WorldWideScience

Sample records for modeling human activity

  1. Complex human activities recognition using interval temporal syntactic model

    Institute of Scientific and Technical Information of China (English)

    夏利民; 韩芬; 王军

    2016-01-01

    A novel method based on interval temporal syntactic model was proposed to recognize human activities in video flow. The method is composed of two parts: feature extract and activities recognition. Trajectory shape descriptor, speeded up robust features (SURF) and histograms of optical flow (HOF) were proposed to represent human activities, which provide more exhaustive information to describe human activities on shape, structure and motion. In the process of recognition, a probabilistic latent semantic analysis model (PLSA) was used to recognize sample activities at the first step. Then, an interval temporal syntactic model, which combines the syntactic model with the interval algebra to model the temporal dependencies of activities explicitly, was introduced to recognize the complex activities with a time relationship. Experiments results show the effectiveness of the proposed method in comparison with other state-of-the-art methods on the public databases for the recognition of complex activities.

  2. Detection of Unusual Human Activities Based on Behavior Modeling

    OpenAIRE

    Hiraishi, Kunihiko; Kobayashi, Koichi

    2014-01-01

    A type of services that require human physical actions and intelligent decision making exists in various real fields, such as nursing in hospitals and caregiving in nursing homes. In this paper, we propose new formalism for modeling human behavior in such services. Behavior models are estimated from event-logs, and can be used for analysis of human activities. We show two analysis methods: one is to detect unusual human activities that appear in event-logs, and the other is to find staffs tha...

  3. Modeling and Visualization of Human Activities for Multicamera Networks

    Directory of Open Access Journals (Sweden)

    Aswin C. Sankaranarayanan

    2009-01-01

    Full Text Available Multicamera networks are becoming complex involving larger sensing areas in order to capture activities and behavior that evolve over long spatial and temporal windows. This necessitates novel methods to process the information sensed by the network and visualize it for an end user. In this paper, we describe a system for modeling and on-demand visualization of activities of groups of humans. Using the prior knowledge of the 3D structure of the scene as well as camera calibration, the system localizes humans as they navigate the scene. Activities of interest are detected by matching models of these activities learnt a priori against the multiview observations. The trajectories and the activity index for each individual summarize the dynamic content of the scene. These are used to render the scene with virtual 3D human models that mimic the observed activities of real humans. In particular, the rendering framework is designed to handle large displays with a cluster of GPUs as well as reduce the cognitive dissonance by rendering realistic weather effects and illumination. We envision use of this system for immersive visualization as well as summarization of videos that capture group behavior.

  4. 3D active workspace of human hand anatomical model

    Directory of Open Access Journals (Sweden)

    Ungureanu Loredana

    2007-05-01

    Full Text Available Abstract Background If the model of the human hand is created with accuracy by respecting the type of motion provided by each articulation and the dimensions of articulated bones, it can function as the real organ providing the same motions. Unfortunately, the human hand is hard to model due to its kinematical chains submitted to motion constraints. On the other hand, if an application does not impose a fine manipulation it is not necessary to create a model as complex as the human hand is. But always the hand model has to perform a certain space of motions in imposed workspace architecture no matter what the practical application does. Methods Based on Denavit-Hartenberg convention, we conceived the kinematical model of the human hand, having in mind the structure and the behavior of the natural model. We obtained the kinematical equations describing the motion of every fingertip with respect to the general coordinate system, placed on the wrist. For every joint variable, a range of motion was established. Dividing these joint variables to an appropriate number of intervals and connecting them, the complex surface bordering the active hand model workspace was obtained. Results Using MATLAB 7.0, the complex surface described by fingertips, when hand articulations are all simultaneously moving, was obtained. It can be seen that any point on surface has its own coordinates smaller than the maximum length of the middle finger in static position. Therefore, a sphere having the centre in the origin of the general coordinate system and the radius which equals this length covers the represented complex surface. Conclusion We propose a human hand model that represents a new solution compared to the existing ones. This model is capable to make special movements like power grip and dexterous manipulations. During them, the fingertips do not exceed the active workspace encapsulated by determined surfaces. The proposed kinematical model can help to choose

  5. Workshop on Human Activity at Scale in Earth System Models

    Energy Technology Data Exchange (ETDEWEB)

    Allen, Melissa R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Aziz, H. M. Abdul [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Coletti, Mark A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Kennedy, Joseph H. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Nair, Sujithkumar S. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Omitaomu, Olufemi A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2017-01-26

    Changing human activity within a geographical location may have significant influence on the global climate, but that activity must be parameterized in such a way as to allow these high-resolution sub-grid processes to affect global climate within that modeling framework. Additionally, we must have tools that provide decision support and inform local and regional policies regarding mitigation of and adaptation to climate change. The development of next-generation earth system models, that can produce actionable results with minimum uncertainties, depends on understanding global climate change and human activity interactions at policy implementation scales. Unfortunately, at best we currently have only limited schemes for relating high-resolution sectoral emissions to real-time weather, ultimately to become part of larger regions and well-mixed atmosphere. Moreover, even our understanding of meteorological processes at these scales is imperfect. This workshop addresses these shortcomings by providing a forum for discussion of what we know about these processes, what we can model, where we have gaps in these areas and how we can rise to the challenge to fill these gaps.

