Sample records for ad animal model

  1. Animal models

    Gøtze, Jens Peter; Krentz, Andrew


    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....

  2. An $xp$ model on $AdS_2$ spacetime

    Molina-Vilaplana, Javier


    In this paper we formulate the $xp$ model on the AdS$_2$ spacetime. We find that the spectrum of the Hamiltonian has positive and negative eigenvalues, equal in magnitude, given by a harmonic oscillator with a zero point energy parameterized by the AdS radius, measured in units of a fundamental length of the model. We also construct the generators of the isometry group SO(2,1) of the AdS$_2$ spacetime, and discuss the relation with conformal quantum mechanics.

  3. Animal models of dementia

    Olsson, I. Anna S.; Sandøe, Peter


    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?...

  4. An $xp$ model on $AdS_2$ spacetime


    In this paper we formulate the $xp$ model on the AdS$_2$ spacetime. We find that the spectrum of the Hamiltonian has positive and negative eigenvalues, whose absolute values are given by a harmonic oscillator spectrum, which in turn coincides with that of a massive Dirac fermion in AdS$_2$. We extend this result to generic $xp$ models which are shown to be equivalent to a massive Dirac fermion on spacetimes whose metric depend of the $xp$ Hamiltonian. Finally, we construct the generators of t...

  5. Animal models of neurodegenerative diseases

    Fabiola Mara Ribeiro


    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.

  6. Animal models of scoliosis.

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


    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.

  7. N=2 supersymmetric sigma-models in AdS

    Butter, Daniel


    We construct the most general N=2 supersymmetric nonlinear sigma-model in four-dimensional anti-de Sitter (AdS) space in terms of N=1 chiral superfields. The target space is shown to be a non-compact hyperkahler manifold restricted to possess a special Killing vector field. A remarkable property of the sigma-model constructed is that the algebra of OSp(2|4) transformations is closed off the mass shell.

  8. Animal models for osteoporosis

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


    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.

  9. Modelling Farm Animal Welfare.

    Collins, Lisa M; Part, Chérie E


    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.

  10. Modelling Farm Animal Welfare

    Chérie E. Part


    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.

  11. Heavy quark potential from deformed AdS5 models

    Zhang, Zi-qiang; Hou, De-fu; Chen, Gang


    In this paper, we investigate the heavy quark potential in some holographic QCD models. The calculation relies on a modified renormalization scheme mentioned in a previous work of Albacete et al. After studying the heavy quark potential in Pirner-Galow model and Andreev-Zakharov model, we extend the discussion to a general deformed AdS5 case. It is shown that the obtained potential is negative definite for all quark-antiquark separations, differs from that using the usual renormalization scheme.

  12. Animal Models of Narcolepsy

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


    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...

  13. Animal models of candidiasis.

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


    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.

  14. Animal models of narcolepsy.

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


    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.

  15. Adding immigrants to microsimulation models.

    Duleep, Harriet Orcutt; Dowhan, Daniel J


    Forecasts of the financial status of Social Security's Old-Age, Survivors, and Disability Insurance (OASDI) programs and forecasts of the effects of various OASDI policy options on Americans would be improved if information about the earnings and labor force behavior of various population subgroups were included in projection models. Focusing on the projection of immigrant earnings, this article proffers a conceptual basis for incorporating immigration into microsimulation models. Key results from research on immigrant earnings, as described in the first article in this trilogy--"Research on Immigrant Earnings"--are linked to methods for forecasting individual earnings in microsimulation models. The research on immigrant earnings also inspires new methods for forecasting earnings in microsimulation models as well as the projection of immigrant emigration. Forecasting immigrant earnings and emigration is discussed in the context of a "closed system"--that is, forecasts are only made for a given population, which is represented in the base sample of the microsimulation model. The third article in our trilogy--"Incorporating Immigrant Flows into Microsimulation Models"--explores how to project immigrant earnings in the context of an "open system," which includes future immigrants.

  16. Queueing models for mobile ad hoc networks

    Haan, de Roland


    This thesis presents models for the performance analysis of a recent communication paradigm: mobile ad hoc networking. The objective of mobile ad hoc networking is to provide wireless connectivity between stations in a highly dynamic environment. These dynamics are driven by the mobility of stations

  17. Revisiting the thermodynamic relations in AdS /CMT models

    Hyun, Seungjoon; Park, Sang-A.; Yi, Sang-Heon


    Motivated by the recent unified approach to the Smarr-like relation of anti-de Sitter (AdS) planar black holes in conjunction with the quasilocal formalism on conserved charges, we revisit the quantum statistical and thermodynamic relations of hairy AdS planar black holes. By extending the previous results, we identify the hairy contribution in the bulk and show that the holographic computation can be improved so that it is consistent with the bulk computation. We argue that the first law can be retained in its universal form and that the relation between the on-shell renormalized Euclidean action and its free energy interpretation in gravity may also be undeformed even with the hairy contribution in hairy AdS black holes.

  18. Refining Animal Models to Enhance Animal Welfare

    Patricia V.Turner


    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.

  19. AdS5×S(5) mirror model as a string sigma model.

    Arutyunov, Gleb; van Tongeren, Stijn J


    Doing a double Wick rotation in the world sheet theory of the light cone AdS5×S(5) superstring results in an inequivalent, so-called mirror theory that plays a central role in the field of integrability in the AdS-CFT correspondence. We show that this mirror theory can be interpreted as the light cone theory of a free string on a different background. This background is related to dS5×H(5) by a double T-duality, and has hidden supersymmetry. The geometry can also be extracted from an integrable deformation of the AdS5×S(5) sigma model, and we prove the observed mirror duality of these deformed models at the bosonic level as a byproduct. While we focus on AdS5×S(5), our results apply more generally.

  20. Animal models of cerebral ischemia

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


    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.

  1. Value-Added Modeling in Physical Education

    Hushman, Glenn; Hushman, Carolyn


    The educational reform movement in the United States has resulted in a variety of states moving toward a system of value-added modeling (VAM) to measure a teacher's contribution to student achievement. Recently, many states have begun using VAM scores as part of a larger system to evaluate teacher performance. In the past decade, only "core…

  2. Research progress on animal models of Alzheimer's disease

    Wen DONG


    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

  3. Animal models for candidiasis.

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


    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.

  4. Animal models of portal hypertension

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


    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.

  5. Optogenetics in psychiatric animal models.

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


    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.

  6. Animal welfare and use of silkworm as a model animal.

    Sekimizu, N; Paudel, A; Hamamoto, H


    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.

  7. XX. Animal models of pneumocystosis

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


    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...

  8. Animal Models of Cardiovascular Diseases

    Carlos Zaragoza


    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.

  9. Animal models for diseases of respiratory system

    R. Adil


    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.

  10. Animal Models for Periodontal Disease

    Helieh S. Oz


    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.

  11. Hadrons in AdS/QCD models

    de Paula, W; 10.1007/s00601-011-0267-0


    We discuss applications of gauge/gravity duality to describe the spectrum of light hadrons. We compare two particular 5-dimensional approaches: a model with an infrared deformed Anti-de Sitter metric and another one based on a dynamical AdS/QCD framework with back-reacted geometry in a dilaton/gravity background. The models break softly the scale invariance in the infrared region and allow mass gap for the field excitations in the gravity description, while keeping the conformal property of the metric close to the four-dimensional boundary. The models provide linear Regge trajectories for light mesons, associated with specially designed infrared gravity properties. We also review the results for the decay widths of the f0's into two pions, as overlap integrals between mesonic string amplitudes, which are in qualitative agreement with data.

  12. Animal models for auditory streaming.

    Itatani, Naoya; Klump, Georg M


    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'.


    ZHANG Chao; WANG Qiuju; SUN Wei


    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.

  14. Animal models of source memory.

    Crystal, Jonathon D


    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.

  15. Animal models of drug addiction.

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


    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.

  16. Animal Models of Tuberculosis: Zebrafish

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


    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

  17. Modelling group dynamic animal movement

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


    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...

  18. Animal models of eating disorders

    Sangwon F Kim


    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...

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

    Morton, A Jennifer; Howland, David S


    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.

  20. Software Validation via Model Animation

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


    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.

  1. Animal Models of Allergic Diseases

    Domenico Santoro


    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.

  2. The $AdS_{5}xS^(5)$ fermionic model

    Abdalla, Elcio


    We consider the $AdS_{5}xS^(5)$ integrable model. As it turns out, relying on well known arguments, we claim that the conformally invariant fermionic model is solvable, the resulting solution given in terms of two current algebras realizations.

  3. Animal models of skin regeneration.

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


    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.

  4. Higher spin holography and the AdS string sigma model

    Polyakov, Dimitri


    We analyse the cubic spin-3 interaction in AdS space using the higher spin extension of the string-theoretic sigma-model constructed in our previous work, whose low energy limit is described by the AdS vacuum solution. We find that, in the leading order of the cosmological constant, the spin-3 correlator on the AdS4 string theory side reproduces the structure of the three-point function of composite operators, quadratic in free fields, in the dual d = 3 vector model. The cancellation of holography violating terms in d = 3 is related to the value of the Liouville background charge in d = 4. This article is part of a special issue of Journal of Physics A: Mathematical and Theoretical devoted to ‘Higher spin theories and holography’.

  5. Extended supersymmetric sigma models in AdS_4 from projective superspace

    Butter, Daniel; Lindstrom, Ulf; Tartaglino-Mazzucchelli, Gabriele


    There exist two superspace approaches to describe N=2 supersymmetric nonlinear sigma models in four-dimensional anti-de Sitter (AdS_4) space: (i) in terms of N=1 AdS chiral superfields, as developed in arXiv:1105.3111 and arXiv:1108.5290; and (ii) in terms of N=2 polar supermultiplets using the AdS projective-superspace techniques developed in arXiv:0807.3368. The virtue of the approach (i) is that it makes manifest the geometric properties of the N=2 supersymmetric sigma-models in AdS_4. The target space must be a non-compact hyperkahler manifold endowed with a Killing vector field which generates an SO(2) group of rotations on the two-sphere of complex structures. The power of the approach (ii) is that it allows us, in principle, to generate hyperkahler metrics as well as to address the problem of deformations of such metrics. Here we show how to relate the formulation (ii) to (i) by integrating out an infinite number of N=1 AdS auxiliary superfields and performing a superfield duality transformation. We al...

  6. Multilevel security model for ad hoc networks

    Wang Changda; Ju Shiguang


    Modern battlefield doctrine is based on mobility, flexibility, and rapid response to changing situations.As is well known, mobile ad hoc network systems are among the best utilities for battlefield activity. Although much research has been done on secure routing, security issues have largely been ignored in applying mobile ad hoc network theory to computer technology. An ad hoc network is usually assumed to be homogeneous, which is an irrational assumption for armies. It is clear that soldiers, commanders, and commanders-in-chief should have different security levels and computation powers as they have access to asymmetric resources. Imitating basic military rank levels in battlefield situations, how multilevel security can be introduced into ad hoc networks is indicated, thereby controlling restricted classified information flows among nodes that have different security levels.

  7. Animal models and conserved processes

    Greek Ray


    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

  8. Simplified TBA equations of the AdS5 × S5 mirror model

    Arutyunov, G.E.; Frolov, S.


    We use the recently found integral representation for the dressing phase in the kinematic region of the mirror theory to simplify the TBA equations for the AdS5 × S5 mirror model. The resulting set of equations provides an efficient starting point for both analytic and numerical studies.

  9. Animal models of recurrent or bipolar depression.

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


    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.

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

    Gootenberg, D B; Turnbaugh, P J


    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.

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

    Mazur, J E


    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.

  12. The Added Value of Business Models

    Vliet, Harry van


    An overview of innovations in a particular area, for example retail developments in the fashion sector (Van Vliet, 2014), and a subsequent discussion about the probability as to whether these innovations will realise a ‘breakthrough’, has to be supplemented with the question of what the added value

  13. Potency of Animal Models in KANSEI Engineering

    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.

  14. Chronobiology of ethanol: animal models.

    Rosenwasser, Alan M


    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.

  15. Nonlinear sigma models with AdS supersymmetry in three dimensions

    Butter, Daniel; Tartaglino-Mazzucchelli, Gabriele


    In three-dimensional anti-de Sitter (AdS) space, there exist several realizations of N-extended supersymmetry, which are traditionally labelled by two non-negative integers p>=q such that p+q=N. Different choices of p and q, with N fixed, prove to lead to different restrictions on the target space geometry of supersymmetric nonlinear sigma-models. We classify all possible types of hyperkahler target spaces for the cases N=3 and N=4 by making use of two different realizations for the most general (p,q) supersymmetric sigma-models: (i) off-shell formulations in terms of N=3 and N=4 projective supermultiplets; and (ii) on-shell formulations in terms of covariantly chiral scalar superfields in (2,0) AdS superspace. Depending on the type of N=3,4 AdS supersymmetry, nonlinear sigma-models can support one of the following target space geometries: (i) hyperkahler cones; (ii) non-compact hyperkahler manifolds with a U(1) isometry group which acts non-trivially on the two-sphere of complex structures; (iii) arbitrary h...

  16. Modeling Terrain Impact on Mobile Ad Hoc Networks (MANET) Connectivity


    Modeling Terrain Impact on Mobile Ad Hoc Networks ( MANET ) Connectivity Lance Joneckis Corinne Kramer David Sparrow David Tate I N S T I T U T E F...SUBTITLE Modeling Terrain Impact on Mobile Ad Hoc Networks ( MANET ) Connectivity 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...1882 Abstract—Terrain affects connectivity in mobile ad hoc net- works ( MANET ). Both average pairwise link closure and the rate


    Madhu Devi* and Ramica Sharma


    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.

  18. Vehicular Ad Hoc Network Mobility Model

    Budi Rahmadya


    Full Text Available Indonesia is one of developing countries with high land traffic density. This traffic density could cause traffic jam, traffic accidents and other disturbances. This research had developed a simulator that could calculate the traffic density of roads in urban areas. With the use of this simulator, the researcher could calculate the time needed if the source node transports the message to the destination node by using the ad hoc network communication facility. In this research, every vehicle utilizes multi-hop communication in a communication network. The vehicle sends the message through flooding message and passes on the received message to other vehicles. Based on the simulation done on map size 10 km x 10 km with a total of 20 vehicles on the road, it was calculated that the simulator could transmit the message to its destination on the 106th second from node 3 and with the total of 200 vehicles on the road, the simulator could transmit the message to its destination on the 22nd second from node 5. 

  19. Pain assessment in animal models of osteoarthritis.

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


    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.

  20. Towards a reliable animal model of migraine

    Olesen, Jes; Jansen-Olesen, Inger


    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....

  1. Experimental Animal Models in Periodontology: A Review

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


    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...

  2. Evaluation of spinal cord injury animal models

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


    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.

  3. Animal model and neurobiology of suicide.

    Preti, Antonio


    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.

  4. Limitations of Animal Models of Parkinson's Disease

    J. A. Potashkin


    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.


    Madhu Devi* and Ramica Sharma


    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...

  6. On Performance Modeling of Ad Hoc Routing Protocols

    Khayam SyedAli


    Full Text Available Simulation studies have been the predominant method of evaluating ad hoc routing algorithms. Despite their wide use and merits, simulations are generally time consuming. Furthermore, several prominent ad hoc simulations report inconsistent and unrepeatable results. We, therefore, argue that simulation-based evaluation of ad hoc routing protocols should be complemented with mathematical verification and comparison. In this paper, we propose a performance evaluation framework that can be used to model two key performance metrics of an ad hoc routing algorithm, namely, routing overhead and route optimality. We also evaluate derivatives of the two metrics, namely, total energy consumption and route discovery latency. Using the proposed framework, we evaluate the performance of four prominent ad hoc routing algorithms: DSDV, DSR, AODV-LL, and Gossiping. We show that the modeled metrics not only allow unbiased performance comparison but also provide interesting insight about the impact of different parameters on the behavior of these protocols.

  7. Engineering large animal models of human disease.

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


    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.

  8. Animal models of chronic wound care

    Trostrup, Hannah; Thomsen, Kim; Calum, Henrik


    . 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...

  9. Null-polygonal minimal surfaces in AdS_4 from perturbed W minimal models

    Hatsuda, Yasuyuki; Satoh, Yuji


    We study the null-polygonal minimal surfaces in AdS_4, which correspond to the gluon scattering amplitudes/Wilson loops in N=4 super Yang-Mills theory at strong coupling. The area of the minimal surfaces with n cusps is characterized by the thermodynamic Bethe ansatz (TBA) integral equations or the Y-system of the homogeneous sine-Gordon model, which is regarded as the SU(n-4)_4/U(1)^{n-5} generalized parafermion theory perturbed by the weight-zero adjoint operators. Based on the relation to the TBA systems of the perturbed W minimal models, we solve the TBA equations by using the conformal perturbation theory, and obtain the analytic expansion of the remainder function around the UV/regular-polygonal limit for n=6 and 7. We compare the rescaled remainder function for n=6 with the two-loop one, to observe that they are close to each other similarly to the AdS_3 case.

  10. Animal models for simulating weightlessness

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


    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.

  11. Retinal Cell Degeneration in Animal Models

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


    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...

  12. Supergravity background of lambda-deformed model for AdS2 x S2 supercoset

    Borsato, R; Wulff, L


    Starting with the F/G supercoset model corresponding to the AdS_n x S^n superstring one can define the lambda-model of arXiv:1409.1538 either as a deformation of the F/F gauged WZW model or as an integrable one-parameter generalization of the non-abelian T-dual of the AdS_n x S^n superstring sigma model with respect to the whole supergroup F. Here we consider the case of n=2 and find the explicit form of the 4d target space background for the lambda-model for the PSU(1,1|2)/[SO(1,1) x SO(2)] supercoset. We show that this background represents a solution of type IIB 10d supergravity compactified on a 6-torus with only metric, dilaton Phi and the RR 5-form (represented by a 2-form F in 4d) being non-trivial. This implies that the lambda-model is Weyl invariant at the quantum level and thus defines a consistent superstring sigma model. The supergravity solution we find is different from the one in arXiv:1410.1886 which should correspond to a version of the lambda-model where only the bosonic subgroup of F is gau...

  13. Evaluation of animal models of neurobehavioral disorders

    Nordquist Rebecca E


    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

  14. 3-D Human Modeling and Animation

    Ratner, Peter


    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

  15. VMQL: A Visual Language for Ad-Hoc Model Querying

    Störrle, Harald


    In large scale model based development, analysis level models are more like knowledge bases than engineering artifacts. Their effectiveness depends, to a large degree, on the ability of domain experts to retrieve information from them ad hoc. For large scale models, however, existing query facili...

  16. Animal models: an important tool in mycology.

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


    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.

  17. Virtual reality mobility model for wireless ad hoc networks

    Yu Ziyue; Gong Bo; He Xingui


    For wireless ad hoc networks simulation.node's mobility pattern and traffic pattern are two key elements.A new simulation model is presented based on the virtual reality collision detection algorithm in obstacle environment,and the model uses the path planning method to avoid obstacles and to compute the node's moving path.Obstacles also affect node's signal propagation.Considering these factors,this study implements the mobility model for wireless ad hoc networks.Simulation results show that the model has a significant impact on the performance of protocols.

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

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


    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. Matrix Model Maps and Reconstruction of AdS SUGRA Interactions

    Cremonini, Sera; Jevicki, Antal


    We consider the question of reconstructing (cubic) SUGRA interactions in AdS/CFT. The method we introduce is based on the matrix model maps (MMP) which were previously successfully employed at the linearized level. The strategy is to start with the map for 1/2 BPS configurations which is exactly known (to all orders) in the hamiltonian framework. We then use the extension of the matrix model map with the corresponding Ward identities to completely specify the interaction. A central point in this construction is the non-vanishing of off-shell interactions (even for highest-weight states).

  20. Animal models of osteoporosis - necessity and limitations

    Turner A. Simon


    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.

  1. A cognitive model's view of animal cognition

    Sidney D'MELLO, Stan FRANKLIN


    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].

  2. Progress With Nonhuman Animal Models of Addiction.

    Crabbe, John C


    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.

