Considerations for Infectious Disease Research Studies Using Animals

PubMed Central

Colby, Lesley A; Quenee, Lauriane E; Zitzow, Lois A

2017-01-01

Animal models are vital in understanding the transmission and pathogenesis of infectious organisms and the host immune response to infection. In addition, animal models are essential in vaccine and therapeutic drug development and testing. Prior to selecting an animal model to use when studying an infectious agent, the scientific team must determine that sufficient in vitro and ex vivo data are available to justify performing research in an animal model, that ethical considerations are addressed, and that the data generated from animal work will add useful information to the body of scientific knowledge. Once it is established that an animal should be used, the questions become ‘Which animal model is most suitable?’ and ‘Which experimental design issues should be considered?’ The answers to these questions take into account numerous factors, including scientific, practical, welfare, and regulatory considerations, which are the focus of this article. PMID:28662751

Research and implementation of group animation based on normal cloud model

NASA Astrophysics Data System (ADS)

Li, Min; Wei, Bin; Peng, Bao

2011-12-01

Group Animation is a difficult technology problem which always has not been solved in computer Animation technology, All current methods have their limitations. This paper put forward a method: the Motion Coordinate and Motion Speed of true fish group was collected as sample data, reverse cloud generator was designed and run, expectation, entropy and super entropy are gotten. Which are quantitative value of qualitative concept. These parameters are used as basis, forward cloud generator was designed and run, Motion Coordinate and Motion Speed of two-dimensional fish group animation are produced, And two spirit state variable about fish group : the feeling of hunger, the feeling of fear are designed. Experiment is used to simulated the motion state of fish Group Animation which is affected by internal cause and external cause above, The experiment shows that the Group Animation which is designed by this method has strong Realistic.

Poststroke Seizures and Epilepsy: Clinical Studies and Animal Models

PubMed Central

Kelly, Kevin M.

2002-01-01

Poststroke seizures and epilepsy have been described in numerous clinical studies for many years. Most studies are retrospective in design, include relatively small numbers of patients, have limited periods of follow-up, and report a diversity of findings. Well-designed clinical trials and population studies in the recent past addressed several critical clinical issues and generated important findings regarding the occurrence of poststroke seizures and epilepsy. In contrast, the pathophysiologic events of injured brain that establish poststroke epileptogenesis are not well understood, and animal modeling has had limited development. Reviews of several important clinical studies and animal models that hold promise for a better understanding of poststroke epileptogenesis are presented. PMID:15309107

An overview of animal models of pain: disease models and outcome measures

PubMed Central

Gregory, N; Harris, AL; Robinson, CR; Dougherty, PM; Fuchs, PN; Sluka, KA

2013-01-01

Pain is ultimately a perceptual phenomenon. It is built from information gathered by specialized pain receptors in tissue, modified by spinal and supraspinal mechanisms, and integrated into a discrete sensory experience with an emotional valence in the brain. Because of this, studying intact animals allows the multidimensional nature of pain to be examined. A number of animal models have been developed, reflecting observations that pain phenotypes are mediated by distinct mechanisms. Animal models of pain are designed to mimic distinct clinical diseases to better evaluate underlying mechanisms and potential treatments. Outcome measures are designed to measure multiple parts of the pain experience including reflexive hyperalgesia measures, sensory and affective dimensions of pain and impact of pain on function and quality of life. In this review we discuss the common methods used for inducing each of the pain phenotypes related to clinical pain syndromes, as well as the main behavioral tests for assessing pain in each model. PMID:24035349

Combining High-Speed Cameras and Stop-Motion Animation Software to Support Students' Modeling of Human Body Movement

NASA Astrophysics Data System (ADS)

Lee, Victor R.

2015-04-01

Biomechanics, and specifically the biomechanics associated with human movement, is a potentially rich backdrop against which educators can design innovative science teaching and learning activities. Moreover, the use of technologies associated with biomechanics research, such as high-speed cameras that can produce high-quality slow-motion video, can be deployed in such a way to support students' participation in practices of scientific modeling. As participants in classroom design experiment, fifteen fifth-grade students worked with high-speed cameras and stop-motion animation software (SAM Animation) over several days to produce dynamic models of motion and body movement. The designed series of learning activities involved iterative cycles of animation creation and critique and use of various depictive materials. Subsequent analysis of flipbooks of human jumping movements created by the students at the beginning and end of the unit revealed a significant improvement in both the epistemic fidelity of students' representations. Excerpts from classroom observations highlight the role that the teacher plays in supporting students' thoughtful reflection of and attention to slow-motion video. In total, this design and research intervention demonstrates that the combination of technologies, activities, and teacher support can lead to improvements in some of the foundations associated with students' modeling.

A freely-moving monkey treadmill model.

PubMed

Foster, Justin D; Nuyujukian, Paul; Freifeld, Oren; Gao, Hua; Walker, Ross; I Ryu, Stephen; H Meng, Teresa; Murmann, Boris; J Black, Michael; Shenoy, Krishna V

2014-08-01

Motor neuroscience and brain-machine interface (BMI) design is based on examining how the brain controls voluntary movement, typically by recording neural activity and behavior from animal models. Recording technologies used with these animal models have traditionally limited the range of behaviors that can be studied, and thus the generality of science and engineering research. We aim to design a freely-moving animal model using neural and behavioral recording technologies that do not constrain movement. We have established a freely-moving rhesus monkey model employing technology that transmits neural activity from an intracortical array using a head-mounted device and records behavior through computer vision using markerless motion capture. We demonstrate the flexibility and utility of this new monkey model, including the first recordings from motor cortex while rhesus monkeys walk quadrupedally on a treadmill. Using this monkey model, we show that multi-unit threshold-crossing neural activity encodes the phase of walking and that the average firing rate of the threshold crossings covaries with the speed of individual steps. On a population level, we find that neural state-space trajectories of walking at different speeds have similar rotational dynamics in some dimensions that evolve at the step rate of walking, yet robustly separate by speed in other state-space dimensions. Freely-moving animal models may allow neuroscientists to examine a wider range of behaviors and can provide a flexible experimental paradigm for examining the neural mechanisms that underlie movement generation across behaviors and environments. For BMIs, freely-moving animal models have the potential to aid prosthetic design by examining how neural encoding changes with posture, environment and other real-world context changes. Understanding this new realm of behavior in more naturalistic settings is essential for overall progress of basic motor neuroscience and for the successful translation of BMIs to people with paralysis.

Improving Perceptual Skills with 3-Dimensional Animations.

ERIC Educational Resources Information Center

Johns, Janet Faye; Brander, Julianne Marie

1998-01-01

Describes three-dimensional computer aided design (CAD) models for every component in a representative mechanical system; the CAD models made it easy to generate 3-D animations that are ideal for teaching perceptual skills in multimedia computer-based technical training. Fifteen illustrations are provided. (AEF)

Animal models of ulcerative colitis and their application in drug research

PubMed Central

Low, Daren; Nguyen, Deanna D; Mizoguchi, Emiko

2013-01-01

The specific pathogenesis underlying inflammatory bowel disease is complex, and it is even more difficult to decipher the pathophysiology to explain for the similarities and differences between two of its major subtypes, Crohn’s disease and ulcerative colitis (UC). Animal models are indispensable to pry into mechanistic details that will facilitate better preclinical drug/therapy design to target specific components involved in the disease pathogenesis. This review focuses on common animal models that are particularly useful for the study of UC and its therapeutic strategy. Recent reports of the latest compounds, therapeutic strategies, and approaches tested on UC animal models are also discussed. PMID:24250223

Animal Models of Hemophilia and Related Bleeding Disorders

PubMed Central

Lozier, Jay N.; Nichols, Timothy C.

2013-01-01

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

Associating Animations with Concrete Models to Enhance Students' Comprehension of Different Visual Representations in Organic Chemistry

ERIC Educational Resources Information Center

Al-Balushi, Sulaiman M.; Al-Hajri, Sheikha H.

2014-01-01

The purpose of the current study is to explore the impact of associating animations with concrete models on eleventh-grade students' comprehension of different visual representations in organic chemistry. The study used a post-test control group quasi-experimental design. The experimental group (N = 28) used concrete models, submicroscopic…

Modeling the Western Diet for Preclinical Investigations.

PubMed

Hintze, Korry J; Benninghoff, Abby D; Cho, Clara E; Ward, Robert E

2018-05-01

Rodent models have been invaluable for biomedical research. Preclinical investigations with rodents allow researchers to investigate diseases by using study designs that are not suitable for human subjects. The primary criticism of preclinical animal models is that results are not always translatable to humans. Some of this lack of translation is due to inherent differences between species. However, rodent models have been refined over time, and translatability to humans has improved. Transgenic animals have greatly aided our understanding of interactions between genes and disease and have narrowed the translation gap between humans and model animals. Despite the technological innovations of animal models through advances in genetics, relatively little attention has been given to animal diets. Namely, developing diets that replicate what humans eat will help make animal models more relevant to human populations. This review focuses on commonly used rodent diets that are used to emulate the Western dietary pattern in preclinical studies of obesity and type 2 diabetes, nonalcoholic liver disease, maternal nutrition, and colorectal cancer.

Insights into the latent multinomial model through mark-resight data on female grizzly bears with cubs-of-the-year

USGS Publications Warehouse

Higgs, Megan D.; Link, William; White, Gary C.; Haroldson, Mark A.; Bjornlie, Daniel D.

2013-01-01

Mark-resight designs for estimation of population abundance are common and attractive to researchers. However, inference from such designs is very limited when faced with sparse data, either from a low number of marked animals, a low probability of detection, or both. In the Greater Yellowstone Ecosystem, yearly mark-resight data are collected for female grizzly bears with cubs-of-the-year (FCOY), and inference suffers from both limitations. To overcome difficulties due to sparseness, we assume homogeneity in sighting probabilities over 16 years of bi-annual aerial surveys. We model counts of marked and unmarked animals as multinomial random variables, using the capture frequencies of marked animals for inference about the latent multinomial frequencies for unmarked animals. We discuss undesirable behavior of the commonly used discrete uniform prior distribution on the population size parameter and provide OpenBUGS code for fitting such models. The application provides valuable insights into subtleties of implementing Bayesian inference for latent multinomial models. We tie the discussion to our application, though the insights are broadly useful for applications of the latent multinomial model.

Animal models for percutaneous-device-related infections: a review.

PubMed

Shao, Jinlong; Kolwijck, Eva; Jansen, John A; Yang, Fang; Walboomers, X Frank

2017-06-01

This review focuses on the construction of animal models for percutaneous-device-related infections, and specifically the role of inoculation of bacteria in such models. Infections around percutaneous devices, such as catheters, dental implants and limb prostheses, are a recurrent and persistent clinical problem. To promote the research on this clinical problem, the establishment of a reliable and validated animal model would be of keen interest. In this review, literature related to percutaneous devices was evaluated, and particular attention was paid to studies involving the use of bacteria. The design of percutaneous devices, susceptibility of various animal species, bacterial strains, amounts of bacteria, method of inoculation and methods for subsequent evaluation of the infection are discussed in detail. Given that an ideal animal model for study of percutaneous-device-related infection is still not existent, this article presents the basis for the construction of such a standardized animal model for percutaneous-device-related infection studies. The inoculation of bacteria is critical to obtain an animal model for standardized studies for percutaneous-device-related infections. Copyright © 2017. Published by Elsevier B.V.

Animal models of contraception: utility and limitations

PubMed Central

Liechty, Emma R; Bergin, Ingrid L; Bell, Jason D

2015-01-01

Appropriate animal modeling is vital for the successful development of novel contraceptive devices. Advances in reproductive biology have identified novel pathways for contraceptive intervention. Here we review species-specific anatomic and physiologic considerations impacting preclinical contraceptive testing, including efficacy testing, mechanistic studies, device design, and modeling off-target effects. Emphasis is placed on the use of nonhuman primate models in contraceptive device development. PMID:29386922

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

PubMed

Auer, Jorg A; Goodship, Allen; Arnoczky, Steven; Pearce, Simon; Price, Jill; Claes, Lutz; von Rechenberg, Brigitte; Hofmann-Amtenbrinck, Margarethe; Schneider, Erich; Müller-Terpitz, R; Thiele, F; Rippe, Klaus-Peter; Grainger, David W

2007-08-01

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. The group narrowed the field to fracture research. The consensus opinion resulting from this workshop can be summarized as follows: 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; 10) Criteria for funding agencies to include requirements related to animal experiments as part of the overall scientific proposal review protocols. Such agencies are also encouraged to seriously consider and adopt the recommendations described here when awarding funds for specific projects. Specific new requirements and mandates related both to improving the welfare and scientific rigour of animal-based research models are urgently needed as part of international harmonization of standards.

Review: To be or not to be an identifiable model. Is this a relevant question in animal science modelling?

PubMed

Muñoz-Tamayo, R; Puillet, L; Daniel, J B; Sauvant, D; Martin, O; Taghipoor, M; Blavy, P

2018-04-01

What is a good (useful) mathematical model in animal science? For models constructed for prediction purposes, the question of model adequacy (usefulness) has been traditionally tackled by statistical analysis applied to observed experimental data relative to model-predicted variables. However, little attention has been paid to analytic tools that exploit the mathematical properties of the model equations. For example, in the context of model calibration, before attempting a numerical estimation of the model parameters, we might want to know if we have any chance of success in estimating a unique best value of the model parameters from available measurements. This question of uniqueness is referred to as structural identifiability; a mathematical property that is defined on the sole basis of the model structure within a hypothetical ideal experiment determined by a setting of model inputs (stimuli) and observable variables (measurements). Structural identifiability analysis applied to dynamic models described by ordinary differential equations (ODEs) is a common practice in control engineering and system identification. This analysis demands mathematical technicalities that are beyond the academic background of animal science, which might explain the lack of pervasiveness of identifiability analysis in animal science modelling. To fill this gap, in this paper we address the analysis of structural identifiability from a practitioner perspective by capitalizing on the use of dedicated software tools. Our objectives are (i) to provide a comprehensive explanation of the structural identifiability notion for the community of animal science modelling, (ii) to assess the relevance of identifiability analysis in animal science modelling and (iii) to motivate the community to use identifiability analysis in the modelling practice (when the identifiability question is relevant). We focus our study on ODE models. By using illustrative examples that include published mathematical models describing lactation in cattle, we show how structural identifiability analysis can contribute to advancing mathematical modelling in animal science towards the production of useful models and, moreover, highly informative experiments via optimal experiment design. Rather than attempting to impose a systematic identifiability analysis to the modelling community during model developments, we wish to open a window towards the discovery of a powerful tool for model construction and experiment design.

Diet composition as a source of variation in experimental animal models of cancer cachexia.

PubMed

Giles, Kaitlin; Guan, Chen; Jagoe, Thomas R; Mazurak, Vera

2016-05-01

A variety of experimental animal models are used extensively to study mechanisms underlying cancer cachexia, and to identify potential treatments. The important potential confounding effect of dietary composition and intake used in many preclinical studies of cancer cachexia is frequently overlooked. Dietary designs applied in experimental studies should maximize the applicability to human cancer cachexia, meeting the essential requirements of the species used in the study, matched between treatment and control groups as well as also being generally similar to human consumption. A literature review of scientific studies using animal models of cancer and cancer cachexia with dietary interventions was performed. Studies that investigated interventions using lipid sources were selected as the focus of discussion. The search revealed a number of nutrient intervention studies (n = 44), with the majority including n-3 fatty acids (n = 16), mainly eicosapentaenoic acid and/or docosahexaenoic acid. A review of the literature revealed that the majority of studies do not provide information about dietary design; food intake or pair-feeding is rarely reported. Further, there is a lack of standardization in dietary design, content, source, and overall composition in animal models of cancer cachexia. A model is proposed with the intent of guiding dietary design in preclinical studies to enable comparisons of dietary treatments within the same study, translation across different study designs, as well as application to human nutrient intakes. The potential for experimental endpoints to be affected by variations in food intake, macronutrient content, and diet composition is likely. Diet content and composition should be reported, and food intake assessed. Minimum standards for diet definition in cachexia studies would improve reproducibility of pre-clinical studies and aid the interpretation and translation of results to humans with cancer.

Diet composition as a source of variation in experimental animal models of cancer cachexia

PubMed Central

Giles, Kaitlin; Guan, Chen; Jagoe, Thomas R.

2015-01-01

Abstract Background A variety of experimental animal models are used extensively to study mechanisms underlying cancer cachexia, and to identify potential treatments. The important potential confounding effect of dietary composition and intake used in many preclinical studies of cancer cachexia is frequently overlooked. Dietary designs applied in experimental studies should maximize the applicability to human cancer cachexia, meeting the essential requirements of the species used in the study, matched between treatment and control groups as well as also being generally similar to human consumption. Methods A literature review of scientific studies using animal models of cancer and cancer cachexia with dietary interventions was performed. Studies that investigated interventions using lipid sources were selected as the focus of discussion. Results The search revealed a number of nutrient intervention studies (n = 44), with the majority including n‐3 fatty acids (n = 16), mainly eicosapentaenoic acid and/or docosahexaenoic acid. A review of the literature revealed that the majority of studies do not provide information about dietary design; food intake or pair‐feeding is rarely reported. Further, there is a lack of standardization in dietary design, content, source, and overall composition in animal models of cancer cachexia. A model is proposed with the intent of guiding dietary design in preclinical studies to enable comparisons of dietary treatments within the same study, translation across different study designs, as well as application to human nutrient intakes. Conclusion The potential for experimental endpoints to be affected by variations in food intake, macronutrient content, and diet composition is likely. Diet content and composition should be reported, and food intake assessed. Minimum standards for diet definition in cachexia studies would improve reproducibility of pre‐clinical studies and aid the interpretation and translation of results to humans with cancer. PMID:27493865

A novel open-source drug-delivery system that allows for first-of-kind simulation of nonadherence to pharmacological interventions in animal disease models.

PubMed

Thomson, Kyle E; White, H Steve

2014-12-30

Nonadherence to a physician-prescribed therapeutic intervention is a costly, dangerous, and sometimes fatal concern in healthcare. To date, the study of nonadherence has been constrained to clinical studies. The novel approach described herein allows for the preclinical study of nonadherence in etiologically relevant disease animal model systems. The method herein describes a novel computer-automated pellet delivery system which allows for the study of nonadherence in animals. This system described herein allows for tight experimenter control of treatment using a drug-in-food protocol. Food-restricted animals receive either medicated or unmedicated pellets, designed to mimic either "taking" or "missing" a drug. The system described permits the distribution of medicated or unmedicated food pellets on an experimenter-defined feeding schedule. The flexibility of this system permits the delivery of drug according to the known pharmacokinetics of investigational drugs. Current clinical adherence research relies on medication-event monitoring system (MEMS) tracking caps, which allows clinicians to directly monitor patient adherence. However, correlating the effects of nonadherence to efficacy still relies on the accuracy of patient journals. This system allows for the design of studies to address the impact of nonadherence in an etiologically relevant animal model. Given methodological and ethical concerns of designing clinical studies of nonadherence, animal studies are critical to better understand medication adherence. While the system described was designed to measure the impact of nonadherence on seizure control, it is clear that the utility of this system extends beyond epilepsy to include other disease states. Copyright © 2014 Elsevier B.V. All rights reserved.

Optimized design and analysis of preclinical intervention studies in vivo

PubMed Central

Laajala, Teemu D.; Jumppanen, Mikael; Huhtaniemi, Riikka; Fey, Vidal; Kaur, Amanpreet; Knuuttila, Matias; Aho, Eija; Oksala, Riikka; Westermarck, Jukka; Mäkelä, Sari; Poutanen, Matti; Aittokallio, Tero

2016-01-01

Recent reports have called into question the reproducibility, validity and translatability of the preclinical animal studies due to limitations in their experimental design and statistical analysis. To this end, we implemented a matching-based modelling approach for optimal intervention group allocation, randomization and power calculations, which takes full account of the complex animal characteristics at baseline prior to interventions. In prostate cancer xenograft studies, the method effectively normalized the confounding baseline variability, and resulted in animal allocations which were supported by RNA-seq profiling of the individual tumours. The matching information increased the statistical power to detect true treatment effects at smaller sample sizes in two castration-resistant prostate cancer models, thereby leading to saving of both animal lives and research costs. The novel modelling approach and its open-source and web-based software implementations enable the researchers to conduct adequately-powered and fully-blinded preclinical intervention studies, with the aim to accelerate the discovery of new therapeutic interventions. PMID:27480578

Optimized design and analysis of preclinical intervention studies in vivo.

PubMed

Laajala, Teemu D; Jumppanen, Mikael; Huhtaniemi, Riikka; Fey, Vidal; Kaur, Amanpreet; Knuuttila, Matias; Aho, Eija; Oksala, Riikka; Westermarck, Jukka; Mäkelä, Sari; Poutanen, Matti; Aittokallio, Tero

2016-08-02

Recent reports have called into question the reproducibility, validity and translatability of the preclinical animal studies due to limitations in their experimental design and statistical analysis. To this end, we implemented a matching-based modelling approach for optimal intervention group allocation, randomization and power calculations, which takes full account of the complex animal characteristics at baseline prior to interventions. In prostate cancer xenograft studies, the method effectively normalized the confounding baseline variability, and resulted in animal allocations which were supported by RNA-seq profiling of the individual tumours. The matching information increased the statistical power to detect true treatment effects at smaller sample sizes in two castration-resistant prostate cancer models, thereby leading to saving of both animal lives and research costs. The novel modelling approach and its open-source and web-based software implementations enable the researchers to conduct adequately-powered and fully-blinded preclinical intervention studies, with the aim to accelerate the discovery of new therapeutic interventions.

Convection-Enhanced Delivery (CED) in an Animal Model of Malignant Peripheral Nerve Sheath Tumors and Plexiform Neurofibromas

DTIC Science & Technology

2011-09-01

with an accelerated schedule Convection-Enhanced Delivery ( CED ), Malignant Peripheral Nerve Sheath ( MPNST ), Plexiform Neurofibromas (PN...the distribution of macromolecules delivered to intraneural PNs and MPNST via CED . Design: Orthotopic xenograft models of sciatic intraneural NF1...determine the efficacy CED of the epidermal growth factor receptor (EGFR) inhibitor erlotinib in animal models of intraneural PNs and MPNST

Teaching Habitat and Animal Classification to Fourth Graders Using an Engineering-Design Model

ERIC Educational Resources Information Center

Marulcu, Ismail

2014-01-01

Background: The motivation for this work is built upon the premise that there is a need for research-based materials for design-based science instruction. In this paper, a small portion of our work investigating the impact of a LEGO[TM] engineering unit on fourth grade students' preconceptions and understanding of animals is presented. Purpose:…

A freely-moving monkey treadmill model

NASA Astrophysics Data System (ADS)

Foster, Justin D.; Nuyujukian, Paul; Freifeld, Oren; Gao, Hua; Walker, Ross; Ryu, Stephen I.; Meng, Teresa H.; Murmann, Boris; Black, Michael J.; Shenoy, Krishna V.

2014-08-01

Objective. Motor neuroscience and brain-machine interface (BMI) design is based on examining how the brain controls voluntary movement, typically by recording neural activity and behavior from animal models. Recording technologies used with these animal models have traditionally limited the range of behaviors that can be studied, and thus the generality of science and engineering research. We aim to design a freely-moving animal model using neural and behavioral recording technologies that do not constrain movement. Approach. We have established a freely-moving rhesus monkey model employing technology that transmits neural activity from an intracortical array using a head-mounted device and records behavior through computer vision using markerless motion capture. We demonstrate the flexibility and utility of this new monkey model, including the first recordings from motor cortex while rhesus monkeys walk quadrupedally on a treadmill. Main results. Using this monkey model, we show that multi-unit threshold-crossing neural activity encodes the phase of walking and that the average firing rate of the threshold crossings covaries with the speed of individual steps. On a population level, we find that neural state-space trajectories of walking at different speeds have similar rotational dynamics in some dimensions that evolve at the step rate of walking, yet robustly separate by speed in other state-space dimensions. Significance. Freely-moving animal models may allow neuroscientists to examine a wider range of behaviors and can provide a flexible experimental paradigm for examining the neural mechanisms that underlie movement generation across behaviors and environments. For BMIs, freely-moving animal models have the potential to aid prosthetic design by examining how neural encoding changes with posture, environment and other real-world context changes. Understanding this new realm of behavior in more naturalistic settings is essential for overall progress of basic motor neuroscience and for the successful translation of BMIs to people with paralysis.

Latest animal models for anti-HIV drug discovery.

PubMed

Sliva, Katja

2015-02-01

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

Animal models for microbicide safety and efficacy testing.

PubMed

Veazey, Ronald S

2013-07-01

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

Invited review: Experimental design, data reporting, and sharing in support of animal systems modeling research.

PubMed

McNamara, J P; Hanigan, M D; White, R R

2016-12-01

The National Animal Nutrition Program "National Research Support Project 9" supports efforts in livestock nutrition, including the National Research Council's committees on the nutrient requirements of animals. Our objective was to review the status of experimentation and data reporting in animal nutrition literature and to provide suggestions for the advancement of animal nutrition research and the ongoing improvement of field-applied nutrient requirement models. Improved data reporting consistency and completeness represent a substantial opportunity to improve nutrition-related mathematical models. We reviewed a body of nutrition research; recorded common phrases used to describe diets, animals, housing, and environmental conditions; and proposed equivalent numerical data that could be reported. With the increasing availability of online supplementary material sections in journals, we developed a comprehensive checklist of data that should be included in publications. To continue to improve our research effectiveness, studies utilizing multiple research methodologies to address complex systems and measure multiple variables will be necessary. From the current body of animal nutrition literature, we identified a series of opportunities to integrate research focuses (nutrition, reproduction and genetics) to advance the development of nutrient requirement models. From our survey of current experimentation and data reporting in animal nutrition, we identified 4 key opportunities to advance animal nutrition knowledge: (1) coordinated experiments should be designed to employ multiple research methodologies; (2) systems-oriented research approaches should be encouraged and supported; (3) publication guidelines should be updated to encourage and support sharing of more complete data sets; and (4) new experiments should be more rapidly integrated into our knowledge bases, research programs and practical applications. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Animal models in burn research.

PubMed

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

2014-09-01

Burn injury is a severe form of trauma affecting more than 2 million people in North America each year. Burn trauma is not a single pathophysiological event but a devastating injury that causes structural and functional deficits in numerous organ systems. Due to its complexity and the involvement of multiple organs, in vitro experiments cannot capture this complexity nor address the pathophysiology. In the past two decades, a number of burn animal models have been developed to replicate the various aspects of burn injury, to elucidate the pathophysiology, and to explore potential treatment interventions. Understanding the advantages and limitations of these animal models is essential for the design and development of treatments that are clinically relevant to humans. This review aims to highlight the common animal models of burn injury in order to provide investigators with a better understanding of the benefits and limitations of these models for translational applications. While many animal models of burn exist, we limit our discussion to the skin healing of mouse, rat, and pig. Additionally, we briefly explain hypermetabolic characteristics of burn injury and the animal model utilized to study this phenomena. Finally, we discuss the economic costs associated with each of these models in order to guide decisions of choosing the appropriate animal model for burn research.

Animal Models in Burn Research

PubMed Central

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

2014-01-01

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

a Geo-Visual Analytics Approach to Biological Shepherding: Modelling Animal Movements and Impacts

NASA Astrophysics Data System (ADS)

Benke, K. K.; Sheth, F.; Betteridge, K.; Pettit, C. J.; Aurambout, J.-P.

2012-07-01

The lamb industry in Victoria is a significant component of the state economy with annual exports in the vicinity of 1 billion. GPS and visualisation tools can be used to monitor grazing animal movements at the farm scale and observe interactions with the environment. Modelling the spatial-temporal movements of grazing animals in response to environmental conditions provides input for the design of paddocks with the aim of improving management procedures, animal performance and animal welfare. The term "biological shepherding" is associated with the re-design of environmental conditions and the analysis of responses from grazing animals. The combination of biological shepherding with geo-visual analytics (geo-spatial data analysis with visualisation) provides a framework for improving landscape design and supports research in grazing behaviour in variable landscapes, heat stress avoidance behaviour during summer months, and modelling excreta distributions (with respect to nitrogen emissions and nitrogen return for fertilising the paddock). Nitrogen losses due to excreta are mainly in the form of gaseous emissions to the atmosphere and leaching into the groundwater. In this study, background and context are provided in the case of biological shepherding and tracking animal movements. Examples are provided of recent applications in regional Australia and New Zealand. Based on experimental data and computer simulation, and using data visualisation and feature extraction, it was demonstrated that livestock excreta are not always randomly located, but concentrated around localised gathering points, sometimes separated by the nature of the excretion. Farmers require information on the nitrogen losses in order to reduce emissions to meet local and international nitrogen leaching and greenhouse gas targets and to improve the efficiency of nutrient management.

Zoning the territory of the Republic of Kazakhstan as to the risk of rabies among various categories of animals.

PubMed

Abdrakhmanov, Sarsenbay K; Sultanov, Akhmetzhan A; Beisembayev, Kanatzhan K; Korennoy, Fedor I; Кushubaev, Dosym B; Каdyrov, Ablaikhan S

2016-05-31

This paper presents the zoning of the territory of the Republic of Kazakhstan with respect to the risk of rabies outbreaks in domestic and wild animals considering environmental and climatic conditions. The national database of rabies outbreaks in Kazakhstan in the period 2003-2014 has been accessed in order to find which zones are consistently most exposed to the risk of rabies in animals. The database contains information on the cases in demes of farm livestock, domestic animals and wild animals. To identify the areas with the highest risk of outbreaks, we applied the maximum entropy modelling method. Designated outbreaks were used as input presence data, while the bioclim set of ecological and climatic variables, together with some geographic factors, were used as explanatory variables. The model demonstrated a high predictive ability. The area under the curve for farm livestock was 0.782, for domestic animals -0.859 and for wild animals - 0.809. Based on the model, the map of integral risk was designed by following four categories: negligible risk (disease-free or favourable zone), low risk (surveillance zone), medium risk (vaccination zone), and high risk (unfavourable zone). The map was produced to allow developing a set of preventive measures and is expected to contribute to a better distribution of supervisory efforts from the veterinary service of the country.

[Construction of EZH2 Knockout Animal Model by CRISPR/Cas9 Technology].

PubMed

Meng, Fanrong; Zhao, Dan; Zhou, Qinghua; Liu, Zhe

2018-05-20

It has been proven that CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated 9) system was the modern gene-editing technology through the constitutive expression of nucleases Cas9 in the mammalian, which binds to the specific site in the genome mediated by single-guide RNA (sgRNA) at desired genomic loci. The aim of this study is that the animal model of EZH2 gene knockout was constructed using CRISPR/Cas9 technology. In this study, we designed two single-guide RNAs targeting the Exon3 and Exon4 of EZH2 gene. Then, their gene-targeting efficiency were detected by SURVEYOR assay. The lentivirus was perfused into the lungs of mice by using a bronchial tube and detected by immunohistochemistry and qRT-PCR. The experimental results of NIH-3T3 cells verify that the designed sgEZH2 can efficiently effect the cleavage of target DNA by Cas9 in vitro. The immunohistochemistry and qRT-PCR results showed that the EZH2 expression in experimental group was significantly decreased in the mouse lung tissue. The study successfully designed two sgRNA which can play a knock-out EZH2 function. An EZH2 knockout animal model was successfully constructed by CRISPR/Cas9 system, and it will be an effective animal model for studying the functions and mechanisms of EZH2.

A Probablistic Diagram to Guide Chemical Design with ...

EPA Pesticide Factsheets

Toxicity is a concern with many chemicals currently in commerce, and with new chemicals that are introduced each year. The standard approach to testing chemicals is to run studies in laboratory animals (e.g. rats, mice, dogs), but because of the expense of these studies and concerns for animal welfare, few chemicals besides pharmaceuticals and pesticides are fully tested. Over the last decade there have been significant developments in the field of computational toxicology which combines in vitro tests and computational models. The ultimate goal of this ?field is to test all chemicals in a rapid, cost effective manner with minimal use of animals. One of the simplest measures of toxicity is provided by high-throughput in vitro cytotoxicity assays, which measure the concentration of a chemical that kills particular types of cells. Chemicals that are cytotoxic at low concentrations tend to be more toxic to animals than chemicals that are less cytotoxic. We employed molecular characteristics derived from density functional theory (DFT) and predicted values of log(octanol-water partition coe?fficient) (logP)to construct a design variable space, and built a predictive model for cytotoxicity using a Naive Bayesian algorithm. External evaluation showed that the area under the curve (AUC) for the receiver operating characteristic (ROC) of the model to be 0.81. Using this model, we provide design rules to help synthetic chemists minimize the chance that a newly synthesize

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

PubMed Central

Auer, Jorg A; Goodship, Allen; Arnoczky, Steven; Pearce, Simon; Price, Jill; Claes, Lutz; von Rechenberg, Brigitte; Hofmann-Amtenbrinck, Margarethe; Schneider, Erich; Müller-Terpitz, R; Thiele, F; Rippe, Klaus-Peter; Grainger, David W

2007-01-01

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; 10) Criteria for funding agencies to include requirements related to animal experiments as part of the overall scientific proposal review protocols. Such agencies are also encouraged to seriously consider and adopt the recommendations described here when awarding funds for specific projects. Specific new requirements and mandates related both to improving the welfare and scientific rigour of animal-based research models are urgently needed as part of international harmonization of standards. PMID:17678534

Convection-Enhanced Delivery (CED) in an Animal Model of Malignant Peripheral Nerve Sheath (MPNST) Tumors and Plexiform Neurofibromas (PN)

DTIC Science & Technology

2012-09-01

TITLE: Convection-Enhanced Delivery ( CED ) in an Animal Model of Malignant Peripheral Nerve Sheath ( MPNST ) Tumors and Plexiform Neurofibromas (PN...within the sciatic nerve. 15. SUBJECT TERMS Convection-Enhanced Delivery ( CED ), Malignant Peripheral Nerve Sheath ( MPNST ), Plexiform Neurofibromas...determine the distribution of macromolecules delivered to intraneural PNs and MPNST via CED . Design: Orthotopic xenograft models of sciatic intraneural

From sensor data to animal behaviour: an oystercatcher example.

PubMed

Shamoun-Baranes, Judy; Bom, Roeland; van Loon, E Emiel; Ens, Bruno J; Oosterbeek, Kees; Bouten, Willem

2012-01-01

Animal-borne sensors enable researchers to remotely track animals, their physiological state and body movements. Accelerometers, for example, have been used in several studies to measure body movement, posture, and energy expenditure, although predominantly in marine animals. In many studies, behaviour is often inferred from expert interpretation of sensor data and not validated with direct observations of the animal. The aim of this study was to derive models that could be used to classify oystercatcher (Haematopus ostralegus) behaviour based on sensor data. We measured the location, speed, and tri-axial acceleration of three oystercatchers using a flexible GPS tracking system and conducted simultaneous visual observations of the behaviour of these birds in their natural environment. We then used these data to develop three supervised classification trees of behaviour and finally applied one of the models to calculate time-activity budgets. The model based on accelerometer data developed to classify three behaviours (fly, terrestrial locomotion, and no movement) was much more accurate (cross-validation error = 0.14) than the model based on GPS-speed alone (cross-validation error = 0.35). The most parsimonious acceleration model designed to classify eight behaviours could distinguish five: fly, forage, body care, stand, and sit (cross-validation error = 0.28); other behaviours that were observed, such as aggression or handling of prey, could not be distinguished. Model limitations and potential improvements are discussed. The workflow design presented in this study can facilitate model development, be adapted to a wide range of species, and together with the appropriate measurements, can foster the study of behaviour and habitat use of free living animals throughout their annual routine.

The use of neurocomputational models as alternatives to animal models in the development of electrical brain stimulation treatments.

PubMed

Beuter, Anne

2017-05-01

Recent publications call for more animal models to be used and more experiments to be performed, in order to better understand the mechanisms of neurodegenerative disorders, to improve human health, and to develop new brain stimulation treatments. In response to these calls, some limitations of the current animal models are examined by using Deep Brain Stimulation (DBS) in Parkinson's disease as an illustrative example. Without focusing on the arguments for or against animal experimentation, or on the history of DBS, the present paper argues that given recent technological and theoretical advances, the time has come to consider bioinspired computational modelling as a valid alternative to animal models, in order to design the next generation of human brain stimulation treatments. However, before computational neuroscience is fully integrated in the translational process and used as a substitute for animal models, several obstacles need to be overcome. These obstacles are examined in the context of institutional, financial, technological and behavioural lock-in. Recommendations include encouraging agreement to change long-term habitual practices, explaining what alternative models can achieve, considering economic stakes, simplifying administrative and regulatory constraints, and carefully examining possible conflicts of interest. 2017 FRAME.

An improved mounting device for attaching intracranial probes in large animal models.

PubMed

Dunster, Kimble R

2015-12-01

The rigid support of intracranial probes can be difficult when using animal models, as mounting devices suitable for the probes are either not available, or designed for human use and not suitable in animal skulls. A cheap and reliable mounting device for securing intracranial probes in large animal models is described. Using commonly available clinical consumables, a universal mounting device for securing intracranial probes to the skull of large animals was developed and tested. A simply made mounting device to hold a variety of probes from 500 μm to 1.3 mm in diameter to the skull was developed. The device was used to hold probes to the skulls of sheep for up to 18 h. No adhesives or cements were used. The described device provides a reliable method of securing probes to the skull of animals.

Creating speech-synchronized animation.

PubMed

King, Scott A; Parent, Richard E

2005-01-01

We present a facial model designed primarily to support animated speech. Our facial model takes facial geometry as input and transforms it into a parametric deformable model. The facial model uses a muscle-based parameterization, allowing for easier integration between speech synchrony and facial expressions. Our facial model has a highly deformable lip model that is grafted onto the input facial geometry to provide the necessary geometric complexity needed for creating lip shapes and high-quality renderings. Our facial model also includes a highly deformable tongue model that can represent the shapes the tongue undergoes during speech. We add teeth, gums, and upper palate geometry to complete the inner mouth. To decrease the processing time, we hierarchically deform the facial surface. We also present a method to animate the facial model over time to create animated speech using a model of coarticulation that blends visemes together using dominance functions. We treat visemes as a dynamic shaping of the vocal tract by describing visemes as curves instead of keyframes. We show the utility of the techniques described in this paper by implementing them in a text-to-audiovisual-speech system that creates animation of speech from unrestricted text. The facial and coarticulation models must first be interactively initialized. The system then automatically creates accurate real-time animated speech from the input text. It is capable of cheaply producing tremendous amounts of animated speech with very low resource requirements.

Experimental liver fibrosis research: update on animal models, legal issues and translational aspects

PubMed Central

2013-01-01

Liver fibrosis is defined as excessive extracellular matrix deposition and is based on complex interactions between matrix-producing hepatic stellate cells and an abundance of liver-resident and infiltrating cells. Investigation of these processes requires in vitro and in vivo experimental work in animals. However, the use of animals in translational research will be increasingly challenged, at least in countries of the European Union, because of the adoption of new animal welfare rules in 2013. These rules will create an urgent need for optimized standard operating procedures regarding animal experimentation and improved international communication in the liver fibrosis community. This review gives an update on current animal models, techniques and underlying pathomechanisms with the aim of fostering a critical discussion of the limitations and potential of up-to-date animal experimentation. We discuss potential complications in experimental liver fibrosis and provide examples of how the findings of studies in which these models are used can be translated to human disease and therapy. In this review, we want to motivate the international community to design more standardized animal models which might help to address the legally requested replacement, refinement and reduction of animals in fibrosis research. PMID:24274743

[The design and development of a quality system for the diagnosis of exotic animal diseases at the National Centre for Animal and Plant Health in Cuba].

PubMed

de Oca, N Montes; Villoch, A; Pérez Ruano, M

2004-12-01

A quality system for the diagnosis of exotic animal diseases was developed at the national centre for animal and plant health (CENSA), responsible for coordinating the clinical, epizootiological and laboratory diagnosis of causal agents of exotic animal diseases in Cuba. A model was designed on the basis of standard ISO 9001:2000 of the International Organization for Standardization (ISO), standard ISO/IEC 17025:1999 of ISO and the International Electrotechnical Commission, recommendations of the World Organisation for Animal Health (OIE) and other regulatory documents from international and national organisations that deal specifically with the treatment of emerging diseases. Twenty-nine standardised operating procedures were developed, plus 13 registers and a checklist to facilitate the evaluation of the system. The effectiveness of the quality system was confirmed in the differential diagnosis of classical swine fever at an animal virology laboratory in Cuba.

Treatment of severe porcine tracheomalacia with a 3-dimensionally printed, bioresorbable, external airway splint

PubMed Central

Zopf, David A.; Flanagan, Colleen L.; Wheeler, Matthew; Hollister, Scott J.; Green, Glenn E.

2015-01-01

Importance The study demonstrates an application for 3-dimensional (3D) printing that may serve as an effective intervention for severe tracheobronchomalacia. Objective A novel 3D printed, bioresorbable airway splint is tested for efficacy in extending survival in an animal model of severe, life-threatening tracheobronchomalacia. Participants Evaluation of an external airway splint for severe, life-threatening tracheobronchomalacia in a porcine animal model. Setting Multi-institutional and multidisciplinary collaboration between biomedical engineering laboratories and an academic animal surgery center. Interventions Experimental analysis of a 3D printed, bioresorbable airway splint is assessed in a porcine animal model of life-threatening tracheobronchomalacia. The open-cylindrical, bellow shaped porous polycaprolactone splint is placed externally and designed to suspend the underlying collapsed airway. Control animals (n=3) undergoing tracheal cartilage division and inner tracheal lumen dissociation and experimental animals (n=3) receiving the same model with overlying placement of the newly developed airway splint were evaluated. Main Outcomes and Measures An animal model for severe, life-threatening tracheobronchomalacia is proposed. Complete or near complete tracheal lumen collapse was observed in each animal with resolution of symptoms in all of the experimental animals after splint placement. Using our severe tracheobronchomalacia animal model, survival was significantly longer in duration in the experimental group receiving the airway splint after model creation when compared to model creation alone (p = 0.0495). Mortality in the experimental group was related to infection. Conclusions A multidisciplinary effort producing a CAD/CAM, bioresorbable tracheobronchial splint was tested in a porcine model of severe tracheomalacia and was found to extend survival. PMID:24232078

Considerations for Experimental Animal Models of Concussion, Traumatic Brain Injury, and Chronic Traumatic Encephalopathy—These Matters Matter

PubMed Central

Wojnarowicz, Mark W.; Fisher, Andrew M.; Minaeva, Olga; Goldstein, Lee E.

2017-01-01

Animal models of concussion, traumatic brain injury (TBI), and chronic traumatic encephalopathy (CTE) are widely available and routinely deployed in laboratories around the world. Effective animal modeling requires careful consideration of four basic principles. First, animal model use must be guided by clarity of definitions regarding the human disease or condition being modeled. Concussion, TBI, and CTE represent distinct clinical entities that require clear differentiation: concussion is a neurological syndrome, TBI is a neurological event, and CTE is a neurological disease. While these conditions are all associated with head injury, the pathophysiology, clinical course, and medical management of each are distinct. Investigators who use animal models of these conditions must take into account these clinical distinctions to avoid misinterpretation of results and category mistakes. Second, model selection must be grounded by clarity of purpose with respect to experimental questions and frame of reference of the investigation. Distinguishing injury context (“inputs”) from injury consequences (“outputs”) may be helpful during animal model selection, experimental design and execution, and interpretation of results. Vigilance is required to rout out, or rigorously control for, model artifacts with potential to interfere with primary endpoints. The widespread use of anesthetics in many animal models illustrates the many ways that model artifacts can confound preclinical results. Third, concordance between key features of the animal model and the human disease or condition being modeled is required to confirm model biofidelity. Fourth, experimental results observed in animals must be confirmed in human subjects for model validation. Adherence to these principles serves as a bulwark against flawed interpretation of results, study replication failure, and confusion in the field. Implementing these principles will advance basic science discovery and accelerate clinical translation to benefit people affected by concussion, TBI, and CTE. PMID:28620350

Animal Models of Bone Metastasis

PubMed Central

Simmons, J. K.; Hildreth, B. E.; Supsavhad, W.; Elshafae, S. M.; Hassan, B. B.; Dirksen, W. P.; Toribio, R. E.; Rosol, T. J.

2015-01-01

Bone is one of the most common sites of cancer metastasis in humans and is a significant source of morbidity and mortality. Bone metastases are considered incurable and result in pain, pathologic fracture, and decreased quality of life. Animal models of skeletal metastases are essential to improve the understanding of the molecular pathways of cancer metastasis and growth in bone and to develop new therapies to inhibit and prevent bone metastases. The ideal animal model should be clinically relevant, reproducible, and representative of human disease. Currently, an ideal model does not exist; however, understanding the strengths and weaknesses of the available models will lead to proper study design and successful cancer research. This review provides an overview of the current in vivo animal models used in the study of skeletal metastases or local tumor invasion into bone and focuses on mammary and prostate cancer, lymphoma, multiple myeloma, head and neck squamous cell carcinoma, and miscellaneous tumors that metastasize to bone. PMID:26021553

How can animal models inform on the transition to chronic symptoms in whiplash?

PubMed Central

Winkelstein, Beth A.

2011-01-01

Study Design A non-systematic review of the literature. Objective The objective was to present general schema for mechanisms of whiplash pain and review the role of animal models in understanding the development of chronic pain from whiplash injury. Summary of Background Data Extensive biomechanical and clinical studies of whiplash have been performed to understand the injury mechanisms and symptoms of whiplash injury. However, only recently have animal models of this painful disorder been developed based on other pain models in the literature. Methods A non-systematic review was performed and findings were integrated to formulate a generalized picture of mechanisms by chronic whiplash pain develops from mechanical tissue injuries. Results The development of chronic pain from tissue injuries in the neck due to whiplash involves complex interactions between the injured tissue and spinal neuroimmune circuits. A variety of animal models are beginning to define these mechanisms. Conclusion Continued work is needed in developing appropriate animal models to investigate chronic pain from whiplash injuries and care must be taken to determine whether such models aim to model the injury event or the pain symptom. PMID:22020616

Medical Illustration

MedlinePlus

... or designers in the development of educational games, documentaries, or public education campaigns. They also may organize ... design, visual storytelling, three-dimensional modeling and animation, management and business practices, and professional ethics. Certification/Registration ...

A Protocol for Using Gene Set Enrichment Analysis to Identify the Appropriate Animal Model for Translational Research.

PubMed

Weidner, Christopher; Steinfath, Matthias; Wistorf, Elisa; Oelgeschläger, Michael; Schneider, Marlon R; Schönfelder, Gilbert

2017-08-16

Recent studies that compared transcriptomic datasets of human diseases with datasets from mouse models using traditional gene-to-gene comparison techniques resulted in contradictory conclusions regarding the relevance of animal models for translational research. A major reason for the discrepancies between different gene expression analyses is the arbitrary filtering of differentially expressed genes. Furthermore, the comparison of single genes between different species and platforms often is limited by technical variance, leading to misinterpretation of the con/discordance between data from human and animal models. Thus, standardized approaches for systematic data analysis are needed. To overcome subjective gene filtering and ineffective gene-to-gene comparisons, we recently demonstrated that gene set enrichment analysis (GSEA) has the potential to avoid these problems. Therefore, we developed a standardized protocol for the use of GSEA to distinguish between appropriate and inappropriate animal models for translational research. This protocol is not suitable to predict how to design new model systems a-priori, as it requires existing experimental omics data. However, the protocol describes how to interpret existing data in a standardized manner in order to select the most suitable animal model, thus avoiding unnecessary animal experiments and misleading translational studies.

From the track to the ocean: Using flow control to improve marine bio-logging tags for cetaceans

PubMed Central

Fiore, Giovani; Anderson, Erik; Garborg, C. Spencer; Murray, Mark; Johnson, Mark; Moore, Michael J.; Howle, Laurens

2017-01-01

Bio-logging tags are an important tool for the study of cetaceans, but superficial tags inevitably increase hydrodynamic loading. Substantial forces can be generated by tags on fast-swimming animals, potentially affecting behavior and energetics or promoting early tag removal. Streamlined forms have been used to reduce loading, but these designs can accelerate flow over the top of the tag. This non-axisymmetric flow results in large lift forces (normal to the animal) that become the dominant force component at high speeds. In order to reduce lift and minimize total hydrodynamic loading this work presents a new tag design (Model A) that incorporates a hydrodynamic body, a channel to reduce fluid speed differences above and below the housing and wing to redirect flow to counter lift. Additionally, three derivatives of the Model A design were used to examine the contribution of individual flow control features to overall performance. Hydrodynamic loadings of four models were compared using computational fluid dynamics (CFD). The Model A design eliminated all lift force and generated up to ~30 N of downward force in simulated 6 m/s aligned flow. The simulations were validated using particle image velocimetry (PIV) to experimentally characterize the flow around the tag design. The results of these experiments confirm the trends predicted by the simulations and demonstrate the potential benefit of flow control elements for the reduction of tag induced forces on the animal. PMID:28196148

Computed tomography-based tissue-engineered scaffolds in craniomaxillofacial surgery.

PubMed

Smith, M H; Flanagan, C L; Kemppainen, J M; Sack, J A; Chung, H; Das, S; Hollister, S J; Feinberg, S E

2007-09-01

Tissue engineering provides an alternative modality allowing for decreased morbidity of donor site grafting and decreased rejection of less compatible alloplastic tissues. Using image-based design and computer software, a precisely sized and shaped scaffold for osseous tissue regeneration can be created via selective laser sintering. Polycaprolactone has been used to create a condylar ramus unit (CRU) scaffold for application in temporomandibular joint reconstruction in a Yucatan minipig animal model. Following sacrifice, micro-computed tomography and histology was used to demonstrate the efficacy of this particular scaffold design. A proof-of-concept surgery has demonstrated cartilaginous tissue regeneration along the articulating surface with exuberant osseous tissue formation. Bone volumes and tissue mineral density at both the 1 and 3 month time points demonstrated significant new bone growth interior and exterior to the scaffold. Computationally designed scaffolds can support masticatory function in a large animal model as well as both osseous and cartilage regeneration. Our group is continuing to evaluate multiple implant designs in both young and mature Yucatan minipig animals. 2007 John Wiley & Sons, Ltd.

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

PubMed Central

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

2007-01-01

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

Animal behavioral assessments in current research of Parkinson's disease.

PubMed

Asakawa, Tetsuya; Fang, Huan; Sugiyama, Kenji; Nozaki, Takao; Hong, Zhen; Yang, Yilin; Hua, Fei; Ding, Guanghong; Chao, Dongman; Fenoy, Albert J; Villarreal, Sebastian J; Onoe, Hirotaka; Suzuki, Katsuaki; Mori, Norio; Namba, Hiroki; Xia, Ying

2016-06-01

Parkinson's disease (PD), a neurodegenerative disorder, is traditionally classified as a movement disorder. Patients typically suffer from many motor dysfunctions. Presently, clinicians and scientists recognize that many non-motor symptoms are associated with PD. There is an increasing interest in both motor and non-motor symptoms in clinical studies on PD patients and laboratory research on animal models that imitate the pathophysiologic features and symptoms of PD patients. Therefore, appropriate behavioral assessments are extremely crucial for correctly understanding the mechanisms of PD and accurately evaluating the efficacy and safety of novel therapies. This article systematically reviews the behavioral assessments, for both motor and non-motor symptoms, in various animal models involved in current PD research. We addressed the strengths and weaknesses of these behavioral tests and their appropriate applications. Moreover, we discussed potential mechanisms behind these behavioral tests and cautioned readers against potential experimental bias. Since most of the behavioral assessments currently used for non-motor symptoms are not particularly designed for animals with PD, it is of the utmost importance to greatly improve experimental design and evaluation in PD research with animal models. Indeed, it is essential to develop specific assessments for non-motor symptoms in PD animals based on their characteristics. We concluded with a prospective view for behavioral assessments with real-time assessment with mobile internet and wearable device in future PD research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Role of Animal Models in Coronary Stenting.

PubMed

Iqbal, Javaid; Chamberlain, Janet; Francis, Sheila E; Gunn, Julian

2016-02-01

Coronary angioplasty initially employed balloon dilatation only. This technique revolutionized the treatment of coronary artery disease, although outcomes were compromised by acute vessel closure, late constrictive remodeling, and restenosis due to neointimal proliferation. These processes were studied in animal models, which contributed to understanding the biology of endovascular arterial injury. Coronary stents overcome acute recoil, with improvements in the design and metallurgy since then, leading to the development of drug-eluting stents and bioresorbable scaffolds. These devices now undergo computer modeling and benchtop and animal testing before evaluation in clinical trials. Animal models, including rabbit, sheep, dog and pig are available, all with individual benefits and limitations. In smaller mammals, such as mouse and rabbit, the target for stenting is generally the aorta; whereas in larger animals, such as the pig, it is generally the coronary artery. The pig coronary stenting model is a gold-standard for evaluating safety; but insights into biomechanical properties, the biology of stenting, and efficacy in controlling neointimal proliferation can also be gained. Intra-coronary imaging modalities such as intravascular ultrasound and optical coherence tomography allow precise serial evaluation in vivo, and recent developments in genetically modified animal models of atherosclerosis provide realistic test beds for future stents and scaffolds.

Understanding Gulf War Illness: An Integrative Modeling Approach

DTIC Science & Technology

2017-10-01

group (Task 2; Subtask1). The latest iteration of this analysis focused on n=11 animals control and n=11 DFP exposed animals without corticosterone... Groups : 1 – Control Group (Male and Female Intact) 2 – GWI Model – Cort+DFP (Male and Female OVX) 3 – Control OVX (Female) 4 – GWI Model + Enbrel...The designed protocol counts with five basic experimental groups : Group 1 (Untreated Control no toxic exposure); Group 2 (Toxic exposed, no

A Guide to Neurotoxic Animal Models of Parkinson’s Disease

PubMed Central

Tieu, Kim

2011-01-01

Parkinson’s disease (PD) is a neurological movement disorder primarily resulting from damage to the nigrostriatal dopaminergic pathway. To elucidate the pathogenesis, mechanisms of cell death, and to evaluate therapeutic strategies for PD, numerous animal models have been developed. Understanding the strengths and limitations of these models can significantly impact the choice of model, experimental design, and data interpretation. The primary objectives of this article are twofold: First, to assist new investigators who are contemplating embarking on PD research to navigate through the available animal models. Emphasis will be placed on common neurotoxic murine models in which toxic molecules are used to lesion the nigrostriatal dopaminergic system. And second, to provide an overview of basic technical requirements for assessing the pathology, structure, and function of the nigrostriatal pathway. PMID:22229125

Operational Details of the Five Domains Model and Its Key Applications to the Assessment and Management of Animal Welfare

PubMed Central

Mellor, David J.

2017-01-01

Simple Summary The Five Domains Model is a focusing device to facilitate systematic, structured, comprehensive and coherent assessment of animal welfare; it is not a definition of animal welfare, nor is it intended to be an accurate representation of body structure and function. The purpose of each of the five domains is to draw attention to areas that are relevant to both animal welfare assessment and management. This paper begins by briefly describing the major features of the Model and the operational interactions between the five domains, and then it details seven interacting applications of the Model. These underlie its utility and increasing application to welfare assessment and management in diverse animal use sectors. Abstract In accord with contemporary animal welfare science understanding, the Five Domains Model has a significant focus on subjective experiences, known as affects, which collectively contribute to an animal’s overall welfare state. Operationally, the focus of the Model is on the presence or absence of various internal physical/functional states and external circumstances that give rise to welfare-relevant negative and/or positive mental experiences, i.e., affects. The internal states and external circumstances of animals are evaluated systematically by referring to each of the first four domains of the Model, designated “Nutrition”, “Environment”, “Health” and “Behaviour”. Then affects, considered carefully and cautiously to be generated by factors in these domains, are accumulated into the fifth domain, designated “Mental State”. The scientific foundations of this operational procedure, published in detail elsewhere, are described briefly here, and then seven key ways the Model may be applied to the assessment and management of animal welfare are considered. These applications have the following beneficial objectives—they (1) specify key general foci for animal welfare management; (2) highlight the foundations of specific welfare management objectives; (3) identify previously unrecognised features of poor and good welfare; (4) enable monitoring of responses to specific welfare-focused remedial interventions and/or maintenance activities; (5) facilitate qualitative grading of particular features of welfare compromise and/or enhancement; (6) enable both prospective and retrospective animal welfare assessments to be conducted; and, (7) provide adjunct information to support consideration of quality of life evaluations in the context of end-of-life decisions. However, also noted is the importance of not overstating what utilisation of the Model can achieve. PMID:28792485

A virtual reality task based on animal research – spatial learning and memory in patients after the first episode of schizophrenia

PubMed Central

Fajnerová, Iveta; Rodriguez, Mabel; Levčík, David; Konrádová, Lucie; Mikoláš, Pavol; Brom, Cyril; Stuchlík, Aleš; Vlček, Kamil; Horáček, Jiří

2014-01-01

Objectives: Cognitive deficit is considered to be a characteristic feature of schizophrenia disorder. A similar cognitive dysfunction was demonstrated in animal models of schizophrenia. However, the poor comparability of methods used to assess cognition in animals and humans could be responsible for low predictive validity of current animal models. In order to assess spatial abilities in schizophrenia and compare our results with the data obtained in animal models, we designed a virtual analog of the Morris water maze (MWM), the virtual Four Goals Navigation (vFGN) task. Methods: Twenty-nine patients after the first psychotic episode with schizophrenia symptoms and a matched group of healthy volunteers performed the vFGN task. They were required to find and remember four hidden goal positions in an enclosed virtual arena. The task consisted of two parts. The Reference memory (RM) session with a stable goal position was designed to test spatial learning. The Delayed-matching-to-place (DMP) session presented a modified working memory protocol designed to test the ability to remember a sequence of three hidden goal positions. Results: Data obtained in the RM session show impaired spatial learning in schizophrenia patients compared to the healthy controls in pointing and navigation accuracy. The DMP session showed impaired spatial memory in schizophrenia during the recall of spatial sequence and a similar deficit in spatial bias in the probe trials. The pointing accuracy and the quadrant preference showed higher sensitivity toward the cognitive deficit than the navigation accuracy. Direct navigation to the goal was affected by sex and age of the tested subjects. The age affected spatial performance only in healthy controls. Conclusions: Despite some limitations of the study, our results correspond well with the previous studies in animal models of schizophrenia and support the decline of spatial cognition in schizophrenia, indicating the usefulness of the vFGN task in comparative research. PMID:24904329

The virtual lover: variable and easily guided 3D fish animations as an innovative tool in mate-choice experiments with sailfin mollies-I. Design and implementation

PubMed Central

Smielik, Ievgen; Hütwohl, Jan-Marco; Gierszewski, Stefanie; Witte, Klaudia; Kuhnert, Klaus-Dieter

2017-01-01

Abstract Animal behavior researchers often face problems regarding standardization and reproducibility of their experiments. This has led to the partial substitution of live animals with artificial virtual stimuli. In addition to standardization and reproducibility, virtual stimuli open new options for researchers since they are easily changeable in morphology and appearance, and their behavior can be defined. In this article, a novel toolchain to conduct behavior experiments with fish is presented by a case study in sailfin mollies Poecilia latipinna. As the toolchain holds many different and novel features, it offers new possibilities for studies in behavioral animal research and promotes the standardization of experiments. The presented method includes options to design, animate, and present virtual stimuli to live fish. The designing tool offers an easy and user-friendly way to define size, coloration, and morphology of stimuli and moreover it is able to configure virtual stimuli randomly without any user influence. Furthermore, the toolchain brings a novel method to animate stimuli in a semiautomatic way with the help of a game controller. These created swimming paths can be applied to different stimuli in real time. A presentation tool combines models and swimming paths regarding formerly defined playlists, and presents the stimuli onto 2 screens. Experiments with live sailfin mollies validated the usage of the created virtual 3D fish models in mate-choice experiments. PMID:29491963

The virtual lover: variable and easily guided 3D fish animations as an innovative tool in mate-choice experiments with sailfin mollies-I. Design and implementation.

PubMed

Müller, Klaus; Smielik, Ievgen; Hütwohl, Jan-Marco; Gierszewski, Stefanie; Witte, Klaudia; Kuhnert, Klaus-Dieter

2017-02-01

Animal behavior researchers often face problems regarding standardization and reproducibility of their experiments. This has led to the partial substitution of live animals with artificial virtual stimuli. In addition to standardization and reproducibility, virtual stimuli open new options for researchers since they are easily changeable in morphology and appearance, and their behavior can be defined. In this article, a novel toolchain to conduct behavior experiments with fish is presented by a case study in sailfin mollies Poecilia latipinna . As the toolchain holds many different and novel features, it offers new possibilities for studies in behavioral animal research and promotes the standardization of experiments. The presented method includes options to design, animate, and present virtual stimuli to live fish. The designing tool offers an easy and user-friendly way to define size, coloration, and morphology of stimuli and moreover it is able to configure virtual stimuli randomly without any user influence. Furthermore, the toolchain brings a novel method to animate stimuli in a semiautomatic way with the help of a game controller. These created swimming paths can be applied to different stimuli in real time. A presentation tool combines models and swimming paths regarding formerly defined playlists, and presents the stimuli onto 2 screens. Experiments with live sailfin mollies validated the usage of the created virtual 3D fish models in mate-choice experiments.