  6. Modelling large scale human activity in San Francisco

    Science.gov (United States)

    Gonzalez, Marta

    2010-03-01

    Diverse group of people with a wide variety of schedules, activities and travel needs compose our cities nowadays. This represents a big challenge for modeling travel behaviors in urban environments; those models are of crucial interest for a wide variety of applications such as traffic forecasting, spreading of viruses, or measuring human exposure to air pollutants. The traditional means to obtain knowledge about travel behavior is limited to surveys on travel journeys. The obtained information is based in questionnaires that are usually costly to implement and with intrinsic limitations to cover large number of individuals and some problems of reliability. Using mobile phone data, we explore the basic characteristics of a model of human travel: The distribution of agents is proportional to the population density of a given region, and each agent has a characteristic trajectory size contain information on frequency of visits to different locations. Additionally we use a complementary data set given by smart subway fare cards offering us information about the exact time of each passenger getting in or getting out of the subway station and the coordinates of it. This allows us to uncover the temporal aspects of the mobility. Since we have the actual time and place of individual's origin and destination we can understand the temporal patterns in each visited location with further details. Integrating two described data set we provide a dynamical model of human travels that incorporates different aspects observed empirically.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-06-01

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

  8. Information Flow Model of Human Extravehicular Activity Operations

    Science.gov (United States)

    Miller, Matthew J.; McGuire, Kerry M.; Feigh, Karen M.

    2014-01-01

    Future human spaceflight missions will face the complex challenge of performing human extravehicular activity (EVA) beyond the low Earth orbit (LEO) environment. Astronauts will become increasingly isolated from Earth-based mission support and thus will rely heavily on their own decision-making capabilities and onboard tools to accomplish proposed EVA mission objectives. To better address time delay communication issues, EVA characters, e.g. flight controllers, astronauts, etc., and their respective work practices and roles need to be better characterized and understood. This paper presents the results of a study examining the EVA work domain and the personnel that operate within it. The goal is to characterize current and historical roles of ground support, intravehicular (IV) crew and EV crew, their communication patterns and information needs. This work provides a description of EVA operations and identifies issues to be used as a basis for future investigation.

  9. Human Activity Modeling and Simulation with High Biofidelity

    Science.gov (United States)

    2013-01-01

    Jeanne Smith Isiah Davenport Infoscitex 4027 Colonel Glenn Hwy Beavercreek, OH 45431 John Camp Darrell Lochtefeld Human Signatures Branch...AND ADDRESS(ES) 8. PERFORMING ORGANIZATION *Infoscitex 4027 Col Glenn Hwy Beavercreek, OH 45431 REPORT NUMBER 9. SPONSORING

  10. Biofidelic Human Activity Modeling and Simulation with Large Variability

    Science.gov (United States)

    2014-11-25

    Human Signatures Branch Zhiqing Cheng Isiah Davenport Tim MtCastle Steve Mosher Jeanne Smith Max Grattan Infoscitex 4027 Col Glenn Hwy...Zhiqing Cheng Isiah Davenport Tim MtCastle Stephen Mosher Jeanne Smith Max Grattan 5d. PROJECT NUMBER 2830 5e. TASK NUMBER HP 5f. WORK...Isiah Davenport, Tim MtCastle 711th Human Performance Wing Steve Mosher , Jeanne Smith, and Max Grattan Air Force Research Laboratory Infoscitex

  11. Noise-driven activation in human intermittent control: a double-well potential model

    CERN Document Server

    Zgonnikov, Arkady

    2014-01-01

    In controlling unstable systems humans switch intermittently between the passive and active behavior instead of controlling the system in a continuous manner. The notion of noise-driven control activation provides a richer alternative to the conventional threshold-based models of intermittent motor control. The present study represents the control activation as a random walk in a continuously changing double-well potential. The match between the proposed model and the previous data on human balancing of virtual stick prompts that the double-well approach can aid in explaining complex dynamics of human behavior in control processes.

  12. Accelerometer signal-based human activity recognition using augmented autoregressive model coefficients and artificial neural nets.

    Science.gov (United States)

    Khan, A M; Lee, Y K; Kim, T S

    2008-01-01

    Automatic recognition of human activities is one of the important and challenging research areas in proactive and ubiquitous computing. In this work, we present some preliminary results of recognizing human activities using augmented features extracted from the activity signals measured using a single triaxial accelerometer sensor and artificial neural nets. The features include autoregressive (AR) modeling coefficients of activity signals, signal magnitude areas (SMA), and title angles (TA). We have recognized four human activities using AR coefficients (ARC) only, ARC with SMA, and ARC with SMA and TA. With the last augmented features, we have achieved the recognition rate above 99% for all four activities including lying, standing, walking, and running. With our proposed technique, real time recognition of some human activities is possible.