  3. The structure of N=2 supersymmetric nonlinear sigma models in AdS_4

    Butter, Daniel


    We present a detailed study of the most general N=2 supersymmetric sigma models in four-dimensional anti-de Sitter space AdS_4 formulated in terms of N=1 chiral superfields. The target space is demonstrated to be a non-compact hyperkahler manifold restricted to possess a special Killing vector field which generates an SO(2) group of rotations on the two-sphere of complex structures and necessarily leaves one of them invariant. All hyperkahler cones, that is the target spaces of N=2 superconformal sigma models, prove to possess such a vector field that belongs to the Lie algebra of an isometry group SU(2) acting by rotations on the complex structures. A unique property of the N=2 sigma models constructed is that the algebra of OSp(2|4) transformations closes off the mass shell. We uncover the underlying N=2 superfield formulation for the N=2 sigma models constructed and compute the associated N=2 supercurrent. We give a special analysis of the most general systems of self-interacting N=2 tensor multiplets in A...

  4. What's the Value of VAM (Value-Added Modeling)?

    Scherrer, Jimmy


    The use of value-added modeling (VAM) in school accountability is expanding, but deciding how to embrace VAM is difficult. Various experts say it's too unreliable, causes more harm than good, and has a big margin for error. Others assert VAM is imperfect but useful, and provides valuable feedback. A closer look at the models, and their use,…

  5. Animal models in motion sickness research

    Daunton, Nancy G.


    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.

  6. Towards More Realistic Mobility Model in Vehicular Ad Hoc Network

    Dhananjay S. Gaikwad; Mahesh Lagad; Prashant Suryawanshi; Vaibhav Maske


    Mobility models or the movement patterns of nodes communicating wirelessely, play a vital role in the simulation-based evaluation of vehicular Ad Hoc Networks (VANETs). Even though recent research has developed models that better corresponds to real world mobility, we still have a limited understanding of the level of the required level of mobility details for modeling and simulating VANETs. In this paper, we propose a new mobility model for VANETs that works on the city area and map the topo...

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

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


    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.

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

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


    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

  9. Final model of multicriterionevaluation of animal welfare

    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...

  10. Molecular Thermodynamic Model for Polyelectrolyte Solutions with Added Salts

    ZHANGBo; CAIJun; 等


    A molecular thermodynamic model of polyelectrolyte developed previously was extended to polyelectrolyte solutions with added salts.Thermodynamic properties,such as activity coefficients of polyelectrolytes or added salts and osmotic coefficients of solvent, of a number of aqueous mixtures of polyelectrolytes and salts are analyzed with the proposed model.Successful correlation is obtained in the range of moderate or higher polyion concentration.For the same sample,thermodynamic properties of polyelectrolytes with and without simple electrolytes can be predicted mutually using parameters from regression data.

  11. A toy model for the AdS/CFT correspondence

    Berenstein, D E


    We study the large N gauged quantum mechanics for a single Hermitian matrix in the Harmonic oscillator potential well as a toy model for the AdS/CFT correspondence. We argue that the dual geometry should be a string in two dimensions with a curvature of stringy size. Even though the dual geometry is not weakly curved, one can still gain knowledge of the system from a detailed study of the open-closed string duality. We give a mapping between the basis of states made of traces (closed strings) and the eigenvalues of the matrix (D-brane picture) in terms of Schur polynomials. We connect this model with the study of giant gravitons in AdS_5 x S^5$. We show that the two giant gravitons that expand along AdS_5 and S^5 can be interpreted in the matrix model as taking an eigenvalue from the Fermi sea and exciting it very much, or as making a hole in the Fermi sea respectively. This is similar to recent studies of the c=1 string. This connection gives new insight on how to perform calculations for giant gravitons.

  12. Current status: Animal models of nausea

    Fox, Robert A.


    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.

  13. Optogenetics in animal model of alcohol addiction

    Nalberczak, Maria; Radwanska, Kasia


    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.

  14. Diabetes Mellitus Induces Alzheimer’s Disease Pathology: Histopathological Evidence from Animal Models

    Nobuyuki Kimura


    Full Text Available Alzheimer’s disease (AD is the major causative disease of dementia and is characterized pathologically by the accumulation of senile plaques (SPs and neurofibrillary tangles (NFTs in the brain. Although genetic studies show that β-amyloid protein (Aβ, the major component of SPs, is the key factor underlying AD pathogenesis, it remains unclear why advanced age often leads to AD. Interestingly, several epidemiological and clinical studies show that type II diabetes mellitus (DM patients are more likely to exhibit increased susceptibility to AD. Moreover, growing evidence suggests that there are several connections between the neuropathology that underlies AD and DM, and there is evidence that the experimental induction of DM can cause cognitive dysfunction, even in rodent animal models. This mini-review summarizes histopathological evidence that DM induces AD pathology in animal models and discusses the possibility that aberrant insulin signaling is a key factor in the induction of AD pathology.

  15. Animal models of preeclampsia; uses and limitations.

    McCarthy, F P


    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.

  16. Large animal models for stem cell therapy.

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


    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

  17. Classroom Learning Centers: Animals, Levels A-D. A Supplementary Approach for Teaching Science and Art.

    Doughty, Ted G.; Richiger, Georgina M.

    This publication includes curriculum materials on animals for grades K-4. The major purposes of this publication are to foster individualized and interdisciplinary science and art activities within elementary classrooms and to provide pupils and teachers with suggestions to encourage the use of zoos, animal parks, and natural history museums.…

  18. Cost-effectiveness analysis: adding value to assessment of animal health welfare and production.

    Babo Martins, S; Rushton, J


    Cost-effectiveness analysis (CEA) has been extensively used in economic assessments in fields related to animal health, namely in human health where it provides a decision-making framework for choices about the allocation of healthcare resources. Conversely, in animal health, cost-benefit analysis has been the preferred tool for economic analysis. In this paper, the use of CEA in related areas and the role of this technique in assessments of animal health, welfare and production are reviewed. Cost-effectiveness analysis can add further value to these assessments, particularly in programmes targeting animal welfare or animal diseases with an impact on human health, where outcomes are best valued in natural effects rather than in monetary units. Importantly, CEA can be performed during programme implementation stages to assess alternative courses of action in real time.

  19. Animal models for Gaucher disease research

    Tamar Farfel-Becker


    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. Laboratory animal models for esophageal cancer

    Dhanya Venugopalan Nair


    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.

  1. Animal models of anorexia and cachexia

    DeBoer, Mark Daniel


    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

  2. Animal models for studying penile hemodynamics

    HiroyaMizusawa; OsamuIshizuka


    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.

  3. Requirements for Logical Models for Value-Added Tax Legislation

    Nielsen, Morten Ib; Simonsen, Jakob Grue; Larsen, Ken Friis

    Enterprise resource planning (ERP) systems are ubiquitous in commercial enterprises of all sizes and invariably need to account for the notion of value-added tax (VAT). The legal and technical difficulties in handling VAT are exacerbated by spanning a broad and chaotic spectrum of intricate country...... such a model automatically into programs that essentially will replace customisation and localisation by con¿guration by changing parameters in the model. In particular, we: (1) identify a number of requirements for such modeling, including requirements for the underlying logic; (2) model salient parts...

  4. An animated model of reticulorumen motility.

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


    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.

  5. Cancer immunotherapy : insights from transgenic animal models

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


    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

  6. Animal models of trauma-induced coagulopathy.

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


    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.

  7. The modelling cycle for collective animal behaviour.

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


    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.

  8. Animal models of age related macular degeneration

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


    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 ...

  9. Animal models of psoriasis and pustular psoriasis.

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


    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.

  10. Quark confinement due to creation of micro AdS black holes in quarkonium model

    Taki, Mehran


    We use the solution of the Dirac equation for quarkonium atom in the 4D Anti de sitter (AdS$_{4}$) space to investigate the effect of the large negative cosmological constant on the phenomenon of quark confinement. We do the required calculations in the AdS$_{4}$ space to indicate that large cosmological constant can describe the quark confinement. In fact using the coulomb potential in Dirac equation while we employ the AdS metric will additionally lead us to a linear potential in the quark-antiquark interaction which can be considered to explain the quark confinement. This confining term is arising essentially from the geometrical features of the space. On the other hand the origin of the large cosmological constant can be justified by assuming the appearance of micro black holes in the recent hadronic collision process which is now current, for instance, at the LHC project.

  11. Production of value-added chars and activated carbons from animal manure

    The United States has a strong agricultural foundation that leaves behind large quantities of animal wastes. In the United States, an estimated 9 billion broilers, 256 million turkeys, 62 million pigs and 97 million dairy cows were produced in 2006 producing 5 times the waste of the U.S. human popu...

  12. Entropic information of dynamical AdS/QCD holographic models

    Bernardini, Alex E


    In this paper we investigate the entropic information that underlies five-dimensional Einstein-Hilbert gravity coupled to a dilaton field, in the context of dynamical holographic AdS/QCD models. The conditional entropy (CE) shall be studied for the dynamical AdS/QCD holographic model, in the UV and IR dominance limits, corroborating with the existence of light-flavour mesons of lower spins in nature. Light-flavour mesons of lower spins have entropically stable configurations. The entropic information content in the CE, further, provides an exact explanation for the lower observational/experimental/phenomenological occurrence in nature of higher spin mesons, for entropic informational grounds. A quantitative theoretical apparatus for predicting the instability of high spin light-flavour mesons is also introduced.

  13. Animal Migraine Models for Drug Development

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


    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

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


    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 of insulin resistance: A review.

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


    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.

  16. Animal models of anxiety disorders and stress

    Alline C. Campos


    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.

  17. A holistic model for Islamic accountants and its value added

    El-Halaby, Sherif; Hussainey, Khaled


    Purpose – The core objective for this study is introduce the holistic model for Islamic accountants through exploring the perspectives of Muslim scholars; Islamic sharia and AAOIFI ethical standards. The study also contributes to existing literature by exploring the main added value of Muslim accountant towards stakeholders through investigates the main roles of an Islamic accountants. Design/methodology/approach – The paper critically reviews historical debates about Islamic accounting and t...

  18. Imaging of cerebrovascular pathology in animal models of Alzheimer's disease

    Klohs, Jan; Rudin, Markus; Shimshek, Derya R.; Beckmann, Nicolau


    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

  19. Towards an animal model of food addiction.

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


    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

  20. Animal models of epilepsy: use and limitations

    Kandratavicius L


    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

  1. Experimental animal modelling for TB vaccine development

    Pere-Joan Cardona


    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.

  2. Correlated Inflammatory Responses and Neurodegeneration in Peptide-Injected Animal Models of Alzheimer’s Disease

    James G. McLarnon


    Full Text Available Animal models of Alzheimer’s disease (AD which emphasize activation of microglia may have particular utility in correlating proinflammatory activity with neurodegeneration. This paper reviews injection of amyloid-β (Aβ into rat brain as an alternative AD animal model to the use of transgenic animals. In particular, intrahippocampal injection of Aβ1-42 peptide demonstrates prominent microglial mobilization and activation accompanied by a significant loss of granule cell neurons. Furthermore, pharmacological inhibition of inflammatory reactivity is demonstrated by a broad spectrum of drugs with a common endpoint in conferring neuroprotection in peptide-injected animals. Peptide-injection models provide a focus on glial cell responses to direct peptide injection in rat brain and offer advantages in the study of the mechanisms underlying neuroinflammation in AD brain.

  3. Deformation Models Tracking, Animation and Applications

    Torres, Arnau; Gómez, Javier


    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...

  4. Animal models of alcohol and drug dependence

    Cleopatra S. Planeta


    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.

  5. Animal models of age related macular degeneration.

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


    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.

  6. Experimental Diabetes Mellitus in Different Animal Models

    Amin Al-awar


    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.

  7. Beamforming in Ad Hoc Networks: MAC Design and Performance Modeling

    Khalil Fakih


    Full Text Available We examine in this paper the benefits of beamforming techniques in ad hoc networks. We first devise a novel MAC paradigm for ad hoc networks when using these techniques in multipath fading environment. In such networks, the use of conventional directional antennas does not necessarily improve the system performance. On the other hand, the exploitation of the potential benefits of smart antenna systems and especially beamforming techniques needs a prior knowledge of the physical channel. Our proposition performs jointly channel estimation and radio resource sharing. We validate the fruitfulness of the proposed MAC and we evaluate the effects of the channel estimation on the network performance. We then present an accurate analytical model for the performance of IEEE 802.11 MAC protocol. We extend the latter model, by introducing the fading probability, to derive the saturation throughput for our proposed MAC when the simplest beamforming strategy is used in real multipath fading ad hoc networks. Finally, numerical results validate our proposition.

  8. Metallothionein-I and -III expression in animal models of Alzheimer disease

    Carrasco, J; Adlard, P; Cotman, C


    diseases, the use of animal models is a valuable tool. Several transgenic mouse models of AD amyloid deposits are currently available. These models express human beta-amyloid precursor protein (AbetaPP) carrying different mutations that subsequently result in a varied pattern of beta-amyloid (Abeta...... suggesting that the various MT isoforms may have different roles in these experimental systems, and perhaps also in human AD....

  9. Animal Models of Varicella Zoster Virus Infection

    Ilhem Messaoudi


    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.

  10. Colon preneoplastic lesions in animal models.

    Suzui, Masumi; Morioka, Takamitsu; Yoshimi, Naoki


    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.

  11. Animal Models of Compulsive Eating Behavior

    Matteo Di Segni


    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.

  12. An animal model to train Lichtenstein inguinal hernia repair

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


    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...

  13. Flying Ad-Hoc Networks: Routing Protocols, Mobility Models, Issues

    Muneer Bani Yassein


    Full Text Available Flying Ad-Hoc Networks (FANETs is a group of Unmanned Air Vehicles (UAVs which completed their work without human intervention. There are some problems in this kind of networks: the first one is the communication between (UAVs. Various routing protocols introduced classified into three categories, static, proactive, reactive routing protocols in order to solve this problem. The second problem is the network design, which depends on the network mobility, in which is the process of cooperation and collaboration between the UAV. Mobility model of FANET is introduced in order to solve this problem. In Mobility Model, the path and speed variations of the UAV and represents their position are defined. As of today, Random Way Point Model is utilized as manufactured one for Mobility in the greater part of recreation situations. The Arbitrary Way Point model is not relevant for the UAV in light of the fact that UAV do not alter their course and versatility, speed quickly at one time because of this reason, we consider more practical models, called Semi-Random Circular Movement (SRCM Mobility Model. Also, we consider different portability models, Mission Plan-Based (MPB Mobility Model, Pheromone-Based Model. Moreover, Paparazzi Mobility Model (PPRZM. This paper presented and discussed the main routing protocols and main mobility models used to solve the communication, cooperation, and collaboration in FANET networks.

  14. Animal models in drug development for MRSA.

    Marra, Andrea


    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.

  15. Animal Models Utilized in HTLV-1 Research.

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


    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.

  16. Realistic Mobility Modeling for Vehicular Ad Hoc Networks

    Akay, Hilal; Tugcu, Tuna


    Simulations used for evaluating the performance of routing protocols for Vehicular Ad Hoc Networks (VANET) are mostly based on random mobility and fail to consider individual behaviors of the vehicles. Unrealistic assumptions about mobility produce misleading results about the behavior of routing protocols in real deployments. In this paper, a realistic mobility modeling tool, Mobility for Vehicles (MOVE), which considers the basic mobility behaviors of vehicles, is proposed for a more accurate evaluation. The proposed model is tested against the Random Waypoint (RWP) model using AODV and OLSR protocols. The results show that the mobility model significantly affects the number of nodes within the transmission range of a node, the volume of control traffic, and the number of collisions. It is shown that number of intersections, grid size, and node density are important parameters when dealing with VANET performance.

  17. Physically based modeling and animation of tornado

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


    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.

  18. Supergravity background of λ-deformed model for AdS2×S2 supercoset

    R. Borsato


    Full Text Available Starting with the Fˆ/G supercoset model corresponding to the AdSn×Sn superstring one can define the λ-model of arXiv:1409.1538 either as a deformation of the Fˆ/Fˆ gauged WZW model or as an integrable one-parameter generalisation of the non-abelian T-dual of the AdSn×Sn superstring sigma model with respect to the whole supergroup Fˆ. Here we consider the case of n=2 and find the explicit form of the 4d target space background for the λ-model for the PSU(1,1|2/SO(1,1×SO(2 supercoset. We show that this background represents a solution of type IIB 10d supergravity compactified on a 6-torus with only metric, dilaton Φ and the RR 5-form (represented by a 2-form F in 4d being non-trivial. This implies that the λ-model is Weyl invariant at the quantum level and thus defines a consistent superstring sigma model. The supergravity solution we find is different from the one in arXiv:1410.1886 which should correspond to a version of the λ-model where only the bosonic subgroup of Fˆ is gauged. Still, the two solutions have equivalent scaling limit of arXiv:1504.07213 leading to the isometric background for the metric and eΦF which is related to the η-deformed AdS2×S2 sigma model of arXiv:1309.5850. Similar results are expected in the AdS3×S3 and AdS5×S5 cases.

  19. Animal models of addiction: fat and sugar.

    Morgan, Drake; Sizemore, Glen M


    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.

  20. Plausible cloth animation using dynamic bending model

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


    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.

  1. Phenotyping animal models of diabetic neuropathy

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


    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...

  2. Homogeneous Yang-Baxter deformations as non-abelian duals of the AdS_5 sigma-model

    Hoare, B


    We propose that the Yang-Baxter deformation of the symmetric space sigma-model parameterized by an r-matrix solving the homogeneous (classical) Yang-Baxter equation is equivalent to the non-abelian dual of the undeformed model with respect to a subgroup determined by the structure of the r-matrix. We explicitly demonstrate this on numerous examples in the case of the AdS_5 sigma-model. The same should also be true for the full AdS_5 x S^5 supercoset model, providing an explanation for and generalizing several recent observations relating homogeneous Yang-Baxter deformations based on non-abelian r-matrices to the undeformed AdS_5 x S^5 model by a combination of T-dualities and non-linear coordinate redefinitions. This also includes the special case of deformations based on abelian r-matrices, which correspond to TsT transformations: they are equivalent to non-abelian duals of the original model with respect to a central extension of abelian subalgebras.

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

    Vandeputte Caroline


    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.

  4. Animal models of anxiety: an ethological perspective

    Rodgers R.J.


    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

  5. Domestic animals as models for biomedical research.

    Andersson, Leif


    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.

  6. Animal models of glucocorticoid-induced glaucoma.

    Overby, Darryl R; Clark, Abbot F


    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.

  7. Animal models of premature and retarded ejaculation.

    Waldinger, Marcel D; Olivier, Berend


    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.

  8. Macrophages and Uveitis in Experimental Animal Models

    Salvador Mérida


    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.

  9. The wobbler mouse, an ALS animal model

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


    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...

  10. Geometric free energy of toric AdS4/CFT3 models

    Lee, Sangmin


    We study the supersymmetric free energy of three dimensional Chern-Simons-matter theories holographically dual to AdS$_4$ times toric Sasaki-Einstein seven-manifolds. In the large $N$ limit, we argue that the square of the free energy can be written as a quartic polynomial of trial R-charges. The coefficients of the polynomial are determined geometrically from the toric diagrams. We present the coefficients of the quartic polynomial explicitly for generic toric diagrams with up to 6 vertices, and some particular diagrams with 8 vertices. Decomposing the trial R-charges into mesonic and baryonic variables, and eliminating the baryonic ones, we show that the quartic polynomial reproduces the inverse of the Martelli-Sparks-Yau volume function. On the gravity side, we explore the possibility of using the same quartic polynomial as the prepotential in the AdS gauged supergravity. Comparing Kaluza-Klein gravity and gauged supergravity descriptions, we find perfect agreement in the mesonic sector but some discrepanc...

  11. Animal model of neuropathic tachycardia syndrome

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


    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.

  12. Mefenamic Acid Induced Nephrotoxicity: An Animal Model

    Muhammad Nazrul Somchit


    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.

  13. Animal Models of Colitis-Associated Carcinogenesis

    Manasa Kanneganti


    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.

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

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


    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

  15. Animal models in obesity and hypertension.

    Segal-Lieberman, Gabriella; Rosenthal, Talma


    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.

  16. Animal models for human craniofacial malformations.

    Johnston, M C; Bronsky, P T


    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.

