague risk areas. To address this issue, epidemiological observations and multi-locus variable number tandem repeat analyses (MLVA) were used to preliminarily identify chipmunks as an under-sampled, but potentially important, species for human plague risk in Colorado.

  20. Amphibians as animal models for laboratory research in physiology.

    Science.gov (United States)

    Burggren, Warren W; Warburton, Stephen

    2007-01-01

    The concept of animal models is well honored, and amphibians have played a prominent part in the success of using key species to discover new information about all animals. As animal models, amphibians offer several advantages that include a well-understood basic physiology, a taxonomic diversity well suited to comparative studies, tolerance to temperature and oxygen variation, and a greater similarity to humans than many other currently popular animal models. Amphibians now account for approximately 1/4 to 1/3 of lower vertebrate and invertebrate research, and this proportion is especially true in physiological research, as evident from the high profile of amphibians as animal models in Nobel Prize research. Currently, amphibians play prominent roles in research in the physiology of musculoskeletal, cardiovascular, renal, respiratory, reproductive, and sensory systems. Amphibians are also used extensively in physiological studies aimed at generating new insights in evolutionary biology, especially in the investigation of the evolution of air breathing and terrestriality. Environmental physiology also utilizes amphibians, ranging from studies of cryoprotectants for tissue preservation to physiological reactions to hypergravity and space exploration. Amphibians are also playing a key role in studies of environmental endocrine disruptors that are having disproportionately large effects on amphibian populations and where specific species can serve as sentinel species for environmental pollution. Finally, amphibian genera such as Xenopus, a genus relatively well understood metabolically and physiologically, will continue to contribute increasingly in this new era of systems biology and "X-omics."

  1. What can we learn from animal models of Alopecia areata?

    Science.gov (United States)

    McElwee, Kevin J; Yu, Mei; Park, Sung-Wook; Ross, Elizabeth K; Finner, Andreas; Shapiro, Jerry

    2005-01-01

    Alopecia areata (AA) is a hair loss disease marked by a focal inflammatory infiltrate of dystrophic anagen stage hair follicles by CD4+ and CD8+ lymphocytes. Although AA is thought to be an autoimmune disorder, definitive proof is lacking. Moreover, characterization of the primary pathogenic mechanisms by which hair loss is induced in AA is limited. In this context, animal models may provide a vital contribution to understanding AA. Recent research using animal models of AA has focused on providing evidence in support of a lymphocyte-mediated pathogenic mechanism consistent with AA as an autoimmune disease. In the future, research with both humans and animal models shall likely concentrate on identifying the primary antigenic epitopes involved in AA and the genetics of AA susceptibility. With a comprehensive understanding of the key elements in AA pathogenesis, new avenues for therapeutic research and intervention will be defined.

  2. Rabbit as an animal model for experimental research.

    Science.gov (United States)

    Mapara, Manjeet; Thomas, Betsy Sara; Bhat, K M

    2012-01-01

    Animal experimentation is carried out in consultation with the veterinary wing but it is essential that be familiar with experimental protocols of animal model to be able to design an approriate study. This is more so in place where the veterinary facilities are not easily available.Span Rabbits are commonly used as subjects for screening implant material. They have gained favour for their numerous advantages even though they should be ideally used prior to testing in a larger animal model. Though experimentation on rabbits seems to be easy there are many pitfalls. Our endeavor in this article is to integrate all the data about maintaining rabbits as a model and to critically analyze it on the basis of our experimentation.

  3. Comparison of Prediction-Error-Modelling Criteria

    DEFF Research Database (Denmark)

    Jørgensen, John Bagterp; Jørgensen, Sten Bay

    2007-01-01

    is a realization of a continuous-discrete multivariate stochastic transfer function model. The proposed prediction error-methods are demonstrated for a SISO system parameterized by the transfer functions with time delays of a continuous-discrete-time linear stochastic system. The simulations for this case suggest......Single and multi-step prediction-error-methods based on the maximum likelihood and least squares criteria are compared. The prediction-error methods studied are based on predictions using the Kalman filter and Kalman predictors for a linear discrete-time stochastic state space model, which...... computational resources. The identification method is suitable for predictive control....

  4. Using spatiotemporal statistical models to estimate animal abundance and infer ecological dynamics from survey counts

    Science.gov (United States)

    Conn, Paul B.; Johnson, Devin S.; Ver Hoef, Jay M.; Hooten, Mevin B.; London, Joshua M.; Boveng, Peter L.

    2015-01-01

    Ecologists often fit models to survey data to estimate and explain variation in animal abundance. Such models typically require that animal density remains constant across the landscape where sampling is being conducted, a potentially problematic assumption for animals inhabiting dynamic landscapes or otherwise exhibiting considerable spatiotemporal variation in density. We review several concepts from the burgeoning literature on spatiotemporal statistical models, including the nature of the temporal structure (i.e., descriptive or dynamical) and strategies for dimension reduction to promote computational tractability. We also review several features as they specifically relate to abundance estimation, including boundary conditions, population closure, choice of link function, and extrapolation of predicted relationships to unsampled areas. We then compare a suite of novel and existing spatiotemporal hierarchical models for animal count data that permit animal density to vary over space and time, including formulations motivated by resource selection and allowing for closed populations. We gauge the relative performance (bias, precision, computational demands) of alternative spatiotemporal models when confronted with simulated and real data sets from dynamic animal populations. For the latter, we analyze spotted seal (Phoca largha) counts from an aerial survey of the Bering Sea where the quantity and quality of suitable habitat (sea ice) changed dramatically while surveys were being conducted. Simulation analyses suggested that multiple types of spatiotemporal models provide reasonable inference (low positive bias, high precision) about animal abundance, but have potential for overestimating precision. Analysis of spotted seal data indicated that several model formulations, including those based on a log-Gaussian Cox process, had a tendency to overestimate abundance. By contrast, a model that included a population closure assumption and a scale prior on total

  5. Minireview: Epigenetic programming of diabetes and obesity: animal models.

    Science.gov (United States)

    Seki, Yoshinori; Williams, Lyda; Vuguin, Patricia M; Charron, Maureen J

    2012-03-01

    A growing body of evidence suggests that the intrauterine (IU) environment has a significant and lasting effect on the long-term health of the growing fetus and the development of metabolic disease in later life as put forth in the fetal origins of disease hypothesis. Metabolic diseases have been associated with alterations in the epigenome that occur without changes in the DNA sequence, such as cytosine methylation of DNA, histone posttranslational modifications, and micro-RNA. Animal models of epigenetic modifications secondary to an altered IU milieu are an invaluable tool to study the mechanisms that determine the development of metabolic diseases, such as diabetes and obesity. Rodent and nonlitter bearing animals are good models for the study of disease, because they have similar embryology, anatomy, and physiology to humans. Thus, it is feasible to monitor and modify the IU environment of animal models in order to gain insight into the molecular basis of human metabolic disease pathogenesis. In this review, the database of PubMed was searched for articles published between 1999 and 2011. Key words included epigenetic modifications, IU growth retardation, small for gestational age, animal models, metabolic disease, and obesity. The inclusion criteria used to select studies included animal models of epigenetic modifications during fetal and neonatal development associated with adult metabolic syndrome. Experimental manipulations included: changes in the nutritional status of the pregnant female (calorie-restricted, high-fat, or low-protein diets during pregnancy), as well as the father; interference with placenta function, or uterine blood flow, environmental toxin exposure during pregnancy, as well as dietary modifications during the neonatal (lactation) as well as pubertal period. This review article is focused solely on studies in animal models that demonstrate epigenetic changes that are correlated with manifestation of metabolic disease, including diabetes

  6. Continuous-time discrete-space models for animal movement

    Science.gov (United States)

    Hanks, Ephraim M.; Hooten, Mevin B.; Alldredge, Mat W.

    2015-01-01

    The processes influencing animal movement and resource selection are complex and varied. Past efforts to model behavioral changes over time used Bayesian statistical models with variable parameter space, such as reversible-jump Markov chain Monte Carlo approaches, which are computationally demanding and inaccessible to many practitioners. We present a continuous-time discrete-space (CTDS) model of animal movement that can be fit using standard generalized linear modeling (GLM) methods. This CTDS approach allows for the joint modeling of location-based as well as directional drivers of movement. Changing behavior over time is modeled using a varying-coefficient framework which maintains the computational simplicity of a GLM approach, and variable selection is accomplished using a group lasso penalty. We apply our approach to a study of two mountain lions (Puma concolor) in Colorado, USA.

  7. Rhythm and blues: animal models of epilepsy and depression comorbidity.

    Science.gov (United States)

    Epps, S Alisha; Weinshenker, David

    2013-01-15

    Clinical evidence shows a strong, bidirectional comorbidity between depression and epilepsy that is associated with decreased quality of life and responsivity to pharmacotherapies. At present, the neurobiological underpinnings of this comorbidity remain hazy. To complicate matters, anticonvulsant drugs can cause mood disturbances, while antidepressant drugs can lower seizure threshold, making it difficult to treat patients suffering from both depression and epilepsy. Animal models have been created to untangle the mechanisms behind the relationship between these disorders and to serve as screening tools for new therapies targeted to treat both simultaneously. These animal models are based on chemical interventions (e.g. pentylenetetrazol, kainic acid, pilocarpine), electrical stimulations (e.g. kindling, electroshock), and genetic/selective breeding paradigms (e.g. genetically epilepsy-prone rats (GEPRs), genetic absence epilepsy rat from Strasbourg (GAERS), WAG/Rij rats, swim lo-active rats (SwLo)). Studies on these animal models point to some potential mechanisms that could explain epilepsy and depression comorbidity, such as various components of the dopaminergic, noradrenergic, serotonergic, and GABAergic systems, as well as key brain regions, like the amygdala and hippocampus. These models have also been used to screen possible therapies. The purpose of the present review is to highlight the importance of animal models in research on comorbid epilepsy and depression and to explore the contributions of these models to our understanding of the mechanisms and potential treatments for these disorders.

  8. Animal models of skin disease for drug discovery

    Science.gov (United States)

    Avci, Pinar; Sadasivam, Magesh; Gupta, Asheesh; De Melo, Wanessa CMA; Huang, Ying-Ying; Yin, Rui; Rakkiyappan, Chandran; Kumar, Raj; Otufowora, Ayodeji; Nyame, Theodore; Hamblin, Michael R

    2013-01-01

    Introduction Discovery of novel drugs, treatments, and testing of consumer products in the field of dermatology is a multi-billion dollar business. Due to the distressing nature of many dermatological diseases, and the enormous consumer demand for products to reverse the effects of skin photodamage, aging, and hair loss, this is a very active field. Areas covered In this paper, we will cover the use of animal models that have been reported to recapitulate to a greater or lesser extent the features of human dermatological disease. There has been a remarkable increase in the number and variety of transgenic mouse models in recent years, and the basic strategy for constructing them is outlined. Expert opinion Inflammatory and autoimmune skin diseases are all represented by a range of mouse models both transgenic and normal. Skin cancer is mainly studied in mice and fish. Wound healing is studied in a wider range of animal species, and skin infections such as acne and leprosy also have been studied in animal models. Moving to the more consumer-oriented area of dermatology, there are models for studying the harmful effect of sunlight on the skin, and testing of sunscreens, and several different animal models of hair loss or alopecia. PMID:23293893

  9. Near-infrared reflectance spectroscopy for predicting amino acids content in intact processed animal proteins.

    Science.gov (United States)

    De la Haba, Maria José; Garrido-Varo, Ana; Guerrero-Ginel, José Emilio; Pérez-Marín, Dolores C

    2006-10-01

    Near-infrared calibrations were developed for the instantaneous prediction of amino acids composition of processed animal proteins (PAPs). Two sample presentation modes were compared (ground vs intact) for demonstrating the viability of the analysis in the intact form, avoiding the need for milling. Modified partial least-squares (MPLS) equations for the prediction of amino acids in PAPs were developed using the same set of samples (N = 92 PAPs) analyzed in ground and intact form and in three cups differing in the optical window size. The standard error for cross validation (SECV) and the coefficient of determination (1-VR) values yielded with the calibrations developed using the samples analyzed in the intact form showed similar or even better accuracy than those obtained with finely ground samples. The excellent predictive ability (1-VR > 0.90; CV < 3.0%) obtained for the prediction of amino acids in intact processed animal proteins opens an enormous expectative for the on-line implementation of NIRS technology in the processing and marketing of these important protein feed ingredients, alleviating the costs and time associated with the routine quality controls.

  10. Case studies in archaeological predictive modelling

    NARCIS (Netherlands)

    Verhagen, Jacobus Wilhelmus Hermanus Philippus

    2007-01-01

    In this thesis, a collection of papers is put together dealing with various quantitative aspects of predictive modelling and archaeological prospection. Among the issues covered are the effects of survey bias on the archaeological data used for predictive modelling, and the complexities of testing p

  11. Childhood asthma prediction models: a systematic review.

    Science.gov (United States)

    Smit, Henriette A; Pinart, Mariona; Antó, Josep M; Keil, Thomas; Bousquet, Jean; Carlsen, Kai H; Moons, Karel G M; Hooft, Lotty; Carlsen, Karin C Lødrup

    2015-12-01

    Early identification of children at risk of developing asthma at school age is crucial, but the usefulness of childhood asthma prediction models in clinical practice is still unclear. We systematically reviewed all existing prediction models to identify preschool children with asthma-like symptoms at risk of developing asthma at school age. Studies were included if they developed a new prediction model or updated an existing model in children aged 4 years or younger with asthma-like symptoms, with assessment of asthma done between 6 and 12 years of age. 12 prediction models were identified in four types of cohorts of preschool children: those with health-care visits, those with parent-reported symptoms, those at high risk of asthma, or children in the general population. Four basic models included non-invasive, easy-to-obtain predictors only, notably family history, allergic disease comorbidities or precursors of asthma, and severity of early symptoms. Eight extended models included additional clinical tests, mostly specific IgE determination. Some models could better predict asthma development and other models could better rule out asthma development, but the predictive performance of no single model stood out in both aspects simultaneously. This finding suggests that there is a large proportion of preschool children with wheeze for which prediction of asthma development is difficult.

  12. Combining Spatial and Telemetric Features for Learning Animal Movement Models

    CERN Document Server

    Kapicioglu, Berk; Wikelski, Martin; Broderick, Tamara

    2012-01-01

    We introduce a new graphical model for tracking radio-tagged animals and learning their movement patterns. The model provides a principled way to combine radio telemetry data with an arbitrary set of userdefined, spatial features. We describe an efficient stochastic gradient algorithm for fitting model parameters to data and demonstrate its effectiveness via asymptotic analysis and synthetic experiments. We also apply our model to real datasets, and show that it outperforms the most popular radio telemetry software package used in ecology. We conclude that integration of different data sources under a single statistical framework, coupled with appropriate parameter and state estimation procedures, produces both accurate location estimates and an interpretable statistical model of animal movement.

  13. Animal models for implant biomaterial research in bone: A review

    Directory of Open Access Journals (Sweden)

    A I Pearce

    2007-03-01

    Full Text Available Development of an optimal interface between bone and orthopaedic and dental implants has taken place for many years. In order to determine whether a newly developed implant material conforms to the requirements of biocompatibility, mechanical stability and safety, it must undergo rigorous testing both in vitro and in vivo. Results from in vitro studies can be difficult to extrapolate to the in vivo situation. For this reason the use of animal models is often an essential step in the testing of orthopaedic and dental implants prior to clinical use in humans. This review discusses some of the more commonly available and frequently used animal models such as the dog, sheep, goat, pig and rabbit models for the evaluation of bone-implant interactions. Factors for consideration when choosing an animal model and implant design are discussed. Various bone specific features are discussed including the usage of the species, bone macrostructure and microstructure and bone composition and remodelling, with emphasis being placed on the similarity between the animal model and the human clinical situation. While the rabbit was the most commonly used of the species discussed in this review, it is clear that this species showed the least similarities to human bone. There were only minor differences in bone composition between the various species and humans. The pig demonstrated a good likeness with human bone however difficulties may be encountered in relation to their size and ease of handling. In this respect the dog and sheep/goat show more promise as animal models for the testing of bone implant materials. While no species fulfils all of the requirements of an ideal model, an understanding of the differences in bone architecture and remodelling between the species is likely to assist in the selection of a suitable species for a defined research question.

  14. Social conflict exacerbates an animal model of multiple sclerosis.

    Science.gov (United States)

    Meagher, Mary W; Johnson, Robin R; Vichaya, Elisabeth Good; Young, Erin E; Lunt, Shannon; Welsh, C Jane

    2007-07-01

    A growing body of evidence suggests that social conflict is associated with inflammatory disease onset and exacerbations in multiple sclerosis (MS) patients and in animal models of MS. This review illustrates how animal research can be used to elucidate the biobehavioral mechanisms underlying the adverse health effects of social conflict. The authors review studies indicating that social conflict exacerbates a virally initiated animal model of MS. This research suggests that the deleterious effects of social conflict may be partially mediated by stress-induced increases in pro-inflammatory cytokine levels in the central nervous system. In addition, they provide evidence that the adverse health effects of social conflict can be prevented by blocking the stress-induced increases in cytokine activity. This suggests that interventions designed to prevent or reverse the stress-induced increases in cytokine activity may be able to prevent or reverse some of the negative health effects of social conflict in humans.

  15. Evolution of animal models in cancer vaccine development.

    Science.gov (United States)

    Wei, Wei-Zen; Jones, Richard F; Juhasz, Csaba; Gibson, Heather; Veenstra, Jesse

    2015-12-16

    Advances in cancer vaccine development are facilitated by animal models reflecting key features of human cancer and its interface with host immunity. Several series of transplantable preneoplastic and neoplastic mouse mammary lesions have been used to delineate mechanisms of anti-tumor immunity. Mimicking immune tolerance to tumor-associated antigens (TAA) such as HER2/neu, transgenic mice developing spontaneous mammary tumors are strong model systems for pre-clinical vaccine testing. In these models, HER2 DNA vaccines are easily administered, well-tolerated, and induce both humoral and cellular immunity. Although engineered mouse strains have advanced cancer immunotherapy, basic shortcomings remain. For example, multiple mouse strains have to be tested to recapitulate genetic regulation of immune tolerance in humans. Outbred domestic felines more closely parallel humans in the natural development of HER2 positive breast cancer and their varying genetic background. Electrovaccination with heterologous HER2 DNA induces robust adaptive immune responses in cats. Importantly, homologous feline HER2 DNA with a single amino acid substitution elicits unique antibodies to feline mammary tumor cells, unlocking a new vaccine principle. As an alternative approach to targeted vaccination, non-surgical tumor ablation such as cryoablation induces anti-tumor immunity via in situ immunization, particularly when combined with toll-like receptor (TLR) agonist. As strategies for vaccination advance, non-invasive monitoring of host response becomes imperative. As an example, magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning following administration of tryptophan metabolism tracer [11C]-alpha-methyl-tryptophan (AMT) provides non-invasive imaging of both tumor growth and metabolic activities. Because AMT is a substrate of indoleamine-pyrrole 2,3-dioxygenase (IDO), an enzyme that produces the immune regulatory molecule kynurenine, AMT imaging can provide

  16. Predicting the kinetics of chelating agents in man from animal data

    Energy Technology Data Exchange (ETDEWEB)

    Durbin, P.W.; Schmidt, C.T. (Lawrence Berkeley Lab., CA (USA))

    1989-01-01

    Published data were collected on clearance of 82Br, 24Na, inulin, and the ligands CaNa2-EDTA and CaNa3-DTPA from plasma of rats, dogs, and adult men. Data were restructured to a common base and reanalyzed using a two-compartment open-system kinetic model with an outlet from plasma to urinary excretion or from interstitial fluid to deposition in tissues. This was used to obtain transfer rates, distribution volumes, renal clearance, tracer content of interstitial fluid, and cumulative urinary excretion. The validity of the approach was demonstrated by good agreement of the calculated distribution volumes and renal clearances of the selected tracers with published values obtained by other analytical methods. The values of the parameters of the plasma curves and the transfer rates for EDTA and DTPA in the animals were combined with physiological data to evaluate the kinetic parameters of those substances in man. The human kinetic parameters of the ligands predicted from rat or dog data differed, on the average, from the values calculated from human data by +/- 13 and +/- 38%, respectively. The effective concentration of EDTA or DTPA in body fluids from time of injection to complete excretion and the mean concentration for the first 360 min after injection was calculated to be about four times greater in man than in rats and 3.5 times greater than in dogs for equimolar amounts injected. Based on the pharmacokinetics of DTPA, chelation therapy immediately after an actinide accident involving inhalation or extensive skin damage will be more efficient and more effective if a fraction of the standard clinical ZnNa3-DTPA dosage is administered every few hours instead of as a single daily injection.

  17. Animal models of major depression and their clinical implications.

    Science.gov (United States)

    Czéh, Boldizsár; Fuchs, Eberhard; Wiborg, Ove; Simon, Mária

    2016-01-04

    Major depressive disorder is a common, complex, and potentially life-threatening mental disorder that imposes a severe social and economic burden worldwide. Over the years, numerous animal models have been established to elucidate pathophysiology that underlies depression and to test novel antidepressant treatment strategies. Despite these substantial efforts, the animal models available currently are of limited utility for these purposes, probably because none of the models mimics this complex disorder fully. It is presumable that psychiatric illnesses, such as affective disorders, are related to the complexity of the human brain. Here, we summarize the animal models that are used most commonly for depression, and discuss their advantages and limitations. We discuss genetic models, including the recently developed optogenetic tools and the stress models, such as the social stress, chronic mild stress, learned helplessness, and early-life stress paradigms. Moreover, we summarize briefly the olfactory bulbectomy model, as well as models that are based on pharmacological manipulations and disruption of the circadian rhythm. Finally, we highlight common misinterpretations and often-neglected important issues in this field.

  18. 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

    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...... 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...

  19. Concise Review: Stem Cell Trials Using Companion Animal Disease Models.

    Science.gov (United States)

    Hoffman, Andrew M; Dow, Steven W

    2016-07-01

    Studies to evaluate the therapeutic potential of stem cells in humans would benefit from more realistic animal models. In veterinary medicine, companion animals naturally develop many diseases that resemble human conditions, therefore, representing a novel source of preclinical models. To understand how companion animal disease models are being studied for this purpose, we reviewed the literature between 2008 and 2015 for reports on stem cell therapies in dogs and cats, excluding laboratory animals, induced disease models, cancer, and case reports. Disease models included osteoarthritis, intervertebral disc degeneration, dilated cardiomyopathy, inflammatory bowel diseases, Crohn's fistulas, meningoencephalomyelitis (multiple sclerosis-like), keratoconjunctivitis sicca (Sjogren's syndrome-like), atopic dermatitis, and chronic (end-stage) kidney disease. Stem cells evaluated in these studies included mesenchymal stem-stromal cells (MSC, 17/19 trials), olfactory ensheathing cells (OEC, 1 trial), or neural lineage cells derived from bone marrow MSC (1 trial), and 16/19 studies were performed in dogs. The MSC studies (13/17) used adipose tissue-derived MSC from either allogeneic (8/13) or autologous (5/13) sources. The majority of studies were open label, uncontrolled studies. Endpoints and protocols were feasible, and the stem cell therapies were reportedly safe and elicited beneficial patient responses in all but two of the trials. In conclusion, companion animals with naturally occurring diseases analogous to human conditions can be recruited into clinical trials and provide realistic insight into feasibility, safety, and biologic activity of novel stem cell therapies. However, improvements in the rigor of manufacturing, study design, and regulatory compliance will be needed to better utilize these models. Stem Cells 2016;34:1709-1729.

  20. Infectious diseases among animals : combining models with data

    NARCIS (Netherlands)

    Koeijer, A.A. de

    2003-01-01

    To eradicate or control the spread of infectious diseases, knowledge on the spread of the infection between (groups of) animals is necessary. Models can include such information and can subsequently be used to observe the efficacy of various control measures in fighting the infection. However, the a

  1. Getting neurorehabilitation right: what can be learned from animal models?

    Science.gov (United States)

    Krakauer, John W; Carmichael, S Thomas; Corbett, Dale; Wittenberg, George F

    2012-10-01

    Animal models suggest that a month of heightened plasticity occurs in the brain after stroke, accompanied by most of the recovery from impairment. This period of peri-infarct and remote plasticity is associated with changes in excitatory/inhibitory balance and the spatial extent and activation of cortical maps and structural remodeling. The best time for experience and training to improve outcome is unclear. In animal models, very early (30 days) is much less effective both in terms of outcome and morphological changes associated with plasticity. In clinical practice, rehabilitation after disabling stroke involves a relatively brief period of inpatient therapy that does not come close to matching intensity levels investigated in animal models and includes the training of compensatory strategies that have minimal impact on impairment. Current rehabilitation treatments have a disappointingly modest effect on impairment early or late after stroke. Translation from animal models will require the following: (1) substantial increases in the intensity and dosage of treatments offered in the first month after stroke with an emphasis on impairment; (2) combinational approaches such as noninvasive brain stimulation with robotics, based on current understanding of motor learning and brain plasticity; and (3) research that emphasizes mechanistic phase II studies over premature phase III clinical trials.

  2. Social Stress in Rats : An Animal Model of Depression?

    NARCIS (Netherlands)

    Koolhaas, J.M.; Meerlo, P.; De Boer, S..; Strubbe, J.H.; Bohus, B.

    1995-01-01

    Our current understanding of the physiological mechanisms underlying depressive disorders is not only based on behavioral, neuroendocrine and pharmacological studies in depressed humans, but also on experimental studies in a wide variety of animal models of depression. Ideally, the two approaches sh

  3. Animation Model to Conceptualize ATP Generation: A Mitochondrial Oxidative Phosphorylation

    Science.gov (United States)

    Jena, Ananta Kumar

    2015-01-01

    Adenosine triphosphate (ATP) is the molecular unit of intracellular energy and it is the product of oxidative phosphorylation of cellular respiration uses in cellular processes. The study explores the growth of the misconception levels amongst the learners and evaluates the effectiveness of animation model over traditional methods. The data…

  4. In search for animal models of female sexual dysfunction

    NARCIS (Netherlands)

    Snoeren, E.M.S.

    2010-01-01

    Female Sexual Dysfunction (FSD) is a disorder that affects around 40% of the population. Low sexual arousal and low sexual desire are the most common problems. The mechanisms underlying the disorder are still unclear. The aims of this thesis were 1) the search for animal models of FSD, 2) the develo

  5. Replacement, refinement, and reduction: necessity of standardization and computational models for long bone fracture repair in animals.

    Science.gov (United States)

    Reifenrath, Janin; Angrisani, Nina; Lalk, Mareike; Besdo, Silke

    2014-08-01

    In the field of fracture healing it is essential to know the impacts of new materials. Fracture healing of long bones is studied in various animal models and extrapolated for use in humans, although there are differences between the micro- and macrostructure of human versus animal bone. Unfortunately, recommended standardized models for fracture repair studies do not exist. Many different study designs with various animal models are used. Concerning the general principles of replacement, refinement and reduction in animal experiments (three "Rs"), a standardization would be desirable to facilitate better comparisons between different studies. In addition, standardized methods allow better prediction of bone healing properties and implant requirements with computational models. In this review, the principles of bone fracture healing and differences between osteotomy and artificial fracture models as well as influences of fixation devices are summarized. Fundamental considerations regarding animal model choice are discussed, as it is very important to know the limitations of the chosen model. In addition, a compendium of common animal models is assembled with special focus on rats, rabbits, and sheep as most common fracture models. Fracture healing simulation is a basic tool in reducing the number of experimental animals, so its progress is also presented here. In particular, simulation of different animal models is presented. In conclusion, a standardized fracture model is of utmost importance for the best adaption of simulation to experimental setups and comparison between different studies. One of the basic goals should be to reach a consensus for standardized fracture models.

  6. Animal models for Alzheimer's disease and frontotemporal dementia: a perspective

    Directory of Open Access Journals (Sweden)

    Jürgen Götz

    2009-11-01

    Full Text Available In dementia research, animal models have become indispensable tools. They not only model aspects of the human condition, but also simulate processes that occur in humans and hence provide insight into how disease is initiated and propagated. The present review discusses two prominent human neurodegenerative disorders, Alzheimer's disease and frontotemporal dementia. It discusses what we would like to model in animals and highlights some of the more recent achievements using species as diverse as mice, fish, flies and worms. Advances in imaging and therapy are explored. We also discuss some anticipated new models and developments. These will reveal how key players in the pathogenesis of Alzheimer's disease and frontotemporal dementia, such as the peptide Aβ (amyloid β and the protein tau, cause neuronal dysfunction and eventually, neuronal demise. Understanding these processes fully will lead to early diagnosis and therapy.

  7. Establishing of the Transplanted Animal Models for Human Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Xingli Zhang; Jinchang Wu

    2009-01-01

    Lung cancer is the leading cause of cancer mortality worldwide.Even with the applications of excision,radiotherapy,chemotherapy,and gene therapy,the 5 year survival rate is only 15% in the USA.Clinically relevant laboratory animal models of the disease could greatly facilitate understanding of the pathogenesis of lung cancer,its progression,invasion and metastasis.Transplanted lung cancer models are of special interest and are widely used today.Such models are essential tools in accelerating development of new therapies for lung cancer.In this communication we will present a brief overview of the hosts,sites and pathways used to establish transplanted animal lung tumor models.

  8. Model predictive control classical, robust and stochastic

    CERN Document Server

    Kouvaritakis, Basil

    2016-01-01

    For the first time, a textbook that brings together classical predictive control with treatment of up-to-date robust and stochastic techniques. Model Predictive Control describes the development of tractable algorithms for uncertain, stochastic, constrained systems. The starting point is classical predictive control and the appropriate formulation of performance objectives and constraints to provide guarantees of closed-loop stability and performance. Moving on to robust predictive control, the text explains how similar guarantees may be obtained for cases in which the model describing the system dynamics is subject to additive disturbances and parametric uncertainties. Open- and closed-loop optimization are considered and the state of the art in computationally tractable methods based on uncertainty tubes presented for systems with additive model uncertainty. Finally, the tube framework is also applied to model predictive control problems involving hard or probabilistic constraints for the cases of multiplic...

  9. A Knowledge Representation Model for Video—Based Animation

    Institute of Scientific and Technical Information of China (English)

    劳志强; 潘云鹤

    1998-01-01

    In this paper,a brief survey on knowledge-based animation techniques is given.Then a VideoStream-based Knowledge Representation Model(VSKRM)for Joint Objects is presented which includes the knowledge representation of :Graphic Object,Action and VideoStream.Next a general description of the UI framework of a system is given based on the VSKRM model.Finally,a conclusion is reached.

  10. In search for animal models of female sexual dysfunction

    OpenAIRE

    2010-01-01

    Female Sexual Dysfunction (FSD) is a disorder that affects around 40% of the population. Low sexual arousal and low sexual desire are the most common problems. The mechanisms underlying the disorder are still unclear. The aims of this thesis were 1) the search for animal models of FSD, 2) the development of new treatments and 3) to investigate the effects of common used antidepressants on female sexual behavior. In the first part, two rat models are described which were validated with pharmac...

  11. The Cambridge MRI database for animal models of Huntington disease.

    Science.gov (United States)

    Sawiak, Stephen J; Morton, A Jennifer

    2016-01-01

    We describe the Cambridge animal brain magnetic resonance imaging repository comprising 400 datasets to date from mouse models of Huntington disease. The data include raw images as well as segmented grey and white matter images with maps of cortical thickness. All images and phenotypic data for each subject are freely-available without restriction from (http://www.dspace.cam.ac.uk/handle/1810/243361/). Software and anatomical population templates optimised for animal brain analysis with MRI are also available from this site.