  13. A Deep Structured Model with Radius-Margin Bound for 3D Human Activity Recognition

    OpenAIRE

    Lin, Liang; Wang, Keze; Zuo, Wangmeng; Wang, Meng; Luo, Jiebo; Zhang, Lei

    2015-01-01

    Understanding human activity is very challenging even with the recently developed 3D/depth sensors. To solve this problem, this work investigates a novel deep structured model, which adaptively decomposes an activity instance into temporal parts using the convolutional neural networks (CNNs). Our model advances the traditional deep learning approaches in two aspects. First, { we incorporate latent temporal structure into the deep model, accounting for large temporal variations of diverse huma...

  14. Transcriptome-based network analysis reveals a spectrum model of human macrophage activation.

    Science.gov (United States)

    Xue, Jia; Schmidt, Susanne V; Sander, Jil; Draffehn, Astrid; Krebs, Wolfgang; Quester, Inga; De Nardo, Dominic; Gohel, Trupti D; Emde, Martina; Schmidleithner, Lisa; Ganesan, Hariharasudan; Nino-Castro, Andrea; Mallmann, Michael R; Labzin, Larisa; Theis, Heidi; Kraut, Michael; Beyer, Marc; Latz, Eicke; Freeman, Tom C; Ulas, Thomas; Schultze, Joachim L

    2014-02-20

    Macrophage activation is associated with profound transcriptional reprogramming. Although much progress has been made in the understanding of macrophage activation, polarization, and function, the transcriptional programs regulating these processes remain poorly characterized. We stimulated human macrophages with diverse activation signals, acquiring a data set of 299 macrophage transcriptomes. Analysis of this data set revealed a spectrum of macrophage activation states extending the current M1 versus M2-polarization model. Network analyses identified central transcriptional regulators associated with all macrophage activation complemented by regulators related to stimulus-specific programs. Applying these transcriptional programs to human alveolar macrophages from smokers and patients with chronic obstructive pulmonary disease (COPD) revealed an unexpected loss of inflammatory signatures in COPD patients. Finally, by integrating murine data from the ImmGen project we propose a refined, activation-independent core signature for human and murine macrophages. This resource serves as a framework for future research into regulation of macrophage activation in health and disease.

  15. Modelling temporal networks of human face-to-face contacts with public activity and individual reachability

    Science.gov (United States)

    Zhang, Yi-Qing; Cui, Jing; Zhang, Shu-Min; Zhang, Qi; Li, Xiang

    2016-02-01

    Modelling temporal networks of human face-to-face contacts is vital both for understanding the spread of airborne pathogens and word-of-mouth spreading of information. Although many efforts have been devoted to model these temporal networks, there are still two important social features, public activity and individual reachability, have been ignored in these models. Here we present a simple model that captures these two features and other typical properties of empirical face-to-face contact networks. The model describes agents which are characterized by an attractiveness to slow down the motion of nearby people, have event-triggered active probability and perform an activity-dependent biased random walk in a square box with periodic boundary. The model quantitatively reproduces two empirical temporal networks of human face-to-face contacts which are testified by their network properties and the epidemic spread dynamics on them.

  16. Active numerical model of human body for reconstruction of falls from height.

    Science.gov (United States)

    Milanowicz, Marcin; Kędzior, Krzysztof

    2017-01-01

    Falls from height constitute the largest group of incidents out of approximately 90,000 occupational accidents occurring each year in Poland. Reconstruction of the exact course of a fall from height is generally difficult due to lack of sufficient information from the accident scene. This usually results in several contradictory versions of an incident and impedes, for example, determination of the liability in a judicial process. In similar situations, in many areas of human activity, researchers apply numerical simulation. They use it to model physical phenomena to reconstruct their real course over time; e.g. numerical human body models are frequently used for investigation and reconstruction of road accidents. However, they are validated in terms of specific road traffic accidents and are considerably limited when applied to the reconstruction of other types of accidents. The objective of the study was to develop an active numerical human body model to be used for reconstruction of accidents associated with falling from height. Development of the model involved extension and adaptation of the existing Pedestrian human body model (available in the MADYMO package database) for the purposes of reconstruction of falls from height by taking into account the human reaction to the loss of balance. The model was developed by using the results of experimental tests of the initial phase of the fall from height. The active numerical human body model covering 28 sets of initial conditions related to various human reactions to the loss of balance was developed. The application of the model was illustrated by using it to reconstruct a real fall from height. From among the 28 sets of initial conditions, those whose application made it possible to reconstruct the most probable version of the incident was selected. The selection was based on comparison of the results of the reconstruction with information contained in the accident report. Results in the form of estimated

  17. Independent component feature-based human activity recognition via Linear Discriminant Analysis and Hidden Markov Model.