Development and Training of a Neural Controller for Hind Leg Walking in a Dog Robot

PubMed Central

Hunt, Alexander; Szczecinski, Nicholas; Quinn, Roger

2017-01-01

Animals dynamically adapt to varying terrain and small perturbations with remarkable ease. These adaptations arise from complex interactions between the environment and biomechanical and neural components of the animal's body and nervous system. Research into mammalian locomotion has resulted in several neural and neuro-mechanical models, some of which have been tested in simulation, but few “synthetic nervous systems” have been implemented in physical hardware models of animal systems. One reason is that the implementation into a physical system is not straightforward. For example, it is difficult to make robotic actuators and sensors that model those in the animal. Therefore, even if the sensorimotor circuits were known in great detail, those parameters would not be applicable and new parameter values must be found for the network in the robotic model of the animal. This manuscript demonstrates an automatic method for setting parameter values in a synthetic nervous system composed of non-spiking leaky integrator neuron models. This method works by first using a model of the system to determine required motor neuron activations to produce stable walking. Parameters in the neural system are then tuned systematically such that it produces similar activations to the desired pattern determined using expected sensory feedback. We demonstrate that the developed method successfully produces adaptive locomotion in the rear legs of a dog-like robot actuated by artificial muscles. Furthermore, the results support the validity of current models of mammalian locomotion. This research will serve as a basis for testing more complex locomotion controllers and for testing specific sensory pathways and biomechanical designs. Additionally, the developed method can be used to automatically adapt the neural controller for different mechanical designs such that it could be used to control different robotic systems. PMID:28420977

Animal models of ischemic stroke and their application in clinical research.

PubMed

Fluri, Felix; Schuhmann, Michael K; Kleinschnitz, Christoph

2015-01-01

This review outlines the most frequently used rodent stroke models and discusses their strengths and shortcomings. Mimicking all aspects of human stroke in one animal model is not feasible because ischemic stroke in humans is a heterogeneous disorder with a complex pathophysiology. The transient or permanent middle cerebral artery occlusion (MCAo) model is one of the models that most closely simulate human ischemic stroke. Furthermore, this model is characterized by reliable and well-reproducible infarcts. Therefore, the MCAo model has been involved in the majority of studies that address pathophysiological processes or neuroprotective agents. Another model uses thromboembolic clots and thus is more convenient for investigating thrombolytic agents and pathophysiological processes after thrombolysis. However, for many reasons, preclinical stroke research has a low translational success rate. One factor might be the choice of stroke model. Whereas the therapeutic responsiveness of permanent focal stroke in humans declines significantly within 3 hours after stroke onset, the therapeutic window in animal models with prompt reperfusion is up to 12 hours, resulting in a much longer action time of the investigated agent. Another major problem of animal stroke models is that studies are mostly conducted in young animals without any comorbidity. These models differ from human stroke, which particularly affects elderly people who have various cerebrovascular risk factors. Choosing the most appropriate stroke model and optimizing the study design of preclinical trials might increase the translational potential of animal stroke models.

Animal models of ischemic stroke and their application in clinical research

PubMed Central

Fluri, Felix; Schuhmann, Michael K; Kleinschnitz, Christoph

2015-01-01

This review outlines the most frequently used rodent stroke models and discusses their strengths and shortcomings. Mimicking all aspects of human stroke in one animal model is not feasible because ischemic stroke in humans is a heterogeneous disorder with a complex pathophysiology. The transient or permanent middle cerebral artery occlusion (MCAo) model is one of the models that most closely simulate human ischemic stroke. Furthermore, this model is characterized by reliable and well-reproducible infarcts. Therefore, the MCAo model has been involved in the majority of studies that address pathophysiological processes or neuroprotective agents. Another model uses thromboembolic clots and thus is more convenient for investigating thrombolytic agents and pathophysiological processes after thrombolysis. However, for many reasons, preclinical stroke research has a low translational success rate. One factor might be the choice of stroke model. Whereas the therapeutic responsiveness of permanent focal stroke in humans declines significantly within 3 hours after stroke onset, the therapeutic window in animal models with prompt reperfusion is up to 12 hours, resulting in a much longer action time of the investigated agent. Another major problem of animal stroke models is that studies are mostly conducted in young animals without any comorbidity. These models differ from human stroke, which particularly affects elderly people who have various cerebrovascular risk factors. Choosing the most appropriate stroke model and optimizing the study design of preclinical trials might increase the translational potential of animal stroke models. PMID:26170628

Vaxar: A Web-Based Database of Laboratory Animal Responses to Vaccinations and Its Application in the Meta-Analysis of Different Animal Responses to Tuberculosis Vaccinations

PubMed Central

Todd, Thomas; Dunn, Natalie; Xiang, Zuoshuang; He, Yongqun

2016-01-01

Animal models are indispensable for vaccine research and development. However, choosing which species to use and designing a vaccine study that is optimized for that species is often challenging. Vaxar (http://www.violinet.org/vaxar/) is a web-based database and analysis system that stores manually curated data regarding vaccine-induced responses in animals. To date, Vaxar encompasses models from 35 animal species including rodents, rabbits, ferrets, primates, and birds. These 35 species have been used to study more than 1300 experimentally tested vaccines for 164 pathogens and diseases significant to humans and domestic animals. The responses to vaccines by animals in more than 1500 experimental studies are recorded in Vaxar; these data can be used for systematic meta-analysis of various animal responses to a particular vaccine. For example, several variables, including animal strain, animal age, and the dose or route of either vaccination or challenge, might affect host response outcomes. Vaxar can also be used to identify variables that affect responses to different vaccines in a specific animal model. All data stored in Vaxar are publically available for web-based queries and analyses. Overall Vaxar provides a unique systematic approach for understanding vaccine-induced host immunity. PMID:27053566

Large animal models for vaccine development and testing.

PubMed

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

2015-01-01

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

A Guide for the Design of Pre-clinical Studies on Sex Differences in Metabolism.

PubMed

Mauvais-Jarvis, Franck; Arnold, Arthur P; Reue, Karen

2017-06-06

In animal models, the physiological systems involved in metabolic homeostasis exhibit a sex difference. Investigators often use male rodents because they show metabolic disease better than females. Thus, females are not used precisely because of an acknowledged sex difference that represents an opportunity to understand novel factors reducing metabolic disease more in one sex than the other. The National Institutes of Health (NIH) mandate to consider sex as a biological variable in preclinical research places new demands on investigators and peer reviewers who often lack expertise in model systems and experimental paradigms used in the study of sex differences. This Perspective discusses experimental design and interpretation in studies addressing the mechanisms of sex differences in metabolic homeostasis and disease, using animal models and cells. We also highlight current limitations in research tools and attitudes that threaten to delay progress in studies of sex differences in basic animal research. Copyright © 2017 Elsevier Inc. All rights reserved.

Fidelity in Animal Modeling: Prerequisite for a Mechanistic Research Front Relevant to the Inflammatory Incompetence of Acute Pediatric Malnutrition.

PubMed

Woodward, Bill

2016-04-11

Inflammatory incompetence is characteristic of acute pediatric protein-energy malnutrition, but its underlying mechanisms remain obscure. Perhaps substantially because the research front lacks the driving force of a scholarly unifying hypothesis, it is adrift and research activity is declining. A body of animal-based research points to a unifying paradigm, the Tolerance Model, with some potential to offer coherence and a mechanistic impetus to the field. However, reasonable skepticism prevails regarding the relevance of animal models of acute pediatric malnutrition; consequently, the fundamental contributions of the animal-based component of this research front are largely overlooked. Design-related modifications to improve the relevance of animal modeling in this research front include, most notably, prioritizing essential features of pediatric malnutrition pathology rather than dietary minutiae specific to infants and children, selecting windows of experimental animal development that correspond to targeted stages of pediatric immunological ontogeny, and controlling for ontogeny-related confounders. In addition, important opportunities are presented by newer tools including the immunologically humanized mouse and outbred stocks exhibiting a magnitude of genetic heterogeneity comparable to that of human populations. Sound animal modeling is within our grasp to stimulate and support a mechanistic research front relevant to the immunological problems that accompany acute pediatric malnutrition.

Animal models for osteoporosis

NASA Technical Reports Server (NTRS)

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

2001-01-01

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

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

PubMed

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

2011-10-01

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

Laboratory animal science: a resource to improve the quality of science.

PubMed

Forni, M

2007-08-01

The contribution of animal experimentation to biomedical research is of undoubted value, nevertheless the real usefulness of animal models is still being hotly debated. Laboratory Animal Science is a multidisciplinary approach to humane animal experimentation that allows the choice of the correct animal model and the collection of unbiased data. Refinement, Reduction and Replacement, the "3Rs rule", are now widely accepted and have a major influence on animal experimentation procedures. Refinement, namely any decrease in the incidence or severity of inhumane procedures applied to animals, has been today extended to the entire lives of the experimental animals. Reduction of the number of animals used to obtain statistically significant data may be achieved by improving experimental design and statistical analysis of data. Replacement refers to the development of validated alternative methods. A Laboratory Animal Science training program in biomedical degrees can promote the 3Rs and improve the welfare of laboratory animals as well as the quality of science with ethical, scientific and economic advantages complying with the European requirement that "persons who carry out, take part in, or supervise procedures on animals, or take care of animals used in procedures, shall have had appropriate education and training".

Artificial pigs in space: using artificial intelligence and artificial life techniques to design animal housing.

PubMed

Stricklin, W R; de Bourcier, P; Zhou, J Z; Gonyou, H W

1998-10-01

Computer simulations have been used by us since the early 1970s to gain an understanding of the spacing and movement patterns of confined animals. The work has progressed from the early stages, in which we used randomly positioned points, to current investigations of animats (computer-simulated animals), which show low levels of learning via artificial neural networks. We have determined that 1) pens of equal floor area but of different shape result in different spatial and movement patterns for randomly positioned and moving animats; 2) when group size increases under constant density, freedom of movement approaches an asymptote at approximately six animats; 3) matching the number of animats with the number of corners results in optimal freedom of movement for small groups of animats; and 4) perimeter positioning occurs in groups of animats that maximize their distance to first- and second-nearest neighbors. Recently, we developed animats that move, compete for social dominance, and are motivated to obtain resources (food, resting sites, etc.). We are currently developing an animat that learns its behavior from the spatial and movement data collected on live pigs. The animat model is then used to pretest pen designs, followed by new pig spatial data fed into the animat model, resulting in a new pen design to be tested, and the steps are repeated. We believe that methodologies from artificial-life and artificial intelligence can contribute to the understanding of basic animal behavior principles, as well as to the solving of problems in production agriculture in areas such as animal housing design.

A guide to using functional magnetic resonance imaging to study Alzheimer's disease in animal models.

PubMed

Asaad, Mazen; Lee, Jin Hyung

2018-05-18

Alzheimer's disease is a leading healthcare challenge facing our society today. Functional magnetic resonance imaging (fMRI) of the brain has played an important role in our efforts to understand how Alzheimer's disease alters brain function. Using fMRI in animal models of Alzheimer's disease has the potential to provide us with a more comprehensive understanding of the observations made in human clinical fMRI studies. However, using fMRI in animal models of Alzheimer's disease presents some unique challenges. Here, we highlight some of these challenges and discuss potential solutions for researchers interested in performing fMRI in animal models. First, we briefly summarize our current understanding of Alzheimer's disease from a mechanistic standpoint. We then overview the wide array of animal models available for studying this disease and how to choose the most appropriate model to study, depending on which aspects of the condition researchers seek to investigate. Finally, we discuss the contributions of fMRI to our understanding of Alzheimer's disease and the issues to consider when designing fMRI studies for animal models, such as differences in brain activity based on anesthetic choice and ways to interrogate more specific questions in rodents beyond those that can be addressed in humans. The goal of this article is to provide information on the utility of fMRI, and approaches to consider when using fMRI, for studies of Alzheimer's disease in animal models. © 2018. Published by The Company of Biologists Ltd.

A guide to using functional magnetic resonance imaging to study Alzheimer's disease in animal models

PubMed Central

Asaad, Mazen

2018-01-01

ABSTRACT Alzheimer's disease is a leading healthcare challenge facing our society today. Functional magnetic resonance imaging (fMRI) of the brain has played an important role in our efforts to understand how Alzheimer's disease alters brain function. Using fMRI in animal models of Alzheimer's disease has the potential to provide us with a more comprehensive understanding of the observations made in human clinical fMRI studies. However, using fMRI in animal models of Alzheimer's disease presents some unique challenges. Here, we highlight some of these challenges and discuss potential solutions for researchers interested in performing fMRI in animal models. First, we briefly summarize our current understanding of Alzheimer's disease from a mechanistic standpoint. We then overview the wide array of animal models available for studying this disease and how to choose the most appropriate model to study, depending on which aspects of the condition researchers seek to investigate. Finally, we discuss the contributions of fMRI to our understanding of Alzheimer's disease and the issues to consider when designing fMRI studies for animal models, such as differences in brain activity based on anesthetic choice and ways to interrogate more specific questions in rodents beyond those that can be addressed in humans. The goal of this article is to provide information on the utility of fMRI, and approaches to consider when using fMRI, for studies of Alzheimer's disease in animal models. PMID:29784664

Development of computational small animal models and their applications in preclinical imaging and therapy research.

PubMed

Xie, Tianwu; Zaidi, Habib

2016-01-01

The development of multimodality preclinical imaging techniques and the rapid growth of realistic computer simulation tools have promoted the construction and application of computational laboratory animal models in preclinical research. Since the early 1990s, over 120 realistic computational animal models have been reported in the literature and used as surrogates to characterize the anatomy of actual animals for the simulation of preclinical studies involving the use of bioluminescence tomography, fluorescence molecular tomography, positron emission tomography, single-photon emission computed tomography, microcomputed tomography, magnetic resonance imaging, and optical imaging. Other applications include electromagnetic field simulation, ionizing and nonionizing radiation dosimetry, and the development and evaluation of new methodologies for multimodality image coregistration, segmentation, and reconstruction of small animal images. This paper provides a comprehensive review of the history and fundamental technologies used for the development of computational small animal models with a particular focus on their application in preclinical imaging as well as nonionizing and ionizing radiation dosimetry calculations. An overview of the overall process involved in the design of these models, including the fundamental elements used for the construction of different types of computational models, the identification of original anatomical data, the simulation tools used for solving various computational problems, and the applications of computational animal models in preclinical research. The authors also analyze the characteristics of categories of computational models (stylized, voxel-based, and boundary representation) and discuss the technical challenges faced at the present time as well as research needs in the future.

Teaching veterinary obstetrics using three-dimensional animation technology.

PubMed

Scherzer, Jakob; Buchanan, M Flint; Moore, James N; White, Susan L

2010-01-01

In this three-year study, test scores for students taught veterinary obstetrics in a classroom setting with either traditional media (photographs, text, and two-dimensional graphical presentations) were compared with those for students taught by incorporating three-dimensional (3D) media (linear animations and interactive QuickTime Virtual Reality models) into the classroom lectures. Incorporation of the 3D animations and interactive models significantly increased students' scores on essay questions designed to assess their comprehension of the subject matter. This approach to education may help to better prepare students for dealing with obstetrical cases during their final clinical year and after graduation.

Animal models in myopia research.

PubMed

Schaeffel, Frank; Feldkaemper, Marita

2015-11-01

Our current understanding of the development of refractive errors, in particular myopia, would be substantially limited had Wiesel and Raviola not discovered by accident that monkeys develop axial myopia as a result of deprivation of form vision. Similarly, if Josh Wallman and colleagues had not found that simple plastic goggles attached to the chicken eye generate large amounts of myopia, the chicken model would perhaps not have become such an important animal model. Contrary to previous assumptions about the mechanisms of myopia, these animal models suggested that eye growth is visually controlled locally by the retina, that an afferent connection to the brain is not essential and that emmetropisation uses more sophisticated cues than just the magnitude of retinal blur. While animal models have shown that the retina can determine the sign of defocus, the underlying mechanism is still not entirely clear. Animal models have also provided knowledge about the biochemical nature of the signal cascade converting the output of retinal image processing to changes in choroidal thickness and scleral growth; however, a critical question was, and still is, can the results from animal models be applied to myopia in children? While the basic findings from chickens appear applicable to monkeys, some fundamental questions remain. If eye growth is guided by visual feedback, why is myopic development not self-limiting? Why does undercorrection not arrest myopic progression even though positive lenses induce myopic defocus, which leads to the development of hyperopia in emmetropic animals? Why do some spectacle or contact lens designs reduce myopic progression and others not? It appears that some major differences exist between animals reared with imposed defocus and children treated with various optical corrections, although without the basic knowledge obtained from animal models, we would be lost in an abundance of untestable hypotheses concerning human myopia. © 2015 Optometry Australia.

Design of a recovery system for a reentry vehicle

NASA Technical Reports Server (NTRS)

Von Eckroth, Wulf; Garrard, William L.; Miller, Norman

1993-01-01

Engineers are often required to design decelerator systems which are deployed in cross-wind orientations. If the system is not designed to minimize 'line sail', damage to the parachutes could result. A Reentry Vehicle Analysis Code (RVAC) and an accompanying graphics animation software program (DISPLAY) are presented in this paper. These computer codes allow the user to quickly apply the Purvis line sail modeling technique to any vehicle and then observe the relative motion of the vehicle, nose cap, suspension lines, pilot and drogue bags and canopies on a computer screen. Data files are created which allow plots of velocities, spacial positions, and dynamic pressures versus time to be generated. The code is an important tool for the design engineer because it integrates two degrees of freedom (DOF) line sail equations with a three DOF model of the reentry body and jettisoned nose cap to provide an animated output.

The guinea pig as an animal model for developmental and reproductive toxicology studies.

PubMed

Rocca, Meredith S; Wehner, Nancy G

2009-04-01

Regulatory guidelines for developmental and reproductive toxicology (DART) studies require selection of "relevant" animal models as determined by kinetic, pharmacological, and toxicological data. Traditionally, rats, mice, and rabbits are the preferred animal models for these studies. However, for test articles that are pharmacologically inactive in the traditional animal models, the guinea pig may be a viable option. This choice should not be made lightly, as guinea pigs have many disadvantages compared to the traditional species, including limited historical control data, variability in pregnancy rates, small and variable litter size, long gestation, relative maturity at birth, and difficulty in dosing and breeding. This report describes methods for using guinea pigs in DART studies and provides results of positive and negative controls. Standard study designs and animal husbandry methods were modified to allow mating on the postpartum estrus in fertility studies and were used for producing cohorts of pregnant females for developmental studies. A positive control study with the pregnancy-disrupting agent mifepristone resulted in the anticipated failure of embryo implantation and supported the use of the guinea pig model. Control data for reproductive endpoints collected from 5 studies are presented. In cases where the traditional animal models are not relevant, the guinea pig can be used successfully for DART studies. (c) 2009 Wiley-Liss, Inc.

Zebrafish housing systems: a review of basic operating principles and considerations for design and functionality.

PubMed

Lawrence, Christian; Mason, Timothy

2012-01-01

The strategies for housing zebrafish used in biomedical research have evolved considerably over the past three decades. To keep pace with the rapid expansion and development of the zebrafish model system, the field has generally moved from keeping fish at the level of aquarium hobbyist to that of industrialized, recirculating aquaculture. Numerous commercial system vendors now offer increasingly sophisticated housing systems based on design principles that maximize the number of animals that can be housed in a given space footprint, and they are thus able to support large and diverse research programs. This review is designed to provide managers, lab animal veterinarians, investigators, and other parties responsible for care and use of these animals with a comprehensive overview of the basic operating and design principles of zebrafish housing systems. This information can be used to help plan the construction of new facilities and/or the upgrade and maintenance of existing operations.

True Numerical Cognition in the Wild.

PubMed

Piantadosi, Steven T; Cantlon, Jessica F

2017-04-01

Cognitive and neural research over the past few decades has produced sophisticated models of the representations and algorithms underlying numerical reasoning in humans and other animals. These models make precise predictions for how humans and other animals should behave when faced with quantitative decisions, yet primarily have been tested only in laboratory tasks. We used data from wild baboons' troop movements recently reported by Strandburg-Peshkin, Farine, Couzin, and Crofoot (2015) to compare a variety of models of quantitative decision making. We found that the decisions made by these naturally behaving wild animals rely specifically on numerical representations that have key homologies with the psychophysics of human number representations. These findings provide important new data on the types of problems human numerical cognition was designed to solve and constitute the first robust evidence of true numerical reasoning in wild animals.

Robots in the service of animal behavior.

PubMed

Klein, Barrett A; Stein, Joey; Taylor, Ryan C

2012-09-01

As reading fiction can challenge us to better understand fact, using fake animals can sometimes serve as our best solution to understanding the behavior of real animals. The use of dummies, doppelgangers, fakes, and physical models have served to elicit behaviors in animal experiments since the early history of behavior studies, and, more recently, robotic animals have been employed by researchers to further coax behaviors from their study subjects. Here, we review the use of robots in the service of animal behavior, and describe in detail the production and use of one type of robot - "faux" frogs - to test female responses to multisensory courtship signals. The túngara frog (Physalaemus pustulosus) has been a study subject for investigating multimodal signaling, and we discuss the benefits and drawbacks of using the faux frogs we have designed, with the larger aim of inspiring other scientists to consider the appropriate application of physical models and robots in their research.

Mathematical models used to inform study design or surveillance systems in infectious diseases: a systematic review.

PubMed

Herzog, Sereina A; Blaizot, Stéphanie; Hens, Niel

2017-12-18

Mathematical models offer the possibility to investigate the infectious disease dynamics over time and may help in informing design of studies. A systematic review was performed in order to determine to what extent mathematical models have been incorporated into the process of planning studies and hence inform study design for infectious diseases transmitted between humans and/or animals. We searched Ovid Medline and two trial registry platforms (Cochrane, WHO) using search terms related to infection, mathematical model, and study design from the earliest dates to October 2016. Eligible publications and registered trials included mathematical models (compartmental, individual-based, or Markov) which were described and used to inform the design of infectious disease studies. We extracted information about the investigated infection, population, model characteristics, and study design. We identified 28 unique publications but no registered trials. Focusing on compartmental and individual-based models we found 12 observational/surveillance studies and 11 clinical trials. Infections studied were equally animal and human infectious diseases for the observational/surveillance studies, while all but one between humans for clinical trials. The mathematical models were used to inform, amongst other things, the required sample size (n = 16), the statistical power (n = 9), the frequency at which samples should be taken (n = 6), and from whom (n = 6). Despite the fact that mathematical models have been advocated to be used at the planning stage of studies or surveillance systems, they are used scarcely. With only one exception, the publications described theoretical studies, hence, not being utilised in real studies.

Reproducibility of preclinical animal research improves with heterogeneity of study samples

PubMed Central

Vogt, Lucile; Sena, Emily S.; Würbel, Hanno

2018-01-01

Single-laboratory studies conducted under highly standardized conditions are the gold standard in preclinical animal research. Using simulations based on 440 preclinical studies across 13 different interventions in animal models of stroke, myocardial infarction, and breast cancer, we compared the accuracy of effect size estimates between single-laboratory and multi-laboratory study designs. Single-laboratory studies generally failed to predict effect size accurately, and larger sample sizes rendered effect size estimates even less accurate. By contrast, multi-laboratory designs including as few as 2 to 4 laboratories increased coverage probability by up to 42 percentage points without a need for larger sample sizes. These findings demonstrate that within-study standardization is a major cause of poor reproducibility. More representative study samples are required to improve the external validity and reproducibility of preclinical animal research and to prevent wasting animals and resources for inconclusive research. PMID:29470495

Adaptive optimal training of animal behavior

NASA Astrophysics Data System (ADS)

Bak, Ji Hyun; Choi, Jung Yoon; Akrami, Athena; Witten, Ilana; Pillow, Jonathan

Neuroscience experiments often require training animals to perform tasks designed to elicit various sensory, cognitive, and motor behaviors. Training typically involves a series of gradual adjustments of stimulus conditions and rewards in order to bring about learning. However, training protocols are usually hand-designed, and often require weeks or months to achieve a desired level of task performance. Here we combine ideas from reinforcement learning and adaptive optimal experimental design to formulate methods for efficient training of animal behavior. Our work addresses two intriguing problems at once: first, it seeks to infer the learning rules underlying an animal's behavioral changes during training; second, it seeks to exploit these rules to select stimuli that will maximize the rate of learning toward a desired objective. We develop and test these methods using data collected from rats during training on a two-interval sensory discrimination task. We show that we can accurately infer the parameters of a learning algorithm that describes how the animal's internal model of the task evolves over the course of training. We also demonstrate by simulation that our method can provide a substantial speedup over standard training methods.

Designing peptide inhibitor of insulin receptor to induce diabetes mellitus type 2 in animal model Mus musculus.

PubMed

Permatasari, Galuh W; Utomo, Didik H; Widodo

2016-10-01

A designing peptide as agent for inducing diabetes mellitus type 2 (T2DM) in an animal model is challenging. The computational approach provides a sophisticated tool to design a functional peptide that may block the insulin receptor activity. The peptide that able to inhibit the binding between insulin and insulin receptor is a warrant for inducing T2DM. Therefore, we designed a potential peptide inhibitor of insulin receptor as an agent to generate T2DM animal model by bioinformatics approach. The peptide has been developed based on the structure of insulin receptor binding site of insulin and then modified it to obtain the best properties of half life, hydrophobicity, antigenicity, and stability binding into insulin receptor. The results showed that the modified peptide has characteristics 100h half-life, high-affinity -95.1±20, and high stability 28.17 in complex with the insulin receptor. Moreover, the modified peptide has molecular weight 4420.8g/Mol and has no antigenic regions. Based on the molecular dynamic simulation, the complex of modified peptide-insulin receptor is more stable than the commercial insulin receptor blocker. This study suggested that the modified peptide has the promising performance to block the insulin receptor activity that potentially induce diabetes mellitus type 2 in mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

77 FR 18251 - Development of Animal Models of Pregnancy To Address Medical Countermeasures for Influenza in the...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-27

... during pregnancy. Specifically, this workshop will address experimental design issues in selecting the... countermeasures, including influenza therapies, that may be used during pregnancy; and (3) experimental design... pharmacokinetic studies, and (3) additional issues in experimental design. Background information on the public...

Meeting the challenges with the Douglas Aircraft Company Aeroelastic Design Optimization Program (ADOP)

NASA Technical Reports Server (NTRS)

Rommel, Bruce A.

1989-01-01

An overview of the Aeroelastic Design Optimization Program (ADOP) at the Douglas Aircraft Company is given. A pilot test program involving the animation of mode shapes with solid rendering as well as wire frame displays, a complete aircraft model of a high-altitude hypersonic aircraft to test ADOP procedures, a flap model, and an aero-mesh modeler for doublet lattice aerodynamics are discussed.

How animal models of leukaemias have already benefited patients.

PubMed

Ablain, Julien; Nasr, Rihab; Zhu, Jun; Bazarbachi, Ali; Lallemand-Breittenbach, Valérie; de Thé, Hugues

2013-04-01

The relative genetic simplicity of leukaemias, the development of which likely relies on a limited number of initiating events has made them ideal for disease modelling, particularly in the mouse. Animal models provide incomparable insights into the mechanisms of leukaemia development and allow exploration of the molecular pillars of disease maintenance, an aspect often biased in cell lines or ex vivo systems. Several of these models, which faithfully recapitulate the characteristics of the human disease, have been used for pre-clinical purposes and have been instrumental in predicting therapy response in patients. We plea for a wider use of genetically defined animal models in the design of clinical trials, with a particular focus on reassessment of existing cancer or non-cancer drugs, alone or in combination. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Sound field simulation and acoustic animation in urban squares

NASA Astrophysics Data System (ADS)

Kang, Jian; Meng, Yan

2005-04-01

Urban squares are important components of cities, and the acoustic environment is important for their usability. While models and formulae for predicting the sound field in urban squares are important for their soundscape design and improvement, acoustic animation tools would be of great importance for designers as well as for public participation process, given that below a certain sound level, the soundscape evaluation depends mainly on the type of sounds rather than the loudness. This paper first briefly introduces acoustic simulation models developed for urban squares, as well as empirical formulae derived from a series of simulation. It then presents an acoustic animation tool currently being developed. In urban squares there are multiple dynamic sound sources, so that the computation time becomes a main concern. Nevertheless, the requirements for acoustic animation in urban squares are relatively low compared to auditoria. As a result, it is important to simplify the simulation process and algorithms. Based on a series of subjective tests in a virtual reality environment with various simulation parameters, a fast simulation method with acceptable accuracy has been explored. [Work supported by the European Commission.

Prototype design of singles processing unit for the small animal PET

NASA Astrophysics Data System (ADS)

Deng, P.; Zhao, L.; Lu, J.; Li, B.; Dong, R.; Liu, S.; An, Q.

2018-05-01

Position Emission Tomography (PET) is an advanced clinical diagnostic imaging technique for nuclear medicine. Small animal PET is increasingly used for studying the animal model of disease, new drugs and new therapies. A prototype of Singles Processing Unit (SPU) for a small animal PET system was designed to obtain the time, energy, and position information. The energy and position is actually calculated through high precison charge measurement, which is based on amplification, shaping, A/D conversion and area calculation in digital signal processing domian. Analysis and simulations were also conducted to optimize the key parameters in system design. Initial tests indicate that the charge and time precision is better than 3‰ FWHM and 350 ps FWHM respectively, while the position resolution is better than 3.5‰ FWHM. Commination tests of the SPU prototype with the PET detector indicate that the system time precision is better than 2.5 ns, while the flood map and energy spectra concored well with the expected.

Concepts in Cancer Modeling: A Brief History

PubMed Central

Thomas, Renee M.; Van Dyke, Terry; Merlino, Glenn; Day, Chi-Ping

2016-01-01

Modeling, an experimental approach to investigate complex biological systems, has significantly contributed to our understanding of cancer. While extensive cancer research has been conducted utilizing animal models for elucidating mechanisms and developing therapeutics, the concepts in a good model design and its application have not been well elaborated. In this review, we discuss the theory underlying biological modeling and the process of producing a valuable and relevant animal model. Several renowned examples in the history of cancer research will be used to illustrate how modeling can be translatable to clinical applications. Finally, we will also discuss how the advances in cancer genomics and cancer modeling will influence each other going forward. PMID:27694601

ERAIZDA: a model for holistic annotation of animal infectious and zoonotic diseases

PubMed Central

Buza, Teresia M.; Jack, Sherman W.; Kirunda, Halid; Khaitsa, Margaret L.; Lawrence, Mark L.; Pruett, Stephen; Peterson, Daniel G.

2015-01-01

There is an urgent need for a unified resource that integrates trans-disciplinary annotations of emerging and reemerging animal infectious and zoonotic diseases. Such data integration will provide wonderful opportunity for epidemiologists, researchers and health policy makers to make data-driven decisions designed to improve animal health. Integrating emerging and reemerging animal infectious and zoonotic disease data from a large variety of sources into a unified open-access resource provides more plausible arguments to achieve better understanding of infectious and zoonotic diseases. We have developed a model for interlinking annotations of these diseases. These diseases are of particular interest because of the threats they pose to animal health, human health and global health security. We demonstrated the application of this model using brucellosis, an infectious and zoonotic disease. Preliminary annotations were deposited into VetBioBase database (http://vetbiobase.igbb.msstate.edu). This database is associated with user-friendly tools to facilitate searching, retrieving and downloading of disease-related information. Database URL: http://vetbiobase.igbb.msstate.edu PMID:26581408

Irradiation Design for an Experimental Murine Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ballesteros-Zebadua, P.; Moreno-Jimenez, S.; Suarez-Campos, J. E.

2010-12-07

In radiotherapy and stereotactic radiosurgery, small animal experimental models are frequently used, since there are still a lot of unsolved questions about the biological and biochemical effects of ionizing radiation. This work presents a method for small-animal brain radiotherapy compatible with a dedicated 6MV Linac. This rodent model is focused on the research of the inflammatory effects produced by ionizing radiation in the brain. In this work comparisons between Pencil Beam and Monte Carlo techniques, were used in order to evaluate accuracy of the calculated dose using a commercial planning system. Challenges in this murine model are discussed.

Experimental Animal Models for Studies on the Mechanisms of Blast-Induced Neurotrauma

PubMed Central

Risling, Mårten; Davidsson, Johan

2012-01-01

A blast injury is a complex type of physical trauma resulting from the detonation of explosive compounds and has become an important issue due to the use of improvised explosive devices (IED) in current military conflicts. Blast-induced neurotrauma (BINT) is a major concern in contemporary military medicine and includes a variety of injuries that range from mild to lethal. Extreme forces and their complex propagation characterize BINT. Modern body protection and the development of armored military vehicles can be assumed to have changed the outcome of BINT. Primary blast injuries are caused by overpressure waves whereas secondary, tertiary, and quaternary blast injuries can have more varied origins such as the impact of fragments, abnormal movements, or heat. The characteristics of the blast wave can be assumed to be significantly different in open field detonations compared to explosions in a confined space, such an armored vehicle. Important parameters include peak pressure, duration, and shape of the pulse. Reflections from walls and armor can make the prediction of effects in individual cases very complex. Epidemiological data do not contain information of the comparative importance of the different blast mechanisms. It is therefore important to generate data in carefully designed animal models. Such models can be selective reproductions of a primary blast, penetrating injuries from fragments, acceleration movements, or combinations of such mechanisms. It is of crucial importance that the physical parameters of the employed models are well characterized so that the experiments can be reproduced in different laboratory settings. Ideally, pressure recordings should be calibrated by using the same equipment in several laboratories. With carefully designed models and thoroughly evaluated animal data it should be possible to achieve a translation of data between animal and clinical data. Imaging and computer simulation represent a possible link between experiments and studies of human cases. However, in order for mathematical simulations to be completely useful, the predictions will most likely have to be validated by detailed data from animal experiments. Some aspects of BINT can conceivably be studied in vitro. However, factors such as systemic response, brain edema, inflammation, vasospasm, or changes in synaptic transmission and behavior must be evaluated in experimental animals. Against this background, it is necessary that such animal experiments are carefully developed imitations of actual components in the blast injury. This paper describes and discusses examples of different designs of experimental models relevant to BINT. PMID:22485104

Biorobotics: using robots to emulate and investigate agile locomotion.

PubMed

Ijspeert, Auke J

2014-10-10

The graceful and agile movements of animals are difficult to analyze and emulate because locomotion is the result of a complex interplay of many components: the central and peripheral nervous systems, the musculoskeletal system, and the environment. The goals of biorobotics are to take inspiration from biological principles to design robots that match the agility of animals, and to use robots as scientific tools to investigate animal adaptive behavior. Used as physical models, biorobots contribute to hypothesis testing in fields such as hydrodynamics, biomechanics, neuroscience, and prosthetics. Their use may contribute to the design of prosthetic devices that more closely take human locomotion principles into account. Copyright © 2014, American Association for the Advancement of Science.

Low-dose or low-dose-rate ionizing radiation–induced bioeffects in animal models

PubMed Central

Loke, Weng Keong; Khoo, Boo Cheong

2017-01-01

Abstract Animal experimental studies indicate that acute or chronic low-dose ionizing radiation (LDIR) (≤100 mSv) or low-dose-rate ionizing radiation (LDRIR) (<6 mSv/h) exposures may be harmful. It induces genetic and epigenetic changes and is associated with a range of physiological disturbances that includes altered immune system, abnormal brain development with resultant cognitive impairment, cataractogenesis, abnormal embryonic development, circulatory diseases, weight gain, premature menopause in female animals, tumorigenesis and shortened lifespan. Paternal or prenatal LDIR/LDRIR exposure is associated with reduced fertility and number of live fetuses, and transgenerational genomic aberrations. On the other hand, in some experimental studies, LDIR/LDRIR exposure has also been reported to bring about beneficial effects such as reduction in tumorigenesis, prolonged lifespan and enhanced fertility. The differences in reported effects of LDIR/LDRIR exposure are dependent on animal genetic background (susceptibility), age (prenatal or postnatal days), sex, nature of radiation exposure (i.e. acute, fractionated or chronic radiation exposure), type of radiation, combination of radiation with other toxic agents (such as smoking, pesticides or other chemical toxins) or animal experimental designs. In this review paper, we aimed to update radiation researchers and radiologists on the current progress achieved in understanding the LDIR/LDRIR-induced bionegative and biopositive effects reported in the various animal models. The roles played by a variety of molecules that are implicated in LDIR/LDRIR-induced health effects will be elaborated. The review will help in future investigations of LDIR/LDRIR-induced health effects by providing clues for designing improved animal research models in order to clarify the current controversial/contradictory findings from existing studies. PMID:28077626

Development of computational small animal models and their applications in preclinical imaging and therapy research

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xie, Tianwu; Zaidi, Habib, E-mail: habib.zaidi@hcuge.ch; Geneva Neuroscience Center, Geneva University, Geneva CH-1205

The development of multimodality preclinical imaging techniques and the rapid growth of realistic computer simulation tools have promoted the construction and application of computational laboratory animal models in preclinical research. Since the early 1990s, over 120 realistic computational animal models have been reported in the literature and used as surrogates to characterize the anatomy of actual animals for the simulation of preclinical studies involving the use of bioluminescence tomography, fluorescence molecular tomography, positron emission tomography, single-photon emission computed tomography, microcomputed tomography, magnetic resonance imaging, and optical imaging. Other applications include electromagnetic field simulation, ionizing and nonionizing radiation dosimetry, and themore » development and evaluation of new methodologies for multimodality image coregistration, segmentation, and reconstruction of small animal images. This paper provides a comprehensive review of the history and fundamental technologies used for the development of computational small animal models with a particular focus on their application in preclinical imaging as well as nonionizing and ionizing radiation dosimetry calculations. An overview of the overall process involved in the design of these models, including the fundamental elements used for the construction of different types of computational models, the identification of original anatomical data, the simulation tools used for solving various computational problems, and the applications of computational animal models in preclinical research. The authors also analyze the characteristics of categories of computational models (stylized, voxel-based, and boundary representation) and discuss the technical challenges faced at the present time as well as research needs in the future.« less

Overview of large animal myocardial infarction models (review).

PubMed

Lukács, E; Magyari, B; Tóth, L; Petrási, Zs; Repa, I; Koller, A; Horváth, Iván

2012-12-01

There are several experimental models for the in vivo investigation of myocardial infarction (MI) in small (mouse, rat) and large animals (dog, pig, sheep and baboons). The application of large animal models raises ethical concerns, the design of experiments needs longer follow-up times, requiring proper breeding and housing conditions, therefore resulting in higher cost, than in vitro or small animal studies. On the other hand, the relevance of large animal models is very important, since they mostly resemble to human physiological and pathophysiological processes. The first main difference among MI models is the method of induction (open or closed chest, e.g. surgical or catheter based); the second main difference is the presence or absence of reperfusion. The former (i.e. reperfused MI) allows the investigation of reperfusion injury and new catheter based techniques during percutaneous coronary interventions, while the latter (i.e. nonreperfused MI) serves as a traditional coronary occlusion model, to test the effects of new pharmacological agents and biological therapies, as cell therapy. The reperfused and nonreperfused myocardial infarction has different outcomes, regarding left ventricular function, remodelling, subsequent heart failure, aneurysm formation and mortality. Our aim was to review the literature and report our findings regarding experimental MI models, regarding the differences among species, methods, reproducibility and interpretation.

Guidelines for pre-clinical assessment of the acetylcholine receptor-specific passive transfer myasthenia gravis model - recommendations for methods and experimental designs

PubMed Central

Kusner, Linda L.; Losen, Mario; Vincent, Angela; Lindstrom, Jon; Tzartos, Socrates; Lazaridis, Konstantinos; Martinez-Martinez, Pilar

2015-01-01

Antibodies against the muscle acetylcholine receptor (AChR) are the most common cause of myasthenia gravis (MG). Passive transfer of AChR antibodies from MG patients into animals reproduces key features of human disease, including antigenic modulation of the AChR, complement-mediated damage of the neuromuscular junction, and muscle weakness. Similarly, AChR antibodies generated by active immunization in experimental autoimmune MG models can subsequently be passively transferred to other animals and induce weakness. The passive transfer model is useful to test therapeutic strategies aimed at the effector mechanism of the autoantibodies. Here we summarize published and unpublished experience using the AChR passive transfer MG model in mice, rats and rhesus monkeys, and give recommendations for the design of preclinical studies in order to facilitate translation of positive and negative results to improve MG therapies. PMID:25743217

Applications of computational fluid dynamics (CFD) in the modelling and design of ventilation systems in the agricultural industry: a review.

PubMed

Norton, Tomás; Sun, Da-Wen; Grant, Jim; Fallon, Richard; Dodd, Vincent

2007-09-01

The application of computational fluid dynamics (CFD) in the agricultural industry is becoming ever more important. Over the years, the versatility, accuracy and user-friendliness offered by CFD has led to its increased take-up by the agricultural engineering community. Now CFD is regularly employed to solve environmental problems of greenhouses and animal production facilities. However, due to a combination of increased computer efficacy and advanced numerical techniques, the realism of these simulations has only been enhanced in recent years. This study provides a state-of-the-art review of CFD, its current applications in the design of ventilation systems for agricultural production systems, and the outstanding challenging issues that confront CFD modellers. The current status of greenhouse CFD modelling was found to be at a higher standard than that of animal housing, owing to the incorporation of user-defined routines that simulate crop biological responses as a function of local environmental conditions. Nevertheless, the most recent animal housing simulations have addressed this issue and in turn have become more physically realistic.

Model-Driven Development of Interactive Multimedia Applications with MML

NASA Astrophysics Data System (ADS)

Pleuss, Andreas; Hussmann, Heinrich

There is an increasing demand for high-quality interactive applications which combine complex application logic with a sophisticated user interface, making use of individual media objects like graphics, animations, 3D graphics, audio or video. Their development is still challenging as it requires the integration of software design, user interface design, and media design.

From cineradiography to biorobots: an approach for designing robots to emulate and study animal locomotion.

PubMed

Karakasiliotis, K; Thandiackal, R; Melo, K; Horvat, T; Mahabadi, N K; Tsitkov, S; Cabelguen, J M; Ijspeert, A J

2016-06-01

Robots are increasingly used as scientific tools to investigate animal locomotion. However, designing a robot that properly emulates the kinematic and dynamic properties of an animal is difficult because of the complexity of musculoskeletal systems and the limitations of current robotics technology. Here, we propose a design process that combines high-speed cineradiography, optimization, dynamic scaling, three-dimensional printing, high-end servomotors and a tailored dry-suit to construct Pleurobot: a salamander-like robot that closely mimics its biological counterpart, Pleurodeles waltl Our previous robots helped us test and confirm hypotheses on the interaction between the locomotor neuronal networks of the limbs and the spine to generate basic swimming and walking gaits. With Pleurobot, we demonstrate a design process that will enable studies of richer motor skills in salamanders. In particular, we are interested in how these richer motor skills can be obtained by extending our spinal cord models with the addition of more descending pathways and more detailed limb central pattern generator networks. Pleurobot is a dynamically scaled amphibious salamander robot with a large number of actuated degrees of freedom (DOFs: 27 in total). Because of our design process, the robot can capture most of the animal's DOFs and range of motion, especially at the limbs. We demonstrate the robot's abilities by imposing raw kinematic data, extracted from X-ray videos, to the robot's joints for basic locomotor behaviours in water and on land. The robot closely matches the behaviour of the animal in terms of relative forward speeds and lateral displacements. Ground reaction forces during walking also resemble those of the animal. Based on our results, we anticipate that future studies on richer motor skills in salamanders will highly benefit from Pleurobot's design. © 2016 The Author(s).

From cineradiography to biorobots: an approach for designing robots to emulate and study animal locomotion

PubMed Central

Karakasiliotis, K.; Thandiackal, R.; Melo, K.; Horvat, T.; Mahabadi, N. K.; Tsitkov, S.; Cabelguen, J. M.; Ijspeert, A. J.

2016-01-01

Robots are increasingly used as scientific tools to investigate animal locomotion. However, designing a robot that properly emulates the kinematic and dynamic properties of an animal is difficult because of the complexity of musculoskeletal systems and the limitations of current robotics technology. Here, we propose a design process that combines high-speed cineradiography, optimization, dynamic scaling, three-dimensional printing, high-end servomotors and a tailored dry-suit to construct Pleurobot: a salamander-like robot that closely mimics its biological counterpart, Pleurodeles waltl. Our previous robots helped us test and confirm hypotheses on the interaction between the locomotor neuronal networks of the limbs and the spine to generate basic swimming and walking gaits. With Pleurobot, we demonstrate a design process that will enable studies of richer motor skills in salamanders. In particular, we are interested in how these richer motor skills can be obtained by extending our spinal cord models with the addition of more descending pathways and more detailed limb central pattern generator networks. Pleurobot is a dynamically scaled amphibious salamander robot with a large number of actuated degrees of freedom (DOFs: 27 in total). Because of our design process, the robot can capture most of the animal's DOFs and range of motion, especially at the limbs. We demonstrate the robot's abilities by imposing raw kinematic data, extracted from X-ray videos, to the robot's joints for basic locomotor behaviours in water and on land. The robot closely matches the behaviour of the animal in terms of relative forward speeds and lateral displacements. Ground reaction forces during walking also resemble those of the animal. Based on our results, we anticipate that future studies on richer motor skills in salamanders will highly benefit from Pleurobot's design. PMID:27358276

Animal models of chronic obstructive pulmonary disease.

PubMed

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

2015-03-01

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

Animal models of surgically manipulated flow velocities to study shear stress-induced atherosclerosis.

PubMed

Winkel, Leah C; Hoogendoorn, Ayla; Xing, Ruoyu; Wentzel, Jolanda J; Van der Heiden, Kim

2015-07-01

Atherosclerosis is a chronic inflammatory disease of the arterial tree that develops at predisposed sites, coinciding with locations that are exposed to low or oscillating shear stress. Manipulating flow velocity, and concomitantly shear stress, has proven adequate to promote endothelial activation and subsequent plaque formation in animals. In this article, we will give an overview of the animal models that have been designed to study the causal relationship between shear stress and atherosclerosis by surgically manipulating blood flow velocity profiles. These surgically manipulated models include arteriovenous fistulas, vascular grafts, arterial ligation, and perivascular devices. We review these models of manipulated blood flow velocity from an engineering and biological perspective, focusing on the shear stress profiles they induce and the vascular pathology that is observed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effects of Geometry and Kinematics on Animals Leaping Out of Water

NASA Astrophysics Data System (ADS)

Chang, Brian; Myeong, Jihye; Virot, Emmanuel; Kim, Ho-Young; Jung, Sunghwan

2017-11-01

Leaping out of water is a phenomenon exhibited by a variety of aquatic and semi-aquatic animals, such as frogs and whales. In this study, we aim to elucidate the effects of geometric and kinematic conditions on the propulsive and drag force required for an animal to jump through the water interface. A simple mechanism was designed to measure the propulsive thrust produced by a flapping appendage. In a separate experiment to measure the opposing drag, simplified models of animals are 3D printed and fitted with pressure sensors. The model is accelerated from rest and covers a range of Re from 103 to 105. Using a high-speed camera and pressure sensors, we observed a deformation of the free surface prior to water exit, and correlated this to the drag force. Finally, we discuss a scaling law to describe the general physics which allow animals to leap out of water. NSF EAPSI.

Oligonucleotide Antiviral Therapeutics: Antisense and RNA Interference for Highly Pathogenic RNA Viruses

DTIC Science & Technology

2008-01-01

siRNA delivery method in his animal model, it remains to be studied whether this general pproach is safe in humans. Often cited as an advantage of siRNAs...way studying the intravenous delivery f ASO drug candidates targeting Bcl-2 (Genasense®, Genta) nd c-myc (Resten-NG®, AVI BioPharma), while completed... studies have been published investigating MOs as a treatment for EBOV infection, with both showing fficacy in animal models. PMOs were designed to

Quality of Reporting and Adherence to ARRIVE Guidelines in Animal Studies for Chagas Disease Preclinical Drug Research: A Systematic Review.

PubMed

Gulin, Julián Ernesto Nicolás; Rocco, Daniela Marisa; García-Bournissen, Facundo

2015-11-01

Publication of accurate and detailed descriptions of methods in research articles involving animals is essential for health scientists to accurately interpret published data, evaluate results and replicate findings. Inadequate reporting of key aspects of experimental design may reduce the impact of studies and could act as a barrier to translation of research findings. Reporting of animal use must be as comprehensive as possible in order to take advantage of every study and every animal used. Animal models are essential to understanding and assessing new chemotherapy candidates for Chagas disease pathology, a widespread parasitic disease with few treatment options currently available. A systematic review was carried out to compare ARRIVE guidelines recommendations with information provided in publications of preclinical studies for new anti-Trypanosoma cruzi compounds. A total of 83 publications were reviewed. Before ARRIVE guidelines, 69% of publications failed to report any macroenvironment information, compared to 57% after ARRIVE publication. Similar proportions were observed when evaluating reporting of microenvironmental information (56% vs. 61%). Also, before ARRIVE guidelines publication, only 13% of papers described animal gender, only 18% specified microbiological status and 13% reported randomized treatment assignment, among other essential information missing or incomplete. Unfortunately, publication of ARRIVE guidelines did not seem to enhance reporting quality, compared to papers appeared before ARRIVE publication. Our results suggest that there is a strong need for the scientific community to improve animal use description, animal models employed, transparent reporting and experiment design to facilitate its transfer and application to the affected human population. Full compliance with ARRIVE guidelines, or similar animal research reporting guidelines, would be an excellent start in this direction.

Quality of Reporting and Adherence to ARRIVE Guidelines in Animal Studies for Chagas Disease Preclinical Drug Research: A Systematic Review

PubMed Central

Gulin, Julián Ernesto Nicolás; Rocco, Daniela Marisa; García-Bournissen, Facundo

2015-01-01

Publication of accurate and detailed descriptions of methods in research articles involving animals is essential for health scientists to accurately interpret published data, evaluate results and replicate findings. Inadequate reporting of key aspects of experimental design may reduce the impact of studies and could act as a barrier to translation of research findings. Reporting of animal use must be as comprehensive as possible in order to take advantage of every study and every animal used. Animal models are essential to understanding and assessing new chemotherapy candidates for Chagas disease pathology, a widespread parasitic disease with few treatment options currently available. A systematic review was carried out to compare ARRIVE guidelines recommendations with information provided in publications of preclinical studies for new anti-Trypanosoma cruzi compounds. A total of 83 publications were reviewed. Before ARRIVE guidelines, 69% of publications failed to report any macroenvironment information, compared to 57% after ARRIVE publication. Similar proportions were observed when evaluating reporting of microenvironmental information (56% vs. 61%). Also, before ARRIVE guidelines publication, only 13% of papers described animal gender, only 18% specified microbiological status and 13% reported randomized treatment assignment, among other essential information missing or incomplete. Unfortunately, publication of ARRIVE guidelines did not seem to enhance reporting quality, compared to papers appeared before ARRIVE publication. Our results suggest that there is a strong need for the scientific community to improve animal use description, animal models employed, transparent reporting and experiment design to facilitate its transfer and application to the affected human population. Full compliance with ARRIVE guidelines, or similar animal research reporting guidelines, would be an excellent start in this direction. PMID:26587586

A new approach to tag design in dolphin telemetry: Computer simulations to minimise deleterious effects

NASA Astrophysics Data System (ADS)

Pavlov, V. V.; Wilson, R. P.; Lucke, K.

2007-02-01

Remote-sensors and transmitters are powerful devices for studying cetaceans at sea. However, despite substantial progress in microelectronics and miniaturisation of systems, dolphin tags are imperfectly designed; additional drag from tags increases swim costs, compromises swimming capacity and manoeuvrability, and leads to extra loads on the animal's tissue. We propose a new approach to tag design, elaborating basic principles and incorporating design stages to minimise device effects by using computer-aided design. Initially, the operational conditions of the device are defined by quantifying the shape, hydrodynamics and range of the natural deformation of the dolphin body at the tag attachment site (such as close to the dorsal fin). Then, parametric models of both of the dorsal fin and a tag are created using the derived data. The link between parameters of the fin and a tag model allows redesign of tag models according to expected changes of fin geometry (difference in fin shape related with species, sex, and age peculiarities, simulation of the bend of the fin during manoeuvres). A final virtual modelling stage uses iterative improvement of a tag model in a computer fluid dynamics (CFD) environment to enhance tag performance. This new method is considered as a suitable tool of tag design before creation of the physical model of a tag and testing with conventional wind/water tunnel technique. Ultimately, tag materials are selected to conform to the conditions identified by the modelling process and thus help create a physical model of a tag, which should minimise its impact on the animal carrier and thus increase the reliability and quality of the data obtained.

Zebrafish Housing Systems: A Review of Basic Operating Principles and Considerations for Design and Functionality

PubMed Central

Lawrence, Christian; Mason, Timothy

2015-01-01

The strategies for housing zebrafish used in biomedical research have evolved considerably over the past three decades. To keep pace with the rapid expansion and development of the zebrafish model system, the field has generally moved from keeping fish at the level of aquarium hobbyist to that of industrialized, recirculating aquaculture. Numerous commercial system vendors now offer increasingly sophisticated housing systems based on design principles that maximize the number of animals that can be housed in a given space footprint, and they are thus able to support large and diverse research programs. This review is designed to provide managers, lab animal veterinarians, investigators, and other parties responsible for care and use of these animals with a comprehensive overview of the basic operating and design principles of zebrafish housing systems. This information can be used to help plan the construction of new facilities and/or the upgrade and maintenance of existing operations. PMID:23382349

Robots in the service of animal behavior

PubMed Central

Klein, Barrett A.; Stein, Joey; Taylor, Ryan C.

2012-01-01

As reading fiction can challenge us to better understand fact, using fake animals can sometimes serve as our best solution to understanding the behavior of real animals. The use of dummies, doppelgangers, fakes, and physical models have served to elicit behaviors in animal experiments since the early history of behavior studies, and, more recently, robotic animals have been employed by researchers to further coax behaviors from their study subjects. Here, we review the use of robots in the service of animal behavior, and describe in detail the production and use of one type of robot – “faux” frogs – to test female responses to multisensory courtship signals. The túngara frog (Physalaemus pustulosus) has been a study subject for investigating multimodal signaling, and we discuss the benefits and drawbacks of using the faux frogs we have designed, with the larger aim of inspiring other scientists to consider the appropriate application of physical models and robots in their research. PMID:23181162

Wound Models for Periodontal and Bone Regeneration: the role of biological research

PubMed Central

Sculean, Anton; Chapple, Iain L.C.; Giannobile, William V.

2015-01-01

The ultimate goal of periodontal therapy remains the complete regeneration of those periodontal tissues lost to the destructive inflammatory-immune response, or to trauma, with tissues that possess the same structure and function, and to reestablish and sustain a heath promoting biofilm from one characterised by dysbiosis. This volume discusses the multiple facets of a transition during the late 1960’s to the present day, towards regenerative therapies founded upon a clearer understanding of the biophysiology of normal structure and function, rather than empiricism. This introductory manuscript provides an overview on the requirements of appropriate in-vitro laboratory models (e.g. cell culture), of pre-clinical (i.e. animal) models and human studies for periodontal wound and bone repair. Laboratory studies may provide valuable fundamental insights into basic mechanisms involved in wound repair and regeneration, but also suffer from a uni-dimensional and simplistic approach that does not account for the complexities of the in vivo situation, where multiple cell types and interactions all contribute to definitive outcomes. Therefore, such laboratory studies require validatory research employing preclinical models specifically designed to demonstrate proof-of-concept efficacy, preliminary safety and adaptation to human disease scenarios. Small animal models provide the most economic and logistically feasible preliminary approaches, but outcomes do not necessarily translate to larger animal or human models. The advantages and limitations of all periodontal regeneration models need to be carefully considered when planning investigations to ensure that the optimal design is adopted to answer the specific research question posed. Future challenges lie in the areas of stem cell research, scaffold designs, cell delivery and choice of growth factors, along with research to ensure appropriate gingival coverage in order to prevent gingival recession during the healing phase. PMID:25867976

Teaching habitat and animal classification to fourth graders using an engineering-design model

NASA Astrophysics Data System (ADS)

Marulcu, Ismail

2014-05-01

Background: The motivation for this work is built upon the premise that there is a need for research-based materials for design-based science instruction. In this paper, a small portion of our work investigating the impact of a LEGOTM engineering unit on fourth grade students' preconceptions and understanding of animals is presented. Purpose: The driving questions for our work are: (1) What is the impact of an engineering-design-based curricular module on students' understanding of habitat and animal classification? (2) What are students' misconceptions regarding animal classification and habitat? Sample: The study was conducted in an inner-city K-8 school in the northeastern region of the United States. There were two fourth grade classrooms in the school. The first classroom included seven girls and nine boys, whereas the other classroom included eight girls and eight boys. All fourth grade students participated in the study. Design and methods: In answering the research questions mixed-method approaches are used. Data collection methods included pre- and post-tests, pre- and post-interviews, student journals, and classroom observations. Identical pre- and post-tests were administered to measure students' understanding of animals. They included four multiple-choice and six open-ended questions. Identical pre- and post-interviews were administered to explore students' in-depth understanding of animals. Results: Our results show that students significantly increased their performance after instruction on both the multiple-choice questions (t = -3.586, p = .001) and the open-ended questions (t = -5.04, p = .000). They performed better on the post interviews as well. Also, it is found that design-based instruction helped students comprehend core concepts of a life science subject, animals. Conclusions: Based on these results, the main argument of the study is that engineering design is a useful framework for teaching not only physical science-related subjects, but also life science subjects in elementary science classrooms.

The basics of animal biosafety and biocontainment training.

PubMed

Pritt, Stacy; Hankenson, F Claire; Wagner, Ted; Tate, Mallory

2007-06-01

The threat of biocontamination in an animal facility is best subdued by training. 'Training' is an ambiguous designation that may not be adequately appreciated in all animal facilities. The authors set down concrete training topics and provide practical advice on incorporating the basic principles of facility biosafety training--as well as the precautions and procedures that employees must know in case of accident or emergency--into various training models. They also discuss the current biosafety publications and guidelines and their relationship to biosafety training.

Effects of gravity perturbation on developing animal systems

NASA Technical Reports Server (NTRS)

Malacinski, G. M.; Neff, A. W.

1986-01-01

The use of developing animal systems to analyze the effects of microgravity on animals is discussed. Some of the key features of developing systems, especially embryos, are reviewed and relevant space data are summarized. Issues to be addressed in the design of future space experiments are discussed. It is noted that an embryo which exhibits ground based gravity effects should be selected for use as a model system and individual variation in gravity response among batches of embryos should be taken into account.

Incorporating Eco-Evolutionary Processes into Population Models:Design and Applications

EPA Science Inventory

Eco-evolutionary population models are powerful new tools for exploring howevolutionary processes influence plant and animal population dynamics andvice-versa. The need to manage for climate change and other dynamicdisturbance regimes is creating a demand for the incorporation of...

ELOPTA: a novel microcontroller-based operant device.

PubMed

Hoffman, Adam M; Song, Jianjian; Tuttle, Elaina M

2007-11-01

Operant devices have been used for many years in animal behavior research, yet such devices a regenerally highly specialized and quite expensive. Although commercial models are somewhat adaptable and resilient, they are also extremely expensive and are controlled by difficult to learn proprietary software. As an alternative to commercial devices, we have designed and produced a fully functional, programmable operant device, using a PICmicro microcontroller (Microchip Technology, Inc.). The electronic operant testing apparatus (ELOPTA) is designed to deliver food when a study animal, in this case a bird, successfully depresses the correct sequence of illuminated keys. The device logs each keypress and can detect and log whenever a test animal i spositioned at the device. Data can be easily transferred to a computer and imported into any statistical analysis software. At about 3% the cost of a commercial device, ELOPTA will advance behavioral sciences, including behavioral ecology, animal learning and cognition, and ethology.

Animal models in translational studies of PTSD.

PubMed

Daskalakis, Nikolaos P; Yehuda, Rachel; Diamond, David M

2013-09-01

Understanding the neurobiological mechanisms of post-traumatic stress disorder (PTSD) is of vital importance for developing biomarkers and more effective pharmacotherapy for this disorder. The design of bidirectional translational studies addressing all facets of PTSD is needed. Animal models of PTSD are needed not only to capture the complexity of PTSD behavioral characteristics, but also to address experimentally the influence of variety of factors which might determine an individual's vulnerability or resilience to trauma, e.g., genetic predisposition, early-life experience and social support. The current review covers recent translational approaches to bridge the gap between human and animal PTSD research and to create a framework for discovery of biomarkers and novel therapeutics. Published by Elsevier Ltd.

Translational neuropharmacology and the appropriate and effective use of animal models

PubMed Central

Green, AR; Gabrielsson, J; Fone, KCF

2011-01-01

This issue of the British Journal of Pharmacology is dedicated to reviews of the major animal models used in neuropharmacology to examine drugs for both neurological and psychiatric conditions. Almost all major conditions are reviewed. In general, regulatory authorities require evidence for the efficacy of novel compounds in appropriate animal models. However, the failure of many compounds in clinical trials following clear demonstration of efficacy in animal models has called into question both the value of the models and the discovery process in general. These matters are expertly reviewed in this issue and proposals for better models outlined. In this editorial, we further suggest that more attention be made to incorporate pharmacokinetic knowledge into the studies (quantitative pharmacology). We also suggest that more attention be made to ensure that full methodological details are published and recommend that journals should be more amenable to publishing negative data. Finally, we propose that new approaches must be used in drug discovery so that preclinical studies become more reflective of the clinical situation, and studies using animal models mimic the anticipated design of studies to be performed in humans, as closely as possible. LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-4 PMID:21545411

Fast I/O for Massively Parallel Applications

NASA Technical Reports Server (NTRS)

OKeefe, Matthew T.

1996-01-01

The two primary goals for this report were the design, contruction and modeling of parallel disk arrays for scientific visualization and animation, and a study of the IO requirements of highly parallel applications. In addition, further work in parallel display systems required to project and animate the very high-resolution frames resulting from our supercomputing simulations in ocean circulation and compressible gas dynamics.

Measurement in Learning Games Evolution: Review of Methodologies Used in Determining Effectiveness of "Math Snacks" Games and Animations

ERIC Educational Resources Information Center

Trujillo, Karen; Chamberlin, Barbara; Wiburg, Karin; Armstrong, Amanda

2016-01-01

This article captures the evolution of research goals and methodologies used to assess the effectiveness and impact of a set of mathematical educational games and animations for middle-school aged students. The researchers initially proposed using a mixed model research design of formative and summative measures, such as user-testing,…

ERAIZDA: a model for holistic annotation of animal infectious and zoonotic diseases.