  17. Probabilistic Models and Process Calculi for Mobile Ad Hoc Networks

    Song, Lei

    Due to the wide use of communicating mobile devices, mobile ad hoc networks (MANETs) have gained in popularity in recent years. In order that the devices communicate properly, many protocols have been proposed working at different levels. Devices in an MANET are not stationary but may keep moving......, thus the network topology may undergo constant changes. Moreover the devices in an MANET are loosely connected not depending on pre-installed infrastructure or central control components, they exchange messages via wireless connections which are less reliable compared to wired connections. Therefore...... issues in MANETs e.g. mobility and unreliable connections. Specially speaking, 1. We first propose a discrete probabilistic process calculus with which we can model in an MANET that the wireless connection is not reliable, and the network topology may undergo changes. We equip each wireless connection...

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

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


    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.


    Manuel Eduardo Góngora


    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.

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

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


    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.

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

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


    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

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

    Mohan Kumar Pasupuleti


    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.

  3. Animal models for HCV and HBV studies

    Isabelle Chemin


    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

  4. Practical experiences with animal fat as added fuel in the Ingolstadt power station; Praktische Erfahrungen bei der versuchsweisen Mitverbrennung von Tierfett im Kraftwerk Ingolstadt

    Gerischer, C.N. [E.ON Kraftwerke GmbH, Kraftwerksgruppe Ingolstadt/Irsching, Grossmehring (Germany)


    In 2001 the market was overflowing with animal fat due to the discussion about the bovine spongiform encephalopathy disease. One solution was the use as additional fuel in power plants. The fundamental technical requirements existed in Ingolstadt power station. Economical considerations led to the decision to test animal fat as added fuel. The main experiences are presented and discussed. (orig.)

  5. On Performance Modeling of Ad Hoc Routing Protocols

    Khayam SyedAli; Farooq Muddassar; Saleem Muhammad


    Simulation studies have been the predominant method of evaluating ad hoc routing algorithms. Despite their wide use and merits, simulations are generally time consuming. Furthermore, several prominent ad hoc simulations report inconsistent and unrepeatable results. We, therefore, argue that simulation-based evaluation of ad hoc routing protocols should be complemented with mathematical verification and comparison. In this paper, we propose a performance evaluation framework that can be used ...

  6. Preferential survival in models of complex ad hoc networks

    Kong, Joseph S.; Roychowdhury, Vwani P.


    There has been a rich interplay in recent years between (i) empirical investigations of real-world dynamic networks, (ii) analytical modeling of the microscopic mechanisms that drive the emergence of such networks, and (iii) harnessing of these mechanisms to either manipulate existing networks, or engineer new networks for specific tasks. We continue in this vein, and study the deletion phenomenon in the web by the following two different sets of websites (each comprising more than 150,000 pages) over a one-year period. Empirical data show that there is a significant deletion component in the underlying web networks, but the deletion process is not uniform. This motivates us to introduce a new mechanism of preferential survival (PS), where nodes are removed according to the degree-dependent deletion kernel, D(k)∝k, with α≥0. We use the mean-field rate equation approach to study a general dynamic model driven by Preferential Attachment (PA), Double PA (DPA), and a tunable PS (i.e., with any α>0), where c nodes ( cdynamics reported in this work can be used to design and engineer stable ad hoc networks and explain the stability of the power-law exponents observed in real-world networks.

  7. RASopathies: unraveling mechanisms with animal models

    Granton A. Jindal


    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.

  8. Using animal models to determine the significance of complement activation in Alzheimer's disease

    Loeffler David A


    Full Text Available Abstract Complement inflammation is a major inflammatory mechanism whose function is to promote the removal of microorganisms and the processing of immune complexes. Numerous studies have provided evidence for an increase in this process in areas of pathology in the Alzheimer's disease (AD brain. Because complement activation proteins have been demonstrated in vitro to exert both neuroprotective and neurotoxic effects, the significance of this process in the development and progression of AD is unclear. Studies in animal models of AD, in which brain complement activation can be experimentally altered, should be of value for clarifying this issue. However, surprisingly little is known about complement activation in the transgenic animal models that are popular for studying this disorder. An optimal animal model for studying the significance of complement activation on Alzheimer's – related neuropathology should have complete complement activation associated with senile plaques, neurofibrillary tangles (if present, and dystrophic neurites. Other desirable features include both classical and alternative pathway activation, increased neuronal synthesis of native complement proteins, and evidence for an increase in complement activation prior to the development of extensive pathology. In order to determine the suitability of different animal models for studying the role of complement activation in AD, the extent of complement activation and its association with neuropathology in these models must be understood.


    S. Baskar


    Full Text Available The Mobile Ad-hoc Networks (MANETs has gain an essential part of the attention of researchers and become very well-liked in last few years. MANETs can operate with no fixed communications and can live rapid changes in the network topology. They can be studied officially as graphs in which the set of boundaries varies in time. One of the main methods to determine the presentation of MANETs is simulation. This study proposes Enhanced Probabilistic Adhoc on Demand Distance Vector (EPAODV routing protocol, which solves the broadcast storm problem of Adhoc on Demand Distance Vector (AODV. Our evaluation of MANETs is based on the evaluation of the throughput, end to end delay and packet delivery ratio. We evaluated the end to end delay as it is one of the most important characteristic evaluation metric in computer networks. In our proposed algorithm, using a queueing model M/M/C: ∞/FIFO, we are able to enhance that better results are obtained in the case EPAODV protocol such as increasing throughput, data delivery ratio and then decreasing the end delay compare to the existing protocols.

  10. The maternal deprivation animal model revisited.

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


    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.

  11. Animal model of Mycoplasma fermentans respiratory infection

    Yáñez Antonio


    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.

  12. Epidemiological models to support animal disease surveillance activities

    Willeberg, Preben; Paisley, Larry; Lind, Peter


    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...

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

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


    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....

  14. 2004 Florida Greenway ADS40 Orthoimagery and Digital Elevation Model

    National Oceanic and Atmospheric Administration, Department of Commerce — EarthData International collected ADS-40/ISTAR-derived orthophotos at a 50 centimeter pixel resolution to produce natural color and color infrared ortho photo tiles....

  15. The Wess-Zumino Model and the $AdS_{4}/CFT_{3}$ Correspondence

    Mück, W


    We consider the non-interacting massive Wess-Zumino model in four-dimensional anti-de Sitter space and show that the conformal dimensions of the corresponding boundary fields do not always satisfy the relation expected from superconformal invariance.

  16. Lifshitz from AdS at finite temperature and top down models

    Korovin, Yegor; Taylor, Marika


    We construct analytically an asymptotically Lifshitz black brane with dynamical exponent z=1+epsilon^2 in an Einstein-Proca model, where epsilon is a small parameter. In previous work we showed that the holographic dual QFT is a deformation of a CFT by the time component of a vector operator and the parameter epsilon is the corresponding deformation parameter. In the black brane background this operator additionally acquires a vacuum expectation value. We explain how the QFT Ward identity associated with Lifshitz invariance leads to a conserved mass and compute analytically the thermodynamic quantities showing that they indeed take the form implied by Lifshitz invariance. In the second part of the paper we consider top down Lifshitz models with dynamical exponent close to one and show that they can be understood in terms of vector deformations of conformal field theories. However, in all known cases, both the conformal field theory and its Lifshitz deformations have modes that violate the Breitenlohner-Freedm...

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

    McNamee, Kay; Williams, Richard; Seed, Michael


    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.

  18. Animal models to study gluten sensitivity.

    Marietta, Eric V; Murray, Joseph A


    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.

  19. Increased hippocampal excitability in the 3xTgAD mouse model for Alzheimer's disease in vivo.

    Katherine E Davis

    Full Text Available Mouse Alzheimer's disease (AD models develop age- and region-specific pathology throughout the hippocampal formation. One recently established pathological correlate is an increase in hippocampal excitability in vivo. Hippocampal pathology also produces episodic memory decline in human AD and we have shown a similar episodic deficit in 3xTg AD model mice aged 3-6 months. Here, we tested whether hippocampal synaptic dysfunction accompanies this cognitive deficit by probing dorsal CA1 and DG synaptic responses in anaesthetized, 4-6 month-old 3xTgAD mice. As our previous reports highlighted a decline in episodic performance in aged control mice, we included aged cohorts for comparison. CA1 and DG responses to low-frequency perforant path stimulation were comparable between 3xTgAD and controls at both age ranges. As expected, DG recordings in controls showed paired-pulse depression; however, paired-pulse facilitation was observed in DG and CA1 of young and old 3xTgAD mice. During stimulus trains both short-latency (presumably monosynaptic: 'direct' and long-latency (presumably polysynaptic: 're-entrant' responses were observed. Facilitation of direct responses was modest in 3xTgAD animals. However, re-entrant responses in DG and CA1 of young 3xTgAD mice developed earlier in the stimulus train and with larger amplitude when compared to controls. Old mice showed less DG paired-pulse depression and no evidence for re-entrance. In summary, DG and CA1 responses to low-frequency stimulation in all groups were comparable, suggesting no loss of synaptic connectivity in 3xTgAD mice. However, higher-frequency activation revealed complex change in synaptic excitability in DG and CA1 of 3xTgAD mice. In particular, short-term plasticity in DG and CA1 was facilitated in 3xTgAD mice, most evidently in younger animals. In addition, re-entrance was facilitated in young 3xTgAD mice. Overall, these data suggest that the episodic-like memory deficit in 3xTgAD mice

  20. A moving mirror in AdS space as a toy model for holographic thermalization

    Erdmenger, Johanna; Ngo, Thanh Hai


    It is expected that thermalization may be described within gauge/gravity duality by considering time-dependent configurations on the gravity side of the correspondence, for instance a gravitational collapse of a matter configuration in Anti-de Sitter space. As a step towards the ambitious goal of describing such a configuration, we investigate a simple time-dependent toy model in which a mirror moves in the radial direction of Anti-de Sitter space. For this configuration, we establish a procedure for calculating two-point functions of scalar fluctuations, based on a WKB approximation. We test our method on two sample trajectories for the mirror, and find that the singularity structure of the two-point functions is in agreement with geometric optics.

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

    Gremonprez, Félix; Willaert, Wouter; Ceelen, Wim


    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.

  2. The complete guide to blender graphics computer modeling and animation

    Blain, John M


    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

  3. Performance modeling of data dissemination in vehicular ad hoc networks

    Chaqfeh, Moumena; Lakas, Abderrahmane; Lazarova-Molnar, Sanja


    Vehicular Ad hoc Networks (VANETs) have become a cornerstone component of Intelligent Transportation Systems (ITS). VANET applications present a huge potential for improving road safety and travel comfort, hence the growing interest of both academia and industry. The main advantage of VANETs is its...

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

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


    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

  5. An Integrated Approach to Flexible Modelling and Animated Simulation

    Li Shuliang; Wu Zhenye


    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.

  6. Animation of 3D Model of Human Head

    V. Michalcin


    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.

  7. Flying Ad-Hoc Networks: Routing Protocols, Mobility Models, Issues

    Muneer Bani Yassein; “Nour Alhuda” Damer


    Flying Ad-Hoc Networks (FANETs) is a group of Unmanned Air Vehicles (UAVs) which completed their work without human intervention. There are some problems in this kind of networks: the first one is the communication between (UAVs). Various routing protocols introduced classified into three categories, static, proactive, reactive routing protocols in order to solve this problem. The second problem is the network design, which depends on the network mobility, in which is the process of cooperati...

  8. Hierarchical animal movement models for population-level inference

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


    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.

  9. Rabbit as an animal model for experimental research

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


    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...

  10. Application of Animal Modeling to Biodefense Research

    Mark; A.; Suckow; ACLAM


    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...

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

    Gottlieb, Gilbert; Lickliter, Robert


    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…

  12. Aspects of animal models for major neuropsychiatric disorders

    Lefter Radu


    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.

  13. Towards an Integrated Value Adding Management Model for FM and CREM

    Jensen, Per Anker; van der Voordt, Theo


    : The process model still has to be tested on its empirical validity and practical applicability. This is being done and will be presented in a forthcoming book on how to manage and measure value adding by FM and CREM. Originality/value : The Value Adding Management process model condensates research......Purpose : To present an integrated process model of adding value by Facilities Management (FM) and Corporate Real Estate Management (CREM) that is a generalisation of existing conceptual frameworks and aims to be a basis for management of added value in practice. Background : The growing research...... aims at supporting the practical management and measurement of added value. A typology with six types of FM/CREM interventions is developed from earlier research. The concept of Value Adding Management is investigated and the 12 most important added value parameters are identified. Research limitations...

  14. Technical intelligence in animals: the kea model.

    Huber, Ludwig; Gajdon, Gyula K


    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

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

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


    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.

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

    Prabhakar, Sharma


    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.

  17. Commonly used animal models of non-alcoholic steatohepatitis

    Jian-Gao Fan; Liang Qiao


    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.

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

    Greek, Ray; Menache, Andre


    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.

  19. Penile autotransplantation in rats: An animal model

    Raouf M Seyam


    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.

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

    Ma, Xiaohan; Deng, Zhigang


    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.

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

    Vestergaard, Bill; Agersø, Henrik; Lykkesfeldt, Jens


    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.

  2. A New Tube Gastrostomy Model in Animal Experiments

    Atakan Sezer


    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

  3. Deciding the economic value added: an alternative model

    Cecilia Gallegos Muñoz


    Full Text Available The economic value creation is something that affects all companies, that is why, it is crucial to establish , for which purpose, there are a variety of procedures. Among which, especially the method of economic value added (EVA, which can compare the yield of investment to its financial cost. This methodology is very useful, but its definition does not distinguish EVA from the business effects with EVA generated results, so in this article we propose a new way to determine the EVA that allows differentiation and the EVA distinction created by many results achievable by the company. Finally, an explanatory case it is presented to demonstrate if the new proposal it is applicable or not.

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

    Md. Shahidul Islam


    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.

  5. Animal models of attention-deficit hyperactivity disorder

    Sagvolden Terje


    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

  6. Animals

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


    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.

  7. Large animal models for vaccine development and testing.

    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


    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.

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

    Nuermberger, Eric


    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.

  9. Requirements for Logical Models for Value-Added Tax Legislation

    Nielsen, Morten Ib; Simonsen, Jakob Grue; Larsen, Ken Friis

    -specific needs. Currently, these difficulties are handled in most major ERP systems by customising and localising the native code of the ERP systems for each specific country and industry. We propose an alternative that uses logical modeling of VAT legislation. The potential benefit is to eventually transform...... such a model automatically into programs that essentially will replace customisation and localisation by con¿guration by changing parameters in the model. In particular, we: (1) identify a number of requirements for such modeling, including requirements for the underlying logic; (2) model salient parts...

  10. Animal models for the study of arterial hypertension

    Waleska C Dornas; Marcelo E Silva


    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.

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


    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...

  12. Social defeat as an animal model for depression.

    Hollis, Fiona; Kabbaj, Mohamed


    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.

  13. Value-Added Models of Assessment: Implications for Motivation and Accountability

    Anderman, Eric M.; Anderman, Lynley H.; Yough, Michael S.; Gimbert, Belinda G.


    In this article, we examine the relations of value-added models of measuring academic achievement to student motivation. Using an achievement goal orientation theory perspective, we argue that value-added models, which focus on the progress of individual students over time, are more closely aligned with research on student motivation than are more…

  14. Animal Models of Human Placentation - A Review

    Carter, Anthony Michael


    , 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...

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

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


    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.

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

    W Reizner


    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.

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

    Harris, Craig


    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.

  18. MOCQL: A Declarative Language for Ad-Hoc Model Querying

    Störrle, Harald


    Language (MOCQL), an experimental declarative textual language to express queries (and constraints) on models. We introduce MOCQL by examples and its grammar, evaluate its usability by means of controlled experiments, and find that modelers perform better and experience less cognitive load when working...

  19. Strategies for fitting nonlinear ecological models in R, AD Model Builder, and BUGS

    Bolker, Benjamin M.; Gardner, Beth; Maunder, Mark; Berg, Casper W.; Brooks, Mollie; Comita, Liza; Crone, Elizabeth; Cubaynes, Sarah; Davies, Trevor; de Valpine, Perry; Ford, Jessica; Gimenez, Olivier; Kéry, Marc; Kim, Eun Jung; Lennert-Cody, Cleridy; Magunsson, Arni; Martell, Steve; Nash, John; Nielson, Anders; Regentz, Jim; Skaug, Hans; Zipkin, Elise


    1. Ecologists often use nonlinear fitting techniques to estimate the parameters of complex ecological models, with attendant frustration. This paper compares three open-source model fitting tools and discusses general strategies for defining and fitting models. 2. R is convenient and (relatively) easy to learn, AD Model Builder is fast and robust but comes with a steep learning curve, while BUGS provides the greatest flexibility at the price of speed. 3. Our model-fitting suggestions range from general cultural advice (where possible, use the tools and models that are most common in your subfield) to specific suggestions about how to change the mathematical description of models to make them more amenable to parameter estimation. 4. A companion web site ( presents detailed examples of application of the three tools to a variety of typical ecological estimation problems; each example links both to a detailed project report and to full source code and data.

  20. Animal models for testing anti-prion drugs.

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


    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.

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

    Fineman, R M; Schoenwolf, G C


    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.

  2. Medulloblastoma: Molecular Genetics and Animal Models

    Corey Raffel


    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.

  3. Assessment of Venous Thrombosis in Animal Models.

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


    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.

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

    Mirian Watanabe


    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.

  5. Effect of Xanthone Derivatives on Animal Models of Depression

    Xu Zhao, MD


    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.

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

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


    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.

  7. Technical Note: How to use Winbugs to infer animal models

    Damgaard, Lars Holm


    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...

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

    Keizo Kanasaki


    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.

  9. Analysis of animal accelerometer data using hidden Markov models


    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...

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

    Md. Shahidul Islam


    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...

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

    Benedikz, Eirikur; Kloskowska, Ewa; Winblad, Bengt


    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....

  12. Stop staring facial modeling and animation done right

    Osipa, Jason


    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;

  13. Elements of episodic-like memory in animal models.

    Crystal, Jonathon D


    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.

  14. Proteomics in farm animals models of human diseases.

    Ceciliani, Fabrizio; Restelli, Laura; Lecchi, Cristina


    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.

  15. Adding Curvature to Minimum Description Length Shape Models

    Thodberg, Hans Henrik; Ólafsdóttir, Hildur


    The Minimum Description Length (MDL) approach to shape modelling seeks a compact description of a set of shapes in terms of the coordinates of marks on the shapes. It has been shown that the mark positions resulting from this optimisation to a large extent solve the so-called point correspondence...

  16. 75 FR 54349 - Animal Models-Essential Elements To Address Efficacy Under the Animal Rule; Notice of Public...


    ... 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: ; or Susie...

  17. Animal Models Used to Explore Abdominal Aortic Aneurysms

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


    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...

  18. 75 FR 31800 - Substances Generally Recognized as Safe Added to Food for Animals; Notice of Pilot Program


    ... HUMAN SERVICES Food and Drug Administration Substances Generally Recognized as Safe Added to Food for... in food) to be safe under the conditions of their intended use. B. Elements of the GRAS Standard... determination that a food additive is safe requires technical evidence of safety, a determination that...

  19. Animals



    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.

  20. Ocular Changes in TgF344-AD Rat Model of Alzheimer's Disease


    In this study, we observed pathological changes in the choroid and in RPE cells in the TgF344-AD rat model; choroidal thinning was further observed in human AD retina. Along with Aβ deposition, the inflammatory response was manifested by microglial recruitment and complement activation.

  1. Adding Missing-Data-Relevant Variables to FIML-Based Structural Equation Models

    Graham, John W.


    Conventional wisdom in missing data research dictates adding variables to the missing data model when those variables are predictive of (a) missingness and (b) the variables containing missingness. However, it has recently been shown that adding variables that are correlated with variables containing missingness, whether or not they are related to…

  2. Rethinking Teacher Evaluation: A Conversation about Statistical Inferences and Value-Added Models

    Callister Everson, Kimberlee; Feinauer, Erika; Sudweeks, Richard R.


    In this article, the authors provide a methodological critique of the current standard of value-added modeling forwarded in educational policy contexts as a means of measuring teacher effectiveness. Conventional value-added estimates of teacher quality are attempts to determine to what degree a teacher would theoretically contribute, on average,…

  3. Review of Animal Models of Prostate Cancer Bone Metastasis

    Jessica K. Simmons


    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.