    Science.gov (United States)

    Uddin, Md; Lee, J J; Kim, T S

    2008-01-01

    In proactive computing, human activity recognition from image sequences is an active research area. This paper presents a novel approach of human activity recognition based on Linear Discriminant Analysis (LDA) of Independent Component (IC) features from shape information. With extracted features, Hidden Markov Model (HMM) is applied for training and recognition. The recognition performance using LDA of IC features has been compared to other approaches including Principle Component Analysis (PCA), LDA of PC, and ICA. The preliminary results show much improved performance in the recognition rate with our proposed method.

  18. Active controlled muscles in numerical model of human arm for movement in two degrees of freedom

    NARCIS (Netherlands)

    Budziszewski, P.; Nunen, E. van; Mordaka, J.K.; Kȩdzior, K.

    2008-01-01

    This paper describes the development of numerical model of human upper extremity able to perform movements and stabilization tasks in two degrees of freedom as a result of muscle activation controlled by a PID-based controller. These tasks are defined by functions of specified angle for every degree

  19. QSAR modeling for anti-human African trypanosomiasis activity of substituted 2-Phenylimidazopyridines

    Science.gov (United States)

    Masand, Vijay H.; El-Sayed, Nahed N. E.; Mahajan, Devidas T.; Mercader, Andrew G.; Alafeefy, Ahmed M.; Shibi, I. G.

    2017-02-01

    In the present work, sixty substituted 2-Phenylimidazopyridines previously reported with potent anti-human African trypanosomiasis (HAT) activity were selected to build genetic algorithm (GA) based QSAR models to determine the structural features that have significant correlation with the activity. Multiple QSAR models were built using easily interpretable descriptors that are directly associated with the presence or the absence of a structural scaffold, or a specific atom. All the QSAR models have been thoroughly validated according to the OECD principles. All the QSAR models are statistically very robust (R2 = 0.80-0.87) with high external predictive ability (CCCex = 0.81-0.92). The QSAR analysis reveals that the HAT activity has good correlation with the presence of five membered rings in the molecule.

  20. Assessing impact of changes in human resources features on enterprise activities: simulation model

    Directory of Open Access Journals (Sweden)

    Kalmykova Svetlana

    2017-01-01

    Full Text Available The need for creating programs of human resources development is shown; the impact of these programs on organizational effectiveness is taken into account. The stages of development tools and HRD programs on the basis of cognitive modelling are disclosed; these stages will help assess the impact of HR-practices on the key indicators of organization activity at the design stage. The method of HR-practices’ pre-selection in professional development of the employees is represented.

  1. Human activated protein C variants in a rat model of arterial thrombosis

    Directory of Open Access Journals (Sweden)

    Dahlbäck Björn

    2008-10-01

    Full Text Available Abstract Background Activated protein C (APC inhibits coagulation by degrading activated factor V (FVa and factor VIII (FVIIIa, protein S (PS functioning as a cofactor to APC. Methods By mutagenesis of the vitamin K-dependent Gla domain of APC, we have recently created an APC variant having enhanced anticoagulant activity due to increased affinity for negatively charged phospholipid membranes. In the present study, the potential antithrombotic effects of this APC variant, and of a variant APC that is additionally mutated in the serine protease domain, have been evaluated in a blind randomized study in a rat model of arterial thrombosis. In this model, we have previously found the combination of bovine APC and PS to be highly antithrombotic. Four treatment groups each containing 10 rats were, in a blind random fashion, given intravenous bolus injections of wild-type or mutant variants of APC (0.8 mg/kg together with human PS (0.6 mg/kg or human PS (0.6 mg/kg alone. A control group with 20 animals where given vehicle only. Results A trend to increased patency rates was noted in a group receiving one of the APC variants, but it did not reach statistical significance. Conclusion In conclusion, administration of human APC variants having enhanced anticoagulant efficacy together with human PS in a rat model of arterial thrombosis did not give an efficient antithrombotic effect. The lack of effect may be due to species-specific differences between the human protein C system and the rat hemostatic system.

  2. Finite element crash simulations of the human body: Passive and active muscle modelling

    Indian Academy of Sciences (India)

    S Mukherjee; A Chawla; B Karthikeyan; A Soni

    2007-08-01

    Conventional dummy based testing procedures suffer from known limitations. This report addresses issues in finite element human body models in evaluating pedestrian and occupant crash safety measures. A review of material properties of soft tissues and characterization methods show a scarcity of material properties for characterizing soft tissues in dynamic loading. Experiments imparting impacts to tissues and subsequent inverse finite element mapping to extract material properties are described. The effect of muscle activation due to voluntary and non-voluntary reflexes on injuries has been investigated through finite element modelling.