PubMed

Buza, Teresia M; Jack, Sherman W; Kirunda, Halid; Khaitsa, Margaret L; Lawrence, Mark L; Pruett, Stephen; Peterson, Daniel G

2015-01-01

There is an urgent need for a unified resource that integrates trans-disciplinary annotations of emerging and reemerging animal infectious and zoonotic diseases. Such data integration will provide wonderful opportunity for epidemiologists, researchers and health policy makers to make data-driven decisions designed to improve animal health. Integrating emerging and reemerging animal infectious and zoonotic disease data from a large variety of sources into a unified open-access resource provides more plausible arguments to achieve better understanding of infectious and zoonotic diseases. We have developed a model for interlinking annotations of these diseases. These diseases are of particular interest because of the threats they pose to animal health, human health and global health security. We demonstrated the application of this model using brucellosis, an infectious and zoonotic disease. Preliminary annotations were deposited into VetBioBase database (http://vetbiobase.igbb.msstate.edu). This database is associated with user-friendly tools to facilitate searching, retrieving and downloading of disease-related information. Database URL: http://vetbiobase.igbb.msstate.edu. © The Author(s) 2015. Published by Oxford University Press.

A mobile, high-throughput semi-automated system for testing cognition in large non-primate animal models of Huntington disease.

PubMed

McBride, Sebastian D; Perentos, Nicholas; Morton, A Jennifer

2016-05-30

For reasons of cost and ethical concerns, models of neurodegenerative disorders such as Huntington disease (HD) are currently being developed in farm animals, as an alternative to non-human primates. Developing reliable methods of testing cognitive function is essential to determining the usefulness of such models. Nevertheless, cognitive testing of farm animal species presents a unique set of challenges. The primary aims of this study were to develop and validate a mobile operant system suitable for high throughput cognitive testing of sheep. We designed a semi-automated testing system with the capability of presenting stimuli (visual, auditory) and reward at six spatial locations. Fourteen normal sheep were used to validate the system using a two-choice visual discrimination task. Four stages of training devised to acclimatise animals to the system are also presented. All sheep progressed rapidly through the training stages, over eight sessions. All sheep learned the 2CVDT and performed at least one reversal stage. The mean number of trials the sheep took to reach criterion in the first acquisition learning was 13.9±1.5 and for the reversal learning was 19.1±1.8. This is the first mobile semi-automated operant system developed for testing cognitive function in sheep. We have designed and validated an automated operant behavioural testing system suitable for high throughput cognitive testing in sheep and other medium-sized quadrupeds, such as pigs and dogs. Sheep performance in the two-choice visual discrimination task was very similar to that reported for non-human primates and strongly supports the use of farm animals as pre-clinical models for the study of neurodegenerative diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

Capture-recapture survival models taking account of transients

USGS Publications Warehouse

Pradel, R.; Hines, J.E.; Lebreton, J.D.; Nichols, J.D.

1997-01-01

The presence of transient animals, common enough in natural populations, invalidates the estimation of survival by traditional capture- recapture (CR) models designed for the study of residents only. Also, the study of transit is interesting in itself. We thus develop here a class of CR models to describe the presence of transients. In order to assess the merits of this approach we examme the bias of the traditional survival estimators in the presence of transients in relation to the power of different tests for detecting transients. We also compare the relative efficiency of an ad hoc approach to dealing with transients that leaves out the first observation of each animal. We then study a real example using lazuli bunting (Passerina amoena) and, in conclusion, discuss the design of an experiment aiming at the estimation of transience. In practice, the presence of transients is easily detected whenever the risk of bias is high. The ad hoc approach, which yields unbiased estimates for residents only, is satisfactory in a time-dependent context but poorly efficient when parameters are constant. The example shows that intermediate situations between strict 'residence' and strict 'transience' may exist in certain studies. Yet, most of the time, if the study design takes into account the expected length of stay of a transient, it should be possible to efficiently separate the two categories of animals.

Catheter-based tricuspid valve replacement: first experimental data of a newly designed bileaflet stent graft prosthesis.

PubMed

Lausberg, Henning F; Gryszkiewicz, Rafal; Kuetting, Maximilian; Baumgaertner, Moritz; Centola, Marcos; Wendel, Hans-Peter; Nowak-Machen, Martina; Schibilsky, David; Kruger, Tobias; Schlensak, Christian

2017-07-01

Moderate or severe degree tricuspid valve regurgitation (TVR) is associated with high rates of morbidity and mortality. Surgical correction as the only therapeutic option offers unsatisfactory results. Recently, several interventional procedures have been introduced clinically in a limited cohort. We present our initial experiments with an innovative interventional valved stent graft for treatment of TVR. A newly designed porcine pericardium-covered nitinol stent graft with a lateral bicuspid valve was adapted to size in a cadaver study. After haemodynamic testing in an ex vivo perfusion setup, vascular access, valve delivery and function were investigated in an ovine animal model ( n  = 7). The device was implanted successfully in all animals. Vascular access was established surgically via the femoral vein without any vascular complications. Angiography demonstrated the correct position of the device with proper sealing of both venae cavae in 6 animals. In 1 extremely large animal, the position of the device was considered too cranial but still acceptable. Correct valve function was verified in all animals by both angiography and echocardiography. There were no persistent arrhythmias other than during valve implant. All animals survived the implant procedure and were sacrificed electively. This study demonstrated that this new valved stent graft could be delivered safely with correct positioning and valve function in this ovine model. Further long-term studies in animals implanted with the device after creation of tricuspid regurgitation are necessary to prove the haemodynamic benefit of this procedure. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Mathematical modeling and simulation in animal health - Part II: principles, methods, applications, and value of physiologically based pharmacokinetic modeling in veterinary medicine and food safety assessment.

PubMed

Lin, Z; Gehring, R; Mochel, J P; Lavé, T; Riviere, J E

2016-10-01

This review provides a tutorial for individuals interested in quantitative veterinary pharmacology and toxicology and offers a basis for establishing guidelines for physiologically based pharmacokinetic (PBPK) model development and application in veterinary medicine. This is important as the application of PBPK modeling in veterinary medicine has evolved over the past two decades. PBPK models can be used to predict drug tissue residues and withdrawal times in food-producing animals, to estimate chemical concentrations at the site of action and target organ toxicity to aid risk assessment of environmental contaminants and/or drugs in both domestic animals and wildlife, as well as to help design therapeutic regimens for veterinary drugs. This review provides a comprehensive summary of PBPK modeling principles, model development methodology, and the current applications in veterinary medicine, with a focus on predictions of drug tissue residues and withdrawal times in food-producing animals. The advantages and disadvantages of PBPK modeling compared to other pharmacokinetic modeling approaches (i.e., classical compartmental/noncompartmental modeling, nonlinear mixed-effects modeling, and interspecies allometric scaling) are further presented. The review finally discusses contemporary challenges and our perspectives on model documentation, evaluation criteria, quality improvement, and offers solutions to increase model acceptance and applications in veterinary pharmacology and toxicology. © 2016 John Wiley & Sons Ltd.

Gut Microbiome Standardization in Control and Experimental Mice.

PubMed

McCoy, Kathy D; Geuking, Markus B; Ronchi, Francesca

2017-04-03

Mouse models are used extensively to study human health and to investigate the mechanisms underlying human disease. In the past, most animal studies were performed without taking into consideration the impact of the microbiota. However, the microbiota that colonizes all body surfaces, including the gastrointestinal tract, respiratory tract, genitourinary tract, and skin, heavily impacts nearly every aspect of host physiology. When performing studies utilizing mouse models it is critical to understand that the microbiome is heavily impacted by environmental factors, including (but not limited to) food, bedding, caging, and temperature. In addition, stochastic changes in the microbiota can occur over time that also play a role in shaping microbial composition. These factors lead to massive variability in the composition of the microbiota between animal facilities and research institutions, and even within a single facility. Lack of experimental reproducibility between research groups has highlighted the necessity for rigorously controlled experimental designs in order to standardize the microbiota between control and experimental animals. Well controlled experiments are mandatory in order to reduce variability and allow correct interpretation of experimental results, not just of host-microbiome studies but of all mouse models of human disease. The protocols presented are aimed to design experiments that control the microbiota composition between different genetic strains of experimental mice within an animal unit. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

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

PubMed Central

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

2014-01-01

Tissue engineering and regenerative medicine (TERM) approaches may provide alternatives for gastrointestinal tissue in urinary diversion. To continue to clinically translatable studies, TERM alternatives need to be evaluated in (large) controlled and standardized animal studies. Here, we investigated all evidence for the efficacy of tissue engineered constructs in animal models for urinary diversion. Studies investigating this subject were identified through a systematic search of three different databases (PubMed, Embase and Web of Science). From each study, animal characteristics, study characteristics and experimental outcomes for meta-analyses were tabulated. Furthermore, the reporting of items vital for study replication was assessed. The retrieved studies (8 in total) showed extreme heterogeneity in study design, including animal models, biomaterials and type of urinary diversion. All studies were feasibility studies, indicating the novelty of this field. None of the studies included appropriate control groups, i.e. a comparison with the classical treatment using GI tissue. The meta-analysis showed a trend towards successful experimentation in larger animals although no specific animal species could be identified as the most suitable model. Larger animals appear to allow a better translation to the human situation, with respect to anatomy and surgical approaches. It was unclear whether the use of cells benefits the formation of a neo urinary conduit. The reporting of the methodology and data according to standardized guidelines was insufficient and should be improved to increase the value of such publications. In conclusion, animal models in the field of TERM for urinary diversion have probably been chosen for reasons other than their predictive value. Controlled and comparative long term animal studies, with adequate methodological reporting are needed to proceed to clinical translatable studies. This will aid in good quality research with the reduction in the use of animals and an increase in empirical evidence of biomedical research. PMID:24964011

A New Tool to Facilitate Learning Reading for Early Childhood

ERIC Educational Resources Information Center

Puspitasari, Cita; Subiyanto

2017-01-01

This paper proposes a new android application for early childhood learning reading. The description includes a design, development, and an evaluation experiment of an educational game for learning reading on android. Before developing the game, Unified Modeling Language (UML) diagrams, interfaces, animation, narrative or audio were designed.…

A review of fundamental principles for animal models of DOHaD research: an Australian perspective.

PubMed

Dickinson, H; Moss, T J; Gatford, K L; Moritz, K M; Akison, L; Fullston, T; Hryciw, D H; Maloney, C A; Morris, M J; Wooldridge, A L; Schjenken, J E; Robertson, S A; Waddell, B J; Mark, P J; Wyrwoll, C S; Ellery, S J; Thornburg, K L; Muhlhausler, B S; Morrison, J L

2016-10-01

Epidemiology formed the basis of 'the Barker hypothesis', the concept of 'developmental programming' and today's discipline of the Developmental Origins of Health and Disease (DOHaD). Animal experimentation provided proof of the underlying concepts, and continues to generate knowledge of underlying mechanisms. Interventions in humans, based on DOHaD principles, will be informed by experiments in animals. As knowledge in this discipline has accumulated, from studies of humans and other animals, the complexity of interactions between genome, environment and epigenetics, has been revealed. The vast nature of programming stimuli and breadth of effects is becoming known. As a result of our accumulating knowledge we now appreciate the impact of many variables that contribute to programmed outcomes. To guide further animal research in this field, the Australia and New Zealand DOHaD society (ANZ DOHaD) Animals Models of DOHaD Research Working Group convened at the 2nd Annual ANZ DOHaD Congress in Melbourne, Australia in April 2015. This review summarizes the contributions of animal research to the understanding of DOHaD, and makes recommendations for the design and conduct of animal experiments to maximize relevance, reproducibility and translation of knowledge into improving health and well-being.

A computational approach to animal breeding.

PubMed

Berger-Wolf, Tanya Y; Moore, Cristopher; Saia, Jared

2007-02-07

We propose a computational model of mating strategies for controlled animal breeding programs. A mating strategy in a controlled breeding program is a heuristic with some optimization criteria as a goal. Thus, it is appropriate to use the computational tools available for analysis of optimization heuristics. In this paper, we propose the first discrete model of the controlled animal breeding problem and analyse heuristics for two possible objectives: (1) breeding for maximum diversity and (2) breeding a target individual. These two goals are representative of conservation biology and agricultural livestock management, respectively. We evaluate several mating strategies and provide upper and lower bounds for the expected number of matings. While the population parameters may vary and can change the actual number of matings for a particular strategy, the order of magnitude of the number of expected matings and the relative competitiveness of the mating heuristics remains the same. Thus, our simple discrete model of the animal breeding problem provides a novel viable and robust approach to designing and comparing breeding strategies in captive populations.

Transcranial magnetic stimulation of mouse brain using high-resolution anatomical models

NASA Astrophysics Data System (ADS)

Crowther, L. J.; Hadimani, R. L.; Kanthasamy, A. G.; Jiles, D. C.

2014-05-01

Transcranial magnetic stimulation (TMS) offers the possibility of non-invasive treatment of brain disorders in humans. Studies on animals can allow rapid progress of the research including exploring a variety of different treatment conditions. Numerical calculations using animal models are needed to help design suitable TMS coils for use in animal experiments, in particular, to estimate the electric field induced in animal brains. In this paper, we have implemented a high-resolution anatomical MRI-derived mouse model consisting of 50 tissue types to accurately calculate induced electric field in the mouse brain. Magnetic field measurements have been performed on the surface of the coil and compared with the calculations in order to validate the calculated magnetic and induced electric fields in the brain. Results show how the induced electric field is distributed in a mouse brain and allow investigation of how this could be improved for TMS studies using mice. The findings have important implications in further preclinical development of TMS for treatment of human diseases.

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

PubMed

Hoffman, Andrew M; Dow, Steven W

2016-07-01

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

Virtual Environment for Surgical Room of the Future.

DTIC Science & Technology

1995-10-01

Design; 1. wire frame Dynamic Interaction 2. surface B. Acoustic Three-Dimensional Modeling; 3. solid based on radiosity modeling B. Dynamic...infection control of people and E. Rendering and Shadowing equipment 1. ray tracing D. Fluid Flow 2. radiosity F. Animation OBJECT RECOGNITION COMMUNICATION

Pupils' Response to a Model for Water Transport.

ERIC Educational Resources Information Center

Johnstone, A. H.; Mahmoud, N. A.

1981-01-01

Described is a model, based on the physical sciences, designed to teach secondary students about water transport through the use of an animated film. Pupils (N=440) taught by this method developed a self-consistent, although reduced, picture and understanding of osmosis. (Author/DC)

From basic to clinical neuropharmacology: targetophilia or pharmacodynamics?

PubMed

Green, A Richard; Aronson, Jeffrey K

2012-06-01

Historically, much drug discovery and development in psychopharmacology tended to be empirical. However, over the last 20 years it has primarily been target oriented, with synthesis and selection of compounds designed to act at a specific neurochemical site. Such compounds are then examined in functional animal models of disease. There is little evidence that this approach (which we call 'targetophilia') has enhanced the discovery process and some indications that it may have retarded it. A major problem is the weakness of many animal models in mimicking the disease and the lack of appropriate biochemical markers of drug action in animals and patients. In this review we argue that preclinical studies should be conducted as if they were clinical studies in design, analysis, and reporting, and that clinical pharmacologists should be involved at the earliest stages, to help ensure that animal models reflect as closely as possible the clinical disease. In addition, their familiarity with pharmacokinetic-pharmacodynamic integration (PK-PD) would help ensure that appropriate dosing and drug measurement techniques are applied to the discovery process, thereby producing results with relevance to therapeutics. Better integration of experimental and clinical pharmacologists early in the discovery process would allow observations in animals and patients to be quickly exchanged between the two disciplines. This non-linear approach to discovery used to be the way research proceeded, and it resulted in productivity that has never been bettered. It also follows that occasionally 'look-see' studies, a proven technique for drug discovery, deserve to be reintroduced. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Guidelines for pre-clinical assessment of the acetylcholine receptor--specific passive transfer myasthenia gravis model-Recommendations for methods and experimental designs.

PubMed

Kusner, Linda L; Losen, Mario; Vincent, Angela; Lindstrom, Jon; Tzartos, Socrates; Lazaridis, Konstantinos; Martinez-Martinez, Pilar

2015-08-01

Antibodies against the muscle acetylcholine receptor (AChR) are the most common cause of myasthenia gravis (MG). Passive transfer of AChR antibodies from MG patients into animals reproduces key features of human disease, including antigenic modulation of the AChR, complement-mediated damage of the neuromuscular junction, and muscle weakness. Similarly, AChR antibodies generated by active immunization in experimental autoimmune MG models can subsequently be passively transferred to other animals and induce weakness. The passive transfer model is useful to test therapeutic strategies aimed at the effector mechanism of the autoantibodies. Here we summarize published and unpublished experience using the AChR passive transfer MG model in mice, rats and rhesus monkeys, and give recommendations for the design of preclinical studies in order to facilitate translation of positive and negative results to improve MG therapies. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Enhancing the Ability of Experimental Autoimmune Encephalomyelitis to Serve as a More Rigorous Model of Multiple Sclerosis through Refinement of the Experimental Design

PubMed Central

Emerson, Mitchell R; Gallagher, Ryan J; Marquis, Janet G; LeVine, Steven M

2009-01-01

Advancing the understanding of the mechanisms involved in the pathogenesis of multiple sclerosis (MS) likely will lead to new and better therapeutics. Although important information about the disease process has been obtained from research on pathologic specimens, peripheral blood lymphocytes and MRI studies, the elucidation of detailed mechanisms has progressed largely through investigations using animal models of MS. In addition, animal models serve as an important tool for the testing of putative interventions. The most commonly studied model of MS is experimental autoimmune encephalomyelitis (EAE). This model can be induced in a variety of species and by various means, but there has been concern that the model may not accurately reflect the disease process, and more importantly, it may give rise to erroneous findings when it is used to test possible therapeutics. Several reasons have been given to explain the shortcomings of this model as a useful testing platform, but one idea provides a framework for improving the value of this model, and thus, it deserves careful consideration. In particular, the idea asserts that EAE studies are inadequately designed to enable appropriate evaluation of putative therapeutics. Here we discuss problem areas within EAE study designs and provide suggestions for their improvement. This paper is principally directed at investigators new to the field of EAE, although experienced investigators may find useful suggestions herein. PMID:19389303

Modified animal model and computer-assisted approach for dentoalveolar distraction osteogenesis to reconstruct unilateral maxillectomy defect.

PubMed

Feng, Zhihong; Zhao, Jinlong; Zhou, Libin; Dong, Yan; Zhao, Yimin

2009-10-01

The purpose of this report is to show the establishment of an animal model with a unilateral maxilla defect, application of virtual reality and rapid prototyping in the surgical planning for dentoalveolar distraction osteogenesis (DO). Two adult dogs were used to develop an animal model with a unilateral maxillary defect. The 3-dimensional model of the canine craniofacial skeleton was reconstructed with computed tomography data using the software Mimics, version 12.0 (Materialise Group, Leuven, Belgium). A virtual individual distractor was designed and transferred onto the model with the defect, and the osteotomies and distraction processes were simulated. A precise casting technique and numeric control technology were applied to produce the titanium distraction device, which was installed on the physical model with the defect, which was generated using Selective Laser Sintering technology, and the in vitro simulation of osteotomies and DO was done. The 2 dogs survived the operation and were lively. The osteotomies and distraction process were simulated successfully whether on the virtual or the physical model. The bone transport could be distracted to the desired position both in the virtual environment and on the physical model. The novel method to develop an animal model with a unilateral maxillary defect was feasible, and the animal model was suitable to develop the reconstruction method for unilateral maxillary defect cases with dentoalveolar DO. Computer-assisted surgical planning and simulation improved the reliability of the maxillofacial surgery, especially for the complex cases. The novel idea to reconstruct the unilateral maxillary defect with dentoalveolar DO was proved through the model experiment.

Flaws in animal studies exploring statins and impact on meta-analysis.

PubMed

Moja, Lorenzo; Pecoraro, Valentina; Ciccolallo, Laura; Dall'Olmo, Luigi; Virgili, Gianni; Garattini, Silvio

2014-06-01

Animal experiments should be appropriately designed, correctly analysed and transparently reported to increase their scientific validity and maximise the knowledge gained from each experiment. This systematic review of animal experiments investigating statins evaluates their quality of reporting and methodological aspects as well as their implications for the conduction of meta-analyses. We searched medline and embase for studies reporting research on statins in mice, rats and rabbits. We collected detailed information about the characteristics of studies, animals and experimental methods. We retrieved 161 studies. A little over half did not report randomisation (55%) and most did not describe blinding (88%). All studies reported details on the experimental procedure, although many omitted information about animal gender, age or weight. Four percent did not report the number of animals used. None reported the sample size. Fixed- and random-effects models gave different results (ratio of effect size increased by five folds). Heterogeneity was consistently substantial within animal models, for which accounting for covariates had minimal impact. Publication bias is highly suspected across studies. Although statins showed efficacy in animal models, preclinical studies highlighted fundamental problems in the way in which such research is conducted and reported. Results were often difficult to interpret and reproduce. Different meta-analytic approaches were highly inconsistent: a reliable approach to estimate the true parameter was imperceptible. Policies that address these issues are required from investigators, editors and institutions that care about the quality standards and ethics of animal research. © 2014 Stichting European Society for Clinical Investigation Journal Foundation.

Temporal variability of local abundance, sex ratio and activity in the Sardinian chalk hill blue butterfly

USGS Publications Warehouse

Casula, P.; Nichols, J.D.

2003-01-01

When capturing and marking of individuals is possible, the application of newly developed capture-recapture models can remove several sources of bias in the estimation of population parameters such as local abundance and sex ratio. For example, observation of distorted sex ratios in counts or captures can reflect either different abundances of the sexes or different sex-specific capture probabilities, and capture-recapture models can help distinguish between these two possibilities. Robust design models and a model selection procedure based on information-theoretic methods were applied to study the local population structure of the endemic Sardinian chalk hill blue butterfly, Polyommatus coridon gennargenti. Seasonal variations of abundance, plus daily and weather-related variations of active populations of males and females were investigated. Evidence was found of protandry and male pioneering of the breeding space. Temporary emigration probability, which describes the proportion of the population not exposed to capture (e.g. absent from the study area) during the sampling process, was estimated, differed between sexes, and was related to temperature, a factor known to influence animal activity. The correlation between temporary emigration and average daily temperature suggested interpreting temporary emigration as inactivity of animals. Robust design models were used successfully to provide a detailed description of the population structure and activity in this butterfly and are recommended for studies of local abundance and animal activity in the field.

Animal models for HIV/AIDS research

PubMed Central

Hatziioannou, Theodora; Evans, David T.

2015-01-01

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

Animal Models for the Study of Female Sexual Dysfunction

PubMed Central

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

2017-01-01

Introduction Significant progress has been made in elucidating the physiological and pharmacological mechanisms of female sexual function through preclinical animal research. The continued development of animal models is vital for the understanding and treatment of the many diverse disorders that occur in women. Aim To provide an updated review of the experimental models evaluating female sexual function that may be useful for clinical translation. Methods Review of English written, peer-reviewed literature, primarily from 2000 to 2012, that described studies on female sexual behavior related to motivation, arousal, physiological monitoring of genital function and urogenital pain. Main Outcomes Measures Analysis of supporting evidence for the suitability of the animal model to provide measurable indices related to desire, arousal, reward, orgasm, and pelvic pain. Results The development of female animal models has provided important insights in the peripheral and central processes regulating sexual function. Behavioral models of sexual desire, motivation, and reward are well developed. Central arousal and orgasmic responses are less well understood, compared with the physiological changes associated with genital arousal. Models of nociception are useful for replicating symptoms and identifying the neurobiological pathways involved. While in some cases translation to women correlates with the findings in animals, the requirement of circulating hormones for sexual receptivity in rodents and the multifactorial nature of women’s sexual function requires better designed studies and careful analysis. The current models have studied sexual dysfunction or pelvic pain in isolation; combining these aspects would help to elucidate interactions of the pathophysiology of pain and sexual dysfunction. Conclusions Basic research in animals has been vital for understanding the anatomy, neurobiology, and physiological mechanisms underlying sexual function and urogenital pain. These models are important for understanding the etiology of female sexual function and for future development of pharmacological treatments for sexual dysfunctions with or without pain. PMID:27784584

Animating streamlines with repeated asymmetric patterns for steady flow visualization

NASA Astrophysics Data System (ADS)

Yeh, Chih-Kuo; Liu, Zhanping; Lee, Tong-Yee

2012-01-01

Animation provides intuitive cueing for revealing essential spatial-temporal features of data in scientific visualization. This paper explores the design of Repeated Asymmetric Patterns (RAPs) in animating evenly-spaced color-mapped streamlines for dense accurate visualization of complex steady flows. We present a smooth cyclic variable-speed RAP animation model that performs velocity (magnitude) integral luminance transition on streamlines. This model is extended with inter-streamline synchronization in luminance varying along the tangential direction to emulate orthogonal advancing waves from a geometry-based flow representation, and then with evenly-spaced hue differing in the orthogonal direction to construct tangential flow streaks. To weave these two mutually dual sets of patterns, we propose an energy-decreasing strategy that adopts an iterative yet efficient procedure for determining the luminance phase and hue of each streamline in HSL color space. We also employ adaptive luminance interleaving in the direction perpendicular to the flow to increase the contrast between streamlines.

Non-clinical studies required for new drug development - Part I: early in silico and in vitro studies, new target discovery and validation, proof of principles and robustness of animal studies.

PubMed

Andrade, E L; Bento, A F; Cavalli, J; Oliveira, S K; Freitas, C S; Marcon, R; Schwanke, R C; Siqueira, J M; Calixto, J B

2016-10-24

This review presents a historical overview of drug discovery and the non-clinical stages of the drug development process, from initial target identification and validation, through in silico assays and high throughput screening (HTS), identification of leader molecules and their optimization, the selection of a candidate substance for clinical development, and the use of animal models during the early studies of proof-of-concept (or principle). This report also discusses the relevance of validated and predictive animal models selection, as well as the correct use of animal tests concerning the experimental design, execution and interpretation, which affect the reproducibility, quality and reliability of non-clinical studies necessary to translate to and support clinical studies. Collectively, improving these aspects will certainly contribute to the robustness of both scientific publications and the translation of new substances to clinical development.

Microphysiological Human Brain and Neural Systems-on-a-Chip: Potential Alternatives to Small Animal Models and Emerging Platforms for Drug Discovery and Personalized Medicine.

PubMed

Haring, Alexander P; Sontheimer, Harald; Johnson, Blake N

2017-06-01

Translational challenges associated with reductionist modeling approaches, as well as ethical concerns and economic implications of small animal testing, drive the need for developing microphysiological neural systems for modeling human neurological diseases, disorders, and injuries. Here, we provide a comprehensive review of microphysiological brain and neural systems-on-a-chip (NSCs) for modeling higher order trajectories in the human nervous system. Societal, economic, and national security impacts of neurological diseases, disorders, and injuries are highlighted to identify critical NSC application spaces. Hierarchical design and manufacturing of NSCs are discussed with distinction for surface- and bulk-based systems. Three broad NSC classes are identified and reviewed: microfluidic NSCs, compartmentalized NSCs, and hydrogel NSCs. Emerging areas and future directions are highlighted, including the application of 3D printing to design and manufacturing of next-generation NSCs, the use of stem cells for constructing patient-specific NSCs, and the application of human NSCs to 'personalized neurology'. Technical hurdles and remaining challenges are discussed. This review identifies the state-of-the-art design methodologies, manufacturing approaches, and performance capabilities of NSCs. This work suggests NSCs appear poised to revolutionize the modeling of human neurological diseases, disorders, and injuries.

Spatially explicit dynamic N-mixture models

USGS Publications Warehouse

Zhao, Qing; Royle, Andy; Boomer, G. Scott

2017-01-01

Knowledge of demographic parameters such as survival, reproduction, emigration, and immigration is essential to understand metapopulation dynamics. Traditionally the estimation of these demographic parameters requires intensive data from marked animals. The development of dynamic N-mixture models makes it possible to estimate demographic parameters from count data of unmarked animals, but the original dynamic N-mixture model does not distinguish emigration and immigration from survival and reproduction, limiting its ability to explain important metapopulation processes such as movement among local populations. In this study we developed a spatially explicit dynamic N-mixture model that estimates survival, reproduction, emigration, local population size, and detection probability from count data under the assumption that movement only occurs among adjacent habitat patches. Simulation studies showed that the inference of our model depends on detection probability, local population size, and the implementation of robust sampling design. Our model provides reliable estimates of survival, reproduction, and emigration when detection probability is high, regardless of local population size or the type of sampling design. When detection probability is low, however, our model only provides reliable estimates of survival, reproduction, and emigration when local population size is moderate to high and robust sampling design is used. A sensitivity analysis showed that our model is robust against the violation of the assumption that movement only occurs among adjacent habitat patches, suggesting wide applications of this model. Our model can be used to improve our understanding of metapopulation dynamics based on count data that are relatively easy to collect in many systems.

Translational value of animal models of kidney failure.

PubMed

Ortiz, Alberto; Sanchez-Niño, Maria D; Izquierdo, Maria C; Martin-Cleary, Catalina; Garcia-Bermejo, Laura; Moreno, Juan A; Ruiz-Ortega, Marta; Draibe, Juliana; Cruzado, Josep M; Garcia-Gonzalez, Miguel A; Lopez-Novoa, Jose M; Soler, Maria J; Sanz, Ana B

2015-07-15

Acute kidney injury (AKI) and chronic kidney disease (CKD) are associated with decreased renal function and increased mortality risk, while the therapeutic armamentarium is unsatisfactory. The availability of adequate animal models may speed up the discovery of biomarkers for disease staging and therapy individualization as well as design and testing of novel therapeutic strategies. Some longstanding animal models have failed to result in therapeutic advances in the clinical setting, such as kidney ischemia-reperfusion injury and diabetic nephropathy models. In this regard, most models for diabetic nephropathy are unsatisfactory in that they do not evolve to renal failure. Satisfactory models for additional nephropathies are needed. These include anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, IgA nephropathy, anti-phospholipase-A2-receptor (PLA2R) membranous nephropathy and Fabry nephropathy. However, recent novel models hold promise for clinical translation. Thus, the AKI to CKD translation has been modeled, in some cases with toxins of interest for human CKD such as aristolochic acid. Genetically modified mice provide models for Alport syndrome evolving to renal failure that have resulted in clinical recommendations, polycystic kidney disease models that have provided clues for the development of tolvaptan, that was recently approved for the human disease in Japan; and animal models also contributed to target C5 with eculizumab in hemolytic uremic syndrome. Some ongoing trials explore novel concepts derived from models, such TWEAK targeting as tissue protection for lupus nephritis. We now review animal models reproducing diverse, genetic and acquired, causes of AKI and CKD evolving to kidney failure and discuss the contribution to clinical translation and prospects for the future. Copyright © 2015 Elsevier B.V. All rights reserved.

Guidelines for the welfare and use of animals in cancer research

PubMed Central

Workman, P; Aboagye, E O; Balkwill, F; Balmain, A; Bruder, G; Chaplin, D J; Double, J A; Everitt, J; Farningham, D A H; Glennie, M J; Kelland, L R; Robinson, V; Stratford, I J; Tozer, G M; Watson, S; Wedge, S R; Eccles, S A

2010-01-01

Animal experiments remain essential to understand the fundamental mechanisms underpinning malignancy and to discover improved methods to prevent, diagnose and treat cancer. Excellent standards of animal care are fully consistent with the conduct of high quality cancer research. Here we provide updated guidelines on the welfare and use of animals in cancer research. All experiments should incorporate the 3Rs: replacement, reduction and refinement. Focusing on animal welfare, we present recommendations on all aspects of cancer research, including: study design, statistics and pilot studies; choice of tumour models (e.g., genetically engineered, orthotopic and metastatic); therapy (including drugs and radiation); imaging (covering techniques, anaesthesia and restraint); humane endpoints (including tumour burden and site); and publication of best practice. PMID:20502460

Permeability Evaluation Through Chitosan Membranes Using Taguchi Design

PubMed Central

Sharma, Vipin; Marwaha, Rakesh Kumar; Dureja, Harish

2010-01-01

In the present study, chitosan membranes capable of imitating permeation characteristics of diclofenac diethylamine across animal skin were prepared using cast drying method. The effect of concentration of chitosan, concentration of cross-linking agent (NaTPP), crosslinking time was studied using Taguchi design. Taguchi design ranked concentration of chitosan as the most important factor influencing the permeation parameters of diclofenac diethylamine. The flux of the diclofenac diethylamine solution through optimized chitosan membrane (T9) was found to be comparable to that obtained across rat skin. The mathematical model developed using multilinear regression analysis can be used to formulate chitosan membranes that can mimic the desired permeation characteristics. The developed chitosan membranes can be utilized as a substitute to animal skin for in vitro permeation studies. PMID:21179329

Permeability evaluation through chitosan membranes using taguchi design.

PubMed

Sharma, Vipin; Marwaha, Rakesh Kumar; Dureja, Harish

2010-01-01

In the present study, chitosan membranes capable of imitating permeation characteristics of diclofenac diethylamine across animal skin were prepared using cast drying method. The effect of concentration of chitosan, concentration of cross-linking agent (NaTPP), crosslinking time was studied using Taguchi design. Taguchi design ranked concentration of chitosan as the most important factor influencing the permeation parameters of diclofenac diethylamine. The flux of the diclofenac diethylamine solution through optimized chitosan membrane (T9) was found to be comparable to that obtained across rat skin. The mathematical model developed using multilinear regression analysis can be used to formulate chitosan membranes that can mimic the desired permeation characteristics. The developed chitosan membranes can be utilized as a substitute to animal skin for in vitro permeation studies.

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.

PubMed

Christensen, Jette; Vallières, André

2016-01-01

"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 claim. The generic AD scenario tree model demonstrated the benefit of combining three sources of surveillance data and helped to design the surveillance for the next year. The generic AD scenario model is one piece in Canada's self-declaration of freedom from AD. The model is strongly supported by the fact that AD has never been detected in Canada. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

"Mouse Clone Model" for evaluating the immunogenicity and tumorigenicity of pluripotent stem cells.

PubMed

Zhang, Gang; Zhang, Yi

2015-12-18

To investigate the immune-rejection and tumor-formation potentials of induced pluripotent stem cells and other stem cells, we devised a model-designated the "Mouse Clone Model"-which combined the theory of somatic animal cloning, tetraploid complementation, and induced pluripotent stem cells to demonstrate the applicability of stem cells for transplantation therapy.

Energy and time determine scaling in biological and computer designs

PubMed Central

Bezerra, George; Edwards, Benjamin; Brown, James; Forrest, Stephanie

2016-01-01

Metabolic rate in animals and power consumption in computers are analogous quantities that scale similarly with size. We analyse vascular systems of mammals and on-chip networks of microprocessors, where natural selection and human engineering, respectively, have produced systems that minimize both energy dissipation and delivery times. Using a simple network model that simultaneously minimizes energy and time, our analysis explains empirically observed trends in the scaling of metabolic rate in mammals and power consumption and performance in microprocessors across several orders of magnitude in size. Just as the evolutionary transitions from unicellular to multicellular animals in biology are associated with shifts in metabolic scaling, our model suggests that the scaling of power and performance will change as computer designs transition to decentralized multi-core and distributed cyber-physical systems. More generally, a single energy–time minimization principle may govern the design of many complex systems that process energy, materials and information. This article is part of the themed issue ‘The major synthetic evolutionary transitions’. PMID:27431524

Energy and time determine scaling in biological and computer designs.

PubMed

Moses, Melanie; Bezerra, George; Edwards, Benjamin; Brown, James; Forrest, Stephanie

2016-08-19

Metabolic rate in animals and power consumption in computers are analogous quantities that scale similarly with size. We analyse vascular systems of mammals and on-chip networks of microprocessors, where natural selection and human engineering, respectively, have produced systems that minimize both energy dissipation and delivery times. Using a simple network model that simultaneously minimizes energy and time, our analysis explains empirically observed trends in the scaling of metabolic rate in mammals and power consumption and performance in microprocessors across several orders of magnitude in size. Just as the evolutionary transitions from unicellular to multicellular animals in biology are associated with shifts in metabolic scaling, our model suggests that the scaling of power and performance will change as computer designs transition to decentralized multi-core and distributed cyber-physical systems. More generally, a single energy-time minimization principle may govern the design of many complex systems that process energy, materials and information.This article is part of the themed issue 'The major synthetic evolutionary transitions'. © 2016 The Author(s).

A search theory model of patch-to-patch forager movement with application to pollinator-mediated gene flow.

PubMed

Hoyle, Martin; Cresswell, James E

2007-09-07

We present a spatially implicit analytical model of forager movement, designed to address a simple scenario common in nature. We assume minimal depression of patch resources, and discrete foraging bouts, during which foragers fill to capacity. The model is particularly suitable for foragers that search systematically, foragers that deplete resources in a patch only incrementally, and for sit-and-wait foragers, where harvesting does not affect the rate of arrival of forage. Drawing on the theory of job search from microeconomics, we estimate the expected number of patches visited as a function of just two variables: the coefficient of variation of the rate of energy gain among patches, and the ratio of the expected time exploiting a randomly chosen patch and the expected time travelling between patches. We then consider the forager as a pollinator and apply our model to estimate gene flow. Under model assumptions, an upper bound for animal-mediated gene flow between natural plant populations is approximately proportional to the probability that the animal rejects a plant population. In addition, an upper bound for animal-mediated gene flow in any animal-pollinated agricultural crop from a genetically modified (GM) to a non-GM field is approximately proportional to the proportion of fields that are GM and the probability that the animal rejects a field.

Curiosity as an approach to ethoexperimental analysis: Behavioral neuroscience as seen by students and colleagues of Bob Blanchard.

PubMed

Pearson, Brandon L; Crawley, Jacqueline N; Eilam, David; Pentkowski, Nathan S; Summers, Cliff H

2017-05-01

This review is a synopsis of an International Behavioral Neuroscience Society (IBNS) symposium which focused on the elements of Behavioral Neuroscience for which Robert J. Blanchard was a Pioneer, Leading Expert, Advocate, Mentor, and Sage. Bob Blanchard's work demonstrably changed our broad understanding of animal behavior, and led the way to experimental design and analysis for studies of animal behavior that helped to clarify the deep complexity and subtleties of behavior. Bob's impact on the field of Behavioral Neuroscience includes the behavior, neurocircuitry, neurochemistry, and pharmacology related to social interactions, aggressive behavior, defensive behaviors, flight, freezing, threat, attack, risk assessment, anxiety disorders, animal models, models of social behavior, and autism. The methods and designs developed by Bob Blanchard over a lifetime have been adopted by scientists around the world, and form a standard of excellence in the field. The article addresses these topics in a way that presents developments in the field, describes the newest research data, and pays tribute to a great scientist and founder of this field of work, Bob Blanchard. Copyright © 2016 Elsevier Ltd. All rights reserved.

Systematic review and meta-analysis of efficacy of mesenchymal stem cells on locomotor recovery in animal models of traumatic brain injury.

PubMed

Peng, Weijun; Sun, Jing; Sheng, Chenxia; Wang, Zhe; Wang, Yang; Zhang, Chunhu; Fan, Rong

2015-03-26

The therapeutic potential of mesenchymal stem cells (MSCs) for traumatic brain injury (TBI) is attractive. Conducting systematic review and meta-analyses based on data from animal studies can be used to inform clinical trial design. To conduct a systematic review and meta-analysis to (i) systematically review the literatures describing the effect of MSCs therapy in animal models of TBI, (ii) determine the estimated effect size of functional locomotor recovery after experimental TBI, and (iii) to provide empirical evidence of biological factors associated with greater efficacy. We conducted a systematic search of PubMed, EMBASE, and Web of Science and hand searched related references. Studies were selected if they reported the efficacy of MSCs in animal models of TBI. Two investigators independently assessed the identified studies. We extracted the details of individual study characteristics from each publication, assessed study quality, evaluated the effect sizes of MSCs treatment, and performed stratified meta-analysis and meta-regression, to assess the influence of study design on the estimated effect size. The presence of small effect sizes was investigated using funnel plots and Egger's tests. Twenty-eight eligible controlled studies were identified. The study quality was modest. Between-study heterogeneity was large. Meta-analysis showed that MSCs exert statistically significant positive effects on sensorimotor and neurological motor function. For sensorimotor function, maximum effect size in studies with a quality score of 5 was found in the weight-drop impact injury TBI model established in male SD rats, to which syngeneic umbilical cord-derived MSCs intracerebrally at cell dose of (1-5)×10(6) was administered r 6 hours following TBI, using ketamine as anesthetic agent. For neurological motor function, effect size was maximum for studies with a quality score of 5, in which the weight-drop impact injury TBI models of the female Wistar rats were adopted, with administration syngeneic bone marrow-derived MSCs intravenously at cell dose of 5×10(6) at 2 months after TBI, using sevofluorane as anesthetic agent. We conclude that MSCs therapy may improve locomotor recovery after TBI. However, additional well-designed and well-reported animal studies are needed to guide further clinical studies.

Animal models of viral hemorrhagic fever.

PubMed

Smith, Darci R; Holbrook, Michael R; Gowen, Brian B

2014-12-01

The term "viral hemorrhagic fever" (VHF) designates a syndrome of acute febrile illness, increased vascular permeability and coagulation defects which often progresses to bleeding and shock and may be fatal in a significant percentage of cases. The causative agents are some 20 different RNA viruses in the families Arenaviridae, Bunyaviridae, Filoviridae and Flaviviridae, which are maintained in a variety of animal species and are transferred to humans through direct or indirect contact or by an arthropod vector. Except for dengue, which is transmitted among humans by mosquitoes, the geographic distribution of each type of VHF is determined by the range of its animal reservoir. Treatments are available for Argentine HF and Lassa fever, but no approved countermeasures have been developed against other types of VHF. The development of effective interventions is hindered by the sporadic nature of most infections and their occurrence in geographic regions with limited medical resources. Laboratory animal models that faithfully reproduce human disease are therefore essential for the evaluation of potential vaccines and therapeutics. The goal of this review is to highlight the current status of animal models that can be used to study the pathogenesis of VHF and test new countermeasures. Copyright © 2014 Elsevier B.V. All rights reserved.

Captopril and losartan for mitigation of renal injury caused by single-dose total-body irradiation.

PubMed

Moulder, John E; Cohen, Eric P; Fish, Brian L

2011-01-01

It is known that angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) can be used to mitigate radiation-induced renal injury. However, for a variety of reasons, these previous results are not directly applicable to the development of agents for the mitigation of injuries caused by terrorism-related radiation exposure. As part of an effort to develop an animal model that would fit the requirements of the U.S. Food and Drug Administration (FDA) "Animal Efficacy Rule", we designed new studies which used an FDA-approved ACEI (captopril) or an FDA-approved ARB (losartan, Cozaar®) started 10 days after a single total-body irradiation (TBI) at drug doses that are equivalent (on a g/m(2)/day basis) to the doses prescribed to humans. Captopril and losartan were equally effective as mitigators, with DMFs of 1.23 and 1.21, respectively, for delaying renal failure. These studies show that radiation nephropathy in a realistic rodent model can be mitigated with relevant doses of FDA-approved agents. This lays the necessary groundwork for pivotal rodent studies under the FDA Animal Efficacy Rule and provides an outline of how the FDA-required large-animal studies could be designed.

Captopril and Losartan for Mitigation of Renal Injury Caused by Single-Dose Total-Body Irradiation

PubMed Central

Moulder, John E.; Cohen, Eric P.; Fish, Brian L.

2011-01-01

It is known that angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) can be used to mitigate radiation-induced renal injury. However, for a variety of reasons, these previous results are not directly applicable to the development of agents for the mitigation of injuries caused by terrorism-related radiation exposure. As part of an effort to develop an animal model that would fit the requirements of the U.S. Food and Drug Administration (FDA) “Animal Efficacy Rule”, we designed new studies which used an FDA-approved ACEI (captopril) or an FDA-approved ARB (losartan, Cozaar®) started 10 days after a single total-body irradiation (TBI) at drug doses that are equivalent (on a g/m2/day basis) to the doses prescribed to humans. Captopril and losartan were equally effective as mitigators, with DMFs of 1.23 and 1.21, respectively, for delaying renal failure. These studies show that radiation nephropathy in a realistic rodent model can be mitigated with relevant doses of FDA-approved agents. This lays the necessary groundwork for pivotal rodent studies under the FDA Animal Efficacy Rule and provides an outline of how the FDA-required large-animal studies could be designed. PMID:21175344

Use of animal models for space flight physiology studies, with special focus on the immune system

NASA Technical Reports Server (NTRS)

Sonnenfeld, Gerald

2005-01-01

Animal models have been used to study the effects of space flight on physiological systems. The animal models have been used because of the limited availability of human subjects for studies to be carried out in space as well as because of the need to carry out experiments requiring samples and experimental conditions that cannot be performed using humans. Experiments have been carried out in space using a variety of species, and included developmental biology studies. These species included rats, mice, non-human primates, fish, invertebrates, amphibians and insects. The species were chosen because they best fit the experimental conditions required for the experiments. Experiments with animals have also been carried out utilizing ground-based models that simulate some of the effects of exposure to space flight conditions. Most of the animal studies have generated results that parallel the effects of space flight on human physiological systems. Systems studied have included the neurovestibular system, the musculoskeletal system, the immune system, the neurological system, the hematological system, and the cardiovascular system. Hindlimb unloading, a ground-based model of some of the effects of space flight on the immune system, has been used to study the effects of space flight conditions on physiological parameters. For the immune system, exposure to hindlimb unloading has been shown to results in alterations of the immune system similar to those observed after space flight. This has permitted the development of experiments that demonstrated compromised resistance to infection in rodents maintained in the hindlimb unloading model as well as the beginning of studies to develop countermeasures to ameliorate or prevent such occurrences. Although there are limitations to the use of animal models for the effects of space flight on physiological systems, the animal models should prove very valuable in designing countermeasures for exploration class missions of the future.

Preclinical Evidence for the Efficacy of Ischemic Postconditioning against Renal Ischemia-Reperfusion Injury, a Systematic Review and Meta-Analysis

PubMed Central

Jonker, Simone J.; Menting, Theo P.; Warlé, Michiel C.; Ritskes-Hoitinga, Merel; Wever, Kimberley E.

2016-01-01

Background Renal ischemia-reperfusion injury (IRI) is a major cause of kidney damage after e.g. renal surgery and transplantation. Ischemic postconditioning (IPoC) is a promising treatment strategy for renal IRI, but early clinical trials have not yet replicated the promising results found in animal studies. Method We present a systematic review, quality assessment and meta-analysis of the preclinical evidence for renal IPoC, and identify factors which modify its efficacy. Results We identified 39 publications studying >250 control animals undergoing renal IRI only and >290 animals undergoing renal IRI and IPoC. Healthy, male rats undergoing warm ischemia were used in the vast majority of studies. Four studies applied remote IPoC, all others used local IPoC. Meta-analysis showed that both local and remote IPoC ameliorated renal damage after IRI for the outcome measures serum creatinine, blood urea nitrogen and renal histology. Subgroup analysis indicated that IPoC efficacy increased with the duration of index ischemia. Measures to reduce bias were insufficiently reported. Conclusion High efficacy of IPoC is observed in animal models, but factors pertaining to the internal and external validity of these studies may hamper the translation of IPoC to the clinical setting. The external validity of future animal studies should be increased by including females, comorbid animals, and transplantation models, in order to better inform clinical trial design. The severity of renal damage should be taken into account in the design and analysis of future clinical trials. PMID:26963819

Harnessing cognitive neuroscience to develop new treatments for improving cognition in schizophrenia: CNTRICS selected cognitive paradigms for animal models.

PubMed

Moore, Holly; Geyer, Mark A; Carter, Cameron S; Barch, Deanna M

2013-11-01

Over the past two decades, the awareness of the disabling and treatment-refractory effects of impaired cognition in schizophrenia has increased dramatically. In response to this still unmet need in the treatment of schizophrenia, the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative was developed. The goal of CNTRICS is to harness cognitive neuroscience to develop a brain-based set of tools for measuring cognition in schizophrenia and to test new treatments. CNTRICS meetings focused on development of tasks with cognitive construct validity for use in both human and animal model studies. This special issue presents papers discussing the cognitive testing paradigms selected by CNTRICS for animal model systems. These paradigms are designed to measure cognitive constructs within the domains of perception, attention, executive function, working memory, object/relational long-term memory, and social/affective processes. Copyright © 2013. Published by Elsevier Ltd.

Animal models for influenza virus pathogenesis, transmission, and immunology

PubMed Central

Thangavel, Rajagowthamee R.; Bouvier, Nicole M.

2014-01-01

In humans, infection with an influenza A or B virus manifests typically as an acute and self-limited upper respiratory tract illness characterized by fever, cough, sore throat, and malaise. However, influenza can present along a broad spectrum of disease, ranging from sub-clinical or even asymptomatic infection to a severe primary viral pneumonia requiring advanced medical supportive care. Disease severity depends upon the virulence of the influenza virus strain and the immune competence and previous influenza exposures of the patient. Animal models are used in influenza research not only to elucidate the viral and host factors that affect influenza disease outcomes in and spread among susceptible hosts, but also to evaluate interventions designed to prevent or reduce influenza morbidity and mortality in man. This review will focus on the three animal models currently used most frequently in influenza virus research -- mice, ferrets, and guinea pigs -- and discuss the advantages and disadvantages of each. PMID:24709389

Harnessing cognitive neuroscience to develop new treatments for improving cognition in schizophrenia: CNTRICS selected cognitive paradigms for animal models

PubMed Central

Moore, Holly; Geyer, Mark A.; Carter, Cameron S.; Barch, Deanna M.

2014-01-01

Over the past two decades, the awareness of the disabling and treatment-refractory effects of impaired cognition in schizophrenia has increased dramatically. In response to this still unmet need in the treatment of schizophrenia, the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative was developed. The goal of CNTRICS is to harness cognitive neuroscience to develop a brain-based set of tools for measuring cognition in schizophrenia and to test new treatments. CNTRICS meetings focused on development of tasks with cognitive construct validity for use in both human and animal model studies. This special issue presents papers discussing the cognitive testing paradigms selected by CNTRICS for animal model systems. These paradigms are designed to measure cognitive constructs within the domains of perception, attention, executive function, working memory, object/relational long-term memory, and social/affective processes. PMID:24090823

Maternal hypothyroidism: An overview of current experimental models.

PubMed

Ghanbari, Mahboubeh; Ghasemi, Asghar

2017-10-15

Maternal hypothyroidism (MH) is the most common cause of transient congenital hypothyroidism. Different animal models are used for assessing developmental effects of MH in offspring. The severity and status of hypothyroidism in animal models must be a reflection of the actual conditions in humans. To obtain comparable results with different clinical conditions, which lead to MH in humans, several factors have been suggested for researchers to consider before designing the experimental models. Regarding development of fetal body systems during pregnancy, interference at different times provides different results and the appropriate time for induction of hypothyroidism should be selected based on accurate time of development of the system under assessment. Other factors that should be taken into consideration include, physiological and biochemical differences between humans and other species, thyroid hormone-independent effects of anti-thyroid drugs, circadian rhythms in TSH secretion, sex differences, physical and psychological stress. This review addresses essential guidelines for selecting and managing the optimal animal model for MH as well as discussing the pros and cons of currently used models. Copyright © 2017 Elsevier Inc. All rights reserved.

Subcutaneous Crotaline Fab antivenom for the treatment of rattlesnake envenomation in a porcine model.

PubMed

Offerman, Steven R; Barry, J David; Richardson, William H; Tong, Tri; Tanen, Dave; Bush, Sean P; Clark, Richard F

2009-01-01

This study was designed to investigate whether the local, subcutaneous injection of Crotaline Fab antivenom (CroFab) at the rattlesnake envenomation site would result in less extremity edema when compared to intravenous (i.v.) antivenom infusion alone. This is a randomized, three-arm laboratory experiment using a porcine model. Each animal was anesthetized, intubated, and maintained on mechanical ventilation. About 6 mg/kg of Crotalus atrox venom was injected subcutaneously at the hock of the right hind leg. Animals were then randomized to immediately receive subcutaneous and i.v. antivenom (SC/IV), i.v. antivenom only, or saline control. SC/IV animals received two vials of CroFab subcutaneously at the envenomation site and two vials intravenously. IV animals received four vials of CroFab intravenously. Limb edema was tracked by serial circumference and volumetric measurements over an 8-h period. Limb circumference was measured at four pre-determined locations hourly. Limb volume was measured by a water displacement method at baseline, 4, and 8 h. Twenty-six animals were randomized to the three treatment groups. The SC/IV and IV arms included nine animals each. Two animals in the SC/IV group died suddenly during the study, leaving seven animals for data analysis. There were eight controls. Increasing limb edema was observed in all groups. No differences were detected in limb circumferences or limb volumes between control and either treatment arms. In this porcine model of crotaline envenomation, no differences in limb edema were found between animals treated with SC/IV or IV CroFab when compared to saline controls.

Laboratory Animal Facilities. Laboratory Design Notes.

ERIC Educational Resources Information Center

Jonas, Albert M.

1965-01-01

Design of laboratory animal facilities must be functional. Accordingly, the designer should be aware of the complex nature of animal research and specifically the type of animal research which will be conducted in a new facility. The building of animal-care facilities in research institutions requires special knowledge in laboratory animal…

A network control theory approach to modeling and optimal control of zoonoses: case study of brucellosis transmission in sub-Saharan Africa.

PubMed

Roy, Sandip; McElwain, Terry F; Wan, Yan

2011-10-01

Developing control policies for zoonotic diseases is challenging, both because of the complex spread dynamics exhibited by these diseases, and because of the need for implementing complex multi-species surveillance and control efforts using limited resources. Mathematical models, and in particular network models, of disease spread are promising as tools for control-policy design, because they can provide comprehensive quantitative representations of disease transmission. A layered dynamical network model for the transmission and control of zoonotic diseases is introduced as a tool for analyzing disease spread and designing cost-effective surveillance and control. The model development is achieved using brucellosis transmission among wildlife, cattle herds, and human sub-populations in an agricultural system as a case study. Precisely, a model that tracks infection counts in interacting animal herds of multiple species (e.g., cattle herds and groups of wildlife for brucellosis) and in human subpopulations is introduced. The model is then abstracted to a form that permits comprehensive targeted design of multiple control capabilities as well as model identification from data. Next, techniques are developed for such quantitative design of control policies (that are directed to both the animal and human populations), and for model identification from snapshot and time-course data, by drawing on recent results in the network control community. The modeling approach is shown to provide quantitative insight into comprehensive control policies for zoonotic diseases, and in turn to permit policy design for mitigation of these diseases. For the brucellosis-transmission example in particular, numerous insights are obtained regarding the optimal distribution of resources among available control capabilities (e.g., vaccination, surveillance and culling, pasteurization of milk) and points in the spread network (e.g., transhumance vs. sedentary herds). In addition, a preliminary identification of the network model for brucellosis is achieved using historical data, and the robustness of the obtained model is demonstrated. As a whole, our results indicate that network modeling can aid in designing control policies for zoonotic diseases.

A Network Control Theory Approach to Modeling and Optimal Control of Zoonoses: Case Study of Brucellosis Transmission in Sub-Saharan Africa

PubMed Central

Roy, Sandip; McElwain, Terry F.; Wan, Yan

2011-01-01

Background Developing control policies for zoonotic diseases is challenging, both because of the complex spread dynamics exhibited by these diseases, and because of the need for implementing complex multi-species surveillance and control efforts using limited resources. Mathematical models, and in particular network models, of disease spread are promising as tools for control-policy design, because they can provide comprehensive quantitative representations of disease transmission. Methodology/Principal Findings A layered dynamical network model for the transmission and control of zoonotic diseases is introduced as a tool for analyzing disease spread and designing cost-effective surveillance and control. The model development is achieved using brucellosis transmission among wildlife, cattle herds, and human sub-populations in an agricultural system as a case study. Precisely, a model that tracks infection counts in interacting animal herds of multiple species (e.g., cattle herds and groups of wildlife for brucellosis) and in human subpopulations is introduced. The model is then abstracted to a form that permits comprehensive targeted design of multiple control capabilities as well as model identification from data. Next, techniques are developed for such quantitative design of control policies (that are directed to both the animal and human populations), and for model identification from snapshot and time-course data, by drawing on recent results in the network control community. Conclusions/Significance The modeling approach is shown to provide quantitative insight into comprehensive control policies for zoonotic diseases, and in turn to permit policy design for mitigation of these diseases. For the brucellosis-transmission example in particular, numerous insights are obtained regarding the optimal distribution of resources among available control capabilities (e.g., vaccination, surveillance and culling, pasteurization of milk) and points in the spread network (e.g., transhumance vs. sedentary herds). In addition, a preliminary identification of the network model for brucellosis is achieved using historical data, and the robustness of the obtained model is demonstrated. As a whole, our results indicate that network modeling can aid in designing control policies for zoonotic diseases. PMID:22022621

Design of a Model of Knee Joint for Educational Purposes

ERIC Educational Resources Information Center

Jastaniah, Saddig; Alganmi, Ohud

2016-01-01

Uses of models play an important role by simulating the bone, obviating the need to experiment on humans or animals. The aim of the present study was to access local materials as gypsum and wax is to be tested for performing a knee model matching bone in the density also to explore how students can come to understand function through a model-based…

Wound models for periodontal and bone regeneration: the role of biologic research.

PubMed

Sculean, Anton; Chapple, Iain L C; Giannobile, William V

2015-06-01

The ultimate goals of periodontal therapy remain the complete regeneration of those periodontal tissues lost to the destructive inflammatory-immune response, or to trauma, with tissues that possess the same structure and function, and the re-establishment of a sustainable health-promoting biofilm from one characterized by dysbiosis. This volume of Periodontology 2000 discusses the multiple facets of a transition from therapeutic empiricism during the late 1960s, toward regenerative therapies, which is founded on a clearer understanding of the biophysiology of normal structure and function. This introductory article provides an overview on the requirements of appropriate in vitro laboratory models (e.g. cell culture), of preclinical (i.e. animal) models and of human studies for periodontal wound and bone repair. Laboratory studies may provide valuable fundamental insights into basic mechanisms involved in wound repair and regeneration but also suffer from a unidimensional and simplistic approach that does not account for the complexities of the in vivo situation, in which multiple cell types and interactions all contribute to definitive outcomes. Therefore, such laboratory studies require validatory research, employing preclinical models specifically designed to demonstrate proof-of-concept efficacy, preliminary safety and adaptation to human disease scenarios. Small animal models provide the most economic and logistically feasible preliminary approaches but the outcomes do not necessarily translate to larger animal or human models. The advantages and limitations of all periodontal-regeneration models need to be carefully considered when planning investigations to ensure that the optimal design is adopted to answer the specific research question posed. Future challenges lie in the areas of stem cell research, scaffold designs, cell delivery and choice of growth factors, along with research to ensure appropriate gingival coverage in order to prevent gingival recession during the healing phase. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Towards ethically improved animal experimentation in the study of animal reproduction.

PubMed

Blache, D; Martin, G B; Maloney, S K

2008-07-01

The ethics of animal-based research is a continuing area of debate, but ethical research protocols do not prevent scientific progress. In this paper, we argue that our current knowledge of the factors that affect reproductive processes provides researchers with a solid foundation upon which they can conduct more ethical research and simultaneously produce data of higher quality. We support this argument by showing how a deep understanding of the genetics, nutrition and temperament of our experimental animals can improve compliance with two of the '3 Rs', reduction and refinement, simply by offering better control over the variance in our experimental model. The outcome is a better experimental design, on both ethical and scientific grounds.

Average dispersal success: linking home range, dispersal, and metapopulation dynamics to reserve design.

PubMed

Fagan, William F; Lutscher, Frithjof

2006-04-01

Spatially explicit models for populations are often difficult to tackle mathematically and, in addition, require detailed data on individual movement behavior that are not easily obtained. An approximation known as the "average dispersal success" provides a tool for converting complex models, which may include stage structure and a mechanistic description of dispersal, into a simple matrix model. This simpler matrix model has two key advantages. First, it is easier to parameterize from the types of empirical data typically available to conservation biologists, such as survivorship, fecundity, and the fraction of juveniles produced in a study area that also recruit within the study area. Second, it is more amenable to theoretical investigation. Here, we use the average dispersal success approximation to develop estimates of the critical reserve size for systems comprising single patches or simple metapopulations. The quantitative approach can be used for both plants and animals; however, to provide a concrete example of the technique's utility, we focus on a special case pertinent to animals. Specifically, for territorial animals, we can characterize such an estimate of minimum viable habitat area in terms of the number of home ranges that the reserve contains. Consequently, the average dispersal success framework provides a framework through which home range size, natal dispersal distances, and metapopulation dynamics can be linked to reserve design. We briefly illustrate the approach using empirical data for the swift fox (Vulpes velox).

Impact of Comorbidities on Acute Injury and Recovery in Preclinical Stroke Research: Focus on Hypertension and Diabetes

PubMed Central

Ergul, Adviye; Hafez, Sherif; Fouda, Abdelrahman; Fagan, Susan C.

2016-01-01

Human ischemic stroke is very complex and no single preclinical model can comprise all the variables known to contribute to stroke injury and recovery. Hypertension, diabetes and hyperlipidemia are leading comorbidities in stroke patients. The use of predominantly young adult and healthy animals in experimental stroke research has created a barrier for translation of findings to patients. As such, more and more disease models are being incorporated into the research design. This review highlights the major strengths and weaknesses of the most commonly used animal models of these conditions in preclinical stroke research. The goal is to provide guidance in choosing, reporting and executing appropriate disease models that will be subjected to different models of stroke injury. PMID:27026092

9 CFR 98.33 - Ports designated for the importation of certain animal semen.

Code of Federal Regulations, 2011 CFR

2011-01-01

... of certain animal semen. 98.33 Section 98.33 Animals and Animal Products ANIMAL AND PLANT HEALTH... ANIMAL PRODUCTS IMPORTATION OF CERTAIN ANIMAL EMBRYOS AND ANIMAL SEMEN Certain Animal Semen § 98.33 Ports designated for the importation of certain animal semen. (a) Air and ocean ports. The following air and ocean...