  4. AD Model Builder: using automatic differentiation for statistical inference of highly parameterized complex nonlinear models

    Fournier, David A.; Skaug, Hans J.; Ancheta, Johnoel


    of parameters. The benefits of using AD are computational efficiency and high numerical accuracy, both crucial in many practical problems. We describe the basic components and the underlying philosophy of ADMB, with an emphasis on functionality found in no other statistical software. One example......Many criteria for statistical parameter estimation, such as maximum likelihood, are formulated as a nonlinear optimization problem.Automatic Differentiation Model Builder (ADMB) is a programming framework based on automatic differentiation, aimed at highly nonlinear models with a large number...

  5. Animal models for studying dengue pathogenesis and therapy.

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


    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.

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

    Hongo, M; Ryoke, T; Ross, J


    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

  7. Hypoxic preconditioning in an autohypoxic animal model

    Guo Shao; Guo-Wei Lu


    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.

  8. Modeling Leadership Hierarchy in Multilevel Animal Societies

    Ozogány, Katalin


    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...

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

    Yoshihisa Takahashi; Yurie Soejima; Toshio Fukusato


    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.

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

    Takahashi, Yoshihisa; Soejima, Yurie; Fukusato, Toshio


    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.

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

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


    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.

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

    Takahashi, Yoshihisa; Soejima, Yurie; Fukusato, Toshio


    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

  13. Battery Performance Modelling ad Simulation: a Neural Network Based Approach

    Ottavianelli, Giuseppe; Donati, Alessandro


    This project has developed on the background of ongoing researches within the Control Technology Unit (TOS-OSC) of the Special Projects Division at the European Space Operations Centre (ESOC) of the European Space Agency. The purpose of this research is to develop and validate an Artificial Neural Network tool (ANN) able to model, simulate and predict the Cluster II battery system's performance degradation. (Cluster II mission is made of four spacecraft flying in tetrahedral formation and aimed to observe and study the interaction between sun and earth by passing in and out of our planet's magnetic field). This prototype tool, named BAPER and developed with a commercial neural network toolbox, could be used to support short and medium term mission planning in order to improve and maximise the batteries lifetime, determining which are the future best charge/discharge cycles for the batteries given their present states, in view of a Cluster II mission extension. This study focuses on the five Silver-Cadmium batteries onboard of Tango, the fourth Cluster II satellite, but time restrains have allowed so far to perform an assessment only on the first battery. In their most basic form, ANNs are hyper-dimensional curve fits for non-linear data. With their remarkable ability to derive meaning from complicated or imprecise history data, ANN can be used to extract patterns and detect trends that are too complex to be noticed by either humans or other computer techniques. ANNs learn by example, and this is why they can be described as an inductive, or data-based models for the simulation of input/target mappings. A trained ANN can be thought of as an "expert" in the category of information it has been given to analyse, and this expert can then be used, as in this project, to provide projections given new situations of interest and answer "what if" questions. The most appropriate algorithm, in terms of training speed and memory storage requirements, is clearly the Levenberg

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

    Clarke, Iain J


    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.



    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).


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


    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.

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

    Park HJ


    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

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

    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


    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.

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

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


    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.

  20. Research progress in animal models and stem cell therapy for Alzheimer’s disease

    Han F


    Full Text Available Fabin Han,1,2 Wei Wang1, Chao Chen1 1Centre for Stem Cells and Regenerative Medicine, 2Department of Neurology, Liaocheng People’s Hospital/The Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, People’s Republic of China Abstract: Alzheimer’s disease (AD causes degeneration of brain neurons and leads to memory loss and cognitive impairment. Since current therapeutic strategies cannot cure the disease, stem cell therapy represents a powerful tool for the treatment of AD. We first review the advances in molecular pathogenesis and animal models of AD and then discuss recent clinical studies using small molecules and immunoglobulins to target amyloid-beta plaques for AD therapy. Finally, we discuss stem cell therapy for AD using neural stem cells, olfactory ensheathing cells, embryonic stem cells, and mesenchymal stem cell from bone marrow, umbilical cord, and umbilical cord blood. In particular, patient-specific induced pluripotent stem cells are proposed as a future treatment for AD. Keywords: amyloid-beta plaque, neurofibrillary tangle, neural stem cell, olfactory ensheathing cell, mesenchymal stem cell, induced pluripotent stem cell

  1. Voice Communications over 802.11 Ad Hoc Networks: Modeling, Optimization and Call Admission Control

    Xu, Changchun; Xu, Yanyi; Liu, Gan; Liu, Kezhong

    Supporting quality-of-service (QoS) of multimedia communications over IEEE 802.11 based ad hoc networks is a challenging task. This paper develops a simple 3-D Markov chain model for queuing analysis of IEEE 802.11 MAC layer. The model is applied for performance analysis of voice communications over IEEE 802.11 single-hop ad hoc networks. By using the model, we finish the performance optimization of IEEE MAC layer and obtain the maximum number of voice calls in IEEE 802.11 ad hoc networks as well as the statistical performance bounds. Furthermore, we design a fully distributed call admission control (CAC) algorithm which can provide strict statistical QoS guarantee for voice communications over IEEE 802.11 ad hoc networks. Extensive simulations indicate the accuracy of the analytical model and the CAC scheme.

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

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


    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...

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

    Steele, Chad; Wormley, Floyd L


    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.

  4. Animal models of fear and anxiety: neurobehavioral descriptions

    Mora Gallegos, Andrea; Salas Castillo, Sofia


    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...




    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.

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

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


    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

  7. Energy generation for an ad hoc wireless sensor network-based monitoring system using animal head movement

    S. Nadimi, Esmaeil; Blanes-Vidal, Victoria; Jørgensen, Rasmus Nyholm;


    are not easily accessible. Therefore, exploring novel sources of energy generation rather than operating electronics only on limited power supplies such as batteries is a major challenge. Monitoring free-ranging animal behavior is an application in which the entities (animals) within the MANET are not readily...... to this problem, the equations of motion from each neck-mounted sensor as well as the amount of mechanical energy generated per time instant (each second) during upward and downward head movements were calculated. This resulted in the production of 857 mW and 1660 mW during the downward and upward movements......, respectively. Furthermore, the energy consumption of each wireless node within the MANET was estimated to be 117.8 mW per second. Conversion of energy from mechanical to electrical requires miniature electromechanical generators that can currently provide between 25% and 50% conversion efficiency. Even using...

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

    Bovenkerk, Bernice; Kaldewaij, Frederike


    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

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

    Barrett, James E


    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.

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

    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


    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

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

    Burggren, Warren W; Warburton, Stephen


    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."

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

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


    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.

  13. Rabbit as an animal model for experimental research.

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


    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.

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

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


    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

  15. On integrable deformations of superstring sigma models related to AdSn×Sn supercosets

    B. Hoare


    Full Text Available We consider two integrable deformations of 2d sigma models on supercosets associated with AdSn×Sn. The first, the “η-deformation” (based on the Yang–Baxter sigma model, is a one-parameter generalization of the standard superstring action on AdSn×Sn, while the second, the “λ-deformation” (based on the deformed gauged WZW model, is a generalization of the non-abelian T-dual of the AdSn×Sn superstring. We show that the η-deformed model may be obtained from the λ-deformed one by a special scaling limit and analytic continuation in coordinates combined with a particular identification of the parameters of the two models. The relation between the couplings and deformation parameters is consistent with the interpretation of the first model as a real quantum deformation and the second as a root of unity quantum deformation. For the AdS2×S2 case we then explore the effect of this limit on the supergravity background associated with the λ-deformed model. We also suggest that the two models may form a dual Poisson–Lie pair and provide direct evidence for this in the case of the integrable deformations of the coset associated with S2.

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

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


    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.

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

    Epps, S Alisha; Weinshenker, David


    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.

  18. Animal models of skin disease for drug discovery

    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


    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

  19. Three Family N=1 SUSY Models from Z_n Orbifolded AdS/CFT

    Kephart, T W; Kephart, Thomas W.


    We present an analysis of compactifications of the type IIB superstring on AdS_5 x S^5 / \\Gamma, where \\Gamma is an abelian cyclic group. Every \\Gamma =Z_n of order n<= 12 is considered. This results in 60 chiral models, and a systematic analysis with n<8 yields four containing the minimal SUSY standard model with three families. One of these models extends to an infinite sequence of three-family MSSMs. We also give a lower bound on the number of chiral models for all values of n.

  20. Scenario tree model for animal disease freedom framed in the OIE context using the example of a generic swine model for Aujeszky's disease in commercial swine in Canada.

    Christensen, Jette; Vallières, André


    "Freedom from animal disease" is an ambiguous concept that may have a different meaning in trade and science. For trade alone, there are different levels of freedom from OIE listed diseases. A country can: be recognized by OIE to be "officially free"; self-declare freedom, with no official recognition by the OIE; or report animal disease as absent (no occurrence) in six-monthly reports. In science, we apply scenario tree models to calculate the probability of a population being free from disease at a given prevalence to provide evidence of freedom from animal disease. Here, we link science with application by describing how a scenario tree model may contribute to a country's claim of freedom from animal disease. We combine the idea of a standardized presentation of scenario tree models for disease freedom and having a similar model for two different animal diseases to suggest that a simple generic model may help veterinary authorities to build and evaluate scenario tree models for disease freedom. Here, we aim to develop a generic scenario tree model for disease freedom that is: animal species specific, population specific, and has a simple structure. The specific objectives were: to explore the levels of freedom described in the OIE Terrestrial Animal Health Code; to describe how scenario tree models may contribute to a country's claim of freedom from animal disease; and to present a generic swine scenario tree model for disease freedom in Canada's domestic (commercial) swine applied to Aujeszky's disease (AD). In particular, to explore how historical survey data, and data mining may affect the probability of freedom and to explore different sampling strategies. Finally, to frame the generic scenario tree model in the context of Canada's claim of freedom from AD. We found that scenario tree models are useful to support a country's claim of freedom either as "recognized officially free" or as part of a self-declaration but the models should not stand alone in a

  1. Wireless Ad-hoc Network Model for Video Transmission in the Tunnel of Mine

    Zhao Xu


    Full Text Available Wireless ad hoc networks have been widely used for its flexibility and quick development, especially in emergent conditions. Recently they are introduced to coal mines underground for rescuing after disasters such as gas explosions. Significantly, we construct a network model named Chain Model to simulate the special circumstance in the tunnel of the mine. Moreover, for studying effects of different routing protocols used in this model when transmitting video data, Dynamic Destination-Sequenced Distance-Vector (DSDV, Dynamic Source Routing (DSR and Ad hoc On Demand Distance Vector (AODV are compared with each other in the experiment based on our model. The result indicates that AODV performs best among the three protocols in this model in terms of packet loss ratio, end-to-end delay time and throughput, which is significant for our future research on ad hoc networks for rescuing in coal mines underground.

  2. To Establish an Animal Model for Humans Alzheimer Disease(AD) with Closer Pathogenetic Treits bu Jointly Injecting Aβ1-40 and Aluminum into the Lateral Cerebral Ventricle of Rats%Aβ1-40和铝联合注入大鼠侧脑室内致老年性痴呆模型的实验研究

    方芳; 晏勇; 冯占辉; 刘祥琴; 文明


    目的 设计一种更贴近老年性痴呆(AD)行为特征和病理特点的多因素动物模型.方法 SD雄性大鼠侧脑室内连续注入β淀粉样蛋白1-40(Aβ1-40)和1%氯化铝溶液,首次注射时注入重组人类转化生长因子β1.术后1周开始行为学测试、病理染色和免疫组化染色.3个月后重复上述指标检测.结果 (1)大鼠学习记忆能力受损,寻找平台潜伏期比对照组延长,遭受电击次数增多(均P<0.01);(2)神经元变性,出现老年斑和神经纤维缠结;(3) 与对照组相比,胆碱乙酰转移酶活性降低,β-淀粉样蛋白活性增加(均P<0.01).结论 此模型是一种由多种致病因素共同作用的较理想的新AD动物模型.

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

    Kapicioglu, Berk; Wikelski, Martin; Broderick, Tamara


    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.

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

    A I Pearce


    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.

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

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


    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.

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

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


    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.

  7. Characteristics of Period-Adding Bursting Bifurcation Without Chaos in the Chay Neuron Model

    YANG Zhuo-Qin; LU Qi-Shao


    @@ A period-adding bursting sequence without bursting-chaos in the Chay neuron model is studied by bifurcation analysis. The genesis of each periodic bursting is separately evoked by the corresponding periodic spiking patterns through two period-doubling bifurcations, except for the period-1 bursting occurring via Hopf bifurcation. Hence,it is concluded that this period-adding bursting bifurcation without chaos has a compound bifurcation structure closely related to period-doubling bifurcations of periodic spiking in essence.

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

    Hoffman, Andrew M; Dow, Steven W


    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.

  9. Infectious diseases among animals : combining models with data

    Koeijer, A.A. de


    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

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

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


    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.

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

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


    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

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

    Jena, Ananta Kumar


    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…

  13. In search for animal models of female sexual dysfunction

    Snoeren, E.M.S.


    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

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

    Jürgen Götz


    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.

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

    Xingli Zhang; Jinchang Wu


    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.

  16. Chronic Neuroinflammation in Alzheimer’s Disease: New Perspectives on Animal Models and Promising Candidate Drugs

    Christopher Millington


    Full Text Available Chronic neuroinflammation is now considered one of the major factors in the pathogenesis of Alzheimer’s disease (AD. However, the most widely used transgenic AD models (overexpressing mutated forms of amyloid precursor protein, presenilin, and/or tau do not demonstrate the degree of inflammation, neurodegeneration (particularly of the cholinergic system, and cognitive decline that is comparable with the human disease. Hence a more suitable animal model is needed to more closely mimic the resulting cognitive decline and memory loss in humans in order to investigate the effects of neuroinflammation on neurodegeneration. One of these models is the glial fibrillary acidic protein-interleukin 6 (GFAP-IL6 mouse, in which chronic neuroinflammation triggered constitutive expression of the cytokine interleukin-6 (IL-6 in astrocytes. These transgenic mice show substantial and progressive neurodegeneration as well as a decline in motor skills and cognitive function, starting from 6 months of age. This animal model could serve as an excellent tool for drug discovery and validation in vivo. In this review, we have also selected three potential anti-inflammatory drugs, curcumin, apigenin, and tenilsetam, as candidate drugs, which could be tested in this model.

  17. A Knowledge Representation Model for Video—Based Animation

    劳志强; 潘云鹤


    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.

  18. In search for animal models of female sexual dysfunction


    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...

  19. Modelling microbial fuel cells with suspended cells and added electron transfer mediator

    Picoreanu, C.; Katuri, K.P.; Van Loosdrecht, M.C.M.; Head, I.M.; Scott, K.


    Derivation of a mathematical model for microbial fuel cells (MFC) with suspended biomass and added electron-transfer mediator is described. The model is based on mass balances for several dissolved chemical species such as substrate, oxidized mediator and reduced mediator. Biological, chemical and e

  20. Atmospheric Models of Flare Stars The Quiescent State of Ad Leo

    Mauas, P


    We compute a semi-empirical atmospheric model for the dMe star AD Leo, which constitutes the first model computed to match the continuum observations, as well as a wide set of chromospheric spectral lines. We find good agreement between the computed and observed spectral features, with the exception of the Ca II K line.

  1. Development of an AD/RANS model for predicting wind turbine wakes

    Tian, Linlin; Zhu, Wei Jun; Shen, Wen Zhong;


    methods together. The simulations are performed by using the in-house flow solver EllipSys3D coupled with the actuator disc (AD) methodology. The main objective of the proposed model is to control the turbulence decay caused by the intrinsic property of the two-equation turbu-lence model and further...

  2. Adding a medicine to the WHO model list of essential medicines.

    Kishore, S P; Herbstman, B J


    Although the concept of essential medicines is not new, the processes that lead to placement of these medicines on the World Health Organization Model List of Essential Medicines are not well understood. Here, we describe the process by which we added a class of drugs, statins, to the Model List to help combat the growing global epidemic of cardiovascular disease.

  3. Ad hoc modeling in agronomy: What have we learned in the last 15 years?

    Affholder, F.; Tittonell, P.A.; Corbeels, M.; Roux, S.; Motisi, N.; Tixier, P.; Wery, J.


    The “Use and Abuse of Crop Simulation Models” special issue of Agronomy Journal published in 1996 ended with the myth of the universal crop model. Sinclair and Seligman consequently recommended tailoring models to specific problems. This paper reviews the fate of the idea of such ad hoc approaches t

  4. Value-Added Models for Teacher Preparation Programs: Validity and Reliability Threats, and a Manageable Alternative

    Brady, Michael P.; Heiser, Lawrence A.; McCormick, Jazarae K.; Forgan, James


    High-stakes standardized student assessments are increasingly used in value-added evaluation models to connect teacher performance to P-12 student learning. These assessments are also being used to evaluate teacher preparation programs, despite validity and reliability threats. A more rational model linking student performance to candidates who…

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

    Sawiak, Stephen J; Morton, A Jennifer


    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 ( Software and anatomical population templates optimised for animal brain analysis with MRI are also available from this site.

  6. Extracts from two ubiquitous Mediterranean plants ameliorate cellular and animal models of neurodegenerative proteinopathies.

    Briffa, Michelle; Ghio, Stephanie; Neuner, Johanna; Gauci, Alison J; Cacciottolo, Rebecca; Marchal, Christelle; Caruana, Mario; Cullin, Christophe; Vassallo, Neville; Cauchi, Ruben J


    A signature feature of age-related neurodegenerative proteinopathies is the misfolding and aggregation of proteins, typically amyloid-β (Aβ) in Alzheimer's disease (AD) and α-synuclein (α-syn) in Parkinson's disease (PD), into soluble oligomeric structures that are highly neurotoxic. Cellular and animal models that faithfully replicate the hallmark features of these disorders are being increasing exploited to identify disease-modifying compounds. Natural compounds have been identified as a useful source of bioactive molecules with promising neuroprotective capabilities. In the present report, we investigated whether extracts derived from two ubiquitous Mediterranean plants namely, the prickly pear Opuntia ficus-indica (EOFI) and the brown alga Padina pavonica (EPP) alleviate neurodegenerative phenotypes in yeast (Saccharomyces cerevisiae) and fly (Drosophila melanogaster) models of AD and PD. Pre-treatment with EPP or EOFI in the culture medium significantly improved the viability of yeast expressing the Arctic Aβ42 (E22G) mutant. Supplementing food with EOFI or EPP dramatically ameliorated lifespan and behavioural signs of flies with brain-specific expression of wild-type Aβ42 (model of late-onset AD) or the Arctic Aβ42 variant (model of early-onset AD). Additionally, we show that either extract prolonged the survival of a PD fly model based on transgenic expression of the human α-syn A53T mutant. Taken together, our findings suggest that the plant-derived extracts interfere with shared mechanisms of neurodegeneration in AD and PD. This notion is strengthened by evidence demonstrating that EOFI and to a greater extent EPP, while strongly inhibiting the fibrillogenesis of both Aβ42 and α-syn, accumulate remodelled oligomeric aggregates that are less effective at disrupting lipid membrane integrity. Our work therefore opens new avenues for developing therapeutic applications of these natural plant extracts in the treatment of amyloidogenic

  7. A New Multivariate Markov Chain Model for Adding a New Categorical Data Sequence


    We propose a new multivariate Markov chain model for adding a new categorical data sequence. The number of the parameters in the new multivariate Markov chain model is only (3s) less than ((s+1)2) the number of the parameters in the former multivariate Markov chain model. Numerical experiments demonstrate the benefits of the new multivariate Markov chain model on saving computational resources.

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

    Carboni, Lucia


    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.

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

    Slater, Leo B


    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.

  10. Animal models for Ebola and Marburg virus infections

    Eri eNakayama


    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.

  11. Animal models for Ebola and Marburg virus infections.

    Nakayama, Eri; Saijo, Masayuki


    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.