  3. Development of a multi-body human model that predicts active and passive human behaviour

    NARCIS (Netherlands)

    Meijer, R.; Hassel, E. van; Broos, J.; Elrofai, H.; Rooij, L. van; Hooijdonk, P. van

    2012-01-01

    Active safety systems that start to act moments before the crash might be capable of anticipating the occupant’s position, either by correcting it, or by taking the out-of-position into account. To develop such active safety systems, computer simulations of the occupant’s pre-crash behaviour are

  4. Probabilistic image modeling with an extended chain graph for human activity recognition and image segmentation.

    Science.gov (United States)

    Zhang, Lei; Zeng, Zhi; Ji, Qiang

    2011-09-01

    Chain graph (CG) is a hybrid probabilistic graphical model (PGM) capable of modeling heterogeneous relationships among random variables. So far, however, its application in image and video analysis is very limited due to lack of principled learning and inference methods for a CG of general topology. To overcome this limitation, we introduce methods to extend the conventional chain-like CG model to CG model with more general topology and the associated methods for learning and inference in such a general CG model. Specifically, we propose techniques to systematically construct a generally structured CG, to parameterize this model, to derive its joint probability distribution, to perform joint parameter learning, and to perform probabilistic inference in this model. To demonstrate the utility of such an extended CG, we apply it to two challenging image and video analysis problems: human activity recognition and image segmentation. The experimental results show improved performance of the extended CG model over the conventional directed or undirected PGMs. This study demonstrates the promise of the extended CG for effective modeling and inference of complex real-world problems.

  5. Modeling activity-dependent plasticity in BCM spiking neural networks with application to human behavior recognition.

    Science.gov (United States)

    Meng, Yan; Jin, Yaochu; Yin, Jun

    2011-12-01

    Spiking neural networks (SNNs) are considered to be computationally more powerful than conventional NNs. However, the capability of SNNs in solving complex real-world problems remains to be demonstrated. In this paper, we propose a substantial extension of the Bienenstock, Cooper, and Munro (BCM) SNN model, in which the plasticity parameters are regulated by a gene regulatory network (GRN). Meanwhile, the dynamics of the GRN is dependent on the activation levels of the BCM neurons. We term the whole model "GRN-BCM." To demonstrate its computational power, we first compare the GRN-BCM with a standard BCM, a hidden Markov model, and a reservoir computing model on a complex time series classification problem. Simulation results indicate that the GRN-BCM significantly outperforms the compared models. The GRN-BCM is then applied to two widely used datasets for human behavior recognition. Comparative results on the two datasets suggest that the GRN-BCM is very promising for human behavior recognition, although the current experiments are still limited to the scenarios in which only one object is moving in the considered video sequences.

  6. Therapeutic activity of two xanthones in a xenograft murine model of human chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Berthou Christian

    2010-12-01

    Full Text Available Abstract Background We previously reported that allanxanthone C and macluraxanthone, two xanthones purified from Guttiferae trees, display in vitro antiproliferative and proapoptotic activities in leukemic cells from chronic lymphocytic leukemia (CLL and leukemia B cell lines. Results Here, we investigated the in vivo therapeutic effects of the two xanthones in a xenograft murine model of human CLL, developed by engrafting CD5-transfected chronic leukemia B cells into SCID mice. Treatment of the animals with five daily injections of either allanxanthone C or macluraxanthone resulted in a significant prolongation of their survival as compared to control animals injected with the solvent alone (p = 0.0006 and p = 0.0141, respectively. The same treatment of mice which were not xenografted induced no mortality. Conclusion These data show for the first time the in vivo antileukemic activities of two plant-derived xanthones, and confirm their potential interest for CLL therapy.

  7. Time-Elastic Generative Model for Acceleration Time Series in Human Activity Recognition.

    Science.gov (United States)

    Munoz-Organero, Mario; Ruiz-Blazquez, Ramona

    2017-02-08

    Body-worn sensors in general and accelerometers in particular have been widely used in order to detect human movements and activities. The execution of each type of movement by each particular individual generates sequences of time series of sensed data from which specific movement related patterns can be assessed. Several machine learning algorithms have been used over windowed segments of sensed data in order to detect such patterns in activity recognition based on intermediate features (either hand-crafted or automatically learned from data). The underlying assumption is that the computed features will capture statistical differences that can properly classify different movements and activities after a training phase based on sensed data. In order to achieve high accuracy and recall rates (and guarantee the generalization of the system to new users), the training data have to contain enough information to characterize all possible ways of executing the activity or movement to be detected. This could imply large amounts of data and a complex and time-consuming training phase, which has been shown to be even more relevant when automatically learning the optimal features to be used. In this paper, we present a novel generative model that is able to generate sequences of time series for characterizing a particular movement based on the time elasticity properties of the sensed data. The model is used to train a stack of auto-encoders in order to learn the particular features able to detect human movements. The results of movement detection using a newly generated database with information on five users performing six different movements are presented. The generalization of results using an existing database is also presented in the paper. The results show that the proposed mechanism is able to obtain acceptable recognition rates (F = 0.77) even in the case of using different people executing a different sequence of movements and using different hardware.