9 CFR 98.33 - Ports designated for the importation of certain animal semen.

Code of Federal Regulations, 2010 CFR

2010-01-01

... of certain animal semen. 98.33 Section 98.33 Animals and Animal Products ANIMAL AND PLANT HEALTH... ANIMAL PRODUCTS IMPORTATION OF CERTAIN ANIMAL EMBRYOS AND ANIMAL SEMEN Certain Animal Semen § 98.33 Ports designated for the importation of certain animal semen. (a) Air and ocean ports. The following air and ocean...

Direct Behavioral Evidence for Retronasal Olfaction in Rats

PubMed Central

Gautam, Shree Hari; Verhagen, Justus V.

2012-01-01

The neuroscience of flavor perception is becoming increasingly important to understand abnormal feeding behaviors and associated chronic diseases such as obesity. Yet, flavor research has mainly depended on human subjects due to the lack of an animal model. A crucial step towards establishing an animal model of flavor research is to determine whether the animal uses the retronasal mode of olfaction, an essential element of flavor perception. We designed a go- no go behavioral task to test the rat's ability to detect and discriminate retronasal odorants. In this paradigm, tasteless aqueous solutions of odorants were licked by water-restricted head-fixed rats from a lick spout. Orthonasal contamination was avoided by employing a combination of a vacuum around the lick-spout and blowing clean air toward the nose. Flow models support the effectiveness of both approaches. The licked odorants were successfully discriminated by rats. Moreover, the tasteless odorant amyl acetate was reliably discriminated against pure distilled water in a concentration-dependent manner. The results from this retronasal odor discrimination task suggest that rats are capable of smelling retronasally. This direct behavioral evidence establishes the rat as a useful animal model for flavor research. PMID:22970305

Novel In Vitro/Ex Vivo Animal Modeling for Filovirus Aerosol Infection

DTIC Science & Technology

2013-09-01

CONTRACTING ORGANIZATION: Sanofi Pasteur VaxDesign Corporation Orlando, Florida, 32826...Ayesha.Mahmood@sanofi.com 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Sanofi Pasteur VaxDesign Corporation...between the military USAMRIID labs and Sanofi Pasteur, to investigate the application of the Mucosal Tissue Equivalent (MTE) module of the MIMIC

The Complexity of Biomechanics Causing Primary Blast-Induced Traumatic Brain Injury: A Review of Potential Mechanisms

PubMed Central

Courtney, Amy; Courtney, Michael

2015-01-01

Primary blast-induced traumatic brain injury (bTBI) is a prevalent battlefield injury in recent conflicts, yet biomechanical mechanisms of bTBI remain unclear. Elucidating specific biomechanical mechanisms is essential to developing animal models for testing candidate therapies and for improving protective equipment. Three hypothetical mechanisms of primary bTBI have received the most attention. Because translational and rotational head accelerations are primary contributors to TBI from non-penetrating blunt force head trauma, the acceleration hypothesis suggests that blast-induced head accelerations may cause bTBI. The hypothesis of direct cranial transmission suggests that a pressure transient traverses the skull into the brain and directly injures brain tissue. The thoracic hypothesis of bTBI suggests that some combination of a pressure transient reaching the brain via the thorax and a vagally mediated reflex result in bTBI. These three mechanisms may not be mutually exclusive, and quantifying exposure thresholds (for blasts of a given duration) is essential for determining which mechanisms may be contributing for a level of blast exposure. Progress has been hindered by experimental designs, which do not effectively expose animal models to a single mechanism and by over-reliance on poorly validated computational models. The path forward should be predictive validation of computational models by quantitative confirmation with blast experiments in animal models, human cadavers, and biofidelic human surrogates over a range of relevant blast magnitudes and durations coupled with experimental designs, which isolate a single injury mechanism. PMID:26539158

What's the Technology For? Teacher Attention and Pedagogical Goals in a Modeling-Focused Professional Development Workshop

ERIC Educational Resources Information Center

Wilkerson, Michelle Hoda; Andrews, Chelsea; Shaban, Yara; Laina, Vasiliki; Gravel, Brian E.

2016-01-01

This paper explores the role that technology can play in engaging pre-service teachers with the iterative, "messy" nature of model-based inquiry. Over the course of 5 weeks, 11 pre-service teachers worked in groups to construct models of diffusion using a computational animation and simulation toolkit, and designed lesson plans for the…

A conceptual and practical guide to the behavioural evaluation of animal models of the symptomatology and therapy of schizophrenia

PubMed Central

Yee, Benjamin K.; Singer, Philipp

2013-01-01

Schizophrenia is a chronic debilitating brain disorder characterized by a complex set of perceptual and behavioural symptoms that severely disrupt and undermine the patient’s psychological well-being and quality of life. Since the exact disease mechanisms remain essentially unknown, holistic animal models are indispensable tools for any serious investigation into the neurobiology of schizophrenia, including the search of remedies, prevention, and possible biological markers. This review provides some practical advice to those confronted with the task of evaluating their animal models for relevance to schizophrenia that inevitably involves behavioural tests with animals. To a novice, this challenge is not only a technical one, as it also entails attention to interpretative issues concerning validity and translational power. Here, we attempt to offer some guidance to help overcome these obstacles by drawing on our experience on diverse animal models of schizophrenia based on genetics, strain difference, brain lesions, pharmacological induction, and early life developmental manipulations. The review pays equal emphasis on the general (theoretical) considerations in experimental design and the illustration of the problematics related to test parameters and data analysis of selected exemplar behavioural tests. Finally, the individual difference of behavioural expression in relevant tests observed in wild type animals may offer an alternative approach to explore the mechanism of schizophrenia-related behavioural dysfunction at the molecular, cellular and structural levels that are of more immediate relevance to cell and tissue research. PMID:23579553

Biological and aerodynamic problems with the flight of animals

NASA Technical Reports Server (NTRS)

Holst, E. V.; Kuchemann, D.

1980-01-01

Biological and aerodynamic considerations related to birds and insects are discussed. A wide field is open for comparative biological, physiological, and aerodynamic investigations. Considerable mathematics related to the flight of animals is presented, including 20 equations. The 15 figures included depict the design of bird and insect wings, diagrams of propulsion efficiency, thrust, lift, and angles of attack and photographs of flapping wing free flying wing only models which were built and flown.

On the value of therapeutic interventions targeting the complement system in acute myocardial infarction.

PubMed

Emmens, Reindert W; Wouters, Diana; Zeerleder, Sacha; van Ham, S Marieke; Niessen, Hans W M; Krijnen, Paul A J

2017-04-01

The complement system plays an important role in the inflammatory response subsequent to acute myocardial infarction (AMI). The aim of this study is to create a systematic overview of studies that have investigated therapeutic administration of complement inhibitors in both AMI animal models and human clinical trials. To enable extrapolation of observations from included animal studies toward post-AMI clinical trials, ex vivo studies on isolated hearts and proof-of-principle studies on inhibitor administration before experimental AMI induction were excluded. Positive therapeutic effects in AMI animal models have been described for cobra venom factor, soluble complement receptor 1, C1-esterase inhibitor (C1-inh), FUT-175, C1s-inhibitor, anti-C5, ADC-1004, clusterin, and glycosaminoglycans. Two types of complement inhibitors have been tested in clinical trials, being C1-inh and anti-C5. Pexelizumab (anti-C5) did not result in reproducible beneficial effects for AMI patients. Beneficial effects were reported in AMI patients for C1-inhibitor, albeit in small patient groups. In general, despite the absence of consistent positive effects in clinical trials thus far, the complement system remains a potentially interesting target for therapy in AMI patients. Based on the study designs of previous animal studies and clinical trials, we discuss several issues which require attention in the design of future studies: adjustment of clinical trial design to precise mechanism of action of administered inhibitor, optimizing the duration of therapy, and optimization of time point(s) on which therapeutic effects will be evaluated. Copyright © 2016 Elsevier Inc. All rights reserved.

Risk-based methods for fish and terrestrial animal disease surveillance.

PubMed

Oidtmann, Birgit; Peeler, Edmund; Lyngstad, Trude; Brun, Edgar; Bang Jensen, Britt; Stärk, Katharina D C

2013-10-01

Over recent years there have been considerable methodological developments in the field of animal disease surveillance. The principles of risk analysis were conceptually applied to surveillance in order to further develop approaches and tools (scenario tree modelling) to design risk-based surveillance (RBS) programmes. In the terrestrial animal context, examples of risk-based surveillance have demonstrated the substantial potential for cost saving, and a similar benefit is expected also for aquatic animals. RBS approaches are currently largely absent for aquatic animal diseases. A major constraint in developing RBS designs in the aquatic context is the lack of published data to assist in the design of RBS: this applies to data on (i) the relative risk of farm sites becoming infected due to the presence or absence of a given risk factor; (ii) the sensitivity of diagnostic tests (specificity is often addressed by follow-up investigation and re-testing and therefore less of a concern); (iii) data on the variability of prevalence of infection for fish within a holding unit, between holding units and at farm level. Another constraint is that some of the most basic data for planning surveillance are missing, e.g. data on farm location and animal movements. In Europe, registration or authorisation of fish farms has only recently become a requirement under EU Directive 2006/88. Additionally, the definition of the epidemiological unit (at site or area level) in the context of aquaculture is a challenge due to the often high level of connectedness (mainly via water) of aquaculture facilities with the aquatic environment. This paper provides a review of the principles, methods and examples of RBS in terrestrial, farmed and wild animals. It discusses the special challenges associated with surveillance for aquatic animal diseases (e.g. accessibility of animals for inspection and sampling, complexity of rearing systems) and provides an overview of current developments relevant for the design of RBS for fish diseases. Suggestions are provided on how the current constraints to applying RBS to fish diseases can be overcome. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Some useful innovations with TRASYS and SINDA-85

NASA Technical Reports Server (NTRS)

Amundsen, Ruth M.

1993-01-01

Several innovative methods were used to allow more efficient and accurate thermal analysis using SINDA-85 and TRASYS, including model integration and reduction, planetary surface calculations, and model animation. Integration with other modeling and analysis codes allows an analyst to import a geometry from a solid modeling or computer-aided design (CAD) software package, rather than building the geometry 'by hand.' This is more efficient as well as potentially more accurate. However, the use of solid modeling software often generates large analytical models. The problem of reducing large models was elegantly solved using the response of the transient derivative to a forcing step function. The thermal analysis of a lunar rover implemented two unusual features of the TRASYS/SINDA system. A little-known TRASYS routine SURFP calculates the solar heating of a rover on the lunar surface for several different rover positions and orientations. This is used not only to determine the rover temperatures, but also to automatically determine the power generated by the solar arrays. The animation of transient thermal results is an effective tool, especially in a vivid case such as the 14-day progress of the sun over the lunar rover. An animated color map on the solid model displays the progression of temperatures.

Pupils Produce their Own Narratives Inspired by the History of Science: Animation Movies Concerning the Geocentric-Heliocentric Debate

NASA Astrophysics Data System (ADS)

Piliouras, Panagiotis; Siakas, Spyros; Seroglou, Fanny

2011-07-01

In this paper, we present the design and application of a teaching scenario appropriate for 12-years-old pupils in the primary school aiming to a better understanding of scientific concepts and scientific methods, linking the development of individual thinking with the development of scientific ideas and facilitating a better understanding of the nature of science. The design of the instructional material supporting this scenario has been based on the study of the history of astronomy and especially on: (a) The various theories concerning the movement of Earth, our solar system and the universe. (b) Key-stories highlighting the evolutionary character of scientific knowledge as well as the cultural interrelations of science and society. The design of the teaching scenario has focused on the participation of pupils in gradually evolving discourses and practices encouraging an appreciation of aspects of the nature of science (e.g. the role of observation and hypothesis, the use of evidence, the creation and modification of models). In this case, pupils are asked to produce their own narratives: animation movies concerning the geocentric-heliocentric debate inspired by the history of science, as the animation technique presents strong expressional potential and currently has many applications in the field of educational multimedia. The research design of this current case study has been based on the SHINE research model, while data coming from pupils' animation movies, questionnaires, interviews, worksheets, story-boards and drawings have been studied and analyzed using the GNOSIS research model. Elaborated data coming from our analysis approach reveal the appearance, transformation and evolution of aspects of nature of science appreciated by pupils and presented in their movies. Data analysis shows that during the application pupils gradually consider more and more the existence of multiple answers in scientific questions, appreciate the effect of culture on the way science functions and the way scientists work as well as the effect of new scientific interpretations that replace the old ones in the light of new evidence. The development of pupils' animation movies carrying aspects of the history of astronomy with a strong focus on the understanding of the nature of science creates a dynamic educational environment that facilitates pupils' introduction to a demanding teaching content (e.g. planet, model, retrograde motion) placing it in context (key-stories from the history of science) and at the same time offers to pupils the opportunity to engage their personal habits, interests and hobbies in the development of their science movies.

Animal Models of Depression: Molecular Perspectives

PubMed Central

Krishnan, Vaishnav; Nestler, Eric J.

2012-01-01

Much of the current understanding about the pathogenesis of altered mood, impaired concentration and neurovegetative symptoms in major depression has come from animal models. However, because of the unique and complex features of human depression, the generation of valid and insightful depression models has been less straightforward than modeling other disabling diseases like cancer or autoimmune conditions. Today’s popular depression models creatively merge ethologically valid behavioral assays with the latest technological advances in molecular biology and automated video-tracking. This chapter reviews depression assays involving acute stress (e.g., forced swim test), models consisting of prolonged physical or social stress (e.g., social defeat), models of secondary depression, genetic models, and experiments designed to elucidate the mechanisms of antidepressant action. These paradigms are critically evaluated in relation to their ease, validity and replicability, the molecular insights that they have provided, and their capacity to offer the next generation of therapeutics for depression. PMID:21225412

Lidar: shedding new light on habitat characterization and modeling.

Treesearch

Kerri T. Vierling; Lee A. Vierling; William A. Gould; Sebastian Martinuzzi; Rick M. Clawges

2008-01-01

Ecologists need data on animal–habitat associations in terrestrial and aquatic environments to design and implement effective conservation strategies. Habitat characteristics used in models typically incorporate (1) field data of limited spatial extent and/or (2) remote sensing data that do not characterize the vertical habitat structure. Remote sensing tools that...

Training for laparoscopic Nissen fundoplication with a newly designed model: a replacement for animal tissue models?

PubMed Central

Christie, Lorna; Goossens, Richard; Jakimowicz, Jack J.

2010-01-01

Background To bridge the early learning curve for laparoscopic Nissen fundoplication from the clinical setting to a safe environment, training models can be used. This study aimed to develop a reusable, low-cost model to be used for training in laparoscopic Nissen fundoplication procedure as an alternative to the use of animal tissue models. Methods From artificial organs and tissue, an anatomic model of the human upper abdomen was developed for training in performing laparoscopic Nissen fundoplication. The 20 participants and tutors in the European Association for Endoscopic Surgery (EAES) upper gastrointestinal surgery course completed four complementary tasks of laparoscopic Nissen fundoplication with the artificial model, then compared the realism, haptic feedback, and training properties of the model with those of animal tissue models. Results The main difference between the two training models was seen in the properties of the stomach. The wrapping of the stomach in the artificial model was rated significantly lower than that in the animal tissue model (mean, 3.6 vs. 4.2; p = 0.010). The main criticism of the stomach of the artificial model was that it was too rigid for making a proper wrap. The suturing of the stomach wall, however, was regarded as fairly realistic (mean, 3.6). The crura on the artificial model were rated better (mean, 4.3) than those on the animal tissue (mean, 4.0), although the difference was not significant. The participants regarded the model as a good to excellent (mean, 4.3) training tool. Conclusion The newly developed model is regarded as a good tool for training in laparoscopic Nissen fundoplication procedure. It is cheaper, more durable, and more readily available for training and can therefore be used in every training center. The stomach of this model, however, still needs improvement because it is too rigid for making the wrap. PMID:20526629

A Bone-Implant Interaction Mouse Model for Evaluating Molecular Mechanism of Biomaterials/Bone Interaction.

PubMed

Liu, Wenlong; Dan, Xiuli; Wang, Ting; Lu, William W; Pan, Haobo

2016-11-01

The development of an optimal animal model that could provide fast assessments of the interaction between bone and orthopedic implants is essential for both preclinical and theoretical researches in the design of novel biomaterials. Compared with other animal models, mice have superiority in accessing the well-developed transgenic modification techniques (e.g., cell tracing, knockoff, knockin, and so on), which serve as powerful tools in studying molecular mechanisms. In this study, we introduced the establishment of a mouse model, which was specifically tailored for the assessment of bone-implant interaction in a load-bearing bone marrow microenvironment and could potentially allow the molecular mechanism study of biomaterials by using transgenic technologies. The detailed microsurgery procedures for developing a bone defect (Φ = 0.8 mm) at the metaphysis region of the mouse femur were recorded. According to our results, the osteoconductive and osseointegrative properties of a well-studied 45S5 bioactive glass were confirmed by utilizing our mouse model, verifying the reliability of this model. The feasibility and reliability of the present model were further checked by using other materials as objects of study. Furthermore, our results indicated that this animal model provided a more homogeneous tissue-implant interacting surface than the rat at the early stage of implantation and this is quite meaningful for conducting quantitative analysis. The availability of transgenic techniques to mechanism study of biomaterials was further testified by establishing our model on Nestin-GFP transgenic mice. Intriguingly, the distribution of Nestin + cells was demonstrated to be recruited to the surface of 45S5 glass as early as 3 days postsurgery, indicating that Nestin + lineage stem cells may participate in the subsequent regeneration process. In summary, the bone-implant interaction mouse model could serve as a potential candidate to evaluate the early stage tissue response near the implant surface in a bone marrow microenvironment, and it also shows great potential in making transgenic animal resource applicable to biomaterial studies, so that the design of novel biomaterials could be better guided.

Estimating temporary emigration and breeding proportions using capture-recapture data with Pollock's robust design

USGS Publications Warehouse

Kendall, W.L.; Nichols, J.D.; Hines, J.E.

1997-01-01

Statistical inference for capture-recapture studies of open animal populations typically relies on the assumption that all emigration from the studied population is permanent. However, there are many instances in which this assumption is unlikely to be met. We define two general models for the process of temporary emigration, completely random and Markovian. We then consider effects of these two types of temporary emigration on Jolly-Seber (Seber 1982) estimators and on estimators arising from the full-likelihood approach of Kendall et al. (1995) to robust design data. Capture-recapture data arising from Pollock's (1982) robust design provide the basis for obtaining unbiased estimates of demographic parameters in the presence of temporary emigration and for estimating the probability of temporary emigration. We present a likelihood-based approach to dealing with temporary emigration that permits estimation under different models of temporary emigration and yields tests for completely random and Markovian emigration. In addition, we use the relationship between capture probability estimates based on closed and open models under completely random temporary emigration to derive three ad hoc estimators for the probability of temporary emigration, two of which should be especially useful in situations where capture probabilities are heterogeneous among individual animals. Ad hoc and full-likelihood estimators are illustrated for small mammal capture-recapture data sets. We believe that these models and estimators will be useful for testing hypotheses about the process of temporary emigration, for estimating demographic parameters in the presence of temporary emigration, and for estimating probabilities of temporary emigration. These latter estimates are frequently of ecological interest as indicators of animal movement and, in some sampling situations, as direct estimates of breeding probabilities and proportions.

Mathematical Modeling Of Life-Support Systems

NASA Technical Reports Server (NTRS)

Seshan, Panchalam K.; Ganapathi, Balasubramanian; Jan, Darrell L.; Ferrall, Joseph F.; Rohatgi, Naresh K.

1994-01-01

Generic hierarchical model of life-support system developed to facilitate comparisons of options in design of system. Model represents combinations of interdependent subsystems supporting microbes, plants, fish, and land animals (including humans). Generic model enables rapid configuration of variety of specific life support component models for tradeoff studies culminating in single system design. Enables rapid evaluation of effects of substituting alternate technologies and even entire groups of technologies and subsystems. Used to synthesize and analyze life-support systems ranging from relatively simple, nonregenerative units like aquariums to complex closed-loop systems aboard submarines or spacecraft. Model, called Generic Modular Flow Schematic (GMFS), coded in such chemical-process-simulation languages as Aspen Plus and expressed as three-dimensional spreadsheet.

21 CFR 516.30 - Annual reports for a MUMS-designated drug.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.30 Annual reports for a MUMS-designated drug... investigational new animal drug file addressed to the Director of the Office of Minor Use and Minor Species Animal...

21 CFR 516.30 - Annual reports for a MUMS-designated drug.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.30 Annual reports for a MUMS-designated drug... investigational new animal drug file addressed to the Director of the Office of Minor Use and Minor Species Animal...

21 CFR 516.30 - Annual reports for a MUMS-designated drug.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.30 Annual reports for a MUMS-designated drug... investigational new animal drug file addressed to the Director of the Office of Minor Use and Minor Species Animal...

21 CFR 516.30 - Annual reports for a MUMS-designated drug.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.30 Annual reports for a MUMS-designated drug... investigational new animal drug file addressed to the Director of the Office of Minor Use and Minor Species Animal...

21 CFR 516.30 - Annual reports for a MUMS-designated drug.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.30 Annual reports for a MUMS-designated drug... investigational new animal drug file addressed to the Director of the Office of Minor Use and Minor Species Animal...

Multidisciplinary Design Optimization for Aeropropulsion Engines and Solid Modeling/Animation via the Integrated Forced Methods

NASA Technical Reports Server (NTRS)

2004-01-01

The grant closure report is organized in the following four chapters: Chapter describes the two research areas Design optimization and Solid mechanics. Ten journal publications are listed in the second chapter. Five highlights is the subject matter of chapter three. CHAPTER 1. The Design Optimization Test Bed CometBoards. CHAPTER 2. Solid Mechanics: Integrated Force Method of Analysis. CHAPTER 3. Five Highlights: Neural Network and Regression Methods Demonstrated in the Design Optimization of a Subsonic Aircraft. Neural Network and Regression Soft Model Extended for PX-300 Aircraft Engine. Engine with Regression and Neural Network Approximators Designed. Cascade Optimization Strategy with Neural network and Regression Approximations Demonstrated on a Preliminary Aircraft Engine Design. Neural Network and Regression Approximations Used in Aircraft Design.

Modeling Collective Animal Behavior with a Cognitive Perspective: A Methodological Framework

PubMed Central

Weitz, Sebastian; Blanco, Stéphane; Fournier, Richard; Gautrais, Jacques; Jost, Christian; Theraulaz, Guy

2012-01-01

The last decades have seen an increasing interest in modeling collective animal behavior. Some studies try to reproduce as accurately as possible the collective dynamics and patterns observed in several animal groups with biologically plausible, individual behavioral rules. The objective is then essentially to demonstrate that the observed collective features may be the result of self-organizing processes involving quite simple individual behaviors. Other studies concentrate on the objective of establishing or enriching links between collective behavior researches and cognitive or physiological ones, which then requires that each individual rule be carefully validated. Here we discuss the methodological consequences of this additional requirement. Using the example of corpse clustering in ants, we first illustrate that it may be impossible to discriminate among alternative individual rules by considering only observational data collected at the group level. Six individual behavioral models are described: They are clearly distinct in terms of individual behaviors, they all reproduce satisfactorily the collective dynamics and distribution patterns observed in experiments, and we show theoretically that it is strictly impossible to discriminate two of these models even in the limit of an infinite amount of data whatever the accuracy level. A set of methodological steps are then listed and discussed as practical ways to partially overcome this problem. They involve complementary experimental protocols specifically designed to address the behavioral rules successively, conserving group-level data for the overall model validation. In this context, we highlight the importance of maintaining a sharp distinction between model enunciation, with explicit references to validated biological concepts, and formal translation of these concepts in terms of quantitative state variables and fittable functional dependences. Illustrative examples are provided of the benefits expected during the often long and difficult process of refining a behavioral model, designing adapted experimental protocols and inversing model parameters. PMID:22761685

Modeling collective animal behavior with a cognitive perspective: a methodological framework.

PubMed

Weitz, Sebastian; Blanco, Stéphane; Fournier, Richard; Gautrais, Jacques; Jost, Christian; Theraulaz, Guy

2012-01-01

The last decades have seen an increasing interest in modeling collective animal behavior. Some studies try to reproduce as accurately as possible the collective dynamics and patterns observed in several animal groups with biologically plausible, individual behavioral rules. The objective is then essentially to demonstrate that the observed collective features may be the result of self-organizing processes involving quite simple individual behaviors. Other studies concentrate on the objective of establishing or enriching links between collective behavior researches and cognitive or physiological ones, which then requires that each individual rule be carefully validated. Here we discuss the methodological consequences of this additional requirement. Using the example of corpse clustering in ants, we first illustrate that it may be impossible to discriminate among alternative individual rules by considering only observational data collected at the group level. Six individual behavioral models are described: They are clearly distinct in terms of individual behaviors, they all reproduce satisfactorily the collective dynamics and distribution patterns observed in experiments, and we show theoretically that it is strictly impossible to discriminate two of these models even in the limit of an infinite amount of data whatever the accuracy level. A set of methodological steps are then listed and discussed as practical ways to partially overcome this problem. They involve complementary experimental protocols specifically designed to address the behavioral rules successively, conserving group-level data for the overall model validation. In this context, we highlight the importance of maintaining a sharp distinction between model enunciation, with explicit references to validated biological concepts, and formal translation of these concepts in terms of quantitative state variables and fittable functional dependences. Illustrative examples are provided of the benefits expected during the often long and difficult process of refining a behavioral model, designing adapted experimental protocols and inversing model parameters.

Measurement of flying and diving metabolic rate in wild animals: Review and recommendations.

PubMed

Elliott, Kyle H

2016-12-01

Animals' abilities to fly long distances and dive to profound depths fascinate earthbound researchers. Due to the difficulty of making direct measurements during flying and diving, many researchers resort to modeling so as to estimate metabolic rate during each of those activities in the wild, but those models can be inaccurate. Fortunately, the miniaturization, customization and commercialization of biologgers has allowed researchers to increasingly follow animals on their journeys, unravel some of their mysteries and test the accuracy of biomechanical models. I provide a review of the measurement of flying and diving metabolic rate in the wild, paying particular attention to mass loss, doubly-labelled water, heart rate and accelerometry. Biologgers can impact animal behavior and influence the very measurements they are designed to make, and I provide seven guidelines for the ethical use of biologgers. If biologgers are properly applied, quantification of metabolic rate across a range of species could produce robust allometric relationships that could then be generally applied. As measuring flying and diving metabolic rate in captivity is difficult, and often not directly translatable to field conditions, I suggest that applying multiple techniques in the field to reinforce one another may be a viable alternative. The coupling of multi-sensor biologgers with biomechanical modeling promises to improve precision in the measurement of flying and diving metabolic rate in wild animals. Copyright © 2016 Elsevier Inc. All rights reserved.

A miniature mechanical ventilator for newborn mice.

PubMed

Kolandaivelu, K; Poon, C S

1998-02-01

Transgenic/knockout mice with pre-defined mutations have become increasingly popular in biomedical research as models of human diseases. In some instances, the resulting mutation may cause cardiorespiratory distress in the neonatal or adult animals and may necessitate resuscitation. Here we describe the design and testing of a miniature and versatile ventilator that can deliver varying ventilatory support modes, including conventional mechanical ventilation and high-frequency ventilation, to animals as small as the newborn mouse. With a double-piston body chamber design, the device circumvents the problem of air leakage and obviates the need for invasive procedures such as endotracheal intubation, which are particularly important in ventilating small animals. Preliminary tests on newborn mice as early as postnatal day O demonstrated satisfactory restoration of pulmonary ventilation and the prevention of respiratory failure in mutant mice that are prone to respiratory depression. This device may prove useful in the postnatal management of transgenic/knockout mice with genetically inflicted respiratory disorders.

The Implementation of Blended Learning Using Android-Based Tutorial Video in Computer Programming Course II

NASA Astrophysics Data System (ADS)

Huda, C.; Hudha, M. N.; Ain, N.; Nandiyanto, A. B. D.; Abdullah, A. G.; Widiaty, I.

2018-01-01

Computer programming course is theoretical. Sufficient practice is necessary to facilitate conceptual understanding and encouraging creativity in designing computer programs/animation. The development of tutorial video in an Android-based blended learning is needed for students’ guide. Using Android-based instructional material, students can independently learn anywhere and anytime. The tutorial video can facilitate students’ understanding about concepts, materials, and procedures of programming/animation making in detail. This study employed a Research and Development method adapting Thiagarajan’s 4D model. The developed Android-based instructional material and tutorial video were validated by experts in instructional media and experts in physics education. The expert validation results showed that the Android-based material was comprehensive and very feasible. The tutorial video was deemed feasible as it received average score of 92.9%. It was also revealed that students’ conceptual understanding, skills, and creativity in designing computer program/animation improved significantly.

Pre-clinical research in small animals using radiotherapy technology--a bidirectional translational approach.

PubMed

Tillner, Falk; Thute, Prasad; Bütof, Rebecca; Krause, Mechthild; Enghardt, Wolfgang

2014-12-01

For translational cancer research, pre-clinical in-vivo studies using small animals have become indispensable in bridging the gap between in-vitro cell experiments and clinical implementation. When setting up such small animal experiments, various biological, technical and methodical aspects have to be considered. In this work we present a comprehensive topical review based on relevant publications on irradiation techniques used for pre-clinical cancer research in mice and rats. Clinical radiotherapy treatment devices for the application of external beam radiotherapy and brachytherapy as well as dedicated research irradiation devices are feasible for small animal irradiation depending on the animal model and the experimental goals. In this work, appropriate solutions for the technological transfer of human radiation oncology to small animal radiation research are summarised. Additionally, important information concerning the experimental design is provided such that reliable and clinically relevant results can be attained. Copyright © 2014. Published by Elsevier GmbH.

Numerical and experimental hydrodynamic analysis of suction cup bio-logging tag designs for marine mammals

NASA Astrophysics Data System (ADS)

Murray, Mark; Shorter, Alex; Howle, Laurens; Johnson, Mark; Moore, Michael

2012-11-01

The improvement and miniaturization of sensing technologies has made bio-logging tags, utilized for the study of marine mammal behavior, more practical. These sophisticated sensing packages require a housing which protects the electronics from the environment and provides a means of attachment to the animal. The hydrodynamic forces on these housings can inadvertently remove the tag or adversely affect the behavior or energetics of the animal. A modification to the original design of a suction cup bio-logging tag housing was desired to minimize the adverse forces. In this work, hydrodynamic loading of two suction cup tag designs, original and modified designs, were analyzed using computational fluid dynamics (CFD) models and validated experimentally. Overall, the simulation and experimental results demonstrated that a tag housing that minimized geometric disruptions to the flow reduced drag forces, and that a tag housing with a small frontal cross-sectional area close to the attachment surface reduced lift forces. Preliminary results from experimental work with a common dolphin cadaver indicates that the suction cups used to attach the tags to the animal provide sufficient attachment force to resist failure at predicted drag and lift forces in 10 m/s flow.

Specific issues in small animal dosimetry and irradiator calibration

PubMed Central

Yoshizumi, Terry; Brady, Samuel L.; Robbins, Mike E.; Bourland, J. Daniel

2013-01-01

Purpose In response to the increased risk of radiological terrorist attack, a network of Centers for Medical Countermeasures against Radiation (CMCR) has been established in the United States, focusing on evaluating animal model responses to uniform, relatively homogenous whole- or partial-body radiation exposures at relatively high dose rates. The success of such studies is dependent not only on robust animal models but on accurate and reproducible dosimetry within and across CMCR. To address this issue, the Education and Training Core of the Duke University School of Medicine CMCR organised a one-day workshop on small animal dosimetry. Topics included accuracy in animal dosimetry accuracy, characteristics and differences of cesium-137 and X-ray irradiators, methods for dose measurement, and design of experimental irradiation geometries for uniform dose distributions. This paper summarises the information presented and discussed. Conclusions Without ensuring accurate and reproducible dosimetry the development and assessment of the efficacy of putative countermeasures will not prove successful. Radiation physics support is needed, but is often the weakest link in the small animal dosimetry chain. We recommend: (i) A user training program for new irradiator users, (ii) subsequent training updates, and (iii) the establishment of a national small animal dosimetry center for all CMCR members. PMID:21961967

Animals Used in Research and Education, 1966-2016: Evolving Attitudes, Policies, and Relationships.

PubMed

Lairmore, Michael D; Ilkiw, Jan

2015-01-01

Since the inception of the Association of American Veterinary Medical Colleges (AAVMC), the use of animals in research and education has been a central element of the programs of member institutions. As veterinary education and research programs have evolved over the past 50 years, so too have societal views and regulatory policies. AAVMC member institutions have continually responded to these events by exchanging best practices in training their students in the framework of comparative medicine and the needs of society. Animals provide students and faculty with the tools to learn the fundamental knowledge and skills of veterinary medicine and scientific discovery. The study of animal models has contributed extensively to medicine, veterinary medicine, and basic sciences as these disciplines seek to understand life processes. Changing societal views over the past 50 years have provided active examination and continued refinement of the use of animals in veterinary medical education and research. The future use of animals to educate and train veterinarians will likely continue to evolve as technological advances are applied to experimental design and educational systems. Natural animal models of both human and animal health will undoubtedly continue to serve a significant role in the education of veterinarians and in the development of new treatments of animal and human disease. As it looks to the future, the AAVMC as an organization will need to continue to support and promote best practices in the humane care and appropriate use of animals in both education and research.

9 CFR 302.2 - Application of requirements in designated States or Territories; and to designated plants...

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Application of requirements in designated States or Territories; and to designated plants endangering public health. 302.2 Section 302.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND...

9 CFR 302.2 - Application of requirements in designated States or Territories; and to designated plants...

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Application of requirements in designated States or Territories; and to designated plants endangering public health. 302.2 Section 302.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND...

Ophiuroid robot that self-organizes periodic and non-periodic arm movements.

PubMed

Kano, Takeshi; Suzuki, Shota; Watanabe, Wataru; Ishiguro, Akio

2012-09-01

Autonomous decentralized control is a key concept for understanding the mechanism underlying adaptive and versatile locomotion of animals. Although the design of an autonomous decentralized control system that ensures adaptability by using coupled oscillators has been proposed previously, it cannot comprehensively reproduce the versatility of animal behaviour. To tackle this problem, we focus on using ophiuroids as a simple model that exhibits versatile locomotion including periodic and non-periodic arm movements. Our existing model for ophiuroid locomotion uses an active rotator model that describes both oscillatory and excitatory properties. In this communication, we develop an ophiuroid robot to confirm the validity of this proposed model in the real world. We show that the robot travels by successfully coordinating periodic and non-periodic arm movements in response to external stimuli.

Does probabilistic modelling of linkage disequilibrium evolution improve the accuracy of QTL location in animal pedigree?

PubMed

Cierco-Ayrolles, Christine; Dejean, Sébastien; Legarra, Andrés; Gilbert, Hélène; Druet, Tom; Ytournel, Florence; Estivals, Delphine; Oumouhou, Naïma; Mangin, Brigitte

2010-10-22

Since 2001, the use of more and more dense maps has made researchers aware that combining linkage and linkage disequilibrium enhances the feasibility of fine-mapping genes of interest. So, various method types have been derived to include concepts of population genetics in the analyses. One major drawback of many of these methods is their computational cost, which is very significant when many markers are considered. Recent advances in technology, such as SNP genotyping, have made it possible to deal with huge amount of data. Thus the challenge that remains is to find accurate and efficient methods that are not too time consuming. The study reported here specifically focuses on the half-sib family animal design. Our objective was to determine whether modelling of linkage disequilibrium evolution improved the mapping accuracy of a quantitative trait locus of agricultural interest in these populations. We compared two methods of fine-mapping. The first one was an association analysis. In this method, we did not model linkage disequilibrium evolution. Therefore, the modelling of the evolution of linkage disequilibrium was a deterministic process; it was complete at time 0 and remained complete during the following generations. In the second method, the modelling of the evolution of population allele frequencies was derived from a Wright-Fisher model. We simulated a wide range of scenarios adapted to animal populations and compared these two methods for each scenario. Our results indicated that the improvement produced by probabilistic modelling of linkage disequilibrium evolution was not significant. Both methods led to similar results concerning the location accuracy of quantitative trait loci which appeared to be mainly improved by using four flanking markers instead of two. Therefore, in animal half-sib designs, modelling linkage disequilibrium evolution using a Wright-Fisher model does not significantly improve the accuracy of the QTL location when compared to a simpler method assuming complete and constant linkage between the QTL and the marker alleles. Finally, given the high marker density available nowadays, the simpler method should be preferred as it gives accurate results in a reasonable computing time.

How to Make a Good Animation: A Grounded Cognition Model of How Visual Representation Design Affects the Construction of Abstract Physics Knowledge

ERIC Educational Resources Information Center

Chen, Zhongzhou; Gladding, Gary

2014-01-01

Visual representations play a critical role in teaching physics. However, since we do not have a satisfactory understanding of how visual perception impacts the construction of abstract knowledge, most visual representations used in instructions are either created based on existing conventions or designed according to the instructor's intuition,…

Using animal models to evaluate the functional consequences of anesthesia during early neurodevelopment.

PubMed

Maloney, Susan E; Creeley, Catherine E; Hartman, Richard E; Yuede, Carla M; Zorumski, Charles F; Jevtovic-Todorovic, Vesna; Dikranian, Krikor; Noguchi, Kevin K; Farber, Nuri B; Wozniak, David F

2018-03-14

Fifteen years ago Olney and colleagues began using animal models to evaluate the effects of anesthetic and sedative agents (ASAs) on neurodevelopment. The results from ongoing studies indicate that, under certain conditions, exposure to these drugs during development induces an acute elevated apoptotic neurodegenerative response in the brain and long-term functional impairments. These animal models have played a significant role in bringing attention to the possible adverse effects of exposing the developing brain to ASAs when few concerns had been raised previously in the medical community. The apoptotic degenerative response resulting from neonatal exposure to ASAs has been replicated in many studies in both rodents and non-human primates, suggesting that a similar effect may occur in humans. In both rodents and non-human primates, significantly increased levels of apoptotic degeneration are often associated with functional impairments later in life. However, behavioral deficits following developmental ASA exposure have not been consistently reported even when significantly elevated levels of apoptotic degeneration have been documented in animal models. In the present work, we review this literature and propose a rodent model for assessing potential functional deficits following neonatal ASA exposure with special reference to experimental design and procedural issues. Our intent is to improve test sensitivity and replicability for detecting subtle behavioral effects, and thus enhance the translational significance of ASA models. Copyright © 2018 Elsevier Inc. All rights reserved.

9 CFR 72.16 - Designated dipping stations to be approved by the Administrator, APHIS on recommendations of...

Code of Federal Regulations, 2014 CFR

2014-01-01

....16 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS BOVINE BABESIOSIS § 72.16... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Designated dipping stations to be...

Animal models of human anxiety disorders: reappraisal from a developmental psychopathology vantage point.

PubMed

Lampis, Valentina; Maziade, Michel; Battaglia, Marco

2011-05-01

We are witnessing a tremendous expansion of strategies and techniques that derive from basic and preclinical science to study the fine genetic, epigenetic, and proteomic regulation of behavior in the laboratory animal. In this endeavor, animal models of psychiatric illness are becoming the almost exclusive domain of basic researchers, with lesser involvement of clinician researchers in their conceptual design, and transfer into practice of new paradigms. From the side of human behavioral research, the growing interest in gene-environment interplay and the fostering of valid endophenotypes are among the few substantial innovations in the effort of linking common mental disorders to cutting-edge clinical research questions. We argue that it is time for cross-fertilization between these camps. In this article, we a) observe that the "translational divide" can-and should-be crossed by having investigators from both the basic and the clinical sides cowork on simpler, valid "endophenotypes" of neurodevelopmental relevance; b) emphasize the importance of unambiguous physiological readouts, more than behavioral equivalents of human symptoms/syndromes, for animal research; c) indicate and discuss how this could be fostered and implemented in a developmental framework of reference for some common anxiety disorders and ultimately lead to better animal models of human mental disorders.

Assessment of phototoxicity, skin irritation, and sensitization potential of polystyrene and TiO2 nanoparticles

NASA Astrophysics Data System (ADS)

Park, Yoon-Hee; Jeong, Sang Hoon; Yi, Sang Min; Hyeok Choi, Byeong; Kim, Yu-Ri; Kim, In-Kyoung; Kim, Meyoung-Kon; Son, Sang Wook

2011-07-01

The human skin equivalent model (HSEM) is well known as an attractive alternative model for evaluation of dermal toxicity. However, only limited data are available on the usefulness of an HSEM for nanotoxicity testing. This study was designed to investigate cutaneous toxicity of polystyrene and TiO2 nanoparticles using cultured keratinocytes, an HSEM, and an animal model. In addition, we also evaluated the skin sensitization potential of nanoparticles using a local lymph node assay with incorporation of BrdU. Findings from the present study indicate that polystyrene and TiO2 nanoparticles do not induce phototoxicity, acute cutaneous irritation, or skin sensitization. Results from evaluation of the HSEMs correspond well with those from animal models. Our findings suggest that the HSEM might be a useful alternative model for evaluation of dermal nanotoxicity.

Relating ranging ecology, limb length, and locomotor economy in terrestrial animals.

PubMed

Pontzer, Herman

2012-03-07

Ecomorphological analyses have identified a number of important evolutionary trends in vertebrate limb design, but the relationships between daily travel distance, locomotor ecology, and limb length in terrestrial animals remain poorly understood. In this paper I model the net rate of energy intake as a function of foraging efficiency, and thus of locomotor economy; improved economy leads to greater net energy intake. However, the relationship between locomotor economy and net intake is highly dependent on foraging efficiency; only species with low foraging efficiencies experience strong selection pressure for improved locomotor economy and increased limb length. Examining 237 terrestrial species, I find that nearly all taxa obtain sufficiently high foraging efficiencies that selection for further increases in economy is weak. Thus selection pressures for increased economy and limb length among living terrestrial animals may be relatively weak and similar in magnitude across ecologically diverse species. The Economy Selection Pressure model for locomotor economy may be useful in investigating the evolution of limb design in early terrestrial taxa and the coevolution of foraging ecology and locomotor anatomy in lineages with low foraging efficiencies. Copyright © 2011 Elsevier Ltd. All rights reserved.

New imaging systems in nuclear medicine. Final report, January 1, 1993--December 31, 1995

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1995-12-31

The aim of this program has been to improve the performance of positron emission tomography (PET) to achieve high resolution with high sensitivity. Towards this aim, the authors have carried out the following studies: (1) explored new techniques for detection of annihilation radiation including new detector materials and system geometries, specific areas that they have studied include--exploration of factors related to resolution and sensitivity of PET instrumentation including geometry, detection materials and coding, and the exploration of technique to improve the image quality by use of depth of interaction and increased sampling; (2) complete much of the final testing ofmore » PCR-II, an analog-coded cylindrical positron tomograph, developed and constructed during the current funding period; (3) developed the design of a positron microtomograph with mm resolution for quantitative studies in small animals, a single slice version of this device has been designed and studied by use of computer simulation; (4) continued and expanded the program of biological studies in animal models. Current studies have included imaging of animal models of Parkinson`s and Huntington`s disease and cancer. These studies have included new radiopharmaceuticals and techniques involving molecular biology.« less

A spatially augmented reality sketching interface for architectural daylighting design.

PubMed

Sheng, Yu; Yapo, Theodore C; Young, Christopher; Cutler, Barbara

2011-01-01

We present an application of interactive global illumination and spatially augmented reality to architectural daylight modeling that allows designers to explore alternative designs and new technologies for improving the sustainability of their buildings. Images of a model in the real world, captured by a camera above the scene, are processed to construct a virtual 3D model. To achieve interactive rendering rates, we use a hybrid rendering technique, leveraging radiosity to simulate the interreflectance between diffuse patches and shadow volumes to generate per-pixel direct illumination. The rendered images are then projected on the real model by four calibrated projectors to help users study the daylighting illumination. The virtual heliodon is a physical design environment in which multiple designers, a designer and a client, or a teacher and students can gather to experience animated visualizations of the natural illumination within a proposed design by controlling the time of day, season, and climate. Furthermore, participants may interactively redesign the geometry and materials of the space by manipulating physical design elements and see the updated lighting simulation. © 2011 IEEE Published by the IEEE Computer Society

9 CFR 11.21 - Inspection procedures for designated qualified persons (DQP's).

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Inspection procedures for designated qualified persons (DQP's). 11.21 Section 11.21 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE HORSE PROTECTION REGULATIONS § 11.21 Inspection...

A model of milk production in lactating dairy cows in relation to energy and nitrogen dynamics.

PubMed

Johnson, I R; France, J; Cullen, B R

2016-02-01

A generic daily time-step model of a dairy cow, designed to be included in whole-system pasture simulation models, is described that includes growth, milk production, and lactation in relation to energy and nitrogen dynamics. It is a development of a previously described animal growth and metabolism model that describes animal body composition in terms of protein, water, and fat, and energy dynamics in relation to growth requirements, resynthesis of degraded protein, and animal activity. This is further developed to include lactation and fetal growth. Intake is calculated in relation to stage of lactation, pasture availability, supplementary feed, and feed quality. Energy costs associated with urine N excretion and methane fermentation are accounted for. Milk production and fetal growth are then calculated in relation to the overall energy and nitrogen dynamics. The general behavior of the model is consistent with expected characteristics. Simulations using the model as part of a whole-system pasture simulation model (DairyMod) are compared with experimental data where good agreement between pasture, concentrate and forage intake, as well as milk production over 3 consecutive lactation cycles, is observed. The model is shown to be well suited for inclusion in large-scale system simulation models. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Intraoperative cerebral blood flow imaging of rodents

NASA Astrophysics Data System (ADS)

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

2014-09-01

Intraoperative monitoring of cerebral blood flow (CBF) is of interest to neuroscience researchers, which offers the assessment of hemodynamic responses throughout the process of neurosurgery and provides an early biomarker for surgical guidance. However, intraoperative CBF imaging has been challenging due to animal's motion and position change during the surgery. In this paper, we presented a design of an operation bench integrated with laser speckle contrast imager which enables monitoring of the CBF intraoperatively. With a specially designed stereotaxic frame and imager, we were able to monitor the CBF changes in both hemispheres during the rodent surgery. The rotatable design of the operation plate and implementation of online image registration allow the technician to move the animal without disturbing the CBF imaging during surgery. The performance of the system was tested by middle cerebral artery occlusion model of rats.

Aggressive behavior in transgenic animal models: A systematic review.

PubMed

Jager, Amanda; Maas, Dorien A; Fricke, Kim; de Vries, Rob B; Poelmans, Geert; Glennon, Jeffrey C

2018-08-01

Aggressive behavior is often core or comorbid to psychiatric and neurodegenerative disorders. Transgenic animal models are commonly used to study the neurobiological mechanisms underlying aggressive phenotypes and have led to new insights into aggression. This systematic review critically evaluates the available literature on transgenic animal models tested for aggression with the resident-intruder test. By combining the available literature on this topic, we sought to highlight effective methods for laboratory aggression testing and provide recommendations for study design as well as aggression induction and measurement in rodents that are translational to humans, taking into consideration possible confounding factors. In addition, we built a molecular landscape of interactions between the proteins encoded by the aggression-linked genes from our systematic search. Some molecular pathways within this landscape overlap with psychiatric and neurodegenerative disorders and the landscapes point towards a number of putative (drug) targets for aggression that need to be validated in future studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Association between Repeated Unpredictable Chronic Mild Stress (UCMS) Procedures with a High Fat Diet: A Model of Fluoxetine Resistance in Mice

PubMed Central

Isingrini, Elsa; Camus, Vincent; Le Guisquet, Anne-Marie; Pingaud, Maryse; Devers, Séverine; Belzung, Catherine

2010-01-01

Major depressive disorder is a debilitating disease. Unfortunately, treatment with antidepressants (ADs) has limited therapeutic efficacy since resistance to AD is common. Research in this field is hampered by the lack of a reliable natural animal model of AD resistance. Depression resistance is related to various factors, including the attendance of cardiovascular risk factors and past depressive episodes. We aimed to design a rodent model of depression resistance to ADs, associating cardiovascular risk factors with repeated unpredicted chronic mild stress (UCMS). Male BALB/c mice were given either a regular (4% fat) or a high fat diet (45% fat) and subjected to two 7-week periods of UCMS separated by 6 weeks. From the second week of each UCMS procedure, vehicle or fluoxetine (10 mg/kg, i.p.) was administrated daily. The effects of the UCMS and fluoxetine in both diet conditions were assessed using physical (coat state and body weight) and behavioural tests (the reward maze test and the splash test). The results demonstrate that during the second procedure, UCMS induced behavioural changes, including coat state degradation, disturbances in self-care behaviour (splash test) and anhedonia (reward maze test) and these were reversed by fluoxetine in the regular diet condition. In contrast, the high-fat diet regimen prevented the AD fluoxetine from abolishing the UCMS-induced changes. In conclusion, by associating UCMS—an already validated animal model of depression—with high-fat diet regimen, we designed a naturalistic animal model of AD resistance related to a sub-nosographic clinical entity of depression. PMID:20436931

Emergence of a snake-like structure in mobile distributed agents: an exploratory agent-based modeling approach.

PubMed

Niazi, Muaz A

2014-01-01

The body structure of snakes is composed of numerous natural components thereby making it resilient, flexible, adaptive, and dynamic. In contrast, current computer animations as well as physical implementations of snake-like autonomous structures are typically designed to use either a single or a relatively smaller number of components. As a result, not only these artificial structures are constrained by the dimensions of the constituent components but often also require relatively more computationally intensive algorithms to model and animate. Still, these animations often lack life-like resilience and adaptation. This paper presents a solution to the problem of modeling snake-like structures by proposing an agent-based, self-organizing algorithm resulting in an emergent and surprisingly resilient dynamic structure involving a minimal of interagent communication. Extensive simulation experiments demonstrate the effectiveness as well as resilience of the proposed approach. The ideas originating from the proposed algorithm can not only be used for developing self-organizing animations but can also have practical applications such as in the form of complex, autonomous, evolvable robots with self-organizing, mobile components with minimal individual computational capabilities. The work also demonstrates the utility of exploratory agent-based modeling (EABM) in the engineering of artificial life-like complex adaptive systems.

Emergence of a Snake-Like Structure in Mobile Distributed Agents: An Exploratory Agent-Based Modeling Approach

PubMed Central

Niazi, Muaz A.

2014-01-01

The body structure of snakes is composed of numerous natural components thereby making it resilient, flexible, adaptive, and dynamic. In contrast, current computer animations as well as physical implementations of snake-like autonomous structures are typically designed to use either a single or a relatively smaller number of components. As a result, not only these artificial structures are constrained by the dimensions of the constituent components but often also require relatively more computationally intensive algorithms to model and animate. Still, these animations often lack life-like resilience and adaptation. This paper presents a solution to the problem of modeling snake-like structures by proposing an agent-based, self-organizing algorithm resulting in an emergent and surprisingly resilient dynamic structure involving a minimal of interagent communication. Extensive simulation experiments demonstrate the effectiveness as well as resilience of the proposed approach. The ideas originating from the proposed algorithm can not only be used for developing self-organizing animations but can also have practical applications such as in the form of complex, autonomous, evolvable robots with self-organizing, mobile components with minimal individual computational capabilities. The work also demonstrates the utility of exploratory agent-based modeling (EABM) in the engineering of artificial life-like complex adaptive systems. PMID:24701135

A Unified Air-Sea Visualization System: Survey on Gridding Structures

NASA Technical Reports Server (NTRS)

Anand, Harsh; Moorhead, Robert

1995-01-01

The goal is to develop a Unified Air-Sea Visualization System (UASVS) to enable the rapid fusion of observational, archival, and model data for verification and analysis. To design and develop UASVS, modelers were polled to determine the gridding structures and visualization systems used, and their needs with respect to visual analysis. A basic UASVS requirement is to allow a modeler to explore multiple data sets within a single environment, or to interpolate multiple datasets onto one unified grid. From this survey, the UASVS should be able to visualize 3D scalar/vector fields; render isosurfaces; visualize arbitrary slices of the 3D data; visualize data defined on spectral element grids with the minimum number of interpolation stages; render contours; produce 3D vector plots and streamlines; provide unified visualization of satellite images, observations and model output overlays; display the visualization on a projection of the users choice; implement functions so the user can derive diagnostic values; animate the data to see the time-evolution; animate ocean and atmosphere at different rates; store the record of cursor movement, smooth the path, and animate a window around the moving path; repeatedly start and stop the visual time-stepping; generate VHS tape animations; work on a variety of workstations; and allow visualization across clusters of workstations and scalable high performance computer systems.

Middle cerebral artery occlusion in Macaca fascicularis: acute and chronic stroke evolution.

PubMed

D'Arceuil, Helen E; Duggan, Michael; He, Julian; Pryor, Johnny; de Crespigny, Alex

2006-04-01

An intravascular stroke model designed for magnetic resonance imaging was developed in Macaca fascicularis (M. fascicularis) to characterize serial stroke lesion evolution. This model produces a range of stroke lesion sizes which closely mimics human stroke evolution. This paper describes the care of animals undergoing this stroke procedure, the range of outcomes we experienced and the cause of mortality in this model. Anesthesia was induced with atropine and ketamine and maintained with isoflurane or propofol. Non-invasive blood pressure, oxygen saturation, heart rate, respiration rate, temperature and end tidal CO2 were monitored continuously. The stroke was created by occluding a distal branch of the middle cerebral artery. During catheter placement animals were heparinized and vasospasm was minimized using verapamil. Anesthetic induction and maintenance were smooth. Animals with small strokes showed very rapid recovery, were able to ambulate and self-feed within 2 hours of recovery. Animals with strokes of >or=4% of the hemispheric volume required lengthy observation during recovery and parenteral nutrition. Large strokes resulted in significant brain edema, herniation and brainstem compression. Intracerebral hemorrhage and or subarachnoid hemorrhage coupled with a stroke of any size was acutely fatal. In the absence of an effective acute stroke therapy, the spectrum of outcomes seen in our primate model is very similar to that observed in human stroke patients.

SCORHE: A novel and practical approach to video monitoring of laboratory mice housed in vivarium cage racks

PubMed Central

Dennis, John U.; Krynitsky, Jonathan; Garmendia-Cedillos, Marcial; Swaroop, Kanchan; Malley, James D.; Pajevic, Sinisa; Abuhatzira, Liron; Bustin, Michael; Gillet, Jean-Pierre; Gottesman, Michael M.; Mitchell, James B.; Pohida, Thomas J.

2015-01-01

The System for Continuous Observation of Rodents in Home-cage Environment (SCORHE) was developed to demonstrate the viability of compact and scalable designs for quantifying activity levels and behavior patterns for mice housed within a commercial ventilated cage rack. The SCORHE in-rack design provides day- and night-time monitoring with the consistency and convenience of the home-cage environment. The dual-video camera custom hardware design makes efficient use of space, does not require home-cage modification, and is animal-facility user-friendly. Given the system’s low cost and suitability for use in existing vivariums without modification to the animal husbandry procedures or housing setup, SCORHE opens up the potential for the wider use of automated video monitoring in animal facilities. SCORHE’s potential uses include day-to-day health monitoring, as well as advanced behavioral screening and ethology experiments, ranging from the assessment of the short- and long-term effects of experimental cancer treatments to the evaluation of mouse models. When used for phenotyping and animal model studies, SCORHE aims to eliminate the concerns often associated with many mouse-monitoring methods, such as circadian rhythm disruption, acclimation periods, lack of night-time measurements, and short monitoring periods. Custom software integrates two video streams to extract several mouse activity and behavior measures. Studies comparing the activity levels of ABCB5 knockout and HMGN1 overexpresser mice with their respective C57BL parental strains demonstrate SCORHE’s efficacy in characterizing the activity profiles for singly- and doubly-housed mice. Another study was conducted to demonstrate the ability of SCORHE to detect a change in activity resulting from administering a sedative. PMID:24706080

SCORHE: a novel and practical approach to video monitoring of laboratory mice housed in vivarium cage racks.

PubMed

Salem, Ghadi H; Dennis, John U; Krynitsky, Jonathan; Garmendia-Cedillos, Marcial; Swaroop, Kanchan; Malley, James D; Pajevic, Sinisa; Abuhatzira, Liron; Bustin, Michael; Gillet, Jean-Pierre; Gottesman, Michael M; Mitchell, James B; Pohida, Thomas J

2015-03-01

The System for Continuous Observation of Rodents in Home-cage Environment (SCORHE) was developed to demonstrate the viability of compact and scalable designs for quantifying activity levels and behavior patterns for mice housed within a commercial ventilated cage rack. The SCORHE in-rack design provides day- and night-time monitoring with the consistency and convenience of the home-cage environment. The dual-video camera custom hardware design makes efficient use of space, does not require home-cage modification, and is animal-facility user-friendly. Given the system's low cost and suitability for use in existing vivariums without modification to the animal husbandry procedures or housing setup, SCORHE opens up the potential for the wider use of automated video monitoring in animal facilities. SCORHE's potential uses include day-to-day health monitoring, as well as advanced behavioral screening and ethology experiments, ranging from the assessment of the short- and long-term effects of experimental cancer treatments to the evaluation of mouse models. When used for phenotyping and animal model studies, SCORHE aims to eliminate the concerns often associated with many mouse-monitoring methods, such as circadian rhythm disruption, acclimation periods, lack of night-time measurements, and short monitoring periods. Custom software integrates two video streams to extract several mouse activity and behavior measures. Studies comparing the activity levels of ABCB5 knockout and HMGN1 overexpresser mice with their respective C57BL parental strains demonstrate SCORHE's efficacy in characterizing the activity profiles for singly- and doubly-housed mice. Another study was conducted to demonstrate the ability of SCORHE to detect a change in activity resulting from administering a sedative.

9 CFR 93.911 - Ports designated for the importation of live VHS-regulated fish species.

Code of Federal Regulations, 2012 CFR

2012-01-01

... of live VHS-regulated fish species. 93.911 Section 93.911 Animals and Animal Products ANIMAL AND... (INCLUDING POULTRY) AND ANIMAL PRODUCTS IMPORTATION OF CERTAIN ANIMALS, BIRDS, FISH, AND POULTRY, AND CERTAIN... Animal Species General Provisions for Vhs-Regulated Fish Species § 93.911 Ports designated for the...

9 CFR 93.911 - Ports designated for the importation of live VHS-regulated fish species.

Code of Federal Regulations, 2014 CFR

2014-01-01

... of live VHS-regulated fish species. 93.911 Section 93.911 Animals and Animal Products ANIMAL AND... (INCLUDING POULTRY) AND ANIMAL PRODUCTS IMPORTATION OF CERTAIN ANIMALS, BIRDS, FISH, AND POULTRY, AND CERTAIN... Animal Species General Provisions for Vhs-Regulated Fish Species § 93.911 Ports designated for the...

9 CFR 93.911 - Ports designated for the importation of live VHS-regulated fish species.

Code of Federal Regulations, 2013 CFR

2013-01-01

... of live VHS-regulated fish species. 93.911 Section 93.911 Animals and Animal Products ANIMAL AND... (INCLUDING POULTRY) AND ANIMAL PRODUCTS IMPORTATION OF CERTAIN ANIMALS, BIRDS, FISH, AND POULTRY, AND CERTAIN... Animal Species General Provisions for Vhs-Regulated Fish Species § 93.911 Ports designated for the...

9 CFR 93.911 - Ports designated for the importation of live VHS-regulated fish species.

Code of Federal Regulations, 2010 CFR

2010-01-01

... of live VHS-regulated fish species. 93.911 Section 93.911 Animals and Animal Products ANIMAL AND... (INCLUDING POULTRY) AND ANIMAL PRODUCTS IMPORTATION OF CERTAIN ANIMALS, BIRDS, FISH, AND POULTRY, AND CERTAIN... Animal Species General Provisions for Vhs-Regulated Fish Species § 93.911 Ports designated for the...

9 CFR 79.4 - Designation of scrapie-positive animals, high-risk animals, exposed animals, suspect animals...

Code of Federal Regulations, 2013 CFR

2013-01-01

... designated scrapie epidemiologist may conduct testing of animals if he or she determines such testing is... epidemiologist will select animals for testing in a manner that will provide a 95 percent confidence of detecting... lambed in the flock are available for testing, may limit the testing to all exposed and suspect animals...

9 CFR 79.4 - Designation of scrapie-positive animals, high-risk animals, exposed animals, suspect animals...

Code of Federal Regulations, 2014 CFR

2014-01-01

... designated scrapie epidemiologist may conduct testing of animals if he or she determines such testing is... epidemiologist will select animals for testing in a manner that will provide a 95 percent confidence of detecting... lambed in the flock are available for testing, may limit the testing to all exposed and suspect animals...

9 CFR 79.4 - Designation of scrapie-positive animals, high-risk animals, exposed animals, suspect animals...

Code of Federal Regulations, 2012 CFR

2012-01-01

... designated scrapie epidemiologist may conduct testing of animals if he or she determines such testing is... epidemiologist will select animals for testing in a manner that will provide a 95 percent confidence of detecting... lambed in the flock are available for testing, may limit the testing to all exposed and suspect animals...

Ampullary Electroreceptors in Neurophysiological Instruction.

ERIC Educational Resources Information Center

Peters, R. C.; And Others

1988-01-01

Presents a model system designed for the electrophysiological investigation of single unit activity in intact anaesthetized animals. Illustrates how information is coded into action potential patterns by sense organs. Uses the ampullary electroreceptor of the brown bullhead catfish as an example. (Author/CW)

Does age matter? The impact of rodent age on study outcomes.