  12. Malarial birds: modeling infectious human disease in animals.

    Science.gov (United States)

    Slater, Leo B

    2005-01-01

    Through the examination of avian malarias as models of infectious human disease, this paper reveals the kinds of claims that scientists and physicians made on the basis of animal models-biological systems in the laboratory and the field-and what characteristics made for congruence between these models and human malaria. The focus is on the period between 1895 and 1945, and on the genesis and trajectory of certain animal models of malaria within specific locations, such as the Johns Hopkins School of Hygiene and Public Health in Baltimore and Bayer (I. G. Farben) in Elberfeld. These exemplars illustrate a diversity of approaches to malaria-as-disease, and the difficulties of framing aspects of this disease complex within an animal or laboratory system. The diversity and nearness to wild types of the birds, protozoan parasites, and mosquitoes that made up these malaria models contributed a great deal to the complexity of the models. Avian malarias, adopted with enthusiasm, were essential to the success of the U.S. antimalarial program during World War II.

  13. 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.

  14. Animal models for Ebola and Marburg virus infections.

    Science.gov (United States)

    Nakayama, Eri; Saijo, Masayuki

    2013-09-05

    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.

  15. Transmission of Helicobacter pyori in an animal model.

    Science.gov (United States)

    Cellini, L; Marzio, L; Ferrero, G; Del Vino, A; Di Campli, E; Grossi, L; Toracchio, S; Artese, L

    2001-01-01

    An experimental murine model was studied to evaluate the orogastrointestinal colonization of Helicobacter pylori and the animal-to-animal transmission. Balb/C mice were infected with H. pylori and housed with uninoculated mice in cages with and without a grate on the floor. Mice were killed after 7, 14, 30, and 45 days, and samples from the esophagus, stomach, small intestine, colon, and rectum were analyzed for H. pylori by PCR and immunohistochemistry and for histological changes. Bacterial colonization was assessed also by culture from stomach samples. H. pylori was cultured by stomach samples of infected mice at 7, 14, and 30 days. Using PCR and immunohistochemistry, H. pylori was detected in inoculated and uninoculated mice in all areas examined, with an high percentage of positive samples in the esophagus and stomach. Moreover transmission was detected, without differences, regardless of whether mice were housed with or without a grate on the floor, supporting an orooral animal transmission.

  16. Collection methods of trematode eggs using experimental animal models.

    Science.gov (United States)

    Tsubokawa, Daigo; Sugiyama, Hiromu; Mikami, Fusako; Shibata, Katsumasa; Shibahara, Toshiyuki; Fukuda, Koichi; Takamiya, Shinzaburo; Yamasaki, Hiroshi; Nakamura, Takeshi; Tsuji, Naotoshi

    2016-10-01

    Although observing the eggs of human parasitic helminth is essential for medical education in parasitology, opportunities for collection of the eggs are limited. Collection of the eggs using experimental animal models is needed for a sustainable supply. The metacercariae of three trematode species, Paragonimus westermani, Clonorchis sinensis and Metagonimus yokogawai, were collected from the second intermediate hosts: freshwater crabs and fishes, which were obtained using online shopping in Japan, and inoculated to experimental animal rat and dog. Consequently, eggs of the three trematode species were obtained abundantly from the feces of the animals. The eggs are being used for student training in several Japanese universities. In this article, we introduce the collection procedures for trematode eggs.

  17. Making animals alcoholic: shifting laboratory models of addiction.

    Science.gov (United States)

    Ramsden, Edmund

    2015-01-01

    The use of animals as experimental organisms has been critical to the development of addiction research from the nineteenth century. They have been used as a means of generating reliable data regarding the processes of addiction that was not available from the study of human subjects. Their use, however, has been far from straightforward. Through focusing on the study of alcoholism, where the nonhuman animal proved a most reluctant collaborator, this paper will analyze the ways in which scientists attempted to deal with its determined sobriety and account for their consistent failure to replicate the volitional consumption of ethanol to the point of physical dependency. In doing so, we will see how the animal model not only served as a means of interrogating a complex pathology, but also came to embody competing definitions of alcoholism as a disease process, and alternative visions for the very structure and purpose of a research field.

  18. Animal models of osteogenesis imperfecta: applications in clinical research

    Directory of Open Access Journals (Sweden)

    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

  19. Energy based prediction models for building acoustics

    DEFF Research Database (Denmark)

    Brunskog, Jonas

    2012-01-01

    In order to reach robust and simplified yet accurate prediction models, energy based principle are commonly used in many fields of acoustics, especially in building acoustics. This includes simple energy flow models, the framework of statistical energy analysis (SEA) as well as more elaborated...... principles as, e.g., wave intensity analysis (WIA). The European standards for building acoustic predictions, the EN 12354 series, are based on energy flow and SEA principles. In the present paper, different energy based prediction models are discussed and critically reviewed. Special attention is placed...

  20. Animal models of transcranial direct current stimulation: Methods and mechanisms.

    Science.gov (United States)

    Jackson, Mark P; Rahman, Asif; Lafon, Belen; Kronberg, Gregory; Ling, Doris; Parra, Lucas C; Bikson, Marom

    2016-11-01

    The objective of this review is to summarize the contribution of animal research using direct current stimulation (DCS) to our understanding of the physiological effects of transcranial direct current stimulation (tDCS). We comprehensively address experimental methodology in animal studies, broadly classified as: (1) transcranial stimulation; (2) direct cortical stimulation in vivo and (3) in vitro models. In each case advantages and disadvantages for translational research are discussed including dose translation and the overarching "quasi-uniform" assumption, which underpins translational relevance in all animal models of tDCS. Terminology such as anode, cathode, inward current, outward current, current density, electric field, and uniform are defined. Though we put key animal experiments spanning decades in perspective, our goal is not simply an exhaustive cataloging of relevant animal studies, but rather to put them in context of ongoing efforts to improve tDCS. Cellular targets, including excitatory neuronal somas, dendrites, axons, interneurons, glial cells, and endothelial cells are considered. We emphasize neurons are always depolarized and hyperpolarized such that effects of DCS on neuronal excitability can only be evaluated within subcellular regions of the neuron. Findings from animal studies on the effects of DCS on plasticity (LTP/LTD) and network oscillations are reviewed extensively. Any endogenous phenomena dependent on membrane potential changes are, in theory, susceptible to modulation by DCS. The relevance of morphological changes (galvanotropy) to tDCS is also considered, as we suggest microscopic migration of axon terminals or dendritic spines may be relevant during tDCS. A majority of clinical studies using tDCS employ a simplistic dose strategy where excitability is singularly increased or decreased under the anode and cathode, respectively. We discuss how this strategy, itself based on classic animal studies, cannot account for the

  1. Reproduction of an animal model of landmine blast injuries

    Directory of Open Access Journals (Sweden)

    Sen ZHANG

    2014-03-01

    Full Text Available Objective To reproduce an animal model of landmine blast injuries for studying its mechanism and characteristics. Methods Fifteen healthy New Zealand white rabbits (body weight 1.9-2.4 kg were prepared as experimental animals. Punctiform burster was used to simulate the landmine, and it was electrically detonated far away to produce landmine blast injuries on unilateral hind limb of rabbits in upright state. The vital signs before and 5min, 15min, 30min, 45min, 1h, 2h, 3h, 6h, 9h and 12h after injuries were recorded. Autopsy of dead animals was performed immediately and the survivors were sacrificed for pathological examination 6h and 12h after the injury. Macroscopic and microscopic changes in the injured limb and distant organs were observed. Fifteen random adult body weights were generated by random number table, and the explosive energy of M14 landmine (about 29g TNT explosive energy was simulated, to compare the ratio of explosive force equivalent to weight calculated between experimental animals and randomly selected adults. Results No significant change in blood pressure was observed at different time points before and after injuries. A broom-like change was found in the injured limb by the general observation. The subareas and pathological changes of injured limb coincided with the typical limb injuries produced by landmine explosion. Damage in different degrees was found in distant organs, and the wound characteristics and injury of major organs were in accordance with the reports of relevant literature. The ratio of explosive equivalent to weight of experimental animals (0.50±0.04g TNT/kg was similar to that of randomly selected adults (0.51±0.05g TNT/kg. Conclusion The present animal model could simulate the landmine explosive injuries, and may be used in research of landmine explosive injuries. DOI: 10.11855/j.issn.0577-7402.2014.01.14

  2. Linking animal models of psychosis to computational models of dopamine function.

    Science.gov (United States)

    Smith, Andrew J; Li, Ming; Becker, Suzanna; Kapur, Shitij

    2007-01-01

    Psychosis is linked to dysregulation of the neuromodulator dopamine and antipsychotic drugs (APDs) work by blocking dopamine receptors. Dopamine-modulated disruption of latent inhibition (LI) and conditioned avoidance response (CAR) have served as standard animal models of psychosis and antipsychotic action, respectively. Meanwhile, the 'temporal difference' algorithm (TD) has emerged as the leading computational model of dopamine neuron firing. In this report TD is extended to include action at the level of dopamine receptors in order to explain a number of behavioral phenomena including the dose-dependent disruption of CAR by APDs, the temporal dissociation of the effects of APDs on receptors vs behavior, the facilitation of LI by APDs, and the disruption of LI by amphetamine. The model also predicts an APD-induced change to the latency profile of CAR--a novel prediction that is verified experimentally. The model's primary contribution is to link dopamine neuron firing, receptor manipulation, and behavior within a common formal framework that may offer insights into clinical observations.

  3. A method of shadow puppet figure modeling and animation

    Institute of Scientific and Technical Information of China (English)

    Xiao-fang HUANG; Shou-qian SUN; Ke-jun ZHANG; Tian-ning XU; Jian-feng WU; Bin ZHU

    2015-01-01

    To promote the development of the intangible cultural heritage of the world, shadow play, many studies have focused on shadow puppet modeling and interaction. Most of the shadow puppet figures are still imaginary, spread by ancients, or carved and painted by shadow puppet artists, without consideration of real dimensions or the appearance of human bodies. This study proposes an algorithm to transform 3D human models to 2D puppet figures for shadow puppets, including automatic location of feature points, automatic segmentation of 3D models, automatic extraction of 2D contours, automatic clothes matching, and animation. Experiment proves that more realistic and attractive figures and animations of the shadow puppet can be generated in real time with this algorithm.

  4. Neuronal and brain morphological changes in animal models of schizophrenia.

    Science.gov (United States)

    Flores, Gonzalo; Morales-Medina, Julio César; Diaz, Alfonso

    2016-03-15

    Schizophrenia, a severe and debilitating disorder with a high social burden, affects 1% of the adult world population. Available therapies are unable to treat all the symptoms, and result in strong side effects. For this reason, numerous animal models have been generated to elucidate the pathophysiology of this disorder. All these models present neuronal remodeling and abnormalities in spine stability. It is well known that the complexity in dendritic arborization determines the number of receptive synaptic contacts. Also the loss of dendritic spines and arbor stability are strongly associated with schizophrenia. This review evaluates changes in spine density and dendritic arborization in animal models of schizophrenia. By understanding these changes, pharmacological treatments can be designed to target specific neural systems to attenuate neuronal remodeling and associated behavioral deficits.

  5. Animal models of antimuscle-specific kinase myasthenia.

    Science.gov (United States)

    Richman, David P; Nishi, Kayoko; Ferns, Michael J; Schnier, Joachim; Pytel, Peter; Maselli, Ricardo A; Agius, Mark A

    2012-12-01

    Antimuscle-specific kinase (anti-MuSK) myasthenia (AMM) differs from antiacetylcholine receptor myasthenia gravis in exhibiting more focal muscle involvement (neck, shoulder, facial, and bulbar muscles) with wasting of the involved, primarily axial, muscles. AMM is not associated with thymic hyperplasia and responds poorly to anticholinesterase treatment. Animal models of AMM have been induced in rabbits, mice, and rats by immunization with purified xenogeneic MuSK ectodomain, and by passive transfer of large quantities of purified serum IgG from AMM patients into mice. The models have confirmed the pathogenic role of the MuSK antibodies in AMM and have demonstrated the involvement of both the presynaptic and postsynaptic components of the neuromuscular junction. The observations in this human disease and its animal models demonstrate the role of MuSK not only in the formation of this synapse but also in its maintenance.

  6. Characterization of animal models for primary sclerosing cholangitis (PSC).

    Science.gov (United States)

    Fickert, Peter; Pollheimer, Marion J; Beuers, Ulrich; Lackner, Carolin; Hirschfield, Gideon; Housset, Chantal; Keitel, Verena; Schramm, Christoph; Marschall, Hanns-Ulrich; Karlsen, Tom H; Melum, Espen; Kaser, Arthur; Eksteen, Bertus; Strazzabosco, Mario; Manns, Michael; Trauner, Michael

    2014-06-01

    Primary sclerosing cholangitis (PSC) is a chronic cholangiopathy characterized by biliary fibrosis, development of cholestasis and end stage liver disease, high risk of malignancy, and frequent need for liver transplantation. The poor understanding of its pathogenesis is also reflected in the lack of effective medical treatment. Well-characterized animal models are utterly needed to develop novel pathogenetic concepts and study new treatment strategies. Currently there is no consensus on how to evaluate and characterize potential PSC models, which makes direct comparison of experimental results and effective exchange of study material between research groups difficult. The International Primary Sclerosing Cholangitis Study Group (IPSCSG) has therefore summarized these key issues in a position paper proposing standard requirements for the study of animal models of PSC.

  7. Molecular bases of myelodysplastic syndromes: lessons from animal models.

    Science.gov (United States)

    Komeno, Yukiko; Kitaura, Jiro; Kitamura, Toshio

    2009-06-01

    Myelodysplastic syndrome (MDS) is a clonal disorder of hematopietic stem cells characterized by ineffective hematopoiesis, peripheral blood cytopenia, morphologic dysplasia, and susceptibility to acute myeloid leukemia. Several mechanisms have been suggested as causes of MDS: unbalanced chromosomal abnormalities reflecting a gain or loss of chromosomal material, point mutations of transcription factors, and inactivation of p53. However, appropriate animal models that mimic MDS have long been lacking. We recently reported a novel murine model of MDS that recapitulates trilineage dysplasia and transformation to AML. In this review, we summarize the animal models of MDS and discuss the molecular bases of MDS as well as those of leukemia and myeloproliferative disorders (MPD). J. Cell. Physiol. 219: 529-534, 2009. (c) 2009 Wiley-Liss, Inc.

  8. Hand Interface in Traditional Modeling and Animation Tasks

    Institute of Scientific and Technical Information of China (English)

    孙汉秋

    1996-01-01

    3-D task space in modeling and animation is usually reduced to the separate control dimensions supported by conventional interactive devices.This limitation maps only partial view of the problem to the device space at a time,and results in tedious and unnatural interface of control.This paper uses the DataGlove interface for modeling and animating scene behaviors.The modeling interface selects,scales,rotates,translates,copies and deletes the instances of the primitives.These basic modeling processes are directly performed in the task space,using hand shapes and motions.Hand shapes are recognized as discrete states that trigger the commands,and hand motion are mapped to the movement of a selected instance.The interactions through hand interface place the user as a participant in the process of behavior simulation.Both event triggering and role switching of hand are experimented in simulation.The event mode of hand triggers control signals or commands through a menu interface.The object mode of hand simulates itself as an object whose appearance or motion influences the motions of other objects in scene.The involvement of hand creates a diversity of dynamic situations for testing variable scene behaviors.Our experiments have shown the potential use of this interface directly in the 3-D modeling and animation task space.

  9. Neuroinflammation in animal models of traumatic brain injury

    Science.gov (United States)

    Chiu, Chong-Chi; Liao, Yi-En; Yang, Ling-Yu; Wang, Jing-Ya; Tweedie, David; Karnati, Hanuma K.; Greig, Nigel H.; Wang, Jia-Yi

    2016-01-01

    Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide. Neuroinflammation is prominent in the short and long-term consequences of neuronal injuries that occur after TBI. Neuroinflammation involves the activation of glia, including microglia and astrocytes, to release inflammatory mediators within the brain, and the subsequent recruitment of peripheral immune cells. Various animal models of TBI have been developed that have proved valuable to elucidate the pathophysiology of the disorder and to assess the safety and efficacy of novel therapies prior to clinical trials. These models provide an excellent platform to delineate key injury mechanisms that associate with types of injury (concussion, contusion, and penetration injuries) that occur clinically for the investigation of mild, moderate, and severe forms of TBI. Additionally, TBI modeling in genetically engineered mice, in particular, has aided the identification of key molecules and pathways for putative injury mechanisms, as targets for development of novel therapies for human TBI. This Review details the evidence showing that neuroinflammation, characterized by the activation of microglia and astrocytes and elevated production of inflammatory mediators, is a critical process occurring in various TBI animal models, provides a broad overview of commonly used animal models of TBI, and overviews representative techniques to quantify markers of the brain inflammatory process. A better understanding of neuroinflammation could open therapeutic avenues for abrogation of secondary cell death and behavioral symptoms that may mediate the progression of TBI. PMID:27382003

  10. Massive Predictive Modeling using Oracle R Enterprise

    CERN Document Server

    CERN. Geneva

    2014-01-01

    R is fast becoming the lingua franca for analyzing data via statistics, visualization, and predictive analytics. For enterprise-scale data, R users have three main concerns: scalability, performance, and production deployment. Oracle's R-based technologies - Oracle R Distribution, Oracle R Enterprise, Oracle R Connector for Hadoop, and the R package ROracle - address these concerns. In this talk, we introduce Oracle's R technologies, highlighting how each enables R users to achieve scalability and performance while making production deployment of R results a natural outcome of the data analyst/scientist efforts. The focus then turns to Oracle R Enterprise with code examples using the transparency layer and embedded R execution, targeting massive predictive modeling. One goal behind massive predictive modeling is to build models per entity, such as customers, zip codes, simulations, in an effort to understand behavior and tailor predictions at the entity level. Predictions...

  11. Surgical animal models of neuropathic pain: Pros and Cons.

    Science.gov (United States)

    Challa, Siva Reddy

    2015-03-01

    One of the biggest challenges for discovering more efficacious drugs for the control of neuropathic pain has been the diversity of chronic pain states in humans. It is now acceptable that different mechanisms contribute to normal physiologic pain, pain arising from tissue damage and pain arising from injury to the nervous system. To study pain transmission, spot novel pain targets and characterize the potential analgesic profile of new chemical entities, numerous experimental animal pain models have been developed that attempt to simulate the many human pain conditions. Among the neuropathic pain models, surgical models have paramount importance in the induction of pain states. Many surgical animal models exist, like the chronic constriction injury (CCI) to the sciatic nerve, partial sciatic nerve ligation (pSNL), spinal nerve ligation (SNL), spared nerve injury (SNI), brachial plexus avulsion (BPA), sciatic nerve transaction (SNT) and sciatic nerve trisection. Most of these models induce responses similar to those found in causalgia, a syndrome of sustained burning pain often seen in the distal extremity after partial peripheral nerve injury in humans. Researchers most commonly use these surgical models in both rats and mice during drug discovery to screen new chemical entities for efficacy in the area of neuropathic pain. However, there is scant literature that provides a comparative discussion of all these surgical models. Each surgical model has its own benefits and limitations. It is very difficult for a researcher to choose a suitable surgical animal model to suit their experimental set-up. Therefore, particular attention has been given in this review to comparatively provide the pros and cons of each model of surgically induced neuropathic pain.

  12. Animal models to investigate the pathogenesis of rheumatic heart disease

    Directory of Open Access Journals (Sweden)

    Catherine M Rush

    2014-11-01

    Full Text Available Rheumatic fever (RF and rheumatic heart disease (RHD are sequelae of group A streptococcal (GAS infection. Although an autoimmune process has long been considered to be responsible for the initiation of RF/RHD, it is only in the last few decades that the mechanisms involved in the pathogenesis of the inflammatory condition have been unravelled partly due to experimentation on animal models.RF/RHD is a uniquely human condition and modelling this disease in animals is challenging. Antibody and T cell responses to recombinant GAS M protein (rM and the subsequent interactions with cardiac tissue have been predominantly investigated using a rat autoimmune valvulitis model. In Lewis rats immunized with rM, the development of hallmark histological features akin to RF/RHD, both in the myocardial and in valvular tissue have been reported, with the generation of heart tissue cross reactive antibodies and T cells. However, studies of cardiac function are more challenging in such a model. Recently a Lewis rat model of Sydenham’s chorea (SC and related neuropsychiatric disorders has also been described. Rodent models are very useful for assessing disease mechanisms due to the availability of reagents to precisely determine sequential events following infection with GAS or post-challenge with specific proteins and or carbohydrate preparations from GAS. However, studies of cardiac function are more problematic in such models. In this review an historical overview of animal models previously used and those that are currently available will be discussed in terms of their usefulness in modelling different aspects of the disease process. Ultimately, cardiologists, microbiologists, immunologists and physiologists may have to resort to diverse models to investigate different aspects of RF/RHD.

  13. Cognitive endophenotypes, gene-environment interactions and experience-dependent plasticity in animal models of schizophrenia.

    Science.gov (United States)

    Burrows, Emma L; Hannan, Anthony J

    2016-04-01

    Schizophrenia is a devastating brain disorder caused by a complex and heterogeneous combination of genetic and environmental factors. In order to develop effective new strategies to prevent and treat schizophrenia, valid animal models are required which accurately model the disorder, and ideally provide construct, face and predictive validity. The cognitive deficits in schizophrenia represent some of the most debilitating symptoms and are also currently the most poorly treated. Therefore it is crucial that animal models are able to capture the cognitive dysfunction that characterizes schizophrenia, as well as the negative and psychotic symptoms. The genomes of mice have, prior to the recent gene-editing revolution, proven the most easily manipulable of mammalian laboratory species, and hence most genetic targeting has been performed using mouse models. Importantly, when key environmental factors of relevance to schizophrenia are experimentally manipulated, dramatic changes in the phenotypes of these animal models are often observed. We will review recent studies in rodent models which provide insight into gene-environment interactions in schizophrenia. We will focus specifically on environmental factors which modulate levels of experience-dependent plasticity, including environmental enrichment, cognitive stimulation, physical activity and stress. The insights provided by this research will not only help refine the establishment of optimally valid animal models which facilitate development of novel therapeutics, but will also provide insight into the pathogenesis of schizophrenia, thus identifying molecular and cellular targets for future preclinical and clinical investigations.

  14. Cervical Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing cervical cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  15. Breast Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing breast cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  16. Liver Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing liver cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  17. Ovarian Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing ovarian cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  18. Prostate Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing prostate cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  19. Pancreatic Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing pancreatic cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  20. Colorectal Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing colorectal cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  1. Bladder Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing bladder cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  2. Esophageal Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing esophageal cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  3. Lung Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing lung cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  4. Testicular Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of testicular cervical cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  5. Sex Differences in Animal Models: Focus on Addiction.

    Science.gov (United States)

    Becker, Jill B; Koob, George F

    2016-04-01

    The purpose of this review is to discuss ways to think about and study sex differences in preclinical animal models. We use the framework of addiction, in which animal models have excellent face and construct validity, to illustrate the importance of considering sex differences. There are four types of sex differences: qualitative, quantitative, population, and mechanistic. A better understanding of the ways males and females can differ will help scientists design experiments to characterize better the presence or absence of sex differences in new phenomena that they are investigating. We have outlined major quantitative, population, and mechanistic sex differences in the addiction domain using a heuristic framework of the three established stages of the addiction cycle: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. Female rats, in general, acquire the self-administration of drugs and alcohol more rapidly, escalate their drug taking with extended access more rapidly, show more motivational withdrawal, and (where tested in animal models of "craving") show greater reinstatement. The one exception is that female rats show less motivational withdrawal to alcohol. The bases for these quantitative sex differences appear to be both organizational, in that estradiol-treated neonatal animals show the male phenotype, and activational, in that the female phenotype depends on the effects of gonadal hormones. In animals, differences within the estrous cycle can be observed but are relatively minor. Such hormonal effects seem to be most prevalent during the acquisition of drug taking and less influential once compulsive drug taking is established and are linked largely to progesterone and estradiol. This review emphasizes not only significant differences in the phenotypes of females and males in the domain of addiction but emphasizes the paucity of data to date in our understanding of those differences.

  6. Automated quantitative gait analysis in animal models of movement disorders

    Directory of Open Access Journals (Sweden)

    Vandeputte Caroline

    2010-08-01

    Full Text Available Abstract Background Accurate and reproducible behavioral tests in animal models are of major importance in the development and evaluation of new therapies for central nervous system disease. In this study we investigated for the first time gait parameters of rat models for Parkinson's disease (PD, Huntington's disease (HD and stroke using the Catwalk method, a novel automated gait analysis test. Static and dynamic gait parameters were measured in all animal models, and these data were compared to readouts of established behavioral tests, such as the cylinder test in the PD and stroke rats and the rotarod tests for the HD group. Results Hemiparkinsonian rats were generated by unilateral injection of the neurotoxin 6-hydroxydopamine in the striatum or in the medial forebrain bundle. For Huntington's disease, a transgenic rat model expressing a truncated huntingtin fragment with multiple CAG repeats was used. Thirdly, a stroke model was generated by a photothrombotic induced infarct in the right sensorimotor cortex. We found that multiple gait parameters were significantly altered in all three disease models compared to their respective controls. Behavioural deficits could be efficiently measured using the cylinder test in the PD and stroke animals, and in the case of the PD model, the deficits in gait essentially confirmed results obtained by the cylinder test. However, in the HD model and the stroke model the Catwalk analysis proved more sensitive than the rotarod test and also added new and more detailed information on specific gait parameters. Conclusion The automated quantitative gait analysis test may be a useful tool to study both motor impairment and recovery associated with various neurological motor disorders.

  7. Nonalcoholic Steatohepatitis: A Search for Factual Animal Models

    Directory of Open Access Journals (Sweden)

    Sheila Cristina L. Sanches

    2015-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is characterized by hepatic steatosis, which occurs in the absence of alcohol abuse. NAFLD can evolve into progressive liver injury and fibrosis in the form of nonalcoholic steatohepatitis (NASH. Several animal models have been developed to attempt to represent the morphological, biochemical, and clinical features of human NASH. The actual review presents a critical analysis of the most commonly used experimental models of NAFLD/NASH development. These models can be classified into genetic, nutritional, and a combination of genetic and nutritional factors. The main genetic models are ob/ob and db/db mutant mice and Zucker rats. The principal nutritional models employ methionine- and choline-deficient, high-fat, high-cholesterol and high-cholate, cafeteria, and high-fructose diets. Currently, associations between high-fructose and various compositions of high-fat diets have been widely studied. Previous studies have encountered significant difficulties in developing animal models capable of reproducing human NASH. Some models produce consistent morphological findings, but the induction method differs significantly compared with the pathophysiology of human NASH. Other models precisely represent the clinical and etiological contexts of this disease but fail to provide accurate histopathological representations mainly in the progression from steatosis to liver fibrosis.

  8. Nonalcoholic Steatohepatitis: A Search for Factual Animal Models.

    Science.gov (United States)

    Sanches, Sheila Cristina L; Ramalho, Leandra Naira Z; Augusto, Marlei Josiele; da Silva, Deisy Mara; Ramalho, Fernando Silva

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, which occurs in the absence of alcohol abuse. NAFLD can evolve into progressive liver injury and fibrosis in the form of nonalcoholic steatohepatitis (NASH). Several animal models have been developed to attempt to represent the morphological, biochemical, and clinical features of human NASH. The actual review presents a critical analysis of the most commonly used experimental models of NAFLD/NASH development. These models can be classified into genetic, nutritional, and a combination of genetic and nutritional factors. The main genetic models are ob/ob and db/db mutant mice and Zucker rats. The principal nutritional models employ methionine- and choline-deficient, high-fat, high-cholesterol and high-cholate, cafeteria, and high-fructose diets. Currently, associations between high-fructose and various compositions of high-fat diets have been widely studied. Previous studies have encountered significant difficulties in developing animal models capable of reproducing human NASH. Some models produce consistent morphological findings, but the induction method differs significantly compared with the pathophysiology of human NASH. Other models precisely represent the clinical and etiological contexts of this disease but fail to provide accurate histopathological representations mainly in the progression from steatosis to liver fibrosis.

  9. Animal models of social contact and drug self-administration.

    Science.gov (United States)

    Strickland, Justin C; Smith, Mark A

    2015-09-01

    Social learning theories of drug abuse propose that individuals imitate drug use behaviors modeled by social peers, and that these behaviors are selectively reinforced and/or punished depending on group norms. Historically, animal models of social influence have focused on distal factors (i.e., those factors outside the drug-taking context) in drug self-administration studies. Recently, several investigators have developed novel models, or significantly modified existing models, to examine the role of proximal factors (i.e., those factors that are immediately present at the time of drug taking) on measures of drug self-administration. Studies using these newer models have revealed several important conclusions regarding the effects of social learning on drug abuse: 1) the presence of a social partner influences drug self-administration, 2) the behavior of a social partner determines whether social contact will increase or decrease drug intake, and 3) social partners can model and imitate specific patterns of drug self-administration. These findings are congruent with those obtained in the human laboratory, providing support for the cross-species generality and validity of these preclinical models. This mini-review describes in detail some of the preclinical animal models used to study social contact and drug self-administration to guide future research on social learning and drug abuse.

  10. Animal models of disease: feline hyperthyroidism: an animal model for toxic nodular goiter.

    Science.gov (United States)

    Peterson, Mark E

    2014-11-01

    Since first discovered just 35 years ago, the incidence of spontaneous feline hyperthyroidism has increased dramatically to the extent that it is now one of the most common disorders seen in middle-aged to senior domestic cats. Hyperthyroid cat goiters contain single or multiple autonomously (i.e. TSH-independent) functioning and growing thyroid nodules. Thus, hyperthyroidism in cats is clinically and histologically similar to toxic nodular goiter in humans. The disease in cats is mechanistically different from Graves' disease, because neither the hyperfunction nor growth of these nodules depends on extrathyroidal circulating stimulators. The basic lesion appears to be an excessive intrinsic growth capacity of some thyroid cells, but iodine deficiency, other nutritional goitrogens, or environmental disruptors may play a role in the disease pathogenesis. Clinical features of feline toxic nodular goiter include one or more palpable thyroid nodules, together with signs of hyperthyroidism (e.g. weight loss despite an increased appetite). Diagnosis of feline hyperthyroidism is confirmed by finding the increased serum concentrations of thyroxine and triiodothyronine, undetectable serum TSH concentrations, or increased thyroid uptake of radioiodine. Thyroid scintigraphy demonstrates a heterogeneous pattern of increased radionuclide uptake, most commonly into both thyroid lobes. Treatment options for toxic nodular goiter in cats are similar to that used in humans and include surgical thyroidectomy, radioiodine, and antithyroid drugs. Most authorities agree that ablative therapy with radioiodine is the treatment of choice for most cats with toxic nodular goiter, because the animals are older, and the disease will never go into remission.

  11. Posterior Predictive Model Checking in Bayesian Networks

    Science.gov (United States)

    Crawford, Aaron

    2014-01-01

    This simulation study compared the utility of various discrepancy measures within a posterior predictive model checking (PPMC) framework for detecting different types of data-model misfit in multidimensional Bayesian network (BN) models. The investigated conditions were motivated by an applied research program utilizing an operational complex…

  12. Neural models on temperature regulation for cold-stressed animals

    Science.gov (United States)

    Horowitz, J. M.