  12. Modeling of Ad-hoc and Infrastructure Dual Mode Mobile Networks

    Yi-Hung Chen; Hui-Nien Hung; Yi-Bing Lin; Nan-Fu Peng


    This paper investigates a mobile telecommunications system that supports both ad hoc and infrastructure mode operations. Based on analytic and simulation models, our study investigates how base station (BS) and ad hoc channel capacity, and the mobility and locality of mobile stations affect the performance of a dual mode system. We show that a dual mode system can significantly outperform a single mode (infrastructure) system when the degree of locality is high. Furthermore, a dual mode system can support much faster mobile users with less BS channels in comparison to an infrastructure mode system. Our study quantitatively identifies the threshold value for the number of ad hoc channels such that beyond this threshold, increasing ad hoc channel capacity will not improve the performance of a dual mode system.

  13. Transmission of Helicobacter pyori in an animal model.

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


    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.

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

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


    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.

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

    Ramsden, Edmund


    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.

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

    Enderli TA


    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

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

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


    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

  18. Reproduction of an animal model of landmine blast injuries

    Sen ZHANG


    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

  19. A method of shadow puppet figure modeling and animation

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


    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.

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

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


    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.

  1. Animal models of antimuscle-specific kinase myasthenia.

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


    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.

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

    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


    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.

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

    Komeno, Yukiko; Kitaura, Jiro; Kitamura, Toshio


    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.

  4. Hand Interface in Traditional Modeling and Animation Tasks



    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.

  5. Neuroinflammation in animal models of traumatic brain injury

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


    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

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

    Challa, Siva Reddy


    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.

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

    Catherine M Rush


    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.

  8. Imaging of Cerebrovascular Pathology in Animal Models of Alzheimer`s Disease

    Jan eKlohs


    Full Text Available 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.

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

    Becker, Jill B; Koob, George F


    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.

  10. Nonalcoholic Steatohepatitis: A Search for Factual Animal Models

    Sheila Cristina L. Sanches


    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.

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

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


    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.

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

    Strickland, Justin C; Smith, Mark A


    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.

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

    Peterson, Mark E


    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.

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

    Horowitz, J. M.


    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.


    Madeleine eDuc Dodon


    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.

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

    Sigurdsson, T


    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.

  17. Behavioral impairments in animal models for zinc deficiency

    Simone eHagmeyer


    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.

  18. Large Animal Models for Foamy Virus Vector Gene Therapy

    Peter A. Horn


    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.

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

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


    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.

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

    LI Liang; SHAO Feng


    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.

  1. On numerical modeling of animal swimming and flight

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


    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.

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

    Morley, P D; Chang, Julius


    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...

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

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


    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.

  4. Cardiovascular Changes in Animal Models of Metabolic Syndrome

    Alexandre M. Lehnen


    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.

  5. Gender Differences in Animal Models of Posttraumatic Stress Disorder

    Hagit Cohen


    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.

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

    Lukashevich, Igor S


    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.

  7. Relevance of animal models to human tardive dyskinesia

    Blanchet Pierre J


    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.

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

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


    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.

  9. Noninvasive Assessment of Tumor Cell Proliferation in Animal Models

    Matthias Edinger


    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

  10. The Guinea Pig as a Model for Sporadic Alzheimer's Disease (AD: The Impact of Cholesterol Intake on Expression of AD-Related Genes.

    Mathew J Sharman

    Full Text Available We investigated the guinea pig, Cavia porcellus, as a model for Alzheimer's disease (AD, both in terms of the conservation of genes involved in AD and the regulatory responses of these to a known AD risk factor - high cholesterol intake. Unlike rats and mice, guinea pigs possess an Aβ peptide sequence identical to human Aβ. Consistent with the commonality between cardiovascular and AD risk factors in humans, we saw that a high cholesterol diet leads to up-regulation of BACE1 (β-secretase transcription and down-regulation of ADAM10 (α-secretase transcription which should increase release of Aβ from APP. Significantly, guinea pigs possess isoforms of AD-related genes found in humans but not present in mice or rats. For example, we discovered that the truncated PS2V isoform of human PSEN2, that is found at raised levels in AD brains and that increases γ-secretase activity and Aβ synthesis, is not uniquely human or aberrant as previously believed. We show that PS2V formation is up-regulated by hypoxia and a high-cholesterol diet while, consistent with observations in humans, Aβ concentrations are raised in some brain regions but not others. Also like humans, but unlike mice, the guinea pig gene encoding tau, MAPT, encodes isoforms with both three and four microtubule binding domains, and cholesterol alters the ratio of these isoforms. We conclude that AD-related genes are highly conserved and more similar to human than the rat or mouse. Guinea pigs represent a superior rodent model for analysis of the impact of dietary factors such as cholesterol on the regulation of AD-related genes.

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


    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...

  12. Shank mutant mice as an animal model of autism

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


    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,...

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

    Anne eAlbrecht; Oliver eStork


    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...

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

    Boutin, Hervé; Pinborg, Lars H.


    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 ...

  15. Animal models of tic disorders: a translational perspective.

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


    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.

  16. Impulsivity in Animal Models for Drug Abuse Disorders

    Jentsch, J. David


    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...

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

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


    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...

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

    Takahashi, Yoshihisa; Soejima, Yurie; Fukusato, Toshio


    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 ...


    Sharma Manisha


    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.

  20. NAFLD, Estrogens, and Physical Exercise: The Animal Model

    Jean-Marc Lavoie


    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.

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

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


    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.

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

    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.

  3. BLESSED with opportunistic beacons: a lightweight data dissemination model for smart mobile ad-hoc networks

    Türkes, Okan; Scholten, Hans; Havinga, Paul J.M.


    This paper introduces BLESSED, a universal opportunistic ad hoc networking model intended for smart mobile devices. It enables fast and lightweight data dissemination in wireless community networks through the complementary utilization of the IEEE 802.11 and Bluetooth Low Energy standards. As a ubiq

  4. Value-Added Model (VAM) Research for Educational Policy: Framing the Issue

    Amrein-Beardsley, Audrey; Collins, Clarin; Polasky, Sarah A.; Sloat, Edward F.


    In this manuscript, the guest editors of the EPAA Special Issue on "Value-Added Model (VAM) Research for Educational Policy" (1) introduce the background and policy context surrounding the increased use of VAMs for teacher evaluation and accountability purposes across the United States; (2) summarize the five research papers and one…

  5. Assessing the "Rothstein Falsification Test": Does It Really Show Teacher Value-Added Models Are Biased?

    Goldhaber, Dan; Chaplin, Duncan Dunbar


    In an influential paper, Jesse Rothstein (2010) shows that standard value-added models (VAMs) suggest implausible and large future teacher effects on past student achievement. This is the basis of a falsification test that "appears" to indicate bias in typical VAM estimates of teacher contributions to student learning on standardized…

  6. Doubly heavy baryons in a quark model with AdS/QCD inspired potential

    Giannuzzi, Floriana


    The spectrum of doubly heavy baryons, hadrons made up of two heavy quarks and one light quark, is computed through a potential model with relativistic kinematics. The expression for the $Q\\bar Q$ potential comes from the AdS/QCD correspondence.

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

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


    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.

  8. Animals models of gastrointestinal and liver diseases. Animal models of alcohol-induced liver disease: pathophysiology, translational relevance, and challenges.

    Mathews, Stephanie; Xu, Mingjiang; Wang, Hua; Bertola, Adeline; Gao, Bin


    Over the last four decades, chronic ethanol feeding studies in rodents using either ad libitum feeding or intragastric infusion models have significantly enhanced our understanding of the pathogenesis of alcoholic liver disease (ALD). Recently, we developed a chronic plus binge alcohol feeding model in mice that is similar to the drinking patterns of many alcoholic hepatitis patients: a history of chronic drinking and recent excessive alcohol consumption. Chronic+binge ethanol feeding synergistically induced steatosis, liver injury, and neutrophil infiltration in mice, which may be useful for the study of early alcoholic liver injury and inflammation. Using this chronic+binge model, researchers have begun to identify novel mechanisms that participate in the pathogenesis of alcoholic liver injury, thereby revealing novel therapeutic targets. In this review article, we briefly discuss several mouse models of ALD with a focus on the chronic+binge ethanol feeding model.

  9. Mobility Models for Next Generation Wireless Networks Ad Hoc, Vehicular and Mesh Networks

    Santi, Paolo


    Mobility Models for Next Generation Wireless Networks: Ad Hoc, Vehicular and Mesh Networks provides the reader with an overview of mobility modelling, encompassing both theoretical and practical aspects related to the challenging mobility modelling task. It also: Provides up-to-date coverage of mobility models for next generation wireless networksOffers an in-depth discussion of the most representative mobility models for major next generation wireless network application scenarios, including WLAN/mesh networks, vehicular networks, wireless sensor networks, and

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

    Bélanger, Mireille; Butterworth, Roger F


    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.

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

    Dearman, R J; Kimber, I


    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.

  12. Impact of Animated Spokes-Characters in Print Direct-to-Consumer Prescription Drug Advertising: An Elaboration Likelihood Model Approach.

    Bhutada, Nilesh S; Rollins, Brent L; Perri, Matthew


    A randomized, posttest-only online survey study of adult U.S. consumers determined the advertising effectiveness (attitude toward ad, brand, company, spokes-characters, attention paid to the ad, drug inquiry intention, and perceived product risk) of animated spokes-characters in print direct-to-consumer (DTC) advertising of prescription drugs and the moderating effects of consumers' involvement. Consumers' responses (n = 490) were recorded for animated versus nonanimated (human) spokes-characters in a fictitious DTC ad. Guided by the elaboration likelihood model, data were analyzed using a 2 (spokes-character type: animated/human) × 2 (involvement: high/low) factorial multivariate analysis of covariance (MANCOVA). The MANCOVA indicated significant main effects of spokes-character type and involvement on the dependent variables after controlling for covariate effects. Of the several ad effectiveness variables, consumers only differed on their attitude toward the spokes-characters between the two spokes-character types (specifically, more favorable attitudes toward the human spokes-character). Apart from perceived product risk, high-involvement consumers reacted more favorably to the remaining ad effectiveness variables compared to the low-involvement consumers, and exhibited significantly stronger drug inquiry intentions during their next doctor visit. Further, the moderating effect of consumers' involvement was not observed (nonsignificant interaction effect between spokes-character type and involvement).

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

    Gigliuto C


    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

  14. Neuroprotective Transcription Factors in Animal Models of Parkinson Disease

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


    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...

  15. An Ad-Hoc Adaptive Pilot Model for Pitch Axis Gross Acquisition Tasks

    Hanson, Curtis E.


    An ad-hoc algorithm is presented for real-time adaptation of the well-known crossover pilot model and applied to pitch axis gross acquisition tasks in a generic fighter aircraft. Off-line tuning of the crossover model to human pilot data gathered in a fixed-based high fidelity simulation is first accomplished for a series of changes in aircraft dynamics to provide expected values for model parameters. It is shown that in most cases, for this application, the traditional crossover model can be reduced to a gain and a time delay. The ad-hoc adaptive pilot gain algorithm is shown to have desirable convergence properties for most types of changes in aircraft dynamics.

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

    Eric Vela


    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.

    Vela, Eric


    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.

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


    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. Emerging Sponge Models of Animal-Microbe Symbioses

    Pita, Lucia; Fraune, Sebastian; Hentschel, Ute


    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

  20. Homoclinic Chaos in Axisymmetric Bianchi-IX cosmological models with an "ad hoc" quantum potential

    Corrêa, G. C.; Stuchi, T. J.; Jorás, S. E.


    In this work we study the dynamics of the axisymmetric Bianchi IX cosmological model with a term of quantum potential added. As it is well known this class of Bianchi IX models are homogeneous and anisotropic with two scale factors, $A(t)$ and $B(t)$, derived from the solution of Einstein's equation for General Relativity. The model we use in this work has a cosmological constant and the matter content is dust. To this model we add a quantum-inspired potential that is intended to represent sh...

  1. Security Extension on Strand Space Model for Ad-hoc Routing Protocols%Ad-hoc路由协议的串空间安全性扩展

    董学文; 牛文生; 马建峰; 盛立杰


    根据Ad-hoc移动网络特点,深入分析了串空间模型的一致性条件,提出路由五段式模型,将中继者可信条件修改为任意中继者可信条件,使串空间适用于Ad-hoc安全路由协议分析.然后以一个攻击实例验证路由五段式模型的正确性和优越性.%based on the characteristics of Ad-hoc mobile network and detail analysis of the consistency condition in strand space model,a concept of five routing segments model was brought up and intermediator credibility condition was changed into the arbitrary intermediator credibility condition, thus the strand space model was adapted to the security analysis for Ad-hoc routing protocols. Then an attack was brought to verify the correctness and superiority of the five routing segments model.

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

    Yoshikawa, Takeo


    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.

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

    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

  4. Understanding the Pathogenesis of Angelman Syndrome through Animal Models

    Nihar Ranjan Jana


    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.


    Jelena Jovanović


    Full Text Available The paper analyses creation of Balanced Scorecard, which includes environmental protection elements in AD Barska Plovidba. Firstly,the paper presents proposed models that include elements of conventional Balanced scorecard, and then we start with proposed models evaluation. In fact, as implementation and evaluation of the model in AD Barska Plovidba takes longer period of time, its evaluation and final choice is based on ISO 14598 and ISO 9126 with use of AHP method. Usually those standards are used for quality evaluation of software products, computer programs and databases inside organisation. After all, they serve as support for their development and acceptance because they provide quality evaluation during the phase when software is not yet implemented inside organistaion, what we assume as very important.

  6. A Novel Approach to Modeling and Flooding in Ad-hoc Wireless Networks

    O. Issaad


    Full Text Available This study proposes a new modeling approach for wireless ad-hoc networks. The new approach is based on the construction of fuzzy neighborhoods and essentially consists of assigning a membership or importance degree to each network radio link which reflects the relative quality of this link. This approach is first used to model the flooding problem and then an algorithm is proposed to solve this problem which is of a great importance in ad-hoc wireless networks intrinsically subject to a certain level of node mobility. Simulations carried out in a dynamic environment show promising results and stability compared to the enhanced dominant pruning algorithm. Such an approach is suitable to take into account the volatile aspect of radio links and the physical layer uncertainty when modeling these networks, particularly when the physical layer offers no or insufficient guaranties to high-level protocols as for the flooding.

  7. Landau-Lifshitz sigma-models, fermions and the AdS/CFT correspondence

    Stefanski, B


    We define Landau-Lifshitz sigma models on general coset space $G/H$, with $H$ a maximal stability sub-group of $G$. These are non-relativistic models that have $G$-valued N\\"other charges, local $H$ invariance and are classically integrable. Using this definition, we construct the $PSU(2,2|4)/PS(U(2|2)^2)$ Landau-Lifshitz sigma-model. This sigma model describes the thermodynamic limit of the spin-chain Hamiltonian obtained from the complete one-loop dilatation operator of the N=4 super Yang-Mills (SYM) theory. In the second part of the paper, we identify a number of consistent truncations of the Type IIB Green-Schwarz action on $AdS_5\\times S^5$ whose field content consists of two real bosons and 4,8 or 16 real fermions. We show that $\\kappa$-symmetry acts trivially in these sub-sectors. In the context of the large spin limit of the AdS/CFT correspondence, we map the Lagrangians of these sub-sectors to corresponding truncations of the $PSU(2,2|4)/PS(U(2|2)^2)$ Landau-Lifshitz sigma-model.

  8. Modeling and Predicting AD Progression by Regression Analysis of Sequential Clinical Data

    Xie, Qing


    Alzheimer\\'s Disease (AD) is currently attracting much attention in elders\\' care. As the increasing availability of massive clinical diagnosis data, especially the medical images of brain scan, it is highly significant to precisely identify and predict the potential AD\\'s progression based on the knowledge in the diagnosis data. In this paper, we follow a novel sequential learning framework to model the disease progression for AD patients\\' care. Different from the conventional approaches using only initial or static diagnosis data to model the disease progression for different durations, we design a score-involved approach and make use of the sequential diagnosis information in different disease stages to jointly simulate the disease progression. The actual clinical scores are utilized in progress to make the prediction more pertinent and reliable. We examined our approach by extensive experiments on the clinical data provided by the Alzheimer\\'s Disease Neuroimaging Initiative (ADNI). The results indicate that the proposed approach is more effective to simulate and predict the disease progression compared with the existing methods.

  9. Science Models as Value-Added Services for Scholarly Information Systems

    Mutschke, Peter; Schaer, Philipp; Sure, York


    The paper introduces scholarly Information Retrieval (IR) as a further dimension that should be considered in the science modeling debate. The IR use case is seen as a validation model of the adequacy of science models in representing and predicting structure and dynamics in science. Particular conceptualizations of scholarly activity and structures in science are used as value-added search services to improve retrieval quality: a co-word model depicting the cognitive structure of a field (used for query expansion), the Bradford law of information concentration, and a model of co-authorship networks (both used for re-ranking search results). An evaluation of the retrieval quality when science model driven services are used turned out that the models proposed actually provide beneficial effects to retrieval quality. From an IR perspective, the models studied are therefore verified as expressive conceptualizations of central phenomena in science. Thus, it could be shown that the IR perspective can significantly...

  10. A Mobility and Traffic Generation Framework for Modeling and Simulating Ad Hoc Communication Networks

    Chris Barrett


    Full Text Available We present a generic mobility and traffic generation framework that can be incorporated into a tool for modeling and simulating large scale ad~hoc networks. Three components of this framework, namely a mobility data generator (MDG, a graph structure generator (GSG and an occlusion modification tool (OMT allow a variety of mobility models to be incorporated into the tool. The MDG module generates positions of transceivers at specified time instants. The GSG module constructs the graph corresponding to the ad hoc network from the mobility data provided by MDG. The OMT module modifies the connectivity of the graph produced by GSG to allow for occlusion effects. With two other modules, namely an activity data generator (ADG which generates packet transmission activities for transceivers and a packet activity simulator (PAS which simulates the movement and interaction of packets among the transceivers, the framework allows the modeling and simulation of ad hoc communication networks. The design of the framework allows a user to incorporate various realistic parameters crucial in the simulation. We illustrate the utility of our framework through a comparative study of three mobility models. Two of these are synthetic models (random waypoint and exponentially correlated mobility proposed in the literature. The third model is based on an urban population mobility modeling tool (TRANSIMS developed at the Los Alamos National Laboratory. This tool is capable of providing comprehensive information about the demographics, mobility and interactions of members of a large urban population. A comparison of these models is carried out by computing a variety of parameters associated with the graph structures generated by the models. There has recently been interest in the structural properties of graphs that arise in real world systems. We examine two aspects of this for the graphs created by the mobility models: change associated with power control (range of

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

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


    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

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

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


    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.

  13. Hepatoprotective activity of Musa paradisiaca on experimental animal models

    Nirmala M; Girija K; Lakshman K; Divya T


    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.

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

    D. M. Hyde


    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.

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

    Hirose, Jun; Tanaka, Sakae


    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.

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

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


    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)

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

    Buschard, Karsten


    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

  18. New insights into autoimmune cholangitis through animal models.

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


    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.

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

    McColl B


    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

  20. Triptolide treatment reduces Alzheimer’s disease (AD-like pathology through inhibition of BACE1 in a transgenic mouse model of AD

    Qi Wang


    Full Text Available The complex pathogenesis of Alzheimer’s disease (AD involves multiple contributing factors, including amyloid β (Aβ peptide accumulation, inflammation and oxidative stress. Effective therapeutic strategies for AD are still urgently needed. Triptolide is the major active compound extracted from Tripterygium wilfordii Hook.f., a traditional Chinese medicinal herb that is commonly used to treat inflammatory diseases. The 5-month-old 5XFAD mice, which carry five familial AD mutations in the β-amyloid precursor protein (APP and presenilin-1 (PS1 genes, were treated with triptolide for 8 weeks. We observed enhanced spatial learning performances, and attenuated Aβ production and deposition in the brain. Triptolide also inhibited the processing of amyloidogenic APP, as well as the expression of βAPP-cleaving enzyme-1 (BACE1 both in vivo and in vitro. In addition, triptolide exerted anti-inflammatory and anti-oxidative effects on the transgenic mouse brain. Triptolide therefore confers protection against the effects of AD in our mouse model and is emerging as a promising therapeutic candidate drug for AD.