  8. Time-Elastic Generative Model for Acceleration Time Series in Human Activity Recognition

    Directory of Open Access Journals (Sweden)

    Mario Munoz-Organero

    2017-02-01

    Full Text Available Body-worn sensors in general and accelerometers in particular have been widely used in order to detect human movements and activities. The execution of each type of movement by each particular individual generates sequences of time series of sensed data from which specific movement related patterns can be assessed. Several machine learning algorithms have been used over windowed segments of sensed data in order to detect such patterns in activity recognition based on intermediate features (either hand-crafted or automatically learned from data. The underlying assumption is that the computed features will capture statistical differences that can properly classify different movements and activities after a training phase based on sensed data. In order to achieve high accuracy and recall rates (and guarantee the generalization of the system to new users, the training data have to contain enough information to characterize all possible ways of executing the activity or movement to be detected. This could imply large amounts of data and a complex and time-consuming training phase, which has been shown to be even more relevant when automatically learning the optimal features to be used. In this paper, we present a novel generative model that is able to generate sequences of time series for characterizing a particular movement based on the time elasticity properties of the sensed data. The model is used to train a stack of auto-encoders in order to learn the particular features able to detect human movements. The results of movement detection using a newly generated database with information on five users performing six different movements are presented. The generalization of results using an existing database is also presented in the paper. The results show that the proposed mechanism is able to obtain acceptable recognition rates (F = 0.77 even in the case of using different people executing a different sequence of movements and using different

  9. SC-535, a Novel Oral Multikinase Inhibitor, Showed Potent Antitumor Activity in Human Melanoma Models

    Directory of Open Access Journals (Sweden)

    Xin Chen

    2013-07-01

    Full Text Available Background: Melanoma is considered as one of the most aggressive and deadliest cancers and current targeted therapies of melanoma often suffer limited efficacy or drug resistance. Discovery of novel multikinase inhibitors as anti-melanoma drug candidates is still needed. Methods: In this investigation, we assessed the in vitro and in vivo anti-melanoma activities of SC-535, which is a novel small molecule multikinase inhibitor discovered by us recently. We analyzed inhibitory effects of SC-535 on various melanoma cell lines and human umbilical vascular endothelial cells (HUVEC in vitro. Tumor xenografts in athymic mice were used to examine the in vivo activity of SC-535. Results: SC-535 could efficiently inhibit vascular endothelial growth factor receptor (VEGFR 1/2/3, B-RAF, and C-RAF kinases. It showed significant antiangiogenic potencies both in vitro and in vivo and considerable anti-proliferative ability against several melanoma cell lines. Oral administration of SC-535 resulted in dose-dependent suppression of tumor growth in WM2664 and C32 xenograft mouse models. Studies of mechanisms of action indicated that SC-535 suppressed the tumor angiogenesis and induced G2/M phase cell cycle arrest in human melanoma cells. SC-535 possesses favorable pharmacokinetic properties. Conclusion: All of these results support SC-535 as a potential candidate for clinical studies in patients with melanoma.

  10. Using structural equation modeling to link human activities to wetland ecological integrity

    Science.gov (United States)

    Schweiger, E. William; Grace, James B.; Cooper, David; Bobowski, Ben; Britten, Mike

    2016-01-01

    The integrity of wetlands is of global concern. A common approach to evaluating ecological integrity involves bioassessment procedures that quantify the degree to which communities deviate from historical norms. While helpful, bioassessment provides little information about how altered conditions connect to community response. More detailed information is needed for conservation and restoration. We have illustrated an approach to addressing this challenge using structural equation modeling (SEM) and long-term monitoring data from Rocky Mountain National Park (RMNP). Wetlands in RMNP are threatened by a complex history of anthropogenic disturbance including direct alteration of hydrologic regimes; elimination of elk, wolves, and grizzly bears; reintroduction of elk (absent their primary predators); and the extirpation of beaver. More recently, nonnative moose were introduced to the region and have expanded into the park. Bioassessment suggests that up to half of the park's wetlands are not in reference condition. We developed and evaluated a general hypothesis about how human alterations influence wetland integrity and then develop a specific model using RMNP wetlands. Bioassessment revealed three bioindicators that appear to be highly sensitive to human disturbance (HD): (1) conservatism, (2) degree of invasion, and (3) cover of native forbs. SEM analyses suggest several ways human activities have impacted wetland integrity and the landscape of RMNP. First, degradation is highest where the combined effects of all types of direct HD have been the greatest (i.e., there is a general, overall effect). Second, specific HDs appear to create a “mixed-bag” of complex indirect effects, including reduced invasion and increased conservatism, but also reduced native forb cover. Some of these effects are associated with alterations to hydrologic regimes, while others are associated with altered shrub production. Third, landscape features created by historical beaver