    1975-01-01

    The present review evaluates several assumptions common to a variety of current models for thermoregulation in cold-stressed animals. Three areas covered by the models are discussed: signals to and from the central nervous system (CNS), portions of the CNS involved, and the arrangement of neurons within networks. Assumptions in each of these categories are considered. The evaluation of the models is based on the experimental foundations of the assumptions. Regions of the nervous system concerned here include the hypothalamus, the skin, the spinal cord, the hippocampus, and the septal area of the brain.

  13. A Course in... Model Predictive Control.

    Science.gov (United States)

    Arkun, Yaman; And Others

    1988-01-01

    Describes a graduate engineering course which specializes in model predictive control. Lists course outline and scope. Discusses some specific topics and teaching methods. Suggests final projects for the students. (MVL)

  14. WHAT WE ARE LEARNING ON HTLV-1 PATHOGENESISFROM ANIMAL MODELS

    Directory of Open Access Journals (Sweden)

    Madeleine eDuc Dodon

    2012-08-01

    Full Text Available Isolated and identified more than 30 years ago, Human T-cell Leukemia Virus type 1 (HTLV-1 is the etiological agent of adult T-cell leukemia/lymphoma (ATL, an aggressive lymphoproliferative disease of activated CD4+ T cells, and other inflammatory disorders such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP. A variety of animal models have contributed to the fundamental knowledge of HTLV-1 transmission, pathogenesis and to the design of novel therapies to treat HTLV-1 associated diseases. Small animal models (rabbits, rats, mice as well as large animal models (monkeys have been utilized to significantly advance characterization of the viral proteins and of virus-infected cells in the early steps of infection, as well as in the development of leukemogenic and immunopathogenic processes. Over the past two decades, the creation of new immuno-compromised mouse strains that are robustly reconstituted with a functional human immune system (HIS after being transplanted with human tissues or progenitor cells has revolutionized the in vivo investigation of viral infection and pathogenesis. Recent observations obtained in HTLV-1-infected humanized HIS mice that develop lymphomas provide the opportunity to study the evolution of the proviral clonality in human T cells present in different lymphoid organs. Current progress in the improvement of those humanized models will favor the testing of drugs and the development of targeted therapies against HTLV-1-associated diseases.

  15. Neural circuit dysfunction in schizophrenia: Insights from animal models.

    Science.gov (United States)

    Sigurdsson, T

    2016-05-03

    Despite decades of research, the neural circuit abnormalities underlying schizophrenia remain elusive. Although studies on schizophrenia patients have yielded important insights they have not been able to fully reveal the details of how neural circuits are disrupted in the disease, which is essential for understanding its pathophysiology and developing new treatment strategies. Animal models of schizophrenia are likely to play an important role in this effort. Such models allow neural circuit dysfunction to be investigated in detail and the role of risk factors and pathophysiological mechanisms to be experimentally assessed. The goal of this review is to summarize what we have learned from electrophysiological studies that have examined neural circuit function in animal models of schizophrenia. Although these studies have revealed diverse manifestations of neural circuit dysfunction spanning multiple levels of analysis, common themes have nevertheless emerged across different studies and animal models, revealing a core set of neural circuit abnormalities. These include an imbalance between excitation and inhibition, deficits in synaptic plasticity, disruptions in local and long-range synchrony and abnormalities in dopaminergic signaling. The relevance of these findings to the pathophysiology of the disease is discussed, as well as outstanding questions for future research.

  16. 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.

  17. Large Animal Models for Foamy Virus Vector Gene Therapy

    Directory of Open Access Journals (Sweden)

    Peter A. Horn

    2012-12-01

    Full Text Available Foamy virus (FV vectors have shown great promise for hematopoietic stem cell (HSC gene therapy. Their ability to efficiently deliver transgenes to multi-lineage long-term repopulating cells in large animal models suggests they will be effective for several human hematopoietic diseases. Here, we review FV vector studies in large animal models, including the use of FV vectors with the mutant O6-methylguanine-DNA methyltransferase, MGMTP140K to increase the number of genetically modified cells after transplantation. In these studies, FV vectors have mediated efficient gene transfer to polyclonal repopulating cells using short ex vivo transduction protocols designed to minimize the negative effects of ex vivo culture on stem cell engraftment. In this regard, FV vectors appear superior to gammaretroviral vectors, which require longer ex vivo culture to effect efficient transduction. FV vectors have also compared favorably with lentiviral vectors when directly compared in the dog model. FV vectors have corrected leukocyte adhesion deficiency and pyruvate kinase deficiency in the dog large animal model. FV vectors also appear safer than gammaretroviral vectors based on a reduced frequency of integrants near promoters and also near proto-oncogenes in canine repopulating cells. Together, these studies suggest that FV vectors should be highly effective for several human hematopoietic diseases, including those that will require relatively high percentages of gene-modified cells to achieve clinical benefit.

  18. Equivalency and unbiasedness of grey prediction models

    Institute of Scientific and Technical Information of China (English)

    Bo Zeng; Chuan Li; Guo Chen; Xianjun Long

    2015-01-01

    In order to deeply research the structure discrepancy and modeling mechanism among different grey prediction mo-dels, the equivalence and unbiasedness of grey prediction mo-dels are analyzed and verified. The results show that al the grey prediction models that are strictly derived from x(0)(k) +az(1)(k) = b have the identical model structure and simulation precision. Moreover, the unbiased simulation for the homoge-neous exponential sequence can be accomplished. However, the models derived from dx(1)/dt+ax(1) =b are only close to those derived from x(0)(k)+az(1)(k)=b provided that|a|has to satisfy|a| < 0.1; neither could the unbiased simulation for the homoge-neous exponential sequence be achieved. The above conclusions are proved and verified through some theorems and examples.

  19. Use of Animal Models to Investigate Major Allergens Associated with Food Allergy

    Directory of Open Access Journals (Sweden)

    Jenna L. Van Gramberg

    2013-01-01

    Full Text Available Food allergy is an emerging epidemic that affects all age groups, with the highest prevalence rates being reported amongst Western countries such as the United States (US, United Kingdom (UK, and Australia. The development of animal models to test various food allergies has been beneficial in allowing more rapid and extensive investigations into the mechanisms involved in the allergic pathway, such as predicting possible triggers as well as the testing of novel treatments for food allergy. Traditionally, small animal models have been used to characterise immunological pathways, providing the foundation for the development of numerous allergy models. Larger animals also merit consideration as models for food allergy as they are thought to more closely reflect the human allergic state due to their physiology and outbred nature. This paper will discuss the use of animal models for the investigation of the major food allergens; cow's milk, hen's egg, and peanut/other tree nuts, highlight the distinguishing features of each of these models, and provide an overview of how the results from these trials have improved our understanding of these specific allergens and food allergy in general.

  20. Exploring host-microbiota interactions in animal models and humans.

    Science.gov (United States)

    Kostic, Aleksandar D; Howitt, Michael R; Garrett, Wendy S

    2013-04-01

    The animal and bacterial kingdoms have coevolved and coadapted in response to environmental selective pressures over hundreds of millions of years. The meta'omics revolution in both sequencing and its analytic pipelines is fostering an explosion of interest in how the gut microbiome impacts physiology and propensity to disease. Gut microbiome studies are inherently interdisciplinary, drawing on approaches and technical skill sets from the biomedical sciences, ecology, and computational biology. Central to unraveling the complex biology of environment, genetics, and microbiome interaction in human health and disease is a deeper understanding of the symbiosis between animals and bacteria. Experimental model systems, including mice, fish, insects, and the Hawaiian bobtail squid, continue to provide critical insight into how host-microbiota homeostasis is constructed and maintained. Here we consider how model systems are influencing current understanding of host-microbiota interactions and explore recent human microbiome studies.

  1. Impaired auditory sensorimotor gating: An animal model of schizophrenia

    Institute of Scientific and Technical Information of China (English)

    LI Liang; SHAO Feng

    2003-01-01

    Establishment of animal models of schizophrenia is critical for both understanding the mechanisms underlying this severe mental disease and developing new antipsychotics. This paper starts from the theoretical root of sensory gating, the "protection-of-processing" theory, then thoroughly describes the representative studies over the past decade on the mechanism underlying prepulse inhibition and on those underlying modulation of prepulse inhibition, which is the normal startle suppression caused by the weak stimulus preceding the intense startling stimulus. The main methods for inducing prepulse inhibition deficits in experimental animals include: i ) modulations of neuro- transmission that are closely associated with schizophrenia; ii )focal lesions or pharmacological manipulations of brain structures in the cortico-striato-pallido-pontine circuit; and iii) maternal deprivation or social isolation. Six essential topics for studies in modeling schizophrenia are suggested at the last part of this review.

  2. On numerical modeling of animal swimming and flight

    Science.gov (United States)

    Deng, Hong-Bin; Xu, Yuan-Qing; Chen, Duan-Duan; Dai, Hu; Wu, Jian; Tian, Fang-Bao

    2013-12-01

    Aquatic and aerial animals have developed their superior and complete mechanisms of swimming and flight. These mechanisms bring excellent locomotion performances to natural creatures, including high efficiency, long endurance ability, high maneuverability and low noise, and can potentially provide inspiration for the design of the man-made vehicles. As an efficient research approach, numerical modeling becomes more and more important in studying the mechanisms of swimming and flight. This review is focused on assessing the recent progress in numerical techniques of solving animal swimming and flight problems. According to the complexity of the problems considered, numerical studies are classified into five stages, of which the main characteristics and the numerical strategies are described and discussed. In addition, the body-conformal mesh, Cartesian-mesh, overset-grid, and meshfree methods are briefly introduced. Finally, several open issues in numerical modeling in this field are highlighted.

  3. Critical Behavior in a Cellular Automata Animal Disease Transmission Model

    CERN Document Server

    Morley, P D; Chang, Julius

    2003-01-01

    Using a cellular automata model, we simulate the British Government Policy (BGP) in the 2001 foot and mouth epidemic in Great Britain. When clinical symptoms of the disease appeared on a farm, there is mandatory slaughter (culling) of all livestock on an infected premise (IP). Those farms that neighbor an IP (contiguous premise, CP), are also culled, aka nearest neighbor interaction. Farms where the disease may be prevalent from animal, human, vehicle or airborne transmission (dangerous contact, DC), are additionally culled, aka next-to-nearest neighbor iteractions and lightning factor. The resulting mathematical model possesses a phase transition, whereupon if the physical disease transmission kernel exceeds a critical value, catastrophic loss of animals ensues. The non-local disease transport probability can be as low as .01% per day and the disease can still be in the high mortality phase. We show that the fundamental equation for sustainable disease transport is the criticality equation for neutron fissio...

  4. Animal models of social anxiety disorder and their validity criteria.

    Science.gov (United States)

    Réus, Gislaine Z; Dos Santos, Maria Augusta B; Abelaira, Helena M; Quevedo, João

    2014-09-26

    Anxiety disorders pose one of the largest threats to global mental health, and they predominantly emerge early in life. Social anxiety disorder, also known as social phobia, is the most common of all anxiety disorders. Moreover, it has severe consequences and is a disabling disorder that can cause an individual to be unable to perform the tasks of daily life. Social anxiety disorder is associated with the subsequent development of major depression and other mental diseases, as well as increased substance abuse. Although some neurobiological alterations have been found to be associated with social anxiety disorder, little is known about this disorder. Animal models are useful tools for the investigation of this disorder, as well as for finding new pharmacological targets for treatment. Thus, this review will highlight the main animal models of anxiety associated with social phobia.

  5. 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.

  6. Gender Differences in Animal Models of Posttraumatic Stress Disorder

    Directory of Open Access Journals (Sweden)

    Hagit Cohen

    2011-01-01

    Full Text Available Epidemiological studies report higher prevalence rates of stress-related disorders such as acute stress disorder and post-traumatic stress disorder (PTSD in women than in men following exposure to trauma. It is still not clear whether this greater prevalence in woman reflects a greater vulnerability to stress-related psychopathology. A number of individual and trauma-related characteristics have been hypothesized to contribute to these gender differences in physiological and psychological responses to trauma, differences in appraisal, interpretation or experience of threat, coping style or social support. In this context, the use of an animal model for PTSD to analyze some of these gender-related differences may be of particular utility. Animal models of PTSD offer the opportunity to distinguish between biological and socio-cultural factors, which so often enter the discussion about gender differences in PTSD prevalence.

  7. The search for animal models for Lassa fever vaccine development.

    Science.gov (United States)

    Lukashevich, Igor S

    2013-01-01

    Lassa virus (LASV) is the most prevalent arenavirus in West Africa and is responsible for several hundred thousand infections and thousands of deaths annually. The sizeable disease burden, numerous imported cases of Lassa fever (LF) and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Currently there is no licensed LF vaccine and research and devlopment is hampered by the high cost of nonhuman primate animal models and by biocontainment requirements (BSL-4). In addition, a successful LF vaccine has to induce a strong cell-mediated cross-protective immunity against different LASV lineages. All of these challenges will be addressed in this review in the context of available and novel animal models recently described for evaluation of LF vaccine candidates.

  8. Risk terrain modeling predicts child maltreatment.

    Science.gov (United States)

    Daley, Dyann; Bachmann, Michael; Bachmann, Brittany A; Pedigo, Christian; Bui, Minh-Thuy; Coffman, Jamye

    2016-12-01

    As indicated by research on the long-term effects of adverse childhood experiences (ACEs), maltreatment has far-reaching consequences for affected children. Effective prevention measures have been elusive, partly due to difficulty in identifying vulnerable children before they are harmed. This study employs Risk Terrain Modeling (RTM), an analysis of the cumulative effect of environmental factors thought to be conducive for child maltreatment, to create a highly accurate prediction model for future substantiated child maltreatment cases in the City of Fort Worth, Texas. The model is superior to commonly used hotspot predictions and more beneficial in aiding prevention efforts in a number of ways: 1) it identifies the highest risk areas for future instances of child maltreatment with improved precision and accuracy; 2) it aids the prioritization of risk-mitigating efforts by informing about the relative importance of the most significant contributing risk factors; 3) since predictions are modeled as a function of easily obtainable data, practitioners do not have to undergo the difficult process of obtaining official child maltreatment data to apply it; 4) the inclusion of a multitude of environmental risk factors creates a more robust model with higher predictive validity; and, 5) the model does not rely on a retrospective examination of past instances of child maltreatment, but adapts predictions to changing environmental conditions. The present study introduces and examines the predictive power of this new tool to aid prevention efforts seeking to improve the safety, health, and wellbeing of vulnerable children.

  9. Relevance of animal models to human tardive dyskinesia

    Directory of Open Access Journals (Sweden)

    Blanchet Pierre J

    2012-03-01

    Full Text Available Abstract Tardive dyskinesia remains an elusive and significant clinical entity that can possibly be understood via experimentation with animal models. We conducted a literature review on tardive dyskinesia modeling. Subchronic antipsychotic drug exposure is a standard approach to model tardive dyskinesia in rodents. Vacuous chewing movements constitute the most common pattern of expression of purposeless oral movements and represent an impermanent response, with individual and strain susceptibility differences. Transgenic mice are also used to address the contribution of adaptive and maladaptive signals induced during antipsychotic drug exposure. An emphasis on non-human primate modeling is proposed, and past experimental observations reviewed in various monkey species. Rodent and primate models are complementary, but the non-human primate model appears more convincingly similar to the human condition and better suited to address therapeutic issues against tardive dyskinesia.

  10. Multiple sclerosis animal models: a clinical and histopathological perspective.

    Science.gov (United States)

    Kipp, Markus; Nyamoya, Stella; Hochstrasser, Tanja; Amor, Sandra

    2017-03-01

    There is a broad consensus that multiple sclerosis (MS) represents more than an inflammatory disease: it harbors several characteristic aspects of a classical neurodegenerative disorder, that is, damage to axons, synapses and nerve cell bodies. While we are equipped with appropriate therapeutic options to prevent immune-cell driven relapses, effective therapeutic options to prevent the progressing neurodegeneration are still missing. In this review article, we will discuss to what extent pathology of the progressive disease stage can be modeled in MS animal models. While acute and relapsing-remitting forms of experimental autoimmune encephalomyelitis (EAE), which are T cell dependent, are aptly suited to model relapsing-remitting phases of MS, other EAE models, especially the secondary progressive EAE stage in Biozzi ABH mice is better representing the secondary progressive phase of MS, which is refractory to many immune therapies. Besides EAE, the cuprizone model is rapidly gaining popularity to study the formation and progression of demyelinating CNS lesions without T cell involvement. Here, we discuss these two non-popular MS models. It is our aim to point out the pathological hallmarks of MS, and discuss which pathological aspects of the disease can be best studied in the various animal models available.

  11. Property predictions using microstructural modeling

    Energy Technology Data Exchange (ETDEWEB)

    Wang, K.G. [Department of Materials Science and Engineering, Rensselaer Polytechnic Institute, CII 9219, 110 8th Street, Troy, NY 12180-3590 (United States)]. E-mail: wangk2@rpi.edu; Guo, Z. [Sente Software Ltd., Surrey Technology Centre, 40 Occam Road, Guildford GU2 7YG (United Kingdom); Sha, W. [Metals Research Group, School of Civil Engineering, Architecture and Planning, The Queen' s University of Belfast, Belfast BT7 1NN (United Kingdom); Glicksman, M.E. [Department of Materials Science and Engineering, Rensselaer Polytechnic Institute, CII 9219, 110 8th Street, Troy, NY 12180-3590 (United States); Rajan, K. [Department of Materials Science and Engineering, Rensselaer Polytechnic Institute, CII 9219, 110 8th Street, Troy, NY 12180-3590 (United States)

    2005-07-15

    Precipitation hardening in an Fe-12Ni-6Mn maraging steel during overaging is quantified. First, applying our recent kinetic model of coarsening [Phys. Rev. E, 69 (2004) 061507], and incorporating the Ashby-Orowan relationship, we link quantifiable aspects of the microstructures of these steels to their mechanical properties, including especially the hardness. Specifically, hardness measurements allow calculation of the precipitate size as a function of time and temperature through the Ashby-Orowan relationship. Second, calculated precipitate sizes and thermodynamic data determined with Thermo-Calc[copyright] are used with our recent kinetic coarsening model to extract diffusion coefficients during overaging from hardness measurements. Finally, employing more accurate diffusion parameters, we determined the hardness of these alloys independently from theory, and found agreement with experimental hardness data. Diffusion coefficients determined during overaging of these steels are notably higher than those found during the aging - an observation suggesting that precipitate growth during aging and precipitate coarsening during overaging are not controlled by the same diffusion mechanism.

  12. Predicting animal home-range structure and transitions using a multistate Ornstein-Uhlenbeck biased random walk

    Science.gov (United States)

    Breed, Greg A; Golson, Emily A.; Tinker, M. Tim

    2017-01-01

    The home-range concept is central in animal ecology and behavior, and numerous mechanistic models have been developed to understand home range formation and maintenance. These mechanistic models usually assume a single, contiguous home range. Here we describe and implement a simple home-range model that can accommodate multiple home-range centers, form complex shapes, allow discontinuities in use patterns, and infer how external and internal variables affect movement and use patterns. The model assumes individuals associate with two or more home-range centers and move among them with some estimable probability. Movement in and around home-range centers is governed by a two-dimensional Ornstein-Uhlenbeck process, while transitions between centers are modeled as a stochastic state-switching process. We augmented this base model by introducing environmental and demographic covariates that modify transition probabilities between home-range centers and can be estimated to provide insight into the movement process. We demonstrate the model using telemetry data from sea otters (Enhydra lutris) in California. The model was fit using a Bayesian Markov Chain Monte Carlo method, which estimated transition probabilities, as well as unique Ornstein-Uhlenbeck diffusion and centralizing tendency parameters. Estimated parameters could then be used to simulate movement and space use that was virtually indistinguishable from real data. We used Deviance Information Criterion (DIC) scores to assess model fit and determined that both wind and reproductive status were predictive of transitions between home-range centers. Females were less likely to move between home-range centers on windy days, less likely to move between centers when tending pups, and much more likely to move between centers just after weaning a pup. These tendencies are predicted by theoretical movement rules but were not previously known and show that our model can extract meaningful behavioral insight from complex

  13. Minireview: Epigenetic Programming of Diabetes and Obesity: Animal Models

    OpenAIRE

    2012-01-01

    A growing body of evidence suggests that the intrauterine (IU) environment has a significant and lasting effect on the long-term health of the growing fetus and the development of metabolic disease in later life as put forth in the fetal origins of disease hypothesis. Metabolic diseases have been associated with alterations in the epigenome that occur without changes in the DNA sequence, such as cytosine methylation of DNA, histone posttranslational modifications, and micro-RNA. Animal models...

  14. Shank mutant mice as an animal model of autism

    OpenAIRE

    Yoo, Juyoun; Bakes, Joseph; Bradley, Clarrisa; Graham L. Collingridge; Kaang, Bong-Kiun

    2014-01-01

    In this review, we focus on the role of the Shank family of proteins in autism. In recent years, autism research has been flourishing. With genetic, molecular, imaging and electrophysiological studies being supported by behavioural studies using animal models, there is real hope that we may soon understand the fundamental pathology of autism. There is also genuine potential to develop a molecular-level pharmacological treatment that may be able to deal with the most severe symptoms of autism,...

  15. Are NCAM deficient mice an animal model for schizophrenia?

    OpenAIRE

    Anne eAlbrecht; Oliver eStork

    2012-01-01

    Genetic and biomarker studies in patients have identified the Neural Cell Adhesion Molecule (NCAM) and its associated polysialic acid (PSA) as a susceptibility factors for schizophrenia. NCAM and polysialtransferase mutant mice have been generated that may serve as animal models for this disorder and allow to investigate underlying neurodevelopmental alterations. Indeed, various schizophrenia-relevant morphological, cognitive and emotional deficits have been observed in these mutants. Here we...

  16. TSPO imaging in stroke: from animal models to human subjects

    OpenAIRE

    Boutin, Hervé; Pinborg, Lars H.

    2015-01-01

    Stroke is a major health problem in developed countries and neuroinflammation has emerged over the last 2 decades as major contributor to the pathophysiological processes of brain damage following stroke. PET imaging of the translocator 18 kDa protein (TSPO) provides a unique non-invasive point of access to neuroinflammatory processes and more specifically microglial and astrocytic reaction after stroke in both animal models and patients. Here, we are reviewing both the experimental and ...

  17. 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.

  18. Impulsivity in Animal Models for Drug Abuse Disorders

    OpenAIRE

    Jentsch, J. David

    2008-01-01

    Different conceptual frameworks have been generated to explain substance abuse; of relevance to this article, dysfunction of impulse control systems that are required for avoiding or stopping drug-seeking and –taking may play a key role in addiction. This review summarizes work in animal models that explains the pervasive association between impulse control and substance abuse. It further underscores the concept that impulse control may be a critical target for pharmacological intervention in...

  19. The TNBS-induced colitis animal model: An overview

    OpenAIRE

    Efstathios Antoniou; Georgios Antonios Margonis; Anastasios Angelou; Anastasia Pikouli; Paraskevi Argiri; Ioannis Karavokyros; Apostolos Papalois; Emmanouil Pikoulis

    2016-01-01

    Background: Despite recent advances the pathogenesis of Crohn's disease remains incompletely understood. A variety of animal models have been utilized in an effort to provide further insights and develop more therapeutic options. In order to simulate, to an extent, the pathogenesis and the clinical course of the disease, TNBS induced colitis is often used. Various approaches for inducing TNBS -colitis have been described in the literature. Methods/results: In this review, we sought to pres...

  20. Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

    OpenAIRE

    Takahashi, Yoshihisa; Soejima, Yurie; Fukusato, Toshio

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma. NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity, type 2 diabetes, and hyperlipemia. Animal models of NAFLD/NASH ...

  1. Spatial Economics Model Predicting Transport Volume

    Directory of Open Access Journals (Sweden)

    Lu Bo

    2016-10-01

    Full Text Available It is extremely important to predict the logistics requirements in a scientific and rational way. However, in recent years, the improvement effect on the prediction method is not very significant and the traditional statistical prediction method has the defects of low precision and poor interpretation of the prediction model, which cannot only guarantee the generalization ability of the prediction model theoretically, but also cannot explain the models effectively. Therefore, in combination with the theories of the spatial economics, industrial economics, and neo-classical economics, taking city of Zhuanghe as the research object, the study identifies the leading industry that can produce a large number of cargoes, and further predicts the static logistics generation of the Zhuanghe and hinterlands. By integrating various factors that can affect the regional logistics requirements, this study established a logistics requirements potential model from the aspect of spatial economic principles, and expanded the way of logistics requirements prediction from the single statistical principles to an new area of special and regional economics.

  2. ANIMAL MODELS FOR HUNTINGTON’S DISEASES: A REVIEW

    Directory of Open Access Journals (Sweden)

    Sharma Manisha

    2012-10-01

    Full Text Available Huntington's disease (HD is an inherited autosomal, progressive neurodegenerative disorder associated with involuntary abnormal movements (chorea, cognitive impairments and psychiatric disturbances. HD is caused by an abnormal expansion of a CAG region located in exon 1 of the gene encoding the huntingtin protein (Htt and is the causative factor in the pathogenesis of HD Animal models of HD have provided insight into disease pathology and the outcomes of thera- peutic strategies. Earlier studies of HD most often used toxin-induced models to study mitochondrial impairment and excitotoxicity-induced cell death, which are both mechanisms of degeneration seen in the HD brain. These models, based on 3-nitropropionic acid and quinolinic acid, respectively, are still often used in HD studies. The discovery in 1993 of the huntingtin mutation led to the creation of newer models that incorporate a similar genetic defect. These models, which include transgenic and knock-in rodents, are more representative of the HD progression and pathology. An even more recent model that uses a ovine transgenic model (sheep model,fly models ,cell cultures models for better understanding of gene mutation in and in mammalian and nonhuman primates, as it is difficult to produce genetic models in these species. This article examines the aforementioned models and describes their use in HD research, including aspects of the creation, de- livery, pathology, and tested therapies for each model.

  3. 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.

  4. Vestibular animal models: contributions to understanding physiology and disease.

    Science.gov (United States)

    Straka, Hans; Zwergal, Andreas; Cullen, Kathleen E

    2016-04-01

    Our knowledge of the vestibular sensory system, its functional significance for gaze and posture stabilization, and its capability to ensure accurate spatial orientation perception and spatial navigation has greatly benefitted from experimental approaches using a variety of vertebrate species. This review summarizes the attempts to establish the roles of semicircular canal and otolith endorgans in these functions followed by an overview of the most relevant fields of vestibular research including major findings that have advanced our understanding of how this system exerts its influence on reflexive and cognitive challenges encountered during daily life. In particular, we highlight the contributions of different animal models and the advantage of using a comparative research approach. Cross-species comparisons have established that the morpho-physiological properties underlying vestibular signal processing are evolutionarily inherent, thereby disclosing general principles. Based on the documented success of this approach, we suggest that future research employing a balanced spectrum of standard animal models such as fish/frog, mouse and primate will optimize our progress in understanding vestibular processing in health and disease. Moreover, we propose that this should be further supplemented by research employing more "exotic" species that offer unique experimental access and/or have specific vestibular adaptations due to unusual locomotor capabilities or lifestyles. Taken together this strategy will expedite our understanding of the basic principles underlying vestibular computations to reveal relevant translational aspects. Accordingly, studies employing animal models are indispensible and even mandatory for the development of new treatments, medication and technical aids (implants) for patients with vestibular pathologies.

  5. Modeling DNA structure and processes through animation and kinesthetic visualizations

    Science.gov (United States)

    Hager, Christine

    There have been many studies regarding the effectiveness of visual aids that go beyond that of static illustrations. Many of these have been concentrated on the effectiveness of visual aids such as animations and models or even non-traditional visual aid activities like role-playing activities. This study focuses on the effectiveness of three different types of visual aids: models, animation, and a role-playing activity. Students used a modeling kit made of Styrofoam balls and toothpicks to construct nucleotides and then bond nucleotides together to form DNA. Next, students created their own animation to depict the processes of DNA replication, transcription, and translation. Finally, students worked in teams to build proteins while acting out the process of translation. Students were given a pre- and post-test that measured their knowledge and comprehension of the four topics mentioned above. Results show that there was a significant gain in the post-test scores when compared to the pre-test scores. This indicates that the incorporated visual aids were effective methods for teaching DNA structure and processes.

  6. Models in animal collective decision-making: information uncertainty and conflicting preferences.

    Science.gov (United States)

    Conradt, Larissa

    2012-04-01

    Collective decision-making plays a central part in the lives of many social animals. Two important factors that influence collective decision-making are information uncertainty and conflicting preferences. Here, I bring together, and briefly review, basic models relating to animal collective decision-making in situations with information uncertainty and in situations with conflicting preferences between group members. The intention is to give an overview about the different types of modelling approaches that have been employed and the questions that they address and raise. Despite the use of a wide range of different modelling techniques, results show a coherent picture, as follows. Relatively simple cognitive mechanisms can lead to effective information pooling. Groups often face a trade-off between decision accuracy and speed, but appropriate fine-tuning of behavioural parameters could achieve high accuracy while maintaining reasonable speed. The right balance of interdependence and independence between animals is crucial for maintaining group cohesion and achieving high decision accuracy. In conflict situations, a high degree of decision-sharing between individuals is predicted, as well as transient leadership and leadership according to needs and physiological status. Animals often face crucial trade-offs between maintaining group cohesion and influencing the decision outcome in their own favour. Despite the great progress that has been made, there remains one big gap in our knowledge: how do animals make collective decisions in situations when information uncertainty and conflict of interest operate simultaneously?