PubMed

Jackson, Samuel J; Andrews, Nick; Ball, Doug; Bellantuono, Ilaria; Gray, James; Hachoumi, Lamia; Holmes, Alan; Latcham, Judy; Petrie, Anja; Potter, Paul; Rice, Andrew; Ritchie, Alison; Stewart, Michelle; Strepka, Carol; Yeoman, Mark; Chapman, Kathryn

2017-04-01

Rodent models produce data which underpin biomedical research and non-clinical drug trials, but translation from rodents into successful clinical outcomes is often lacking. There is a growing body of evidence showing that improving experimental design is key to improving the predictive nature of rodent studies and reducing the number of animals used in research. Age, one important factor in experimental design, is often poorly reported and can be overlooked. The authors conducted a survey to assess the age used for a range of models, and the reasoning for age choice. From 297 respondents providing 611 responses, researchers reported using rodents most often in the 6-20 week age range regardless of the biology being studied. The age referred to as 'adult' by respondents varied between six and 20 weeks. Practical reasons for the choice of rodent age were frequently given, with increased cost associated with using older animals and maintenance of historical data comparability being two important limiting factors. These results highlight that choice of age is inconsistent across the research community and often not based on the development or cellular ageing of the system being studied. This could potentially result in decreased scientific validity and increased experimental variability. In some cases the use of older animals may be beneficial. Increased scientific rigour in the choice of the age of rodent may increase the translation of rodent models to humans.

Does age matter? The impact of rodent age on study outcomes

PubMed Central

Andrews, Nick; Ball, Doug; Bellantuono, Ilaria; Gray, James; Hachoumi, Lamia; Holmes, Alan; Latcham, Judy; Petrie, Anja; Potter, Paul; Rice, Andrew; Ritchie, Alison; Stewart, Michelle; Strepka, Carol; Yeoman, Mark; Chapman, Kathryn

2016-01-01

Rodent models produce data which underpin biomedical research and non-clinical drug trials, but translation from rodents into successful clinical outcomes is often lacking. There is a growing body of evidence showing that improving experimental design is key to improving the predictive nature of rodent studies and reducing the number of animals used in research. Age, one important factor in experimental design, is often poorly reported and can be overlooked. The authors conducted a survey to assess the age used for a range of models, and the reasoning for age choice. From 297 respondents providing 611 responses, researchers reported using rodents most often in the 6–20 week age range regardless of the biology being studied. The age referred to as ‘adult’ by respondents varied between six and 20 weeks. Practical reasons for the choice of rodent age were frequently given, with increased cost associated with using older animals and maintenance of historical data comparability being two important limiting factors. These results highlight that choice of age is inconsistent across the research community and often not based on the development or cellular ageing of the system being studied. This could potentially result in decreased scientific validity and increased experimental variability. In some cases the use of older animals may be beneficial. Increased scientific rigour in the choice of the age of rodent may increase the translation of rodent models to humans. PMID:27307423

Using physical models to study the gliding performance of extinct animals.

PubMed

Koehl, M A R; Evangelista, Dennis; Yang, Karen

2011-12-01

Aerodynamic studies using physical models of fossil organisms can provide quantitative information about how performance of defined activities, such as gliding, depends on specific morphological features. Such analyses allow us to rule out hypotheses about the function of extinct organisms that are not physically plausible and to determine if and how specific morphological features and postures affect performance. The purpose of this article is to provide a practical guide for the design of dynamically scaled physical models to study the gliding of extinct animals using examples from our research on the theropod dinosaur, †Microraptor gui, which had flight feathers on its hind limbs as well as on its forelimbs. Analysis of the aerodynamics of †M. gui can shed light on the design of gliders with large surfaces posterior to the center of mass and provide functional information to evolutionary biologists trying to unravel the origins of flight in the dinosaurian ancestors and sister groups to birds. Measurements of lift, drag, side force, and moments in pitch, roll, and yaw on models in a wind tunnel can be used to calculate indices of gliding and parachuting performance, aerodynamic static stability, and control effectiveness in maneuvering. These indices permit the aerodynamic performance of bodies of different shape, size, stiffness, texture, and posture to be compared and thus can provide insights about the design of gliders, both biological and man-made. Our measurements of maximum lift-to-drag ratios of 2.5-3.1 for physical models of †M. gui suggest that its gliding performance was similar to that of flying squirrels and that the various leg postures that might have been used by †M. gui make little difference to that aspect of aerodynamic performance. We found that body orientation relative to the movement of air past the animal determines whether it is difficult or easy to maneuver.

Some Useful Innovations with Trasys and Sinda-85

NASA Technical Reports Server (NTRS)

Amundsen, Ruth M.

1993-01-01

Several innovative methods have been used to allow more efficient and accurate thermal analysis using SINDA-85 and TRASYS, including model integration and reduction, planetary surface calculations, and model animation. Integration with other modeling and analysis codes allows an analyst to import a geometry from a solid modeling or computer-aided design (CAD) software package, rather than building the geometry "by hand." This is more efficient as well as potentially more accurate. However, the use of solid modeling software often generates large analytical models. The problem of reducing large models has been elegantly solved using the response of the transient derivative to a forcing step function. The thermal analysis of a lunar rover implemented two unusual features of the TRASYS/SINDA system. A little-known TRASYS routine SURFP calculates the solar heating of a rover on the lunar surface for several different rover positions and orientations. This is used not only to determine the rover temperatures, but also to automatically determine the power generated by the solar arrays. The animation of transient thermal results is an effective tool, especially in a vivid case such as the 14-day progress of the sun over the lunar rover. An animated color map on the solid model displays the progression of temperatures.

Developing models for cachexia and their implications in drug discovery.

PubMed

Konishi, Masaaki; Ebner, Nicole; von Haehling, Stephan; Anker, Stefan D; Springer, Jochen

2015-07-01

Cachexia is a complex metabolic syndrome associated with underlying illness and characterized by loss of muscle with or without loss of fat mass. Systemic inflammation plays a central role in its pathophysiology. As millions of patients are in a cachectic state of chronic disease, cachexia is one of the major causes of death worldwide. Difficulties in the recruitment and follow-up of clinical trials mean that well-characterized animal models are of great importance in developing cachexia therapies. However, some of the widely used animal models have limitations in procedural reproducibility or in recapitulating in the cachectic phenotype, which has warranted the development of novel models for cachexia. This review focuses on some of the currently developing rodent models designed to mimic each co-morbidity in cachexia. Through developing cancer models, researchers have been seeking more targets for intervention. In cardiac cachexia, technical issues have been overcome by transgenic models. Furthermore, the development of new animal models has enabled the elucidation of the roles of inflammation, anabolism/catabolism in muscle/fat tissue and anorexia on cachexia. As metabolic and inflammatory pathways in cachexia may compromise cardiac muscle, the analysis of cardiac function/tissue in non-cardiac cachexia may be a useful component of cachexia assessment common to different underlying diseases and pave the way for novel drug discovery.

Modelling gait transition in two-legged animals

NASA Astrophysics Data System (ADS)

Pinto, Carla M. A.; Santos, Alexandra P.

2011-12-01

The study of locomotor patterns has been a major research goal in the last decades. Understanding how intralimb and interlimb coordination works out so well in animals' locomotion is a hard and challenging task. Many models have been proposed to model animal's rhythms. These models have also been applied to the control of rhythmic movements of adaptive legged robots, namely biped, quadruped and other designs. In this paper we study gait transition in a central pattern generator (CPG) model for bipeds, the 4-cells model. This model is proposed by Golubitsky, Stewart, Buono and Collins and is studied further by Pinto and Golubitsky. We briefly resume the work done by Pinto and Golubitsky. We compute numerically gait transition in the 4-cells CPG model for bipeds. We use Morris-Lecar equations and Wilson-Cowan equations as the internal dynamics for each cell. We also consider two types of coupling between the cells: diffusive and synaptic. We obtain secondary gaits by bifurcation of primary gaits, by varying the coupling strengths. Nevertheless, some bifurcating branches could not be obtained, emphasizing the fact that despite analytically those bifurcations exist, finding them is a hard task and requires variation of other parameters of the equations. We note that the type of coupling did not influence the results.

9 CFR 79.4 - Designation of scrapie-positive animals, high-risk animals, exposed animals, suspect animals...

Code of Federal Regulations, 2011 CFR

2011-01-01

... (INCLUDING POULTRY) AND ANIMAL PRODUCTS SCRAPIE IN SHEEP AND GOATS § 79.4 Designation of scrapie-positive... breeding records that indicate the flock meets the criteria of the relevant definition in § 79.1. (i) A...

9 CFR 79.4 - Designation of scrapie-positive animals, high-risk animals, exposed animals, suspect animals...

Code of Federal Regulations, 2010 CFR

2010-01-01

... (INCLUDING POULTRY) AND ANIMAL PRODUCTS SCRAPIE IN SHEEP AND GOATS § 79.4 Designation of scrapie-positive... breeding records that indicate the flock meets the criteria of the relevant definition in § 79.1. (i) A...

Development of an Aotus nancymaae Model for Shigella Vaccine Immunogenicity and Efficacy Studies

PubMed Central

Gregory, Michael; Lugo-Roman, Luis A.; Galvez Carrillo, Hugo; Tilley, Drake Hamilton; Baldeviano, Christian; Simons, Mark P.; Reynolds, Nathanael D.; Ranallo, Ryan T.; Suvarnapunya, Akamol E.; Venkatesan, Malabi M.; Oaks, Edwin V.

2014-01-01

Several animal models exist to evaluate the immunogenicity and protective efficacy of candidate Shigella vaccines. The two most widely used nonprimate models for vaccine development include a murine pulmonary challenge model and a guinea pig keratoconjunctivitis model. Nonhuman primate models exhibit clinical features and gross and microscopic colonic lesions that mimic those induced in human shigellosis. Challenge models for enterotoxigenic Escherichia coli (ETEC) and Campylobacter spp. have been successfully developed with Aotus nancymaae, and the addition of a Shigella-Aotus challenge model would facilitate the testing of combination vaccines. A series of experiments were designed to identify the dose of Shigella flexneri 2a strain 2457T that induces an attack rate of 75% in the Aotus monkey. After primary challenge, the dose required to induce an attack rate of 75% was calculated to be 1 × 1011 CFU. Shigella-specific immune responses were low after primary challenge and subsequently boosted upon rechallenge. However, preexisting immunity derived from the primary challenge was insufficient to protect against the homologous Shigella serotype. A successive study in A. nancymaae evaluated the ability of multiple oral immunizations with live-attenuated Shigella vaccine strain SC602 to protect against challenge. After three oral immunizations, animals were challenged with S. flexneri 2a 2457T. A 70% attack rate was demonstrated in control animals, whereas animals immunized with vaccine strain SC602 were protected from challenge (efficacy of 80%; P = 0.05). The overall study results indicate that the Shigella-Aotus nancymaae challenge model may be a valuable tool for evaluating vaccine efficacy and investigating immune correlates of protection. PMID:24595138

Large Animal Models for Foamy Virus Vector Gene Therapy

PubMed Central

Trobridge, Grant D.; Horn, Peter A.; Beard, Brian C.; Kiem, Hans-Peter

2012-01-01

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. PMID:23223198

21 CFR 516.29 - Termination of MUMS-drug designation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.29 Termination of MUMS-drug designation. (a... exclusive marketing rights under this subpart. (d) FDA may terminate designation if it independently...

21 CFR 516.29 - Termination of MUMS-drug designation.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.29 Termination of MUMS-drug designation. (a... exclusive marketing rights under this subpart. (d) FDA may terminate designation if it independently...

21 CFR 516.29 - Termination of MUMS-drug designation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.29 Termination of MUMS-drug designation. (a... exclusive marketing rights under this subpart. (d) FDA may terminate designation if it independently...

21 CFR 516.29 - Termination of MUMS-drug designation.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.29 Termination of MUMS-drug designation. (a... exclusive marketing rights under this subpart. (d) FDA may terminate designation if it independently...

21 CFR 516.29 - Termination of MUMS-drug designation.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.29 Termination of MUMS-drug designation. (a... exclusive marketing rights under this subpart. (d) FDA may terminate designation if it independently...

Design and validation of an ontology-driven animal-free testing strategy for developmental neurotoxicity testing.

PubMed

Hessel, Ellen V S; Staal, Yvonne C M; Piersma, Aldert H

2018-03-13

Developmental neurotoxicity entails one of the most complex areas in toxicology. Animal studies provide only limited information as to human relevance. A multitude of alternative models have been developed over the years, providing insights into mechanisms of action. We give an overview of fundamental processes in neural tube formation, brain development and neural specification, aiming at illustrating complexity rather than comprehensiveness. We also give a flavor of the wealth of alternative methods in this area. Given the impressive progress in mechanistic knowledge of human biology and toxicology, the time is right for a conceptual approach for designing testing strategies that cover the integral mechanistic landscape of developmental neurotoxicity. The ontology approach provides a framework for defining this landscape, upon which an integral in silico model for predicting toxicity can be built. It subsequently directs the selection of in vitro assays for rate-limiting events in the biological network, to feed parameter tuning in the model, leading to prediction of the toxicological outcome. Validation of such models requires primary attention to coverage of the biological domain, rather than classical predictive value of individual tests. Proofs of concept for such an approach are already available. The challenge is in mining modern biology, toxicology and chemical information to feed intelligent designs, which will define testing strategies for neurodevelopmental toxicity testing. Copyright © 2018 Elsevier Inc. All rights reserved.

Electrical resistivity measurements in the mammalian cochlea after neural degeneration.

PubMed

Micco, Alan G; Richter, Claus-Peter

2006-08-01

In the present series of experiments, the effect of neural degeneration on the cochlear structure electrical resistivities was evaluated to test if it alters the current flow in the cochlea and if increased current levels are needed to stimulate the impaired cochlea. In cochlear implants, frequency information is encoded in part by stimulating discrete populations of spiral ganglion cells along the cochlea. However, electrical properties of the cochlear structures result in shunting of the current away from the auditory neurons. This consumes energy, makes cochlear implants less efficient, and drastically reduces battery life. Models of the electrically stimulated cochlea serve to make predictions on current paths using modified and improved cochlear implant electrodes. However, one of the model's shortcomings is that most of the values for tissue impedances are not direct measurements. They are derived from bulk impedance measurements, which are fitted to lumped-element models. The four-electrode reflection-coefficient technique was used to measure resistivities in the gerbil cochlea. In vivo and in vitro (the hemicochlea) models were used. Measurements were made in normal and in deafened animals. Cochlear damage was induced by neomycin injection into the animals' middle ears. Neural degeneration was allowed to occur over 2 months before performing the measurements in the deafened animals. The resistivity values in deafened animals were smaller than in the normal-hearing animals, thus altering the current flow within the cochlea. Resistivity changes and subsequent changes in current path should be considered in future designs of cochlear implants.

Predator-based psychosocial stress animal model of PTSD: Preclinical assessment of traumatic stress at cognitive, hormonal, pharmacological, cardiovascular and epigenetic levels of analysis.

PubMed

Zoladz, Phillip R; Diamond, David M

2016-10-01

Research on post-traumatic stress disorder (PTSD) is faced with the challenge of understanding how a traumatic experience produces long-lasting detrimental effects on behavior and brain functioning, and more globally, how stress exacerbates somatic disorders, including cardiovascular disease. Moreover, the design of translational research needs to link animal models of PTSD to clinically relevant risk factors which address why only a subset of traumatized individuals develop persistent psychopathology. In this review, we have summarized our psychosocial stress rodent model of PTSD which is based on well-described PTSD-inducing risk factors, including a life-threatening experience, a sense of horror and uncontrollability, and insufficient social support. Specifically, our animal model of PTSD integrates acute episodes of inescapable exposure of immobilized rats to a predator with chronic daily social instability. This stress regimen produces PTSD-like effects in rats at behavioral, cognitive, physiological, pharmacological and epigenetic levels of analysis. We have discussed a recent extension of our animal model of PTSD in which stress exacerbated coronary pathology following an ischemic event, assessed in vitro. In addition, we have reviewed our research investigating pharmacological and non-pharmacological therapeutic strategies which may have value in clinical approaches toward the treatment of traumatized people. Overall, our translational approach bridges the gap between human and animal PTSD research to create a framework with which to enhance our understanding of the biological basis of trauma-induced pathology and to assess therapeutic approaches in the treatment of psychopathology. Copyright © 2016 Elsevier Inc. All rights reserved.

21 CFR 501.4 - Animal food; designation of ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Animal food; designation of ingredients. 501.4... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ANIMAL FOOD LABELING General Provisions § 501.4 Animal... is an animal feed within the meaning of section 201(w) of the act and meets the requirements for the...

21 CFR 501.4 - Animal food; designation of ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Animal food; designation of ingredients. 501.4... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ANIMAL FOOD LABELING General Provisions § 501.4 Animal... is an animal feed within the meaning of section 201(w) of the act and meets the requirements for the...

21 CFR 501.4 - Animal food; designation of ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Animal food; designation of ingredients. 501.4... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ANIMAL FOOD LABELING General Provisions § 501.4 Animal... is an animal feed within the meaning of section 201(w) of the act and meets the requirements for the...

21 CFR 501.4 - Animal food; designation of ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Animal food; designation of ingredients. 501.4... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ANIMAL FOOD LABELING General Provisions § 501.4 Animal... is an animal feed within the meaning of section 201(w) of the act and meets the requirements for the...

9 CFR 93.902 - Ports designated for the importation of live fish, fertilized eggs, and gametes.

Code of Federal Regulations, 2013 CFR

2013-01-01

... of live fish, fertilized eggs, and gametes. 93.902 Section 93.902 Animals and Animal Products ANIMAL... (INCLUDING POULTRY) AND ANIMAL PRODUCTS IMPORTATION OF CERTAIN ANIMALS, BIRDS, FISH, AND POULTRY, AND CERTAIN... Animal Species General Provisions for Svc-Regulated Fish Species § 93.902 Ports designated for the...

9 CFR 93.902 - Ports designated for the importation of live fish, fertilized eggs, and gametes.

Code of Federal Regulations, 2012 CFR

2012-01-01

... of live fish, fertilized eggs, and gametes. 93.902 Section 93.902 Animals and Animal Products ANIMAL... (INCLUDING POULTRY) AND ANIMAL PRODUCTS IMPORTATION OF CERTAIN ANIMALS, BIRDS, FISH, AND POULTRY, AND CERTAIN... Animal Species General Provisions for Svc-Regulated Fish Species § 93.902 Ports designated for the...

9 CFR 93.902 - Ports designated for the importation of live fish, fertilized eggs, and gametes.

Code of Federal Regulations, 2014 CFR

2014-01-01

... of live fish, fertilized eggs, and gametes. 93.902 Section 93.902 Animals and Animal Products ANIMAL... (INCLUDING POULTRY) AND ANIMAL PRODUCTS IMPORTATION OF CERTAIN ANIMALS, BIRDS, FISH, AND POULTRY, AND CERTAIN... Animal Species General Provisions for Svc-Regulated Fish Species § 93.902 Ports designated for the...

An hourly variation in zoo visitor interest: measurement and significance for animal welfare research.

PubMed

Davey, Gareth

2006-01-01

A methodological difficulty facing welfare research on nonhuman animals in the zoo is the large number of uncontrolled variables due to variation within and between study sites. Zoo visitors act as uncontrolled variables, with number, density, size, and behavior constantly changing. This is worrisome because previous research linked visitor variables to animal behavioral changes indicative of stress. There are implications for research design: Studies not accounting for visitors' effect on animal welfare risk confounding (visitor) variables distorting their findings. Zoos need methods to measure and minimize effects of visitor behavior and to ensure that there are no hidden variables in research models. This article identifies a previously unreported variable--hourly variation (decrease) in visitor interest--that may impinge on animal welfare and validates a methodology for measuring it. That visitor interest wanes across the course of the day has important implications for animal welfare management; visitor effects on animal welfare are likely to occur, or intensify, during the morning or in earlier visits when visitor interest is greatest. This article discusses this issue and possible solutions to reduce visitor effects on animal well-being.

Experimental animal studies of radon and cigarette smoke

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cross, F.T.; Dagle, G.E.; Gies, R.A.

Cigarette-smoking is a dominant cause of lung cancer and confounds risk assessment of exposure to radon decay products. Evidence in humans on the interaction between cigarette-smoking and exposure to radon decay products, although limited, indicates a possible synergy. Experimental animal data, in addition to showing synergy, also show a decrease or no change in risk with added cigarette-smoke exposures. This article reviews previous animal data developed at Compagnie Generale des Matieres Nucleaires and Pacific Northwest Laboratory (PNL) on mixed exposures to radon and cigarette smoke, and highlights new initiation-promotion-initiation (IPI) studies at PNL that were designed within the framework ofmore » a two-mutation carcinogenesis model. Also presented are the PNL exposure system, experimental protocols, dosimetry, and biological data observed to date in IPI animals.« less

Is the Oxygen Atom Static or Dynamic? The Effect of Generating Animations on Students' Mental Models of Atomic Structure

ERIC Educational Resources Information Center

Akaygun, Sevil

2016-01-01

Visualizing the chemical structure and dynamics of particles has been challenging for many students; therefore, various visualizations and tools have been used in chemistry education. For science educators, it has been important to understand how students visualize and represent particular phenomena--i.e., their mental models-- to design more…

A re-evaluation of a case-control model with contaminated controls for resource selection studies

Treesearch

Christopher T. Rota; Joshua J. Millspaugh; Dylan C. Kesler; Chad P. Lehman; Mark A. Rumble; Catherine M. B. Jachowski

2013-01-01

A common sampling design in resource selection studies involves measuring resource attributes at sample units used by an animal and at sample units considered available for use. Few models can estimate the absolute probability of using a sample unit from such data, but such approaches are generally preferred over statistical methods that estimate a relative probability...

Animal models of cachexia and sarcopenia in chronic illness: Cardiac function, body composition changes and therapeutic results.

PubMed

Ishida, Junichi; Saitoh, Masakazu; Doehner, Wolfram; von Haehling, Stephan; Anker, Markus; Anker, Stefan D; Springer, Jochen

2017-07-01

Cachexia is defined as a complex metabolic syndrome associated with underlying illness that is characterized by the loss of body weight consisting of muscle and fat mass wasting. Sarcopenia is defined as the ageing related loss of muscle mass in health and disease that may not have an effect on body weight. As millions of patients are in cachectic or sarcopenic states, both conditions contribute to high numbers to death worldwide. A number of treatments have been proposed for cachexia and sarcopenia, but these are either in the preclinical stage or in clinical trials and hence not available to the general population. Particularly in cachexia there is a massive problem of recruiting patients for trials and also with the follow-up, due to the seriousness of the disease. This underlines the importance of well-characterized animal models. Obviously, most of the widely used cachexia and sarcopenia animal models have limitations in reproducibility of the condition and novel models are warranted in this context. The key findings of developing models in the field of cachexia and sarcopenia are that more types of the conditions have been taken into the researchers' interest. In cardiac cachexia, technical issues, which limit the preciseness and reproducibility in surgical heart failure models, have been overcome by a combination of surgery and the use of transgenic mouse models or salt sensitive rat models. Fatigue is the most pronounced symptom of cachexia and may be caused by reduced cardiac function independent of the underlying disease. Sarcopenia models often suffer from the use of young animals, due to the limited availability and very high costs of using aged animals. This review will focus on rodent models designed to mimic cachexia and sarcopenia including co-morbidities such as cancer, heart failure, as well as other diseases and conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

7 CFR 3201.89 - Animal cleaning products.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 15 2013-01-01 2013-01-01 false Animal cleaning products. 3201.89 Section 3201.89... Designated Items § 3201.89 Animal cleaning products. (a) Definition. Products designed to clean, condition, or remove substances from animal hair or other parts of an animal. (b) Minimum biobased content. The...

7 CFR 3201.89 - Animal cleaning products.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 15 2014-01-01 2014-01-01 false Animal cleaning products. 3201.89 Section 3201.89... Designated Items § 3201.89 Animal cleaning products. (a) Definition. Products designed to clean, condition, or remove substances from animal hair or other parts of an animal. (b) Minimum biobased content. The...

9 CFR 93.102 - Ports designated for the importation of birds.

Code of Federal Regulations, 2010 CFR

2010-01-01

... of birds. 93.102 Section 93.102 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... PRODUCTS IMPORTATION OF CERTAIN ANIMALS, BIRDS, FISH, AND POULTRY, AND CERTAIN ANIMAL, BIRD, AND POULTRY PRODUCTS; REQUIREMENTS FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Birds § 93.102 Ports designated for...

9 CFR 93.102 - Ports designated for the importation of birds.

Code of Federal Regulations, 2011 CFR

2011-01-01

... of birds. 93.102 Section 93.102 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... PRODUCTS IMPORTATION OF CERTAIN ANIMALS, BIRDS, FISH, AND POULTRY, AND CERTAIN ANIMAL, BIRD, AND POULTRY PRODUCTS; REQUIREMENTS FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Birds § 93.102 Ports designated for...

Particle-to-PFU ratio of Ebola virus influences disease course and survival in cynomolgus macaques.

PubMed

Alfson, Kendra J; Avena, Laura E; Beadles, Michael W; Staples, Hilary; Nunneley, Jerritt W; Ticer, Anysha; Dick, Edward J; Owston, Michael A; Reed, Christopher; Patterson, Jean L; Carrion, Ricardo; Griffiths, Anthony

2015-07-01

This study addresses the role of Ebola virus (EBOV) specific infectivity in virulence. Filoviruses are highly lethal, enveloped, single-stranded negative-sense RNA viruses that can cause hemorrhagic fever. No approved vaccines or therapies exist for filovirus infections, and infectious virus must be handled in maximum containment. Efficacy testing of countermeasures, in addition to investigations of pathogenicity and immune response, often requires a well-characterized animal model. For EBOV, an obstacle in performing accurate disease modeling is a poor understanding of what constitutes an infectious dose in animal models. One well-recognized consequence of viral passage in cell culture is a change in specific infectivity, often measured as a particle-to-PFU ratio. Here, we report that serial passages of EBOV in cell culture resulted in a decrease in particle-to-PFU ratio. Notably, this correlated with decreased potency in a lethal cynomolgus macaque (Macaca fascicularis) model of infection; animals were infected with the same viral dose as determined by plaque assay, but animals that received more virus particles exhibited increased disease. This suggests that some particles are unable to form a plaque in a cell culture assay but are able to result in lethal disease in vivo. These results have a significant impact on how future studies are designed to model EBOV disease and test countermeasures. Ebola virus (EBOV) can cause severe hemorrhagic disease with a high case-fatality rate, and there are no approved vaccines or therapies. Specific infectivity can be considered the total number of viral particles per PFU, and its impact on disease is poorly understood. In stocks of most mammalian viruses, there are particles that are unable to complete an infectious cycle or unable to cause cell pathology in cultured cells. We asked if these particles cause disease in nonhuman primates by infecting monkeys with equal infectious doses of genetically identical stocks possessing either high or low specific infectivities. Interestingly, some particles that did not yield plaques in cell culture assays were able to result in lethal disease in vivo. Furthermore, the number of PFU needed to induce lethal disease in animals was very low. Our results have a significant impact on how future studies are designed to model EBOV disease and test countermeasures.

Computer-generated imagery for 4-D meteorological data

NASA Technical Reports Server (NTRS)

Hibbard, William L.

1986-01-01

The University of Wisconsin-Madison Space Science and Engineering Center is developing animated stereo display terminals for use with McIDAS (Man-computer Interactive Data Access System). This paper describes image-generation techniques which have been developed to take maximum advantage of these terminals, integrating large quantities of four-dimensional meteorological data from balloon and satellite soundings, satellite images, Doppler and volumetric radar, and conventional surface observations. The images have been designed to use perspective, shading, hidden-surface removal, and transparency to augment the animation and stereo-display geometry. They create an illusion of a moving three-dimensional model of the atmosphere. This paper describes the design of these images and a number of rules of thumb for generating four-dimensional meteorological displays.

Challenges and opportunities in developmental integrative physiology☆

PubMed Central

Mueller, C.A.; Eme, J.; Burggren, W.W.; Roghair, R.D.; Rundle, S.D.

2015-01-01

This review explores challenges and opportunities in developmental physiology outlined by a symposium at the 2014 American Physiological Society Intersociety Meeting: Comparative Approaches to Grand Challenges in Physiology. Across animal taxa, adverse embryonic/fetal environmental conditions can alter morphological and physiological phenotypes in juveniles or adults, and capacities for developmental plasticity are common phenomena. Human neonates with body sizes at the extremes of perinatal growth are at an increased risk of adult disease, particularly hypertension and cardiovascular disease. There are many rewarding areas of current and future research in comparative developmental physiology. We present key mechanisms, models, and experimental designs that can be used across taxa to investigate patterns in, and implications of, the development of animal phenotypes. Intraspecific variation in the timing of developmental events can be increased through developmental plasticity (heterokairy), and could provide the raw material for selection to produce heterochrony — an evolutionary change in the timing of developmental events. Epigenetics and critical windows research recognizes that in ovo or fetal development represent a vulnerable period in the life history of an animal, when the developing organism may be unable to actively mitigate environmental perturbations. ‘Critical windows’ are periods of susceptibility or vulnerability to environmental or maternal challenges, periods when recovery from challenge is possible, and periods when the phenotype or epigenome has been altered. Developmental plasticity may allow survival in an altered environment, but it also has possible long-term consequences for the animal. “Catch-up growth” in humans after the critical perinatal window has closed elicits adult obesity and exacerbates a programmed hypertensive phenotype (one of many examples of “fetal programing”). Grand challenges for developmental physiology include integrating variation in developmental timing within and across generations, applying multiple stressor dosages and stressor exposure at different developmental timepoints, assessment of epigenetic and parental influences, developing new animal models and techniques, and assessing and implementing these designs and models in human health and development. PMID:25711780

Programming While Construction of Engineering 3D Models of Complex Geometry

NASA Astrophysics Data System (ADS)

Kheyfets, A. L.

2017-11-01

The capabilities of geometrically accurate computational 3D models construction with the use of programming are presented. The construction of models of an architectural arch and a glo-boid worm gear is considered as an example. The models are designed in the AutoCAD pack-age. Three programs of construction are given. The first program is for designing a multi-section architectural arch. The control of the arch’s geometry by impacting its main parameters is shown. The second program is for designing and studying the working surface of a globoid gear’s worm. The article shows how to make the animation for this surface’s formation. The third program is for formation of a worm gear cavity surface. The cavity formation dynamics is studied. The programs are written in the AutoLisp programming language. The program texts are provided.

Multiscale optical imaging of rare-earth-doped nanocomposites in a small animal model

NASA Astrophysics Data System (ADS)

Higgins, Laura M.; Ganapathy, Vidya; Kantamneni, Harini; Zhao, Xinyu; Sheng, Yang; Tan, Mei-Chee; Roth, Charles M.; Riman, Richard E.; Moghe, Prabhas V.; Pierce, Mark C.

2018-03-01

Rare-earth-doped nanocomposites have appealing optical properties for use as biomedical contrast agents, but few systems exist for imaging these materials. We describe the design and characterization of (i) a preclinical system for whole animal in vivo imaging and (ii) an integrated optical coherence tomography/confocal microscopy system for high-resolution imaging of ex vivo tissues. We demonstrate these systems by administering erbium-doped nanocomposites to a murine model of metastatic breast cancer. Short-wave infrared emissions were detected in vivo and in whole organ imaging ex vivo. Visible upconversion emissions and tissue autofluorescence were imaged in biopsy specimens, alongside optical coherence tomography imaging of tissue microstructure. We anticipate that this work will provide guidance for researchers seeking to image these nanomaterials across a wide range of biological models.

TRIENNIAL LACTATION SYMPOSIUM: Systems biology of regulatory mechanisms of nutrient metabolism in lactation.

PubMed

McNamara, J P

2015-12-01

A major role of the dairy cow is to convert low-quality plant materials into high-quality protein and other nutrients for humans. We must select and manage cows with the goal of having animals of the greatest efficiency matched to their environment. We have increased efficiency tremendously over the years, yet the variation in productive and reproductive efficiency among animals is still large. In part, this is because of a lack of full integration of genetic, nutritional, and reproductive biology into management decisions. However, integration across these disciplines is increasing as the biological research findings show specific control points at which genetics, nutrition, and reproduction interact. An ordered systems biology approach that focuses on why and how cells regulate energy and N use and on how and why organs interact through endocrine and neurocrine mechanisms will speed improvements in efficiency. More sophisticated dairy managers will demand better information to improve the efficiency of their animals. Using genetic improvement and animal management to improve milk productive and reproductive efficiency requires a deeper understanding of metabolic processes throughout the life cycle. Using existing metabolic models, we can design experiments specifically to integrate data from global transcriptional profiling into models that describe nutrient use in farm animals. A systems modeling approach can help focus our research to make faster and larger advances in efficiency and determine how this knowledge can be applied on the farms.

Development of an autofluorescent probe designed to help brain tumor removal: study on an animal model

NASA Astrophysics Data System (ADS)

Siebert, R.; Leh, B.; Charon, Y.; Collado-Hilly, M.; Duval, M.-A.; Menard, L.; Monnet, F. P.; Varlet, P.

2010-02-01

The complete resection of the brain tumour is crucial to the patient life quality and prognosis. An autofluorescence probe aiming at helping the surgeon to improve the completeness of the removal is being developed. Autofluorescence spectroscopy is a promising approach to define whether the tissue is cancerous or not. First ex vivo measurements have been realised on an animal model. After tumorous cell injection in rat brain, autofluorescence intensity is revealed from the extracted brain. These autofluorescence data are compared to results from a histological analysis of same brains. First indicators are identified that may have the ability to differentiate tumorous and healthy tissues.

CHIME: A Metadata-Based Distributed Software Development Environment

DTIC Science & Technology

2005-01-01

structures by using typography , graphics , and animation. The Software Im- mersion in our conceptual model for CHIME can be seen as a form of Software...Even small- to medium-sized development efforts may involve hundreds of artifacts -- design documents, change requests, test cases and results, code...for managing and organizing information from all phases of the software lifecycle. CHIME is designed around an XML-based metadata architecture, in

Sex Differences in Animal Models: Focus on Addiction

PubMed Central

Becker, Jill B.

2016-01-01

The purpose of this review is to discuss ways to think about and study sex differences in preclinical animal models. We use the framework of addiction, in which animal models have excellent face and construct validity, to illustrate the importance of considering sex differences. There are four types of sex differences: qualitative, quantitative, population, and mechanistic. A better understanding of the ways males and females can differ will help scientists design experiments to characterize better the presence or absence of sex differences in new phenomena that they are investigating. We have outlined major quantitative, population, and mechanistic sex differences in the addiction domain using a heuristic framework of the three established stages of the addiction cycle: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. Female rats, in general, acquire the self-administration of drugs and alcohol more rapidly, escalate their drug taking with extended access more rapidly, show more motivational withdrawal, and (where tested in animal models of “craving”) show greater reinstatement. The one exception is that female rats show less motivational withdrawal to alcohol. The bases for these quantitative sex differences appear to be both organizational, in that estradiol-treated neonatal animals show the male phenotype, and activational, in that the female phenotype depends on the effects of gonadal hormones. In animals, differences within the estrous cycle can be observed but are relatively minor. Such hormonal effects seem to be most prevalent during the acquisition of drug taking and less influential once compulsive drug taking is established and are linked largely to progesterone and estradiol. This review emphasizes not only significant differences in the phenotypes of females and males in the domain of addiction but emphasizes the paucity of data to date in our understanding of those differences. PMID:26772794

Livestock models in translational medicine.

PubMed

Roth, James A; Tuggle, Christopher K

2015-01-01

This issue of the ILAR Journal focuses on livestock models in translational medicine. Livestock models of selected human diseases present important advantages as compared with rodent models for translating fundamental breakthroughs in biology to useful preventatives and therapeutics for humans. Livestock reflect the complexity of applying medical advances in an outbred species. In many cases, the pathogenesis of infectious, metabolic, genetic, and neoplastic diseases in livestock species more closely resembles that in humans than does the pathogenesis of rodent models. Livestock models also provide the advantage of similar organ size and function and the ability to serially sample an animal throughout the study period. Research using livestock models for human disease often benefits not only human health but animal health and food production as well. This issue of the ILAR Journal presents information on translational research using livestock models in two broad areas: microbiology and infectious disease (transmissible spongiform encephalopathies, mycobacterial infections, influenza A virus infection, vaccine development and testing, the human microbiota) and metabolic, neoplastic, and genetic disorders (stem cell therapy, male germ line cell biology, pulmonary adenocarcinoma, muscular dystrophy, wound healing). In addition, there is a manuscript devoted to Institutional Animal Care and Use Committees' responsibilities for reviewing research using livestock models. Conducting translational research using livestock models requires special facilities and researchers with expertise in livestock. There are many institutions in the world with experienced researchers and facilities designed for livestock research; primarily associated with colleges of agriculture and veterinary medicine or government laboratories. © The Author 2015. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

ADAPT: The Agent Development and Prototyping Testbed.

PubMed

Shoulson, Alexander; Marshak, Nathan; Kapadia, Mubbasir; Badler, Norman I

2014-07-01

We present ADAPT, a flexible platform for designing and authoring functional, purposeful human characters in a rich virtual environment. Our framework incorporates character animation, navigation, and behavior with modular interchangeable components to produce narrative scenes. The animation system provides locomotion, reaching, gaze tracking, gesturing, sitting, and reactions to external physical forces, and can easily be extended with more functionality due to a decoupled, modular structure. The navigation component allows characters to maneuver through a complex environment with predictive steering for dynamic obstacle avoidance. Finally, our behavior framework allows a user to fully leverage a character's animation and navigation capabilities when authoring both individual decision-making and complex interactions between actors using a centralized, event-driven model.

The Effect of Short Moderate Stress on the Midbrain CRF System in a Macaque Model of Functional Hypothalamic Amenorrhea

PubMed Central

Bethea, Cynthia L; Phu, Kenny; Reddy, Arubala P; Cameron, Judy L

2014-01-01

Objective To study the effect of moderate stress on CRF components in the serotonergic midbrain region in a monkey model of FHA. Design After characterization of stress sensitivity, monkeys were moved to a novel room and given 20% less chow for 5 days prior to euthanasia. Setting University of Pittsburgh nonhuman primate facility. Animals Female cynomolgus macaques (Macaca fascicularis) characterized as highly stress resilient (HSR, n=5), medium stress resilient (MSR, N=4) or stress sensitive (SS, n=4). Intervention 5 days of diet in a novel room with unfamiliar conspecifics. Main Outcome Measures Density of CRF axons in the serotonergic dorsal raphe nucleus; the number of UCN1 cells; the density of UCN1 axons; the expression of CRF-R1 and CRF-R2 in the dorsal raphe nucleus. Results CRF innervation was higher in HSR than SS animals; UCN1 cell number was higher in HSR than SS animals and UCN1 axon bouton density was not different, all opposite of non-stressed animals. CRF-R1 was not different between the sensitivity groups, but CRF-R2 was higher in HSR than SS animals. The relative expression of CRF-R1 and R2 was similar to non-stressed animals. Conclusions HSR animals respond to stress with an increase in CRF delivery to serotonin neurons. With stress, UCN1 transport decreases in HSR animals. CRF receptor expression was similar with or without stress. These changes may contribute to resilience in HSR animals. PMID:23849846

Agent Technologies Designed to Facilitate Interactive Knowledge Construction

ERIC Educational Resources Information Center

Graesser, Arthur C.; Jeon, Moongee; Dufty, David

2008-01-01

During the last decade, interdisciplinary researchers have developed technologies with animated pedagogical agents that interact with the student in language and other communication channels (such as facial expressions and gestures). These pedagogical agents model good learning strategies and coach the students in actively constructing knowledge…

Vitamin D in Foot and Ankle Fracture Healing: A Literature Review and Research Design.

PubMed

Bernhard, Andrew; Matuk, Jorge

2015-10-01

Vitamin D is a generic name for a group of essential vitamins, or secosteroids, important in calcium homeostasis and bone metabolism. Specifically, efficacy of vitamin D with regard to bone healing is in question. A literature review was performed, finding mostly large studies involving vitamin D effects on prevention of fractures and randomized animal model studies consisting of controlled fractures with vitamin D interventions. The prevention articles generally focus on at-risk populations, including menopausal women and osteoporotic patients, and also most often include calcium in the treatment group. Few studies look at vitamin D specifically. The animal model studies often focus more on vitamin D supplementation; however the results are still largely inconclusive. While recent case reports appear promising, the ambiguity of results on the topic of fracture healing suggests a need for more, higher level research. A novel study design is proposed to help determine the efficacy on vitamin D in fracture healing. Therapeutic, Level IV: Systematic Review. © 2015 The Author(s).

Morphogenic designer--an efficient tool to digitally design tooth forms.

PubMed

Hajtó, J; Marinescu, C; Silva, N R F A

2014-01-01

Different digital software tools are available today for the purpose of designing anatomically correct anterior and posterior restorations. The current concepts present weaknesses, which can be potentially addressed by more advanced modeling tools, such as the ones already available in professional CAD (Computer Aided Design) graphical software. This study describes the morphogenic designer (MGD) as an efficient and easy method for digitally designing tooth forms for the anterior and posterior dentition. Anterior and posterior tooth forms were selected from a collection of digitalized natural teeth and subjectively assessed as "average". The models in the form of STL files were filtered, cleaned, idealized, and re-meshed to match the specifications of the software used. The shapes were then imported as wavefront ".obj" model into Modo 701, software built for modeling, texturing, visualization, and animation. In order to create a parametric design system, intentional interactive deformations were performed on the average tooth shapes and then further defined as morph targets. By combining various such parameters, several tooth shapes were formed virtually and their images presented. MGD proved to be a versatile and powerful tool for the purpose of esthetic and functional digital crown designs.

SSM/OOM - SSM WITH OOM MANIPULATION CODE

NASA Technical Reports Server (NTRS)

Goza, S. P.

1994-01-01

Creating, animating, and recording solid-shaded and wireframe three-dimensional geometric models can be of great assistance in the research and design phases of product development, in project planning, and in engineering analyses. SSM and OOM are application programs which together allow for interactive construction and manipulation of three-dimensional models of real-world objects as simple as boxes or as complex as Space Station Freedom. The output of SSM, in the form of binary files defining geometric three dimensional models, is used as input to OOM. Animation in OOM is done using 3D models from SSM as well as cameras and light sources. The animated results of OOM can be output to videotape recorders, film recorders, color printers and disk files. SSM and OOM are also available separately as MSC-21914 and MSC-22263, respectively. The Solid Surface Modeler (SSM) is an interactive graphics software application for solid-shaded and wireframe three-dimensional geometric modeling. The program has a versatile user interface that, in many cases, allows mouse input for intuitive operation or keyboard input when accuracy is critical. SSM can be used as a stand-alone model generation and display program and offers high-fidelity still image rendering. Models created in SSM can also be loaded into the Object Orientation Manipulator for animation or engineering simulation. The Object Orientation Manipulator (OOM) is an application program for creating, rendering, and recording three-dimensional computer-generated still and animated images. This is done using geometrically defined 3D models, cameras, and light sources, referred to collectively as animation elements. OOM does not provide the tools necessary to construct 3D models; instead, it imports binary format model files generated by the Solid Surface Modeler (SSM). Model files stored in other formats must be converted to the SSM binary format before they can be used in OOM. SSM is available as MSC-21914 or as part of the SSM/OOM bundle, COS-10047. Among OOM's features are collision detection (with visual and audio feedback), the capability to define and manipulate hierarchical relationships between animation elements, stereographic display, and ray- traced rendering. OOM uses Euler angle transformations for calculating the results of translation and rotation operations. OOM and SSM are written in C-language for implementation on SGI IRIS 4D series workstations running the IRIX operating system. A minimum of 8Mb of RAM is recommended for each program. The standard distribution medium for this program package is a .25 inch streaming magnetic IRIX tape cartridge in UNIX tar format. These versions of OOM and SSM were released in 1993.

The Mini Space Farm—A Food Regenerative System in the Long-term Manned Space Mission.

NASA Astrophysics Data System (ADS)

Zhang, Mao

In this invention we propose rearing six types of small animals which are mainly insects, all the biological wastes (bio-waste) in the space human life environment, including the human and animal feces, inedible parts of the plants and animals, food bits and other bio-wastes,can be feedstuff for rearing these six small animals, each one can recycle and digest the specific wastes to be their nourishing biomass. The biomass of these six animals, combine with the inedible parts of the space plants, will further be used as feedstuff for feeding edible animals of poultry, aquatics, amphibians, even the livestock. The meat, egg and milk from these edible animals are taken as human's animal food. Here we name these animals are as Edible Animal (EA), these six small animals are as Recycling Animals (RA). The water and nutrition left in the residues after rearing the RA can be recycled again by other RA or used to fertilize the space plants. The appropriate space plants include both terrestrial and aquatic species, such as vegetable,grain,feeding plant,edible algae and germs,also be cultivated as vegetarian food which have already successfully developed by NASA and other countries. These RA have strong reproduction ability, short life cycle, rich of nutrition, and can be easily reared in high densities with high efficiency in microgravity. Like the RA, the EA and space plants, they can be continuously reared in cages,boxes and water tanks as the solid manner, their optimal growth temperature and the humidity are same with RA, so they can be fed in the same cabin. Rearing RA, EA and plants together can provide a self-sustaining food system with minimum volume, weight, energy, labor and cost, which is the basis for realizing mini space farm in long term manned space missions. In this way, two kinds of mini space farm models have been designed: A cabin model to be used on ISS and flight craft functioning within a microgravity environment, and a greenhouse model to be used on planetary habitats with low gravity.

A fully implantable pacemaker for the mouse: from battery to wireless power.

PubMed

Laughner, Jacob I; Marrus, Scott B; Zellmer, Erik R; Weinheimer, Carla J; MacEwan, Matthew R; Cui, Sophia X; Nerbonne, Jeanne M; Efimov, Igor R

2013-01-01

Animal models have become a popular platform for the investigation of the molecular and systemic mechanisms of pathological cardiovascular physiology. Chronic pacing studies with implantable pacemakers in large animals have led to useful models of heart failure and atrial fibrillation. Unfortunately, molecular and genetic studies in these large animal models are often prohibitively expensive or not available. Conversely, the mouse is an excellent species for studying molecular mechanisms of cardiovascular disease through genetic engineering. However, the large size of available pacemakers does not lend itself to chronic pacing in mice. Here, we present the design for a novel, fully implantable wireless-powered pacemaker for mice capable of long-term (>30 days) pacing. This design is compared to a traditional battery-powered pacemaker to demonstrate critical advantages achieved through wireless inductive power transfer and control. Battery-powered and wireless-powered pacemakers were fabricated from standard electronic components in our laboratory. Mice (n = 24) were implanted with endocardial, battery-powered devices (n = 14) and epicardial, wireless-powered devices (n = 10). Wireless-powered devices were associated with reduced implant mortality and more reliable device function compared to battery-powered devices. Eight of 14 (57.1%) mice implanted with battery-powered pacemakers died following device implantation compared to 1 of 10 (10%) mice implanted with wireless-powered pacemakers. Moreover, device function was achieved for 30 days with the wireless-powered device compared to 6 days with the battery-powered device. The wireless-powered pacemaker system presented herein will allow electrophysiology studies in numerous genetically engineered mouse models as well as rapid pacing-induced heart failure and atrial arrhythmia in mice.

Advances in animal models of drug addiction.

PubMed

Heidbreder, Christian

2011-01-01

Drug addiction is a syndrome of impaired response inhibition and salience attribution, which involves a complex neurocircuitry underlying drug reinforcement, drug craving, and compulsive drug-seeking and drug-taking behaviors despite adverse consequences. The concept of disease stages with transitions from acute rewarding effects to early- and end-stage addiction has had an important impact on the design of nonclinical animal models. This chapter reviews the main advances in nonclinical paradigms that aim to at model (1) positive and negative reinforcing effects of addictive drugs; (2) relapse to drug-seeking behavior; (3) reconsolidation of drug cue memories, and (4) compulsive/impulsive drug intake. In addition, recent small animal neuroimaging studies and invertebrate models will be briefly discussed (see also Bifone and Gozzi, Animal models of ADHD, 2011). Continuous improvement in modeling drug intake, craving, withdrawal symptoms, relapse, and comorbid psychiatric associations is a necessary step to better understand the etiology of the disease and to ultimately foster the discovery, validation and optimization of new efficacious pharmacotherapeutic approaches. The modeling of specific subprocesses or constructs that address clinically defined criteria will ultimately increase our understanding of the disease as a whole. Future research will have to address the questions of whether some of these constructs can be reliably used as outcome measures to assess the effects of a treatment in clinical settings, whether changes in those measures can be a target of therapeutic efforts, and whether they relate to biological markers of traits such as impulsivity, which contribute to increased drug-seeking and may predict binge-like patterns of drug intake.

Measuring animal personality for use in population management in zoos: suggested methods and rationale.

PubMed

Watters, Jason V; Powell, David M

2012-01-01

The concept that animals have personalities is gaining traction in the scientific community and is well established in zoos and aquariums. Applying knowledge of animal personalities has occurred more slowly and is most often only considered informally. However, animal personalities are likely to affect the welfare animals experience in captivity and thus should be of primary concern to zoo managers. In addition, animal personality likely affects the outcomes of zoo guest experiences and potentially guests' conservation-related behavior. With over 1,000,000 animals in the care of zoos internationally and hundreds of millions of visitors annually, it would be prudent and beneficial to maximize our use of animal personality data in zoos to effect positive conservation outcomes. Understanding how to broaden population planning techniques to include measures of animal personality and the important outcomes of welfare and education value is of prime importance to the zoo industry. In order to succeed, it is necessary to employ techniques that reliably assess animal personalities and provide measures that can easily be used in population planning models. We discuss the outcomes of recent workshops designed to determine the best techniques for measuring animal personalities in the zoo setting with the goal of incorporating personality into population planning. © 2011 Wiley Periodicals, Inc.

Design and Analysis of a Continuous Split Typed Needle-Free Injection System for Animal Vaccination.

PubMed

Chen, Kai; Pan, Min; Liu, Tingting

2017-01-01

Liquid needle-free injection devices (NFIDs) employ a high-velocity liquid jet to deliver drugs and vaccine through transdermal injection. NFIDs for animal vaccination are more complicated than those used for human beings for their much larger and more flexible power sources, as well as rapid, repetitive and continuous injection features. In the paper, spring-powered NFID is designed for animal vaccine injection. For convenience, the device is a split into a power source and handheld injector. A mathematical model is proposed to calculate the injection pressure, taking into the account pressure loss and the strain energy loss in the bendable tube due to elastic deformation. An experimental apparatus was build to verify the calculation results. Under the same system conditions, the calculation results of the dynamic injection pressure match the experimental results. It is found that the bendable tube of the split typed NFID has significant impact on the profile of the injection pressure. The initial peak pressure is less than the initial peak pressure of NFID without bendable tube, and there is occurrence time lag of the peak pressure. The mathematical model is the first attempt to reveal the relationship between the injection pressure and the system variables of split typed NFID.

A new in vivo screening model for posterior spinal bone formation: comparison of ten calcium phosphate ceramic material treatments.

PubMed

Wilson, Clayton E; Kruyt, Moyo C; de Bruijn, Joost D; van Blitterswijk, Clemens A; Oner, F Cumhur; Verbout, Abraham J; Dhert, Wouter J A

2006-01-01

This study presents a new screening model for evaluating the influence of multiple conditions on the initial process of bone formation in the posterior lumbar spine of a large animal. This model uses cages designed for placement on the decorticated transverse process of the goat lumbar spine. Five conduction channels per cage, each be defined by a different material treatment, are open to both the underlying bone and overlying soft tissue. The model was validated in ten adult Dutch milk goats, with each animal implanted with two cages containing a total of ten calcium phosphate material treatments according to a randomized complete block design. The ten calcium phosphate ceramic materials were created through a combination of material chemistry (BCP, TCP, HA), sintering temperature (low, medium, high), calcination and surface roughness treatments. To monitor the bone formation over time, fluorochrome markers were administered at 3, 5 and 7 weeks and the animals were sacrificed at 9 weeks after implantation. Bone formation in the conduction channels was investigated by histology and histomorphometry of non-decalcified sections using traditional light and epifluorescent microscopy. According to both observed and measured bone formation parameters, materials were ranked in order of increasing magnitude as follows: low sintering temperature BCP (rough and smooth) approximately medium sintering temperature BCP approximately = TCP > calcined low sintering temperature HA > non-calcined low sintering temperature HA > high sintering temperature BCP (rough and smooth) > high sintering temperature HA (calcined and non-calcined). These results agree closely with those obtained in previous studies of osteoconduction and bioactivity of ceramics thereby validating the screening model presented in this study.

Estimating survival and breeding probability for pond-breeding amphibians: a modified robust design

USGS Publications Warehouse

Bailey, L.L.; Kendall, W.L.; Church, D.R.; Wilbur, H.M.

2004-01-01

Many studies of pond-breeding amphibians involve sampling individuals during migration to and from breeding habitats. Interpreting population processes and dynamics from these studies is difficult because (1) only a proportion of the population is observable each season, while an unknown proportion remains unobservable (e.g., non-breeding adults) and (2) not all observable animals are captured. Imperfect capture probability can be easily accommodated in capture?recapture models, but temporary transitions between observable and unobservable states, often referred to as temporary emigration, is known to cause problems in both open- and closed-population models. We develop a multistate mark?recapture (MSMR) model, using an open-robust design that permits one entry and one exit from the study area per season. Our method extends previous temporary emigration models (MSMR with an unobservable state) in two ways. First, we relax the assumption of demographic closure (no mortality) between consecutive (secondary) samples, allowing estimation of within-pond survival. Also, we add the flexibility to express survival probability of unobservable individuals (e.g., ?non-breeders?) as a function of the survival probability of observable animals while in the same, terrestrial habitat. This allows for potentially different annual survival probabilities for observable and unobservable animals. We apply our model to a relictual population of eastern tiger salamanders (Ambystoma tigrinum tigrinum). Despite small sample sizes, demographic parameters were estimated with reasonable precision. We tested several a priori biological hypotheses and found evidence for seasonal differences in pond survival. Our methods could be applied to a variety of pond-breeding species and other taxa where individuals are captured entering or exiting a common area (e.g., spawning or roosting area, hibernacula).

9 CFR 11.7 - Certification and licensing of designated qualified persons (DQP's).

Code of Federal Regulations, 2012 CFR

2012-01-01

... instruction on the anatomy and physiology of the limbs of a horse. The instructor teaching the course must be... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Certification and licensing of designated qualified persons (DQP's). 11.7 Section 11.7 Animals and Animal Products ANIMAL AND PLANT HEALTH...

9 CFR 11.7 - Certification and licensing of designated qualified persons (DQP's).

Code of Federal Regulations, 2014 CFR

2014-01-01

... instruction on the anatomy and physiology of the limbs of a horse. The instructor teaching the course must be... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Certification and licensing of designated qualified persons (DQP's). 11.7 Section 11.7 Animals and Animal Products ANIMAL AND PLANT HEALTH...

9 CFR 11.7 - Certification and licensing of designated qualified persons (DQP's).

Code of Federal Regulations, 2013 CFR

2013-01-01

... instruction on the anatomy and physiology of the limbs of a horse. The instructor teaching the course must be... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Certification and licensing of designated qualified persons (DQP's). 11.7 Section 11.7 Animals and Animal Products ANIMAL AND PLANT HEALTH...

9 CFR 11.7 - Certification and licensing of designated qualified persons (DQP's).

Code of Federal Regulations, 2010 CFR

2010-01-01

... instruction on the anatomy and physiology of the limbs of a horse. The instructor teaching the course must be... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Certification and licensing of designated qualified persons (DQP's). 11.7 Section 11.7 Animals and Animal Products ANIMAL AND PLANT HEALTH...

9 CFR 11.7 - Certification and licensing of designated qualified persons (DQP's).

Code of Federal Regulations, 2011 CFR

2011-01-01

... instruction on the anatomy and physiology of the limbs of a horse. The instructor teaching the course must be... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Certification and licensing of designated qualified persons (DQP's). 11.7 Section 11.7 Animals and Animal Products ANIMAL AND PLANT HEALTH...

Design of a multimodal fibers optic system for small animal optical imaging.

PubMed

Spinelli, Antonello E; Pagliazzi, Marco; Boschi, Federico

2015-02-01

Small animals optical imaging systems are widely used in pre-clinical research to image in vivo the bio-distribution of light emitting probes using fluorescence or bioluminescence modalities. In this work we presented a set of simulated results of a novel small animal optical imaging module based on a fibers optics matrix, coupled with a position sensitive detector, devoted to acquire bioluminescence and Cerenkov images. Simulations were performed using GEANT 4 code with the GAMOS architecture using the tissue optics plugin. Results showed that it is possible to image a 30 × 30 mm region of interest using a fiber optics array containing 100 optical fibers without compromising the quality of the reconstruction. The number of fibers necessary to cover an adequate portion of a small animal is thus quite modest. This design allows integrating the module with magnetic resonance (MR) in order to acquire optical and MR images at the same time. A detailed model of the mouse anatomy, obtained by segmentation of 3D MRI images, will improve the quality of optical 3D reconstruction. Copyright © 2014 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Lift calculations based on accepted wake models for animal flight are inconsistent and sensitive to vortex dynamics.

PubMed

Gutierrez, Eric; Quinn, Daniel B; Chin, Diana D; Lentink, David

2016-12-06

There are three common methods for calculating the lift generated by a flying animal based on the measured airflow in the wake. However, these methods might not be accurate according to computational and robot-based studies of flapping wings. Here we test this hypothesis for the first time for a slowly flying Pacific parrotlet in still air using stereo particle image velocimetry recorded at 1000 Hz. The bird was trained to fly between two perches through a laser sheet wearing laser safety goggles. We found that the wingtip vortices generated during mid-downstroke advected down and broke up quickly, contradicting the frozen turbulence hypothesis typically assumed in animal flight experiments. The quasi-steady lift at mid-downstroke was estimated based on the velocity field by applying the widely used Kutta-Joukowski theorem, vortex ring model, and actuator disk model. The calculated lift was found to be sensitive to the applied model and its different parameters, including vortex span and distance between the bird and laser sheet-rendering these three accepted ways of calculating weight support inconsistent. The three models predict different aerodynamic force values mid-downstroke compared to independent direct measurements with an aerodynamic force platform that we had available for the same species flying over a similar distance. Whereas the lift predictions of the Kutta-Joukowski theorem and the vortex ring model stayed relatively constant despite vortex breakdown, their values were too low. In contrast, the actuator disk model predicted lift reasonably accurately before vortex breakdown, but predicted almost no lift during and after vortex breakdown. Some of these limitations might be better understood, and partially reconciled, if future animal flight studies report lift calculations based on all three quasi-steady lift models instead. This would also enable much needed meta studies of animal flight to derive bioinspired design principles for quasi-steady lift generation with flapping wings.

Design and evaluation of a restraint-free small animal inhalation dosing chamber.

PubMed

McConville, Jason T; Williams, Robert O; Carvalho, Thiago C; Iberg, Aimee N; Johnston, Keith P; Talbert, Robert L; Burgess, David; Peters, Jay I

2005-01-01

The aim of research was to design a small, restraint free, low stress animal dosing chamber for inhalation studies, and to investigate distribution of a model drug within the chamber. A small animal dosing chamber was designed that consisted of a polymethylmethacrylate (PMMA) airtight box (40.6 x 11.4 x 21.6 cm) with a hinged top, having a nominal wall thickness of 1.25 cm. The chamber was designed to hold up to 14 mice, each having a floor area of approximately 63 cm2, in accordance with Institutional Animal Care and Use Committee (IACUC) guidelines. A "rodent proof" distribution fan was attached to the center of the hinged closure lid. The chamber was divided into 1 inch2 zones (120 in total) to enable a profile of drug distribution within the chamber to be obtained. Small holes were drilled into the side of the chamber and sealed using Parafilm to allow access to the sampling zones. Syringes (5 mL) with appropriate length polytetrafluoroethylene (PTFE) tubing were inserted into the holes to reach the sampling zones (eight on either side of the chamber giving a total of 16 zones). An aqueous caffeine solution (2% w/v) in glycerol (25% w/v) was prepared and nebulized into the chamber using an Aeroneb Pro nebulizer. Caffeine containing droplets were circulated into the chamber at a flow rate of 1.5 L/min(-1), and the air was recirculated in a closed system for a total of 20 minutes to ensure a high concentration of caffeine droplets throughout. Following nebulization, air samples (5 mL) were withdrawn from the 16 sampling zones of the sealed chamber. The process was repeated in quadruplet until a total of 64 sampling zones had been sampled. The entire experiment was also repeated with the absence of the "rodent-proof" distribution fan. Drug concentrations were calculated from a calibration curve of caffeine using UV absorbance at 272 nm. An average mass of caffeine (Standard Deviation; S.D.) of 5.0 (4.2) mg was detected throughout the chamber when the distribution fan was fitted, and caffeine 12.6 (9.7) mg was detected without the fan. This indicated that presence of the fan caused impingement of the drug on both the chamber walls and fan components; effectively removing nebulized drug from circulation within the chamber. The distribution of drug was plotted using a 3D graph; this revealed a lower concentration at the periphery and a higher concentration in the center of the chamber both with and without the distribution fan in place. In conclusion, a humane, nonrestraint rodent dosing chamber was designed for the efficient delivery of nebulized drugs for up to 14 mice simultaneously. The highest levels of the model drug caffeine were detectable throughout the small animal dosing chamber without the distribution fan. A circulation flow rate of 1.5 L/min(-1) was found to be adequate to distribute drug in the chamber. Surprisingly, the results demonstrate that avoiding the use of a distribution fan altogether maximizes the drug concentration within the chamber by reducing impingement of the nebulized drug. The small animal, restraint-free dosing chamber represents an advancement in reproducible dosing via the pulmonary route in the small animal model. The dosing chamber may be adapted to present the lung with an almost unlimited array of compounds, encompassing drugs, toxic compounds, and even pathogens, while still maintaining a relatively stress-free microenvironment for the test subject and furthermore, total safety for the operator.