  11. General human activity patterns

    CERN Document Server

    Mollgaard, Anders; Mathiesen, Joachim

    2016-01-01

    We investigate the dynamics and interplay between human communication, movement, and social proximity by analyzing data collected from smartphones distributed among 638 individuals. The main question we consider is: to what extent do individuals act according to patterns shared across an entire population? Based on statistics of the entire population, we successfully predict 71\\% of the activity and 85\\% of the inactivity involved in communication, movement, and social proximity. We find that individual level statistics only result in marginally better predictions, indicating a high degree of shared activity patterns across the population. Finally, we predict short-term activity patterns using a generalized linear model, which suggests that a simple linear description might be sufficient to explain a wide range of actions, whether they be of social or of physical character.

  12. Attributing runoff changes to climate variability and human activities: uncertainty analysis using four monthly water balance models

    Energy Technology Data Exchange (ETDEWEB)

    Li, Shuai; Xiong, Lihua; Li, Hong-Yi; Leung, L. Ruby; Demissie, Yonas

    2015-05-26

    Hydrological simulations to delineate the impacts of climate variability and human activities are subjected to uncertainties related to both parameter and structure of the hydrological models. To analyze the impact of these uncertainties on the model performance and to yield more reliable simulation results, a global calibration and multimodel combination method that integrates the Shuffled Complex Evolution Metropolis (SCEM) and Bayesian Model Averaging (BMA) of four monthly water balance models was proposed. The method was applied to the Weihe River Basin (WRB), the largest tributary of the Yellow River, to determine the contribution of climate variability and human activities to runoff changes. The change point, which was used to determine the baseline period (1956-1990) and human-impacted period (1991-2009), was derived using both cumulative curve and Pettitt’s test. Results show that the combination method from SCEM provides more skillful deterministic predictions than the best calibrated individual model, resulting in the smallest uncertainty interval of runoff changes attributed to climate variability and human activities. This combination methodology provides a practical and flexible tool for attribution of runoff changes to climate variability and human activities by hydrological models.

  13. P-gp Protein Expression and Transport Activity in Rodent Seizure Models and Human Epilepsy.

    Science.gov (United States)

    Hartz, Anika M S; Pekcec, Anton; Soldner, Emma L B; Zhong, Yu; Schlichtiger, Juli; Bauer, Bjoern

    2017-03-02

    A cure for epilepsy is currently not available, and seizure genesis, seizure recurrence, and resistance to antiseizure drugs remain serious clinical problems. Studies show that the blood-brain barrier is altered in animal models of epilepsy and in epileptic patients. In this regard, seizures increase expression of blood-brain barrier efflux transporters such as P-glycoprotein (P-gp), which is thought to reduce brain uptake of antiseizure drugs, and thus, contribute to antiseizure drug resistance. The goal of the current study was to assess the viability of combining in vivo and ex vivo preparations of isolated brain capillaries from animal models of seizures and epilepsy as well as from patients with epilepsy to study P-gp at the blood-brain barrier. Exposing isolated rat brain capillaries to glutamate ex vivo upregulated P-gp expression to levels that were similar to those in capillaries isolated from rats that had status epilepticus or chronic epilepsy. Moreover, the fold-increase in P-gp protein expression seen in animal models is consistent with the fold-increase in P-gp observed in human brain capillaries isolated from patients with epilepsy compared to age-matched control individuals. Overall, the in vivo/ex vivo approach presented here allows detailed analysis of the mechanisms underlying seizure-induced changes of P-gp expression and transport activity at the blood-brain barrier. This approach can be extended to other blood-brain barrier proteins that might contribute to drug-resistant epilepsy or other CNS disorders as well.

  14. Human migraine models

    DEFF Research Database (Denmark)

    Iversen, Helle Klingenberg

    2001-01-01

    The need for experimental models is obvious. In animal models it is possible to study vascular responses, neurogenic inflammation, c-fos expression etc. However, the pathophysiology of migraine remains unsolved, why results from animal studies not directly can be related to the migraine attack......, which is a human experience. A set-up for investigations of experimental headache and migraine in humans, has been evaluated and headache mechanisms explored by using nitroglycerin and other headache-inducing agents. Nitric oxide (NO) or other parts of the NO activated cascade seems to be responsible...

  15. An Analysis of Audio Features to Develop a Human Activity Recognition Model Using Genetic Algorithms, Random Forests, and Neural Networks

    Directory of Open Access Journals (Sweden)

    Carlos E. Galván-Tejada

    2016-01-01

    Full Text Available This work presents a human activity recognition (HAR model based on audio features. The use of sound as an information source for HAR models represents a challenge because sound wave analyses generate very large amounts of data. However, feature selection techniques may reduce the amount of data required to represent an audio signal sample. Some of the audio features that were analyzed include Mel-frequency cepstral coefficients (MFCC. Although MFCC are commonly used in voice and instrument recognition, their utility within HAR models is yet to be confirmed, and this work validates their usefulness. Additionally, statistical features were extracted from the audio samples to generate the proposed HAR model. The size of the information is necessary to conform a HAR model impact directly on the accuracy of the model. This problem also was tackled in the present work; our results indicate that we are capable of recognizing a human activity with an accuracy of 85% using the HAR model proposed. This means that minimum computational costs are needed, thus allowing portable devices to identify human activities using audio as an information source.