  7. Predicting the bioaccumulation of polyaromatic hydrocarbons and polychlorinated biphenyls in benthic animals in sediments

    Energy Technology Data Exchange (ETDEWEB)

    Tuikka, A.I., E-mail: anitat@student.uef.fi [University of Eastern Finland, Department of Environmental and Biological Sciences, P.O. Box 111, FI-80101 Joensuu (Finland); Leppänen, M.T., E-mail: Matti.T.Leppanen@ymparisto.fi [Finnish Environment Institute, Laboratories/Research and Innovation Laboratory, P.O. Box 35, University of Jyväskylä, FI-40014 Jyväskylä (Finland); Akkanen, J., E-mail: jarkko.akkanen@uef.fi [University of Eastern Finland, Department of Environmental and Biological Sciences, P.O. Box 111, FI-80101 Joensuu (Finland); Sormunen, A.J., E-mail: Arto.Sormunen@mamk.fi [University of Eastern Finland, Department of Environmental and Biological Sciences, P.O. Box 111, FI-80101 Joensuu (Finland); Leonards, P.E.G., E-mail: pim.leonards@vu.nl [Institute for Environmental Studies, Vrije Universiteit Amsterdam, De Boelelaan 1087, 1081 HV Amsterdam (Netherlands); Hattum, B. van, E-mail: bert.vanhattum@deltares.nl [Institute for Environmental Studies, Vrije Universiteit Amsterdam, De Boelelaan 1087, 1081 HV Amsterdam (Netherlands); Vliet, L.A. van, E-mail: lavanvliet@hotmail.com [Ministry of Transport, Public Works and Water Management, National Institute for Coastal and Marine Management/RIKZ, P.O. Box 207, 9750 AE Haren (Netherlands); Brack, W., E-mail: werner.brack@ufz.de [Helmholtz Centre for Environmental Research - UFZ, Department of Effect-Directed Analysis, Permoserstraße 15, 04318 Leipzig (Germany); Smedes, F., E-mail: smedes@recetox.muni.cz [Ministry of Transport, Public Works and Water Management, National Institute for Coastal and Marine Management/RIKZ, P.O. Box 207, 9750 AE Haren (Netherlands); and others

    2016-09-01

    There were two main objectives in this study. The first was to compare the accuracy of different prediction methods for the chemical concentrations of polyaromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) in the organism, based on the measured chemical concentrations existing in sediment dry matter or pore water. The predicted tissue concentrations were compared to the measured ones after 28-day laboratory test using oligochaeta worms (Lumbriculus variegatus). The second objective was to compare the bioaccumulation of PAHs and PCBs in the laboratory test with the in situ bioaccumulation of these compounds. Using the traditional organic carbon-water partitioning model, tissue concentrations were greatly overestimated, based on the concentrations in the sediment dry matter. Use of an additional correction factor for black carbon with a two-carbon model, significantly improved the bioaccumulation predictions, thus confirming that black carbon was important in binding the chemicals and reducing their accumulation. The predicted PAH tissue concentrations were, however, high compared to the observed values. The chemical concentrations were most accurately predicted from their freely dissolved pore water concentrations, determined using equilibrium passive sampling. The patterns of PCB and PAH accumulation in sediments for laboratory-exposed L. variegatus were similar to those in field-collected Lumbriculidae worms. Field-collected benthic invertebrates and L. variegatus accumulated less PAHs than PCBs with similar lipophilicity. The biota to sediment accumulation factors of PAHs tended to decrease with increasing sediment organic carbon normalized concentrations. The presented data yields bioconcentration factors (BCF) describing the chemical water-lipid partition, which were found to be higher than the octanol-water partition coefficients, but on a similar level with BCFs drawn from relevant literature. In conclusion, using the two-carbon model method

  8. Precision Plate Plan View Pattern Predictive Model

    Institute of Scientific and Technical Information of China (English)

    ZHAO Yang; YANG Quan; HE An-rui; WANG Xiao-chen; ZHANG Yun

    2011-01-01

    According to the rolling features of plate mill, a 3D elastic-plastic FEM (finite element model) based on full restart method of ANSYS/LS-DYNA was established to study the inhomogeneous plastic deformation of multipass plate rolling. By analyzing the simulation results, the difference of head and tail ends predictive models was found and modified. According to the numerical simulation results of 120 different kinds of conditions, precision plate plan view pattern predictive model was established. Based on these models, the sizing MAS (mizushima automatic plan view pattern control system) method was designed and used on a 2 800 mm plate mill. Comparing the rolled plates with and without PVPP (plan view pattern predictive) model, the reduced width deviation indicates that the olate !olan view Dattern predictive model is preeise.

  9. Modeling and Prediction Using Stochastic Differential Equations

    DEFF Research Database (Denmark)

    Juhl, Rune; Møller, Jan Kloppenborg; Jørgensen, John Bagterp

    2016-01-01

    Pharmacokinetic/pharmakodynamic (PK/PD) modeling for a single subject is most often performed using nonlinear models based on deterministic ordinary differential equations (ODEs), and the variation between subjects in a population of subjects is described using a population (mixed effects) setup...... that describes the variation between subjects. The ODE setup implies that the variation for a single subject is described by a single parameter (or vector), namely the variance (covariance) of the residuals. Furthermore the prediction of the states is given as the solution to the ODEs and hence assumed...... deterministic and can predict the future perfectly. A more realistic approach would be to allow for randomness in the model due to e.g., the model be too simple or errors in input. We describe a modeling and prediction setup which better reflects reality and suggests stochastic differential equations (SDEs...

  10. Hypoxia facilitates neurogenic dural plasma protein extravasation in mice : a novel animal model for migraine pathophysiology

    OpenAIRE

    Anika Hunfeld; Daniel Segelcke; Ingo Bäcker; Badreddine Mecheri; Kathrin Hemmer; Elisabeth Dlugosch; Michael Andriske; Frank Paris; Xinran Zhu; Hermann Lübbert

    2015-01-01

    Migraine animal models generally mimic the onset of attacks and acute treatment processes. A guinea pig model used the application of meta-chlorophenylpiperazine (mCPP) to trigger immediate dural plasma protein extravasation (PPE) mediated by 5-HT2B receptors. This model has predictive value for antimigraine drugs but cannot explain the delayed onset of efficacy of 5-HT2B receptor antagonists when clinically used for migraine prophylaxis. We found that mCPP failed to induce dural PPE in mice....

  11. Facial animation on an anatomy-based hierarchical face model

    Science.gov (United States)

    Zhang, Yu; Prakash, Edmond C.; Sung, Eric

    2003-04-01

    In this paper we propose a new hierarchical 3D facial model based on anatomical knowledge that provides high fidelity for realistic facial expression animation. Like real human face, the facial model has a hierarchical biomechanical structure, incorporating a physically-based approximation to facial skin tissue, a set of anatomically-motivated facial muscle actuators and underlying skull structure. The deformable skin model has multi-layer structure to approximate different types of soft tissue. It takes into account the nonlinear stress-strain relationship of the skin and the fact that soft tissue is almost incompressible. Different types of muscle models have been developed to simulate distribution of the muscle force on the skin due to muscle contraction. By the presence of the skull model, our facial model takes advantage of both more accurate facial deformation and the consideration of facial anatomy during the interactive definition of facial muscles. Under the muscular force, the deformation of the facial skin is evaluated using numerical integration of the governing dynamic equations. The dynamic facial animation algorithm runs at interactive rate with flexible and realistic facial expressions to be generated.

  12. Acute liver failure: a critical appraisal of available animal models.

    Science.gov (United States)

    Bélanger, Mireille; Butterworth, Roger F

    2005-12-01

    The availability of adequate experimental models of acute liver failure (ALF) is of prime importance to provide a better understanding of this condition and allow the development and testing of new therapeutic approaches for patients with ALF. However, the numerous etiologies and complications of ALF contribute to the complexity of this condition and render the development of an ideal experimental model of ALF more difficult than expected. Instead, a number of different models that may be used for the study of specific aspects of ALF have been developed. The most common approaches used to induce ALFin experimental animals are surgical procedures, toxic liver injury,or a combination of both. Despite the high prevalence of viral hepatitis worldwide, very few satisfactory viral models of ALF are available. Established and newly developed models of ALF are reviewed.

  13. Using Online Tool (iPrior) for Modeling ToxCast™ Assays Towards Prioritization of Animal Toxicity Testing.

    Science.gov (United States)

    Abdelaziz, Ahmed; Sushko, Yurii; Novotarskyi, Sergii; Körner, Robert; Brandmaier, Stefan; Tetko, Igor V

    2015-01-01

    The use of long-term animal studies for human and environmental toxicity estimation is more discouraged than ever before. Alternative models for toxicity prediction, including QSAR studies, are gaining more ground. A recent approach is to combine in vitro chemical profiling and in silico chemical descriptors with the knowledge about toxicity pathways to derive a unique signature for toxicity endpoints. In this study we investigate the ToxCast™ Phase I data regarding their ability to predict long-term animal toxicity. We investigated thousands of models constructed in an effort to predict 61 toxicity endpoints using multiple descriptor packages and hundreds of in vitro assays. We investigated the use of in vitro assays and biochemical pathways on model performance. We identified 10 toxicity endpoints where biologically derived descriptors from in vitro assays or pathway perturbations improved the model prediction ability. In vivo toxicity endpoints proved generally challenging to model. Few models were possible to readily model with a balanced accuracy (BA) above 0.7. We also constructed in silico models to predict the outcome of 144 in vitro assays. This showed better statistical metrics with 79 out of 144 assays having median balanced accuracy above 0.7. This suggests that the in vitro datasets have a better modelability than in vivo animal toxicities for the given datasets. Moreover, we published an online platform (http://iprior.ochem.eu) that automates large-scale model building and analysis.

  14. Animal models of protein allergenicity: potential benefits, pitfalls and challenges.

    Science.gov (United States)

    Dearman, R J; Kimber, I

    2009-04-01

    Food allergy is an important health issue. With an increasing interest in novel foods derived from transgenic crop plants, there is a growing need for the development of approaches suitable for the characterization of the allergenic potential of proteins. There are methods available currently (such as homology searches and serological testing) that are very effective at identifying proteins that are likely to cross-react with known allergens. However, animal models may play a role in the identification of truly novel proteins, such as bacterial or fungal proteins, that have not been experienced previously in the diet. We consider here the potential benefits, pitfalls and challenges of the selection of various animal models, including the mouse, the rat, the dog and the neonatal swine. The advantages and disadvantages of various experimental end-points are discussed, including the measurement of specific IgE by ELISA, Western blotting or functional tests such as the passive cutaneous anaphylaxis assay, and the assessment of challenge-induced clinical symptoms in previously sensitized animals. The experimental variables of route of exposure to test proteins and the incorporation of adjuvant to increase the sensitivity of the responses are considered also. It is important to emphasize that currently none of these approaches has been validated for the purposes of hazard identification in the context of a safety assessment. However, the available evidence suggests that the judicious use of an accurate and robust animal model could provide important additional data that would contribute significantly to the assessment of the potential allergenicity of novel proteins.

  15. Neuroprotective Transcription Factors in Animal Models of Parkinson Disease

    OpenAIRE

    François-Xavier Blaudin de Thé; Hocine Rekaik; Alain Prochiantz; Julia Fuchs; Joshi, Rajiv L.

    2015-01-01

    A number of transcription factors, including En1/2, Foxa1/2, Lmx1a/b, Nurr1, Otx2, and Pitx3, with key roles in midbrain dopaminergic (mDA) neuron development, also regulate adult mDA neuron survival and physiology. Mouse models with targeted disruption of some of these genes display several features reminiscent of Parkinson disease (PD), in particular the selective and progressive loss of mDA neurons in the substantia nigra pars compacta (SNpc). The characterization of these animal models ha...

  16. Animal Models, Prophylaxis, and Therapeutics for Arenavirus Infections

    Directory of Open Access Journals (Sweden)

    Eric Vela

    2012-09-01

    Full Text Available Arenaviruses are enveloped, bipartite negative single-stranded RNA viruses that can cause a wide spectrum of disease in humans and experimental animals including hemorrhagic fever. The majority of these viruses are rodent-borne and the arenavirus family can be divided into two groups: the Lassa-Lymphocytic choriomeningitis serocomplex and the Tacaribe serocomplex. Arenavirus-induced disease may include characteristic symptoms ranging from fever, malaise, body aches, petechiae, dehydration, hemorrhage, organ failure, shock, and in severe cases death. Currently, there are few prophylactic and therapeutic treatments available for arenavirus-induced symptoms. Supportive care and ribavirin remain the predominant strategies for treating most of the arenavirus-induced diseases. Therefore, efficacy testing of novel therapeutic and prophylactic strategies in relevant animal models is necessary. Because of the potential for person-to-person spread, the ability to cause lethal or debilitating disease in humans, limited treatment options, and potential as a bio-weapon, the development of prophylactics and therapeutics is essential. This article reviews the current arenavirus animal models and prophylactic and therapeutic strategies under development to treat arenavirus infection.

  17. Animal models, prophylaxis, and therapeutics for arenavirus infections.

    Science.gov (United States)

    Vela, Eric

    2012-09-01

    Arenaviruses are enveloped, bipartite negative single-stranded RNA viruses that can cause a wide spectrum of disease in humans and experimental animals including hemorrhagic fever. The majority of these viruses are rodent-borne and the arenavirus family can be divided into two groups: the Lassa-Lymphocytic choriomeningitis serocomplex and the Tacaribe serocomplex. Arenavirus-induced disease may include characteristic symptoms ranging from fever, malaise, body aches, petechiae, dehydration, hemorrhage, organ failure, shock, and in severe cases death. Currently, there are few prophylactic and therapeutic treatments available for arenavirus-induced symptoms. Supportive care and ribavirin remain the predominant strategies for treating most of the arenavirus-induced diseases. Therefore, efficacy testing of novel therapeutic and prophylactic strategies in relevant animal models is necessary. Because of the potential for person-to-person spread, the ability to cause lethal or debilitating disease in humans, limited treatment options, and potential as a bio-weapon, the development of prophylactics and therapeutics is essential. This article reviews the current arenavirus animal models and prophylactic and therapeutic strategies under development to treat arenavirus infection.

  18. Improved animal models for testing gene therapy for atherosclerosis.

    Science.gov (United States)

    Du, Liang; Zhang, Jingwan; De Meyer, Guido R Y; Flynn, Rowan; Dichek, David A

    2014-04-01

    Gene therapy delivered to the blood vessel wall could augment current therapies for atherosclerosis, including systemic drug therapy and stenting. However, identification of clinically useful vectors and effective therapeutic transgenes remains at the preclinical stage. Identification of effective vectors and transgenes would be accelerated by availability of animal models that allow practical and expeditious testing of vessel-wall-directed gene therapy. Such models would include humanlike lesions that develop rapidly in vessels that are amenable to efficient gene delivery. Moreover, because human atherosclerosis develops in normal vessels, gene therapy that prevents atherosclerosis is most logically tested in relatively normal arteries. Similarly, gene therapy that causes atherosclerosis regression requires gene delivery to an existing lesion. Here we report development of three new rabbit models for testing vessel-wall-directed gene therapy that either prevents or reverses atherosclerosis. Carotid artery intimal lesions in these new models develop within 2-7 months after initiation of a high-fat diet and are 20-80 times larger than lesions in a model we described previously. Individual models allow generation of lesions that are relatively rich in either macrophages or smooth muscle cells, permitting testing of gene therapy strategies targeted at either cell type. Two of the models include gene delivery to essentially normal arteries and will be useful for identifying strategies that prevent lesion development. The third model generates lesions rapidly in vector-naïve animals and can be used for testing gene therapy that promotes lesion regression. These models are optimized for testing helper-dependent adenovirus (HDAd)-mediated gene therapy; however, they could be easily adapted for testing of other vectors or of different types of molecular therapies, delivered directly to the blood vessel wall. Our data also supports the promise of HDAd to deliver long

  19. Modelling Chemical Reasoning to Predict Reactions

    CERN Document Server

    Segler, Marwin H S

    2016-01-01

    The ability to reason beyond established knowledge allows Organic Chemists to solve synthetic problems and to invent novel transformations. Here, we propose a model which mimics chemical reasoning and formalises reaction prediction as finding missing links in a knowledge graph. We have constructed a knowledge graph containing 14.4 million molecules and 8.2 million binary reactions, which represents the bulk of all chemical reactions ever published in the scientific literature. Our model outperforms a rule-based expert system in the reaction prediction task for 180,000 randomly selected binary reactions. We show that our data-driven model generalises even beyond known reaction types, and is thus capable of effectively (re-) discovering novel transformations (even including transition-metal catalysed reactions). Our model enables computers to infer hypotheses about reactivity and reactions by only considering the intrinsic local structure of the graph, and because each single reaction prediction is typically ac...

  20. The Use of Computational Fluid Dynamics in Predicting the Tidal Flushing of Animal Burrows

    Science.gov (United States)

    Heron, S. F.; Ridd, P. V.

    2001-04-01

    Numerical hydrodynamic modelling has been used extensively over the last few decades to simulate flow in the ocean, bays and estuaries; however, modelling of much smaller scale phenomena is less common. In this work a commercially available Computational Fluid Dynamics package (FIDAP), normally used for industrial applications, was used to simulate tidally-induced flow in multi-opening animal burrows. U-shaped burrows of varying complexities were modelled to determine the effect of different surface characteristics and burrow geometries on surface water velocities, burrow velocities and burrow flushing times. The turbulent 2D model showed the slope of the surface water was proportional to the square of both the surface and burrow velocities. The effect of placing a root in the surface flow was to reduce the surface water velocity; however, the burrow flow depended upon the root position. For the root location either upstream or downstream of the burrow, the burrow velocity was reduced by 50%. With the root located between the burrow openings the burrow velocity increased by 200%, due to the increase in pressure difference across the burrow openings. A buttress root placed in the flow immediately downstream of the upstream burrow, caused the burrow flushing rate to increase significantly with increasing buttress height. Flushing times for burrows of varying depth were determined computationally by use of a tracer for the burrow water. For a burrow of depth 1·2 m, the flushing times were 5 and 28 min for root location between the burrow openings and downstream of the burrow, respectively. Animal burrows often consist of multiply-connected loops. A second burrow was added to the primary burrow and flushing times were found to be 15 and 38 min, respectively. A burrow system of four connected burrows was modelled which had corresponding flushing times up to 24 and 47 min, respectively. The calculated times are consistent with the hypothesis that a significant flushing

  1. Emerging Sponge Models of Animal-Microbe Symbioses

    Science.gov (United States)

    Pita, Lucia; Fraune, Sebastian; Hentschel, Ute

    2016-01-01

    Sponges have a significant impact on marine benthic communities, they are of biotechnological interest owing to their production of bioactive natural compounds, and they promise to provide insights into conserved mechanisms of host–microbe interactions in basal metazoans. The natural variability of sponge-microbe associations across species and environments provides a meaningful ecological and evolutionary framework to investigate animal-microbial symbiosis through experimentation in the field and also in aquaria. In addition, next-generation sequencing technologies have shed light on the genomic repertoire of the sponge host and revealed metabolic capacities and symbiotic lifestyle features of their microbiota. However, our understanding of symbiotic mechanisms is still in its infancy. Here, we discuss the potential and limitations of the sponge-microbe symbiosis as emerging models for animal-associated microbiota. PMID:28066403

  2. An animal model to train Lichtenstein inguinal hernia repair

    DEFF Research Database (Denmark)

    Rosenberg, J; Presch, I; Pommergaard, H C

    2013-01-01

    pigs, and a total of 55 surgeons have been educated to perform Lichtenstein's hernia repair in these animals. CONCLUSIONS: This new experimental surgical model for training Lichtenstein's hernia repair mimics the human inguinal anatomy enough to make it suitable as a training model. The operation......PURPOSE: Inguinal hernia repair is a common surgical procedure, and the majority of operations worldwide are performed ad modum Lichtenstein (open tension-free mesh repair). Until now, no suitable surgical training model has been available for this procedure. We propose an experimental surgical......, thus complicating the procedure if operation should be done in the inguinal canal. The chain of lymph nodes resembles the human spermatic cord and can be used to perform Lichtenstein's hernia repair. RESULTS: This experimental surgical model has been tested on two adult male pigs and three adult female...

  3. Evaluation of CASP8 model quality predictions

    KAUST Repository

    Cozzetto, Domenico

    2009-01-01

    The model quality assessment problem consists in the a priori estimation of the overall and per-residue accuracy of protein structure predictions. Over the past years, a number of methods have been developed to address this issue and CASP established a prediction category to evaluate their performance in 2006. In 2008 the experiment was repeated and its results are reported here. Participants were invited to infer the correctness of the protein models submitted by the registered automatic servers. Estimates could apply to both whole models and individual amino acids. Groups involved in the tertiary structure prediction categories were also asked to assign local error estimates to each predicted residue in their own models and their results are also discussed here. The correlation between the predicted and observed correctness measures was the basis of the assessment of the results. We observe that consensus-based methods still perform significantly better than those accepting single models, similarly to what was concluded in the previous edition of the experiment. © 2009 WILEY-LISS, INC.

  4. Genetic models of homosexuality: generating testable predictions

    OpenAIRE

    Gavrilets, Sergey; Rice, William R.

    2006-01-01

    Homosexuality is a common occurrence in humans and other species, yet its genetic and evolutionary basis is poorly understood. Here, we formulate and study a series of simple mathematical models for the purpose of predicting empirical patterns that can be used to determine the form of selection that leads to polymorphism of genes influencing homosexuality. Specifically, we develop theory to make contrasting predictions about the genetic characteristics of genes influencing homosexuality inclu...

  5. [Approach to depressogenic genes from genetic analyses of animal models].

    Science.gov (United States)

    Yoshikawa, Takeo

    2004-01-01

    Human depression or mood disorder is defined as a complex disease, making positional cloning of susceptibility genes a formidable task. We have undertaken genetic analyses of three different animal models for depression, comparing our results with advanced database resources. We first performed quantitative trait loci (QTL) analysis on two mouse models of "despair", namely, the forced swim test (FST) and tail suspension test (TST), and detected multiple chromosomal loci that control immobility time in these tests. Since one QTL detected on mouse chromosome 11 harbors the GABA A receptor subunit genes, we tested these genes for association in human mood disorder patients. We obtained significant associations of the alpha 1 and alpha 6 subunit genes with the disease, particularly in females. This result was striking, because we had previously detected an epistatic interaction between mouse chromosomes 11 and X that regulates immobility time in these animals. Next, we performed genome-wide expression analyses using a rat model of depression, learned helplessness (LH). We found that in the frontal cortex of LH rats, a disease implicated region, the LIM kinase 1 gene (Limk 1) showed greatest alteration, in this case down-regulation. By combining data from the QTL analysis of FST/TST and DNA microarray analysis of mouse frontal cortex, we identified adenylyl cyclase-associated CAP protein 1 (Cap 1) as another candidate gene for depression susceptibility. Both Limk 1 and Cap 1 are key players in the modulation of actin G-F conversion. In summary, our current study using animal models suggests disturbances of GABAergic neurotransmission and actin turnover as potential pathophysiologies for mood disorder.

  6. Establishment of animal model of dual liver transplantation in rat.

    Directory of Open Access Journals (Sweden)

    Ying Zhang

    Full Text Available The animal model of the whole-size and reduced-size liver transplantation in both rat and mouse has been successfully established. Because of the difficulties and complexities in microsurgical technology, the animal model of dual liver transplantation was still not established for twelve years since the first human dual liver transplantation has been made a success. There is an essential need to establish this animal model to lay a basic foundation for clinical practice. To study the physiological and histopathological changes of dual liver transplantation, "Y" type vein from the cross part between vena cava and two iliac of donor and "Y' type prosthesis were employed to recanalize portal vein and the bile duct between dual liver grafts and recipient. The dual right upper lobes about 45-50% of the recipient liver volume were taken as donor, one was orthotopically implanted at its original position, the other was rotated 180° sagitally and heterotopically positioned in the left upper quadrant. Microcirculation parameters, liver function, immunohistochemistry and survival were analyzed to evaluate the function of dual liver grafts. No significant difference in the hepatic microcirculatory flow was found between two grafts in the first 90 minutes after reperfusion. Light and electronic microscope showed the liver architecture was maintained without obvious features of cellular destruction and the continuity of the endothelium was preserved. Only 3 heterotopically positioned graft appeared patchy desquamation of endothelial cell, mitochondrial swelling and hepatocytes cytoplasmic vacuolization. Immunohistochemistry revealed there is no difference in hepatocyte activity and the ability of endothelia to contract and relax after reperfusion between dual grafts. Dual grafts made a rapid amelioration of liver function after reperfusion. 7 rats survived more than 7 days with survival rate of 58.3.%. Using "Y" type vein and bile duct prosthesis, we

  7. Understanding the Pathogenesis of Angelman Syndrome through Animal Models

    Directory of Open Access Journals (Sweden)

    Nihar Ranjan Jana

    2012-01-01

    Full Text Available Angelman syndrome (AS is a neurodevelopmental disorder characterized by severe mental retardation, lack of speech, ataxia, susceptibility to seizures, and unique behavioral features such as easily provoked smiling and laughter and autistic features. The disease is primarily caused by deletion or loss-of-function mutations of the maternally inherited UBE3A gene located within chromosome 15q11-q13. The UBE3A gene encodes a 100 kDa protein that functions as ubiquitin ligase and transcriptional coactivator. Emerging evidence now indicates that UBE3A plays a very important role in synaptic function and in regulation of activity-dependent synaptic plasticity. A number of animal models for AS have been generated to understand the disease pathogenesis. The most widely used model is the UBE3A-maternal-deficient mouse that recapitulates most of the essential features of AS including cognitive and motor abnormalities. This paper mainly discusses various animal models of AS and how these models provide fundamental insight into understanding the disease biology for potential therapeutic intervention.

  8. Regulatory acceptance of animal models of disease to support clinical trials of medicines and advanced therapy medicinal products.

    Science.gov (United States)

    Cavagnaro, Joy; Silva Lima, Beatriz

    2015-07-15

    The utility of animal models of disease for assessing the safety of novel therapeutic modalities has become an increasingly important topic of discussion as research and development efforts focus on improving the predictive value of animal studies to support accelerated clinical development. Medicines are approved for marketing based upon a determination that their benefits outweigh foreseeable risks in specific indications, specific populations, and at specific dosages and regimens. No medicine is 100% safe. A medicine is less safe if the actual risks are greater than the predicted risks. The purpose of preclinical safety assessment is to understand the potential risks to aid clinical decision-making. Ideally preclinical studies should identify potential adverse effects and design clinical studies that will minimize their occurrence. Most regulatory documents delineate the utilization of conventional "normal" animal species to evaluate the safety risk of new medicines (i.e., new chemical entities and new biological entities). Animal models of human disease are commonly utilized to gain insight into the pathogenesis of disease and to evaluate efficacy but less frequently utilized in preclinical safety assessment. An understanding of the limitations of the animal disease models together with a better understanding of the disease and how toxicity may be impacted by the disease condition should allow for a better prediction of risk in the intended patient population. Importantly, regulatory authorities are becoming more willing to accept and even recommend data from experimental animal disease models that combine efficacy and safety to support clinical development.

  9. Zebrafish: an animal model for research in veterinary medicine.

    Science.gov (United States)

    Nowik, N; Podlasz, P; Jakimiuk, A; Kasica, N; Sienkiewicz, W; Kaleczyc, J

    2015-01-01

    The zebrafish (Danio rerio) has become known as an excellent model organism for studies of vertebrate biology, vertebrate genetics, embryonal development, diseases and drug screening. Nevertheless, there is still lack of detailed reports about usage of the zebrafish as a model in veterinary medicine. Comparing to other vertebrates, they can lay hundreds of eggs at weekly intervals, externally fertilized zebrafish embryos are accessible to observation and manipulation at all stages of their development, which makes possible to simplify the research techniques such as fate mapping, fluorescent tracer time-lapse lineage analysis and single cell transplantation. Although zebrafish are only 2.5 cm long, they are easy to maintain. Intraperitoneal and intracerebroventricular injections, blood sampling and measurement of food intake are possible to be carry out in adult zebrafish. Danio rerio is a useful animal model for neurobiology, developmental biology, drug research, virology, microbiology and genetics. A lot of diseases, for which the zebrafish is a perfect model organism, affect aquatic animals. For a part of them, like those caused by Mycobacterium marinum or Pseudoloma neutrophila, Danio rerio is a natural host, but the zebrafish is also susceptible to the most of fish diseases including Itch, Spring viraemia of carp and Infectious spleen and kidney necrosis. The zebrafish is commonly used in research of bacterial virulence. The zebrafish embryo allows for rapid, non-invasive and real time analysis of bacterial infections in a vertebrate host. Plenty of common pathogens can be examined using zebrafish model: Streptococcus iniae, Vibrio anguillarum or Listeria monocytogenes. The steps are taken to use the zebrafish also in fungal research, especially that dealing with Candida albicans and Cryptococcus neoformans. Although, the zebrafish is used commonly as an animal model to study diseases caused by external agents, it is also useful in studies of metabolic

  10. Predictive model for segmented poly(urea

    Directory of Open Access Journals (Sweden)

    Frankl P.

    2012-08-01

    Full Text Available Segmented poly(urea has been shown to be of significant benefit in protecting vehicles from blast and impact and there have been several experimental studies to determine the mechanisms by which this protective function might occur. One suggested route is by mechanical activation of the glass transition. In order to enable design of protective structures using this material a constitutive model and equation of state are needed for numerical simulation hydrocodes. Determination of such a predictive model may also help elucidate the beneficial mechanisms that occur in polyurea during high rate loading. The tool deployed to do this has been Group Interaction Modelling (GIM – a mean field technique that has been shown to predict the mechanical and physical properties of polymers from their structure alone. The structure of polyurea has been used to characterise the parameters in the GIM scheme without recourse to experimental data and the equation of state and constitutive model predicts response over a wide range of temperatures and strain rates. The shock Hugoniot has been predicted and validated against existing data. Mechanical response in tensile tests has also been predicted and validated.

  11. Prebiotic effect of Agave fourcroydes fructans: an animal model.

    Science.gov (United States)

    García-Curbelo, Yanelys; Bocourt, Ramón; Savón, Lourdes L; García-Vieyra, Maria Isabel; López, Mercedes G

    2015-09-01

    The use of prebiotics such as fructans has increased in human and animal nutrition because of their productive performance and health benefits. Agave fourcroydes has shown high concentrations of fructans in their stems; however, there is no information on new products derived from this plant that might enhance its added value. Therefore, we evaluated the prebiotic effect of Agave fourcroydes fructans in an animal model. Male mice (C57BL/6J) were fed on parallel form with a standard diet or diets supplemented with 10% of fructans from Cichorium intybus (Raftilose P95) and Agave fourcroydes from Cuba for 35 days. The body weight, food intake, blood glucose, triglycerides and cholesterol, gastrointestinal organ weights, fermentation indicators in cecal and colon contents and mineral content in femurs were determined. The body weight and food intake of mice were not significantly modified by any treatment. However, serum glucose, cholesterol and triglycerides decreased (P fructans groups with respect to the standard diet group; this decrement was higher in the A. fourcroydes group with respect to the Raftilose P95 group. Mice groups supplemented with fructans exhibited increased (P fructans in their diets with respect to the standard diet. The diets supplemented with fructans also increased the mineral concentrations of calcium (P fructans from Agave fourcroydes in the mice diet induced a prebiotic response, similar to or greater than the commercial product (Raftilose P95) and this constitutes a promising alternative with potential use not only in animal but also in human diets.

  12. Animal models of motivation for drinking in rodents with a focus on opioid receptor neuropharmacology.

    Science.gov (United States)

    Koob, George F; Roberts, Amanda J; Kieffer, Brigitte L; Heyser, Charles J; Katner, Simon N; Ciccocioppo, Roberto; Weiss, Friedbert

    2003-01-01

    Ethanol, like other drugs of abuse, has motivating properties that can be developed as animal models of self-administration. A major strength of the operant approach where an animal must work to obtain ethanol is that it reduces confounds due to palatability and controls for nonspecific malaise-inducing effects. In the domain of opioid peptide systems, limited access paradigms have good predictive validity. In addition, animal models of excessive drinking-either environmentally or genetically induced-also appear sensitive to blockade or inactivation of opioid peptide receptors. Ethanol availability can be predicted by cues associated with positive reinforcement, and these models are sensitive to the administration of opioid antagonists. Perhaps most exciting are the recent results suggesting that the key element in opioid peptide systems that is important for the positive reinforcing effects of ethanol is the mu-opioid receptor. How exactly ethanol modulates mu-receptor function will be a major challenge of future research. Nevertheless, the apparently critical role of the mu receptor in ethanol reinforcement refocuses the neuropharmacology of ethanol reinforcement in the opioid peptide domain and opens a novel avenue for exploring medications for treating alcoholism.