Around Marshall

NASA Image and Video Library

1993-09-15

Virtual Reality (VR) can provide cost effective methods to design and evaluate components and systems for maintenance and refurbishment operations. Marshall SPace Flight Center (MSFC) is begirning to utilize VR for design analysis in the X-34 experimental reusable space vehicle. Analysts at MSFC's Computer Applications and Virtual Environments (CAVE) used Head Mounted Displays (HMD) (pictured), spatial trackers and gesture inputs as a means to animate or inhabit a properly sized virtual human model. These models are used in a VR scenario as a way to determine functionality of space and maintenance requirements for the virtual X-34. The primary functions of the virtual X-34 mockup is to support operations development and design analysis for engine removal, the engine compartment and the aft fuselage. This capability provides general visualization support to engineers and designers at MSFC and to the System Design Freeze Review at Orbital Sciences Corporation (OSC).

Around Marshall

NASA Image and Video Library

1993-12-15

Virtual Reality (VR) can provide cost effective methods to design and evaluate components and systems for maintenance and refurbishment operations. Marshall Spce Flight Center (MSFC) is begirning to utilize VR for design analysis in the X-34 experimental reusable space vehicle. Analysts at MSFC's Computer Applications and Virtual Environments (CAVE) used Head Mounted Displays (HMD) (pictured), spatial trackers and gesture inputs as a means to animate or inhabit a properly sized virtual human model. These models are used in a VR scenario as a way to determine functionality of space and maintenance requirements for the virtual X-34. The primary functions of the virtual X-34 mockup is to support operations development and design analysis for engine removal, the engine compartment and the aft fuselage. This capability provides general visualization support to engineers and designers at MSFC and to the System Design Freeze Review at Orbital Sciences Corporation (OSC).

A Single Amino Acid Change in the Marburg Virus Glycoprotein Arises during Serial Cell Culture Passages and Attenuates the Virus in a Macaque Model of Disease.

PubMed

Alfson, Kendra J; Avena, Laura E; Delgado, Jenny; Beadles, Michael W; Patterson, Jean L; Carrion, Ricardo; Griffiths, Anthony

2018-01-01

Marburg virus (MARV) causes disease with high case fatality rates, and there are no approved vaccines or therapies. Licensing of MARV countermeasures will likely require approval via the FDA's Animal Efficacy Rule, which requires well-characterized animal models that recapitulate human disease. This includes selection of the virus used for exposure and ensuring that it retains the properties of the original isolate. The consequences of amplification of MARV for challenge studies are unknown. Here, we serially passaged and characterized MARV through 13 passes from the original isolate. Surprisingly, the viral genome was very stable, except for a single nucleotide change that resulted in an amino acid substitution in the hydrophobic region of the signal peptide of the glycoprotein (GP). The particle/PFU ratio also decreased following passages, suggesting a role for the amino acid in viral infectivity. To determine if amplification introduces a phenotype in an animal model, cynomolgus macaques were exposed to either 100 or 0.01 PFU of low- and high-passage-number MARV. All animals succumbed when exposed to 100 PFU of either passage 3 or 13 viruses, although animals exposed to the high-passage-number virus survived longer. However, none of the passage 13 MARV-exposed animals succumbed to 0.01-PFU exposure compared to 75% of passage 3-exposed animals. This is consistent with other filovirus studies that show some particles that are unable to yield a plaque in cell culture can cause lethal disease in vivo . These results have important consequences for the design of experiments that investigate MARV pathogenesis and that test the efficacy of MARV countermeasures. IMPORTANCE Marburg virus (MARV) causes disease with a high case fatality rate, and there are no approved vaccines or therapies. Serial amplification of viruses in cell culture often results in accumulation of mutations, but the effect of such cell culture passage on MARV is unclear. Serial passages of MARV resulted in a single mutation in the region encoding the glycoprotein (GP). This is a region where mutations can have important consequences on outbreaks and human disease [S. Mahanty and M. Bray, Lancet Infect Dis 4:487-498, 2004, https://doi.org/10.1016/S1473-3099(04)01103-X]. We thus investigated whether this mutation impacted disease by using a cynomolgus macaque model of MARV infection. Monkeys exposed to virus containing the mutation had better clinical outcomes than monkeys exposed to virus without the mutation. We also observed that a remarkably low number of MARV particles was sufficient to cause death. Our results could have a significant impact on how future studies are designed to model MARV disease and test vaccines and therapeutics.

A Single Amino Acid Change in the Marburg Virus Glycoprotein Arises during Serial Cell Culture Passages and Attenuates the Virus in a Macaque Model of Disease

PubMed Central

Alfson, Kendra J.; Avena, Laura E.; Delgado, Jenny; Beadles, Michael W.; Patterson, Jean L.; Carrion, Ricardo

2018-01-01

ABSTRACT Marburg virus (MARV) causes disease with high case fatality rates, and there are no approved vaccines or therapies. Licensing of MARV countermeasures will likely require approval via the FDA’s Animal Efficacy Rule, which requires well-characterized animal models that recapitulate human disease. This includes selection of the virus used for exposure and ensuring that it retains the properties of the original isolate. The consequences of amplification of MARV for challenge studies are unknown. Here, we serially passaged and characterized MARV through 13 passes from the original isolate. Surprisingly, the viral genome was very stable, except for a single nucleotide change that resulted in an amino acid substitution in the hydrophobic region of the signal peptide of the glycoprotein (GP). The particle/PFU ratio also decreased following passages, suggesting a role for the amino acid in viral infectivity. To determine if amplification introduces a phenotype in an animal model, cynomolgus macaques were exposed to either 100 or 0.01 PFU of low- and high-passage-number MARV. All animals succumbed when exposed to 100 PFU of either passage 3 or 13 viruses, although animals exposed to the high-passage-number virus survived longer. However, none of the passage 13 MARV-exposed animals succumbed to 0.01-PFU exposure compared to 75% of passage 3-exposed animals. This is consistent with other filovirus studies that show some particles that are unable to yield a plaque in cell culture can cause lethal disease in vivo. These results have important consequences for the design of experiments that investigate MARV pathogenesis and that test the efficacy of MARV countermeasures. IMPORTANCE Marburg virus (MARV) causes disease with a high case fatality rate, and there are no approved vaccines or therapies. Serial amplification of viruses in cell culture often results in accumulation of mutations, but the effect of such cell culture passage on MARV is unclear. Serial passages of MARV resulted in a single mutation in the region encoding the glycoprotein (GP). This is a region where mutations can have important consequences on outbreaks and human disease [S. Mahanty and M. Bray, Lancet Infect Dis 4:487–498, 2004, https://doi.org/10.1016/S1473-3099(04)01103-X]. We thus investigated whether this mutation impacted disease by using a cynomolgus macaque model of MARV infection. Monkeys exposed to virus containing the mutation had better clinical outcomes than monkeys exposed to virus without the mutation. We also observed that a remarkably low number of MARV particles was sufficient to cause death. Our results could have a significant impact on how future studies are designed to model MARV disease and test vaccines and therapeutics. PMID:29299527

Influence of single hindlimb support during simulated weightlessness in the rat

NASA Technical Reports Server (NTRS)

Stump, Craig S.; Overton, J. Michael; Tipton, Charles M.

1990-01-01

A study was carried out to develop and evaluate a hindlimb suspension model, making it possible to differentiate the effects of non-weight bearing by hindlimbs per se from the systemic influence of simulated weightlessness. A support platform was designed which allowed the animal to maintain one hindlimb in a posture similar to the hindlimbs of the control animals at rest and to maintain one hindlimb in a posture similar to the hindlimbs of the control animals, providing a support for the animal to contract or stretch hindlimb muscles against at any time during suspension. The results of this study indicated that hindlimb support during head-down suspension will maintain muscle-mass/body-mass ratios, glycogen concentration, and blood flow. However, it will not prevent the loss in citrate synthase activity associated with conditions of simulated weightlessness.

The Electronic Guinea Pig.

ERIC Educational Resources Information Center

Angier, Natalie

1983-01-01

Scientists are designing computer models of biological systems, and of compounds with complex molecules, that can be used to get answers once obtainable only by sacrificing laboratory animals. Although most programs are still under development, some are in use by industrial/pharmaceutical companies. The programs and experiments they simulate are…

What's the Technology For? Teacher Attention and Pedagogical Goals in a Modeling-Focused Professional Development Workshop

NASA Astrophysics Data System (ADS)

Wilkerson, Michelle Hoda; Andrews, Chelsea; Shaban, Yara; Laina, Vasiliki; Gravel, Brian E.

2016-02-01

This paper explores the role that technology can play in engaging pre-service teachers with the iterative, "messy" nature of model-based inquiry. Over the course of 5 weeks, 11 pre-service teachers worked in groups to construct models of diffusion using a computational animation and simulation toolkit, and designed lesson plans for the toolkit. Content analyses of group discussions and lesson plans document attention to content, representation, revision, and evaluation as interwoven aspects of modeling over the course of the workshop. When animating, only content and representation were heavily represented in group discussions. When simulating, all four aspects were represented to different extents across groups. Those differences corresponded with different planned uses for the technology during lessons: to teach modeling, to engage learners with one another's ideas, or to reveal student ideas. We identify specific ways in which technology served an important role in eliciting teachers' knowledge and goals related to scientific modeling in the classroom.

Vehicle Sketch Pad: a Parametric Geometry Modeler for Conceptual Aircraft Design

NASA Technical Reports Server (NTRS)

Hahn, Andrew S.

2010-01-01

The conceptual aircraft designer is faced with a dilemma, how to strike the best balance between productivity and fidelity? Historically, handbook methods have required only the coarsest of geometric parameterizations in order to perform analysis. Increasingly, there has been a drive to upgrade analysis methods, but these require considerably more precise and detailed geometry. Attempts have been made to use computer-aided design packages to fill this void, but their cost and steep learning curve have made them unwieldy at best. Vehicle Sketch Pad (VSP) has been developed over several years to better fill this void. While no substitute for the full feature set of computer-aided design packages, VSP allows even novices to quickly become proficient in defining three-dimensional, watertight aircraft geometries that are adequate for producing multi-disciplinary meta-models for higher order analysis methods, wind tunnel and display models, as well as a starting point for animation models. This paper will give an overview of the development and future course of VSP.

Empirical Studies of the Value of Algorithm Animation in Algorithm Understanding

DTIC Science & Technology

1993-08-01

defines program visualization as "the use of the technology of interactive graphics and the crafts of graphic design , typography , animation and...classroom, considerable thought must go into the design of the animation. Guidelines exist for the design of interfaces and for the design of graphical presen...principles are learned which may be applied to several related problem situations. 2.3 Design of Pictures To obtain the maximum benefit of graphics

Anthrax vaccine-induced antibodies provide cross-species prediction of survival to aerosol challenge.

PubMed

Fay, Michael P; Follmann, Dean A; Lynn, Freyja; Schiffer, Jarad M; Stark, Gregory V; Kohberger, Robert; Quinn, Conrad P; Nuzum, Edwin O

2012-09-12

Because clinical trials to assess the efficacy of vaccines against anthrax are not ethical or feasible, licensure for new anthrax vaccines will likely involve the Food and Drug Administration's "Animal Rule," a set of regulations that allow approval of products based on efficacy data only in animals combined with immunogenicity and safety data in animals and humans. U.S. government-sponsored animal studies have shown anthrax vaccine efficacy in a variety of settings. We examined data from 21 of those studies to determine whether an immunological bridge based on lethal toxin neutralization activity assay (TNA) can predict survival against an inhalation anthrax challenge within and across species and genera. The 21 studies were classified into 11 different settings, each of which had the same animal species, vaccine type and formulation, vaccination schedule, time of TNA measurement, and challenge time. Logistic regression models determined the contribution of vaccine dilution dose and TNA on prediction of survival. For most settings, logistic models using only TNA explained more than 75% of the survival effect of the models with dose additionally included. Cross-species survival predictions using TNA were compared to the actual survival and shown to have good agreement (Cohen's κ ranged from 0.55 to 0.78). In one study design, cynomolgus macaque data predicted 78.6% survival in rhesus macaques (actual survival, 83.0%) and 72.6% in rabbits (actual survival, 64.6%). These data add support for the use of TNA as an immunological bridge between species to extrapolate data in animals to predict anthrax vaccine effectiveness in humans.

3α5β-Pregnanolone glutamate, a use-dependent NMDA antagonist, reversed spatial learning deficit in an animal model of schizophrenia.

PubMed

Vales, Karel; Rambousek, Lukas; Holubova, Kristina; Svoboda, Jan; Bubenikova-Valesova, Vera; Chodounska, Hana; Vyklicky, Ladislav; Stuchlik, Ales

2012-11-01

Neuroactive steroids modulate receptors for neurotransmitters in the brain and thus might be efficacious in the treatment of various diseases of the central nervous system such as schizophrenia. We have designed and synthetized a novel use-dependent NMDA receptor antagonist 3α5β-pregnanolone glutamate (3α5β-P-Glu). In this study, we evaluate procognitive properties of 3α5β-P-Glu in an animal model of schizophrenia induced by systemic application of MK-801. The procognitive properties were evaluated using active place avoidance on a rotating arena (Carousel maze). We evaluated effects of 3α5β-P-Glu on the avoidance, on locomotor activity, and anxiety. 3α5β-P-Glu alone altered neither spatial learning nor locomotor activity in control animals. In the model animals, 3α5β-P-Glu reversed the MK-801-induced cognitive deficit without reducing hyperlocomotion. The highest dose of 3α5β-P-Glu also showed anxiolytic properties. Taken together, 3α5β-P-Glu may participate in the restoration of normal brain functioning and these results may facilitate the development of new promising drugs improving cognitive functioning in schizophrenia. Copyright © 2012 Elsevier B.V. All rights reserved.

Emerging new pathways of pathogenesis and targets for treatment in systemic lupus erythematosus and Sjogren's syndrome.

PubMed

Perl, Andras

2009-09-01

Systemic lupus erythematosus (SLE) and Sjogren's syndrome are chronic inflammatory diseases characterized by the dysfunction of T cells, B cells, and dendritic cells and the production of antinuclear autoantibodies. Here, we evaluate newly discovered molecular and cellular targets for the treatment of SLE and Sjogren's syndrome. The mammalian target of rapamycin in T and B cells has been successfully targeted for treatment of SLE with rapamycin or sirolimus both in patients and animal models. Inhibition of oxidative stress, nitric oxide production, interferon alpha, toll-like receptors 7 and 9, histone deacetylase, spleen tyrosine kinase, proteasome function, lysosome function, endosome recycling, and the nuclear factor kappa B pathway showed efficacy in animal models of lupus. B-cell depletion and blockade of anti-DNA antibodies and T-B cell interaction have shown success in animal models, whereas human studies have so far failed to accomplish clinical endpoints, possibly due to inadequacies in study design. Discovery of novel genes and signaling pathways in lupus pathogenesis offers novel biomarker-targeted approaches for treatment of SLE and Sjogren's syndrome.

The use of QSAR methods for determination of n-octanol/water partition coefficient using the example of hydroxyester HE-1

NASA Astrophysics Data System (ADS)

Guziałowska-Tic, Joanna

2017-10-01

According to the Directive of the European Parliament and of the Council concerning the protection of animals used for scientific purposes, the number of experiments involving the use of animals needs to be reduced. The methods which can replace animal testing include computational prediction methods, for instance, the quantitative structure-activity relationships (QSAR). These methods are designed to find a cohesive relationship between differences in the values of the properties of molecules and the biological activity of a series of test compounds. This paper compares the results of the author's own results of examination on the n-octanol/water coefficient for the hydroxyester HE-1 with those generated by means of three models: Kowwin, MlogP, AlogP. The test results indicate that, in the case of molecular similarity, the highest determination coefficient was obtained for the model MlogP and the lowest root-mean square error was obtained for the Kowwin method. When comparing the mean logP value obtained using the QSAR models with the value resulting from the author's own experiments, it was observed that the best conformity was that recorded for the model AlogP, where relative error was 15.2%.

Motion reconstruction of animal groups: From schooling fish to swarming mosquitoes

NASA Astrophysics Data System (ADS)

Butail, Sachit

The long-term goal of this research is to provide kinematic data for the design and validation of spatial models of collective behavior in animal groups. The specific research objective of this dissertation is to apply methods from nonlinear estimation and computer vision to construct multi-target tracking systems that process multi-view calibrated video to reconstruct the three-dimensional movement of animals in a group. We adapt the tracking systems for the study of two animal species: Danio aequipinnatus, a common species of schooling fish, and Anopheles gambiae, the most important vector of malaria in sub-Saharan Africa. Together these tracking systems span variability in target size on image, density, and movement. For tracking fish, we automatically initialize, predict, and reconstruct shape trajectories of multiple fish through occlusions. For mosquitoes, which appear as faded streaks on in-field footage, we provide methods to extract velocity information from the streaks, adaptively seek missing measurements, and resolve occlusions within a multi-hypothesis framework. In each case the research has yielded an unprecedented volume of trajectory data for subsequent analysis. We present kinematic data of fast-start response in fish schools and first-ever trajectories of wild mosquito swarming and mating events. The broader impact of this work is to advance the understanding of animal groups for the design of bio-inspired robotic systems, where, similar to the animal groups we study, the collective is able to perform tasks far beyond the capabilities of a single inexpensive robot.

9 CFR 306.1 - Designation of circuit supervisor and assistants.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Designation of circuit supervisor and assistants. 306.1 Section 306.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY...

9 CFR 306.1 - Designation of circuit supervisor and assistants.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Designation of circuit supervisor and assistants. 306.1 Section 306.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY...

Development of induced glioblastoma by implantation of a human xenograft in Yucatan minipig as a large animal model.

PubMed

Khoshnevis, Mehrdad; Carozzo, Claude; Bonnefont-Rebeix, Catherine; Belluco, Sara; Leveneur, Olivia; Chuzel, Thomas; Pillet-Michelland, Elodie; Dreyfus, Matthieu; Roger, Thierry; Berger, François; Ponce, Frédérique

2017-04-15

Glioblastoma is the most common and deadliest primary brain tumor for humans. Despite many efforts toward the improvement of therapeutic methods, prognosis is poor and the disease remains incurable with a median survival of 12-14.5 months after an optimal treatment. To develop novel treatment modalities for this fatal disease, new devices must be tested on an ideal animal model before performing clinical trials in humans. A new model of induced glioblastoma in Yucatan minipigs was developed. Nine immunosuppressed minipigs were implanted with the U87 human glioblastoma cell line in both the left and right hemispheres. Computed tomography (CT) acquisitions were performed once a week to monitor tumor growth. Among the 9 implanted animals, 8 minipigs showed significant macroscopic tumors on CT acquisitions. Histological examination of the brain after euthanasia confirmed the CT imaging findings with the presence of an undifferentiated glioma. Yucatan minipig, given its brain size and anatomy (gyrencephalic structure) which are comparable to humans, provides a reliable brain tumor model for preclinical studies of different therapeutic METHODS: in realistic conditions. Moreover, the short development time, the lower cyclosporine and caring cost and the compatibility with the size of commercialized stereotactic frames make it an affordable and practical animal model, especially in comparison with large breed pigs. This reproducible glioma model could simulate human anatomical conditions in preclinical studies and facilitate the improvement of novel therapeutic devices, designed at the human scale from the outset. Copyright © 2017 Elsevier B.V. All rights reserved.

Anti-inflammatory activity of Heliotropium strigosum in animal models.

PubMed

Khan, Haroon; Khan, Murad Ali; Gul, Farah; Hussain, Sajjid; Ashraf, Nadeem

2015-12-01

The current project was designed to evaluate the anti-inflammatory activity of crude extract of Heliotropium strigosum and its subsequent solvent fractions in post carrageenan-induced edema and post xylene-induced ear edema at 50, 100, and 200 mg/kg intraperitoneally. The results revealed marked attenuation of edema induced by carrageenan injection in a dose-dependent manner. The ethyl acetate fraction was most dominant with 73.33% inhibition followed by hexane fraction (70.66%). When the extracts were challenged against xylene-induced ear edema, again ethyl acetate and hexane fractions were most impressive with 38.21 and 35.77% inhibition, respectively. It is concluded that various extracts of H. strigosum possessed strong anti-inflammatory activity in animal models. © The Author(s) 2012.

Intrinsic Fluctuations and Driven Response of Insect Swarms

NASA Astrophysics Data System (ADS)

Ni, Rui; Puckett, James G.; Dufresne, Eric R.; Ouellette, Nicholas T.

2015-09-01

Animals of all sizes form groups, as acting together can convey advantages over acting alone; thus, collective animal behavior has been identified as a promising template for designing engineered systems. However, models and observations have focused predominantly on characterizing the overall group morphology, and often focus on highly ordered groups such as bird flocks. We instead study a disorganized aggregation (an insect mating swarm), and compare its natural fluctuations with the group-level response to an external stimulus. We quantify the swarm's frequency-dependent linear response and its spectrum of intrinsic fluctuations, and show that the ratio of these two quantities has a simple scaling with frequency. Our results provide a new way of comparing models of collective behavior with experimental data.

Tools for evaluating Veterinary Services: an external auditing model for the quality assurance process.

PubMed

Melo, E Correa

2003-08-01

The author describes the reasons why evaluation processes should be applied to the Veterinary Services of Member Countries, either for trade in animals and animal products and by-products between two countries, or for establishing essential measures to improve the Veterinary Service concerned. The author also describes the basic elements involved in conducting an evaluation process, including the instruments for doing so. These basic elements centre on the following:--designing a model, or desirable image, against which a comparison can be made--establishing a list of processes to be analysed and defining the qualitative and quantitative mechanisms for this analysis--establishing a multidisciplinary evaluation team and developing a process for standardising the evaluation criteria.

A Medical Student Workshop in Mechanical Ventilation.

ERIC Educational Resources Information Center

And Others; Kushins, Lawrence G.

1980-01-01

In order to teach applied respiratory physiology to medical students, the anesthesiology faculty at the University of Florida College of Medicine has designed and implemented a course that includes a laboratory workshop in mechanical ventilation of an animal model that allows students to apply and expand their knowledge. (JMD)

Effects of Grazing Pressure on Efficiency of Grazing on North American Great Plains Rangelands

USDA-ARS?s Scientific Manuscript database

Robust prediction models describing vegetation and animal responses to stocking rate in North American Great Plains rangelands are lacking as across site comparisons are limited by different qualitative designations of light, moderate and heavy stocking. Comparisons of stocking rates across sites ca...

Endothelialized ePTFE Graft by Nanobiotechnology

ClinicalTrials.gov

2013-11-29

The Apparatus for Processing the Tubular Graft Modification Will be Designed and Evaluated.; The On-site Capturing of the Endothelial (Progenitor) Cells by Peptide-mediated Selective Adhesion in Vitro and in Vivo Will Also be Elucidated.; The Patency Rate of ITRI-made Artificial Blood Vessels Will be Evaluated by the Porcine Animal Model.

Set-up of a multivariate approach based on serum biomarkers as an alternative strategy for the screening evaluation of the potential abuse of growth promoters in veal calves.

PubMed

Pirro, Valentina; Girolami, Flavia; Spalenza, Veronica; Gardini, Giulia; Badino, Paola; Nebbia, Carlo

2015-01-01

A chemometric class modelling strategy (unequal dispersed classes - UNEQ) was applied for the first time as a possible screening method to monitor the abuse of growth promoters in veal calves. Five serum biomarkers, known to reflect the exposure to classes of compounds illegally used as growth promoters, were determined from 50 untreated animals in order to design a model of controls, representing veal calves reared under good, safe and highly standardised breeding conditions. The class modelling was applied to 421 commercially bred veal calves to separate them into 'compliant' and 'non-compliant' with respect to the modelled controls. Part of the non-compliant animals underwent further histological and chemical examinations to confirm the presence of either alterations in target tissues or traces of illegal substances commonly administered for growth-promoting purposes. Overall, the congruence between the histological or chemical methods and the UNEQ non-compliant outcomes was approximately 58%, likely underestimated due to the blindness nature of this examination. Further research is needed to confirm the validity of the UNEQ model in terms of sensitivity in recognising untreated animals as compliant to the controls, and specificity in revealing deviations from ideal breeding conditions, for example due to the abuse of growth promoters.

A less field-intensive robust design for estimating demographic parameters with Mark-resight data

USGS Publications Warehouse

McClintock, B.T.; White, Gary C.

2009-01-01

The robust design has become popular among animal ecologists as a means for estimating population abundance and related demographic parameters with mark-recapture data. However, two drawbacks of traditional mark-recapture are financial cost and repeated disturbance to animals. Mark-resight methodology may in many circumstances be a less expensive and less invasive alternative to mark-recapture, but the models developed to date for these data have overwhelmingly concentrated only on the estimation of abundance. Here we introduce a mark-resight model analogous to that used in mark-recapture for the simultaneous estimation of abundance, apparent survival, and transition probabilities between observable and unobservable states. The model may be implemented using standard statistical computing software, but it has also been incorporated into the freeware package Program MARK. We illustrate the use of our model with mainland New Zealand Robin (Petroica australis) data collected to ascertain whether this methodology may be a reliable alternative for monitoring endangered populations of a closely related species inhabiting the Chatham Islands. We found this method to be a viable alternative to traditional mark-recapture when cost or disturbance to species is of particular concern in long-term population monitoring programs. ?? 2009 by the Ecological Society of America.

A Novel Interactive Exoskeletal Robot for Overground Locomotion Studies in Rats.

PubMed

Song, Yun Seong; Hogan, Neville

2015-07-01

This paper introduces a newly developed apparatus, Iron Rat, for locomotion research in rodents. Its main purpose is to allow maximal freedom of voluntary overground movement of the animal while providing forceful interaction to the hindlimbs. Advantages and challenges of the proposed exoskeletal apparatus over other existing designs are discussed. Design and implementation challenges are presented and discussed, emphasizing their implications for free, voluntary movement of the animal. A live-animal experiment was conducted to assess the design. Unconstrained natural movement of the animal was compared with its movement with the exoskeletal module attached. The compact design and back-drivable implementation of this apparatus will allow novel experimental manipulations that may include forceful yet compliant dynamic interaction with the animal's overground locomotion.

9 CFR 592.5 - Designation of official certificates, memoranda, marks, other identifications, and devices for...

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Designation of official certificates... Section 592.5 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... class, quality, quantity, or condition specified in this part or any symbol, stamp, label, or seal...

9 CFR 592.5 - Designation of official certificates, memoranda, marks, other identifications, and devices for...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Designation of official certificates... Section 592.5 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... class, quality, quantity, or condition specified in this part or any symbol, stamp, label, or seal...

Designating Domestic Terrorist Individuals or Groups

DTIC Science & Technology

2010-09-01

77 V. STOP HUNTINGDON ANIMAL CRUELTY (SHAC) CASE STUDY: A FOCUS ON THE VULNERABILITIES...designated terrorist SHAC Stop Huntingdon Animal Cruelty SMART Sex Offender Sentencing, Monitoring, Apprehending, Registering, and Tracking SORNA...generalizations (p. 136). The first case study analyzed the activities of an Animal Rights Extremist Group known as Stop Huntingdon Animal Cruelty (SHAC

9 CFR 306.1 - Designation of circuit supervisor and assistants.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Designation of circuit supervisor and assistants. 306.1 Section 306.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION...

9 CFR 306.1 - Designation of circuit supervisor and assistants.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Designation of circuit supervisor and assistants. 306.1 Section 306.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION...

9 CFR 306.1 - Designation of circuit supervisor and assistants.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Designation of circuit supervisor and assistants. 306.1 Section 306.1 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION...

9 CFR 381.221 - Designation of States under paragraph 5(c) of the Act.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Designation of States under paragraph 5(c) of the Act. 381.221 Section 381.221 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY...

Learning Inverse Rig Mappings by Nonlinear Regression.

PubMed

Holden, Daniel; Saito, Jun; Komura, Taku

2017-03-01

We present a framework to design inverse rig-functions-functions that map low level representations of a character's pose such as joint positions or surface geometry to the representation used by animators called the animation rig. Animators design scenes using an animation rig, a framework widely adopted in animation production which allows animators to design character poses and geometry via intuitive parameters and interfaces. Yet most state-of-the-art computer animation techniques control characters through raw, low level representations such as joint angles, joint positions, or vertex coordinates. This difference often stops the adoption of state-of-the-art techniques in animation production. Our framework solves this issue by learning a mapping between the low level representations of the pose and the animation rig. We use nonlinear regression techniques, learning from example animation sequences designed by the animators. When new motions are provided in the skeleton space, the learned mapping is used to estimate the rig controls that reproduce such a motion. We introduce two nonlinear functions for producing such a mapping: Gaussian process regression and feedforward neural networks. The appropriate solution depends on the nature of the rig and the amount of data available for training. We show our framework applied to various examples including articulated biped characters, quadruped characters, facial animation rigs, and deformable characters. With our system, animators have the freedom to apply any motion synthesis algorithm to arbitrary rigging and animation pipelines for immediate editing. This greatly improves the productivity of 3D animation, while retaining the flexibility and creativity of artistic input.

Modeling human diseases: an education in interactions and interdisciplinary approaches.

PubMed

Zon, Leonard

2016-06-01

Traditionally, most investigators in the biomedical arena exploit one model system in the course of their careers. Occasionally, an investigator will switch models. The selection of a suitable model system is a crucial step in research design. Factors to consider include the accuracy of the model as a reflection of the human disease under investigation, the numbers of animals needed and ease of husbandry, its physiology and developmental biology, and the ability to apply genetics and harness the model for drug discovery. In my lab, we have primarily used the zebrafish but combined it with other animal models and provided a framework for others to consider the application of developmental biology for therapeutic discovery. Our interdisciplinary approach has led to many insights into human diseases and to the advancement of candidate drugs to clinical trials. Here, I draw on my experiences to highlight the importance of combining multiple models, establishing infrastructure and genetic tools, forming collaborations, and interfacing with the medical community for successful translation of basic findings to the clinic. © 2016. Published by The Company of Biologists Ltd.

Tissue engineering of the bladder--reality or myth? A systematic review.

PubMed

Sloff, Marije; Simaioforidis, Vasileios; de Vries, Rob; Oosterwijk, Egbert; Feitz, Wout

2014-10-01

We systematically reviewed preclinical studies in the literature to evaluate the potential of tissue engineering of the bladder. Study outcomes were compared to the available clinical evidence to assess the feasibility of tissue engineering for future clinical use. Preclinical studies of tissue engineering for bladder augmentation were identified through a systematic search of PubMed and Embase™ from January 1, 1980 to January 1, 2014. Primary studies in English were included if bladder reconstruction after partial cystectomy was performed using a tissue engineered biomaterial in any animal species, with cystometric bladder capacity as an outcome measure. Outcomes were compared to clinical studies available at http://www.clinicaltrials.gov and published clinical studies. A total of 28 preclinical studies are included, demonstrating remarkable heterogeneity in study characteristics and design. Studies in which preoperative bladder volumes were compared to postoperative volumes were considered the most clinically relevant (18 studies). Bladder augmentation through tissue engineering resulted in a normal bladder volume in healthy animals, with the influence of a cellular component being negligible. Furthermore, experiments in large animal models (pigs and dogs) approximated the desired bladder volume more accurately than in smaller species. The initial clinical experience was based on seemingly predictive healthy animal models with a promising outcome. Unfortunately these results were not substantiated in all clinical trials, revealing dissimilar outcomes in different clinical/disease backgrounds. Thus, the translational predictability of a model using healthy animals might be questioned. Through this systematic approach we present an unbiased overview of all published preclinical studies investigating the effect of bladder tissue engineering on cystometric bladder capacity. Preclinical research in healthy animals appears to show the feasibility of bladder augmentation by tissue engineering. However, in view of the disappointing clinical results based on healthy animal models new approaches should also be evaluated in preclinical models using dysfunctional/diseased bladders. This endeavor may aid in the development of clinically applicable tissue engineered bladder augmentation with satisfactory long-term outcome. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Visually based path-planning by Japanese monkeys.

PubMed

Mushiake, H; Saito, N; Sakamoto, K; Sato, Y; Tanji, J

2001-03-01

To construct an animal model of strategy formation, we designed a maze path-finding task. First, we asked monkeys to capture a goal in the maze by moving a cursor on the screen. Cursor movement was linked to movements of each wrist. When the animals learned the association between cursor movement and wrist movement, we established a start and a goal in the maze, and asked them to find a path between them. We found that the animals took the shortest pathway, rather than approaching the goal randomly. We further found that the animals adopted a strategy of selecting a fixed intermediate point in the visually presented maze to select one of the shortest pathways, suggesting a visually based path planning. To examine their capacity to use that strategy flexibly, we transformed the task by blocking pathways in the maze, providing a problem to solve. The animals then developed a strategy of solving the problem by planning a novel shortest path from the start to the goal and rerouting the path to bypass the obstacle.

Learning Science through Creating a `Slowmation': A case study of preservice primary teachers

NASA Astrophysics Data System (ADS)

Hoban, Garry; Nielsen, Wendy

2013-01-01

Many preservice primary teachers have inadequate science knowledge, which often limits their confidence in implementing the subject. This paper proposes a new way for preservice teachers to learn science by designing and making a narrated stop-motion animation as an instructional resource to explain a science concept. In this paper, a simplified way for preservice teachers to design and make an animation called 'slowmation' (abbreviated from 'slow animation') is exemplified. A case study of three preservice primary teachers creating one from start to finish over 2 h was conducted to address the following research question: How do the preservice primary teachers create a slowmation and how does this process influence their science learning? The method of inquiry used a case study design involving pre- and post-individual interviews in conjunction with a discourse analysis of video and audio data recorded as they created a slowmation. The data illustrate how the preservice teachers' science learning was related to their prior knowledge and how they iteratively revisited the content through the construction of five representations as a cumulative semiotic progression: (i) research notes; (ii) storyboard; (iii) models; (iv) digital photographs; culminating in (v) the narrated animation. This progression enabled the preservice teachers to revisit the content in each representation and make decisions about which modes to use and promoted social interaction. Creating a slowmation facilitated the preservice teachers' learning about the life cycle of a ladybird beetle and revised their alternative conceptions.

Testing flow diversion in animal models: a systematic review.

PubMed

Fahed, Robert; Raymond, Jean; Ducroux, Célina; Gentric, Jean-Christophe; Salazkin, Igor; Ziegler, Daniela; Gevry, Guylaine; Darsaut, Tim E

2016-04-01

Flow diversion (FD) is increasingly used to treat intracranial aneurysms. We sought to systematically review published studies to assess the quality of reporting and summarize the results of FD in various animal models. Databases were searched to retrieve all animal studies on FD from 2000 to 2015. Extracted data included species and aneurysm models, aneurysm and neck dimensions, type of flow diverter, occlusion rates, and complications. Articles were evaluated using a checklist derived from the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. Forty-two articles reporting the results of FD in nine different aneurysm models were included. The rabbit elastase-induced aneurysm model was the most commonly used, with 3-month occlusion rates of 73.5%, (95%CI [61.9-82.6%]). FD of surgical sidewall aneurysms, constructed in rabbits or canines, resulted in high occlusion rates (100% [65.5-100%]). FD resulted in modest occlusion rates (15.4% [8.9-25.1%]) when tested in six complex canine aneurysm models designed to reproduce more difficult clinical contexts (large necks, bifurcation, or fusiform aneurysms). Adverse events, including branch occlusion, were rarely reported. There were no hemorrhagic complications. Articles complied with 20.8 ± 3.9 of 41 ARRIVE items; only a small number used randomization (3/42 articles [7.1%]) or a control group (13/42 articles [30.9%]). Preclinical studies on FD have shown various results. Occlusion of elastase-induced aneurysms was common after FD. The model is not challenging but standardized in many laboratories. Failures of FD can be reproduced in less standardized but more challenging surgical canine constructions. The quality of reporting could be improved.

Ensuring animal welfare while meeting scientific aims using a murine pneumonia model of septic shock.

PubMed

Huet, Olivier; Ramsey, Debbie; Miljavec, Sandra; Jenney, Adam; Aubron, Cecile; Aprico, Andrea; Stefanovic, Nada; Balkau, Beverley; Head, Geoff A; de Haan, Judy B; Chin-Dusting, Jaye P F

2013-06-01

With animal models, death as an intentional end point is ethically unacceptable. However, in the study of septic shock, death is still considered the only relevant end point. We defined eight humane end points into four stages of severity (from healthy to moribund) and used to design a clinically relevant scoring tool, termed "the mouse clinical assessment score for sepsis" (M-CASS). The M-CASS was used to enable a consistent approach to the assessment of disease severity. This allowed an ethical and objective assessment of disease after which euthanasia was performed, instead of worsening suffering. The M-CASS displayed a high internal consistency (Cronbach α = 0.97) with a high level of agreement and an intraclass correlation coefficient equal to 0.91. The plasma levels of cytokines and markers of oxidative stress were all associated with the M-CASS score (Kruskal-Wallis test, P < 0.05). The M-CASS allows tracking of disease progression and animal welfare requirements.

Around Marshall

NASA Image and Video Library

1993-09-15

Virtual Reality (VR) can provide cost effective methods to design and evaluate components and systems for maintenance and refurbishment operations. The Marshall Space Flight Centerr (MSFC) in Huntsville, Alabama began to utilize VR for design analysis in the X-34 experimental reusable space vehicle. Analysts at MSFC's Computer Applications and Virtual Environments (CAVE) used Head Mounted Displays (HMD) (pictured), spatial trackers and gesture inputs as a means to animate or inhabit a properly sized virtual human model. These models were used in a VR scenario as a way to determine functionality of space and maintenance requirements for the virtual X-34. The primary functions of the virtual X-34 mockup was to support operations development and design analysis for engine removal, the engine compartment and the aft fuselage. This capability provided general visualization support to engineers and designers at MSFC and to the System Design Freeze Review at Orbital Sciences Corporation (OSC). The X-34 program was cancelled in 2001.

Around Marshall

NASA Image and Video Library

1993-09-15

Virtual Reality (VR) can provide cost effective methods to design and evaluate components and systems for maintenance and refurbishment operations. The Marshall Space Flight Center (MSFC) in Huntsville, Alabama began to utilize VR for design analysis in the X-34 experimental reusable space vehicle. Analysts at MSFC's Computer Applications and Virtual Environments (CAVE) used Head Mounted Displays (HMD) (pictured), spatial trackers and gesture inputs as a means to animate or inhabit a properly sized virtual human model. These models were used in a VR scenario as a way to determine functionality of space and maintenance requirements for the virtual X-34. The primary functions of the virtual X-34 mockup was to support operations development and design analysis for engine removal, the engine compartment and the aft fuselage. This capability providedgeneral visualization support to engineers and designers at MSFC and to the System Design Freeze Review at Orbital Sciences Corporation (OSC). The X-34 program was cancelled in 2001.

Marshall Engineers Use Virtual Reality

NASA Technical Reports Server (NTRS)

1993-01-01

Virtual Reality (VR) can provide cost effective methods to design and evaluate components and systems for maintenance and refurbishment operations. Marshall Spce Flight Center (MSFC) is begirning to utilize VR for design analysis in the X-34 experimental reusable space vehicle. Analysts at MSFC's Computer Applications and Virtual Environments (CAVE) used Head Mounted Displays (HMD) (pictured), spatial trackers and gesture inputs as a means to animate or inhabit a properly sized virtual human model. These models are used in a VR scenario as a way to determine functionality of space and maintenance requirements for the virtual X-34. The primary functions of the virtual X-34 mockup is to support operations development and design analysis for engine removal, the engine compartment and the aft fuselage. This capability provides general visualization support to engineers and designers at MSFC and to the System Design Freeze Review at Orbital Sciences Corporation (OSC).

Computer Applications and Virtual Environments (CAVE)

NASA Technical Reports Server (NTRS)

1993-01-01

Virtual Reality (VR) can provide cost effective methods to design and evaluate components and systems for maintenance and refurbishment operations. Marshall SPace Flight Center (MSFC) is begirning to utilize VR for design analysis in the X-34 experimental reusable space vehicle. Analysts at MSFC's Computer Applications and Virtual Environments (CAVE) used Head Mounted Displays (HMD) (pictured), spatial trackers and gesture inputs as a means to animate or inhabit a properly sized virtual human model. These models are used in a VR scenario as a way to determine functionality of space and maintenance requirements for the virtual X-34. The primary functions of the virtual X-34 mockup is to support operations development and design analysis for engine removal, the engine compartment and the aft fuselage. This capability provides general visualization support to engineers and designers at MSFC and to the System Design Freeze Review at Orbital Sciences Corporation (OSC).

ComputerApplications and Virtual Environments (CAVE)

NASA Technical Reports Server (NTRS)

1993-01-01

Virtual Reality (VR) can provide cost effective methods to design and evaluate components and systems for maintenance and refurbishment operations. The Marshall Space Flight Center (MSFC) in Huntsville, Alabama began to utilize VR for design analysis in the X-34 experimental reusable space vehicle. Analysts at MSFC's Computer Applications and Virtual Environments (CAVE) used Head Mounted Displays (HMD) (pictured), spatial trackers and gesture inputs as a means to animate or inhabit a properly sized virtual human model. These models were used in a VR scenario as a way to determine functionality of space and maintenance requirements for the virtual X-34. The primary functions of the virtual X-34 mockup was to support operations development and design analysis for engine removal, the engine compartment and the aft fuselage. This capability providedgeneral visualization support to engineers and designers at MSFC and to the System Design Freeze Review at Orbital Sciences Corporation (OSC). The X-34 program was cancelled in 2001.

ComputerApplications and Virtual Environments (CAVE)

NASA Technical Reports Server (NTRS)

1993-01-01

Virtual Reality (VR) can provide cost effective methods to design and evaluate components and systems for maintenance and refurbishment operations. The Marshall Space Flight Centerr (MSFC) in Huntsville, Alabama began to utilize VR for design analysis in the X-34 experimental reusable space vehicle. Analysts at MSFC's Computer Applications and Virtual Environments (CAVE) used Head Mounted Displays (HMD) (pictured), spatial trackers and gesture inputs as a means to animate or inhabit a properly sized virtual human model. These models were used in a VR scenario as a way to determine functionality of space and maintenance requirements for the virtual X-34. The primary functions of the virtual X-34 mockup was to support operations development and design analysis for engine removal, the engine compartment and the aft fuselage. This capability provided general visualization support to engineers and designers at MSFC and to the System Design Freeze Review at Orbital Sciences Corporation (OSC). The X-34 program was cancelled in 2001.

Group Housing During Hindlimb Unloading to Simulate Weightlessness

NASA Technical Reports Server (NTRS)

Tahimic, Candice; Lowe, Moniece; Steczina, Sonette; Torres, Samantha; Terada, Masahiro; Schreurs, Ann-Sofie; Ronca, April; Alwood, Joshua; Globus, Ruth K.

2017-01-01

The rodent hindlimb unloading (HU) model was developed in the 1980s to faciliate the study of mechanisms, responses, and treatments for the adverse effects of spaceflight. A number of variations on unloading systems and cage designs have been developed, although most entail individually housing the HU animals. In this study, we performed hindlimb unloading under group housing conditions. Our preliminary results indicate that HU animals that were group housed for 30 days, displayed musculoskeletal decrements associated with disuse, and further, body weights did not differ compared to age-matched controls. In conclusion, group housing of HU mice provides a novel means to simulate weightlessness under conditions that more closely resemble living conditions of Rodent Research Project ISS flight hardware habitats, and minimizes the social stress of isolation, which is consistent with current animal welfare standards (Guide for the Care and Use of Laboratory Animals: Eighth Edition, National Research Council).

Senior Laboratory Animal Technician | Center for Cancer Research

Cancer.gov

PROGRAM DESCRIPTION The Laboratory Animal Sciences Program (LASP) provides exceptional quality animal care and technical support services for animal research performed at the National Cancer Institute at the Frederick National Laboratory for Cancer Research. LASP executes this mission by providing a broad spectrum of state-of-the-art technologies and services that are focused on the design, generation, characterization and application of genetically engineered and biological animal models of human disease, which are aimed at the development of targeted diagnostics and therapies. LASP contributes to advancing human health, developing new treatments, and improving existing treatments for cancer and other diseases while ensuring safe and humane treatment of animals. KEY ROLES/RESPONSIBILITIES The Senior Laboratory Animal Technician will be responsible for: Daily tasks associated with the care, breeding and treatment of research animals for experimental purposes Management of rodent breeding colonies consisting of multiple, genetically complex strains and associated record keeping and database management Colony management procedures including: tail clipping, animal identification, weaning Data entry consistent with complex colony management Collection of routine diagnostic samples Coordinating shipment of live animals and specimens Performing rodent experimental procedures including basic necropsy and blood collection Observation and recording of physical signs of animal health Knowledge of safe working practices using chemical carcinogen and biological hazards Work schedule may include weekend and holiday hours This position is in support of the Center for Cancer Research (CCR).

Scientific uses of animals: harm-benefit analysis and complementary approaches to implementing the three Rs.

PubMed

Griffin, G; Clark, J MacArthur; Zurlo, J; Ritskes-Hoitinga, M

2014-04-01

The principles of humane experimental technique, first described by Russell and Burch in 1959, focus on minimising suffering to animals used for scientific purposes. Internationally, as these principles became embedded in the various systems of oversight for the use of animals in science, attention focused on how to minimise pain, distress and lasting harm to animals while maximising the benefits to be obtained from the work. Suffering can arise from the experimental procedures, but it can also arise from the manner in which the animals are housed and cared for. Increased attention is therefore being paid to the entire lifetime experience of an animal, in order to afford it as good a quality of life as possible. Russell and Burch were also concerned that animals should not be used if alternatives to such use were available, and that animals were not wasted through poor-quality science. This concept is being revisited through new efforts to ensure that experiments are well designed and properly reported in the literature, that all results--positive, negative or neutral--are made available to ensure a complete research record, and that animal models are properly evaluated through periodic systematic reviews. These efforts should ensure that animal use is truly reduced as far as possible and that the benefits derived through the use of animals truly outweigh the harms.

Ethical use of animal models in musculoskeletal research.

PubMed

Allen, Matthew J; Hankenson, Kurt D; Goodrich, Laurie; Boivin, Gregory P; von Rechenberg, Brigitte

2017-04-01

The use of animals in research is under increasing scrutiny from the general public, funding agencies, and regulatory authorities. Our ability to continue to perform in-vivo studies in laboratory animals will be critically determined by how researchers respond to this new reality. This Perspectives article summarizes recent and ongoing initiatives within ORS and allied organizations to ensure that musculoskeletal research is performed to the highest ethical standards. It goes on to present an overview of the practical application of the 3Rs (reduction, refinement, and replacement) into experimental design and execution, and discusses recent guidance with regard to improvements in the way in which animal data are reported in publications. The overarching goal of this review is to challenge the status quo, to highlight the absolute interdependence between animal welfare and rigorous science, and to provide practical recommendations and resources to allow clinicians and scientists to optimize the ways in which they undertake preclinical studies involving animals. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:740-751, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Advances and Limitations of Disease Biogeography Using Ecological Niche Modeling

PubMed Central

Escobar, Luis E.; Craft, Meggan E.

2016-01-01

Mapping disease transmission risk is crucial in public and animal health for evidence based decision-making. Ecology and epidemiology are highly related disciplines that may contribute to improvements in mapping disease, which can be used to answer health related questions. Ecological niche modeling is increasingly used for understanding the biogeography of diseases in plants, animals, and humans. However, epidemiological applications of niche modeling approaches for disease mapping can fail to generate robust study designs, producing incomplete or incorrect inferences. This manuscript is an overview of the history and conceptual bases behind ecological niche modeling, specifically as applied to epidemiology and public health; it does not pretend to be an exhaustive and detailed description of ecological niche modeling literature and methods. Instead, this review includes selected state-of-the-science approaches and tools, providing a short guide to designing studies incorporating information on the type and quality of the input data (i.e., occurrences and environmental variables), identification and justification of the extent of the study area, and encourages users to explore and test diverse algorithms for more informed conclusions. We provide a friendly introduction to the field of disease biogeography presenting an updated guide for researchers looking to use ecological niche modeling for disease mapping. We anticipate that ecological niche modeling will soon be a critical tool for epidemiologists aiming to map disease transmission risk, forecast disease distribution under climate change scenarios, and identify landscape factors triggering outbreaks. PMID:27547199

Advances and Limitations of Disease Biogeography Using Ecological Niche Modeling.

PubMed

Escobar, Luis E; Craft, Meggan E

2016-01-01

Mapping disease transmission risk is crucial in public and animal health for evidence based decision-making. Ecology and epidemiology are highly related disciplines that may contribute to improvements in mapping disease, which can be used to answer health related questions. Ecological niche modeling is increasingly used for understanding the biogeography of diseases in plants, animals, and humans. However, epidemiological applications of niche modeling approaches for disease mapping can fail to generate robust study designs, producing incomplete or incorrect inferences. This manuscript is an overview of the history and conceptual bases behind ecological niche modeling, specifically as applied to epidemiology and public health; it does not pretend to be an exhaustive and detailed description of ecological niche modeling literature and methods. Instead, this review includes selected state-of-the-science approaches and tools, providing a short guide to designing studies incorporating information on the type and quality of the input data (i.e., occurrences and environmental variables), identification and justification of the extent of the study area, and encourages users to explore and test diverse algorithms for more informed conclusions. We provide a friendly introduction to the field of disease biogeography presenting an updated guide for researchers looking to use ecological niche modeling for disease mapping. We anticipate that ecological niche modeling will soon be a critical tool for epidemiologists aiming to map disease transmission risk, forecast disease distribution under climate change scenarios, and identify landscape factors triggering outbreaks.

An integrated theoretical-experimental approach to accelerate translational tissue engineering.

PubMed

Coy, Rachel H; Evans, Owen R; Phillips, James B; Shipley, Rebecca J

2018-01-01

Implantable devices utilizing bioengineered tissue are increasingly showing promise as viable clinical solutions. The design of bioengineered constructs is currently directed according to the results of experiments that are used to test a wide range of different combinations and spatial arrangements of biomaterials, cells and chemical factors. There is an outstanding need to accelerate the design process and reduce financial costs, whilst minimizing the required number of animal-based experiments. These aims could be achieved through the incorporation of mathematical modelling as a preliminary design tool. Here we focus on tissue-engineered constructs for peripheral nerve repair, which are designed to aid nerve and blood vessel growth and repair after peripheral nerve injury. We offer insight into the role that mathematical modelling can play within tissue engineering, and motivate the use of modelling as a tool capable of improving and accelerating the design of nerve repair constructs in particular. Specific case studies are presented in order to illustrate the potential of mathematical modelling to direct construct design. Copyright © 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd. Copyright © 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd.

Rational design of a topical androgen receptor antagonist for the suppression of sebum production with properties suitable for follicular delivery.

PubMed

Mitchell, Lorna H; Johnson, Theodore R; Lu, Guang Wei; Du, Daniel; Datta, Kaushik; Grzemski, Felicity; Shanmugasundaram, Veerabahu; Spence, Julie; Wade, Kim; Wang, Zhi; Sun, Kevin; Lin, Kristin; Hu, Lain-Yen; Sexton, Karen; Raheja, Neil; Kostlan, Catherine; Pocalyko, David

2010-06-10

A novel nonsteroidal androgen receptor antagonist, (R)-4-(1-benzyl-4,4-dimethyl-2-oxopyrrolidin-3-yloxy)-2-(trifluoromethyl)benzonitrile (1), for the topical control of sebum production is reported. This compound, which is potent, selective, and efficacious in the clinically validated golden Syrian hamster ear animal model, was designed to be delivered to the pilosebaceous unit, the site of action, preferentially by the follicular route.

Design and experimental analysis of a new malleovestibulopexy prosthesis using a finite element model of the human middle ear.

PubMed

Vallejo Valdezate, Luis A; Hidalgo Otamendi, Antonio; Hernández, Alberto; Lobo, Fernando; Gil-Carcedo Sañudo, Elisa; Gil-Carcedo García, Luis M

2015-01-01

Many designs of prostheses are available for middle ear surgery. In this study we propose a design for a new prosthesis, which optimises mechanical performance in the human middle ear and improves some deficiencies in the prostheses currently available. Our objective was to design and assess the theoretical acoustic-mechanical behaviour of this new total ossicular replacement prosthesis. The design of this new prosthesis was based on an animal model (an iguana). For the modelling and mechanical analysis of the new prosthesis, we used a dynamic 3D computer model of the human middle ear, based on the finite elements method (FEM). The new malleovestibulopexy prosthesis design demonstrates an acoustical-mechanical performance similar to that of the healthy human middle ear. This new design also has additional advantages, such as ease of implantation and stability in the middle ear. This study shows that computer simulation can be used to design and optimise the vibroacoustic characteristics of middle ear implants and demonstrates the effectiveness of a new malleovestibulopexy prosthesis in reconstructing the ossicular chain. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Otorrinolaringología y Patología Cérvico-Facial. All rights reserved.

A Fully Implantable Pacemaker for the Mouse: From Battery to Wireless Power

PubMed Central

Zellmer, Erik R.; Weinheimer, Carla J.; MacEwan, Matthew R.; Cui, Sophia X.; Nerbonne, Jeanne M.; Efimov, Igor R.

2013-01-01

Animal models have become a popular platform for the investigation of the molecular and systemic mechanisms of pathological cardiovascular physiology. Chronic pacing studies with implantable pacemakers in large animals have led to useful models of heart failure and atrial fibrillation. Unfortunately, molecular and genetic studies in these large animal models are often prohibitively expensive or not available. Conversely, the mouse is an excellent species for studying molecular mechanisms of cardiovascular disease through genetic engineering. However, the large size of available pacemakers does not lend itself to chronic pacing in mice. Here, we present the design for a novel, fully implantable wireless-powered pacemaker for mice capable of long-term (>30 days) pacing. This design is compared to a traditional battery-powered pacemaker to demonstrate critical advantages achieved through wireless inductive power transfer and control. Battery-powered and wireless-powered pacemakers were fabricated from standard electronic components in our laboratory. Mice (n = 24) were implanted with endocardial, battery-powered devices (n = 14) and epicardial, wireless-powered devices (n = 10). Wireless-powered devices were associated with reduced implant mortality and more reliable device function compared to battery-powered devices. Eight of 14 (57.1%) mice implanted with battery-powered pacemakers died following device implantation compared to 1 of 10 (10%) mice implanted with wireless-powered pacemakers. Moreover, device function was achieved for 30 days with the wireless-powered device compared to 6 days with the battery-powered device. The wireless-powered pacemaker system presented herein will allow electrophysiology studies in numerous genetically engineered mouse models as well as rapid pacing-induced heart failure and atrial arrhythmia in mice. PMID:24194832

The effects of sign design features on bicycle pictorial symbols for bicycling facility signs.

PubMed

Oh, Kyunghui; Rogoff, Aaron; Smith-Jackson, Tonya

2013-11-01

The inanimate bicycle symbol has long been used to indicate the animate activity of bicycling facility signs. In contrast, either the inanimate bicycle symbol or the animate bicycle symbol has been used interchangeably for the standard pavement symbols in bike lanes. This has led to confusion among pedestrians and cyclists alike. The purpose of this study was to examine two different designs (inanimate symbol vs. animate symbol) involved in the evaluation of perceived preference and glance legibility, and investigate sign design features on bicycle pictorial symbols. Thirty-five participants compared current bicycle signs (inanimate symbols) to alternative designs (animate symbols) in a controlled laboratory setting. The results indicated that the alternative designs (animate symbols) showed better performance in both preference and glance legibility tests. Conceptual compatibility, familiarity, and perceptual affordances were found to be important factors as well. Copyright © 2013 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Walking model with no energy cost.

PubMed

Gomes, Mario; Ruina, Andy

2011-03-01

We have numerically found periodic collisionless motions of a walking model consisting of linked rigid objects. Unlike previous designs, this model can walk on level ground at noninfinitesimal speed with zero energy input. The model avoids collisional losses by using an internal mode of oscillation: swaying of the upper body coupled to the legs by springs. Appropriate synchronized internal oscillations set the foot-strike collision to zero velocity. The concept might be of use for energy-efficient robots and may also help to explain aspects of human and animal locomotion efficiency.

Threats to validity in the design and conduct of preclinical efficacy studies: a systematic review of guidelines for in vivo animal experiments.

PubMed

Henderson, Valerie C; Kimmelman, Jonathan; Fergusson, Dean; Grimshaw, Jeremy M; Hackam, Dan G

2013-01-01

The vast majority of medical interventions introduced into clinical development prove unsafe or ineffective. One prominent explanation for the dismal success rate is flawed preclinical research. We conducted a systematic review of preclinical research guidelines and organized recommendations according to the type of validity threat (internal, construct, or external) or programmatic research activity they primarily address. We searched MEDLINE, Google Scholar, Google, and the EQUATOR Network website for all preclinical guideline documents published up to April 9, 2013 that addressed the design and conduct of in vivo animal experiments aimed at supporting clinical translation. To be eligible, documents had to provide guidance on the design or execution of preclinical animal experiments and represent the aggregated consensus of four or more investigators. Data from included guidelines were independently extracted by two individuals for discrete recommendations on the design and implementation of preclinical efficacy studies. These recommendations were then organized according to the type of validity threat they addressed. A total of 2,029 citations were identified through our search strategy. From these, we identified 26 guidelines that met our eligibility criteria--most of which were directed at neurological or cerebrovascular drug development. Together, these guidelines offered 55 different recommendations. Some of the most common recommendations included performance of a power calculation to determine sample size, randomized treatment allocation, and characterization of disease phenotype in the animal model prior to experimentation. By identifying the most recurrent recommendations among preclinical guidelines, we provide a starting point for developing preclinical guidelines in other disease domains. We also provide a basis for the study and evaluation of preclinical research practice. Please see later in the article for the Editors' Summary.

9 CFR 354.2 - Designation of official certificates, memoranda, marks, other identifications, and devices for...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Designation of official certificates... Section 354.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... means any symbol, stamp, label, or seal indicating that the product has been officially inspected and/or...

9 CFR 354.2 - Designation of official certificates, memoranda, marks, other identifications, and devices for...

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Designation of official certificates... Section 354.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... means any symbol, stamp, label, or seal indicating that the product has been officially inspected and/or...

Automated Finger Spelling by Highly Realistic 3D Animation

ERIC Educational Resources Information Center

Adamo-Villani, Nicoletta; Beni, Gerardo

2004-01-01

We present the design of a new 3D animation tool for self-teaching (signing and reading) finger spelling the first basic component in learning any sign language. We have designed a highly realistic hand with natural animation of the finger motions. Smoothness of motion (in real time) is achieved via programmable blending of animation segments. The…

9 CFR 592.5 - Designation of official certificates, memoranda, marks, other identifications, and devices for...

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Designation of official certificates, memoranda, marks, other identifications, and devices for purposes of the Agricultural Marketing Act. 592.5 Section 592.5 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION VOLUNTARY...

9 CFR 592.5 - Designation of official certificates, memoranda, marks, other identifications, and devices for...

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Designation of official certificates, memoranda, marks, other identifications, and devices for purposes of the Agricultural Marketing Act. 592.5 Section 592.5 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION VOLUNTARY...

9 CFR 592.5 - Designation of official certificates, memoranda, marks, other identifications, and devices for...

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Designation of official certificates, memoranda, marks, other identifications, and devices for purposes of the Agricultural Marketing Act. 592.5 Section 592.5 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION VOLUNTARY...

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

PubMed

Toyoda, Atsushi

2017-07-01

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

Chemical effects in biological systems (CEBS) object model for toxicology data, SysTox-OM: design and application.

PubMed

Xirasagar, Sandhya; Gustafson, Scott F; Huang, Cheng-Cheng; Pan, Qinyan; Fostel, Jennifer; Boyer, Paul; Merrick, B Alex; Tomer, Kenneth B; Chan, Denny D; Yost, Kenneth J; Choi, Danielle; Xiao, Nianqing; Stasiewicz, Stanley; Bushel, Pierre; Waters, Michael D

2006-04-01

The CEBS data repository is being developed to promote a systems biology approach to understand the biological effects of environmental stressors. CEBS will house data from multiple gene expression platforms (transcriptomics), protein expression and protein-protein interaction (proteomics), and changes in low molecular weight metabolite levels (metabolomics) aligned by their detailed toxicological context. The system will accommodate extensive complex querying in a user-friendly manner. CEBS will store toxicological contexts including the study design details, treatment protocols, animal characteristics and conventional toxicological endpoints such as histopathology findings and clinical chemistry measures. All of these data types can be integrated in a seamless fashion to enable data query and analysis in a biologically meaningful manner. An object model, the SysBio-OM (Xirasagar et al., 2004) has been designed to facilitate the integration of microarray gene expression, proteomics and metabolomics data in the CEBS database system. We now report SysTox-OM as an open source systems toxicology model designed to integrate toxicological context into gene expression experiments. The SysTox-OM model is comprehensive and leverages other open source efforts, namely, the Standard for Exchange of Nonclinical Data (http://www.cdisc.org/models/send/v2/index.html) which is a data standard for capturing toxicological information for animal studies and Clinical Data Interchange Standards Consortium (http://www.cdisc.org/models/sdtm/index.html) that serves as a standard for the exchange of clinical data. Such standardization increases the accuracy of data mining, interpretation and exchange. The open source SysTox-OM model, which can be implemented on various software platforms, is presented here. A universal modeling language (UML) depiction of the entire SysTox-OM is available at http://cebs.niehs.nih.gov and the Rational Rose object model package is distributed under an open source license that permits unrestricted academic and commercial use and is available at http://cebs.niehs.nih.gov/cebsdownloads. Currently, the public toxicological data in CEBS can be queried via a web application based on the SysTox-OM at http://cebs.niehs.nih.gov xirasagars@saic.com Supplementary data are available at Bioinformatics online.