  1. Ad Hoc网络节点毁坏的拟生灭模型%Quasi-Birth-and-Death Model for Destruction of Ad Hoc Network Nodes

    夏文洁; 严悍; 刘凤玉


    Ad hoc网络中由于节点通信是分布式的,网络中的节点毁坏会影响通信链路的中断甚至导致某些书点不可达.为此,基于M/M/C排队系统,通过合理假设,建它一个Ad hoc网络中节点毁坏及处理过程的拟生灭模型.运用矩阵分析法,在给定参数下,求得稳态概率、毁坏节点的平均队长、毁坏节点到达时无需等待的概率等.该模型能够在保证系统正常工作的情况下,提高Ad hoc网络节点维护效率,为制定维护策略提供参考.%This paper presents a Quasi-Birth-and-Death(QBD) model for damaged nodes in Ad hoc network.Since the communication in Ad hoc network is distributed, the destruction of nodes in the route between transmitter and receiver will break off the communication.Too many damaged nodes will result in some nodes unreachable.By assuming damaged vehicles' arrival be subject to Poisson process, repair time and vacation time be exponentially distributed, it creats QBD model for Ad hoc network nodes damage and fix process, uses matrix analysis method to get stationary distribution, and then obtains damage nodes average queue length, the probability of no need to wait and so on.It is helpful on saving resources while keeping the network stability, can be a reference when make maintenance strategy.

  2. Nonrelativistic limit of the abelianized ABJM model and the ADS/CMT correspondence

    Lopez-Arcos, Cristhiam; Murugan, Jeff; Nastase, Horatiu


    We consider the nonrelativistic limit of the abelian reduction of the massive ABJM model proposed in [1], obtaining a supersymmetric version of the Jackiw-Pi model. The system exhibits an mathcal{N}=2 Super-Schrödinger symmetry with the Jackiw-Pi vortices emerging as BPS solutions. We find that this (2 + 1)-dimensional abelian field theory is dual to a certain (3+1)-dimensional gravity theory that differs somewhat from previously considered abelian condensed matter stand-ins for the ABJM model. We close by commenting on progress in the top-down realization of the AdS/CMT correspondence in a critical string theory.

  3. Performance Analysis for Mobile Ad Hoc Network in Random Graph Models with Spatial Reuse

    Han-xing Wang; Xi Hu; Qin Zhang


    In this paper,we present a random graph model with spatial reuse for a mobile ad hoc network (MANET) based on the dynamic source routing protocol.Many important performance parameters of the MANET are obtained,such as the average flooding distance (AFD),the probability generating function of the flooding distance,and the probability of a flooding route to be symmetric.Compared with the random graph model without spatial reuse,this model is much more effective because it has a smaller value of AFD and a larger probability for finding a symmetric valid route.

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

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


    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.


    T.R. Neyestani


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

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


    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.

  7. A joint shadowing process model for multihop/ad-hoc networks in urban environment.

    Wang, Z.(Institute of High Energy Physics, Beijing, China); Tameh, EK; Nix, AR; Gasparini, Otello


    For multihop/Ad-hoc networks, the conventional one-dimensional (1-D) channel model cannot capture the spatial correlation of the shadowing processes. This paper investigates the joint spatial/temporal correlation property the shadowing process for peer-to-peer radio links in urban environments. Statistical analysis reveals that the shadowing process is mainly a result of the movement at the mobile station (MS) side. Furthermore, the joint correlation property of the MS-MS channel shows that M...

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

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


    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.

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

    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: [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)


    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.

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

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


    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

  11. An Agent Based Intrusion Detection Model for Mobile Ad Hoc Networks

    B. M. Reshmi


    Full Text Available Intrusion detection has over the last few years, assumed paramount importance within the broad realm of network security, more so in case of wireless mobile ad hoc networks. The inherently vulnerable characteristics of wireless mobile ad hoc networks make them susceptible to attacks in-spite of some security measures, and it may be too late before any counter action can take effect. As such, there is a need to complement traditional security mechanisms with efficient intrusion detection and response systems. This paper proposes an agent-based model to address the aspect of intrusion detection in cluster based mobile wireless ad hoc network environment. The model comprises of a set of static and mobile agents, which are used to detect intrusions, respond to intrusions, and distribute selected and aggregated intrusion information to all other nodes in the network in an intelligent manner. The model is simulated to test its operation effectiveness by considering the performance parameters such as, detection rate, false positives, agent overheads, and intrusion information distribution time. Agent based approach facilitates flexible and adaptable security services. Also, it supports component based software engineering components such as maintainability, reachability, reusability, adaptability, flexibility, and customization.

  12. A New Model for the Collective Behavior of Animals

    Nguyen, P The; Diep, H T


    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...

  13. An intermediate animal model of spinal cord stimulation

    Thomas Guiho


    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.

  14. Experimental animal data and modeling of late somatic effects

    Fry, R.J.M.


    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.

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

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


    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

  16. Perinatal Cerebellar Injury in Human and Animal Models

    Valerie Biran


    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.

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

    Jeffery L. Larkin


    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.

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

    Bernabeu, Ramon


    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

  19. Renormalised AdS$_5$ Mass for Even Spin Glueball and Pomeron Regge Trajectory from a Modified Holographic softwall model

    Capossoli, Eduardo Folco


    In this work, adopting a $5-$dimensional mass renormalisation within a modified holographic softwall model, we calculate analytically the masses of the scalar glueball with its radial excitations and of higher even glueball spin states, with $P=C=+1$. Using this approach we achieved a unified treatment for both scalar and high even spin glueballs. Furthermore, we also obtain the Regge trajectory associated with the pomeron compatible with other approaches.

  20. Animal Models of Leptospirosis: Of Mice and Hamsters

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


    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

  1. The behavioral, pathological and therapeutic features of the senescence-accelerated mouse prone 8 strain as an Alzheimer's disease animal model.

    Cheng, Xiao-rui; Zhou, Wen-xia; Zhang, Yong-xiang


    Alzheimer's disease (AD) is a widespread and devastating progressive neurodegenerative disease. Disease-modifying treatments remain beyond reach, and the etiology of the disease is uncertain. Animal model are essential for identifying disease mechanisms and developing effective therapeutic strategies. Research on AD is currently being carried out in rodent models. The most common transgenic mouse model mimics familial AD, which accounts for a small percentage of cases. The senescence-accelerated mouse prone 8 (SAMP8) strain is a spontaneous animal model of accelerated aging. Many studies indicate that SAMP8 mice harbor the behavioral and histopathological signatures of AD, namely AD-like cognitive and behavioral alterations, neuropathological phenotypes (neuron and dendrite spine loss, spongiosis, gliosis and cholinergic deficits in the forebrain), β-amyloid deposits resembling senile plaques, and aberrant hyperphosphorylation of Tau-like neurofibrillary tangles. SAMP8 mice are useful in the development of novel therapies, and many pharmacological agents and approaches are effective in SAMP8 mice. SAMP8 mice are considered a robust model for exploring the etiopathogenesis of sporadic AD and a plausible experimental model for developing preventative and therapeutic treatments for late-onset/age-related AD, which accounts for the vast majority of cases.

  2. Packet Transmission Analysis in Vehicular Ad Hoc Networks using Revival Mobility Model



    Full Text Available Vehicular Ad-hoc Networks (VANETs have been recently attracting an increasing attention from both research and industry communities. VANETs are currently deployed on a large scale, research in this area is mostly simulation based. Mobility models or the movement patterns of nodes communicating wirelessly, play a vital role in determining the protocol performance in VANET. We still have a limited understanding of the required level of mobility details for modeling and simulating VANETs. Thus, it is essential to study and analyze various mobility models and their effect on VANET protocols. In this paper, we examine d different mobility models proposed in the recent research literature. We proposed Revival Mobility Model (RMM and evaluate its effect on packet delivery in VANETs by ns-2 simulations.

  3. A Leasing Model to Deal with Partial Failures in Mobile Ad Hoc Networks

    Gonzalez Boix, Elisa; van Cutsem, Tom; Vallejos, Jorge; de Meuter, Wolfgang; D'Hondt, Theo

    In mobile ad hoc networks (MANETs) many partial failures are the result of temporary network partitions due to the intermittent connectivity of mobile devices. Some of these failures will be permanent and require application-level failure handling. However, it is impossible to distinguish a permanent from a transient failure. Leasing provides a solution to this problem based on the temporal restriction of resources. But to date no leasing model has been designed specifically for MANETs. In this paper, we identify three characteristics required for a leasing model to be usable in a MANET, discuss the issues with existing leasing models and then propose the leased object references model, which integrates leasing with remote object references. In addition, we describe an implementation of the model in the programming language AmbientTalk. Leased object references provide an extensible framework that allows programmers to express their own leasing patterns and enables both lease holders (clients) and lease grantors (services) to deal with permanent failures.

  4. Homoclinic Spike adding in a neuronal model in the presence of noise

    Fuwape, Ibiyinka; Neiman, Alexander; Shilnikov, Andrey


    We study the influence of noise on a spike adding transitions within the bursting activity in a Hodgkin-Huxley-type model of the leech heart interneuron. Spike adding in this model occur via homoclinic bifurcation of a saddle periodic orbit. Although narrow chaotic regions are observed near bifurcation transition, overall bursting dynamics is regular and is characterized by a constant number of spikes per burst. Experimental studies, however, show variability of bursting patterns whereby number of spikes per burst varies randomly. Thus, introduction of external synaptic noise is a necessary step to account for variability of burst durations observed experimentally. We show that near every such transition the neuron is highly sensitive to random perturbations that lead to and enhance broadly the regions of chaotic dynamics of the cell. For each spike adding transition there is a critical noise level beyond which the dynamics of the neuron becomes chaotic throughout the entire region of the given transition. Noise-induced chaotic dynamics is characterized in terms of the Lyapunov exponents and the Shannon entropy and reflects variability of firing patterns with various numbers of spikes per burst, traversing wide range of the neuron's parameters

  5. Added Mass Effect and an Extended Unsteady Blade ElementModel of Insect Hovering

    Xingyao Yan; Shanan Zhu; Zhongdi Su; Hongjun Zhang


    During the insect flight,the force peak at the start of each stroke contributes a lot to the total aerodynamic force.Yet how this force is generated is still controversial.Two current explanations to this are wake capture and Added Mass Effect (AME)mechanisms.To study the AME,we present an extended unsteady blade element model which takes both the added mass of fluid and rotational effect of the wing into account.Simulation results show a high force peak at the start of each stroke and are quite similar to the measured forces on the physical wing model.We found that although the Added Mass Force (AMF) of the medium contributes a lot to this force peak,the wake capture effect further augments this force and may play a more important role in delayed mode.Furthermore,we also found that there might be an unknown mechanism which may augment the AME during acceleration period at the start of each stroke,and diminish the AME during deceleration at the end of each stroke.

  6. Modified activity-stress paradigm in an animal model of the female athlete triad.

    Dimarco, Nancy M; Dart, Lyn; Sanborn, Charlotte Barney


    The exercising woman with nutritional deficits and related menstrual irregularities is at risk of compromising long-term bone health, i.e., the female athlete triad. There is no animal model of the female athlete triad. The purpose of this study was to examine long-term energy restriction in voluntary wheel-running female rats on estrous cycling, bone mineral content, and leptin levels. Twelve female Sprague-Dawley rats (age 34 days) were fed ad libitum and given access to running wheels during an initial 14-wk period, providing baseline and age-related data. Daily collection included dietary intake, body weight, estrous cycling, and voluntary running distance. At 4 mo, rats were randomized into two groups, six restrict-fed rats (70% of ad libitum intake) and six rats continuing as ad libitum-fed controls. Energy intake, energy expenditure, and energy availability (energy intake - energy expenditure) were calculated for each animal. Serum estradiol and leptin concentrations were measured by RIA. Femoral and tibial bone mineral density and bone mineral content (BMC) were determined by dual-energy X-ray absorptiometry. Restrict-fed rats exhibited a decrease in energy availability during Weight Loss and Anestrous phases (P = 0.002). Compared with controls after 12 wk, restrict-fed rats showed reduced concentrations of serum estradiol (P = 0.002) and leptin (P = 0.002), lower ovarian weight (P = 0.002), and decreased femoral (P = 0.041) and tibial (P = 0.05) BMC. Decreased energy availability resulted in anestrus and significant decreases in BMC, estrogen and leptin levels, and body weight. Finally, there is a critical level of energy availability to maintain estrous cycling.

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

    Leila O Zanjani


    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

  8. Drug discovery of antimicrobial photosensitizers using animal models.

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


    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

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

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


    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....

  10. Constraints on tachyon inflationary models with an AdS/CFT correspondence

    Bouabdallaoui, Zahra; Bouhmadi-Lopez, Mariam; Ouali, Taoufik


    In order to study the effect of the anti de Sitter/ conformal field theory correspondence (AdS/CFT) on the primordial inflationary era, we consider a universe filled with a tachyon field in a slow-roll regime. In this context, the background and perturbative parameters characterising the inflationary era are related to the standard one by correction terms. We show a clear agreement between the theoretical prediction and the observational data for the above mentioned model. The main results of our work are illustrated for an exponential potential. We show that, for a suitable conformal anomaly coefficient, AdS/CFT correspondence might leave its imprints on the spectrum of the gravitational waves amplitude with a tensor to scalar ratio, $r$, of the perturbations compatible with Planck data.

  11. Constraints on tachyon inflationary models with an AdS/CFT correspondence

    Bouabdallaoui, Zahra; Errahmani, Ahmed; Bouhmadi-López, Mariam; Ouali, Taoufik


    To study the effect of the anti-de Sitter/conformal field theory correspondence (AdS/CFT) on the primordial inflationary era, we consider a universe filled with a tachyon field in a slow-roll regime. In this context, the background and perturbative parameters characterizing the inflationary era are related to the standard one by correction terms. We show a clear agreement between the theoretical prediction and the observational data for the above-mentioned model. The main results of our work are illustrated for an exponential potential. We show that, for a suitable conformal anomaly coefficient, AdS/CFT correspondence might leave its imprints on the spectrum of the gravitational waves amplitude with a tensor to scalar ratio, r , of the perturbations compatible with Planck data.

  12. Stochastic seismic response of structures with added viscoelastic dampers modeled by fractional derivative

    叶昆; 李黎; 唐家祥


    Viscoelastic dampers, as supplementary energy dissipation devices, have been used in building structures under seismic excitation or wind loads. Different analytical models have been proposed to describe their dynamic force deformation characteristics. Among these analytical models, the fractional derivative models have attracted more attention as they can capture the frequency dependence of the material stiffness and damping properties observed from tests very well. In this paper, a Fourier-transform-based technique is presented to obtain the fractional unit impulse function and the response of structures with added viscoelastic dampers whose force-deformation relationship is described by a fractional derivative model. Then, a Duhamel integral-type expression is suggested for the response analysis of a fractional damped dynamic system subjected to deterministic or random excitation. Through numerical verification, it is shown that viscoelastic dampers are effective in reducing structural responses over a wide frequency range, and the proposed schemes can be used to accurately predict the stochastic seismic response of structures with added viscoelastic dampers described by a Kelvin model with fractional derivative.

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

    Chao, Edmund Y S


    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.

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

    Ohlemiller, Kevin K


    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

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

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


    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.

  16. Hair loss and regeneration performed on animal models.

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


    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.

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

    Siro Luvisetto


    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.

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

    Pavone, Flaminia; Luvisetto, Siro


    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.

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

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


    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.

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

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


    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.

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

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


    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.

  2. Man in space - The use of animal models

    Ballard, Rodney W.; Souza, Kenneth A.


    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.

  3. Probabilistic Modelling of Information Propagation in Wireless Mobile Ad-Hoc Network

    Schiøler, Henrik; Hansen, Martin Bøgsted; Schwefel, Hans-Peter


    In this paper the dynamics of broadcasting wireless ad-hoc networks is studied through probabilistic modelling. A randomized transmission discipline is assumed in accordance with existing MAC definitions such as WLAN with Decentralized Coordination or IEEE-802.15.4. Message reception is assumed...... to be governed by node power-down policies and is equivalently assumed to be randomized. Altogether randomization facilitates a probabilistic model in the shape of an integro-differential equation governing the propagation of information, where brownian node mobility may be accounted for by including an extra...... diffusion term. The established model is analyzed for transient behaviour and a travelling wave solution facilitates expressions for propagation speed as well as parametrized analysis of network reliability and node power consumption. Applications of the developed models for node localization and network...

  4. Chronic Anatabine Treatment Reduces Alzheimer's Disease (AD-Like Pathology and Improves Socio-Behavioral Deficits in a Transgenic Mouse Model of AD.

    Megha Verma

    Full Text Available Anatabine is a minor tobacco alkaloid, which is also found in plants of the Solanaceae family and displays a chemical structure similarity with nicotine. We have shown previously that anatabine displays some anti-inflammatory properties and reduces microgliosis and tau phosphorylation in a pure mouse model of tauopathy. We therefore investigated the effects of a chronic oral treatment with anatabine in a transgenic mouse model (Tg PS1/APPswe of Alzheimer's disease (AD which displays pathological Aβ deposits, neuroinflammation and behavioral deficits. In the elevated plus maze, Tg PS1/APPswe mice exhibited hyperactivity and disinhibition compared to wild-type mice. Six and a half months of chronic oral anatabine treatment, suppressed hyperactivity and disinhibition in Tg PS1/APPswe mice compared to Tg PS1/APPswe receiving regular drinking water. Tg PS1/APPswe mice also elicited profound social interaction and social memory deficits, which were both alleviated by the anatabine treatment. We found that anatabine reduces the activation of STAT3 and NFκB in the vicinity of Aβ deposits in Tg PS1/APPswe mice resulting in a reduction of the expression of some of their target genes including Bace1, iNOS and Cox-2. In addition, a significant reduction in microgliosis and pathological deposition of Aβ was observed in the brain of Tg PS1/APPswe mice treated with anatabine. This is the first study to investigate the impact of chronic anatabine treatment on AD-like pathology and behavior in a transgenic mouse model of AD. Overall, our data show that anatabine reduces β-amyloidosis, neuroinflammation and alleviates some behavioral deficits in Tg PS1/APPswe, supporting further exploration of anatabine as a possible disease modifying agent for the treatment of AD.

  5. Directed Dynamic Small-World Network Model for Worm Epidemics in Mobile ad hoc Networks

    ZHU Chen-Ping; WANG Li; LIU Xiao-Ting; YAN Zhi-Jun


    We investigate the worm spreading process in mobile ad hoc networks with a susceptible-infected-recovered model on a two-dimensional plane.A medium access control mechanism operates within it,inhibiting transmission and relaying a message by using other nodes inside the node's transmitting circle during speaking.We measure the rewiring probability p with the transmitting range r and the average relative velocity (v) of the moving nodes,and map the problem into a directed dynamic small-world network.A new scaling relation for the recovered portion of the nodes reveals the effect caused by geometric distance,which has been ignored by previous models.%We investigate the worm spreading process in mobile ad hoc networks with a susceptible-infected-recovered model on a two-dimensional plane. A medium access control mechanism operates within it, inhibiting transmission and relaying a message by using other nodes inside the node's transmitting circle during speaking. We measure the rewiring probability p with the transmitting range r and the average relative velocity (v) of the moving nodes, and map the problem into a directed dynamic small-world network. A new scaling relation for the recovered portion of the nodes reveals the effect caused by geometric distance, which has been ignored by previous models.

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

    Xue Ming


    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. Spin Matrix theory: a quantum mechanical model of the AdS/CFT correspondence

    Harmark, Troels; Orselli, Marta


    We introduce a new quantum mechanical theory called Spin Matrix theory (SMT). The theory is interacting with a single coupling constant g and is based on a Hilbert space of harmonic oscillators with a spin index taking values in a Lie (super)algebra representation as well as matrix indices for the adjoint representation of U( N). We show that SMT describes super-Yang-Mills theory (SYM) near zero-temperature critical points in the grand canonical phase diagram. Equivalently, SMT arises from non-relativistic limits of SYM. Even though SMT is a non-relativistic quantum mechanical theory it contains a variety of phases mimicking the AdS/CFT correspondence. Moreover, the g → ∞ limit of SMT can be mapped to the supersymmetric sector of string theory on AdS5 × S 5. We study SU(2) SMT in detail. At large N and low temperatures it is a theory of spin chains that for small g resembles planar gauge theory and for large g a non-relativistic string theory. When raising the temperature a partial deconfinement transition occurs due to finite- N effects. For sufficiently high temperatures the partially deconfined phase has a classical regime. We find a matrix model description of this regime at any coupling g. Setting g = 0 it is a theory of N 2 + 1 harmonic oscillators while for large g it becomes 2 N harmonic oscillators.