  13. Allostasis: a model of predictive regulation.

    Science.gov (United States)

    Sterling, Peter

    2012-04-12

    The premise of the standard regulatory model, "homeostasis", is flawed: the goal of regulation is not to preserve constancy of the internal milieu. Rather, it is to continually adjust the milieu to promote survival and reproduction. Regulatory mechanisms need to be efficient, but homeostasis (error-correction by feedback) is inherently inefficient. Thus, although feedbacks are certainly ubiquitous, they could not possibly serve as the primary regulatory mechanism. A newer model, "allostasis", proposes that efficient regulation requires anticipating needs and preparing to satisfy them before they arise. The advantages: (i) errors are reduced in magnitude and frequency; (ii) response capacities of different components are matched -- to prevent bottlenecks and reduce safety factors; (iii) resources are shared between systems to minimize reserve capacities; (iv) errors are remembered and used to reduce future errors. This regulatory strategy requires a dedicated organ, the brain. The brain tracks multitudinous variables and integrates their values with prior knowledge to predict needs and set priorities. The brain coordinates effectors to mobilize resources from modest bodily stores and enforces a system of flexible trade-offs: from each organ according to its ability, to each organ according to its need. The brain also helps regulate the internal milieu by governing anticipatory behavior. Thus, an animal conserves energy by moving to a warmer place - before it cools, and it conserves salt and water by moving to a cooler one before it sweats. The behavioral strategy requires continuously updating a set of specific "shopping lists" that document the growing need for each key component (warmth, food, salt, water). These appetites funnel into a common pathway that employs a "stick" to drive the organism toward filling the need, plus a "carrot" to relax the organism when the need is satisfied. The stick corresponds broadly to the sense of anxiety, and the carrot broadly to

  14. To eat and not be eaten: modelling resources and safety in multi-species animal groups.

    Directory of Open Access Journals (Sweden)

    Umesh Srinivasan

    Full Text Available Using mixed-species bird flocks as an example, we model the payoffs for two types of species from participating in multi-species animal groups. Salliers feed on mobile prey, are good sentinels and do not affect prey capture rates of gleaners; gleaners feed on prey on substrates and can enhance the prey capture rate of salliers by flushing prey, but are poor sentinels. These functional types are known from various animal taxa that form multi-species associations. We model costs and benefits of joining groups for a wide range of group compositions under varying abundances of two types of prey-prey on substrates and mobile prey. Our model predicts that gleaners and salliers show a conflict of interest in multi-species groups, because gleaners benefit from increasing numbers of salliers in the group, whereas salliers benefit from increasing gleaner numbers. The model also predicts that the limits to size and variability in composition of multi-species groups are driven by the relative abundance of different types of prey, independent of predation pressure. Our model emphasises resources as a primary driver of temporal and spatial group dynamics, rather than reproductive activity or predation per se, which have hitherto been thought to explain patterns of multi-species group formation and cohesion. The qualitative predictions of the model are supported by empirical patterns from both terrestrial and marine multi-species groups, suggesting that similar mechanisms might underlie group dynamics in a range of taxa. The model also makes novel predictions about group dynamics that can be tested using variation across space and time.

  15. The miniature pig as an animal model in biomedical research.

    Science.gov (United States)

    Vodicka, Petr; Smetana, Karel; Dvoránková, Barbora; Emerick, Teresa; Xu, Yingzhi Z; Ourednik, Jitka; Ourednik, Václav; Motlík, Jan

    2005-05-01

    Crucial prerequisites for the development of safe preclinical protocols in biomedical research are suitable animal models that would allow for human-related validation of valuable research information gathered from experimentation with lower mammals. In this sense, the miniature pig, sharing many physiological similarities with humans, offers several breeding and handling advantages (when compared to non-human primates), making it an optimal species for preclinical experimentation. The present review offers several examples taken from current research in the hope of convincing the reader that the porcine animal model has gained massively in importance in biomedical research during the last few years. The adduced examples are taken from the following fields of investigation: (a) the physiology of reproduction, where pig oocytes are being used to study chromosomal abnormalities (aneuploidy) in the adult human oocyte; (b) the generation of suitable organs for xenotransplantation using transgene expression in pig tissues; (c) the skin physiology and the treatment of skin defects using cell therapy-based approaches that take advantage of similarities between pig and human epidermis; and (d) neurotransplantation using porcine neural stem cells grafted into inbred miniature pigs as an alternative model to non-human primates xenografted with human cells.

  16. Hepatoprotective activity of Musa paradisiaca on experimental animal models

    Institute of Scientific and Technical Information of China (English)

    Nirmala M; Girija K; Lakshman K; Divya T

    2012-01-01

    Objective: To investigate the hepatoprotective activity of stem of Musa paradisiaca (M. paradisiaca) in CCl4 and paracetamol induced hepatotoxicity models in rats. Methods:Hepatoprotective activity of alcoholic and aqueous extracts of stem of M. paradisiaca was demonstrated by using two experimentally induced hepatotoxicity models. Results:Administration of hepatotoxins (CCl4 and paracetamol) showed significant biochemical and histological deteriorations in the liver of experimental animals. Pretreatment with alcoholic extract (500 mg/kg), more significantly and to a lesser extent the alcoholic extract (250 mg/kg) and aqueous extract (500 mg/kg), reduced the elevated levels of the serum enzymes like serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and bilirubin levels and alcoholic and aqueous extracts reversed the hepatic damage towards the normal, which further evidenced the hepatoprotective activity of stem of M.paradisiaca. Conclusions: The alcoholic extract at doses of 250 and 500 mg/kg, p.o. and aqueous extract at a dose of 500 mg/kg, p.o. of stem of M. paradisiaca have significant effect on the liver of CCl4 and paracetamol induced hepatotoxicity animal models.

  17. Asthma: a comparison of animal models using stereological methods

    Directory of Open Access Journals (Sweden)

    D. M. Hyde

    2006-12-01

    Full Text Available Asthma is a worldwide health problem that affects 300 million people, as estimated by the World Health Organization. A key question in light of this statistic is: "what is the most appropriate laboratory animal model for human asthma?" The present authors used stereological methods to assess airways in adults and during post-natal development, and their response to inhaled allergens to compare rodents and nonhuman primates to responses in humans. An epithelial–mesenchymal trophic unit was defined in which all of the compartments interact with each other. Asthma manifests itself by altering not only the epithelial compartment but also other compartments (e.g. interstitial, vascular, immunological and nervous. All of these compartments show significant alteration in an airway generation-specific manner in rhesus monkeys but are limited to the proximal airways in mice. The rhesus monkey model shares many of the key features of human allergic asthma including the following: 1 allergen-specific immunoglobulin (IgE and skin-test positivity; 2 eosinophils and IgE+ cells in airways; 3 a T-helper type 2 cytokine profile in airways; 4 mucus cell hyperplasia; 5 subepithelial fibrosis; 6 basement membrane thickening; and 7 persistent baseline hyperreactivity to histamine or methacholine. In conclusion, the unique responses to inhaled allergens shown in rhesus monkeys make it the most appropriate animal model of human asthma.

  18. [Animal models for bone and joint disease. CIA, CAIA model].

    Science.gov (United States)

    Hirose, Jun; Tanaka, Sakae

    2011-02-01

    The collagen-induced arthritis (collagen-induced arthritis, CIA) is an autoimmune arthritis that resembles rheumatoid arthritis (RA) in many ways, therefore it has been used most commonly as a model of RA. CIA is induced by immunization with an emulsion of complete Freund's adjuvant (CFA) and type II collagen (C II ) . Collagen antibody-induced arthritis (CAIA) is induced by the administration of a cocktail of monoclonal antibodies recognizing conserved epitopes located within the CB11 fragment. CAIA offers several advantages over CIA, including rapid disease onset, high uptake rate, and the capacity to use genetically modified mice, such as transgenics and knockouts.

  19. A model for nonexercising hindlimb muscles in exercising animals.

    Science.gov (United States)

    Bonen, A; Blewett, C; McDermott, J C; Elder, G C

    1990-07-01

    Nonexercising muscles appear to be metabolically active during exercise. Animal models for this purpose have not been established. However, we have been able to teach animals to run on their forelimbs while their hindlimbs are suspended above the treadmill with no visible limb movement. To document that indeed this mode of exercise does not provoke additional muscle activity, we have compared the levels of neural activation of the soleus and plantaris muscles using a computer analysis of the electromyographic interference pattern, recorded from bipolar fine wire electrodes implanted across each muscle. Via computer analyses of the electromyographic interference patterns the frequencies and amplitudes of motor unit action potentials were obtained. The data were sampled during 20 s of every minute of observation. Comparisons were made in four conditions: (i) resting on the treadmill while bearing weight on the hindlimbs (normal rest), (ii) running on the treadmill (15 m/min, 8% grade) on all four limbs (normal exercise), (iii) resting while the hindlimbs were suspended in a harness above the treadmill (suspended rest), and (iv) exercising with the forelimbs (15 m/min, 8% grade) while the hindlimbs were suspended above the treadmill (suspended exercise). All four experimental conditions were carried out for 90 min each and were performed by each animal. The results clearly show that muscle activities (frequencies and amplitudes), when the hindlimbs are suspended above the treadmill, at rest or during exercise, are lower than the activities in these same muscles when the animals are at rest, supporting only their body weight. Activities in the same muscles during exercise were from 300 to 2000% greater than during hindlimb suspension.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. What causes type 1 diabetes? Lessons from animal models.

    Science.gov (United States)

    Buschard, Karsten

    2011-07-01

    To study type 1 diabetes (T1D), excellent animal models exist, both spontaneously diabetic and virus-induced. Based on knowledge from these, this review focuses on the environmental factors leading to T1D, concentrated into four areas which are: (1) The thymus-dependent immune system: T1D is a T cell driven disease and the beta cells are destroyed in an inflammatory insulitis process. Autoimmunity is breakdown of self-tolerance and the balance between regulator T cells and aggressive effector T cells is disturbed. Inhibition of the T cells (by e.g. anti-CD3 antibody or cyclosporine) will stop the T1D process, even if initiated by virus. Theoretically, the risk from immunotherapy elicits a higher frequency of malignancy. (2) The activity of the beta cells: Resting beta cells display less antigenicity and are less sensitive to immune destruction. Beta-cell rest can be induced by giving insulin externally in metabolic doses or by administering potassium-channel openers. Both procedures prevent T1D in animal models, whereas no good human data exist due to the risk of hypoglycemia. (3) NKT cells: According to the hygiene hypothesis, stimulation of NKT cells by non-pathogen microbes gives rise to less T cell reaction and less autoimmunity. Glycolipids presented by CD1 molecules are central in this stimulation. (4) Importance of the intestine and gliadin intake: Gluten-free diet dramatically inhibits T1D in animal models, and epidemiological data are supportive of such an effect in humans. The mechanisms include less subclinical intestinal inflammation and permeability, and changed composition of bacterial flora, which can also be obtained by intake of probiotics. Gluten-free diet is difficult to implement, and short-term intake has no effect. Regarding the onset of the T1D disease process, slow-acting enterovirus and gliadin deposits are speculated to be etiological in genetically susceptible individuals, followed by the mentioned four pathogenetic factors acting in

  1. PREDICTIVE CAPACITY OF ARCH FAMILY MODELS

    Directory of Open Access Journals (Sweden)

    Raphael Silveira Amaro

    2016-03-01

    Full Text Available In the last decades, a remarkable number of models, variants from the Autoregressive Conditional Heteroscedastic family, have been developed and empirically tested, making extremely complex the process of choosing a particular model. This research aim to compare the predictive capacity, using the Model Confidence Set procedure, than five conditional heteroskedasticity models, considering eight different statistical probability distributions. The financial series which were used refers to the log-return series of the Bovespa index and the Dow Jones Industrial Index in the period between 27 October 2008 and 30 December 2014. The empirical evidences showed that, in general, competing models have a great homogeneity to make predictions, either for a stock market of a developed country or for a stock market of a developing country. An equivalent result can be inferred for the statistical probability distributions that were used.

  2. New insights into autoimmune cholangitis through animal models.

    Science.gov (United States)

    Trauner, Michael; Fickert, Peter; Baghdasaryan, Anna; Claudel, Thierry; Halilbasic, Emina; Moustafa, Tarek; Wagner, Martin; Zollner, Gernot

    2010-01-01

    Improving our understanding of the pathogenesis of chronic immune-mediated cholangiopathies such as primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), as well as the development of novel diagnostic, prognostic and therapeutic tools for these disorders critically depends on easily reproducible animal models. Recently, several spontaneous mouse models for PBC (not requiring previous manipulations for breakdown of immunotolerance) have been reported, including NOD.c3c4 and NOD.c3c4-derived mice, IL-2Ralpha(-/-) mice, dominant negative TGF-beta receptor II mice and Ae2(a,b)(-/-) mice. To date, no animal model exhibits all of the attributes of PSC. Rodent models induced by bacterial cell components or colitis may help to explain the strong association between PSC and inflammatory bowel disease. Other models include direct injury to biliary epithelia, peribiliary vascular endothelia or portal venous endothelia. Mice with targeted disruption of the Mdr2 (Abcb4) gene encoding a canalicular phospholipid flippase (Mdr2(-/-) mice) spontaneously develop sclerosing cholangitis with macroscopic and microscopic features of human PSC. Another example for a transporter involved in the pathogenesis of sclerosing cholangitis is the cystic fibrosis transmembrane conductance regulator (CFTR/ABCC7). Xenobiotics and drugs may also lead to bile duct injury and biliary fibrosis via direct toxic and indirect immune-mediated injury. Hydrophobic bile acids, such as lithocholic acid, cause bile duct injury and destructive cholangitis with periductal fibrosis resembling sclerosing cholangitis. These models have enhanced our understanding of the pathogenesis of PBC and PSC and will hopefully result in improved treatment of these disorders.

  3. Animal models of β-hemoglobinopathies: utility and limitations

    Directory of Open Access Journals (Sweden)

    McColl B

    2016-11-01

    Full Text Available Bradley McColl, Jim Vadolas Cell and Gene Therapy Laboratory, Murdoch Childrens Research Institute, Royal Children’s Hospital, Parkville, VIC, Australia Abstract: The structural and functional conservation of hemoglobin throughout mammals has made the laboratory mouse an exceptionally useful organism in which to study both the protein and the individual globin genes. Early researchers looked to the globin genes as an excellent model in which to examine gene regulation – bountifully expressed and displaying a remarkably consistent pattern of developmental activation and silencing. In parallel with the growth of research into expression of the globin genes, mutations within the β-globin gene were identified as the cause of the β-hemoglobinopathies such as sickle cell disease and β-thalassemia. These lines of enquiry stimulated the development of transgenic mouse models, first carrying individual human globin genes and then substantial human genomic fragments incorporating the multigenic human β-globin locus and regulatory elements. Finally, mice were devised carrying mutant human β-globin loci on genetic backgrounds deficient in the native mouse globins, resulting in phenotypes of sickle cell disease or β-thalassemia. These years of work have generated a group of model animals that display many features of the β-hemoglobinopathies and provided enormous insight into the mechanisms of gene regulation. Substantive differences in the expression of human and mouse globins during development have also come to light, revealing the limitations of the mouse model, but also providing opportunities to further explore the mechanisms of globin gene regulation. In addition, animal models of β-hemoglobinopathies have demonstrated the feasibility of gene therapy for these conditions, now showing success in human clinical trials. Such models remain in use to dissect the molecular events of globin gene regulation and to identify novel treatments based

  4. Electromagnetic Model Reliably Predicts Radar Scattering Characteristics of Airborne Organisms

    Science.gov (United States)

    Mirkovic, Djordje; Stepanian, Phillip M.; Kelly, Jeffrey F.; Chilson, Phillip B.

    2016-10-01

    The radar scattering characteristics of aerial animals are typically obtained from controlled laboratory measurements of a freshly harvested specimen. These measurements are tedious to perform, difficult to replicate, and typically yield only a small subset of the full azimuthal, elevational, and polarimetric radio scattering data. As an alternative, biological applications of radar often assume that the radar cross sections of flying animals are isotropic, since sophisticated computer models are required to estimate the 3D scattering properties of objects having complex shapes. Using the method of moments implemented in the WIPL-D software package, we show for the first time that such electromagnetic modeling techniques (typically applied to man-made objects) can accurately predict organismal radio scattering characteristics from an anatomical model: here the Brazilian free-tailed bat (Tadarida brasiliensis). The simulated scattering properties of the bat agree with controlled measurements and radar observations made during a field study of bats in flight. This numerical technique can produce the full angular set of quantitative polarimetric scattering characteristics, while eliminating many practical difficulties associated with physical measurements. Such a modeling framework can be applied for bird, bat, and insect species, and will help drive a shift in radar biology from a largely qualitative and phenomenological science toward quantitative estimation of animal densities and taxonomic identification.

  5. ANTIGENICITY OF COW'S MILK PROTEINS IN TWO ANIMAL MODELS

    Directory of Open Access Journals (Sweden)

    T.R. Neyestani

    2000-08-01

    Full Text Available Antigenicity of proteins found in cow's milk is age dependent. This is primarily due to infants possessing a more permeable intestinal wall than that in adults. Thus infants may acquire cow's milk allergy during their first year of life. While milk antigen specific IgE may cause allergy in susceptible subjects, there is some evidence indicating that milk antigen specific IgG may play some role in chronic disease development. The puropose of this study was to determine the antigenicity of cow's milk proteins in two animal models and to recommend the more sensitivie one, as an evaluation tool, to assess the antigenicity of a poteintial hypoallergenic formula. A crude extract of cow's milk was injected either to young male rabbits or BALB/C mice in four doses. Pure standard proteins of cow's milk were also injected to separate groups of animals to use their anti sera in later stages. The polyclonal pooled serum was then used to evaluate the antigenicity of the extract by indirect enzyme-linked immunossorbeni assay (LEISA. and Western blotting. Both the rabbit and BALB/C murine mode! demonstrated strong ELISA titres against casein and BSA proteins. However, the rabbit model also had a high antibody response against beta-lactoglobulin (/Mg. The lowest antibody response was found against alpha-kictalbumin («-la in both animal models and no response against immunoglobulins (Igs in either model. In Western blotting, rabbit antiserum showed four bands («-la, /Mg, caseins and BSA compared to two bands (caseins and BSA for mouse antiserum. Considering the allergenicity of these proteins in genetically prone subjects, it may be wise to exclude food sources of caseins as well as major whey proteins (BSA, from the diet of infants with a family history of atopy during the first year of life. The rabbit hyperimmunization model was more sensitive than the murine mode! in detecting antibodies against milk proteins. Thus, the rabbii model should be employed when

  6. Incorporating animal behavior into seed dispersal models: implications for seed shadows.

    Science.gov (United States)

    Russo, Sabrina E; Portnoy, Stephen; Augspurger, Carol K

    2006-12-01

    Seed dispersal fundamentally influences plant population and community dynamics but is difficult to quantify directly. Consequently, models are frequently used to describe the seed shadow (the seed deposition pattern of a plant population). For vertebrate-dispersed plants, animal behavior is known to influence seed shadows but is poorly integrated in seed dispersal models. Here, we illustrate a modeling approach that incorporates animal behavior and develop a stochastic, spatially explicit simulation model that predicts the seed shadow for a primate-dispersed tree species (Virola calophylla, Myristicaceae) at the forest stand scale. The model was parameterized from field-collected data on fruit production and seed dispersal, behaviors and movement patterns of the key disperser, the spider monkey (Ateles paniscus), densities of dispersed and non-dispersed seeds, and direct estimates of seed dispersal distances. Our model demonstrated that the spatial scale of dispersal for this V. calophylla population was large, as spider monkeys routinely dispersed seeds >100 m, a commonly used threshold for long-distance dispersal. The simulated seed shadow was heterogeneous, with high spatial variance in seed density resulting largely from behaviors and movement patterns of spider monkeys that aggregated seeds (dispersal at their sleeping sites) and that scattered seeds (dispersal during diurnal foraging and resting). The single-distribution dispersal kernels frequently used to model dispersal substantially underestimated this variance and poorly fit the simulated seed-dispersal curve, primarily because of its multimodality, and a mixture distribution always fit the simulated dispersal curve better. Both seed shadow heterogeneity and dispersal curve multimodality arose directly from these different dispersal processes generated by spider monkeys. Compared to models that did not account for disperser behavior, our modeling approach improved prediction of the seed shadow of this V

  7. Modelling the predictive performance of credit scoring

    Directory of Open Access Journals (Sweden)

    Shi-Wei Shen

    2013-02-01

    Full Text Available Orientation: The article discussed the importance of rigour in credit risk assessment.Research purpose: The purpose of this empirical paper was to examine the predictive performance of credit scoring systems in Taiwan.Motivation for the study: Corporate lending remains a major business line for financial institutions. However, in light of the recent global financial crises, it has become extremely important for financial institutions to implement rigorous means of assessing clients seeking access to credit facilities.Research design, approach and method: Using a data sample of 10 349 observations drawn between 1992 and 2010, logistic regression models were utilised to examine the predictive performance of credit scoring systems.Main findings: A test of Goodness of fit demonstrated that credit scoring models that incorporated the Taiwan Corporate Credit Risk Index (TCRI, micro- and also macroeconomic variables possessed greater predictive power. This suggests that macroeconomic variables do have explanatory power for default credit risk.Practical/managerial implications: The originality in the study was that three models were developed to predict corporate firms’ defaults based on different microeconomic and macroeconomic factors such as the TCRI, asset growth rates, stock index and gross domestic product.Contribution/value-add: The study utilises different goodness of fits and receiver operator characteristics during the examination of the robustness of the predictive power of these factors.

  8. Calibrated predictions for multivariate competing risks models.

    Science.gov (United States)

    Gorfine, Malka; Hsu, Li; Zucker, David M; Parmigiani, Giovanni

    2014-04-01

    Prediction models for time-to-event data play a prominent role in assessing the individual risk of a disease, such as cancer. Accurate disease prediction models provide an efficient tool for identifying individuals at high risk, and provide the groundwork for estimating the population burden and cost of disease and for developing patient care guidelines. We focus on risk prediction of a disease in which family history is an important risk factor that reflects inherited genetic susceptibility, shared environment, and common behavior patterns. In this work family history is accommodated using frailty models, with the main novel feature being allowing for competing risks, such as other diseases or mortality. We show through a simulation study that naively treating competing risks as independent right censoring events results in non-calibrated predictions, with the expected number of events overestimated. Discrimination performance is not affected by ignoring competing risks. Our proposed prediction methodologies correctly account for competing events, are very well calibrated, and easy to implement.

  9. Shigella vaccine development: prospective animal models and current status.

    Science.gov (United States)

    Kim, Yeon-Jeong; Yeo, Sang-Gu; Park, Jae-Hak; Ko, Hyun-Jeong

    2013-01-01

    Shigella was first discovered in 1897 and is a major causative agent of dysenteric diarrhea. The number of affected patients has decreased globally because of improved sanitary conditions; however, Shigella still causes serious problems in many subjects, including young children and the elderly, especially in developing countries. Although antibiotics may be effective, a vaccine would be the most powerful solution to combat shigellosis because of the emergence of drug-resistant strains. However, the development of a vaccine is hampered by several problems. First, there is no suitable animal model that can replace human-based studies for the investigation of the in vivo mechanisms of Shigella vaccines. Mouse, guinea pig, rat, rabbit, and nonhuman primates could be used as models for shigellosis, but they do not represent human shigellosis and each has its own weaknesses. However, a recent murine model based on peritoneal infection with virulent S. flexneri 2a is promising. Moreover, although the inflammatory responses and mechanisms such as pathogenassociated molecular patterns and danger-associated molecular patterns have been studied, the pathology and immunology of Shigella are still not clearly defined. Despite these obstacles, many vaccine candidates have been developed, including live attenuated, killed whole cells, conjugated, and subunit vaccines. The development of Shigella vaccines also demands considerations of the cost, routes of administration, ease of storage (stability), cross-reactivity, safety, and immunogenicity. The main aim of this review is to provide a detailed introduction to the many promising vaccine candidates and animal models currently available, including the newly developed mouse model.

  10. [Pertinence of animal and human models in the evaluation of ventricular anti-arrhythmia agents].

    Science.gov (United States)

    Funck-Brentano, C; Le Heuzey, J Y

    1991-02-01

    The development of antiarrhythmic agents for the treatment of ventricular arrhythmias depends to a large extent on their effects in different animal and human models. The clinical relevance of the data so obtained is debatable. Firstly, in vitro animal models of arrhythmias are not very predictive of the multiple clinical forms of ventricular arrhythmias. Secondly, the intermediary criteria of evaluation of the effects of antiarrhythmic drugs in humans are generally not valid in terms of criteria of substitution for the evaluation of therapeutic effects. Nevertheless, cellular and hemodynamic studies of the electrophysiological properties of drugs are essential for correct clinical usage of antiarrhythmics. They help predict the principal clinical electrocardiographic changes and their modulation with respect to parameters such as ischemia or heart rate, their hemodynamic tolerance and certain undesirable, especially proarrhythmic, effects. However, the clinical pertinence of these studies remains limited for a number of reasons. In particular, most antiarrhythmic agents have multiple electrophysiological effects, the resultant of which is difficult to predict in the clinical situation. In addition, many of these drugs have active metabolites, the formation of which varies from person to person, which also reduces the clinical relevance of studies of the parent molecule alone. Clinical trials in appropriate patient populations should therefore be preferred to the multiplication of studies on experimental models of uncertain relevance.

  11. Effects of sclerostin antibodies in animal models of osteoporosis.

    Science.gov (United States)

    Ominsky, Michael Stuart; Boyce, Rogely Waite; Li, Xiaodong; Ke, Hua Zhu

    2017-03-01

    There is an unmet need for therapies that can restore bone strength and reduce fracture risk among patients at high risk of osteoporotic fracture. To address this need, bone-forming therapies that increase osteoblast activity are required to help restore bone structure and strength. Sclerostin is now recognized as a target for osteoporosis therapy. Sclerostin is predominantly secreted by the osteocyte and acts as an extracellular inhibitor of canonical Wnt signaling by binding to the receptors lipoprotein receptor-related protein-4, 5 and 6. Monoclonal antibodies to sclerostin (Scl-Ab) have been used in both clinical and in preclinical studies of osteoporosis with beneficial outcomes for bone density, structure, strength and fracture risk reduction. In this review paper, we summarize the current literature describing the effects of Scl-Ab in animal models of osteoporosis. In addition, we report new pharmacologic data from three animal studies of Scl-Ab: 1) a 12-month study evaluating bone quality in ovariectomized (OVX) rats; 2) a 6-month study evaluating bone structure and strength in adolescent cynomolgus monkeys; and 3) the effects of transition from Scl-Ab to vehicle or the RANKL inhibitor osteoprotegerin-Fc in OVX rats. Together, these results demonstrate that inhibition of sclerostin by Scl-Ab increased bone formation, and decreased bone resorption, leading to improved bone structure, bone mass and bone strength while maintaining bone quality in multiple animal models of osteoporosis. Further, gains in bone mass induced by Scl-Ab treatment were preserved by antiresorptive agents such as a RANKL inhibitor as a follow-on therapy. The bone-forming effects of Scl-Ab were unaffected by pre- or co-treatment with a bisphosphonate, and were restored following a treatment-free period after initial dosing. These data support the clinical development of Scl-Ab for treatment of conditions with low bone mass such as postmenopausal and male osteoporosis.

  12. Computer-aided pulmonary image analysis in small animal models

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Ziyue; Mansoor, Awais; Mollura, Daniel J. [Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, National Institutes of Health (NIH), Bethesda, Maryland 32892 (United States); Bagci, Ulas, E-mail: ulasbagci@gmail.com [Center for Research in Computer Vision (CRCV), University of Central Florida (UCF), Orlando, Florida 32816 (United States); Kramer-Marek, Gabriela [The Institute of Cancer Research, London SW7 3RP (United Kingdom); Luna, Brian [Microfluidic Laboratory Automation, University of California-Irvine, Irvine, California 92697-2715 (United States); Kubler, Andre [Department of Medicine, Imperial College London, London SW7 2AZ (United Kingdom); Dey, Bappaditya; Jain, Sanjay [Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231 (United States); Foster, Brent [Department of Biomedical Engineering, University of California-Davis, Davis, California 95817 (United States); Papadakis, Georgios Z. [Radiology and Imaging Sciences, National Institutes of Health (NIH), Bethesda, Maryland 32892 (United States); Camp, Jeremy V. [Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky 40202 (United States); Jonsson, Colleen B. [National Institute for Mathematical and Biological Synthesis, University of Tennessee, Knoxville, Tennessee 37996 (United States); Bishai, William R. [Howard Hughes Medical Institute, Chevy Chase, Maryland 20815 and Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231 (United States); Udupa, Jayaram K. [Medical Image Processing Group, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 (United States)

    2015-07-15

    Purpose: To develop an automated pulmonary image analysis framework for infectious lung diseases in small animal models. Methods: The authors describe a novel pathological lung and airway segmentation method for small animals. The proposed framework includes identification of abnormal imaging patterns pertaining to infectious lung diseases. First, the authors’ system estimates an expected lung volume by utilizing a regression function between total lung capacity and approximated rib cage volume. A significant difference between the expected lung volume and the initial lung segmentation indicates the presence of severe pathology, and invokes a machine learning based abnormal imaging pattern detection system next. The final stage of the proposed framework is the automatic extraction of airway tree for which new affinity relationships within the fuzzy connectedness image segmentation framework are proposed by combining Hessian and gray-scale morphological reconstruction filters. Results: 133 CT scans were collected from four different studies encompassing a wide spectrum of pulmonary abnormalities pertaining to two commonly used small animal models (ferret and rabbit). Sensitivity and specificity were greater than 90% for pathological lung segmentation (average dice similarity coefficient > 0.9). While qualitative visual assessments of airway tree extraction were performed by the participating expert radiologists, for quantitative evaluation the authors validated the proposed airway extraction method by using publicly available EXACT’09 data set. Conclusions: The authors developed a comprehensive computer-aided pulmonary image analysis framework for preclinical research applications. The proposed framework consists of automatic pathological lung segmentation and accurate airway tree extraction. The framework has high sensitivity and specificity; therefore, it can contribute advances in preclinical research in pulmonary diseases.

  13. The Animal Model Determines the Results of Aeromonas Virulence Factors

    Science.gov (United States)

    Romero, Alejandro; Saraceni, Paolo R.; Merino, Susana; Figueras, Antonio; Tomás, Juan M.; Novoa, Beatriz

    2016-01-01

    The selection of an experimental animal model is of great importance in the study of bacterial virulence factors. Here, a bath infection of zebrafish larvae is proposed as an alternative model to study the virulence factors of Aeromonas hydrophila. Intraperitoneal infections in mice and trout were compared with bath infections in zebrafish larvae using specific mutants. The great advantage of this model is that bath immersion mimics the natural route of infection, and injury to the tail also provides a natural portal of entry for the bacteria. The implication of T3SS in the virulence of A. hydrophila was analyzed using the AH-1::aopB mutant. This mutant was less virulent than the wild-type strain when inoculated into zebrafish larvae, as described in other vertebrates. However, the zebrafish model exhibited slight differences in mortality kinetics only observed using invertebrate models. Infections using the mutant AH-1ΔvapA lacking the gene coding for the surface S-layer suggested that this protein was not totally necessary to the bacteria once it was inside the host, but it contributed to the inflammatory response. Only when healthy zebrafish larvae were infected did the mutant produce less mortality than the wild-type. Variations between models were evidenced using the AH-1ΔrmlB, which lacks the O-antigen lipopolysaccharide (LPS), and the AH-1ΔwahD, which lacks the O-antigen LPS and part of the LPS outer-core. Both mutants showed decreased mortality in all of the animal models, but the differences between them were only observed in injured zebrafish larvae, suggesting that residues from the LPS outer core must be important for virulence. The greatest differences were observed using the AH-1ΔFlaB-J (lacking polar flagella and unable to swim) and the AH-1::motX (non-motile but producing flagella). They were as pathogenic as the wild-type strain when injected into mice and trout, but no mortalities were registered in zebrafish larvae. This study demonstrates

  14. Modelling language evolution: Examples and predictions

    Science.gov (United States)

    Gong, Tao; Shuai, Lan; Zhang, Menghan

    2014-06-01

    We survey recent computer modelling research of language evolution, focusing on a rule-based model simulating the lexicon-syntax coevolution and an equation-based model quantifying the language competition dynamics. We discuss four predictions of these models: (a) correlation between domain-general abilities (e.g. sequential learning) and language-specific mechanisms (e.g. word order processing); (b) coevolution of language and relevant competences (e.g. joint attention); (c) effects of cultural transmission and social structure on linguistic understandability; and (d) commonalities between linguistic, biological, and physical phenomena. All these contribute significantly to our understanding of the evolutions of language structures, individual learning mechanisms, and relevant biological and socio-cultural factors. We conclude the survey by highlighting three future directions of modelling studies of language evolution: (a) adopting experimental approaches for model evaluation; (b) consolidating empirical foundations of models; and (c) multi-disciplinary collaboration among modelling, linguistics, and other relevant disciplines.