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

PubMed Central

Zhan, Xianbao; Wang, Fan; Bi, Yan

2016-01-01

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

Active walker model for the formation of human and animal trail systems

NASA Astrophysics Data System (ADS)

Helbing, Dirk; Schweitzer, Frank; Keltsch, Joachim; Molnár, Péter

1997-09-01

Active walker models have recently proved their great value for describing the formation of clusters, periodic patterns, and spiral waves as well as the development of rivers, dielectric breakdown patterns, and many other structures. It is shown that they also allow one to simulate the formation of trail systems by pedestrians and ants, yielding a better understanding of human and animal behavior. A comparison with empirical material shows a good agreement between model and reality. Our trail formation model includes an equation of motion, an equation for environmental changes, and an orientation relation. It contains some model functions, which are specified according to the characteristics of the considered animals or pedestrians. Not only the kind of environmental changes differs: Whereas pedestrians leave footprints on the ground, ants produce chemical markings for their orientation. Nevertheless, it is more important that pedestrians steer towards a certain destination, while ants usually find their food sources by chance, i.e., they reach their destination in a stochastic way. As a consequence, the typical structure of the evolving trail systems depends on the respective species. Some ant species produce a dendritic trail system, whereas pedestrians generate a minimal detour system. The trail formation model can be used as a tool for the optimization of pedestrian facilities: It allows urban planners to design convenient way systems which actually meet the route choice habits of pedestrians.

Voluntary exercise enhances activity rhythms and ameliorates anxiety- and depression-like behaviors in the sand rat model of circadian rhythm-related mood changes.

PubMed

Tal-Krivisky, Katy; Kronfeld-Schor, Noga; Einat, Haim

2015-11-01

Physical exercise is a non-pharmacological treatment for affective disorders. The mechanisms of its effects are unknown although some suggest a relationship to synchronization of circadian rhythms. One way to explore mechanisms is to utilize animal models. We previously demonstrated that the diurnal fat sand rat is an advantageous model for studying the interactions between photoperiods and mood. The current study was designed to evaluate the effects of voluntary exercise on activity rhythms and anxiety and depression-like behaviors in sand rats as a step towards better understanding of the underlying mechanisms. Male sand rats were housed in short photoperiod (SP; 5h light/19 h dark) or neutral light (NP; 12h light/12h dark) regimens for 3 weeks and divided into subgroups with or without running wheels. Activity was monitored for 3 additional weeks and then animals were tested in the elevated plus-maze, the forced swim test and the social interaction test. Activity rhythms were enhanced by the running wheels. As hypothesized, voluntary exercise had significant effects on SP animals' anxiety- and depression-like behaviors but not on NP animals. Results are discussed in the context of interactions between physical exercise, circadian rhythms and mood. We suggest that the sand rat model can be used to explore the underlying mechanism of the effects of physical exercise for mood disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Stem cells in animal asthma models: a systematic review.

PubMed

Srour, Nadim; Thébaud, Bernard

2014-12-01

Asthma control frequently falls short of the goals set in international guidelines. Treatment options for patients with poorly controlled asthma despite inhaled corticosteroids and long-acting β-agonists are limited, and new therapeutic options are needed. Stem cell therapy is promising for a variety of disorders but there has been no human clinical trial of stem cell therapy for asthma. We aimed to systematically review the literature regarding the potential benefits of stem cell therapy in animal models of asthma to determine whether a human trial is warranted. The MEDLINE and Embase databases were searched for original studies of stem cell therapy in animal asthma models. Nineteen studies were selected. They were found to be heterogeneous in their design. Mesenchymal stromal cells were used before sensitization with an allergen, before challenge with the allergen and after challenge, most frequently with ovalbumin, and mainly in BALB/c mice. Stem cell therapy resulted in a reduction of bronchoalveolar lavage fluid inflammation and eosinophilia as well as Th2 cytokines such as interleukin-4 and interleukin-5. Improvement in histopathology such as peribronchial and perivascular inflammation, epithelial thickness, goblet cell hyperplasia and smooth muscle layer thickening was universal. Several studies showed a reduction in airway hyper-responsiveness. Stem cell therapy decreases eosinophilic and Th2 inflammation and is effective in several phases of the allergic response in animal asthma models. Further study is warranted, up to human clinical trials. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2009-02-01

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

Application of random effects to the study of resource selection by animals

USGS Publications Warehouse

Gillies, C.S.; Hebblewhite, M.; Nielsen, S.E.; Krawchuk, M.A.; Aldridge, Cameron L.; Frair, J.L.; Saher, D.J.; Stevens, C.E.; Jerde, C.L.

2006-01-01

1. Resource selection estimated by logistic regression is used increasingly in studies to identify critical resources for animal populations and to predict species occurrence.2. Most frequently, individual animals are monitored and pooled to estimate population-level effects without regard to group or individual-level variation. Pooling assumes that both observations and their errors are independent, and resource selection is constant given individual variation in resource availability.3. Although researchers have identified ways to minimize autocorrelation, variation between individuals caused by differences in selection or available resources, including functional responses in resource selection, have not been well addressed.4. Here we review random-effects models and their application to resource selection modelling to overcome these common limitations. We present a simple case study of an analysis of resource selection by grizzly bears in the foothills of the Canadian Rocky Mountains with and without random effects.5. Both categorical and continuous variables in the grizzly bear model differed in interpretation, both in statistical significance and coefficient sign, depending on how a random effect was included. We used a simulation approach to clarify the application of random effects under three common situations for telemetry studies: (a) discrepancies in sample sizes among individuals; (b) differences among individuals in selection where availability is constant; and (c) differences in availability with and without a functional response in resource selection.6. We found that random intercepts accounted for unbalanced sample designs, and models with random intercepts and coefficients improved model fit given the variation in selection among individuals and functional responses in selection. Our empirical example and simulations demonstrate how including random effects in resource selection models can aid interpretation and address difficult assumptions limiting their generality. This approach will allow researchers to appropriately estimate marginal (population) and conditional (individual) responses, and account for complex grouping, unbalanced sample designs and autocorrelation.

Application of random effects to the study of resource selection by animals.

PubMed

Gillies, Cameron S; Hebblewhite, Mark; Nielsen, Scott E; Krawchuk, Meg A; Aldridge, Cameron L; Frair, Jacqueline L; Saher, D Joanne; Stevens, Cameron E; Jerde, Christopher L

2006-07-01

1. Resource selection estimated by logistic regression is used increasingly in studies to identify critical resources for animal populations and to predict species occurrence. 2. Most frequently, individual animals are monitored and pooled to estimate population-level effects without regard to group or individual-level variation. Pooling assumes that both observations and their errors are independent, and resource selection is constant given individual variation in resource availability. 3. Although researchers have identified ways to minimize autocorrelation, variation between individuals caused by differences in selection or available resources, including functional responses in resource selection, have not been well addressed. 4. Here we review random-effects models and their application to resource selection modelling to overcome these common limitations. We present a simple case study of an analysis of resource selection by grizzly bears in the foothills of the Canadian Rocky Mountains with and without random effects. 5. Both categorical and continuous variables in the grizzly bear model differed in interpretation, both in statistical significance and coefficient sign, depending on how a random effect was included. We used a simulation approach to clarify the application of random effects under three common situations for telemetry studies: (a) discrepancies in sample sizes among individuals; (b) differences among individuals in selection where availability is constant; and (c) differences in availability with and without a functional response in resource selection. 6. We found that random intercepts accounted for unbalanced sample designs, and models with random intercepts and coefficients improved model fit given the variation in selection among individuals and functional responses in selection. Our empirical example and simulations demonstrate how including random effects in resource selection models can aid interpretation and address difficult assumptions limiting their generality. This approach will allow researchers to appropriately estimate marginal (population) and conditional (individual) responses, and account for complex grouping, unbalanced sample designs and autocorrelation.

Anti-diabetic effect of Xylopia aethiopica (Dunal) A. Rich. (Annonaceae) fruit acetone fraction in a type 2 diabetes model of rats.

PubMed

Mohammed, Aminu; Koorbanally, Neil Anthony; Islam, Md Shahidul

2016-03-02

In traditional medicine from West Africa, the fruit decoction of Xylopia aethiopica (Dunal) A. Rich. is widely used for the treatment of diabetes mellitus (DM) either alone or in combination with other plants. The present study is designed to investigate the anti-diabetic effects of X. aethiopica acetone fraction (XAAF) from fruit ethanolic extract in a type 2 diabetes (T2D) model of rats. T2D was induced in rats by feeding a 10% fructose solution ad libitum for 2 weeks followed by a single intraperitoneal injection of streptozotocin (40 mg/kg body weight) and the animals were orally treated with 150 or 300 mg/kg body weight (bw) of the XAAF once daily for four weeks. After 4 weeks study period, diabetic untreated animals (DBC) exhibited significantly higher serum glucose, serum fructosamine, LDH, CK-MB, serum lipids, liver glycogen, insulin resistance (HOMA-IR), AI, CRI and lower serum insulin, β-cell function (HOMA-β) and glucose tolerance ability compared to the normal animals. Histopathological examination of their pancreas revealed corresponding pathological changes in the islets and β-cells. These alterations were reverted to near-normal after the treatment of XAAF at 150 (DXAL) and 300 (DXAH) mg/kg bw with the effects being more pronounced in the DXAH group compared to the DXAL group. Moreover, the effects in the animals of DXAH group were comparable to the diabetic metformin (DMF) treated animals. In addition, no significant alterations were observed in non-diabetic animals treated with 300 mg/kg bw of XAAF (NXAH). The results of our study suggest that XAAF treatment showed excellent anti-diabetic effects in a T2D model of rats. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Comparison of Animal Discs Used in Disc Research to Human Lumbar Disc: Torsion Mechanics and Collagen Content

PubMed Central

Showalter, Brent L.; Beckstein, Jesse C.; Martin, John T.; Beattie, Elizabeth E.; Orías, Alejandro A. Espinoza; Schaer, Thomas P.; Vresilovic, Edward J.; Elliott, Dawn M.

2012-01-01

Study Design Experimental measurement and normalization of in vitro disc torsion mechanics and collagen content for several animal species used in intervertebral disc research and comparing these to the human disc. Objective To aid in the selection of appropriate animal models for disc research by measuring torsional mechanical properties and collagen content. Summary of Background Data There is lack of data and variability in testing protocols for comparing animal and human disc torsion mechanics and collagen content. Methods Intervertebral disc torsion mechanics were measured and normalized by disc height and polar moment of inertia for 11 disc types in 8 mammalian species: the calf, pig, baboon, goat, sheep, rabbit, rat, and mouse lumbar, and cow, rat, and mouse caudal. Collagen content was measured and normalized by dry weight for the same discs except the rat and mouse. Collagen fiber stretch in torsion was calculated using an analytical model. Results Measured torsion parameters varied by several orders of magnitude across the different species. After geometric normalization, only the sheep and pig discs were statistically different from human. Fiber stretch was found to be highly dependent on the assumed initial fiber angle. The collagen content of the discs was similar, especially in the outer annulus where only the calf and goat discs were statistically different from human. Disc collagen content did not correlate with torsion mechanics. Conclusion Disc torsion mechanics are comparable to human lumbar discs in 9 of 11 disc types after normalization by geometry. The normalized torsion mechanics and collagen content of the multiple animal discs presented is useful for selecting and interpreting results for animal models of the disc. Structural composition of the disc, such as initial fiber angle, may explain the differences that were noted between species after geometric normalization. PMID:22333953

The Significance of Meaning: Why Do Over 90% of Behavioral Neuroscience Results Fail to Translate to Humans, and What Can We Do to Fix It?

PubMed Central

Garner, Joseph P.

2014-01-01

The vast majority of drugs entering human trials fail. This problem (called “attrition”) is widely recognized as a public health crisis, and has been discussed openly for the last two decades. Multiple recent reviews argue that animals may be just too different physiologically, anatomically, and psychologically from humans to be able to predict human outcomes, essentially questioning the justification of basic biomedical research in animals. This review argues instead that the philosophy and practice of experimental design and analysis is so different in basic animal work and human clinical trials that an animal experiment (as currently conducted) cannot reasonably predict the outcome of a human trial. Thus, attrition does reflect a lack of predictive validity of animal experiments, but it would be a tragic mistake to conclude that animal models cannot show predictive validity. A variety of contributing factors to poor validity are reviewed. The need to adopt methods and models that are highly specific (i.e., which can identify true negative results) in order to complement the current preponderance of highly sensitive methods (which are prone to false positive results) is emphasized. Concepts in biomarker-based medicine are offered as a potential solution, and changes in the use of animal models required to embrace a translational biomarker-based approach are outlined. In essence, this review advocates a fundamental shift, where we treat every aspect of an animal experiment that we can as if it was a clinical trial in a human population. However, it is unrealistic to expect researchers to adopt a new methodology that cannot be empirically justified until a successful human trial. “Validation with known failures” is proposed as a solution. Thus new methods or models can be compared against existing ones using a drug that has translated (a known positive) and one that has failed (a known negative). Current methods should incorrectly identify both as effective, but a more specific method should identify the negative compound correctly. By using a library of known failures we can thereby empirically test the impact of suggested solutions such as enrichment, controlled heterogenization, biomarker-based models, or reverse-translated measures. PMID:25541546

Modelling cognitive affective biases in major depressive disorder using rodents

PubMed Central

Hales, Claire A; Stuart, Sarah A; Anderson, Michael H; Robinson, Emma S J

2014-01-01

Major depressive disorder (MDD) affects more than 10% of the population, although our understanding of the underlying aetiology of the disease and how antidepressant drugs act to remediate symptoms is limited. Major obstacles include the lack of availability of good animal models that replicate aspects of the phenotype and tests to assay depression-like behaviour in non-human species. To date, research in rodents has been dominated by two types of assays designed to test for depression-like behaviour: behavioural despair tests, such as the forced swim test, and measures of anhedonia, such as the sucrose preference test. These tests have shown relatively good predictive validity in terms of antidepressant efficacy, but have limited translational validity. Recent developments in clinical research have revealed that cognitive affective biases (CABs) are a key feature of MDD. Through the development of neuropsychological tests to provide objective measures of CAB in humans, we have the opportunity to use ‘reverse translation’ to develop and evaluate whether similar methods are suitable for research into MDD using animals. The first example of this approach was reported in 2004 where rodents in a putative negative affective state were shown to exhibit pessimistic choices in a judgement bias task. Subsequent work in both judgement bias tests and a novel affective bias task suggest that these types of assay may provide translational methods for studying MDD using animals. This review considers recent work in this area and the pharmacological and translational validity of these new animal models of CABs. Linked Articles This article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-20 PMID:24467454

Human IgG subclass cross-species reactivity to mouse and cynomolgus monkey Fcγ receptors.

PubMed

Derebe, Mehabaw G; Nanjunda, Rupesh K; Gilliland, Gary L; Lacy, Eilyn R; Chiu, Mark L

2018-05-01

In therapeutic antibody discovery and early development, mice and cynomolgus monkey are used as animal models to assess toxicity, efficacy and other properties of candidate molecules. As more candidate antibodies are based on human immunoglobulin (IgG) subclasses, many strategies are pursued to simulate the human system in the test animal. However, translation rate from a successful preclinical trial to an approved drug is extremely low. This may partly be due to differences in interaction of human IgG based candidate molecules to endogenous Fcγ receptors of model animals in comparison to those of human Fcγ receptors. In this study, we compare binding characteristics of human IgG subclasses commonly used in drug development (IgG1, IgG2, IgG4) and their respective Fc silent versions (IgG1σ, IgG2σ, IgG4 PAA) to human, mouse, and cynomolgus monkey Fcγ receptors. To control interactions between Fab and Fc domains, the test IgGs all have the same variable region sequences. We found distinct variations of interaction of human IgG subclasses to model animal Fcγ receptors in comparison to their human counterparts. Particularly, cynomolgus monkey Fcγ receptors showed consistently tighter binding to human IgGs than human Fcγ receptors. Moreover, the presumably Fc silent human IgG4 PAA framework bound to cynomolgus monkey FcγRI with nanomolar affinity while only very weak binding was observed for the human FcγRI. Our results highlighted the need for a thorough in vitro affinity characterization of candidate IgGs against model animal Fcγ receptors and careful design of preclinical studies. Copyright © 2018. Published by Elsevier B.V.

Preclinical evaluation of implantable cardioverter-defibrillator developed for magnetic resonance imaging use.

PubMed

Gold, Michael R; Kanal, Emanuel; Schwitter, Juerg; Sommer, Torsten; Yoon, Hyun; Ellingson, Michael; Landborg, Lynn; Bratten, Tara

2015-03-01

Many patients with an implantable cardioverter-defibrillator (ICD) have indications for magnetic resonance imaging (MRI). However, MRI is generally contraindicated in ICD patients because of potential risks from hazardous interactions between the MRI and ICD system. The purpose of this study was to use preclinical computer modeling, animal studies, and bench and scanner testing to demonstrate the safety of an ICD system developed for 1.5-T whole-body MRI. MRI hazards were assessed and mitigated using multiple approaches: design decisions to increase safety and reliability, modeling and simulation to quantify clinical MRI exposure levels, animal studies to quantify the physiologic effects of MRI exposure, and bench testing to evaluate safety margin. Modeling estimated the incidence of a chronic change in pacing capture threshold >0.5 V and 1.0 V to be less than 1 in 160,000 and less than 1 in 1,000,000 cases, respectively. Modeling also estimated the incidence of unintended cardiac stimulation to occur in less than 1 in 1,000,000 cases. Animal studies demonstrated no delay in ventricular fibrillation detection and no reduction in ventricular fibrillation amplitude at clinical MRI exposure levels, even with multiple exposures. Bench and scanner testing demonstrated performance and safety against all other MRI-induced hazards. A preclinical strategy that includes comprehensive computer modeling, animal studies, and bench and scanner testing predicts that an ICD system developed for the magnetic resonance environment is safe and poses very low risks when exposed to 1.5-T normal operating mode whole-body MRI. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Numerical characterization of a flexible circular coil for magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Bautista, T.; Hernandez, R.; Solis-Najera, S. E.; Rodriguez, A. O.

2012-10-01

Numerical simulations of the magnetic field generated by a flexible surface coil were conducted to study its behavior for applications of animal models at 7 Tesla. This coil design is able to fully cover a volume of interest. The Finite Difference Method in Time Domain (FDTD) was used because of its ability to accurately model complex problems in electromagnetism. This particular coil design is best suited for regions of interests with a spherical shape, since B1 uniformity is not significantly attenuated as in the case of a circular-loop coil. It still remains to investigate the feasibility to actually construct a coil prototype.

The Quadriga Effect Revisited: Designing a “Safety Incision” to Prevent Tendon Repair Rupture and Gap Formation in a Canine Model In Vitro

PubMed Central

Giambini, Hugo; Ikeda, Jun; Amadio, Peter C.; An, Kai-Nan; Zhao, Chunfeng

2012-01-01

Loss of experimental animals due to tendon repair failure results in the need for additional animals to complete the study. We designed a relief proximal to the flexor digitorum profundus (FDP) tendon repair site to serve as a “safety incision” to prevent repair site ruptures and maximize safety incision-to-suture strength. The FDP tendons were dissected in 24 canine forepaws. The 2nd and 5th tendons were lacerated at the proximal interphalangeal joint level and sutured using a modified Kessler technique and peripheral running suture. Tendon width was measured where the FDP tendon separates into each individual digit and a safety incision, equal to the 2nd and 5th tendon widths, was performed 3, 4, or 5 mm (Groups 1, 2, and 3) proximal to the separation. The tendons were pulled at a rate of 1 mm/s until either the “safety incision” ruptured or the repair failed. There was no gap formation at the repair site in Groups 1 and 2. However, all Group 3 tendons failed by repair site rupture with the safety incision intact. An adequate safety incision to protect repair gap and rupture and maintain tendon tension for the FDP animal model should be about 4 mm from where the FDP tendon separates. PMID:20872585

Bone augmentation for cancellous bone- development of a new animal model

PubMed Central

2013-01-01

Background Reproducible and suitable animal models are required for in vivo experiments to investigate new biodegradable and osteoinductive biomaterials for augmentation of bones at risk for osteoporotic fractures. Sheep have especially been used as a model for the human spine due to their size and similar bone metabolism. However, although sheep and human vertebral bodies have similar biomechanical characteristics, the shape of the vertebral bodies, the size of the transverse processes, and the different orientation of the facet joints of sheep are quite different from those of humans making the surgical approach complicated and unpredictable. Therefore, an adequate and safe animal model for bone augmentation was developed using a standardized femoral and tibia augmentation site in sheep. Methods The cancellous bone of the distal femur and proximal tibia were chosen as injection sites with the surgical approach via the medial aspects of the femoral condyle and proximal tibia metaphysis (n = 4 injection sites). For reproducible drilling and injection in a given direction and length, a custom-made c-shaped aiming device was designed. Exact positioning of the aiming device and needle positioning within the intertrabecular space of the intact bone could be validated in a predictable and standardized fashion using fluoroscopy. After sacrifice, bone cylinders (∅ 32 mm) were harvested throughout the tibia and femur by means of a diamond-coated core drill, which was especially developed to harvest the injected bone area exactly. Thereafter, the extracted bone cylinders were processed as non-decalcified specimens for μCT analysis, histomorphometry, histology, and fluorescence evaluation. Results The aiming device could be easily placed in 63 sheep and assured a reproducible, standardized injection area. In four sheep, cardiovascular complications occurred during surgery and pulmonary embolism was detected by computed tomography post surgery in all of these animals. The harvesting and evaluative methods assured a standardized analysis of all samples. Conclusions This experimental animal model provides an excellent basis for testing new biomaterials for their suitability as bone augmentation materials. Concomitantly, similar cardiovascular changes occur during vertebroplasties as in humans, thus making it a suitable animal model for studies related to vertebroplasty. PMID:23819858

Bone augmentation for cancellous bone- development of a new animal model.

PubMed

Klein, Karina; Zamparo, Enrico; Kronen, Peter W; Kämpf, Katharina; Makara, Mariano; Steffen, Thomas; von Rechenberg, Brigitte

2013-07-02

Reproducible and suitable animal models are required for in vivo experiments to investigate new biodegradable and osteoinductive biomaterials for augmentation of bones at risk for osteoporotic fractures. Sheep have especially been used as a model for the human spine due to their size and similar bone metabolism. However, although sheep and human vertebral bodies have similar biomechanical characteristics, the shape of the vertebral bodies, the size of the transverse processes, and the different orientation of the facet joints of sheep are quite different from those of humans making the surgical approach complicated and unpredictable. Therefore, an adequate and safe animal model for bone augmentation was developed using a standardized femoral and tibia augmentation site in sheep. The cancellous bone of the distal femur and proximal tibia were chosen as injection sites with the surgical approach via the medial aspects of the femoral condyle and proximal tibia metaphysis (n = 4 injection sites). For reproducible drilling and injection in a given direction and length, a custom-made c-shaped aiming device was designed. Exact positioning of the aiming device and needle positioning within the intertrabecular space of the intact bone could be validated in a predictable and standardized fashion using fluoroscopy. After sacrifice, bone cylinders (Ø 32 mm) were harvested throughout the tibia and femur by means of a diamond-coated core drill, which was especially developed to harvest the injected bone area exactly. Thereafter, the extracted bone cylinders were processed as non-decalcified specimens for μCT analysis, histomorphometry, histology, and fluorescence evaluation. The aiming device could be easily placed in 63 sheep and assured a reproducible, standardized injection area. In four sheep, cardiovascular complications occurred during surgery and pulmonary embolism was detected by computed tomography post surgery in all of these animals. The harvesting and evaluative methods assured a standardized analysis of all samples. This experimental animal model provides an excellent basis for testing new biomaterials for their suitability as bone augmentation materials. Concomitantly, similar cardiovascular changes occur during vertebroplasties as in humans, thus making it a suitable animal model for studies related to vertebroplasty.

Multiscale optical imaging of rare-earth-doped nanocomposites in a small animal model.

PubMed

Higgins, Laura M; Ganapathy, Vidya; Kantamneni, Harini; Zhao, Xinyu; Sheng, Yang; Tan, Mei-Chee; Roth, Charles M; Riman, Richard E; Moghe, Prabhas V; Pierce, Mark C

2018-03-01

Rare-earth-doped nanocomposites have appealing optical properties for use as biomedical contrast agents, but few systems exist for imaging these materials. We describe the design and characterization of (i) a preclinical system for whole animal in vivo imaging and (ii) an integrated optical coherence tomography/confocal microscopy system for high-resolution imaging of ex vivo tissues. We demonstrate these systems by administering erbium-doped nanocomposites to a murine model of metastatic breast cancer. Short-wave infrared emissions were detected in vivo and in whole organ imaging ex vivo. Visible upconversion emissions and tissue autofluorescence were imaged in biopsy specimens, alongside optical coherence tomography imaging of tissue microstructure. We anticipate that this work will provide guidance for researchers seeking to image these nanomaterials across a wide range of biological models. (2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

Models of sarcopenia: Short review.

PubMed

Palus, S; Springer, J I; Doehner, W; von Haehling, S; Anker, M; Anker, S D; Springer, J

2017-07-01

Approximately 40-50% of the population over 80years of age suffers from sarcopenia making this condition a major geriatric clinical disorder and a key challenge to healthy aging. The hallmark symptom of sarcopenia is the loss of muscle mass and strength without the loss of overall body weight. Sarcopenic patients are likely to have worse clinical outcomes and higher mortality compared to healthy individuals. This review will focus on animal models designed to study sarcopenia including hind-limb unloading, de-nervation, and immobilization by using casts or wire strategies, as well as using aged rodents. Currently there are no registered treatments for sarcopenia. Most sarcopenic individuals show signs of physical frailty, which leads to increases the prevalence of balance disorders, falls, fractures and pain. Therefore, is it essential to develop and use relevant animal models to further the research on sarcopenia therapy? Copyright © 2017 Elsevier B.V. All rights reserved.

Convection-Enhanced Delivery (CED) in an Animal Model of Malignant Peripheral Nerve Sheath Tumors and Plexiform Neurofibromas

DTIC Science & Technology

2013-02-01

successfully establish the xenograft within the sciatic nerve. Convection-Enhanced Delivery ( CED ), Malignant Peripheral Nerve Sheath ( MPNST ), Plexiform...intraneural PNs and MPNST via CED . Design: Orthotopic xenograft models of sciatic intraneural NF1 MPNST and PNs in scid mice as described by Perrin et...using convection-enhanced delivery ( CED ). Relative Growth of MPNST cells in vivo treated with rapamycin, imatinib or erlotinib: Elotinib

The Design and Use of Animal Models for Translational Research in Bone Tissue Engineering and Regenerative Medicine

DTIC Science & Technology

2010-01-07

many domains: mechanical load bearing and force transmission, immunogologic function (leukogenesis and lymphogenesis), mass transport (erythrogenesis...models including NHPs) does not reproduce upright posture of bipedal humans with respect to axial compression and rotational loading in the human lumbar...Schell, M. Mehta, M. A. Schuetz, G. N. Duda, D. W. Hutmacher. 2012. A Tissue Engineering Solution for Segmental Defect Regeneration in Load - Bearing

Designing Empathetic Animated Agents for a B-Learning Training Environment within the Electrical Domain

ERIC Educational Resources Information Center

Hernández, Yasmin; Pérez-Ramírez, Miguel; Zatarain-Cabada, Ramon; Barrón-Estrada, Lucia; Alor-Hernández, Giner

2016-01-01

Electrical tests involve high risk; therefore utility companies require highly qualified electricians and efficient training. Recently, training for electrical tests has been supported by virtual reality systems; nonetheless, these training systems are not yet adaptive. We propose a b-learning model to support adaptive and distance training. The…

Critical Emergency Medicine Procedural Skills: A Comparative Study of Methods for Teaching and Assessment.

ERIC Educational Resources Information Center

Chapman, Dane M.; And Others

Three critical procedural skills in emergency medicine were evaluated using three assessment modalities--written, computer, and animal model. The effects of computer practice and previous procedure experience on skill competence were also examined in an experimental sequential assessment design. Subjects were six medical students, six residents,…

Egg-citing Sixth Graders in Science: A Creative Activity in Cell Structure

ERIC Educational Resources Information Center

Mersch, Margaret; Bryant, Napolean, Jr.

1976-01-01

Sixth-grade pupils at St. Vivian's school recently studied a science lesson on distinguishing between plant and animal cells. Observation of pupils indicated that learning was occurring, but the enthusiasm they had exhibited in earlier science lessons was obviously lacking. Article discussed a model, designed to stimulate learning processes, from…

A Discordant Monozygotic Twin Design Shows Blunted Cortisol Reactivity among Bullied Children

ERIC Educational Resources Information Center

Ouellet-Morin, Isabelle; Danese, Andrea; Bowes, Lucy; Shakoor, Sania; Ambler, Antony; Pariante, Carmine M.; Papadopoulos, Andrew S.; Caspi, Avshalom; Moffitt, Terrie E.; Arseneault, Louise

2011-01-01

Objective: Childhood adverse experiences are known to engender persistent changes in stress-related systems and brain structures involved in mood, cognition, and behavior in animal models. Uncertainty remains about the causal effect of early stressful experiences on physiological response to stress in human beings, as the impact of these…

Automated measurement of mouse social behaviors using depth sensing, video tracking, and machine learning.

PubMed

Hong, Weizhe; Kennedy, Ann; Burgos-Artizzu, Xavier P; Zelikowsky, Moriel; Navonne, Santiago G; Perona, Pietro; Anderson, David J

2015-09-22

A lack of automated, quantitative, and accurate assessment of social behaviors in mammalian animal models has limited progress toward understanding mechanisms underlying social interactions and their disorders such as autism. Here we present a new integrated hardware and software system that combines video tracking, depth sensing, and machine learning for automatic detection and quantification of social behaviors involving close and dynamic interactions between two mice of different coat colors in their home cage. We designed a hardware setup that integrates traditional video cameras with a depth camera, developed computer vision tools to extract the body "pose" of individual animals in a social context, and used a supervised learning algorithm to classify several well-described social behaviors. We validated the robustness of the automated classifiers in various experimental settings and used them to examine how genetic background, such as that of Black and Tan Brachyury (BTBR) mice (a previously reported autism model), influences social behavior. Our integrated approach allows for rapid, automated measurement of social behaviors across diverse experimental designs and also affords the ability to develop new, objective behavioral metrics.

Automated measurement of mouse social behaviors using depth sensing, video tracking, and machine learning

PubMed Central

Hong, Weizhe; Kennedy, Ann; Burgos-Artizzu, Xavier P.; Zelikowsky, Moriel; Navonne, Santiago G.; Perona, Pietro; Anderson, David J.

2015-01-01

A lack of automated, quantitative, and accurate assessment of social behaviors in mammalian animal models has limited progress toward understanding mechanisms underlying social interactions and their disorders such as autism. Here we present a new integrated hardware and software system that combines video tracking, depth sensing, and machine learning for automatic detection and quantification of social behaviors involving close and dynamic interactions between two mice of different coat colors in their home cage. We designed a hardware setup that integrates traditional video cameras with a depth camera, developed computer vision tools to extract the body “pose” of individual animals in a social context, and used a supervised learning algorithm to classify several well-described social behaviors. We validated the robustness of the automated classifiers in various experimental settings and used them to examine how genetic background, such as that of Black and Tan Brachyury (BTBR) mice (a previously reported autism model), influences social behavior. Our integrated approach allows for rapid, automated measurement of social behaviors across diverse experimental designs and also affords the ability to develop new, objective behavioral metrics. PMID:26354123

Hairless pigmented guinea pigs: a new model for the study of mammalian pigmentation.

PubMed

Bolognia, J L; Murray, M S; Pawelek, J M

1990-09-01

A stock of hairless pigmented guinea pigs was developed to facilitate studies of mammalian pigmentation. This stock combines the convenience of a hairless animal with a pigmentary system that is similar to human skin. In both human and guinea pig skin, active melanocytes are located in the basal layer of the interfollicular epidermis. Hairless albino guinea pigs on an outbred Hartley background (CrI:IAF/HA(hr/hr)BR; designated hr/hr) were mated with red-haired guinea pigs (designated Hr/Hr). Red-haired heterozygotes from the F1 generation (Hr/hr) were then mated with each other or with hairless albino guinea pigs. The F2 generation included hairless pigmented guinea pigs that retained their interfollicular epidermal melanocytes and whose skin was red-brown in color. Following UV irradiation, there was an increase in cutaneous pigmentation as well as an increase in the number of active epidermal melanocytes. An additional strain of black hairless guinea pigs was developed using black Hr/Hr animals and a similar breeding scheme. These two strains should serve as useful models for studies of the mammalian pigment system.

Guidelines for pre-clinical animal and cellular models of MuSK-myasthenia gravis.

PubMed

Phillips, W D; Christadoss, P; Losen, M; Punga, A R; Shigemoto, K; Verschuuren, J; Vincent, A

2015-08-01

Muscle-specific tyrosine kinase (MuSK) autoantibodies are the hallmark of a form of myasthenia gravis (MG) that can challenge the neurologist and the experimentalist. The clinical disease can be difficult to treat effectively. MuSK autoantibodies affect the neuromuscular junction in several ways. When added to muscle cells in culture, MuSK antibodies disperse acetylcholine receptor clusters. Experimental animals actively immunized with MuSK develop MuSK autoantibodies and muscle weakness. Weakness is associated with reduced postsynaptic acetylcholine receptor numbers, reduced amplitudes of miniature endplate potentials and endplate potentials, and failure of neuromuscular transmission. Similar impairments have been found in mice injected with IgG from MG patients positive for MuSK autoantibody (MuSK-MG). The active and passive models have begun to reveal the mechanisms by which MuSK antibodies disrupt synaptic function at the neuromuscular junction, and should be valuable in developing therapies for MuSK-MG. However, translation into new and improved treatments for patients requires procedures that are not too cumbersome but suitable for examining different aspects of MuSK function and the effects of potential therapies. Study design, conduct and analysis should be carefully considered and transparently reported. Here we review what has been learnt from animal and culture models of MuSK-MG, and offer guidelines for experimental design and conduct of studies, including sample size determination, randomization, outcome parameters and precautions for objective data analysis. These principles may also be relevant to the increasing number of other antibody-mediated diseases that are now recognized. Copyright © 2014 Elsevier Inc. All rights reserved.

Rational Design of Glucose-Responsive Insulin Using Pharmacokinetic Modeling.

PubMed

Bakh, Naveed A; Bisker, Gili; Lee, Michael A; Gong, Xun; Strano, Michael S

2017-11-01

A glucose responsive insulin (GRI) is a therapeutic that modulates its potency, concentration, or dosing of insulin in relation to a patient's dynamic glucose concentration, thereby approximating aspects of a normally functioning pancreas. Current GRI design lacks a theoretical basis on which to base fundamental design parameters such as glucose reactivity, dissociation constant or potency, and in vivo efficacy. In this work, an approach to mathematically model the relevant parameter space for effective GRIs is induced, and design rules for linking GRI performance to therapeutic benefit are developed. Well-developed pharmacokinetic models of human glucose and insulin metabolism coupled to a kinetic model representation of a freely circulating GRI are used to determine the desired kinetic parameters and dosing for optimal glycemic control. The model examines a subcutaneous dose of GRI with kinetic parameters in an optimal range that results in successful glycemic control within prescribed constraints over a 24 h period. Additionally, it is demonstrated that the modeling approach can find GRI parameters that enable stable glucose levels that persist through a skipped meal. The results provide a framework for exploring the parameter space of GRIs, potentially without extensive, iterative in vivo animal testing. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

PubMed

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

2016-09-01

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

Assessing the effect of immunosuppression on engraftment of pancreatic islets

PubMed Central

Vallabhajosyula, Prashanth; Hirakata, Atsushi; Shimizu, Akira; Okumi, Masayoshi; Tchipashvili, Vaja; Hong, Hanzhou; Yamada, Kazuhiko; Sachs, David H.

2013-01-01

Objective In addition to ischemia and immunologic factors, immunosuppressive drugs have been suggested as a possible contributing factor to the loss of functional islets following allogeneic islet cell transplantation. Using our previously described islet-kidney transplantation model in miniature swine, we studied whether an islet toxic triple-drug immunosuppressive regimen (cyclosporine + azathioprine + prednisone) affects the islet engraftment process and thus long-term islet function. Design and Methods Donor animals underwent partial pancreatectomy, autologous islet preparation and injection of these islets under the autologous kidney capsule to prepare an islet-kidney (IK). Experimental animals received daily triple drug immunosuppression during the islet engraftment period. Control animals did not receive any immunosuppression during this period. Four to eight weeks later, these engrafted IK were transplanted across a minor histocompatibility mismatched barrier into pancreatectomized, nephrectomized recipient animals at an islet dose of ~ 4500 islet equivalents (IE)/kg recipient weight. Cyclosporine was administered for 12 days to the recipients to induce tolerance of the IK grafts and the animals were followed long-term. Results Diabetes was corrected by IK transplantation in all pancreatectomized recipients on both the control (n=3) and the experimental (n=4) arms of the study and all animals showed normal glucose regulation over the follow-up period. Intravenous glucose tolerance tests performed at 1, 2, > 3 months post-IK transplant showed essentially equivalent glycemic control in both control and experimental animals. Conclusion In this pre-clinical, in vivo large animal model of islet transplantation, the effect of triple drug immunosuppression on islet function does not negatively affect islet engraftment, as assessed by the long-term function of engrafted islets. PMID:23883972

The Impact of Designing and Evaluating Molecular Animations on How Well Middle School Students Understand the Particulate Nature of Matter

ERIC Educational Resources Information Center

Chang, Hsin-Yi; Quintana, Chris; Krajcik, Joseph S.

2010-01-01

In this study, we investigated whether the understanding of the particulate nature of matter by students was improved by allowing them to design and evaluate molecular animations of chemical phenomena. We developed Chemation, a learner-centered animation tool, to allow seventh-grade students to construct flipbook-like simple animations to show…

A systematic review and meta-analysis of the ability of analgesic drugs to reduce metastasis in experimental cancer models

PubMed Central

Hooijmans, Carlijn R.; Geessink, Florentine J.; Ritskes-Hoitinga, Merel; Scheffer, Gert-Jan

2015-01-01

Abstract Analgesics are commonly used to manage pain in cancer patients. It has been suggested that there might be a relation between analgesics and the outgrowth of metastases. Opioids might increase and non-steroidal anti-inflammatory drugs decrease the risk of metastasis. Robust analysis of all preclinical evidence, however, has so far been lacking. Therefore, we conducted a systematic review and meta-analysis on the effect of treatment with analgesics on metastasis in experimental animal models. One hundred forty-seven studies met the inclusion criteria. Study characteristics, outcome data on the number, and incidence of metastases were extracted, and methodological quality was assessed. In the meta-analysis, we included 215 (±4000 animals) and 137 (±3000 animals) comparisons between analgesic vs control treatment, respectively, on the number and incidence of metastases. Overall, treatment with analgesics significantly decreases the number and risk of metastasis. This effect appears mainly to be the consequence of the efficacy of NSAIDs. Other factors that modify the efficacy are species, type of NSAIDs administered, timing, and duration of treatment. There is no evidence indicating that treatment with any analgesics increases the occurrence of metastases. Our findings appear robust for the various animal models and designs included in this review, which increases our confidence in the result and translatability to the clinical situation. PMID:26181303

Diffuse fluorescence fiber probe for in vivo detection of circulating cells

NASA Astrophysics Data System (ADS)

Pera, Vivian; Tan, Xuefei; Runnels, Judith; Sardesai, Neha; Lin, Charles P.; Niedre, Mark

2017-03-01

There has been significant recent interest in the development of technologies for enumeration of rare circulating cells directly in the bloodstream in many areas of research, for example, in small animal models of circulating tumor cell dissemination during cancer metastasis. We describe a fiber-based optical probe that allows fluorescence detection of labeled circulating cells in vivo in a diffuse reflectance configuration. We validated this probe in a tissue-mimicking flow phantom model in vitro and in nude mice injected with fluorescently labeled multiple myeloma cells in vivo. Compared to our previous work, this design yields an improvement in detection signal-to-noise ratio of 10 dB, virtually eliminates problematic motion artifacts due to mouse breathing, and potentially allows operation in larger animals and limbs.

Inferring Characteristics of Sensorimotor Behavior by Quantifying Dynamics of Animal Locomotion

NASA Astrophysics Data System (ADS)

Leung, KaWai

Locomotion is one of the most well-studied topics in animal behavioral studies. Many fundamental and clinical research make use of the locomotion of an animal model to explore various aspects in sensorimotor behavior. In the past, most of these studies focused on population average of a specific trait due to limitation of data collection and processing power. With recent advance in computer vision and statistical modeling techniques, it is now possible to track and analyze large amounts of behavioral data. In this thesis, I present two projects that aim to infer the characteristics of sensorimotor behavior by quantifying the dynamics of locomotion of nematode Caenorhabditis elegans and fruit fly Drosophila melanogaster, shedding light on statistical dependence between sensing and behavior. In the first project, I investigate the possibility of inferring noxious sensory information from the behavior of Caenorhabditis elegans. I develop a statistical model to infer the heat stimulus level perceived by individual animals from their stereotyped escape responses after stimulation by an IR laser. The model allows quantification of analgesic-like effects of chemical agents or genetic mutations in the worm. At the same time, the method is able to differentiate perturbations of locomotion behavior that are beyond affecting the sensory system. With this model I propose experimental designs that allows statistically significant identification of analgesic-like effects. In the second project, I investigate the relationship of energy budget and stability of locomotion in determining the walking speed distribution of Drosophila melanogaster during aging. The locomotion stability at different age groups is estimated from video recordings using Floquet theory. I calculate the power consumption of different locomotion speed using a biomechanics model. In conclusion, the power consumption, not stability, predicts the locomotion speed distribution at different ages.

Developing a 3-choice serial reaction time task for examining neural and cognitive function in an equine model.

PubMed

Roberts, Kirsty; Hemmings, Andrew J; McBride, Sebastian D; Parker, Matthew O

2017-12-01

Large animal models of human neurological disorders are advantageous compared to rodent models due to their neuroanatomical complexity, longevity and their ability to be maintained in naturalised environments. Some large animal models spontaneously develop behaviours that closely resemble the symptoms of neural and psychiatric disorders. The horse is an example of this; the domestic form of this species consistently develops spontaneous stereotypic behaviours akin to the compulsive and impulsive behaviours observed in human neurological disorders such as Tourette's syndrome. The ability to non-invasively probe normal and abnormal equine brain function through cognitive testing may provide an extremely useful methodological tool to assess brain changes associated with certain human neurological and psychiatric conditions. An automated operant system with the ability to present visual and auditory stimuli as well as dispense salient food reward was developed. To validate the system, ten horses were trained and tested using a standard cognitive task (three choice serial reaction time task (3-CSRTT)). All animals achieved total learning criterion and performed six probe sessions. Learning criterion was met within 16.30±0.79 sessions over a three day period. During six probe sessions, level of performance was maintained at 80.67±0.57% (mean±SEM) accuracy. This is the first mobile fully automated system developed to examine cognitive function in the horse. A fully-automated operant system for mobile cognitive function of a large animal model has been designed and validated. Horses pose an interesting complementary model to rodents for the examination of human neurological dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

FDA-approved drugs that are spermatotoxic in animals and the utility of animal testing for human risk prediction.

PubMed

Rayburn, Elizabeth R; Gao, Liang; Ding, Jiayi; Ding, Hongxia; Shao, Jun; Li, Haibo

2018-02-01

This study reviews FDA-approved drugs that negatively impact spermatozoa in animals, as well as how these findings reflect on observations in human male gametes. The FDA drug warning labels included in the DailyMed database and the peer-reviewed literature in the PubMed database were searched for information to identify single-ingredient, FDA-approved prescription drugs with spermatotoxic effects. A total of 235 unique, single-ingredient, FDA-approved drugs reported to be spermatotoxic in animals were identified in the drug labels. Forty-nine of these had documented negative effects on humans in either the drug label or literature, while 31 had no effect or a positive impact on human sperm. For the other 155 drugs that were spermatotoxic in animals, no human data was available. The current animal models are not very effective for predicting human spermatotoxicity, and there is limited information available about the impact of many drugs on human spermatozoa. New approaches should be designed that more accurately reflect the findings in men, including more studies on human sperm in vitro and studies using other systems (ex vivo tissue culture, xenograft models, in silico studies, etc.). In addition, the present data is often incomplete or reported in a manner that prevents interpretation of their clinical relevance. Changes should be made to the requirements for pre-clinical testing, drug surveillance, and the warning labels of drugs to ensure that the potential risks to human fertility are clearly indicated.

Pathobiology and management of laboratory rodents administered CDC category A agents.

PubMed

He, Yongqun; Rush, Howard G; Liepman, Rachel S; Xiang, Zuoshuang; Colby, Lesley A

2007-02-01

The Centers for Disease Control and Prevention Category A infectious agents include Bacillus anthracis (anthrax), Clostridium botulinum toxin (botulism), Yersinia pestis (plague), variola major virus (smallpox), Francisella tularensis (tularemia), and the filoviruses and arenaviruses that induce viral hemorrhagic fevers. These agents are regarded as having the greatest potential for adverse impact on public health and therefore are a focus of renewed attention in infectious disease research. Frequently rodent models are used to study the pathobiology of these agents. Although much is known regarding naturally occurring infections in humans, less is documented on the sources of exposures and potential risks of infection to researchers and animal care personnel after the administration of these hazardous substances to laboratory animals. Failure to appropriately manage the animals can result both in the creation of workplace hazards if human exposures occur and in disruption of the research if unintended animal exposures occur. Here we review representative Category A agents, with a focus on comparing the biologic effects in naturally infected humans and rodent models and on considerations specific to the management of infected rodent subjects. The information reviewed for each agent has been curated manually and stored in a unique Internet-based database system called HazARD (Hazards in Animal Research Database, http://helab.bioinformatics.med.umich.edu/hazard/) that is designed to assist researchers, administrators, safety officials, Institutional Biosafety Committees, and veterinary personnel seeking information on the management of risks associated with animal studies involving hazardous substances.

A Hippocampal Cognitive Prosthesis: Multi-Input, Multi-Output Nonlinear Modeling and VLSI Implementation

PubMed Central

Berger, Theodore W.; Song, Dong; Chan, Rosa H. M.; Marmarelis, Vasilis Z.; LaCoss, Jeff; Wills, Jack; Hampson, Robert E.; Deadwyler, Sam A.; Granacki, John J.

2012-01-01

This paper describes the development of a cognitive prosthesis designed to restore the ability to form new long-term memories typically lost after damage to the hippocampus. The animal model used is delayed nonmatch-to-sample (DNMS) behavior in the rat, and the “core” of the prosthesis is a biomimetic multi-input/multi-output (MIMO) nonlinear model that provides the capability for predicting spatio-temporal spike train output of hippocampus (CA1) based on spatio-temporal spike train inputs recorded presynaptically to CA1 (e.g., CA3). We demonstrate the capability of the MIMO model for highly accurate predictions of CA1 coded memories that can be made on a single-trial basis and in real-time. When hippocampal CA1 function is blocked and long-term memory formation is lost, successful DNMS behavior also is abolished. However, when MIMO model predictions are used to reinstate CA1 memory-related activity by driving spatio-temporal electrical stimulation of hippocampal output to mimic the patterns of activity observed in control conditions, successful DNMS behavior is restored. We also outline the design in very-large-scale integration for a hardware implementation of a 16-input, 16-output MIMO model, along with spike sorting, amplification, and other functions necessary for a total system, when coupled together with electrode arrays to record extracellularly from populations of hippocampal neurons, that can serve as a cognitive prosthesis in behaving animals. PMID:22438335

Animal models of Parkinson's disease: limits and relevance to neuroprotection studies.

PubMed

Bezard, Erwan; Yue, Zhenyu; Kirik, Deniz; Spillantini, Maria Grazia

2013-01-01

Over the last two decades, significant strides has been made toward acquiring a better knowledge of both the etiology and pathogenesis of Parkinson's disease (PD). Experimental models are of paramount importance to obtain greater insights into the pathogenesis of the disease. Thus far, neurotoxin-based animal models have been the most popular tools employed to produce selective neuronal death in both in vitro and in vivo systems. These models have been commonly referred to as the pathogenic models. The current trend in modeling PD revolves around what can be called the disease gene-based models or etiologic models. The value of utilizing multiple models with a different mechanism of insult rests on the premise that dopamine-producing neurons die by stereotyped cascades that can be activated by a range of insults, from neurotoxins to downregulation and overexpression of disease-related genes. In this position article, we present the relevance of both pathogenic and etiologic models as well as the concept of clinically relevant designs that, we argue, should be utilized in the preclinical development phase of new neuroprotective therapies before embarking into clinical trials. Copyright © 2013 Movement Disorders Society.

Technology development activities for housing research animals on Space Station Freedom

NASA Technical Reports Server (NTRS)

Jenner, Jeffrey W.; Garin, Vladimir M.; Nguyen, Frank D.

1991-01-01

The development and design of animal facilities are described in terms of the technological needs for NASA's Biological Flight Research Laboratory. Animal habitats are presented with illustrations which encompass waste-collection techniques for microgravity conditions that reduce the need for crew participation. The technology is intended to be highly compatible with animal morphology, and airflow is employed as the primary mechanism of waste control. The airflow can be utilized in the form of localized high-speed directed flow that simultaneously provides a clean animal habitat and low airflow rates. The design of an animal-habitat testbed is presented which capitalizes on contamination-control mechanisms and suitable materials for microgravity conditions. The developments in materials and technologies represent significant contributions for the design of the centrifuge facilities for the Space Station Freedom.

Facilities for animal research in space

NASA Technical Reports Server (NTRS)

Bonting, Sjoerd L.; Kishiyama, Jenny S.; Arno, Roger D.

1991-01-01

The animal facilities used aboard or designed for various spacecraft research missions are described. Consideration is given to the configurations used in Cosmos-1514 (1983) and Cosmos-1887 (1987) missions; the reusable Biosatellite capsule flown three times by NASA between 1966 and 1969; the NASA's Lifesat spacecraft that is being currently designed; the Animal Enclosure Module flown on Shuttle missions in 1983 and 1984; the Research Animal Holding Facility developed for Shuttle-Spacelab missions; the Rhesus Research Facility developed for a Spacelab mission; and the Japanese Animal Holding Facility for the Space Station Freedom. Special attention is given to the designs of NASA's animal facilities developed for Space Station Freedom and the details of various subsystems of these facilities. The main characteristics of the rodent and the primate habitats provided by these various facilities are discussed.

Impact of the 3-D model strategy on science learning of the solar system

NASA Astrophysics Data System (ADS)

Alharbi, Mohammed

The purpose of this mixed method study, quantitative and descriptive, was to determine whether the first-middle grade (seventh grade) students at Saudi schools are able to learn and use the Autodesk Maya software to interact and create their own 3-D models and animations and whether their use of the software influences their study habits and their understanding of the school subject matter. The study revealed that there is value to the science students regarding the use of 3-D software to create 3-D models to complete science assignments. Also, this study aimed to address the middle-school students' ability to learn 3-D software in art class, and then ultimately use it in their science class. The success of this study may open the way to consider the impact of 3-D modeling on other school subjects, such as mathematics, art, and geography. When the students start using graphic design, including 3-D software, at a young age, they tend to develop personal creativity and skills. The success of this study, if applied in schools, will provide the community with skillful young designers and increase awareness of graphic design and the new 3-D technology. Experimental method was used to answer the quantitative research question, are there significant differences applying the learning method using 3-D models (no 3-D, premade 3-D, and create 3-D) in a science class being taught about the solar system and its impact on the students' science achievement scores? Descriptive method was used to answer the qualitative research questions that are about the difficulty of learning and using Autodesk Maya software, time that students take to use the basic levels of Polygon and Animation parts of the Autodesk Maya software, and level of students' work quality.

[REACTIVE CHANGES IN SPINAL CORD MOTONEURONS AFTER SCIATIC NERVE INJURY AFTER HIGH-FREQUENCY ELECTROSURGICAL INSTRUMENT APPLICATION].

PubMed

Korsak, A; Chaikovsky, Yu; Sokurenko, L; Likhodiievskyi, V; Neverovskyi, A

2016-02-01

A new experimental model for tissues connection at peripheral nerve injury site in form of tissues welding was designed. In current study we investigated motoneuron state 1, 3, 6 and 12 weeks after peripheral nerve injury and surgical repair with high-frequency electrosurgical technology. Spinal cord sections was stained by Nissl method and observed with light microscopy. We found that postoperative period in animals from experimental groups characterized by qualitative changes in neurons from spinal motor centers that can be interpreted as compensatory processes as response to alteration. In animals from group with high-frequency electrosurgical technology usage stabilization processes passes more quickly comparatively to animals with epineural sutures. High-frequency electrosurgical technology usage provides less harmful effects on motoneurons than epineural suturing.

Designing a Minimal Intervention Strategy to Control Taenia solium.

PubMed

Lightowlers, Marshall W; Donadeu, Meritxell

2017-06-01

Neurocysticercosis is an important cause of epilepsy in many developing countries. The disease is a zoonosis caused by the cestode parasite Taenia solium. Many potential intervention strategies are available, however none has been able to be implemented and sustained. Here we predict the impact of some T. solium interventions that could be applied to prevent transmission through pigs, the parasite's natural animal intermediate host. These include minimal intervention strategies that are predicted to be effective and likely to be feasible. Logical models are presented which reflect changes in the risk that age cohorts of animals have for their potential to transmit T. solium. Interventions that include a combined application of vaccination, plus chemotherapy in young animals, are the most effective. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Critical evaluation of challenges and future use of animals in experimentation for biomedical research.

PubMed

Singh, Vijay Pal; Pratap, Kunal; Sinha, Juhi; Desiraju, Koundinya; Bahal, Devika; Kukreti, Ritushree

2016-12-01

Animal experiments that are conducted worldwide contribute to significant findings and breakthroughs in the understanding of the underlying mechanisms of various diseases, bringing up appropriate clinical interventions. However, their predictive value is often low, leading to translational failure. Problems like translational failure of animal studies and poorly designed animal experiments lead to loss of animal lives and less translatable data which affect research outcomes ethically and economically. Due to increasing complexities in animal usage with changes in public perception and stringent guidelines, it is becoming difficult to use animals for conducting studies. This review deals with challenges like poor experimental design and ethical concerns and discusses key concepts like sample size, statistics in experimental design, humane endpoints, economic assessment, species difference, housing conditions, and systematic reviews and meta-analyses that are often neglected. If practiced, these strategies can refine the procedures effectively and help translate the outcomes efficiently. © The Author(s) 2016.

Critical evaluation of challenges and future use of animals in experimentation for biomedical research

PubMed Central

Singh, Vijay Pal; Pratap, Kunal; Sinha, Juhi; Desiraju, Koundinya; Bahal, Devika; Kukreti, Ritushree

2016-01-01

Animal experiments that are conducted worldwide contribute to significant findings and breakthroughs in the understanding of the underlying mechanisms of various diseases, bringing up appropriate clinical interventions. However, their predictive value is often low, leading to translational failure. Problems like translational failure of animal studies and poorly designed animal experiments lead to loss of animal lives and less translatable data which affect research outcomes ethically and economically. Due to increasing complexities in animal usage with changes in public perception and stringent guidelines, it is becoming difficult to use animals for conducting studies. This review deals with challenges like poor experimental design and ethical concerns and discusses key concepts like sample size, statistics in experimental design, humane endpoints, economic assessment, species difference, housing conditions, and systematic reviews and meta-analyses that are often neglected. If practiced, these strategies can refine the procedures effectively and help translate the outcomes efficiently. PMID:27694614

Pervasive and opposing effects of Unpredictable Chronic Mild Stress (UCMS) on hippocampal gene expression in BALB/cJ and C57BL/6J mouse strains.

PubMed

Malki, Karim; Mineur, Yann S; Tosto, Maria Grazia; Campbell, James; Karia, Priya; Jumabhoy, Irfan; Sluyter, Frans; Crusio, Wim E; Schalkwyk, Leonard C

2015-04-03

BALB/cJ is a strain susceptible to stress and extremely susceptible to a defective hedonic impact in response to chronic stressors. The strain offers much promise as an animal model for the study of stress related disorders. We present a comparative hippocampal gene expression study on the effects of unpredictable chronic mild stress on BALB/cJ and C57BL/6J mice. Affymetrix MOE 430 was used to measure hippocampal gene expression from 16 animals of two different strains (BALB/cJ and C57BL/6J) of both sexes and subjected to either unpredictable chronic mild stress (UCMS) or no stress. Differences were statistically evaluated through supervised and unsupervised linear modelling and using Weighted Gene Coexpression Network Analysis (WGCNA). In order to gain further understanding into mechanisms related to stress response, we cross-validated our results with a parallel study from the GENDEP project using WGCNA in a meta-analysis design. The effects of UCMS are visible through Principal Component Analysis which highlights the stress sensitivity of the BALB/cJ strain. A number of genes and gene networks related to stress response were uncovered including the Creb1 gene. WGCNA and pathway analysis revealed a gene network centered on Nfkb1. Results from the meta-analysis revealed a highly significant gene pathway centred on the Ubiquitin C (Ubc) gene. All pathways uncovered are associated with inflammation and immune response. The study investigated the molecular mechanisms underlying the response to adverse environment in an animal model using a GxE design. Stress-related differences were visible at the genomic level through PCA analysis highlighting the high sensitivity of BALB/cJ animals to environmental stressors. Several candidate genes and gene networks reported are associated with inflammation and neurogenesis and could serve to inform candidate gene selection in human studies and provide additional insight into the pathology of Major Depressive Disorder.

The influence of discovery learning model application to the higher order thinking skills student of Srijaya Negara Senior High School Palembang on the animal kingdom subject matter

NASA Astrophysics Data System (ADS)

Riandari, F.; Susanti, R.; Suratmi

2018-05-01

This study aimed to find out the information in concerning the influence of discovery learning model application to the higher order thinking skills at the tenth grade students of Srijaya Negara senior high school Palembang on the animal kingdom subject matter. The research method used was pre-experimental with one-group pretest-posttest design. The researchconducted at Srijaya Negara senior high school Palembang academic year 2016/2017. The population sample of this research was tenth grade students of natural science 2. Purposive sampling techniquewas applied in this research. Data was collected by(1) the written test, consist of pretest to determine the initial ability and posttest to determine higher order thinking skills of students after learning by using discovery learning models. (2) Questionnaire sheet, aimed to investigate the response of the students during the learning process by using discovery learning models. The t-test result indicated there was significant increasement of higher order thinking skills students. Thus, it can be concluded that the application of discovery learning modelhad a significant effect and increased to higher order thinking skills students of Srijaya Negara senior high school Palembang on the animal kingdom subject matter.

Light Augmentation Device: A New Surgical Tool for Improved Laparoscopic Visibility and Transillumination: Proof-of-Concept Study.

PubMed

Asti, Emanuele; Nebbia, Fabio; Sironi, Andrea; Bottino, Vincenzo; Bonitta, Gianluca; Bonavina, Luigi

2016-12-01

The light augmentation device (LAD ® ) is a new disposable tool designed to improve observation by transillumination in laparoscopic surgery. It can be introduced into the abdomen through an 11-12 mm port as a supplementary light source. The miniaturized design allows the surgeon to pick up the device with an endograsper and to place it under direct vision where needed. This proof-of-concept study demonstrated safety and efficacy of the device in the animal model.

Parathyroid Hormone-Related Peptide (PTHrP) as a New Target for Metastatic Breast Cancer: Evaluation in Preclinical Models

DTIC Science & Technology

2016-10-01

in PTHrP-ablated and non-ablated animals. Using CRISPr technology, we are developing pre-clinical PTHrP-ablated human triple-negative breast cancer...3.2.2.1 KO of human TNBC cells by Clustered Regularly Interspaced Short Palindromic Repeats ( Crispr ): % COMPLETED: 90% OF TASK. (ON TIME). A unique... CRISPR sequence for PTHrP was chosen from pre-designed sites in the human genome using online tools (Sigma-Aldrich). The sites are designed to

Characterization of mediators of microbial virulence and innate immunity using the Caenorhabditis elegans host-pathogen model.

PubMed

Alegado, Rosanna A; Campbell, Marianne C; Chen, Will C; Slutz, Sandra S; Tan, Man-Wah

2003-07-01

The soil-borne nematode, Caenorhabditis elegans, is emerging as a versatile model in which to study host-pathogen interactions. The worm model has shown to be particularly effective in elucidating both microbial and animal genes involved in toxin-mediated killing. In addition, recent work on worm infection by a variety of bacterial pathogens has shown that a number of virulence regulatory genes mediate worm susceptibility. Many of these regulatory genes, including the PhoP/Q two-component regulators in Salmonella and LasR in Pseudomonas aeruginosa, have also been implicated in mammalian models suggesting that findings in the worm model will be relevant to other systems. In keeping with this concept, experiments aimed at identifying host innate immunity genes have also implicated pathways that have been suggested to play a role in plants and animals, such as the p38 MAP kinase pathway. Despite rapid forward progress using this model, much work remains to be done including the design of more sensitive methods to find effector molecules and further characterization of the exact interaction between invading pathogens and C. elegans' cellular components.

In-silico experiments of zebrafish behaviour: modeling swimming in three dimensions

NASA Astrophysics Data System (ADS)

Mwaffo, Violet; Butail, Sachit; Porfiri, Maurizio

2017-01-01

Zebrafish is fast becoming a species of choice in biomedical research for the investigation of functional and dysfunctional processes coupled with their genetic and pharmacological modulation. As with mammals, experimentation with zebrafish constitutes a complicated ethical issue that calls for the exploration of alternative testing methods to reduce the number of subjects, refine experimental designs, and replace live animals. Inspired by the demonstrated advantages of computational studies in other life science domains, we establish an authentic data-driven modelling framework to simulate zebrafish swimming in three dimensions. The model encapsulates burst-and-coast swimming style, speed modulation, and wall interaction, laying the foundations for in-silico experiments of zebrafish behaviour. Through computational studies, we demonstrate the ability of the model to replicate common ethological observables such as speed and spatial preference, and anticipate experimental observations on the correlation between tank dimensions on zebrafish behaviour. Reaching to other experimental paradigms, our framework is expected to contribute to a reduction in animal use and suffering.