  8. Hierarchical interactions model for predicting Mild Cognitive Impairment (MCI to Alzheimer's Disease (AD conversion.

    Han Li

    Full Text Available Identifying patients with Mild Cognitive Impairment (MCI who are likely to convert to dementia has recently attracted increasing attention in Alzheimer's disease (AD research. An accurate prediction of conversion from MCI to AD can aid clinicians to initiate treatments at early stage and monitor their effectiveness. However, existing prediction systems based on the original biosignatures are not satisfactory. In this paper, we propose to fit the prediction models using pairwise biosignature interactions, thus capturing higher-order relationship among biosignatures. Specifically, we employ hierarchical constraints and sparsity regularization to prune the high-dimensional input features. Based on the significant biosignatures and underlying interactions identified, we build classifiers to predict the conversion probability based on the selected features. We further analyze the underlying interaction effects of different biosignatures based on the so-called stable expectation scores. We have used 293 MCI subjects from Alzheimer's Disease Neuroimaging Initiative (ADNI database that have MRI measurements at the baseline to evaluate the effectiveness of the proposed method. Our proposed method achieves better classification performance than state-of-the-art methods. Moreover, we discover several significant interactions predictive of MCI-to-AD conversion. These results shed light on improving the prediction performance using interaction features.

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

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


    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.

  10. Animal Models for Influenza Virus Pathogenesis and Transmission

    Anice C. Lowen


    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.

  11. An animal model of emotional blunting in schizophrenia.

    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.

  12. Development of a model animal welfare act curriculum.

    VandeWoude, Sue


    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.

  13. Charm structure functions and gluon shadowing effects with the AdS/CFT model

    WANG Hong-Min; HOU Zhao-Yu; LIU Jia-Fu; SUN Xian-Jing


    By means of the UGD function extracted from an AdS/CFT inspired saturation model,the charm and bottom structure functions are studied in fixed-order perturbation theory.It is shown that the theoretical results are in good agreement with the recent HERA data.Then,this UGD function is also used to investigate net-kaon rapidity distribution in Au+Au collisions at RHIC energies and the theoretical results fit well to the BRAHMS data.In the end of this paper,we give the predicted results for nuclear charm structure function at very small x where the popular shadowing parameterizations are invalid.

  14. Charm structure functions and gluon shadowing effects with the AdS/CFT model

    Wang, Hong-Min; Hou, Zhao-Yu; Liu, Jia-Fu; Sun, Xian-Jing


    By means of the UGD function extracted from an AdS/CFT inspired saturation model, the charm and bottom structure functions are studied in fixed-order perturbation theory. It is shown that the theoretical results are in good agreement with the recent HERA data. Then, this UGD function is also used to investigate net-kaon rapidity distribution in Au+Au collisions at RHIC energies and the theoretical results fit well to the BRAHMS data. In the end of this paper, we give the predicted results for nuclear charm structure function at very small x where the popular shadowing parameterizations are invalid.

  15. Thermal width of heavy quarkonia from an AdS/QCD model

    Braga, Nelson R F


    We estimate the thermal width of a heavy quark anti-quark pair inside a strongly coupled plasma using a holographic AdS/QCD model. The imaginary part of the quark potential that produces the thermal width appears in the gravity dual from quantum fluctuations of the string world sheet in the vicinity of the horizon. The results, obtained using a soft wall background that involves an infrared mass scale, are consistent with previous analisys where the mass scale was introduced by averaging over quark anti-quark states.

  16. Nonrelativistic limit of the abelianized ABJM model and the ADS/CMT correspondence

    Lopez-Arcos, Cristhiam; Nastase, Horatiu


    We consider the nonrelativistic limit of the abelian reduction of the massive ABJM model proposed in \\cite{Mohammed:2012gi}, obtaining a supersymmetric version of the Jackiw-Pi model. The system exhibits an ${\\cal N}=2$ Super-Schr\\"odinger symmetry with the Jackiw-Pi vortices emerging as BPS solutions. We find that this $(2+1)$-dimensional abelian field theory is dual to a certain (3+1)-dimensional gravity theory that differs somewhat from previously considered abelian condensed matter stand-ins for the ABJM model. We close by commenting on progress in the top-down realization of the AdS/CMT correspondence in a critical string theory.

  17. Pramipexole reduces inflammation in the experimental animal models of inflammation.

    Sadeghi, Heibatollah; Parishani, Mohammad; Akbartabar Touri, Mehdi; Ghavamzadeh, Mehdi; Jafari Barmak, Mehrzad; Zarezade, Vahid; Delaviz, Hamdollah; Sadeghi, Hossein


    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.

  18. Molecular genetics and animal models in autistic disorder.

    Andres, Christian


    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.

  19. Recent advances in animal models of diabetic nephropathy.

    Betz, Boris; Conway, Bryan R


    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.

  20. Genetic Aspects of Autism Spectrum Disorders: Insights from Animal Models

    Swati eBanerjee


    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.

  1. Evaluation of Medical Cystine Stone Prevention in an Animal Model

    Sagi, Sreedhar; Wendt-Nordahl, Gunnar; Alken, Peter; Knoll, Thomas


    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.

  2. Molecular Imaging of Vulnerable Atherosclerotic Plaques in Animal Models

    Gargiulo, Sara; Gramanzini, Matteo; Mancini, Marcello


    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

  3. Neuropathology and Animal Models of Autism: Genetic and Environmental Factors

    Bharathi S. Gadad


    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.

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

    Herati, Ramin Sedaghat; Wherry, E John


    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. Hill-type muscle model parameters determined from experiments on single muscles show large animal-to-animal variation.

    Blümel, Marcus; Guschlbauer, Christoph; Daun-Gruhn, Silvia; Hooper, Scott L; Büschges, Ansgar


    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.


    Natarajan Meghanathan


    Full Text Available We compare the probability of k-Connectivity of an ad hoc network under Random Way Point (RWP,City Section and Manhattan mobility models. A Network is said to be k-Connected if there exists at least kedge disjoint paths between any pair of nodes in that network at any given time and velocity. Initially, foreach of the three mobility models, the movement of the each node in the ad hoc network at a givenvelocity and time are captured and stored in the Node Movement Database (NMDB. Using themovements in the NMDB, the location of the node at a given time is computed and stored in the NodeLocation Database (NLDB. A weighted graph is created using the location of the nodes from NLDB,which is converted into a residual graph. The k-Connectivity of this residual graph is obtained by runningFord-Fulkerson’s algorithm on it. Ford Fulkerson’s algorithm computes the maximum flow of a networkby recording the flows assigned to different routes from each node to all the other nodes in the network.When run for a particular source-destination pair (s, d pair on a residual network graph with unit edgeweights as capacity, the maximum flow determined by Ford-Fulkerson’ algorithm is the number of edgedisjoint s-d paths on the network graph. Simulations show that the RWP model yields the highestprobability of k-Connectivity compared to City Section and Manhattan mobility models for a majority ofdifferent node densities and velocities considered. Simulation results also show that, for all the threemobility models, as the k value increases, the probability of k-Connectivity decreases for a given densityand velocity and as the density increases the probability of k-Connectivity increases.

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

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


    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.

  8. Null-polygonal minimal surfaces in AdS{sub 4} from perturbed W minimal models

    Hatsuda, Yasuyuki [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Ito, Katsushi [Tokyo Institute of Technology (Japan). Dept. of Physics; Satoh, Yuji [Tsukuba Univ., Sakura, Ibaraki (Japan). Inst. of Physics


    We study the null-polygonal minimal surfaces in AdS{sub 4}, which correspond to the gluon scattering amplitudes/Wilson loops in N=4 super Yang-Mills theory at strong coupling. The area of the minimal surfaces with n cusps is characterized by the thermodynamic Bethe ansatz (TBA) integral equations or the Y-system of the homogeneous sine-Gordon model, which is regarded as the SU(n-4){sub 4}/U(1){sup n-5} generalized parafermion theory perturbed by the weight-zero adjoint operators. Based on the relation to the TBA systems of the perturbed W minimal models, we solve the TBA equations by using the conformal perturbation theory, and obtain the analytic expansion of the remainder function around the UV/regular-polygonal limit for n = 6 and 7. We compare the rescaled remainder function for n=6 with the two-loop one, to observe that they are close to each other similarly to the AdS{sub 3} case.

  9. Nonlinear Dynamical Behavior in BS Evolution Model Based on Small-World Network Added with Mechanism of Preferential Connection


    In this paper, we introduce a modified small-world network added with new links with preferential connection instead of adding randomly, then we apply Bak-Sneppen (BS) evolution model on this network. Several dynamical character of the model such as the evolution graph, fo avalanche, the critical exponent D and τ, and the distribution of mutation times of all the nodes, show particular behaviors different from those of the model based on the regular network and the small-world network.

  10. Research Of A Intelligent Transport Model Based on Ad Hoc Network%基于Ad Hoc网络的智能交通模型研究

    刘钢; 郭晗


    目前,我国多数大中型城市的交通拥堵问题都很严重.若能够合理的分配道路资源、动态获得拥堵路段和准拥堵路段的交通信息,辅助司机做出正确判断,避开车流拥堵的储段,可以从根本上做到缓解整个交通拥堵的目的.本文所讨论的就是建立一个AdHoe网为基础的智能交通模型,车辆可以实时从AdHoe网当中获得交通信息,提前感知到交通拥堵将出现在哪条街道上,并做出合理判断和选择.%On present, our most large and medium - size cities were in very serious trouble of traffic jams. If we can distribute the road resource reasonably, gathering the traffic information of congestion roads and the quasi - congestion road dynamically, that can assist the drivers to make the right judgments. Thus the drivers can avoid the congestion roads and achieve the purpose of ease the traffic congestion fundamentally. What be discussed in this paper is to establish an intelligent model of traffic based on Ad Hoc network. Vehicles can obtained the road information in the Ad Hoc network timely and make right judgment and decisions.

  11. Does Student Sorting Invalidate Value-Added Models of Teacher Effectiveness? An Extended Analysis of the Rothstein Critique

    Koedel, Cory; Betts, Julian R.


    Value-added modeling continues to gain traction as a tool for measuring teacher performance. However, recent research questions the validity of the value-added approach by showing that it does not mitigate student-teacher sorting bias (its presumed primary benefit). Our study explores this critique in more detail. Although we find that estimated…

  12. Assessing State Models of Value-Added Teacher Evaluations: Alignment of Policy, Instruments, and Literature-Based Concepts

    Hadfield, Timothy E.; Hutchison-Lupardus, Tammy R.; Snyder, Jennifer E.


    This problem-based learning project addressed the need to improve the construction and implementation of value-added teacher evaluation policies and instruments. State officials are constructing value-added teacher evaluation models due to accountability initiatives, while ignoring the holes and problems in its implementation. The team's…

  13. A Correlated Random Effects Model for Nonignorable Missing Data in Value-Added Assessment of Teacher Effects

    Karl, Andrew T.; Yang, Yan; Lohr, Sharon L.


    Value-added models have been widely used to assess the contributions of individual teachers and schools to students' academic growth based on longitudinal student achievement outcomes. There is concern, however, that ignoring the presence of missing values, which are common in longitudinal studies, can bias teachers' value-added scores.…

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

    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.

  15. Development of an improved animal model of experimental autoimmune myositis.

    Kang, Juan; Zhang, Hong-Ya; Feng, Guo-Dong; Feng, Dong-Yun; Jia, Hong-Ge


    Multiple animal models of experimental autoimmune myositis (EAM) have been developed. However, these models vary greatly in the severity of disease and reproducibility. The goal of this study was to test whether vaccination twice with increased dose of rat myosin and pertussis toxin (PT) could induce EAM with severer disease in mice. BALB/c mice were injected with 1 mg rat myosin in 50% complete Freund's adjuvant (CFA) weekly for four times and one time of PT (EAM) or twice with 1.5 mg myosin in CFA and PT (M-EAM). In comparison with that in the CFA and PT injected controls, vaccination with rat myosin and injection PT significantly reduced the muscle strength and EMG duration, elevated serum creatine kinase levels, promoted inflammatory infiltration in the muscle tissues, leading to pathological changes in the muscle tissues, demonstrating to induce EAM. Interestingly, we found that vaccination twice with the high dose of myosin and PT prevented EAM-related gain in body weights and caused significantly less muscle strength in mice. More importantly, all of the mice receiving high dose of myosin and PT survived while 3 out of 16 mice with four times of low dose of myosin died. Finally, vaccination with high dose of myosin promoted CD4(+) and CD8(+) T cell infiltration in the muscle tissues and up-regulated MHC-I expression in the muscle tissues of mice. Hence, the new model of EAM is a time-saving, efficient and easily replicable tool for studying autoimmune myositis.

  16. The use of suspension models and comparison with true weightlessness. [Animal Model Workshop on Gravitational Physiology

    Musacchia, X. J.; Ellis, S.


    A resume is presented of various papers concerning the effect of weightlessness on particular physiological and biochemical phenomena in animal model systems. Findings from weightlessness experiments on earth using suspension models are compared with results of experiments in orbit. The biological phenomena considered include muscle atrophy, changes in the endocrine system, reduction in bone formation, and changes in the cardiovascular system.

  17. Strategies for fitting nonlinear ecological models in R, AD Model Builder, and BUGS

    Bolker, B.M.; Gardner, B.; Maunder, M.


    Ecologists often use nonlinear fitting techniques to estimate the parameters of complex ecological models, with attendant frustration. This paper compares three open-source model fitting tools and discusses general strategies for defining and fitting models. R is convenient and (relatively) easy ...

  18. Modelling and Initial Validation of the DYMO Routing Protocol for Mobile Ad-Hoc Networks

    Espensen, Kristian Asbjørn Leth; Kjeldsen, Mads Keblov; Kristensen, Lars Michael


    A mobile ad-hoc network (MANET) is an infrastructureless network established by a set of mobile devices using wireless communication. The Dynamic MANET On-demand (DYMO) protocol is a routing protocol for multi-hop communication in MANETs currently under development by the Internet Engineering Task...... Force (IETF). This paper presents a Coloured Petri Net (CPN) model of the mandatory parts of the DYMO protocol, and shows how scenario-based state space exploration has been used to validate key properties of the protocol. Our CPN modelling and verification work has spanned two revisions of the DYMO...... protocol specification and have had direct impact on the most recent version of the protocol specification....

  19. AdS and stabilized extra dimensions in multidimensional gravitational models with nonlinear scalar curvature terms 1/R and R^4

    Günther, U; Bezerra, V; Romero, C; Guenther, Uwe; Zhuk, Alexander; Bezerra, Valdir; Romero, Carlos


    We study multidimensional gravitational models with scalar curvature nonlinearities of the type 1/R and R^4. It is assumed that the corresponding higher dimensional spacetime manifolds undergo a spontaneous compactification to manifolds with warped product structure. Special attention is paid to the stability of the extra-dimensional factor spaces. It is shown that for certain parameter regions the systems allow for a freezing stabilization of these spaces. In particular, we find for the 1/R model that configurations with stabilized extra dimensions do not provide a late-time acceleration (they are AdS), whereas the solution branch which allows for accelerated expansion (the dS branch) is incompatible with stabilized factor spaces. In the case of the R^4 model, we obtain that the stability region in parameter space depends on the total dimension D=dim(M) of the higher dimensional spacetime M. For D>8 the stability region consists of a single (absolutely stable) sector which is shielded from a conformal singul...

  20. Validation of transpulmonary thermodilution cardiac output measurement in a pediatric animal model.

    Lemson, J.; Boode, W.P. de; Hopman, J.C.W.; Singh, S.K.; Hoeven, J.G. van der


    OBJECTIVE: This study was undertaken to validate the transpulmonary thermodilution cardiac output measurement (CO(TPTD)) in a controlled newborn animal model under various hemodynamic conditions with special emphasis on low cardiac output. DESIGN: Prospective, experimental, pediatric animal study. S

  1. MeCP2-Related Diseases and Animal Models

    Chinelo D. Ezeonwuka


    Full Text Available The role of epigenetics in human disease has become an area of increased research interest. Collaborative efforts from scientists and clinicians have led to a better understanding of the molecular mechanisms by which epigenetic regulation is involved in the pathogenesis of many human diseases. Several neurological and non-neurological disorders are associated with mutations in genes that encode for epigenetic factors. One of the most studied proteins that impacts human disease and is associated with deregulation of epigenetic processes is Methyl CpG binding protein 2 (MeCP2. MeCP2 is an epigenetic regulator that modulates gene expression by translating epigenetic DNA methylation marks into appropriate cellular responses. In order to highlight the importance of epigenetics to development and disease, we will discuss how MeCP2 emerges as a key epigenetic player in human neurodevelopmental, neurological, and non-neurological disorders. We will review our current knowledge on MeCP2-related diseases, including Rett Syndrome, Angelman Syndrome, Fetal Alcohol Spectrum Disorder, Hirschsprung disease, and Cancer. Additionally, we will briefly discuss about the existing MeCP2 animal models that have been generated for a better understanding of how MeCP2 impacts certain human diseases.

  2. MeCP2-Related Diseases and Animal Models

    Ezeonwuka, Chinelo D.; Rastegar, Mojgan


    The role of epigenetics in human disease has become an area of increased research interest. Collaborative efforts from scientists and clinicians have led to a better understanding of the molecular mechanisms by which epigenetic regulation is involved in the pathogenesis of many human diseases. Several neurological and non-neurological disorders are associated with mutations in genes that encode for epigenetic factors. One of the most studied proteins that impacts human disease and is associated with deregulation of epigenetic processes is Methyl CpG binding protein 2 (MeCP2). MeCP2 is an epigenetic regulator that modulates gene expression by translating epigenetic DNA methylation marks into appropriate cellular responses. In order to highlight the importance of epigenetics to development and disease, we will discuss how MeCP2 emerges as a key epigenetic player in human neurodevelopmental, neurological, and non-neurological disorders. We will review our current knowledge on MeCP2-related diseases, including Rett Syndrome, Angelman Syndrome, Fetal Alcohol Spectrum Disorder, Hirschsprung disease, and Cancer. Additionally, we will briefly discuss about the existing MeCP2 animal models that have been generated for a better understanding of how MeCP2 impacts certain human diseases.

  3. Towards an Evolutionary Model of Animal-Associated Microbiomes

    Bryan A. White


    Full Text Available Second-generation sequencing technologies have granted us greater access to the diversity and genetics of microbial communities that naturally reside endo- and ecto-symbiotically with animal hosts. Substantial research has emerged describing the diversity and broader trends that exist within and between host species and their associated microbial ecosystems, yet the application of these data to our evolutionary understanding of microbiomes appears fragmented. For the most part biological perspectives are based on limited observations of oversimplified communities, while mathematical and/or computational modeling of these concepts often lack biological precedence. In recognition of this disconnect, both fields have attempted to incorporate ecological theories, although their applicability is currently a subject of debate because most ecological theories were developed based on observations of macro-organisms and their ecosystems. For the purposes of this review, we attempt to transcend the biological, ecological and computational realms, drawing on extensive literature, to forge a useful framework that can, at a minimum be built upon, but ideally will shape the hypotheses of each field as they move forward. In evaluating the top-down selection pressures that are exerted on a microbiome we find cause to warrant reconsideration of the much-maligned theory of multi-level selection and reason that complexity must be underscored by modularity.

  4. Animal models of brain maldevelopment induced by cycad plant genotoxins.

    Kisby, Glen E; Moore, Holly; Spencer, Peter S


    Cycads are long-lived tropical and subtropical plants that contain azoxyglycosides (e.g., cycasin, macrozamin) and neurotoxic amino acids (notably β-N-methylamino-l-alanine l-BMAA), toxins that have been implicated in the etiology of a disappearing neurodegenerative disease, amyotrophic lateral sclerosis and parkinsonism-dementia complex that has been present in high incidence among three genetically distinct populations in the western Pacific. The neuropathology of amyotrophic lateral sclerosis/parkinsonism-dementia complex includes features suggestive of brain maldevelopment, an experimentally proven property of cycasin attributable to the genotoxic action of its aglycone methylazoxymethanol (MAM). This property of MAM has been exploited by neurobiologists as a tool to study perturbations of brain development. Depending on the neurodevelopmental stage, MAM can induce features in laboratory animals that model certain characteristics of epilepsy, schizophrenia, or ataxia. Studies in DNA repair-deficient mice show that MAM perturbs brain development through a DNA damage-mediated mechanism. The brain DNA lesions produced by systemic MAM appear to modulate the expression of genes that regulate neurodevelopment and contribute to neurodegeneration. Epigenetic changes (histone lysine methylation) have also been detected in the underdeveloped brain after MAM administration. The DNA damage and epigenetic changes produced by MAM and, perhaps by chemically related substances (e.g., nitrosamines, nitrosoureas, hydrazines), might be an important mechanism by which early-life exposure to genotoxicants can induce long-term brain dysfunction.