  15. Modelling language evolution: Examples and predictions.

    Science.gov (United States)

    Gong, Tao; Shuai, Lan; Zhang, Menghan

    2014-06-01

    We survey recent computer modelling research of language evolution, focusing on a rule-based model simulating the lexicon-syntax coevolution and an equation-based model quantifying the language competition dynamics. We discuss four predictions of these models: (a) correlation between domain-general abilities (e.g. sequential learning) and language-specific mechanisms (e.g. word order processing); (b) coevolution of language and relevant competences (e.g. joint attention); (c) effects of cultural transmission and social structure on linguistic understandability; and (d) commonalities between linguistic, biological, and physical phenomena. All these contribute significantly to our understanding of the evolutions of language structures, individual learning mechanisms, and relevant biological and socio-cultural factors. We conclude the survey by highlighting three future directions of modelling studies of language evolution: (a) adopting experimental approaches for model evaluation; (b) consolidating empirical foundations of models; and (c) multi-disciplinary collaboration among modelling, linguistics, and other relevant disciplines.

  16. Global Solar Dynamo Models: Simulations and Predictions

    Indian Academy of Sciences (India)

    Mausumi Dikpati; Peter A. Gilman

    2008-03-01

    Flux-transport type solar dynamos have achieved considerable success in correctly simulating many solar cycle features, and are now being used for prediction of solar cycle timing and amplitude.We first define flux-transport dynamos and demonstrate how they work. The essential added ingredient in this class of models is meridional circulation, which governs the dynamo period and also plays a crucial role in determining the Sun’s memory about its past magnetic fields.We show that flux-transport dynamo models can explain many key features of solar cycles. Then we show that a predictive tool can be built from this class of dynamo that can be used to predict mean solar cycle features by assimilating magnetic field data from previous cycles.

  17. A New Model for the Collective Behavior of Animals

    CERN Document Server

    Nguyen, P The; Diep, H T

    2015-01-01

    We propose a new model in order to study behaviors of self-organized system such as a group of animals. We assume that the individuals have two degrees of freedom corresponding one to their internal state and the other to their external state. The external state is characterized by its moving orientation. The rule of the interaction between the individuals is determined by the internal state which can be either in the non-excited state or in the excited state. The system is put under a source of external perturbation called "noise". To study the behavior of the model with varying noise, we use the Monte-Carlo simulation technique. The result clearly shows two first-order transitions separating the system into three phases: with increasing noise, the system undergoes a phase transition from a frozen dilute phase to an ordered compact phase and then to the disordered dispersed phase. These phases correspond to behaviors of animals: uncollected state at low noise, flocking at medium noise and runaway at high noi...

  18. An intermediate animal model of spinal cord stimulation

    Directory of Open Access Journals (Sweden)

    Thomas Guiho

    2016-06-01

    Full Text Available Spinal cord injuries (SCI result in the loss of movement and sensory feedback as well as organs dysfunctions. For example, nearly all SCI subjects loose their bladder control and are prone to kidney failure if they do not proceed to intermittent (self- catheterization. Electrical stimulation of the sacral spinal roots with an implantable neuroprosthesis is a promising approach, with commercialized products, to restore continence and control micturition. However, many persons do not ask for this intervention since a surgical deafferentation is needed and the loss of sensory functions and reflexes become serious side effects of this procedure. Recent results renewed interest in spinal cord stimulation. Stimulation of existing pre-cabled neural networks involved in physiological processes regulation is suspected to enable synergic recruitment of spinal fibers. The development of direct spinal stimulation strategies aiming at bladder and bowel functions restoration would therefore appear as a credible alternative to existent solutions. However, a lack of suitable large animal model complicates these kinds of studies. In this article, we propose a new animal model of spinal stimulation -pig- and will briefly introduce results from one first acute experimental validation session.

  19. Experimental animal data and modeling of late somatic effects

    Energy Technology Data Exchange (ETDEWEB)

    Fry, R.J.M.

    1988-01-01

    This section is restricted to radiation-induced life shortening and cancer and mainly to studies with external radiation. The emphasis will be on the experimental data that are available and the experimental systems that could provide the type of data with which to either formulate or test models. Genetic effects which are of concern are not discussed in this section. Experimental animal radiation studies fall into those that establish general principles and those that demonstrate mechanisms. General principles include the influence of dose, radiation quality, dose rate, fractionation, protraction and such biological factors as age and gender. The influence of these factors are considered as general principles because they are independent, at least qualitatively, of the species studied. For example, if an increase in the LET of the radiation causes an increased effectiveness in cancer induction in a mouse a comparable increase in effectiveness can be expected in humans. Thus, models, whether empirical or mechanistic, formulated from experimental animal data should be generally applicable.

  20. Model Predictive Control of Sewer Networks

    Science.gov (United States)

    Pedersen, Einar B.; Herbertsson, Hannes R.; Niemann, Henrik; Poulsen, Niels K.; Falk, Anne K. V.

    2017-01-01

    The developments in solutions for management of urban drainage are of vital importance, as the amount of sewer water from urban areas continues to increase due to the increase of the world’s population and the change in the climate conditions. How a sewer network is structured, monitored and controlled have thus become essential factors for effcient performance of waste water treatment plants. This paper examines methods for simplified modelling and controlling a sewer network. A practical approach to the problem is used by analysing simplified design model, which is based on the Barcelona benchmark model. Due to the inherent constraints the applied approach is based on Model Predictive Control.

  1. Modeling Warfare in Social Animals: A "Chemical" Approach

    Science.gov (United States)

    Santarlasci, Alisa; Martelloni, Gianluca; Frizzi, Filippo; Santini, Giacomo; Bagnoli, Franco

    2014-01-01

    We present here a general method for modelling the dynamics of battles among social animals. The proposed method exploits the procedures widely used to model chemical reactions, but still uncommon in behavioural studies. We applied this methodology to the interpretation of experimental observations of battles between two species of ants (Lasius neglectus and Lasius paralienus), but this scheme may have a wider applicability and can be extended to other species as well. We performed two types of experiment labelled as interaction and mortality. The interaction experiments are designed to obtain information on the combat dynamics and lasted one hour. The mortality ones provide information on the casualty rates of the two species and lasted five hours. We modelled the interactions among ants using a chemical model which considers the single ant individuals and fighting groups analogously to atoms and molecules. The mean-field behaviour of the model is described by a set of non-linear differential equations. We also performed stochastic simulations of the corresponding agent-based model by means of the Gillespie event-driven integration scheme. By fitting the stochastic trajectories with the deterministic model, we obtained the probability distribution of the reaction parameters. The main result that we obtained is a dominance phase diagram, that gives the average trajectory of a generic battle, for an arbitrary number of opponents. This phase diagram was validated with some extra experiments. With respect to other war models (e.g., Lanchester's ones), our chemical model considers all phases of the battle and not only casualties. This allows a more detailed description of the battle (with a larger number of parameters), allowing the development of more sophisticated models (e.g., spatial ones), with the goal of distinguishing collective effects from the strategic ones. PMID:25369269

  2. DKIST Polarization Modeling and Performance Predictions

    Science.gov (United States)

    Harrington, David

    2016-05-01

    Calibrating the Mueller matrices of large aperture telescopes and associated coude instrumentation requires astronomical sources and several modeling assumptions to predict the behavior of the system polarization with field of view, altitude, azimuth and wavelength. The Daniel K Inouye Solar Telescope (DKIST) polarimetric instrumentation requires very high accuracy calibration of a complex coude path with an off-axis f/2 primary mirror, time dependent optical configurations and substantial field of view. Polarization predictions across a diversity of optical configurations, tracking scenarios, slit geometries and vendor coating formulations are critical to both construction and contined operations efforts. Recent daytime sky based polarization calibrations of the 4m AEOS telescope and HiVIS spectropolarimeter on Haleakala have provided system Mueller matrices over full telescope articulation for a 15-reflection coude system. AEOS and HiVIS are a DKIST analog with a many-fold coude optical feed and similar mirror coatings creating 100% polarization cross-talk with altitude, azimuth and wavelength. Polarization modeling predictions using Zemax have successfully matched the altitude-azimuth-wavelength dependence on HiVIS with the few percent amplitude limitations of several instrument artifacts. Polarization predictions for coude beam paths depend greatly on modeling the angle-of-incidence dependences in powered optics and the mirror coating formulations. A 6 month HiVIS daytime sky calibration plan has been analyzed for accuracy under a wide range of sky conditions and data analysis algorithms. Predictions of polarimetric performance for the DKIST first-light instrumentation suite have been created under a range of configurations. These new modeling tools and polarization predictions have substantial impact for the design, fabrication and calibration process in the presence of manufacturing issues, science use-case requirements and ultimate system calibration

  3. Raman Model Predicting Hardness of Covalent Crystals

    OpenAIRE

    Zhou, Xiang-Feng; Qian, Quang-Rui; Sun, Jian; Tian, Yongjun; Wang, Hui-Tian

    2009-01-01

    Based on the fact that both hardness and vibrational Raman spectrum depend on the intrinsic property of chemical bonds, we propose a new theoretical model for predicting hardness of a covalent crystal. The quantitative relationship between hardness and vibrational Raman frequencies deduced from the typical zincblende covalent crystals is validated to be also applicable for the complex multicomponent crystals. This model enables us to nondestructively and indirectly characterize the hardness o...

  4. Modelling Chemical Reasoning to Predict Reactions

    OpenAIRE

    Segler, Marwin H. S.; Waller, Mark P.

    2016-01-01

    The ability to reason beyond established knowledge allows Organic Chemists to solve synthetic problems and to invent novel transformations. Here, we propose a model which mimics chemical reasoning and formalises reaction prediction as finding missing links in a knowledge graph. We have constructed a knowledge graph containing 14.4 million molecules and 8.2 million binary reactions, which represents the bulk of all chemical reactions ever published in the scientific literature. Our model outpe...

  5. Predictive Modeling of the CDRA 4BMS

    Science.gov (United States)

    Coker, Robert; Knox, James

    2016-01-01

    Fully predictive models of the Four Bed Molecular Sieve of the Carbon Dioxide Removal Assembly on the International Space Station are being developed. This virtual laboratory will be used to help reduce mass, power, and volume requirements for future missions. In this paper we describe current and planned modeling developments in the area of carbon dioxide removal to support future crewed Mars missions as well as the resolution of anomalies observed in the ISS CDRA.

  6. Predictability of extreme values in geophysical models

    NARCIS (Netherlands)

    Sterk, A.E.; Holland, M.P.; Rabassa, P.; Broer, H.W.; Vitolo, R.

    2012-01-01

    Extreme value theory in deterministic systems is concerned with unlikely large (or small) values of an observable evaluated along evolutions of the system. In this paper we study the finite-time predictability of extreme values, such as convection, energy, and wind speeds, in three geophysical model

  7. A Predictive Model for MSSW Student Success

    Science.gov (United States)

    Napier, Angela Michele

    2011-01-01

    This study tested a hypothetical model for predicting both graduate GPA and graduation of University of Louisville Kent School of Social Work Master of Science in Social Work (MSSW) students entering the program during the 2001-2005 school years. The preexisting characteristics of demographics, academic preparedness and culture shock along with…

  8. Distributed Model Predictive Control via Dual Decomposition

    DEFF Research Database (Denmark)

    Biegel, Benjamin; Stoustrup, Jakob; Andersen, Palle

    2014-01-01

    This chapter presents dual decomposition as a means to coordinate a number of subsystems coupled by state and input constraints. Each subsystem is equipped with a local model predictive controller while a centralized entity manages the subsystems via prices associated with the coupling constraints...

  9. Predictive Modelling of Mycotoxins in Cereals

    NARCIS (Netherlands)

    Fels, van der H.J.; Liu, C.

    2015-01-01

    In dit artikel worden de samenvattingen van de presentaties tijdens de 30e bijeenkomst van de Werkgroep Fusarium weergegeven. De onderwerpen zijn: Predictive Modelling of Mycotoxins in Cereals.; Microbial degradation of DON.; Exposure to green leaf volatiles primes wheat against FHB but boosts produ

  10. Unreachable Setpoints in Model Predictive Control

    DEFF Research Database (Denmark)

    Rawlings, James B.; Bonné, Dennis; Jørgensen, John Bagterp

    2008-01-01

    steady state is established for terminal constraint model predictive control (MPC). The region of attraction is the steerable set. Existing analysis methods for closed-loop properties of MPC are not applicable to this new formulation, and a new analysis method is developed. It is shown how to extend...

  11. Leptogenesis in minimal predictive seesaw models

    CERN Document Server

    Björkeroth, Fredrik; Varzielas, Ivo de Medeiros; King, Stephen F

    2015-01-01

    We estimate the Baryon Asymmetry of the Universe (BAU) arising from leptogenesis within a class of minimal predictive seesaw models involving two right-handed neutrinos and simple Yukawa structures with one texture zero. The two right-handed neutrinos are dominantly responsible for the "atmospheric" and "solar" neutrino masses with Yukawa couplings to $(\

  12. Perinatal Cerebellar Injury in Human and Animal Models

    Directory of Open Access Journals (Sweden)

    Valerie Biran

    2012-01-01

    Full Text Available Cerebellar injury is increasingly recognized through advanced neonatal brain imaging as a complication of premature birth. Survivors of preterm birth demonstrate a constellation of long-term neurodevelopmental deficits, many of which are potentially referable to cerebellar injury, including impaired motor functions such as fine motor incoordination, impaired motor sequencing and also cognitive, behavioral dysfunction among older patients. This paper reviews the morphogenesis and histogenesis of the human and rodent developing cerebellum, and its more frequent injuries in preterm. Most cerebellar lesions are cerebellar hemorrhage and infarction usually leading to cerebellar abnormalities and/or atrophy, but the exact pathogenesis of lesions of the cerebellum is unknown. The different mechanisms involved have been investigated with animal models and are primarily hypoxia, ischemia, infection, and inflammation Exposure to drugs and undernutrition can also induce cerebellar abnormalities. Different models are detailed to analyze these various disturbances of cerebellar development around birth.

  13. Shopping Centers as Panther Habitat: Inferring Animal Locations from Models

    Directory of Open Access Journals (Sweden)

    Jeffery L. Larkin

    2004-12-01

    Full Text Available A recent model of Florida panther (Puma concolor coryi habitat erred in arbitrarily creating buffers around radio locations collected during daylight hours on the assumption that study animals were only at rest during these times. The buffers generated by this method likely cause an overestimation of the amounts and kinds of habitats that are used by the panther. This, and other errors, could lead to the impression that unfragmented forest cover is unimportant to panther conservation, and could encourage inaccurate characterizations of panther habitat. Previous 24-hour monitoring of activity and activity readings made during routine telemetry flights indicate that high levels of activity occur in the early morning hours. Literature on the behavior of the species does not support the creation of large buffers around telemetry locations to compensate for the lack of nighttime telemetry data. A thorough examination of ongoing studies that use global positioning systems may help calibrate future Florida panther habitat models.

  14. Nicotine addiction: studies about vulnerability, epigenesis and animal models

    Directory of Open Access Journals (Sweden)

    Bernabeu, Ramon

    2013-07-01

    Full Text Available This article is a summary about the current research of nicotine effects on the nervous system and its relationship to the generation of an addictive behavior. Like other drugs of abuse, nicotine activates the reward pathway, which in turn is involved in certain psychiatric diseases. There are individuals who have a high vulnerability to nicotine addiction. This may be due to genetic and epigenetic factors and/or the environment. In this review, we described some epigenetic factors that may be involved in those phenomena. The two animal models most widely used for studying the reinforcing effects of nicotine are: self-administration and conditioning place preference (CPP. Here, we emphasized the CPP, due to its potential application in humans. In addition, we described the locomotor activity model (as a measure of psychostimulant effects to study vulnerability to drugs of abuse

  15. Animal Models of Leptospirosis: Of Mice and Hamsters

    Science.gov (United States)

    Gomes-Solecki, Maria; Santecchia, Ignacio; Werts, Catherine

    2017-01-01

    Pathogenic Leptospira sp. are spirochetal bacteria responsible for leptospirosis, an emerging worldwide zoonosis. These spirochetes are very successful pathogens that infect a wide range of hosts such as fish, reptiles, birds, marsupials, and mammals. Transmission occurs when chronically infected animals excrete live bacteria in their urine, contaminating the environment. Leptospira sp. enter their hosts through damaged skin and mucosa. Chronically infected rats and mice are asymptomatic and are considered as important reservoirs of the disease. Infected humans may develop either a flu-like, usually mild illness with or without chronic asymptotic renal colonization, or a severe acute disease with kidney, liver, and heart failure, potentially leading to death. Leptospirosis is an economic burden on society due to health-care costs related to elevated morbidity of humans and loss of animals of agricultural interest. There are no effective vaccines against leptospirosis. Leptospira sp. are difficult to genetically manipulate which delays the pace of research progress. In this review, we discuss in an historical perspective how animal models have contributed to further our knowledge of leptospirosis. Hamsters, guinea pigs, and gerbils have been instrumental to study the pathophysiology of acute lethal leptospirosis and the Leptospira sp. genes involved in virulence. Chronic renal colonization has been mostly studied using experimentally infected rats. A special emphasis will be placed on mouse models, long thought to be irrelevant since they survive lethal infection. However, mice have recently been shown to be good models of sublethal infection leading to chronic colonization. Furthermore, congenic and transgenic mice have proven essential to study how innate immune cells interact with the pathogen and to understand the role of the toll-like receptor 4, which is important to control Leptospira sp. load and disease. The use of inbred and transgenic mouse models opens

  16. Disease prediction models and operational readiness.

    Directory of Open Access Journals (Sweden)

    Courtney D Corley

    Full Text Available The objective of this manuscript is to present a systematic review of biosurveillance models that operate on select agents and can forecast the occurrence of a disease event. We define a disease event to be a biological event with focus on the One Health paradigm. These events are characterized by evidence of infection and or disease condition. We reviewed models that attempted to predict a disease event, not merely its transmission dynamics and we considered models involving pathogens of concern as determined by the US National Select Agent Registry (as of June 2011. We searched commercial and government databases and harvested Google search results for eligible models, using terms and phrases provided by public health analysts relating to biosurveillance, remote sensing, risk assessments, spatial epidemiology, and ecological niche modeling. After removal of duplications and extraneous material, a core collection of 6,524 items was established, and these publications along with their abstracts are presented in a semantic wiki at http://BioCat.pnnl.gov. As a result, we systematically reviewed 44 papers, and the results are presented in this analysis. We identified 44 models, classified as one or more of the following: event prediction (4, spatial (26, ecological niche (28, diagnostic or clinical (6, spread or response (9, and reviews (3. The model parameters (e.g., etiology, climatic, spatial, cultural and data sources (e.g., remote sensing, non-governmental organizations, expert opinion, epidemiological were recorded and reviewed. A component of this review is the identification of verification and validation (V&V methods applied to each model, if any V&V method was reported. All models were classified as either having undergone Some Verification or Validation method, or No Verification or Validation. We close by outlining an initial set of operational readiness level guidelines for disease prediction models based upon established Technology

  17. Caries risk assessment models in caries prediction

    Directory of Open Access Journals (Sweden)

    Amila Zukanović

    2013-11-01

    Full Text Available Objective. The aim of this research was to assess the efficiency of different multifactor models in caries prediction. Material and methods. Data from the questionnaire and objective examination of 109 examinees was entered into the Cariogram, Previser and Caries-Risk Assessment Tool (CAT multifactor risk assessment models. Caries risk was assessed with the help of all three models for each patient, classifying them as low, medium or high-risk patients. The development of new caries lesions over a period of three years [Decay Missing Filled Tooth (DMFT increment = difference between Decay Missing Filled Tooth Surface (DMFTS index at baseline and follow up], provided for examination of the predictive capacity concerning different multifactor models. Results. The data gathered showed that different multifactor risk assessment models give significantly different results (Friedman test: Chi square = 100.073, p=0.000. Cariogram is the model which identified the majority of examinees as medium risk patients (70%. The other two models were more radical in risk assessment, giving more unfavorable risk –profiles for patients. In only 12% of the patients did the three multifactor models assess the risk in the same way. Previser and CAT gave the same results in 63% of cases – the Wilcoxon test showed that there is no statistically significant difference in caries risk assessment between these two models (Z = -1.805, p=0.071. Conclusions. Evaluation of three different multifactor caries risk assessment models (Cariogram, PreViser and CAT showed that only the Cariogram can successfully predict new caries development in 12-year-old Bosnian children.

  18. APP physiological and pathophysiological functions:insights from animal models

    Institute of Scientific and Technical Information of China (English)

    Qinxi Guo; Zilai Wang; Hongmei Li; Mary Wiese; Hui Zheng

    2012-01-01

    The amyloid precursor protein (APP) has been under intensive study in recent years,mainly due to its critical role in the pathogenesis of Alzheimer's disease (AD).β-Amyloid (Aβ) peptides generated from APP proteolytic cleavage can aggregate,leading to plaque formation in human AD brains.Point mutations of APP affecting Aβ production are found to be causal for hereditary early onset familial AD.It is very likely that elucidating the physiological properties of APP will greatly facilitate the understanding of its role in AD pathogenesis.A number of APP loss- and gainof-function models have been established in model organisms including Caenorhabditis elegans,Drosophila,zebrafish and mouse.These in vivo models provide us valuable insights into APP physiological functions.In addition,several knock-in mouse models expressing mutant APP at a physiological level are available to allow us to study AD pathogenesis without APP overexpression.This article will review the current physiological and pathophysiological animal models of APP.

  19. Model Predictive Control based on Finite Impulse Response Models

    DEFF Research Database (Denmark)

    Prasath, Guru; Jørgensen, John Bagterp

    2008-01-01

    We develop a regularized l2 finite impulse response (FIR) predictive controller with input and input-rate constraints. Feedback is based on a simple constant output disturbance filter. The performance of the predictive controller in the face of plant-model mismatch is investigated by simulations...

  20. Experimental animal models for studies on the mechanisms of blast-induced neurotrauma.

    Science.gov (United States)

    Risling, Mårten; Davidsson, Johan

    2012-01-01

    A blast injury is a complex type of physical trauma resulting from the detonation of explosive compounds and has become an important issue due to the use of improvised explosive devices (IED) in current military conflicts. Blast-induced neurotrauma (BINT) is a major concern in contemporary military medicine and includes a variety of injuries that range from mild to lethal. Extreme forces and their complex propagation characterize BINT. Modern body protection and the development of armored military vehicles can be assumed to have changed the outcome of BINT. Primary blast injuries are caused by overpressure waves whereas secondary, tertiary, and quaternary blast injuries can have more varied origins such as the impact of fragments, abnormal movements, or heat. The characteristics of the blast wave can be assumed to be significantly different in open field detonations compared to explosions in a confined space, such an armored vehicle. Important parameters include peak pressure, duration, and shape of the pulse. Reflections from walls and armor can make the prediction of effects in individual cases very complex. Epidemiological data do not contain information of the comparative importance of the different blast mechanisms. It is therefore important to generate data in carefully designed animal models. Such models can be selective reproductions of a primary blast, penetrating injuries from fragments, acceleration movements, or combinations of such mechanisms. It is of crucial importance that the physical parameters of the employed models are well characterized so that the experiments can be reproduced in different laboratory settings. Ideally, pressure recordings should be calibrated by using the same equipment in several laboratories. With carefully designed models and thoroughly evaluated animal data it should be possible to achieve a translation of data between animal and clinical data. Imaging and computer simulation represent a possible link between experiments

  1. Gas explosion prediction using CFD models

    Energy Technology Data Exchange (ETDEWEB)

    Niemann-Delius, C.; Okafor, E. [RWTH Aachen Univ. (Germany); Buhrow, C. [TU Bergakademie Freiberg Univ. (Germany)

    2006-07-15

    A number of CFD models are currently available to model gaseous explosions in complex geometries. Some of these tools allow the representation of complex environments within hydrocarbon production plants. In certain explosion scenarios, a correction is usually made for the presence of buildings and other complexities by using crude approximations to obtain realistic estimates of explosion behaviour as can be found when predicting the strength of blast waves resulting from initial explosions. With the advance of computational technology, and greater availability of computing power, computational fluid dynamics (CFD) tools are becoming increasingly available for solving such a wide range of explosion problems. A CFD-based explosion code - FLACS can, for instance, be confidently used to understand the impact of blast overpressures in a plant environment consisting of obstacles such as buildings, structures, and pipes. With its porosity concept representing geometry details smaller than the grid, FLACS can represent geometry well, even when using coarse grid resolutions. The performance of FLACS has been evaluated using a wide range of field data. In the present paper, the concept of computational fluid dynamics (CFD) and its application to gas explosion prediction is presented. Furthermore, the predictive capabilities of CFD-based gaseous explosion simulators are demonstrated using FLACS. Details about the FLACS-code, some extensions made to FLACS, model validation exercises, application, and some results from blast load prediction within an industrial facility are presented. (orig.)

  2. A Study On Distributed Model Predictive Consensus

    CERN Document Server

    Keviczky, Tamas

    2008-01-01

    We investigate convergence properties of a proposed distributed model predictive control (DMPC) scheme, where agents negotiate to compute an optimal consensus point using an incremental subgradient method based on primal decomposition as described in Johansson et al. [2006, 2007]. The objective of the distributed control strategy is to agree upon and achieve an optimal common output value for a group of agents in the presence of constraints on the agent dynamics using local predictive controllers. Stability analysis using a receding horizon implementation of the distributed optimal consensus scheme is performed. Conditions are given under which convergence can be obtained even if the negotiations do not reach full consensus.

  3. Electrostatic ion thrusters - towards predictive modeling

    Energy Technology Data Exchange (ETDEWEB)

    Kalentev, O.; Matyash, K.; Duras, J.; Lueskow, K.F.; Schneider, R. [Ernst-Moritz-Arndt Universitaet Greifswald, D-17489 (Germany); Koch, N. [Technische Hochschule Nuernberg Georg Simon Ohm, Kesslerplatz 12, D-90489 Nuernberg (Germany); Schirra, M. [Thales Electronic Systems GmbH, Soeflinger Strasse 100, D-89077 Ulm (Germany)

    2014-02-15

    The development of electrostatic ion thrusters so far has mainly been based on empirical and qualitative know-how, and on evolutionary iteration steps. This resulted in considerable effort regarding prototype design, construction and testing and therefore in significant development and qualification costs and high time demands. For future developments it is anticipated to implement simulation tools which allow for quantitative prediction of ion thruster performance, long-term behavior and space craft interaction prior to hardware design and construction. Based on integrated numerical models combining self-consistent kinetic plasma models with plasma-wall interaction modules a new quality in the description of electrostatic thrusters can be reached. These open the perspective for predictive modeling in this field. This paper reviews the application of a set of predictive numerical modeling tools on an ion thruster model of the HEMP-T (High Efficiency Multi-stage Plasma Thruster) type patented by Thales Electron Devices GmbH. (copyright 2014 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  4. Genetic models of homosexuality: generating testable predictions.

    Science.gov (United States)

    Gavrilets, Sergey; Rice, William R

    2006-12-22

    Homosexuality is a common occurrence in humans and other species, yet its genetic and evolutionary basis is poorly understood. Here, we formulate and study a series of simple mathematical models for the purpose of predicting empirical patterns that can be used to determine the form of selection that leads to polymorphism of genes influencing homosexuality. Specifically, we develop theory to make contrasting predictions about the genetic characteristics of genes influencing homosexuality including: (i) chromosomal location, (ii) dominance among segregating alleles and (iii) effect sizes that distinguish between the two major models for their polymorphism: the overdominance and sexual antagonism models. We conclude that the measurement of the genetic characteristics of quantitative trait loci (QTLs) found in genomic screens for genes influencing homosexuality can be highly informative in resolving the form of natural selection maintaining their polymorphism.

  5. Comparison and Evaluation of Current Animal Models for Perineural Scar Formation in Rat

    Directory of Open Access Journals (Sweden)

    Leila O Zanjani

    2013-07-01

    Our study suggests that none of the applied animal models reproduce all essential features of clinical perineural scar formation. Therefore, more studies are needed to develop optimal animal models for translating preclinical investigations

  6. Drug discovery of antimicrobial photosensitizers using animal models.

    Science.gov (United States)

    Sharma, Sulbha K; Dai, Tianhong; Kharkwal, Gitika B; Huang, Ying-Ying; Huang, Liyi; De Arce, Vida J Bil; Tegos, George P; Hamblin, Michael R

    2011-01-01

    Antimicrobial photodynamic therapy (aPDT) is an emerging alternative to antibiotics motivated by growing problems with multi-drug resistant pathogens. aPDT uses non-toxic dyes or photosensitizers (PS) in combination with harmless visible of the correct wavelength to be absorbed by the PS. The excited state PS can form a long-lived triplet state that can interact with molecular oxygen to produce reactive oxygen species such as singlet oxygen and hydroxyl radical that kill the microbial cells. To obtain effective PS for treatment of infections it is necessary to use cationic PS with positive charges that are able to bind to and penetrate different classes of microbial cells. Other drug design criteria require PS with high absorption coefficients in the red/near infra-red regions of the spectrum where light penetration into tissue is maximum, high photostability to minimize photobleaching, and devising compounds that will selectively bind to microbial cells rather than host mammalian cells. Several molecular classes fulfill many of these requirements including phenothiazinium dyes, cationic tetrapyrroles such as porphyrins, phthalocyanines and bacteriochlorins, cationic fullerenes and cationic derivatives of other known PS. Larger structures such as conjugates between PS and cationic polymers, cationic nanoparticles and cationic liposomes that contain PS are also effective. In order to demonstrate in vivo efficacy it is necessary to use animal models of localized infections in which both PS and light can be effectively delivered into the infected area. This review will cover a range of mouse models we have developed using bioluminescent pathogens and a sensitive low light imaging system to non-invasively monitor the progress of the infection in real time. Effective aPDT has been demonstrated in acute lethal infections and chronic biofilm infections; in infections caused by Gram-positive, Gram-negative bacteria and fungi; in infections in wounds, third degree burns

  7. Is it acceptable to use animals to model obese humans?

    DEFF Research Database (Denmark)

    Lund, Thomas Bøker; Sørensen, Thorkild I.A.; Olsson, I. Anna S.

    2014-01-01

    Animal use in medical research is widely accepted on the basis that it may help to save human lives and improve their quality of life. Recently, however, objections have been made specifically to the use of animals in scientific investigation of human obesity. This paper discusses two arguments...... for the view that this form of animal use, unlike some other forms of animal-based medical research, cannot be defended. The first argument leans heavily on the notion that people themselves are responsible for developing obesity and so-called 'lifestyle' diseases; the second involves the claim that animal...... of animals in obesity research as especially problematic....

  8. ENSO Prediction using Vector Autoregressive Models

    Science.gov (United States)

    Chapman, D. R.; Cane, M. A.; Henderson, N.; Lee, D.; Chen, C.