Design Virtual Reality Scene Roam for Tour Animations Base on VRML and Java

NASA Astrophysics Data System (ADS)

Cao, Zaihui; hu, Zhongyan

Virtual reality has been involved in a wide range of academic and commercial applications. It can give users a natural feeling of the environment by creating realistic virtual worlds. Implementing a virtual tour through a model of a tourist area on the web has become fashionable. In this paper, we present a web-based application that allows a user to, walk through, see, and interact with a fully three-dimensional model of the tourist area. Issues regarding navigation and disorientation areaddressed and we suggest a combination of the metro map and an intuitive navigation system. Finally we present a prototype which implements our ideas. The application of VR techniques integrates the visualization and animation of the three dimensional modelling to landscape analysis. The use of the VRML format produces the possibility to obtain some views of the 3D model and to explore it in real time. It is an important goal for the spatial information sciences.

3D Printing of Tissue Engineered Constructs for In Vitro Modeling of Disease Progression and Drug Screening.

PubMed

Vanderburgh, Joseph; Sterling, Julie A; Guelcher, Scott A

2017-01-01

2D cell culture and preclinical animal models have traditionally been implemented for investigating the underlying cellular mechanisms of human disease progression. However, the increasing significance of 3D vs. 2D cell culture has initiated a new era in cell culture research in which 3D in vitro models are emerging as a bridge between traditional 2D cell culture and in vivo animal models. Additive manufacturing (AM, also known as 3D printing), defined as the layer-by-layer fabrication of parts directed by digital information from a 3D computer-aided design file, offers the advantages of simultaneous rapid prototyping and biofunctionalization as well as the precise placement of cells and extracellular matrix with high resolution. In this review, we highlight recent advances in 3D printing of tissue engineered constructs that recapitulate the physical and cellular properties of the tissue microenvironment for investigating mechanisms of disease progression and for screening drugs.

3D Printing of Tissue Engineered Constructs for in vitro Modeling of Disease Progression and Drug Screening

PubMed Central

Vanderburgh, Joseph; Sterling, Julie A.

2016-01-01

2D cell culture and preclinical animal models have traditionally been implemented for investigating the underlying cellular mechanisms of human disease progression. However, the increasing significance of 3D versus 2D cell culture has initiated a new era in cell culture research in which 3D in vitro models are emerging as a bridge between traditional 2D cell culture and in vivo animal models. Additive manufacturing (AM, also known as 3D printing), defined as the layer-by-layer fabrication of parts directed by digital information from a 3D computer-aided design (CAD) file, offers the advantages of simultaneous rapid prototyping and biofunctionalization as well as the precise placement of cells and extracellular matrix with high resolution. In this review, we highlight recent advances in 3D printing of tissue engineered constructs (TECs) that recapitulate the physical and cellular properties of the tissue microenvironment for investigating mechanisms of disease progression and for screening drugs. PMID:27169894

On use of the multistage dose-response model for assessing laboratory animal carcinogenicity

PubMed Central

Nitcheva, Daniella; Piegorsch, Walter W.; West, R. Webster

2007-01-01

We explore how well a statistical multistage model describes dose-response patterns in laboratory animal carcinogenicity experiments from a large database of quantal response data. The data are collected from the U.S. EPA’s publicly available IRIS data warehouse and examined statistically to determine how often higher-order values in the multistage predictor yield significant improvements in explanatory power over lower-order values. Our results suggest that the addition of a second-order parameter to the model only improves the fit about 20% of the time, while adding even higher-order terms apparently does not contribute to the fit at all, at least with the study designs we captured in the IRIS database. Also included is an examination of statistical tests for assessing significance of higher-order terms in a multistage dose-response model. It is noted that bootstrap testing methodology appears to offer greater stability for performing the hypothesis tests than a more-common, but possibly unstable, “Wald” test. PMID:17490794

In-silico experiments of zebrafish behaviour: modeling swimming in three dimensions

PubMed Central

Mwaffo, Violet; Butail, Sachit; Porfiri, Maurizio

2017-01-01

Zebrafish is fast becoming a species of choice in biomedical research for the investigation of functional and dysfunctional processes coupled with their genetic and pharmacological modulation. As with mammals, experimentation with zebrafish constitutes a complicated ethical issue that calls for the exploration of alternative testing methods to reduce the number of subjects, refine experimental designs, and replace live animals. Inspired by the demonstrated advantages of computational studies in other life science domains, we establish an authentic data-driven modelling framework to simulate zebrafish swimming in three dimensions. The model encapsulates burst-and-coast swimming style, speed modulation, and wall interaction, laying the foundations for in-silico experiments of zebrafish behaviour. Through computational studies, we demonstrate the ability of the model to replicate common ethological observables such as speed and spatial preference, and anticipate experimental observations on the correlation between tank dimensions on zebrafish behaviour. Reaching to other experimental paradigms, our framework is expected to contribute to a reduction in animal use and suffering. PMID:28071731

Animal Models and the Development of Vaccines to Treat Substance Use Disorders.

PubMed

Ohia-Nwoko, O; Kosten, T A; Haile, C N

2016-01-01

The development of pharmacotherapies for substance use disorders (SUDs) is a high priority in addiction research. At present, there are no approved pharmacotherapies for cocaine and methamphetamine use disorders, while treatments for nicotine and opioid use are moderately effective. Indeed, many of these treatments can cause adverse drug side effects and have poor medication compliance, which often results in increased drug relapse rates. An alternative to these traditional pharmacological interventions is immunotherapy or vaccines that can target substances associated with SUDs. In this chapter, we discuss the current knowledge on the efficacy of preclinical vaccines, particularly immunogens that target methamphetamine, cocaine, nicotine, or opioids to attenuate drug-induced behaviors in animal models of SUDs. We also review vaccines (and antibodies) against cocaine, nicotine, and methamphetamine that have been assessed in human clinical trials. While preclinical studies indicate that several vaccines show promise, these findings have not necessarily translated to the clinical population. Thus, continued effort to design more effective vaccine immunogens using SUD animal models is necessary in order to support the use of immunotherapy as a viable option for individuals with SUDs. © 2016 Elsevier Inc. All rights reserved.

A metabolic cage for the hindlimb suspended rat

NASA Technical Reports Server (NTRS)

Evans, J.; Mulenburg, G. M.; Harper, J. S.; Skundberg, T. L.; Navidi, M.; Arnaud, S. B.

1994-01-01

Hindlimb suspension has been successfully used to simulate the effects of microgravity in rats. The cage and suspension system developed by E. R. Holton is designed to produce a headward shift of fluid and unload the hindlimbs in rodents, causing changes in bone and muscle similar to those in animals and humans exposed to spaceflight. While the Holton suspension system simulates many of the conditions observed in the spaceflight animal, it does not provide for the collection of urine and feces needed to monitor some metabolic activities. As a result, only limited information has been gathered on the nutritional status, and the gastrointestinal and renal function of animals using that model. Although commercial metabolic cages are available, they are usually cylindrical and require a centrally located suspension system and thus, do not readily permit movement of the rats. The limited floor space of commercial cages may affect comparisons with studies using the Holton model which has more than twice the living space of most commercially available cages. To take advantage of the extra living space and extensive data base that has been developed with the Holton model, Holton's cage was modified to make urine and fecal collections possible.

Ligand design for riboswitches, an emerging target class for novel antibiotics.

PubMed

Rekand, Illimar Hugo; Brenk, Ruth

2017-09-01

Riboswitches are cis-acting gene regulatory elements and constitute potential targets for new antibiotics. Recent studies in this field have started to explore these targets for drug discovery. New ligands found by fragment screening, design of analogs of the natural ligands or serendipitously by phenotypic screening have shown antibacterial effects in cell assays against a range of bacteria strains and in animal models. In this review, we highlight the most advanced drug design work of riboswitch ligands and discuss the challenges in the field with respect to the development of antibiotics with a new mechanism of action.

Closing the phosphorus cycle in a food system: insights from a modelling exercise.

PubMed

van Kernebeek, H R J; Oosting, S J; van Ittersum, M K; Ripoll-Bosch, R; de Boer, I J M

2018-05-21

Mineral phosphorus (P) used to fertilise crops is derived from phosphate rock, which is a finite resource. Preventing and recycling mineral P waste in the food system, therefore, are essential to sustain future food security and long-term availability of mineral P. The aim of our modelling exercise was to assess the potential of preventing and recycling P waste in a food system, in order to reduce the dependency on phosphate rock. To this end, we modelled a hypothetical food system designed to produce sufficient food for a fixed population with a minimum input requirement of mineral P. This model included representative crop and animal production systems, and was parameterised using data from the Netherlands. We assumed no import or export of feed and food. We furthermore assumed small P soil losses and no net P accumulation in soils, which is typical for northwest European conditions. We first assessed the minimum P requirement in a baseline situation, that is 42% of crop waste is recycled, and humans derived 60% of their dietary protein from animals (PA). Results showed that about 60% of the P waste in this food system resulted from wasting P in human excreta. We subsequently evaluated P input for alternative situations to assess the (combined) effect of: (1) preventing waste of crop and animal products, (2) fully recycling waste of crop products, (3) fully recycling waste of animal products and (4) fully recycling human excreta and industrial processing water. Recycling of human excreta showed most potential to reduce P waste from the food system, followed by prevention and finally recycling of agricultural waste. Fully recycling P could reduce mineral P input by 90%. Finally, for each situation, we studied the impact of consumption of PA in the human diet from 0% to 80%. The optimal amount of animal protein in the diet depended on whether P waste from animal products was prevented or fully recycled: if it was, then a small amount of animal protein in the human diet resulted in the most sustainable use of P; but if it was not, then the most sustainable use of P would result from a complete absence of animal protein in the human diet. Our results apply to our hypothetical situation. The principles included in our model however, also hold for food systems with, for example, different climatic and soil conditions, farming practices, representative types of crops and animals and population densities.

A new exposure model to evaluate smoked illicit drugs in rodents: A study of crack cocaine.

PubMed

Hueza, Isis M; Ponce, Fernando; Garcia, Raphael C T; Marcourakis, Tânia; Yonamine, Maurício; Mantovani, Cínthia de C; Kirsten, Thiago B

2016-01-01

The use of smoked illicit drugs has spread dramatically, but few studies use proper devices to expose animals to inhalational abused drugs despite the availability of numerous smoking devices that mimic tobacco exposure in rodents. Therefore, the present study developed an inexpensive device to easily expose laboratory animals to smoked drugs. We used crack cocaine as the drug of abuse, and the cocaine plasma levels and the behaviors of animals intoxicated with the crack cocaine were evaluated to prove inhaled drug absorption and systemic activity. We developed an acrylic device with two chambers that were interconnected and separated by a hatch. Three doses of crack (100, 250, or 500 mg), which contained 63.7% cocaine, were burned in a pipe, and the rats were exposed to the smoke for 5 or 10 min (n=5/amount/period). Exposure to the 250-mg dose for 10 min achieved cocaine plasma levels that were similar to those of users (170 ng/mL). Behavioral evaluations were also performed to validate the methodology. Rats (n=10/group) for these evaluations were exposed to 250 mg of crack cocaine or air for 10 min, twice daily, for 28 consecutive days. Open-field evaluations were performed at three different periods throughout the experimental design. Exposed animals exhibited transient anorexia, increased motor activity, and shorter stays in central areas of the open field, which suggests reduced anxiety. Therefore, the developed model effectively exposed animals to crack cocaine, and this model may be useful for the investigation of other inhalational abused drugs. Copyright © 2015 Elsevier Inc. All rights reserved.

The jABC Approach to Rigorous Collaborative Development of SCM Applications

NASA Astrophysics Data System (ADS)

Hörmann, Martina; Margaria, Tiziana; Mender, Thomas; Nagel, Ralf; Steffen, Bernhard; Trinh, Hong

Our approach to the model-driven collaborative design of IKEA's P3 Delivery Management Process uses the jABC [9] for model driven mediation and choreography to complement a RUP-based (Rational Unified Process) development process. jABC is a framework for service development based on Lightweight Process Coordination. Users (product developers and system/software designers) easily develop services and applications by composing reusable building-blocks into (flow-) graph structures that can be animated, analyzed, simulated, verified, executed, and compiled. This way of handling the collaborative design of complex embedded systems has proven to be effective and adequate for the cooperation of non-programmers and non-technical people, which is the focus of this contribution, and it is now being rolled out in the operative practice.

9 CFR 311.31 - Livers affected with carotenosis; livers designated as “telangiectatic,” “sawdust,” or “spotted.”

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Livers affected with carotenosis; livers designated as âtelangiectatic,â âsawdust,â or âspotted.â 311.31 Section 311.31 Animals and Animal... DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.31 Livers affected with carotenosis; livers...

Comparison of Allogeneic and Syngeneic Rat Glioma Models by Using MRI and Histopathologic Evaluation.

PubMed

Biasibetti, Elena; Valazza, Alberto; Capucchio, Maria T; Annovazzi, Laura; Battaglia, Luigi; Chirio, Daniela; Gallarate, Marina; Mellai, Marta; Muntoni, Elisabetta; Peira, Elena; Riganti, Chiara; Schiffer, Davide; Panciani, Pierpaolo; Lanotte, Michele

2017-03-01

Research in neurooncology traditionally requires appropriate in vivo animal models, on which therapeutic strategies are tested before human trials are designed and proceed. Several reproducible animal experimental models, in which human physiologic conditions can be mimicked, are available for studying glioblastoma multiforme. In an ideal rat model, the tumor is of glial origin, grows in predictable and reproducible patterns, closely resembles human gliomas histopathologically, and is weakly or nonimmunogenic. In the current study, we used MRI and histopathologic evaluation to compare the most widely used allogeneic rat glioma model, C6-Wistar, with the F98-Fischer syngeneic rat glioma model in terms of percentage tumor growth or regression and growth rate. In vivo MRI demonstrated considerable variation in tumor volume and frequency between the 2 rat models despite the same stereotactic implantation technique. Faster and more reproducible glioma growth occurred in the immunoresponsive environment of the F98-Fischer model, because the immune response is minimized toward syngeneic cells. The marked inability of the C6-Wistar allogeneic system to generate a reproducible model and the episodes of spontaneous tumor regression with this system may have been due to the increased humoral and cellular immune responses after tumor implantation.

Evaluation of Polyurethane Nasolacrimal Duct Stents: In Vivo Studies in New Zealand Rabbits

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilhelm, K.E., E-mail: wilhelm@uni-bonn.de; Grabolle, B.; Urbach, H.

2006-10-15

The purpose of this study was to evaluate the radiographic and biological effects of different polyurethane nasolacrimal duct stents in an animal model. Fifteen polyurethane nasolacrimal duct stents (n = 5 mushroom-type stents, n = 5 newly designed S-shaped TearLeader stents without hydrophilic coating, and n = 5 S-shaped TearLeader stents with hydrophilic coating) were implanted in the nasolacrimal ducts of eight unaffected New Zealand rabbits. One nasolacrimal system served as control. Clinical and radiographic follow-up was performed at 1-, 2-, and 4-week intervals, then after a 3-month interval, after which the animals were euthanized. All stents were implanted withoutmore » major periprocedural complications. The stents proved to be patent by the end of the procedure. During follow-up, all mushroom-type stents were occluded at 4 weeks. None of these stents opened to forced irrigation. Clinically, all rabbits demonstrated severe dacryocystitis. Three out of five TearLeader stents without hydrophilic coating were blocked at 4 weeks; one out of five was open to irrigation. Best results were observed in the stent group with hydrophilic coating. Follow-up dacryocystography demonstrated patent stents in nasolacrimal ducts of all animals after 4 weeks. In only one of five cases, the coated stent became partially occluded after 2 months. These animals were free of clinical symptoms. After 3 months, at least three out of five stents still opened to forced irrigation and only one stent was completely blocked. Dislocation of the stents was not observed. Refinement of the stent surface and stent design improves the results of nasolacrimal duct stenting in this animal model. Implantation of hydrophilic-coated S-shaped stents is highly superior to conventional mushroom-type stents and noncoated stent types. Hydrophilic coating seems to prevent foreign-body reactions, resulting in maximized stent patency.« less

Set-up of a multivariate approach based on serum biomarkers as an alternative strategy for the screening evaluation of the potential abuse of growth promoters in veal calves

PubMed Central

Pirro, Valentina; Girolami, Flavia; Spalenza, Veronica; Gardini, Giulia; Badino, Paola; Nebbia, Carlo

2015-01-01

A chemometric class modelling strategy (unequal dispersed classes – UNEQ) was applied for the first time as a possible screening method to monitor the abuse of growth promoters in veal calves. Five serum biomarkers, known to reflect the exposure to classes of compounds illegally used as growth promoters, were determined from 50 untreated animals in order to design a model of controls, representing veal calves reared under good, safe and highly standardised breeding conditions. The class modelling was applied to 421 commercially bred veal calves to separate them into ‘compliant’ and ‘non-compliant’ with respect to the modelled controls. Part of the non-compliant animals underwent further histological and chemical examinations to confirm the presence of either alterations in target tissues or traces of illegal substances commonly administered for growth-promoting purposes. Overall, the congruence between the histological or chemical methods and the UNEQ non-compliant outcomes was approximately 58%, likely underestimated due to the blindness nature of this examination. Further research is needed to confirm the validity of the UNEQ model in terms of sensitivity in recognising untreated animals as compliant to the controls, and specificity in revealing deviations from ideal breeding conditions, for example due to the abuse of growth promoters. PMID:25730172

Neurobiology of comorbid post-traumatic stress disorder and alcohol-use disorder

PubMed Central

Gilpin, N. W.; Weiner, J. L.

2016-01-01

Post-traumatic stress disorder (PTSD) and alcohol-use disorder (AUD) are highly comorbid in humans. Although we have some understanding of the structural and functional brain changes that define each of these disorders, and how those changes contribute to the behavioral symptoms that define them, little is known about the neurobiology of comorbid PTSD and AUD, which may be due in part to a scarcity of adequate animal models for examining this research question. The goal of this review is to summarize the current state-of-the-science on comorbid PTSD and AUD. We summarize epidemiological data documenting the prevalence of this comorbidity, review what is known about the potential neurobiological basis for the frequent co-occurrence of PTSD and AUD and discuss successes and failures of past and current treatment strategies. We also review animal models that aim to examine comorbid PTSD and AUD, highlighting where the models parallel the human condition, and we discuss the strengths and weaknesses of each model. We conclude by discussing key gaps in our knowledge and strategies for addressing them: in particular, we (1) highlight the need for better animal models of the comorbid condition and better clinical trial design, (2) emphasize the need for examination of subpopulation effects and individual differences and (3) urge cross-talk between basic and clinical researchers that is reflected in collaborative work with forward and reverse translational impact. PMID:27749004

Role of observation of live cases done by Japanese experts in the acquisition of ESD skills by a western endoscopist.

PubMed

Draganov, Peter V; Chang, Myron; Coman, Roxana M; Wagh, Mihir S; An, Qi; Gotoda, Takuji

2014-04-28

To evaluate the role of observation of experts performing endoscopic submucosal dissection (ESD) in the acquisition of ESD skills. This prospective study is documenting the learning curve of one Western endoscopist. The study consisted of three periods. In the first period (pre-observation), the trainee performed ESDs in animal models in his home institution in the United States. The second period (observation) consisted of visit to Japan and observation of live ESD cases done by experts. The observation of cases occurred over a 5-wk period. During the third period (post-observation), the trainee performed ESD in animal models in a similar fashion as in the first period. Three animal models were used: live 40-50 kg Yorkshire pig, explanted pig stomach model, and explanted pig rectum model. The outcomes from the ESDs done in the animal models before and after observation of live human cases (main study intervention) were compared. Statistical analysis of the data included: Fisher's exact test to compare distributions of a categorical variable, Wilcoxon rank sum test to compare distributions of a continuous variable between the two groups (pre-observation and post-observation), and Kruskal-Wallis test to evaluate the impact of lesion location and type of model (ex-vivo vs live pig) on lesion removal time. The trainee performed 38 ESDs in animal model (29 pre-observation/9 post-observation). The removal times post-observation were significantly shorter than those pre-observation (32.7 ± 15.0 min vs 63.5 ± 9.8 min, P < 0.001). To minimize the impact of improving physician skill, the 9 lesions post-observation were compared to the last 9 lesions pre-observation and the removal times remained significantly shorter (32.7 ± 15.0 min vs 61.0 ± 7.4 min, P = 0.0011). Regression analysis showed that ESD observation significantly reduced removal time when controlling for the sequence of lesion removal (P = 0.025). Furthermore, it was also noted a trend towards decrease in failure to remove lesions and decrease in complications after the period of observation. This study did not find a significant difference in the time needed to remove lesions in different animal models. This finding could have important implications in designing training programs due to the substantial difference in cost between live animal and explanted organ models. The main limitation of this study is that it reflects the experience of a single endoscopist. Observation of experts performing ESD over short period of time can significantly contribute to the acquisition of ESD skills.

Design and assessment of a novel SPECT system for desktop open-gantry imaging of small animals: A simulation study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zeraatkar, Navid; Farahani, Mohammad Hossein; Rahmim, Arman

Purpose: Given increasing efforts in biomedical research utilizing molecular imaging methods, development of dedicated high-performance small-animal SPECT systems has been growing rapidly in the last decade. In the present work, we propose and assess an alternative concept for SPECT imaging enabling desktop open-gantry imaging of small animals. Methods: The system, PERSPECT, consists of an imaging desk, with a set of tilted detector and pinhole collimator placed beneath it. The object to be imaged is simply placed on the desk. Monte Carlo (MC) and analytical simulations were utilized to accurately model and evaluate the proposed concept and design. Furthermore, a dedicatedmore » image reconstruction algorithm, finite-aperture-based circular projections (FABCP), was developed and validated for the system, enabling more accurate modeling of the system and higher quality reconstructed images. Image quality was quantified as a function of different tilt angles in the acquisition and number of iterations in the reconstruction algorithm. Furthermore, more complex phantoms including Derenzo, Defrise, and mouse whole body were simulated and studied. Results: The sensitivity of the PERSPECT was 207 cps/MBq. It was quantitatively demonstrated that for a tilt angle of 30°, comparable image qualities were obtained in terms of normalized squared error, contrast, uniformity, noise, and spatial resolution measurements, the latter at ∼0.6 mm. Furthermore, quantitative analyses demonstrated that 3 iterations of FABCP image reconstruction (16 subsets/iteration) led to optimally reconstructed images. Conclusions: The PERSPECT, using a novel imaging protocol, can achieve comparable image quality performance in comparison with a conventional pinhole SPECT with the same configuration. The dedicated FABCP algorithm, which was developed for reconstruction of data from the PERSPECT system, can produce high quality images for small-animal imaging via accurate modeling of the system as incorporated in the forward- and back-projection steps. Meanwhile, the developed MC model and the analytical simulator of the system can be applied for further studies on development and evaluation of the system.« less

Development of Newborn and Infant Vaccines

PubMed Central

Sanchez-Schmitz, Guzman; Levy, Ofer

2014-01-01

Vaccines for early-life immunization are a crucial biomedical intervention to reduce global morbidity and mortality, yet their developmental path has been largely ad hoc, empiric, and inconsistent. Immune responses of human newborns and infants are distinct and cannot be predicted from those of human adults or animal models. Therefore, understanding and modeling age-specific human immune responses will be vital to the rational design and development of safe and effective vaccines for newborns and infants. PMID:21734174

Guidelines for standard preclinical experiments in the mouse model of myasthenia gravis induced by acetylcholine receptor immunization.

PubMed

Tuzun, Erdem; Berrih-Aknin, Sonia; Brenner, Talma; Kusner, Linda L; Le Panse, Rozen; Yang, Huan; Tzartos, Socrates; Christadoss, Premkumar

2015-08-01

Myasthenia gravis (MG) is an autoimmune disorder characterized by generalized muscle weakness due to neuromuscular junction (NMJ) dysfunction brought by acetylcholine receptor (AChR) antibodies in most cases. Although steroids and other immunosuppressants are effectively used for treatment of MG, these medications often cause severe side effects and a complete remission cannot be obtained in many cases. For pre-clinical evaluation of more effective and less toxic treatment methods for MG, the experimental autoimmune myasthenia gravis (EAMG) induced by Torpedo AChR immunization has become one of the standard animal models. Although numerous compounds have been recently proposed for MG mostly by using the active immunization EAMG model, only a few have been proven to be effective in MG patients. The variability in the experimental design, immunization methods and outcome measurements of pre-clinical EAMG studies make it difficult to interpret the published reports and assess the potential for application to MG patients. In an effort to standardize the active immunization EAMG model, we propose standard procedures for animal care conditions, sampling and randomization of mice, experimental design and outcome measures. Utilization of these standard procedures might improve the power of pre-clinical EAMG experiments and increase the chances for identifying promising novel treatment methods that can be effectively translated into clinical trials for MG. Copyright © 2015 Elsevier Inc. All rights reserved.

Models for preclinical studies in aging-related disorders: One is not for all

PubMed Central

Santulli, Gaetano; Borras, Consuelo; Bousquet, Jean; Calzà, Laura; Cano, Antonio; Illario, Maddalena; Franceschi, Claudio; Liotta, Giuseppe; Maggio, Marcello; Molloy, William D.; Montuori, Nunzia; O’Caoimh, Rónán; Orfila, Francesc; Rauter, Amelia P.; Santoro, Aurelia; Iaccarino, Guido

2015-01-01

Preclinical studies are essentially based on animal models of a particular disease. The primary purpose of preclinical efficacy studies is to support generalization of treatment–effect relationships to human subjects. Researchers aim to demonstrate a causal relationship between an investigational agent and a disease-related phenotype in such models. Numerous factors can muddle reliable inferences about such cause-effect relationships, including biased outcome assessment due to experimenter expectations. For instance, responses in a particular inbred mouse might be specific to the strain, limiting generalizability. Selecting well-justified and widely acknowledged model systems represents the best start in designing preclinical studies, especially to overcome any potential bias related to the model itself. This is particularly true in the research that focuses on aging, which carries unique challenges, mainly attributable to the fact that our already long lifespan makes designing experiments that use people as subjects extremely difficult and largely impractical. PMID:27042427

Quantifying Migration Behaviour Using Net Squared Displacement Approach: Clarifications and Caveats.

PubMed

Singh, Navinder J; Allen, Andrew M; Ericsson, Göran

2016-01-01

Estimating migration parameters of individuals and populations is vital for their conservation and management. Studies on animal movements and migration often depend upon location data from tracked animals and it is important that such data are appropriately analyzed for reliable estimates of migration and effective management of moving animals. The Net Squared Displacement (NSD) approach for modelling animal movement is being increasingly used as it can objectively quantify migration characteristics and separate different types of movements from migration. However, the ability of NSD to properly classify the movement patterns of individuals has been criticized and issues related to study design arise with respect to starting locations of the data/animals, data sampling regime and extent of movement of species. We address the issues raised over NSD using tracking data from 319 moose (Alces alces) in Sweden. Moose is an ideal species to test this approach, as it can be sedentary, nomadic, dispersing or migratory and individuals vary in their extent, timing and duration of migration. We propose a two-step process of using the NSD approach by first classifying movement modes using mean squared displacement (MSD) instead of NSD and then estimating the extent, duration and timing of migration using NSD. We show that the NSD approach is robust to the choice of starting dates except when the start date occurs during the migratory phase. We also show that the starting location of the animal has a marginal influence on the correct quantification of migration characteristics. The number of locations per day (1-48) did not significantly affect the performance of non-linear mixed effects models, which correctly distinguished migration from other movement types, however, high-resolution data had a significant negative influence on estimates for the timing of migrations. The extent of movement, however, had an effect on the classification of movements, and individuals undertaking short- distance migrations can be misclassified as other movements such as sedentary or nomadic. Our study raises important considerations for designing, analysing and interpreting movement ecology studies, and how these should be determined by the biology of the species and the ecological and conservation questions in focus.

9 CFR 93.503 - Ports designated for the importation of swine.

Code of Federal Regulations, 2014 CFR

2014-01-01

... of swine. 93.503 Section 93.503 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... PRODUCTS; REQUIREMENTS FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Swine § 93.503 Ports designated for the importation of swine. (a) Air and ocean ports. The following ports have APHIS inspection and...

9 CFR 93.503 - Ports designated for the importation of swine.

Code of Federal Regulations, 2012 CFR

2012-01-01

... of swine. 93.503 Section 93.503 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... PRODUCTS; REQUIREMENTS FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Swine § 93.503 Ports designated for the importation of swine. (a) Air and ocean ports. The following ports have APHIS inspection and...

9 CFR 93.503 - Ports designated for the importation of swine.

Code of Federal Regulations, 2013 CFR

2013-01-01

... of swine. 93.503 Section 93.503 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... PRODUCTS; REQUIREMENTS FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Swine § 93.503 Ports designated for the importation of swine. (a) Air and ocean ports. The following ports have APHIS inspection and...

9 CFR 93.503 - Ports designated for the importation of swine.

Code of Federal Regulations, 2011 CFR

2011-01-01

... of swine. 93.503 Section 93.503 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... PRODUCTS; REQUIREMENTS FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Swine § 93.503 Ports designated for the importation of swine. (a) Air and ocean ports. The following ports have APHIS inspection and...

Improving planning, design, reporting and scientific quality of animal experiments by using the Gold Standard Publication Checklist, in addition to the ARRIVE guidelines.

PubMed

Hooijmans, Carlijn R; de Vries, Rob; Leenaars, Marlies; Curfs, Jo; Ritskes-Hoitinga, Merel

2011-03-01

Several studies have demonstrated serious omissions in the way research that use animals is reported. In order to improve the quality of reporting of animal experiments, the Animals in research: reporting in vivo experiments (ARRIVE) Guidelines were published in the British Journal of Pharmacology in August 2010. However, not only the quality of reporting of completed animal studies needs to be improved, but also the design and execution of new experiments. With both these goals in mind, we published the Gold Standard Publication Checklist (GSPC) in May 2010, a few months before the ARRIVE guidelines appeared. In this letter, we compare the GSPC checklist with the ARRIVE Guidelines. The GSPC describes certain items in more detail, which makes it both easier to use when designing and conducting an experiment and particularly suitable for making systematic reviews of animal studies more feasible. In order to improve not only the reporting but also the planning, design, execution and thereby, the scientific quality of animal experiments, we strongly recommend to all scientists involved in animal experimentation and to editors of journals publishing animal studies to take a closer look at the contents of both the ARRIVE guidelines and GSPC, and select the set of guidelines which is most appropriate for their particular situation. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

GPR Imaging of Prehistoric Animal Bone-beds

NASA Astrophysics Data System (ADS)

Schneider, Blair Benson

This research investigates the detection capabilities of Ground-penetrating radar for imaging prehistoric animal bone-beds. The first step of this investigation was to determine the dielectric properties of modern animal bone as a proxy for applying non-invasive ground-penetrating radar (GPR) for detecting prehistoric animal remains. Over 90 thin section samples were cut from four different modern faunal skeleton remains: bison, cow, deer, and elk. One sample of prehistoric mammoth core was also analyzed. Sample dielectric properties (relative permittivity, loss factor, and loss-tangent values) were measured with an impedance analyzer over frequencies ranging from 10 MHz to 1 GHz. The results reveal statistically significant dielectric-property differences among different animal fauna, as well as variation as a function of frequency. The measured sample permittivity values were then compared to modeled sample permittivity values using common dielectric-mixing models. The dielectric mixing models were used to report out new reported values of dry bone mineral of 3-5 in the frequency range of 10 MHz to 1 GHz. The second half of this research collected controlled GPR experiments over a sandbox containing buried bison bone elements to evaluate GPR detection capabilities of buried animal bone. The results of the controlled GPR sandbox tests were then compared to numerical models in order to predict the ability of GPR to detect buried animal bone given a variety of different depositional factors, the size and orientation of the bone target and the degree of bone weathering. The radar profiles show that GPR is an effective method for imaging the horizontal and vertical extent of buried animal bone. However, increased bone weathering and increased bone dip were both found to affect GPR reflection signal strength. Finally, the controlled sandbox experiments were also utilized to investigate the impact of survey design for imaging buried animal bone. In particular, the effects of GPR antenna orientation relative to the survey line (broad-side mode versus end-fire mode) and polarization effects of the buried bone targets were investigated. The results reveal that animal bone does exhibit polarization effects. However, the polarization results are greatly affected by the irregular shape and size of the bone, which ultimately limits the potential usefulness of trying to utilize polarization data to determine the orientation of buried bone targets. In regard to antenna orientation, end-fire mode was found to have little difference in amplitude response as compared to the more commonly used broad-side mode and in fact sometimes outperformed the broad-side mode. Future GPR investigations should consider utilizing multiple antenna orientations during data collection.

Design and Evaluation of Wood Processing Facilities Using Object-Oriented Simulation

Treesearch

D. Earl Kline; Philip A. Araman

1992-01-01

Managers of hardwood processing facilities need timely information on which to base important decisions such as when to add costly equipment or how to improve profitability subject to time-varying demands. The overall purpose of this paper is to introduce a tool that can effectively provide such timely information. A simulation/animation modeling procedure is described...

Technology-Assisted Sheltered Instruction: Instructional Streaming Video in an EFL Multi-Purpose Computer Course

ERIC Educational Resources Information Center

Huang, Yun-Hsuan; Chuang, Tsung-Yen

2016-01-01

Content-based instruction (CBI) has been widely adopted for decades. However, existing CBI models cannot always be effectively put into practice, especially for learners of lower English proficiency in English as a foreign language (EFL) context. This study examined an animation design course adopting CBI to promote reading abilities of English…

Combining High-Speed Cameras and Stop-Motion Animation Software to Support Students' Modeling of Human Body Movement

ERIC Educational Resources Information Center

Lee, Victor R.

2015-01-01

Biomechanics, and specifically the biomechanics associated with human movement, is a potentially rich backdrop against which educators can design innovative science teaching and learning activities. Moreover, the use of technologies associated with biomechanics research, such as high-speed cameras that can produce high-quality slow-motion video,…

Designing natural and synthetic immune tissues

NASA Astrophysics Data System (ADS)

Gosselin, Emily A.; Eppler, Haleigh B.; Bromberg, Jonathan S.; Jewell, Christopher M.

2018-06-01

Vaccines and immunotherapies have provided enormous improvements for public health, but there are fundamental disconnects between where most studies are performed—in cell culture and animal models—and the ultimate application in humans. Engineering immune tissues and organs, such as bone marrow, thymus, lymph nodes and spleen, could be instrumental in overcoming these hurdles. Fundamentally, designed immune tissues could serve as in vitro tools to more accurately study human immune function and disease, while immune tissues engineered for implantation as next-generation vaccines or immunotherapies could enable direct, on-demand control over generation and regulation of immune function. In this Review, we discuss recent interdisciplinary strategies that are merging materials science and immunology to create engineered immune tissues in vitro and in vivo. We also highlight the hurdles facing these approaches and the need for comparison to existing clinical options, relevant animal models, and other emerging technologies.

Improving Large Cetacean Implantable Satellite Tag Designs to Maximize Tag Robustness and Minimize Health Effects to Individual Animals

DTIC Science & Technology

2013-09-30

Designs to Maximize Tag Robustness and Minimize Health Effects to Individual Animals Alexandre N. Zerbini Cascadia Research Collective 218 ½ 4th...the blubber-muscle interface and minimize physical and physiological effects of body penetrating tags to individual animals . OBJECTIVES (1...integrity of designs created in Objective (1) during laboratory experiments and in cetacean carcasses ; (3) Examine structural tissue damage in the

A Kenyan perspective on the use of animals in science education and scientific research in Africa and prospects for improvement

PubMed Central

Kimwele, Charles; Matheka, Duncan; Ferdowsian, Hope

2011-01-01

Introduction Animal experimentation is common in Africa, a region that accords little priority on animal protection in comparison to economic and social development. The current study aimed at investigating the prevalence of animal experimentation in Kenya, and to review shortfalls in policy, legislation, implementation and enforcement that result in inadequate animal care in Kenya and other African nations. Methods Data was collected using questionnaires, administered at 39 highly ranked academic and research institutions aiming to identify those that used animals, their sources of animals, and application of the three Rs. Perceived challenges to the use of non-animal alternatives and common methods of euthanasia were also queried. Data was analyzed using Epidata, SPSS 16.0 and Microsoft Excel. Results Thirty-eight (97.4%) of thirty-nine institutions reported using animals for education and/or research. Thirty (76.9%) institutions reported using analgesics or anesthetics on a regular basis. Thirteen (33.3%) institutions regularly used statistical methods to minimize the use of animals. Overall, sixteen (41.0%) institutions explored the use of alternatives to animals such as cell cultures and computer simulation techniques, with one (2.6%) academic institution having completely replaced animals with computer modeling, manikins and visual illustrations. The commonest form of euthanasia employed was chloroform administration, reportedly in fourteen (29.8%) of 47 total methods (some institutions used more than one method). Twenty-eight (71.8%) institutions had no designated ethics committee to review or monitor protocols using animals. Conclusion Animals are commonly used in academic and research institutions in Kenya. The relative lack of ethical guidance and oversight regarding the use of animals in research and education presents significant concerns. PMID:22355442

A Kenyan perspective on the use of animals in science education and scientific research in Africa and prospects for improvement.

PubMed

Kimwele, Charles; Matheka, Duncan; Ferdowsian, Hope

2011-01-01

Animal experimentation is common in Africa, a region that accords little priority on animal protection in comparison to economic and social development. The current study aimed at investigating the prevalence of animal experimentation in Kenya, and to review shortfalls in policy, legislation, implementation and enforcement that result in inadequate animal care in Kenya and other African nations. Data was collected using questionnaires, administered at 39 highly ranked academic and research institutions aiming to identify those that used animals, their sources of animals, and application of the three Rs. Perceived challenges to the use of non-animal alternatives and common methods of euthanasia were also queried. Data was analyzed using Epidata, SPSS 16.0 and Microsoft Excel. Thirty-eight (97.4%) of thirty-nine institutions reported using animals for education and/or research. Thirty (76.9%) institutions reported using analgesics or anesthetics on a regular basis. Thirteen (33.3%) institutions regularly used statistical methods to minimize the use of animals. Overall, sixteen (41.0%) institutions explored the use of alternatives to animals such as cell cultures and computer simulation techniques, with one (2.6%) academic institution having completely replaced animals with computer modeling, manikins and visual illustrations. The commonest form of euthanasia employed was chloroform administration, reportedly in fourteen (29.8%) of 47 total methods (some institutions used more than one method). Twenty-eight (71.8%) institutions had no designated ethics committee to review or monitor protocols using animals. Animals are commonly used in academic and research institutions in Kenya. The relative lack of ethical guidance and oversight regarding the use of animals in research and education presents significant concerns.

Crazy like a fox. Validity and ethics of animal models of human psychiatric disease.

PubMed

Rollin, Michael D H; Rollin, Bernard E

2014-04-01

Animal models of human disease play a central role in modern biomedical science. Developing animal models for human mental illness presents unique practical and philosophical challenges. In this article we argue that (1) existing animal models of psychiatric disease are not valid, (2) attempts to model syndromes are undermined by current nosology, (3) models of symptoms are rife with circular logic and anthropomorphism, (4) any model must make unjustified assumptions about subjective experience, and (5) any model deemed valid would be inherently unethical, for if an animal adequately models human subjective experience, then there is no morally relevant difference between that animal and a human.

Using animal models to study post-partum psychiatric disorders

PubMed Central

Perani, C V; Slattery, D A

2014-01-01

The post-partum period represents a time during which all maternal organisms undergo substantial plasticity in a wide variety of systems in order to ensure the well-being of the offspring. Although this time is generally associated with increased calmness and decreased stress responses, for a substantial subset of mothers, this period represents a time of particular risk for the onset of psychiatric disorders. Thus, post-partum anxiety, depression and, to a lesser extent, psychosis may develop, and not only affect the well-being of the mother but also place at risk the long-term health of the infant. Although the risk factors for these disorders, as well as normal peripartum-associated adaptations, are well known, the underlying aetiology of post-partum psychiatric disorders remains poorly understood. However, there have been a number of attempts to model these disorders in basic research, which aim to reveal their underlying mechanisms. In the following review, we first discuss known peripartum adaptations and then describe post-partum mood and anxiety disorders, including their risk factors, prevalence and symptoms. Thereafter, we discuss the animal models that have been designed in order to study them and what they have revealed about their aetiology to date. Overall, these studies show that it is feasible to study such complex disorders in animal models, but that more needs to be done in order to increase our knowledge of these severe and debilitating mood and anxiety disorders. Linked Articles This article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-20 PMID:24527704

The aerodynamic cost of flight in the short-tailed fruit bat (Carollia perspicillata): comparing theory with measurement

PubMed Central

von Busse, Rhea; Waldman, Rye M.; Swartz, Sharon M.; Voigt, Christian C.; Breuer, Kenneth S.

2014-01-01

Aerodynamic theory has long been used to predict the power required for animal flight, but widely used models contain many simplifications. It has been difficult to ascertain how closely biological reality matches model predictions, largely because of the technical challenges of accurately measuring the power expended when an animal flies. We designed a study to measure flight speed-dependent aerodynamic power directly from the kinetic energy contained in the wake of bats flying in a wind tunnel. We compared these measurements with two theoretical predictions that have been used for several decades in diverse fields of vertebrate biology and to metabolic measurements from a previous study using the same individuals. A high-accuracy displaced laser sheet stereo particle image velocimetry experimental design measured the wake velocities in the Trefftz plane behind four bats flying over a range of speeds (3–7 m s−1). We computed the aerodynamic power contained in the wake using a novel interpolation method and compared these results with the power predicted by Pennycuick's and Rayner's models. The measured aerodynamic power falls between the two theoretical predictions, demonstrating that the models effectively predict the appropriate range of flight power, but the models do not accurately predict minimum power or maximum range speeds. Mechanical efficiency—the ratio of aerodynamic power output to metabolic power input—varied from 5.9% to 9.8% for the same individuals, changing with flight speed. PMID:24718450

Subchondral drilling for articular cartilage repair: a systematic review of translational research.

PubMed

Gao, Liang; Goebel, Lars K H; Orth, Patrick; Cucchiarini, Magali; Madry, Henning

2018-05-03

Articular cartilage defects may initiate osteoarthritis. Subchondral drilling, a widely applied clinical technique to treat small cartilage defects, does not yield cartilage regeneration. Various translational studies aiming to improve the outcome of drilling have been performed, however, a robust systematic analysis of its translational evidence has been still lacking. Here, we performed a systematic review of the outcome of subchondral drilling for knee cartilage repair in translational animal models. A total of 12 relevant publications studying 198 animals were identified, detailed study characteristics were extracted, and methodological quality and risk of bias were analyzed. Subchondral drilling was superior to defects untreated or treated with abrasion arthroplasty for cartilage repair in multiple translational models. Considerable subchondral bone changes were observed, including subchondral bone cysts and intralesional osteophytes. Furthermore, extensive alterations of the subchondral bone microarchitecture appeared in a temporal pattern in small and large animal models, together with specific topographic aspects of repair. Moreover, variable technical aspects directly affected the outcomes of osteochondral repair. The data from this systematic review indicate that subchondral drilling yields improved short-term structural articular cartilage repair compared with spontaneous repair in multiple small and large animal models. These results have important implications for future investigations aimed at an enhanced translation into clinical settings for the treatment of cartilage defects, highlighting the importance of considering specific aspects of modifiable variables such as improvements in the design and reporting of preclinical studies, together with the need to better understand the underlying mechanisms of cartilage repair following subchondral drilling. © 2018. Published by The Company of Biologists Ltd.

Suprapubic track pressure and force--deformation measurements in a (live) human subject and in animal models post-mortem.

PubMed

Coveney, V A; Gepi-Attee, S; Gröver, D; Painter, D

2001-01-01

Tests have been performed on animal models shortly post-mortem and on a healthy human subject in order to obtain estimates of the forces which act on suprapubic urinary catheters and similar devices and to develop an abdominal wall simulator. Such data and test methods are required for the systematic design of suprapubic devices because of the dual need to maintain the functionality of devices and to avoid excessive pressure on soft body tissue which could lead to ischaemia and in turn necrosis. In the post-mortem animal models, electrical excitation was applied to the abdominal wall in order to stimulate muscle activity. Two types of transducers were used: a soft membrane transducer (SMT) for pressure measurement and novel instrumented 'tongs' to determine indentation stiffness characteristics in the suprapubic track or artificial pathway created for a device. The SMT has been extensively used in the urethras and bladders of human subjects while the tongs were built specifically for these tests. Only the well-established SMT was used with the human subject; a peak pressure of 22 kPa was obtained. In the animal models the pressure profile given by the SMT had a peak whose position corresponded well with the estimated location of the rectus muscle measured on the fixed tissue section. The peak value was 5.5 kPa, comparable with values likely to cause necrosis if maintained for more than 1 day. Remarkably consistent indentation stiffness values were obtained with the instrumented tongs; all values were close to 0.45 N/mm (33 kPa/mm).

Recording EEG in immature rats with a novel miniature telemetry system

PubMed Central

Zayachkivsky, A.; Lehmkuhle, M. J.; Fisher, J. H.; Ekstrand, J. J.

2013-01-01

Serial EEG recordings from immature rat pups are extremely difficult to obtain but important for analyzing animal models of neonatal seizures and other pediatric neurological conditions as well as normal physiology. In this report, we describe the features and applications of a novel miniature telemetry system designed to record EEG in rat pups as young as postnatal day 6 (P6). First, we have recorded electrographic seizure activity in two animal models of neonatal seizures, hypoxia- and kainate-induced seizures at P7. Second, we describe a viable approach for long-term continuous EEG monitoring of naturally reared rat pups implanted with EEG at P6. Third, we have used serial EEG recordings to record age-dependent changes in the background EEG signal as the animals matured from P7 to P11. The important advantages of using miniature wireless EEG technology are: 1) minimally invasive surgical implantation; 2) a device form-factor that is compatible with housing of rat pups with the dam and littermates; 3) serial recordings of EEG activity; and 4) low power consumption of the unit, theoretically allowing continuous monitoring for up to 2 yr without surgical reimplantation. The miniature EEG telemetry system provides a technical advance that allows researchers to record continuous and serial EEG recordings in neonatal rodent models of human neurological disorders, study the progression of the disease, and then assess possible therapies using quantitative EEG as an outcome measure. This new technical approach should improve animal models of human conditions that rely on EEG monitoring for diagnosis and therapy. PMID:23114207

Running over rough terrain reveals limb control for intrinsic stability.

PubMed

Daley, Monica A; Biewener, Andrew A

2006-10-17

Legged animals routinely negotiate rough, unpredictable terrain with agility and stability that outmatches any human-built machine. Yet, we know surprisingly little about how animals accomplish this. Current knowledge is largely limited to studies of steady movement. These studies have revealed fundamental mechanisms used by terrestrial animals for steady locomotion. However, it is unclear whether these models provide an appropriate framework for the neuromuscular and mechanical strategies used to achieve dynamic stability over rough terrain. Perturbation experiments shed light on this issue, revealing the interplay between mechanics and neuromuscular control. We measured limb mechanics of helmeted guinea fowl (Numida meleagris) running over an unexpected drop in terrain, comparing their response to predictions of the mass-spring running model. Adjustment of limb contact angle explains 80% of the variation in stance-phase limb loading following the perturbation. Surprisingly, although limb stiffness varies dramatically, it does not influence the response. This result agrees with a mass-spring model, although it differs from previous findings on humans running over surfaces of varying compliance. However, guinea fowl sometimes deviate from mass-spring dynamics through posture-dependent work performance of the limb, leading to substantial energy absorption following the perturbation. This posture-dependent actuation allows the animal to absorb energy and maintain desired velocity on a sudden substrate drop. Thus, posture-dependent work performance of the limb provides inherent velocity control over rough terrain. These findings highlight how simple mechanical models extend to unsteady conditions, providing fundamental insights into neuromuscular control of movement and the design of dynamically stable legged robots and prosthetic devices.

9 CFR 93.203 - Ports designated for the importation of poultry.

Code of Federal Regulations, 2010 CFR

2010-01-01

... of poultry. 93.203 Section 93.203 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EXPORTATION AND IMPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS IMPORTATION OF CERTAIN ANIMALS, BIRDS, FISH, AND POULTRY, AND CERTAIN ANIMAL, BIRD, AND POULTRY...

Genetics and child psychiatry: I Advances in quantitative and molecular genetics.

PubMed

Rutter, M; Silberg, J; O'Connor, T; Simonoff, E

1999-01-01

Advances in quantitative psychiatric genetics as a whole are reviewed with respect to conceptual and methodological issues in relation to statistical model fitting, new genetic designs, twin and adoptee studies, definition of the phenotype, pervasiveness of genetic influences, pervasiveness of environmental influences, shared and nonshared environmental effects, and nature-nurture interplay. Advances in molecular genetics are discussed in relation to the shifts in research strategies to investigate multifactorial disorders (affected relative linkage designs, association strategies, and quantitative trait loci studies); new techniques and identified genetic mechanisms (expansion of trinucleotide repeats, genomic imprinting, mitochondrial DNA, fluorescent in-situ hybridisation, behavioural phenotypes, and animal models); and the successful localisation of genes.

Adhesion design maps for bio-inspired attachment systems.

PubMed

Spolenak, Ralph; Gorb, Stanislav; Arzt, Eduard

2005-01-01

Fibrous surface structures can improve the adhesion of objects to other surfaces. Animals, such as flies and geckos, take advantage of this principle by developing "hairy" contact structures which ensure controlled and repeatable adhesion and detachment. Mathematical models for fiber adhesion predict pronounced dependencies of contact performance on the geometry and the elastic properties of the fibers. In this paper the limits of such contacts imposed by fiber strength, fiber condensation, compliance, and ideal contact strength are modeled for spherical contact tips. Based on this, we introduce the concept of "adhesion design maps" which visualize the predicted mechanical behavior. The maps are useful for understanding biological systems and for guiding experimentation to achieve optimum artificial contacts.

Animal Models for Studying Triazole Resistance in Aspergillus fumigatus.

PubMed

Lewis, Russell E; Verweij, Paul E

2017-08-15

Infections caused by triazole-resistant Aspergillus fumigatus are associated with a higher probability of treatment failure and mortality. Because clinical experience in managing these infections is still limited, mouse models of invasive aspergillosis fulfill a critical void for studying treatment regimens designed to overcome resistance. The type of immunosuppression, the route of infection, the timing of antifungal administration, and the end points used to assess antifungal activity affect the interpretation of data from these models. Nevertheless, these models provide important insights that help guide treatment decisions in patients with triazole-resistant invasive aspergillosis. Animal models confirmed that a high triazole minimal inhibitory concentration corresponded with triazole treatment failure and that the efficacy of other classes of drugs, such as the polyenes and echinocandins, was not affected by the presence of triazole resistance mutations. Furthermore, the feasibility of triazole dose escalation, combination therapy, and prophylaxis were explored as strategies to overcome resistance. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Nonhuman Primate Models in the Genomic Era: A Paradigm Shift

PubMed Central

Vallender, Eric J.; Miller, Gregory M.

2013-01-01

Because of their strong similarities to humans across physiologic, developmental, behavioral, immunologic, and genetic levels, nonhuman primates are essential models for a wide spectrum of biomedical research. But unlike other animal models, nonhuman primates possess substantial outbred genetic variation, reducing statistical power and potentially confounding interpretation of results in research studies. Although unknown genetic variation is a hindrance in studies that allocate animals randomly, taking genetic variation into account in study design affords an opportunity to transform the way that nonhuman primates are used in biomedical research. New understandings of how the function of individual genes in rhesus macaques mimics that seen in humans are greatly advancing the rhesus macaques utility as research models, but epistatic interaction, epigenetic regulatory mechanisms, and the intricacies of gene networks limit model development. We are now entering a new era of nonhuman primate research, brought on by the proliferation and rapid expansion of genomic data. Already the cost of a rhesus macaque genome is dwarfed by its purchase and husbandry costs, and complete genomic datasets will inevitably encompass each rhesus macaque used in biomedical research. Advancing this outcome is paramount. It represents an opportunity to transform the way animals are assigned and used in biomedical research and to develop new models of human disease. The genetic and genomic revolution brings with it a paradigm shift for nonhuman primates and new mandates on how nonhuman primates are used in biomedical research. PMID:24174439

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

PubMed

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

2012-12-01

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

Mutant mice: experimental organisms as materialised models in biomedicine.

PubMed

Huber, Lara; Keuck, Lara K

2013-09-01

Animal models have received particular attention as key examples of material models. In this paper, we argue that the specificities of establishing animal models-acknowledging their status as living beings and as epistemological tools-necessitate a more complex account of animal models as materialised models. This becomes particularly evident in animal-based models of diseases that only occur in humans: in these cases, the representational relation between animal model and human patient needs to be generated and validated. The first part of this paper presents an account of how disease-specific animal models are established by drawing on the example of transgenic mice models for Alzheimer's disease. We will introduce an account of validation that involves a three-fold process including (1) from human being to experimental organism; (2) from experimental organism to animal model; and (3) from animal model to human patient. This process draws upon clinical relevance as much as scientific practices and results in disease-specific, yet incomplete, animal models. The second part of this paper argues that the incompleteness of models can be described in terms of multi-level abstractions. We qualify this notion by pointing to different experimental techniques and targets of modelling, which give rise to a plurality of models for a specific disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Experimental Oral Candidiasis in Animal Models

PubMed Central

Samaranayake, Yuthika H.; Samaranayake, Lakshman P.

2001-01-01

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

Volumetric analysis of tumors in rodents using the variable resolution x-ray (VRX) CT-scanner

NASA Astrophysics Data System (ADS)

Gaber, M. Waleed; Wilson, Christy M.; Duntsch, Christopher D.; Shukla, Hemant; Zawaski, Janice A.; Jordan, Lawrence M.; Rendon, David A.; Vangalaa, Sravanthi; Keyes, Gary S.; DiBianca, Frank A.

2005-04-01

The Variable Resolution X-ray (VRX) CT system, developed at the UTHSC, Memphis, has the potential for use in animal imaging. Animal models of tumor progression and pharmacological impact are becoming increasingly important in understanding the molecular and mechanistic basis of tumor development. In general, CT-imaging offers several advantages in animal research: a fast throughput of seconds to minutes reducing the physiological stress animals are exposed to, and it is an inexpensive modality affordable to many animal laboratories. We are developing the VRX CT scanner as a non-invasive imaging modality to measure tumor volume, progression, and metastasis. From the axial images taken by the VRX CT-scanner, tumor area was measured and the tumor volume was calculated. Animals were also imaged using an optical liquid nitrogen-cooled CCD camera to detect tumor fluorescence. A simple image fusion with a planner x-ray image was used to ascertain the position of the tumors, animals were then sacrificed the tumors excised, and the tumor volume calculated by physical measurements. Furthermore, using a specially designed phantom with three spheres of different volumes, we demonstrated that our system allowed us to estimate the volume with up to 10% accuracy; we expect this to increase dramatically in the next few months.

Increase in seizure susceptibility in sepsis like condition explained by spiking cytokines and altered adhesion molecules level with impaired blood brain barrier integrity in experimental model of rats treated with lipopolysaccharides.

PubMed

Sewal, Rakesh K; Modi, Manish; Saikia, Uma Nahar; Chakrabarti, Amitava; Medhi, Bikash

2017-09-01

Epilepsy is a neurological disorder characterized by recurrent unprovoked seizures. Sepsis is a condition which initiates a cascade of a surge of inflammatory mediators. Interplay between seizures and inflammation other than of brain origin is yet to be explored. The present study was designed to evaluate the seizure susceptibility in experimental models of lipopolysaccharide (LPS) induced sepsis. Experimental sepsis was induced using lipopolysaccharides in Wistar rats. Valproic acid, dexametasone were given to two different groups of animals along with LPS. Two groups of animals were subjected to administration of vehicle and LPS respectively with no other treatment. 24h later, animals were subjected to seizures by using either maximal electro shock or pentylenetetrazole. Seizures related parameters, oxidative stress and TNF-α, IL-6, IL-1β, ICAM-1, ICAM-2, VCAM-1, MMP-9 level in serum and brain samples were evaluated. Histopathological and blood brain barrier permeability studies were conducted. Seizures were decreased in valproic acid treated animals. Reduced oxidative stress was seen in dexamethasone plus valproic acid treated groups as compared to LPS alone treated group. TNF-α, IL-6, IL-1β, ICAM-1, VCAM-1, MMP-9 levels were found increased in LPS treated animals whereas a reverse observation was noted for ICAM-2 level in brain and serum. Histopathological findings confirmed the successful establishment of sepsis like state in animals. Blood brain barrier permeability was found increased in LPS treated groups of animals. Seizure susceptibility may escalate during the sepsis like inflammatory conditions and curbing the inflammatory state might reverse the phenomenon. Copyright © 2017. Published by Elsevier B.V.

Curcumin attenuates inflammatory response and cognitive deficits in experimental model of chronic epilepsy.

PubMed

Kaur, Harpreet; Patro, Ishan; Tikoo, Kulbhushan; Sandhir, Rajat

2015-10-01

Evidence suggests that glial cells play a critical role in inflammation in chronic epilepsy, contributing to perpetuation of seizures and cognitive dysfunctions. The present study was designed to evaluate the beneficial effect of curcumin, a polyphenol with pleiotropic properties, on cognitive deficits and inflammation in chronic epilepsy. Kindled model of epilepsy was induced by administering sub-convulsive dose of pentylenetetrazole (PTZ) at 40 mg/kg, i.p. every alternative day for 30 days to Wistar rats. The animals were assessed for cognitive deficits by Morris water maze and inflammatory response in terms of microglial and astrocyte activation. PTZ treated animals had increased escape latency suggesting impaired cognitive functions. Further, an increased expression of astrocyte (GFAP) and microglial (Iba-1) activation markers were observed in terms of mRNA and protein levels in the PTZ treated animals. Concomitantly, mRNA and protein levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and chemokine (MCP-1) were increased in hippocampus and cortex. Immunoreactivity to anti-GFAP and anti-Iba-1 antibodies was also enhanced in hippocampus and cortex suggesting gliosis in PTZ treated animals. However, curcumin administration at a dose of 100 mg/kg to PTZ animals prevented cognitive deficits. A significant decrease in pro-inflammatory cytokines and chemokine expression was observed in hippocampus and cortex of PTZ treated rats supplemented with curcumin. In addition, curcumin also attenuated increased expression of GFAP and Iba-1 in animals with PTZ induced chronic epilepsy. Moreover, immunohistochemical analysis also showed significant reduction in number of activated glial cells on curcumin administration to PTZ treated animals. Taken together, these findings suggest that curcumin is effective in attenuating glial activation and ameliorates cognitive deficits in chronic epilepsy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Simultaneous scanning of two mice in a small-animal PET scanner: a simulation-based assessment of the signal degradation

NASA Astrophysics Data System (ADS)

Reilhac, Anthonin; Boisson, Frédéric; Wimberley, Catriona; Parmar, Arvind; Zahra, David; Hamze, Hasar; Davis, Emma; Arthur, Andrew; Bouillot, Caroline; Charil, Arnaud; Grégoire, Marie-Claude

2016-02-01

In PET imaging, research groups have recently proposed different experimental set ups allowing multiple animals to be simultaneously imaged in a scanner in order to reduce the costs and increase the throughput. In those studies, the technical feasibility was demonstrated and the signal degradation caused by additional mice in the FOV characterized, however, the impact of the signal degradation on the outcome of a PET study has not yet been studied. Here we thoroughly investigated, using Monte Carlo simulated [18F]FDG and [11C]Raclopride PET studies, different experimental designs for whole-body and brain acquisitions of two mice and assessed the actual impact on the detection of biological variations as compared to a single-mouse setting. First, we extended the validation of the PET-SORTEO Monte Carlo simulation platform for the simultaneous simulation of two animals. Then, we designed [18F]FDG and [11C]Raclopride input mouse models for the simulation of realistic whole-body and brain PET studies. Simulated studies allowed us to accurately estimate the differences in detection between single- and dual-mode acquisition settings that are purely the result of having two animals in the FOV. Validation results showed that PET-SORTEO accurately reproduced the spatial resolution and noise degradations that were observed with actual dual phantom experiments. The simulated [18F]FDG whole-body study showed that the resolution loss due to the off-center positioning of the mice was the biggest contributing factor in signal degradation at the pixel level and a minimal inter-animal distance as well as the use of reconstruction methods with resolution modeling should be preferred. Dual mode acquisition did not have a major impact on ROI-based analysis except in situations where uptake values in organs from the same subject were compared. The simulated [11C]Raclopride study however showed that dual-mice imaging strongly reduced the sensitivity to variations when mice were positioned side-by-side while no sensitivity reduction was observed when they were facing each other. This is the first study showing the impact of different experimental designs for whole-body and brain acquisitions of two mice on the quality of the results using Monte Carlo simulated [18F]FDG and [11C]Raclopride PET studies.

Conformal phased surfaces for wireless powering of bioelectronic microdevices

PubMed Central

Agrawal, Devansh R.; Tanabe, Yuji; Weng, Desen; Ma, Andrew; Hsu, Stephanie; Liao, Song-Yan; Zhen, Zhe; Zhu, Zi-Yi; Sun, Chuanbowen; Dong, Zhenya; Yang, Fengyuan; Tse, Hung Fat; Poon, Ada S. Y.; Ho, John S.

2017-01-01

Wireless powering could enable the long-term operation of advanced bioelectronic devices within the human body. Although both enhanced powering depth and device miniaturization can be achieved by shaping the field pattern within the body, existing electromagnetic structures do not provide the spatial phase control required to synthesize such patterns. Here, we describe the design and operation of conformal electromagnetic structures, termed phased surfaces, that interface with non-planar body surfaces and optimally modulate the phase response to enhance the performance of wireless powering. We demonstrate that the phased surfaces can wirelessly transfer energy across anatomically heterogeneous tissues in large animal models, powering miniaturized semiconductor devices (<12 mm3) deep within the body (>4 cm). As an illustration of in vivo operation, we wirelessly regulated cardiac rhythm by powering miniaturized stimulators at multiple endocardial sites in a porcine animal model. PMID:29226018