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

    Anne eAlbrecht


    Full Text Available Genetic and biomarker studies in patients have identified the Neural Cell Adhesion Molecule (NCAM and its associated polysialic acid 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 studied social interaction and attention of NCAM null mutant (NCAM-/- mice as further hallmarks of schizophrenia. Nest building, which is generally associated with social behavior in rodents, was severely impaired, as NCAM-/- mice continuously collected smaller amounts of nest building material than their wild type littermates and built nests of poorer quality. However, social approach tested in a three- compartment- box was not affected and latent inhibition of Pavlovian fear memory was not disturbed in NCAM-/- mice. Although NCAM deficient mice do not display a typical schizophrenia-like phenotype, they may be useful for studying specific endophenotypes with relevance to the disease.

  6. Phage therapy of staphylococcal chronic osteomyelitis in experimental animal model

    Chandan Kishor


    Full Text Available Background & objectives: Methicillin resistant Staphylococcus aureus (MRSA are the commonest cause of osteomyelitis. The aim of this study was to evaluate the role of an alternative therapy i.e. application of S. aureus specific bacteriophages in cases of osteomyelitis caused by MRSA in animal model. Methods: Twenty two rabbits were included in this study. The first two rabbits were used to test the safety of phage cocktail while the remaining 20 rabbits were divided into three groups; group A (n=4 to assess the establishment of osteomyelitis; group B (n=4 osteomyelitis developed but therapy started only after six weeks; and group C (n=12 osteomyelitis developed and therapy started after three weeks. Groups B and C rabbits were treated with four doses of cocktail of seven virulent bacteriophages at the interval of 48 h. Comparison between three groups was made on the basis of observation of clinical, radiological, microbiological, and histopathological examinations. Results: Experimental group rabbits recovered from the illness in the subsequent two weeks of the therapy. Appetite and activity of the rabbits improved, local oedema, erythema and induration subsided. There were minimal changes associated with osteomyelitis in X-ray and histopathology also showed no signs of infection with new bone formation. Control B group rabbits also recovered well from the infection. Interpretation & conclusions: The present study shows a potential of phage therapy to treat difficult infections caused by multidrug resistant bacteria.

  7. Effects of (-)stepholidine in animal models for schizophrenia

    Bart A ELLENBROEK; Xue-xiang ZHANG; Guo-zhang JIN


    Aim: (-)Stepholidine (SPD) is an active ingredient of the Chinese herb Stephania intermedia, which binds to the dopamine D1 and D2 like receptors. Biochemical, electrophysiological and behavioural experiments have provided strong evidence that SPD is both a D1 and a D2 antagonist, which could make SPD a unique antipsychotic drug. The present study aimed to investigate the antipsychotic properties of SPD in two animal models for schizophrenia. Methods: The effects of SPD, clozapine and haloperidol in increasing forelimb and hindlimb retraction time in the paw test and in reversing the apomorphine and MK801-induced disruption of prepulse inhibition was investigated. Results: In the paw test, clozapine and SPD increased the hindlimb retraction time, with only a marginal effect on the forelimb retraction time, whereas haloperidol potently increased both. In the prepulse inhibition paradigm, all three drugs reverse the apomorphine-induced disruption in prepulse inhibition, while none of the drugs could reverse the MK801-induced disruption. SPD even slightly, but significantly, potentiated the effects of MK801. Conclusion: The data show that SPD showed antipsychotic-like effects in both the prepulse inhibition paradigm and in the paw test. Moreover, the results of the paw test suggest that SPD has an atypical character with a relatively small potency to induce extrapyramidal side effects.

  8. Solitary mammals provide an animal model for autism spectrum disorders.

    Reser, Jared Edward


    Species of solitary mammals are known to exhibit specialized, neurological adaptations that prepare them to focus working memory on food procurement and survival rather than on social interaction. Solitary and nonmonogamous mammals, which do not form strong social bonds, have been documented to exhibit behaviors and biomarkers that are similar to endophenotypes in autism. Both individuals on the autism spectrum and certain solitary mammals have been reported to be low on measures of affiliative need, bodily expressiveness, bonding and attachment, direct and shared gazing, emotional engagement, conspecific recognition, partner preference, separation distress, and social approach behavior. Solitary mammals also exhibit certain biomarkers that are characteristic of autism, including diminished oxytocin and vasopressin signaling, dysregulation of the endogenous opioid system, increased Hypothalamic-pituitary-adrenal axis (HPA) activity to social encounters, and reduced HPA activity to separation and isolation. The extent of these similarities suggests that solitary mammals may offer a useful model of autism spectrum disorders and an opportunity for investigating genetic and epigenetic etiological factors. If the brain in autism can be shown to exhibit distinct homologous or homoplastic similarities to the brains of solitary animals, it will reveal that they may be central to the phenotype and should be targeted for further investigation. Research of the neurological, cellular, and molecular basis of these specializations in other mammals may provide insight for behavioral analysis, communication intervention, and psychopharmacology for autism.

  9. Defective membrane remodeling in neuromuscular diseases: insights from animal models.

    Belinda S Cowling

    Full Text Available Proteins involved in membrane remodeling play an essential role in a plethora of cell functions including endocytosis and intracellular transport. Defects in several of them lead to human diseases. Myotubularins, amphiphysins, and dynamins are all proteins implicated in membrane trafficking and/or remodeling. Mutations in myotubularin, amphiphysin 2 (BIN1, and dynamin 2 lead to different forms of centronuclear myopathy, while mutations in myotubularin-related proteins cause Charcot-Marie-Tooth neuropathies. In addition to centronuclear myopathy, dynamin 2 is also mutated in a dominant form of Charcot-Marie-Tooth neuropathy. While several proteins from these different families are implicated in similar diseases, mutations in close homologues or in the same protein in the case of dynamin 2 lead to diseases affecting different tissues. This suggests (1 a common molecular pathway underlying these different neuromuscular diseases, and (2 tissue-specific regulation of these proteins. This review discusses the pathophysiology of the related neuromuscular diseases on the basis of animal models developed for proteins of the myotubularin, amphiphysin, and dynamin families. A better understanding of the common mechanisms between these neuromuscular disorders will lead to more specific health care and therapeutic approaches.

  10. Cytokines and VEGF Induction in Orthodontic Movement in Animal Models

    M. Di Domenico


    Full Text Available Orthodontics is a branch of dentistry that aims at the resolution of dental malocclusions. The specialist carries out the treatment using intraoral or extraoral orthodontic appliances that require forces of a given load level to obtain a tooth movement in a certain direction in dental arches. Orthodontic tooth movement is dependent on efficient remodeling of periodontal ligament and alveolar bone, correlated with several biological and mechanical responses of the tissues surrounding the teeth. A periodontal ligament placed under pressure will result in bone resorption whereas a periodontal ligament under tension results in bone formation. In the primary stage of the application of orthodontic forces, an acute inflammation occurs in periodontium. Several proinflammatory cytokines are produced by immune-competent cells migrating by means of dilated capillaries. In this paper we summarize, also through the utilization of animal models, the role of some of these molecules, namely, interleukin-1β and vascular endothelial growth factor, that are some proliferation markers of osteoclasts and osteoblasts, and the macrophage colony stimulating factor.

  11. Animal models of social avoidance and social fear.

    Toth, Iulia; Neumann, Inga D


    Social fear and avoidance of social situations represent the main behavioral symptoms of social anxiety disorder (SAD), a highly prevalent anxiety disorder that is poorly elucidated and has rather unsatisfactory therapeutic options. Therefore, animal models are needed to study the underlying etiology and pathophysiology of SAD and to verify the efficacy of possible novel treatment approaches. In this review, we describe and discuss the most important paradigms that have been shown to induce social avoidance and fear in rodents, including foot shock exposure, restraint stress, social isolation, social instability, social defeat, conditioned defeat, social defeat/overcrowding, chronic subordinate colony housing, chronic mild stress, maternal separation and social fear conditioning. We also describe some of the behavioral paradigms used to assess social avoidance and fear in rodents, including the social interaction test, the social preference-avoidance test, the social approach-avoidance test, the three-chambered social approach test, the partition test and the modified Y-maze test. We focus on the behavioral alterations these paradigms induce, especially on social interaction, general anxiety and depressive-like behavior given that SAD is strongly comorbid with anxiety and affective disorders.

  12. System identification of perilymphatic fistula in an animal model

    Wall, C. 3rd; Casselbrant, M. L.


    An acute animal model has been developed in the chinchilla for the study of perilymphatic fistulas. Micropunctures were made in three sites to simulate bony, round window, and oval window fistulas. The eye movements in response to pressure applied to the external auditory canal were recorded after micropuncture induction and in preoperative controls. The main pressure stimulus was a pseudorandom binary sequence (PRBS) that rapidly changed between plus and minus 200 mm of water. The PRBS stimulus, with its wide frequency bandwidth, produced responses clearly above the preoperative baseline in 78 percent of the runs. The response was better between 0.5 and 3.3 Hz than it was below 0.5 Hz. The direction of horizontal eye movement was toward the side of the fistula with positive pressure applied in 92 percent of the runs. Vertical eye movements were also observed. The ratio of vertical eye displacement to horizontal eye displacement depended upon the site of the micropuncture induction. Thus, such a ratio measurement may be clinically useful in the noninvasive localization of perilymphatic fistulas in humans.

  13. Animal models of peripheral neuropathy due to environmental toxicants.

    Rao, Deepa B; Jortner, Bernard S; Sills, Robert C


    Despite the progress in our understanding of pathogeneses and the identification of etiologies of peripheral neuropathy, idiopathic neuropathy remains common. Typically, attention to peripheral neuropathies resulting from exposure to environmental agents is limited relative to more commonly diagnosed causes of peripheral neuropathy (diabetes and chemotherapeutic agents). Given that there are more than 80,000 chemicals in commerce registered with the Environmental Protection Agency and that at least 1000 chemicals are known to have neurotoxic potential, very few chemicals have been established to affect the peripheral nervous system (mainly after occupational exposures). A wide spectrum of exposures, including pesticides, metals, solvents, nutritional sources, and pharmaceutical agents, has been related, both historically and recently, to environmental toxicant-induced peripheral neuropathy. A review of the literature shows that the toxicity and pathogeneses of chemicals adversely affecting the peripheral nervous system have been studied using animal models. This article includes an overview of five prototypical environmental agents known to cause peripheral neuropathy--namely, organophosphates, carbon disulfide, pyridoxine (Vitamin B6), acrylamide, and hexacarbons (mainly n-hexane, 2,5-hexanedione, methyl n-butyl ketone). Also included is a brief introduction to the structural components of the peripheral nervous system and pointers on common methodologies for histopathologic evaluation of the peripheral nerves.

  14. ras activation in human tumors and in animal model systems

    Corominas, M.; Sloan, S.R.; Leon, J.; Kamino, Hideko; Newcomb, E.W.; Pellicer, A. (New York Univ. Medical Center, New York (United States))


    Environmental agents such as radiation and chemicals are known to cause genetic damage. Alterations in a limited set of cellular genes called proto-oncogenes lead to unregulated proliferation and differentiation. The authors have studied the role of the ras gene family in carcinogenesis using two different animal models. In one case, thymic lymphomas were induced in mice by either gamma or neutron radiation, and in the other, keratoacanthomas were induced in rabbit skin with dimethylbenzanthracene. Human keratoacanthomas similar to the ones induced in rabbits were also analyzed. They found that different types of radiation such as gamma rays and neutrons, induced different point mutations in ras genes. A novel K-ras mutation in codon 146 has been found in thymic lymphomas induced by neutrons. Keratoacanthomas induced in rabbit skin by dimethylbenzanthracene show a high frequency of H-ras-activated genes carrying a mutation in codon 61. The same is observed in human keratoacanthomas, although mutations are in both the 12th and the 61st codons of the H-ras gene. H-ras activation is less frequent in human squamous cell carcinomas than in keratoacanthomas, suggesting that ras genes could play a role in vivo in differentiation as well as in proliferation.

  15. Effect of Saraswatarishta in animal models of behavior despair

    Reshma R Parekar


    Full Text Available Background: Saraswatarishta (SA is a herbo-mineral formulation consisting of 18 plants some of which are Medhyarasayanas. It has been claimed to be useful in treating central nervous system disorders. Objective: To evaluate antidepressant effect of ′Saraswatarishta′(SA alone and in combination with imipramine and fluoxetine in animal models of depression. Materials and Methods: After obtaining IAEC permission, 144 rats (n = 36/part were randomized into 6 groups- Group 1: Distilled water (1 mL, Group 2: Imipramine (30 mg/kg, Group 3: Fluoxetine (10 mg/kg, Group 4: SA (1.8 mL/kg, Group 5: Imipramine + SA, Group 6: Fluoxetine + SA. Effects of study drugs were evaluated in forced swim test (FST with single exposure to FST (Part 1 and repeated exposure for 14 days (Part 2. In Part 3, reserpine was used with FST and effects of study drugs were evaluated against single exposure to FST. Same model was used with repeated exposures to FST (Part 4. In each part, rats were subjected to open field test (OFT for 5 min prior to final FST. The variables measured: Immobility time in FST; line crossing, rearing and defecation in the OFT. Results: In all four parts, individual drugs and combinations thereof produced significant decrease in immobility time as compared to control, and extent of decrease was comparable amongst these groups. However, values for combination of fluoxetine with SA group were found to be lesser than that for individual agents in Parts 2 and 3. Combination of SA with imipramine did not enhance its anti-depressant effect in any of the parts. OFT findings did not vary significantly amongst the study groups. Conclusion: Decreased immobility in FST and absence of generalized stimulation or depression of motor activity in OFT point towards potential antidepressant effect of Saraswatarishta. Its co-administration with fluoxetine showed more promising effects.

  16. Function of the hemochromatosis protein HFE: Lessons from animal models

    Kostas Pantopoulos


    Hereditary hemochromatosis (HH) is caused by chronic hyperabsorption of dietary iron. Progressive accumulation of excess iron within tissue parenchymal cells may lead to severe organ damage. The most prevalent type of HH is linked to mutations in the HFE gene, encoding an atypical major histocompatibility complex class Ⅰ molecule. Shortly after its discovery in 1996, the hemochromatosis protein HFE was shown to physically interact with transferrin receptor 1 (TfR1)and impair the uptake of transferrin-bound iron in cells. However, these findings provided no clue why /-/FE mutations associate with systemic iron overload.It was later established that all forms of HH result from misregulation of hepcidin expression. This liverderived circulating peptide hormone controls iron efflux from duodenal enterocytes and reticuloendothelial macrophages by promoting the degradation of the iron exporter ferroportin. Recent studies with animal models of HH uncover a crucial role of HFE as a hepatocyte iron sensor and upstream regulator of helpcidin. Thus,hepatocyte HFE is indispensable for signaling to hepcidin, presumably as a constituent of a larger ironsensing complex. A working model postulates that the signaling activity of HFE is silenced when the protein is bound to TfR1. An increase in the iron saturation of plasma transferrin leads to displacement of TfR1 from HFE and assembly of the putative iron-sensing complex.In this way, iron uptake by the hepatocyte is translated into upregulation of hepcidin, reinforcing the concept that the liver is the major regulatory site for systemic iron homeostasis, and not merely an iron storage depot.


    Adib M. Monzer Habbal


    Full Text Available Transmission Control Protocol (TCP is a fundamental protocol in the TCP/IP Protocol Suite.TCP was well designed and optimized to work over wired networks where most packet loss occurs due to network congestion. In theory, TCP should not care whether it is running over wired networks, WLANs, or Mobile Ad hoc Networks (MANETs. In practice, it does matter because most TCP deployments have been carefully designed based on the assumption that congestion is the main factor of network instability. However, MANETs have other dominating factors that cause network instability. Forgetting the impact of these factors violates some design principles of TCP congestion control and open questions for future research to address. This study aims to introduce a model that shows the impact of MANET factors on TCP congestion control. To achieve this aim, Design Research Methodology (DRM proposed by BLESSING was used as a guide to present this model. The proposed model describes the existing situation of TCP congestion control. Furthermore, it points to the factors that are most suitable to be addressed by researchers in order to improve TCP performance. This research proposes a novel model to present the impact of MANET factors on TCP congestion control. The model is expected to serve as a benchmark for any intended improvement and enhancement of TCP congestion control over MANET.

  18. Refining animal models in fracture research: seeking consensus in optimising both animal welfare and scientific validity for appropriate biomedical use

    Schneider Erich


    Full Text Available Abstract Background In an attempt to establish some consensus on the proper use and design of experimental animal models in musculoskeletal research, AOVET (the veterinary specialty group of the AO Foundation in concert with the AO Research Institute (ARI, and the European Academy for the Study of Scientific and Technological Advance, convened a group of musculoskeletal researchers, veterinarians, legal experts, and ethicists to discuss, in a frank and open forum, the use of animals in musculoskeletal research. Methods The group narrowed the field to fracture research. The consensus opinion resulting from this workshop can be summarized as follows: Results & Conclusion Anaesthesia and pain management protocols for research animals should follow standard protocols applied in clinical work for the species involved. This will improve morbidity and mortality outcomes. A database should be established to facilitate selection of anaesthesia and pain management protocols for specific experimental surgical procedures and adopted as an International Standard (IS according to animal species selected. A list of 10 golden rules and requirements for conduction of animal experiments in musculoskeletal research was drawn up comprising 1 Intelligent study designs to receive appropriate answers; 2 Minimal complication rates (5 to max. 10%; 3 Defined end-points for both welfare and scientific outputs analogous to quality assessment (QA audit of protocols in GLP studies; 4 Sufficient details for materials and methods applied; 5 Potentially confounding variables (genetic background, seasonal, hormonal, size, histological, and biomechanical differences; 6 Post-operative management with emphasis on analgesia and follow-up examinations; 7 Study protocols to satisfy criteria established for a "justified animal study"; 8 Surgical expertise to conduct surgery on animals; 9 Pilot studies as a critical part of model validation and powering of the definitive study design

  19. Evolution of animal models in cancer vaccine development.

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


    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

  20. An animal model of differential genetic risk for methamphetamine intake

    Tamara ePhillips


    Full Text Available The question of whether genetic factors contribute to risk for methamphetamine (MA use and dependence has not been intensively investigated. Compared to human populations, genetic animal models offer the advantages of control over genetic family history and drug exposure. Using selective breeding, we created lines of mice that differ in genetic risk for voluntary MA intake and identified the chromosomal addresses of contributory genes. A quantitative trait locus was identified on chromosome 10 that accounts for more than 50% of the genetic variance in MA intake in the selected mouse lines. In addition, behavioral and physiological screening identified differences corresponding with risk for MA intake that have generated hypotheses that are testable in humans. Heightened sensitivity to aversive and certain physiological effects of MA, such as MA-induced reduction in body temperature, are hallmarks of mice bred for low MA intake. Furthermore, unlike MA-avoiding mice, MA-preferring mice are sensitive to rewarding and reinforcing MA effects, and to MA-induced increases in brain extracellular dopamine levels. Gene expression analyses implicate the importance of a network enriched in transcription factor genes, some of which regulate the mu opioid receptor gene, Oprm1, in risk for MA use. Neuroimmune factors appear to play a role in differential response to MA between the mice bred for high and low intake. In addition, chromosome 10 candidate gene studies provide strong support for a trace amine associated receptor 1 gene, Taar1, polymorphism in risk for MA intake. MA is a trace amine-associated receptor 1 (TAAR1 agonist, and a non-functional Taar1 allele segregates with high MA consumption. Thus, reduced TAAR1 function has the potential to increase risk for MA use. Overall, existing findings support the MA drinking lines as a powerful model for identifying genetic factors involved in determining risk for harmful MA use. Future directions include the