    2013-12-01

    A recent comparison (Barnston et al, 2012 BAMS) shows the ENSO forecasting skill of dynamical models now exceeds that of statistical models, but the best statistical models are comparable to all but the very best dynamical models. In this comparison the leading statistical model is the one based on the Empirical Model Reduction (EMR) method. Here we report on experiments with multilevel Vector Autoregressive models using only sea surface temperatures (SSTs) as predictors. VAR(L) models generalizes Linear Inverse Models (LIM), which are a VAR(1) method, as well as multilevel univariate autoregressive models. Optimal forecast skill is achieved using 12 to 14 months of prior state information (i.e 12-14 levels), which allows SSTs alone to capture the effects of other variables such as heat content as well as seasonality. The use of multiple levels allows the model advancing one month at a time to perform at least as well for a 6 month forecast as a model constructed to explicitly forecast 6 months ahead. We infer that the multilevel model has fully captured the linear dynamics (cf. Penland and Magorian, 1993 J. Climate). Finally, while VAR(L) is equivalent to L-level EMR, we show in a 150 year cross validated assessment that we can increase forecast skill by improving on the EMR initialization procedure. The greatest benefit of this change is in allowing the prediction to make effective use of information over many more months.

  9. DEBkiss or the quest for the simplest generic model of animal life history.

    Science.gov (United States)

    Jager, Tjalling; Martin, Benjamin T; Zimmer, Elke I

    2013-07-07

    Understanding the life cycle of individual animals, and how it responds to stress, requires a model that causally links life-history traits (feeding, growth, development and reproduction). Dynamic Energy Budget (DEB) theory offers a powerful and formalised framework for building process-based models for organism life cycles. However, it takes some serious investment to understand the resulting equations and to implement them into software, and a substantial amount of data to parameterise. For many practical applications, there is therefore a need for further simplification. Here, we present a simple and transparent model that fully specifies the life cycle of an (invertebrate) animal, applies a strict mass balance, and has direct access to the primary parameters that determine the metabolic processes. We derive our 'DEBkiss' in a formalised manner, starting from an explicit formulation of the simplifying assumptions. The presented model can serve as a teaching tool and a smooth introduction into the much richer world of DEB theory. Furthermore, the model may prove useful as a building block for individual-based population modelling (where simplicity of the blocks is essential), and for the analysis of toxicity data (where ease of model verification and parameterisation is crucial). The model is illustrated using a fit on growth and reproduction data for the pond snail (Lymnaea stagnalis) at three food levels, and subsequent predictions for embryonic growth and respiration (oxygen use), and weight loss on starvation, for the same species.

  10. NONLINEAR MODEL PREDICTIVE CONTROL OF CHEMICAL PROCESSES

    Directory of Open Access Journals (Sweden)

    R. G. SILVA

    1999-03-01

    Full Text Available A new algorithm for model predictive control is presented. The algorithm utilizes a simultaneous solution and optimization strategy to solve the model's differential equations. The equations are discretized by equidistant collocation, and along with the algebraic model equations are included as constraints in a nonlinear programming (NLP problem. This algorithm is compared with the algorithm that uses orthogonal collocation on finite elements. The equidistant collocation algorithm results in simpler equations, providing a decrease in computation time for the control moves. Simulation results are presented and show a satisfactory performance of this algorithm.

  11. Graphic-based musculoskeletal model for biomechanical analyses and animation.

    Science.gov (United States)

    Chao, Edmund Y S

    2003-04-01

    The ability to combine physiology and engineering analyses with computer sciences has opened the door to the possibility of creating the 'Virtual Human' reality. This paper presents a broad foundation for a full-featured biomechanical simulator for the human musculoskeletal system physiology. This simulation technology unites the expertise in biomechanical analysis and graphic modeling to investigate joint and connective tissue mechanics at the structural level and to visualize the results in both static and animated forms together with the model. Adaptable anatomical models including prosthetic implants and fracture fixation devices and a robust computational infrastructure for static, kinematic, kinetic, and stress analyses under varying boundary and loading conditions are incorporated on a common platform, the VIMS (Virtual Interactive Musculoskeletal System). Within this software system, a manageable database containing long bone dimensions, connective tissue material properties and a library of skeletal joint system functional activities and loading conditions are also available and they can easily be modified, updated and expanded. Application software is also available to allow end-users to perform biomechanical analyses interactively. This paper details the design, capabilities, and features of the VIMS development at Johns Hopkins University, an effort possible only through academic and commercial collaborations. Examples using these models and the computational algorithms in a virtual laboratory environment are used to demonstrate the utility of this unique database and simulation technology. This integrated system will impact on medical education, basic research, device development and application, and clinical patient care related to musculoskeletal diseases, trauma, and rehabilitation.

  12. Improving prediction of carcinogenicity to reduce, refine, and replace the use of experimental animals.

    Science.gov (United States)

    Bourcier, Todd; McGovern, Tim; Stavitskaya, Lidiya; Kruhlak, Naomi; Jacobson-Kram, David

    2015-03-01

    Cancer risk assessment of new pharmaceuticals is crucial to protect public health. However, clinical trials lack the duration needed to clearly detect drug-related tumor emergence, and biomarkers suggestive of increased cancer risk from a drug typically are not measured in clinical trials. Therefore, the carcinogenic potential of a new pharmaceutical is extrapolated predominately based on 2-y bioassays in rats and mice. A key drawback to this practice is that the results are frequently positive for tumors and can be irrelevant to human cancer risk for reasons such as dose, mode of action, and species specificity. Alternative approaches typically strive to reduce, refine, and replace rodents in carcinogenicity assessments by leveraging findings in short-term studies, both in silico and in vivo, to predict the likely tumor outcome in rodents or, more broadly, to identify a cancer risk to patients. Given the complexities of carcinogenesis and the perceived impracticality of assessing risk in the course of clinical trials, studies conducted in animals will likely remain the standard by which potential cancer risks are characterized for new pharmaceuticals in the immediate foreseeable future. However, a weight-of-evidence evaluation based on short-term toxicologic, in silico, and pharmacologic data is a promising approach to identify with reasonable certainty those pharmaceuticals that present a likely cancer risk in humans and, conversely, those that do not present a human cancer risk.

  13. Mechanisms and genes in human strial presbycusis from animal models.

    Science.gov (United States)

    Ohlemiller, Kevin K

    2009-06-24

    Schuknecht proposed a discrete form of presbycusis in which hearing loss results principally from degeneration of cochlear stria vascularis and decline of the endocochlear potential (EP). This form was asserted to be genetically linked, and to arise independently from age-related pathology of either the organ of Corti or cochlear neurons. Although extensive strial degeneration in humans coincides with hearing loss, EPs have never been measured in humans, and age-related EP reduction has never been verified. No human genes that promote strial presbycusis have been identified, nor is its pathophysiology well understood. Effective application of animal models to this issue requires models demonstrating EP decline, and preferably, genetically distinct strains that vary in patterns of EP decline and its cellular correlates. Until recently, only two models, Mongolian gerbils and Tyrp1(B-lt) mice, were known to undergo age-associated EP reduction. Detailed studies of seven inbred mouse strains have now revealed three strains (C57BL/6J, B6.CAST-Cdh23(CAST), CBA/J) showing essentially no EP decline with age, and four strains ranging from modest to severe EP reduction (C57BL/6-Tyr(c-2J), BALB/cJ, CBA/CaJ, NOD.NON-H2(nbl)/LtJ). Collectively, animal models support five basic principles regarding a strial form of presbycusis: 1) Progressive EP decline from initially normal levels as a defining characteristic; 2) Non-universality, not all age-associated hearing loss involves EP decline; 3) A clear genetic basis; 4) Modulation by environment or stochastic events; and 5) Independent strial, organ of Corti, and neural pathology. Shared features between human strial presbycusis, gerbils, and BALB/cJ and C57BL/6-Tyr(c-2J) mice further suggest this condition frequently begins with strial marginal cell dysfunction and loss. By contrast, NOD.NON-H2(nbl) mice may model a sequence more closely associated with strial microvascular disease. Additional studies of these and other inbred mouse

  14. Criteria of validity for animal models of psychiatric disorders: focus on anxiety disorders and depression

    Directory of Open Access Journals (Sweden)

    Belzung Catherine

    2011-11-01

    Full Text Available Abstract Animal models of psychiatric disorders are usually discussed with regard to three criteria first elaborated by Willner; face, predictive and construct validity. Here, we draw the history of these concepts and then try to redraw and refine these criteria, using the framework of the diathesis model of depression that has been proposed by several authors. We thus propose a set of five major criteria (with sub-categories for some of them; homological validity (including species validity and strain validity, pathogenic validity (including ontopathogenic validity and triggering validity, mechanistic validity, face validity (including ethological and biomarker validity and predictive validity (including induction and remission validity. Homological validity requires that an adequate species and strain be chosen: considering species validity, primates will be considered to have a higher score than drosophila, and considering strains, a high stress reactivity in a strain scores higher than a low stress reactivity in another strain. Pathological validity corresponds to the fact that, in order to shape pathological characteristics, the organism has been manipulated both during the developmental period (for example, maternal separation: ontopathogenic validity and during adulthood (for example, stress: triggering validity. Mechanistic validity corresponds to the fact that the cognitive (for example, cognitive bias or biological mechanisms (such as dysfunction of the hormonal stress axis regulation underlying the disorder are identical in both humans and animals. Face validity corresponds to the observable behavioral (ethological validity or biological (biomarker validity outcomes: for example anhedonic behavior (ethological validity or elevated corticosterone (biomarker validity. Finally, predictive validity corresponds to the identity of the relationship between the triggering factor and the outcome (induction validity and between the effects of

  15. Performance model to predict overall defect density

    Directory of Open Access Journals (Sweden)

    J Venkatesh

    2012-08-01

    Full Text Available Management by metrics is the expectation from the IT service providers to stay as a differentiator. Given a project, the associated parameters and dynamics, the behaviour and outcome need to be predicted. There is lot of focus on the end state and in minimizing defect leakage as much as possible. In most of the cases, the actions taken are re-active. It is too late in the life cycle. Root cause analysis and corrective actions can be implemented only to the benefit of the next project. The focus has to shift left, towards the execution phase than waiting for lessons to be learnt post the implementation. How do we pro-actively predict defect metrics and have a preventive action plan in place. This paper illustrates the process performance model to predict overall defect density based on data from projects in an organization.

  16. Neuro-fuzzy modeling in bankruptcy prediction

    Directory of Open Access Journals (Sweden)

    Vlachos D.

    2003-01-01

    Full Text Available For the past 30 years the problem of bankruptcy prediction had been thoroughly studied. From the paper of Altman in 1968 to the recent papers in the '90s, the progress of prediction accuracy was not satisfactory. This paper investigates an alternative modeling of the system (firm, combining neural networks and fuzzy controllers, i.e. using neuro-fuzzy models. Classical modeling is based on mathematical models that describe the behavior of the firm under consideration. The main idea of fuzzy control, on the other hand, is to build a model of a human control expert who is capable of controlling the process without thinking in a mathematical model. This control expert specifies his control action in the form of linguistic rules. These control rules are translated into the framework of fuzzy set theory providing a calculus, which can stimulate the behavior of the control expert and enhance its performance. The accuracy of the model is studied using datasets from previous research papers.

  17. Pressure prediction model for compression garment design.

    Science.gov (United States)

    Leung, W Y; Yuen, D W; Ng, Sun Pui; Shi, S Q

    2010-01-01

    Based on the application of Laplace's law to compression garments, an equation for predicting garment pressure, incorporating the body circumference, the cross-sectional area of fabric, applied strain (as a function of reduction factor), and its corresponding Young's modulus, is developed. Design procedures are presented to predict garment pressure using the aforementioned parameters for clinical applications. Compression garments have been widely used in treating burning scars. Fabricating a compression garment with a required pressure is important in the healing process. A systematic and scientific design method can enable the occupational therapist and compression garments' manufacturer to custom-make a compression garment with a specific pressure. The objectives of this study are 1) to develop a pressure prediction model incorporating different design factors to estimate the pressure exerted by the compression garments before fabrication; and 2) to propose more design procedures in clinical applications. Three kinds of fabrics cut at different bias angles were tested under uniaxial tension, as were samples made in a double-layered structure. Sets of nonlinear force-extension data were obtained for calculating the predicted pressure. Using the value at 0° bias angle as reference, the Young's modulus can vary by as much as 29% for fabric type P11117, 43% for fabric type PN2170, and even 360% for fabric type AP85120 at a reduction factor of 20%. When comparing the predicted pressure calculated from the single-layered and double-layered fabrics, the double-layered construction provides a larger range of target pressure at a particular strain. The anisotropic and nonlinear behaviors of the fabrics have thus been determined. Compression garments can be methodically designed by the proposed analytical pressure prediction model.

  18. Large animal models of rare genetic disorders: sheep as phenotypically relevant models of human genetic disease.

    Science.gov (United States)

    Pinnapureddy, Ashish R; Stayner, Cherie; McEwan, John; Baddeley, Olivia; Forman, John; Eccles, Michael R

    2015-09-02

    Animals that accurately model human disease are invaluable in medical research, allowing a critical understanding of disease mechanisms, and the opportunity to evaluate the effect of therapeutic compounds in pre-clinical studies. Many types of animal models are used world-wide, with the most common being small laboratory animals, such as mice. However, rodents often do not faithfully replicate human disease, despite their predominant use in research. This discordancy is due in part to physiological differences, such as body size and longevity. In contrast, large animal models, including sheep, provide an alternative to mice for biomedical research due to their greater physiological parallels with humans. Completion of the full genome sequences of many species, and the advent of Next Generation Sequencing (NGS) technologies, means it is now feasible to screen large populations of domesticated animals for genetic variants that resemble human genetic diseases, and generate models that more accurately model rare human pathologies. In this review, we discuss the notion of using sheep as large animal models, and their advantages in modelling human genetic disease. We exemplify several existing naturally occurring ovine variants in genes that are orthologous to human disease genes, such as the Cln6 sheep model for Batten disease. These, and other sheep models, have contributed significantly to our understanding of the relevant human disease process, in addition to providing opportunities to trial new therapies in animals with similar body and organ size to humans. Therefore sheep are a significant species with respect to the modelling of rare genetic human disease, which we summarize in this review.

  19. Hair loss and regeneration performed on animal models.

    Science.gov (United States)

    Orasan, Meda Sandra; Roman, Iulia Ioana; Coneac, Andrei; Muresan, Adriana; Orasan, Remus Ioan

    2016-01-01

    Research in the field of reversal hair loss remains a challenging subject. As Minoxidil 2% or 5% and Finasteride are so far the only FDA approved topical treatments for inducing hair regrowth, research is necessary in order to improve therapeutical approach in alopecia. In vitro studies have focused on cultures of a cell type - dermal papilla or organ culture of isolated cell follicles. In vivo research on this topic was performed on mice, rats, hamsters, rabbits, sheep and monkeys, taking into consideration the advantages and disadvantages of each animal model and the depilation options. Further studies are required not only to compare the efficiency of different therapies but more importantly to establish their long term safety.

  20. Botulinum Neurotoxin for Pain Management: Insights from Animal Models

    Directory of Open Access Journals (Sweden)

    Siro Luvisetto

    2010-12-01

    Full Text Available The action of botulinum neurotoxins (BoNTs at the neuromuscular junction has been extensively investigated and knowledge gained in this field laid the foundation for the use of BoNTs in human pathologies characterized by excessive muscle contractions. Although much more is known about the action of BoNTs on the peripheral system, growing evidence has demonstrated several effects also at the central level. Pain conditions, with special regard to neuropathic and intractable pain, are some of the pathological states that have been recently treated with BoNTs with beneficial effects. The knowledge of the action and potentiality of BoNTs utilization against pain, with emphasis for its possible use in modulation and alleviation of chronic pain, still represents an outstanding challenge for experimental research. This review highlights recent findings on the effects of BoNTs in animal pain models.

  1. Botulinum neurotoxin for pain management: insights from animal models.

    Science.gov (United States)

    Pavone, Flaminia; Luvisetto, Siro

    2010-12-01

    The action of botulinum neurotoxins (BoNTs) at the neuromuscular junction has been extensively investigated and knowledge gained in this field laid the foundation for the use of BoNTs in human pathologies characterized by excessive muscle contractions. Although much more is known about the action of BoNTs on the peripheral system, growing evidence has demonstrated several effects also at the central level. Pain conditions, with special regard to neuropathic and intractable pain, are some of the pathological states that have been recently treated with BoNTs with beneficial effects. The knowledge of the action and potentiality of BoNTs utilization against pain, with emphasis for its possible use in modulation and alleviation of chronic pain, still represents an outstanding challenge for experimental research. This review highlights recent findings on the effects of BoNTs in animal pain models.

  2. Shank mutant mice as an animal model of autism.

    Science.gov (United States)

    Yoo, Juyoun; Bakes, Joseph; Bradley, Clarrisa; Collingridge, Graham L; Kaang, Bong-Kiun

    2014-01-05

    In this review, we focus on the role of the Shank family of proteins in autism. In recent years, autism research has been flourishing. With genetic, molecular, imaging and electrophysiological studies being supported by behavioural studies using animal models, there is real hope that we may soon understand the fundamental pathology of autism. There is also genuine potential to develop a molecular-level pharmacological treatment that may be able to deal with the most severe symptoms of autism, and clinical trials are already underway. The Shank family of proteins has been strongly implicated as a contributing factor in autism in certain individuals and sits at the core of the alleged autistic pathway. Here, we analyse studies that relate Shank to autism and discuss what light this sheds on the possible causes of autism.

  3. Pathogenesis of presbycusis in animal models: a review.

    Science.gov (United States)

    Fetoni, Anna R; Picciotti, Pasqualina M; Paludetti, Gaetano; Troiani, Diana

    2011-06-01

    Presbycusis is the most common cause of hearing loss in aged subjects, reducing individual's communicative skills. Age related hearing loss can be defined as a progressive, bilateral, symmetrical hearing loss due to age related degeneration and it can be considered a multifactorial complex disorder, with both environmental and genetic factors contributing to the aetiology of the disease. The decline in hearing sensitivity caused by ageing is related to the damage at different levels of the auditory system (central and peripheral). Histologically, the aged cochlea shows degeneration of the stria vascularis, the sensorineural epithelium, and neurons of the central auditory pathways. The mechanisms responsible for age-associated hearing loss are still incompletely characterized. This work aims to give a broad overview of the scientific findings related to presbycusis, focusing mainly on experimental studies in animal models.

  4. BDNF in schizophrenia, depression and corresponding animal models.

    Science.gov (United States)

    Angelucci, F; Brenè, S; Mathé, A A

    2005-04-01

    Understanding the etiology and pathogenesis schizophrenia and depression is a major challenge facing psychiatry. One hypothesis is that these disorders are secondary to a malfunction of neurotrophic factors. Inappropriate neurotrophic support during brain development could lead to structural disorganisation in which neuronal networks are established in a nonoptimal manner. Inadequate neurotrophic support in adult individuals could ultimately be an underlying mechanism leading to decreased capacity of brain to adaptive changes and increased vulnerability to neurotoxic damage. Brain-derived neurotrophic factor (BDNF) is a mediator involved in neuronal survival and plasticity of dopaminergic, cholinergic, and serotonergic neurons in the central nervous system (CNS). In this review, we summarize findings regarding altered BDNF in schizophrenia and depression and animal models, as well as the effects of antipsychotic and antidepressive treatments on the expression of BDNF.

  5. Man in space - The use of animal models

    Science.gov (United States)

    Ballard, Rodney W.; Souza, Kenneth A.

    1991-01-01

    The use of animal surrogates as experimental subjects in order to provide essential missing information on the effects of long-term spaceflights, to validate countermeasures, and to test medical treatment techniques is discussed. Research needs also include the definition of biomedical adaptations to flight, and the developments of standards for safe space missions to assure human health and productivity during and following flight. NASA research plans in this area are outlined. Over the next 40 years, NASA plans to concentrate on the use of rodents and nonhuman primates as the models of choice for various physiological responses observed in humans during extended stays in space. This research will include flights on the Space Shuttle, unmanned biosatellites, and the Space Station Freedom.

  6. Evidence of Oxidative Stress in Autism Derived from Animal Models

    Directory of Open Access Journals (Sweden)

    Xue Ming

    2008-01-01

    Full Text Available Autism is a pervasive neurodevelopmental disorder that leads to deficits in social interaction, communication and restricted, repetitive motor movements. Autism is a highly heritable disorder, however, there is mounting evidence to suggest that toxicant-induced oxidative stress may play a role. The focus of this article will be to review our animal model of autism and discuss our evidence that oxidative stress may be a common underlying mechanism of neurodevelopmental damage. We have shown that mice exposed to either methylmercury (MeHg or valproic acid (VPA in early postnatal life display aberrant social, cognitive and motor behavior. Interestingly, early exposure to both compounds has been clinically implicated in the development of autism. We recently found that Trolox, a water-soluble vitamin E derivative, is capable of attenuating a number of neurobehavioral alterations observed in mice postnatally exposed to MeHg. In addition, a number of other investigators have shown that oxidative stress plays a role in neural injury following MeHg exposure both in vitro and in vivo. New data presented here will show that VPA-induced neurobehavioral deficits are attenuated by vitamin E as well and that the level of glial fibrillary acidic protein (GFAP, a marker of astrocytic neural injury, is altered following VPA exposure. Collectively, these data indicate that vitamin E and its derivative are capable of protecting against neurobehavioral deficits induced by both MeHg and VPA. This antioxidant protection suggests that oxidative stress may be a common mechanism of injury leading to aberrant behavior in both our animal model as well as in the human disease state.

  7. Seasonal Predictability in a Model Atmosphere.

    Science.gov (United States)

    Lin, Hai

    2001-07-01

    The predictability of atmospheric mean-seasonal conditions in the absence of externally varying forcing is examined. A perfect-model approach is adopted, in which a global T21 three-level quasigeostrophic atmospheric model is integrated over 21 000 days to obtain a reference atmospheric orbit. The model is driven by a time-independent forcing, so that the only source of time variability is the internal dynamics. The forcing is set to perpetual winter conditions in the Northern Hemisphere (NH) and perpetual summer in the Southern Hemisphere.A significant temporal variability in the NH 90-day mean states is observed. The component of that variability associated with the higher-frequency motions, or climate noise, is estimated using a method developed by Madden. In the polar region, and to a lesser extent in the midlatitudes, the temporal variance of the winter means is significantly greater than the climate noise, suggesting some potential predictability in those regions.Forecast experiments are performed to see whether the presence of variance in the 90-day mean states that is in excess of the climate noise leads to some skill in the prediction of these states. Ensemble forecast experiments with nine members starting from slightly different initial conditions are performed for 200 different 90-day means along the reference atmospheric orbit. The serial correlation between the ensemble means and the reference orbit shows that there is skill in the 90-day mean predictions. The skill is concentrated in those regions of the NH that have the largest variance in excess of the climate noise. An EOF analysis shows that nearly all the predictive skill in the seasonal means is associated with one mode of variability with a strong axisymmetric component.

  8. Animal models of hematogenous Staphylococcus aureus osteomyelitis in long bones: a review

    Directory of Open Access Journals (Sweden)

    Johansen LK

    2013-08-01

    Full Text Available Louise Kruse Johansen, Henrik Elvang JensenDepartment of Veterinary Disease Biology, Faculty of Health and Medical Science, University of Copenhagen, Frederiksberg, DenmarkAbstract: Hematogenous osteomyelitis (HO, especially due to Staphylococcus aureus, is primarily reported in children and occurs when blood-borne bacteria settle in the metaphysis of a long bone and mediate an inflammatory response. The literature contains several reports on animal models aiming to simulate pediatric HO, in order to investigate the pathogenesis and for therapeutic use. In these models, osteomyelitis lesions develop subsequently to bacteremia, which can be induced by either intravenous or intra-arterial inoculation of bacteria. Intravenous inoculation is not optimal because of the ethical aspects of the extensive systemic reaction and the unpredictable identity of bones being infected. Also, intravenous inoculation often has to be combined with the induction of artificial bone necrosis in order to have macroscopic lesions. In contrast, models based on intra-arterial inoculation and subsequent development of local osteomyelitis, are the most accurate and predictable way to extrapolate to pediatric cases of HO. The most commonly used animal species for modeling of HO are rabbits, chickens, and mice, whereas, less frequently, dogs, rats, and pigs have been applied. The use of intra-arterial inoculation, without simultaneous artificial bone necrosis for the development of HO lesions has only been used in porcine models. Because of the similarity of human and porcine physiology, metabolic rate, and size, porcine models of HO are advantageous. Therefore, porcine models based on the intra-arterial induction of osteomyelitis are the most refined HO models.Keywords: hematogenous osteomyelitis, animal models, Staphylococcus aureus

  9. Mathematical modeling and simulation in animal health. Part I: Moving beyond pharmacokinetics.

    Science.gov (United States)

    Riviere, J E; Gabrielsson, J; Fink, M; Mochel, J

    2016-06-01

    The application of mathematical modeling to problems in animal health has a rich history in the form of pharmacokinetic modeling applied to problems in veterinary medicine. Advances in modeling and simulation beyond pharmacokinetics have the potential to streamline and speed-up drug research and development programs. To foster these goals, a series of manuscripts will be published with the following goals: (i) expand the application of modeling and simulation to issues in veterinary pharmacology; (ii) bridge the gap between the level of modeling and simulation practiced in human and veterinary pharmacology; (iii) explore how modeling and simulation concepts can be used to improve our understanding of common issues not readily addressed in human pharmacology (e.g. breed differences, tissue residue depletion, vast weight ranges among adults within a single species, interspecies differences, small animal species research where data collection is limited to sparse sampling, availability of different sampling matrices); and (iv) describe how quantitative pharmacology approaches could help understanding key pharmacokinetic and pharmacodynamic characteristics of a drug candidate, with the goal of providing explicit, reproducible, and predictive evidence for optimizing drug development plans, enabling critical decision making, and eventually bringing safe and effective medicines to patients. This study introduces these concepts and introduces new approaches to modeling and simulation as well as clearly articulate basic assumptions and good practices. The driving force behind these activities is to create predictive models that are based on solid physiological and pharmacological principles as well as adhering to the limitations that are fundamental to applying mathematical and statistical models to biological systems.

  10. MicroRNA regulation of TLRs in a post-influenza animal model

    DEFF Research Database (Denmark)

    Brogaard, Louise; Heegaard, Peter M. H.; Larsen, Lars Erik

    to secondary infections. Methods and outcome Pigs were experimentally challenged with a Danish reassortant IAV strain (A/sw/Denmark/12687/03(H1N2)). Lung tissue was harvested 14 days after challenge, as well as from uninfected control animals. Using RNAseq and high-throughput RT-qPCR, we quantified...... in the post-IAV infected individual. Using the pig as an animal model, we have identified microRNAs (miRNAs) that are differentially expressed in lung tissue two weeks after challenge compared to uninfected controls, i.e. well after the infection has cleared. The role for differential expression of mi......RNAs experimentally validated or in silico predicted to bind to and regulate transcripts of TLRs and relevant co-factors and transcription factors (online tools). The antiviral immune response elicited by IAV infection thus includes late miRNA regulation, which in turn may be at the expense of host responsiveness...

  11. A kinetic model for predicting biodegradation.

    Science.gov (United States)

    Dimitrov, S; Pavlov, T; Nedelcheva, D; Reuschenbach, P; Silvani, M; Bias, R; Comber, M; Low, L; Lee, C; Parkerton, T; Mekenyan, O

    2007-01-01

    Biodegradation plays a key role in the environmental risk assessment of organic chemicals. The need to assess biodegradability of a chemical for regulatory purposes supports the development of a model for predicting the extent of biodegradation at different time frames, in particular the extent of ultimate biodegradation within a '10 day window' criterion as well as estimating biodegradation half-lives. Conceptually this implies expressing the rate of catabolic transformations as a function of time. An attempt to correlate the kinetics of biodegradation with molecular structure of chemicals is presented. A simplified biodegradation kinetic model was formulated by combining the probabilistic approach of the original formulation of the CATABOL model with the assumption of first order kinetics of catabolic transformations. Nonlinear regression analysis was used to fit the model parameters to OECD 301F biodegradation kinetic data for a set of 208 chemicals. The new model allows the prediction of biodegradation multi-pathways, primary and ultimate half-lives and simulation of related kinetic biodegradation parameters such as biological oxygen demand (BOD), carbon dioxide production, and the nature and amount of metabolites as a function of time. The model may also be used for evaluating the OECD ready biodegradability potential of a chemical within the '10-day window' criterion.

  12. Evaluation of probiotic treatment in a neonatal animal model.

    Science.gov (United States)

    Lee, D J; Drongowski, R A; Coran, A G; Harmon, C M

    2000-01-01

    The clinical use of probiotic agents such as enteral Lactobacillus to enhance intestinal defense against potential luminal pathogens has been tested in vivo; however, an understanding of the mechanisms responsible for the observed protection is lacking. The purpose of this study was to evaluate the effects of Lactobacillus on bacterial translocation (BT) in a neonatal animal model. Newborn New Zealand white rabbit pups were enterally fed a 10% Formulac solution inoculated with or without a 10(8) suspension of ampicillin-resistant Escherichia coli K1 (E. coli K1A) and/or Lactobacillus casei GG (Lacto GG). Pups received either no bacteria (n = 10), Lacto GG (n = 8), E. coli K1A (n = 26), or a combination of Lacto GG and E. coli K1A (n = 33). On day 3, representative tissue specimens from the mesenteric lymph nodes (MLN), spleen (SPL), and liver (LIV) were aseptically harvested in addition to a small-bowel (SB) sample that was rinsed to remove luminal contents. The specimens were then cultured in organism-specific media. Statistical analysis was by one-way ANOVA with P values less than 0.05 considered significant. Neonatal rabbits receiving Lacto GG-supplemented formula exhibited a 25% decrease (P rabbit model. These results may have significant implications for the treatment of BT and sepsis in the human neonate and provide a model for further studies.

  13. Animal Models for Influenza Virus Pathogenesis and Transmission

    Directory of Open Access Journals (Sweden)

    Anice C. Lowen

    2010-07-01

    Full Text Available Influenza virus infection of humans results in a respiratory disease that ranges in severity from sub-clinical infection to primary viral pneumonia that can result in death. The clinical effects of infection vary with the exposure history, age and immune status of the host, and also the virulence of the influenza strain. In humans, the virus is transmitted through either aerosol or contact-based transfer of infectious respiratory secretions. As is evidenced by most zoonotic influenza virus infections, not all strains that can infect humans are able to transmit from person-to-person. Animal models of influenza are essential to research efforts aimed at understanding the viral and host factors that contribute to the disease and transmission outcomes of influenza virus infection in humans. These models furthermore allow the pre-clinical testing of antiviral drugs and vaccines aimed at reducing morbidity and mortality in the population through amelioration of the virulence or transmissibility of influenza viruses. Mice, ferrets, guinea pigs, cotton rats, hamsters and macaques have all been used to study influenza viruses and therapeutics targeting them. Each model presents unique advantages and disadvantages, which will be discussed herein.

  14. An animal model of emotional blunting in schizophrenia.

    Directory of Open Access Journals (Sweden)

    Charmaine Y Pietersen

    Full Text Available Schizophrenia is often associated with emotional blunting--the diminished ability to respond to emotionally salient stimuli--particularly those stimuli representative of negative emotional states, such as fear. This disturbance may stem from dysfunction of the amygdala, a brain region involved in fear processing. The present article describes a novel animal model of emotional blunting in schizophrenia. This model involves interfering with normal fear processing (classical conditioning in rats by means of acute ketamine administration. We confirm, in a series of experiments comprised of cFos staining, behavioral analysis and neurochemical determinations, that ketamine interferes with the behavioral expression of fear and with normal fear processing in the amygdala and related brain regions. We further show that the atypical antipsychotic drug clozapine, but not the typical antipsychotic haloperidol nor an experimental glutamate receptor 2/3 agonist, inhibits ketamine's effects and retains normal fear processing in the amygdala at a neurochemical level, despite the observation that fear-related behavior is still inhibited due to ketamine administration. Our results suggest that the relative resistance of emotional blunting to drug treatment may be partially due to an inability of conventional therapies to target the multiple anatomical and functional brain systems involved in emotional processing. A conceptual model reconciling our findings in terms of neurochemistry and behavior is postulated and discussed.

  15. Nonlinear model predictive control theory and algorithms

    CERN Document Server

    Grüne, Lars

    2017-01-01

    This book offers readers a thorough and rigorous introduction to nonlinear model predictive control (NMPC) for discrete-time and sampled-data systems. NMPC schemes with and without stabilizing terminal constraints are detailed, and intuitive examples illustrate the performance of different NMPC variants. NMPC is interpreted as an approximation of infinite-horizon optimal control so that important properties like closed-loop stability, inverse optimality and suboptimality can be derived in a uniform manner. These results are complemented by discussions of feasibility and robustness. An introduction to nonlinear optimal control algorithms yields essential insights into how the nonlinear optimization routine—the core of any nonlinear model predictive controller—works. Accompanying software in MATLAB® and C++ (downloadable from extras.springer.com/), together with an explanatory appendix in the book itself, enables readers to perform computer experiments exploring the possibilities and limitations of NMPC. T...

  16. Disease Prediction Models and Operational Readiness

    Energy Technology Data Exchange (ETDEWEB)

    Corley, Courtney D.; Pullum, Laura L.; Hartley, David M.; Benedum, Corey M.; Noonan, Christine F.; Rabinowitz, Peter M.; Lancaster, Mary J.

    2014-03-19

    INTRODUCTION: The objective of this manuscript is to present a systematic review of biosurveillance models that operate on select agents and can forecast the occurrence of a disease event. One of the primary goals of this research was to characterize the viability of biosurveillance models to provide operationally relevant information for decision makers to identify areas for future research. Two critical characteristics differentiate this work from other infectious disease modeling reviews. First, we reviewed models that attempted to predict the disease event, not merely its transmission dynamics. Second, we considered models involving pathogens of concern as determined by the US National Select Agent Registry (as of June 2011). Methods: We searched dozens of commercial and government databases and harvested Google search results for eligible models utilizing terms and phrases provided by public health analysts relating to biosurveillance, remote sensing, risk assessments, spatial epidemiology, and ecological niche-modeling, The publication date of search results returned are bound by the dates of coverage of each database and the date in which the search was performed, however all searching was completed by December 31, 2010. This returned 13,767 webpages and 12,152 citations. After de-duplication and removal of extraneous material, a core collection of 6,503 items was established and these publications along with their abstracts are presented in a semantic wiki at http://BioCat.pnnl.gov. Next, PNNL’s IN-SPIRE visual analytics software was used to cross-correlate these publications with the definition for a biosurveillance model resulting in the selection of 54 documents that matched the criteria resulting Ten of these documents, However, dealt purely with disease spread models, inactivation of bacteria, or the modeling of human immune system responses to pathogens rather than predicting disease events. As a result, we systematically reviewed 44 papers and the

  17. Development of a model animal welfare act curriculum.

    Science.gov (United States)

    VandeWoude, Sue

    2007-01-01

    Animal-welfare issues are often controversial and frequently have an emotional component. Veterinarians have extensive knowledge, experience, and scientific perspective and are arguably the professionals best suited to advise and develop recommendations on animal welfare. The development of an Animal Welfare Act (AWA) teaching module is a first step toward educating veterinary students about animal welfare. This article presents the current development status of this curriculum project, which is intended to be a valuable addition to the evolving veterinary education on animal welfare.

  18. Predictive Modeling in Actinide Chemistry and Catalysis

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Ping [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-05-16

    These are slides from a presentation on predictive modeling in actinide chemistry and catalysis. The following topics are covered in these slides: Structures, bonding, and reactivity (bonding can be quantified by optical probes and theory, and electronic structures and reaction mechanisms of actinide complexes); Magnetic resonance properties (transition metal catalysts with multi-nuclear centers, and NMR/EPR parameters); Moving to more complex systems (surface chemistry of nanomaterials, and interactions of ligands with nanoparticles); Path forward and conclusions.

  19. A New Tube Gastrostomy Model in Animal Experiments

    Directory of Open Access Journals (Sweden)

    Atakan Sezer

    2013-01-01

    Full Text Available Aim: The orogastric route is the most preferred application method in the vast majority of the animal experiments in which application can be achieved by adding the material to the water of the experiment animal, through an orogastric tube or with a surgically managed ostomy. Material and Method: This experiment was constructed with twelve male Sprague-Dawley rats which were randomly assigned to one of two groups consist of control group ( group C, n: 6 and tube gastrostomy group ( group TG, n: 6.A novel and simple gastrostomy tube was derivated from a silicone foley catheter. Tube gastrostomy apparatus was constituted with a silicone foley catheter (6 French. In the group TG an incision was performed, and the stomach was visualized. A 1 cm incision was made in the midline and opening of the peritoneum. Anchoring sutures were placed and anterior gastric wall was lifted. The gastric wall is then opened. The apparatus was placed into the stomach and pulled through from a tunnel under the skin and fixed to the lateral abdominal wall with a 2/0 silk suture. Result: The procedure was ended in the 10th day of experiment. No mortality was observed in group C. The rats were monitored daily and no abnormal behavior consists of self harming incision site, resistance to oral intake or attending to displace. There was statistically significant difference in increasing alanine transaminase level (p<0.05 and decrease in the total protein and body weight (p<0.05 at the group TG at the end of experiment. There was significant increase in urea levels in Group C (p<0.05 at the end of experiment. The statistically significant decrease was observed in the same period in group C between aspartate transaminase, albumin, total protein, and body weight (p<0.05.  Glucose (p=0.047 and aspartate transaminase (p=0.050 level decrease changes and weight loose (p=0.034 from preoperative period to the end of the experiment between gastrostomy and laparotomy groups were

  20. Probabilistic prediction models for aggregate quarry siting

    Science.gov (United States)

    Robinson, G.R.; Larkins, P.M.

    2007-01-01

    Weights-of-evidence (WofE) and logistic regression techniques were used in a GIS framework to predict the spatial likelihood (prospectivity) of crushed-stone aggregate quarry development. The joint conditional probability models, based on geology, transportation network, and population density variables, were defined using quarry location and time of development data for the New England States, North Carolina, and South Carolina, USA. The Quarry Operation models describe the distribution of active aggregate quarries, independent of the date of opening. The New Quarry models describe the distribution of aggregate quarries when they open. Because of the small number of new quarries developed in the study areas during the last decade, independent New Quarry models have low parameter estimate reliability. The performance of parameter estimates derived for Quarry Operation models, defined by a larger number of active quarries in the study areas, were tested and evaluated to predict the spatial likelihood of new quarry development. Population density conditions at the time of new quarry development were used to modify the population density variable in the Quarry Operation models to apply to new quarry development sites. The Quarry Operation parameters derived for the New England study area, Carolina study area, and the combined New England and Carolina study areas were all similar in magnitude and relative strength. The Quarry Operation model parameters, using the modified population density variables, were found to be a good predictor of new quarry locations. Both the aggregate industry and the land management community can use the model approach to target areas for more detailed site evaluation for quarry location. The models can be revised easily to reflect actual or anticipated changes in transportation and population features. ?? International Association for Mathematical Geology 2007.

  1. Predicting Footbridge Response using Stochastic Load Models

    DEFF Research Database (Denmark)

    Pedersen, Lars; Frier, Christian

    2013-01-01

    Walking parameters such as step frequency, pedestrian mass, dynamic load factor, etc. are basically stochastic, although it is quite common to adapt deterministic models for these parameters. The present paper considers a stochastic approach to modeling the action of pedestrians, but when doing s...... as it pinpoints which decisions to be concerned about when the goal is to predict footbridge response. The studies involve estimating footbridge responses using Monte-Carlo simulations and focus is on estimating vertical structural response to single person loading....

  2. Nonconvex Model Predictive Control for Commercial Refrigeration

    DEFF Research Database (Denmark)

    Hovgaard, Tobias Gybel; Larsen, Lars F.S.; Jørgensen, John Bagterp

    2013-01-01

    the iterations, which is more than fast enough to run in real-time. We demonstrate our method on a realistic model, with a full year simulation and 15 minute time periods, using historical electricity prices and weather data, as well as random variations in thermal load. These simulations show substantial cost...... is to minimize the total energy cost, using real-time electricity prices, while obeying temperature constraints on the zones. We propose a variation on model predictive control to achieve this goal. When the right variables are used, the dynamics of the system are linear, and the constraints are convex. The cost...

  3. Animal models of listeriosis: a comparative review of the current state of the art and lessons learned

    Directory of Open Access Journals (Sweden)

    Hoelzer Karin

    2012-03-01

    Full Text Available Abstract Listeriosis is a leading cause of hospitalization and death due to foodborne illness in the industrialized world. Animal models have played fundamental roles in elucidating the pathophysiology and immunology of listeriosis, and will almost certainly continue to be integral components of the research on listeriosis. Data derived from animal studies helped for example characterize the importance of cell-mediated immunity in controlling infection, allowed evaluation of chemotherapeutic treatments for listeriosis, and contributed to quantitative assessments of the public health risk associated with L. monocytogenes contaminated food commodities. Nonetheless, a number of pivotal questions remain unresolved, including dose-response relationships, which represent essential components of risk assessments. Newly emerging data about species-specific differences have recently raised concern about the validity of most traditional animal models of listeriosis. However, considerable uncertainty about the best choice of animal model remains. Here we review the available data on traditional and potential new animal models to summarize currently recognized strengths and limitations of each model. This knowledge is instrumental for devising future studies and for interpreting current data. We deliberately chose a historical, comparative and cross-disciplinary approach, striving to reveal clues that may help predict the ultimate value of each animal model in spite of incomplete data.

  4. Statistical Seasonal Sea Surface based Prediction Model

    Science.gov (United States)

    Suarez, Roberto; Rodriguez-Fonseca, Belen; Diouf, Ibrahima

    2014-05-01

    The interannual variability of the sea surface temperature (SST) plays a key role in the strongly seasonal rainfall regime on the West African region. The predictability of the seasonal cycle of rainfall is a field widely discussed by the scientific community, with results that fail to be satisfactory due to the difficulty of dynamical models to reproduce the behavior of the Inter Tropical Convergence Zone (ITCZ). To tackle this problem, a statistical model based on oceanic predictors has been developed at the Universidad Complutense of Madrid (UCM) with the aim to complement and enhance the predictability of the West African Monsoon (WAM) as an alternative to the coupled models. The model, called S4CAST (SST-based Statistical Seasonal Forecast) is based on discriminant analysis techniques, specifically the Maximum Covariance Analysis (MCA) and Canonical Correlation Analysis (CCA). Beyond the application of the model to the prediciton of rainfall in West Africa, its use extends to a range of different oceanic, atmospheric and helth related parameters influenced by the temperature of the sea surface as a defining factor of variability.

  5. A genomic biomarker signature can predict skin sensitizers using a cell-based in vitro alternative to animal tests

    Directory of Open Access Journals (Sweden)

    Albrekt Ann-Sofie

    2011-08-01

    Full Text Available Abstract Background Allergic contact dermatitis is an inflammatory skin disease that affects a significant proportion of the population. This disease is caused by an adverse immune response towards chemical haptens, and leads to a substantial economic burden for society. Current test of sensitizing chemicals rely on animal experimentation. New legislations on the registration and use of chemicals within pharmaceutical and cosmetic industries have stimulated significant research efforts to develop alternative, human cell-based assays for the prediction of sensitization. The aim is to replace animal experiments with in vitro tests displaying a higher predictive power. Results We have developed a novel cell-based assay for the prediction of sensitizing chemicals. By analyzing the transcriptome of the human cell line MUTZ-3 after 24 h stimulation, using 20 different sensitizing chemicals, 20 non-sensitizing chemicals and vehicle controls, we have identified a biomarker signature of 200 genes with potent discriminatory ability. Using a Support Vector Machine for supervised classification, the prediction performance of the assay revealed an area under the ROC curve of 0.98. In addition, categorizing the chemicals according to the LLNA assay, this gene signature could also predict sensitizing potency. The identified markers are involved in biological pathways with immunological relevant functions, which can shed light on the process of human sensitization. Conclusions A gene signature predicting sensitization, using a human cell line in vitro, has been identified. This simple and robust cell-based assay has the potential to completely replace or drastically reduce the utilization of test systems based on experimental animals. Being based on human biology, the assay is proposed to be more accurate for predicting sensitization in humans, than the traditional animal-based tests.

  6. Pramipexole reduces inflammation in the experimental animal models of inflammation.

    Science.gov (United States)

    Sadeghi, Heibatollah; Parishani, Mohammad; Akbartabar Touri, Mehdi; Ghavamzadeh, Mehdi; Jafari Barmak, Mehrzad; Zarezade, Vahid; Delaviz, Hamdollah; Sadeghi, Hossein

    2017-04-01

    Pramipexole is a dopamine (DA) agonist (D2 subfamily receptors) that widely use in the treatment of Parkinson's diseases. Some epidemiological and genetic studies propose a role of inflammation in the pathophysiology of Parkinson's disease. To our knowledge, there is no study regarding the anti-inflammatory activity of pramipexol. Therefore, the aim of the study was to investigate anti-inflammatory effect of pramipexol. Anti-inflammatory effects of pramipexole were studied in three well-characterized animal models of inflammation, including carrageenan- or formalin-induced paw inflammation in rats, and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema in mice. The animals received pramipexol (0.25, 0.5 and 1 mg/kg, I.P.) 30 min before subplantar injection of carrageenan or formalin. Pramipexol (0.5 and 1 mg/kg) was also injected 30 min before topical application of TPA on the ear mice. Serum malondialdehyde (MDA) levels were evaluated in the carrageenan test. Finally, pathological examination of the inflamed tissues was carried out. Pramipexole significantly inhibited paw inflammation 1, 2, 3 and 4 h after carrageenan challenge compared with the control group (p Pramipexol also showed considerable anti-inflammatory activity against formalin-evoked paw edema over a period of 24 h (p pramipexol (p pramipexole reduced tissue injury, neutrophil infiltration, and subcutaneous edema. Pramipexole did not alter the increased serum levels of MDA due to carrageenan injection. These data clearly indicate that pramipexol possesses significant anti-inflammatory activity. It seems that its antioxidants do not play an important role in these effects.

  7. Imaging of cerebrovascular pathology in animal models of Alzheimer's disease

    Science.gov (United States)

    Klohs, Jan; Rudin, Markus; Shimshek, Derya R.; Beckmann, Nicolau

    2014-01-01

    In Alzheimer's disease (AD), vascular pathology may interact with neurodegeneration and thus aggravate cognitive decline. As the relationship between these two processes is poorly understood, research has been increasingly focused on understanding the link between cerebrovascular alterations and AD. This has at last been spurred by the engineering of transgenic animals, which display pathological features of AD and develop cerebral amyloid angiopathy to various degrees. Transgenic models are versatile for investigating the role of amyloid deposition and vascular dysfunction, and for evaluating novel therapeutic concepts. In addition, research has benefited from the development of novel imaging techniques, which are capable of characterizing vascular pathology in vivo. They provide vascular structural read-outs and have the ability to assess the functional consequences of vascular dysfunction as well as to visualize and monitor the molecular processes underlying these pathological alterations. This article focusses on recent in vivo small animal imaging studies addressing vascular aspects related to AD. With the technical advances of imaging modalities such as magnetic resonance, nuclear and microscopic imaging, molecular, functional and structural information related to vascular pathology can now be visualized in vivo in small rodents. Imaging vascular and parenchymal amyloid-β (Aβ) deposition as well as Aβ transport pathways have been shown to be useful to characterize their dynamics and to elucidate their role in the development of cerebral amyloid angiopathy and AD. Structural and functional imaging read-outs have been employed to describe the deleterious affects of Aβ on vessel morphology, hemodynamics and vascular integrity. More recent imaging studies have also addressed how inflammatory processes partake in the pathogenesis of the disease. Moreover, imaging can be pivotal in the search for novel therapies targeting the vasculature. PMID:24659966

  8. Molecular genetics and animal models in autistic disorder.

    Science.gov (United States)

    Andres, Christian

    2002-01-01

    better knowledge of the pathophysiology of these disorders can help to understand autism. Different other candidate genes have been tested, positive results await replications in other samples. Animal models have been developed, generally by knocking out the different candidate genes. Behaviour studies have mainly focused on anxiety and learning paradigms. Another group of models results from surgical or toxic lesions of candidate regions in the brain, in general during development. The tools to analyse these animals are not yet standardised, and an important effort needs to be undertaken.

  9. Revealing the hidden networks of interaction in mobile animal groups allows prediction of complex behavioral contagion.

    Science.gov (United States)

    Rosenthal, Sara Brin; Twomey, Colin R; Hartnett, Andrew T; Wu, Hai Shan; Couzin, Iain D

    2015-04-14

    Coordination among social animals requires rapid and efficient transfer of information among individuals, which may depend crucially on the underlying structure of the communication network. Establishing the decision-making circuits and networks that give rise to individual behavior has been a central goal of neuroscience. However, the analogous problem of determining the structure of the communication network among organisms that gives rise to coordinated collective behavior, such as is exhibited by schooling fish and flocking birds, has remained almost entirely neglected. Here, we study collective evasion maneuvers, manifested through rapid waves, or cascades, of behavioral change (a ubiquitous behavior among taxa) in schooling fish (Notemigonus crysoleucas). We automatically track the positions and body postures, calculate visual fields of all individuals in schools of ∼150 fish, and determine the functional mapping between socially generated sensory input and motor response during collective evasion. We find that individuals use simple, robust measures to assess behavioral changes in neighbors, and that the resulting networks by which behavior propagates throughout groups are complex, being weighted, directed, and heterogeneous. By studying these interaction networks, we reveal the (complex, fractional) nature of social contagion and establish that individuals with relatively few, but strongly connected, neighbors are both most socially influential and most susceptible to social influence. Furthermore, we demonstrate that we can predict complex cascades of behavioral change at their moment of initiation, before they actually occur. Consequently, despite the intrinsic stochasticity of individual behavior, establishing the hidden communication networks in large self-organized groups facilitates a quantitative understanding of behavioral contagion.

  10. Recent advances in animal models of diabetic nephropathy.

    Science.gov (United States)

    Betz, Boris; Conway, Bryan R

    2014-01-01

    Diabetic nephropathy (DN) is the single most common cause of end-stage kidney disease. Therefore, it is imperative that novel therapies are developed. Progress has been hindered, however, by the lack of robust animal models. In the current review we describe recent advances in the field, including the impact of background strain, hypertension and transcriptomic profiling. While the C57BL/6J strain is relatively resistant to DN, the FVB strain appears more susceptible and Ove26 and db/db mice on this background may be useful in modelling types 1 and 2 DN, respectively. Black and tan, brachyury (BTBR) mice deficient for the leptin receptor (ob/ob) develop many of the pathological features of human DN and, remarkably, treatment with exogenous leptin ameliorates hyperglycaemia, albuminuria and glomerulosclerosis. Hypertension plays a key role in the progression of human DN and exacerbates nephropathy in diabetic rodents. Endothelial nitric oxide synthase deficiency (eNOS(-/-)) results in moderate hypertension and the development of nodular glomerulosclerosis and hyaline arteriosclerosis in streptozotocin-induced diabetic C57BL/6J mice. In Cyp1a1mRen2 rats, renin-dependent hypertension synergises with streptozotocin-induced hyperglycaemia to produce a 500-fold increase in albuminuria, glomerulosclerosis and tubulointerstitial fibrosis. Renal transcriptional profiling suggests that many of the gene expression changes observed in human DN are replicated in eNOS(-/-) mice and Cyp1a1mRen2 rats. Despite these advances, no model faithfully recapitulates all the features of human DN and further refinements are required. In the interim, it is likely that researchers may use publically available transcriptomic data to select the most appropriate model to study their molecule or pathway of interest.

  11. Genetic Aspects of Autism Spectrum Disorders: Insights from Animal Models

    Directory of Open Access Journals (Sweden)

    Swati eBanerjee

    2014-02-01

    Full Text Available Autism spectrum disorders (ASD are a complex neurodevelopmental disorder that display a triad of core behavioral deficits including restricted interests, often accompanied by repetitive behavior, deficits in language and communication, and an inability to engage in reciprocal social interactions. ASD is among the most heritable disorders but is not a simple disorder with a singular pathology and has a rather complex etiology. It is interesting to note that perturbations in synaptic growth, development and stability underlie a variety of neuropsychiatric disorders, including ASD, schizophrenia, epilepsy and intellectual disability. Biological characterization of an increasing repertoire of synaptic mutants in various model organisms indicates synaptic dysfunction as causal in the pathophysiology of ASD. Our understanding of the genes and genetic pathways that contribute towards the formation, stabilization and maintenance of functional synapses coupled with an in-depth phenotypic analysis of the cellular and behavioral characteristics is therefore essential to unraveling the pathogenesis of these disorders. In this review, we discuss the genetic aspects of ASD emphasizing on the well conserved set of genes and genetic pathways implicated in this disorder, many of which contribute to synapse assembly and maintenance across species. We also review how fundamental research using animal models is providing key insights into the various facets of human ASD.

  12. Evaluation of Medical Cystine Stone Prevention in an Animal Model

    Science.gov (United States)

    Sagi, Sreedhar; Wendt-Nordahl, Gunnar; Alken, Peter; Knoll, Thomas

    2007-04-01

    Medical treatment for cystinuria aims to decrease the concentration of cystine in the urine, increase its solubility and therefore prevent stone formation. Ascorbic acid and captopril have been recommended as alternatives to thiol drugs, though conflicting data undermining their efficacy has been widely reported, too. The aim of this study was to verify the effects of ascorbic acid and captopril on cystine stone formation in the cystinuria mouse model. A total of 28 male homozygous pebbles mice were used for characterizing the mice on normal diet, ascorbic acid and captopril supplemented diets. The baseline physiological parameters of the mice were determined initially. The normal diet was then replaced with the supplemented diet (ascorbic acid/captopril) for the next 48 weeks and various biochemical parameters in urine and plasma were analyzed. All homozygous mice developed urinary cystine stones during the first year of life. No reduction in the urinary cystine concentration was seen with either of the supplemented diets. The stone mass varied widely in the study and a beneficial effect of ascorbic acid in some of the animals was possible though an overall statistical significance was not seen. Conclusions: The cystinuria mouse model provides an ideal tool for evaluation of stone preventive measures in a standardized environment. This study confirms that ascorbic acid and captopril are not effective in cystinuria.

  13. Molecular Imaging of Vulnerable Atherosclerotic Plaques in Animal Models

    Science.gov (United States)

    Gargiulo, Sara; Gramanzini, Matteo; Mancini, Marcello

    2016-01-01

    Atherosclerosis is characterized by intimal plaques of the arterial vessels that develop slowly and, in some cases, may undergo spontaneous rupture with subsequent heart attack or stroke. Currently, noninvasive diagnostic tools are inadequate to screen atherosclerotic lesions at high risk of acute complications. Therefore, the attention of the scientific community has been focused on the use of molecular imaging for identifying vulnerable plaques. Genetically engineered murine models such as ApoE−/− and ApoE−/−Fbn1C1039G+/− mice have been shown to be useful for testing new probes targeting biomarkers of relevant molecular processes for the characterization of vulnerable plaques, such as vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, intercellular adhesion molecule (ICAM)-1, P-selectin, and integrins, and for the potential development of translational tools to identify high-risk patients who could benefit from early therapeutic interventions. This review summarizes the main animal models of vulnerable plaques, with an emphasis on genetically altered mice, and the state-of-the-art preclinical molecular imaging strategies. PMID:27618031

  14. Neuropathology and Animal Models of Autism: Genetic and Environmental Factors

    Directory of Open Access Journals (Sweden)

    Bharathi S. Gadad

    2013-01-01

    Full Text Available Autism is a heterogeneous behaviorally defined neurodevelopmental disorder. It is defined by the presence of marked social deficits, specific language abnormalities, and stereotyped repetitive patterns of behavior. Because of the variability in the behavioral phenotype of the disorder among patients, the term autism spectrum disorder has been established. In the first part of this review, we provide an overview of neuropathological findings from studies of autism postmortem brains and identify the cerebellum as one of the key brain regions that can play a role in the autism phenotype. We review research findings that indicate possible links between the environment and autism including the role of mercury and immune-related factors. Because both genes and environment can alter the structure of the developing brain in different ways, it is not surprising that there is heterogeneity in the behavioral and neuropathological phenotypes of autism spectrum disorders. Finally, we describe animal models of autism that occur following insertion of different autism-related genes and exposure to environmental factors, highlighting those models which exhibit both autism-like behavior and neuropathology.

  15. Animal models to guide clinical drug development in ADHD: lost in translation?

    Science.gov (United States)

    Wickens, Jeffery R; Hyland, Brian I; Tripp, Gail

    2011-10-01

    We review strategies for developing animal models for examining and selecting compounds with potential therapeutic benefit in attention-deficit hyperactivity disorder (ADHD). ADHD is a behavioural disorder of unknown aetiology and pathophysiology. Current understanding suggests that genetic factors play an important role in the aetiology of ADHD. The involvement of dopaminergic and noradrenergic systems in the pathophysiology of ADHD is probable. We review the clinical features of ADHD including inattention, hyperactivity and impulsivity and how these are operationalized for laboratory study. Measures of temporal discounting (but not premature responding) appear to predict known drug effects well (treatment validity). Open-field measures of overactivity commonly used do not have treatment validity in human populations. A number of animal models have been proposed that simulate the symptoms of ADHD. The most commonly used are the spontaneously hypertensive rat (SHR) and the 6-hydroxydopamine-lesioned (6-OHDA) animals. To date, however, the SHR lacks treatment validity, and the effects of drugs on symptoms of impulsivity and inattention have not been studied extensively in 6-OHDA-lesioned animals. At the present stage of development, there are no in vivo models of proven effectiveness for examining and selecting compounds with potential therapeutic benefit in ADHD. However, temporal discounting is an emerging theme in theories of ADHD, and there is good evidence of increased value of delayed reward following treatment with stimulant drugs. Therefore, operant behaviour paradigms that measure the effects of drugs in situations of delayed reinforcement, whether in normal rats or selected models, show promise for the future.

  16. Predictive modeling by the cerebellum improves proprioception.

    Science.gov (United States)

    Bhanpuri, Nasir H; Okamura, Allison M; Bastian, Amy J

    2013-09-04

    Because sensation is delayed, real-time movement control requires not just sensing, but also predicting limb position, a function hypothesized for the cerebellum. Such cerebellar predictions could contribute to perception of limb position (i.e., proprioception), particularly when a person actively moves the limb. Here we show that human cerebellar patients have proprioceptive deficits compared with controls during active movement, but not when the arm is moved passively. Furthermore, when healthy subjects move in a force field with unpredictable dynamics, they have active proprioceptive deficits similar to cerebellar patients. Therefore, muscle activity alone is likely insufficient to enhance proprioception and predictability (i.e., an internal model of the body and environment) is important for active movement to benefit proprioception. We conclude that cerebellar patients have an active proprioceptive deficit consistent with disrupted movement prediction rather than an inability to generally enhance peripheral proprioceptive signals during action and suggest that active proprioceptive deficits should be considered a fundamental cerebellar impairment of clinical importance.

  17. Hill-type muscle model parameters determined from experiments on single muscles show large animal-to-animal variation.

    Science.gov (United States)

    Blümel, Marcus; Guschlbauer, Christoph; Daun-Gruhn, Silvia; Hooper, Scott L; Büschges, Ansgar

    2012-11-01

    Models built using mean data can represent only a very small percentage, or none, of the population being modeled, and produce different activity than any member of it. Overcoming this "averaging" pitfall requires measuring, in single individuals in single experiments, all of the system's defining characteristics. We have developed protocols that allow all the parameters in the curves used in typical Hill-type models (passive and active force-length, series elasticity, force-activation, force-velocity) to be determined from experiments on individual stick insect muscles (Blümel et al. 2012a). A requirement for means to not well represent the population is that the population shows large variation in its defining characteristics. We therefore used these protocols to measure extensor muscle defining parameters in multiple animals. Across-animal variability in these parameters can be very large, ranging from 1.3- to 17-fold. This large variation is consistent with earlier data in which extensor muscle responses to identical motor neuron driving showed large animal-to-animal variability (Hooper et al. 2006), and suggests accurate modeling of extensor muscles requires modeling individual-by-individual. These complete characterizations of individual muscles also allowed us to test for parameter correlations. Two parameter pairs significantly co-varied, suggesting that a simpler model could as well reproduce muscle response.

  18. Decisions on control of foot-and-mouth disease informed using model predictions

    DEFF Research Database (Denmark)

    Hisham Beshara Halasa, Tariq; Willeberg, P.; Christiansen, Lasse Engbo;

    2013-01-01

    , epidemic duration, geographical size and costs. The first 14 days spatial spread (FFS) was also included to further support the prediction. The epidemic data was obtained from a Danish version (DTU-DADS) of a pre-existing FMD simulation model (Davis Animal Disease Spread – DADS) adapted to model the spread...

  19. Ground Motion Prediction Models for Caucasus Region

    Science.gov (United States)

    Jorjiashvili, Nato; Godoladze, Tea; Tvaradze, Nino; Tumanova, Nino

    2016-04-01

    Ground motion prediction models (GMPMs) relate ground motion intensity measures to variables describing earthquake source, path, and site effects. Estimation of expected ground motion is a fundamental earthquake hazard assessment. The most commonly used parameter for attenuation relation is peak ground acceleration or spectral acceleration because this parameter gives useful information for Seismic Hazard Assessment. Since 2003 development of Georgian Digital Seismic Network has started. In this study new GMP models are obtained based on new data from Georgian seismic network and also from neighboring countries. Estimation of models is obtained by classical, statistical way, regression analysis. In this study site ground conditions are additionally considered because the same earthquake recorded at the same distance may cause different damage according to ground conditions. Empirical ground-motion prediction models (GMPMs) require adjustment to make them appropriate for site-specific scenarios. However, the process of making such adjustments remains a challenge. This work presents a holistic framework for the development of a peak ground acceleration (PGA) or spectral acceleration (SA) GMPE that is easily adjustable to different seismological conditions and does not suffer from the practical problems associated with adjustments in the response spectral domain.

  20. Gamma-Ray Pulsars Models and Predictions

    CERN Document Server

    Harding, A K

    2001-01-01

    Pulsed emission from gamma-ray pulsars originates inside the magnetosphere, from radiation by charged particles accelerated near the magnetic poles or in the outer gaps. In polar cap models, the high energy spectrum is cut off by magnetic pair production above an energy that is dependent on the local magnetic field strength. While most young pulsars with surface fields in the range B = 10^{12} - 10^{13} G are expected to have high energy cutoffs around several GeV, the gamma-ray spectra of old pulsars having lower surface fields may extend to 50 GeV. Although the gamma-ray emission of older pulsars is weaker, detecting pulsed emission at high energies from nearby sources would be an important confirmation of polar cap models. Outer gap models predict more gradual high-energy turnovers at around 10 GeV, but also predict an inverse Compton component extending to TeV energies. Detection of pulsed TeV emission, which would not survive attenuation at the polar caps, is thus an important test of outer gap models. N...