  16. Cognitive improvement by activation of alpha7 nicotinic acetylcholine receptors: from animal models to human pathophysiology

    DEFF Research Database (Denmark)

    Thomsen, Morten S; Hansen, Henrik H; Timmerman, Daniel B

    2010-01-01

    AChR agonists improves learning, memory, and attentional function in variety of animal models, and pro-cognitive effects of alpha(7) nAChR agonists have recently been demonstrated in patients with schizophrenia or Alzheimer's disease. The alpha(7) nAChR desensitizes rapidly in vitro, and this has been a major...... concern in the development of alpha(7) nAChR agonists as putative drugs. Our review of the existing literature shows that development of tolerance to the behavioral effects of alpha(7) nAChR agonists does not occur in animal models or humans. However, the long-term memory-enhancing effects seen in animal...... models are not mimicked in healthy humans and schizophrenic patients, where attentional improvement predominates. This discrepancy may result from inherent differences in testing methods or from species differences in the level of expression of alpha(7) nAChRs in limbic brain regions, and may hamper...

  17. Evidence for a lectin activity for human interleukin 3 and modeling of its carbohydrate recognition domain.

    Science.gov (United States)

    Zanetta, Jean-Pierre; Bindeus, Roland; Normand, Guy; Durier, Viviane; Lagant, Philippe; Maes, Emmanuel; Vergoten, Gérard

    2002-10-11

    We demonstrate that human interleukin 3 (IL-3) is a lectin recognizing specifically the glycosaminoglycan part of a chondroitin sulfate proteoglycan (PGS3; Normand, G., Kuchler, S., Meyer, A., Vincendon, G., and Zanetta, J. P. (1988) J. Neurochem. 51, 665-676) isolated from the adult rat brain. The specificity of the interaction of this particular proteoglycan with IL-3 is due to the abundance of GlcA(2S)beta 1,3GalNAc(4S)beta 1 disaccharide units as suggested by (1)H NMR. Computational docking experiments of the lower energy conformers of the different disaccharides from chondroitin sulfates reveal a privileged binding site for GlcA(2S)beta 1,3GalNAc(4S)beta 1 (involving His-26, Arg-29, Asn-70, and Trp-104) localized in an area of IL-3 different from the receptor-binding domain previously identified by others (Bagley, C. J., Phillips, J., Cambareri, B., Vadas, M. A., and Lopez, A. F. (1996) J. Biol. Chem. 271, 31922-31928). Molecular modeling of the mutation P33G, described as increasing the biological activity of IL-3 without affecting its receptor binding (Lokker, N. A., Movva, N. R., Strittmatter, U., Fagg, B., and Zenke, G. (1991) J. Biol. Chem. 266, 10624-10631) provokes a change of the three-dimensional structure of IL-3, especially in the area of the putative carbohydrate recognition domain defined above. Computational docking experiments of the different disaccharides of chondroitin sulfates indicate a loss of affinity for the previous ligand but a higher affinity for the classic disaccharide of chondroitin-4-sulfate. This change from a rare and specific ligand to a more abundant constituent of proteoglycans could induce an increased quantitative association between the IL-3 receptors and its ligands and, consequently, an increased signaling.

  18. Scalability of human models

    NARCIS (Netherlands)

    Rodarius, C.; Rooij, L. van; Lange, R. de

    2007-01-01

    The objective of this work was to create a scalable human occupant model that allows adaptation of human models with respect to size, weight and several mechanical parameters. Therefore, for the first time two scalable facet human models were developed in MADYMO. First, a scalable human male was

  19. FINITE MARKOV CHAINS IN THE MODEL REPRESENTATION OF THE HUMAN OPERATOR ACTIVITY IN QUASI-FUNCTIONAL ENVIRONMENT

    Directory of Open Access Journals (Sweden)

    M. V. Serzhantova

    2016-05-01

    Full Text Available Subject of Research. We analyze the problems of finite Markov chains apparatus application for simulating a human operator activity in the quasi-static functional environment. It is shown that the functional environment stochastic nature is generated by a factor of interval character of human operator properties. Method. The problem is solved in the class of regular (recurrent finite Markov chains with three states of the human operator: with a favorable, median and unfavorable combination of the values of mathematical model parameters of the human operator in a quasi-static functional environment. The finite Markov chain is designed taking into account the factors of human operator tiredness and interval character of parameters of the model representation of his properties. The device is based on the usage of mathematical approximation of the standard curve of the human operator activity performance during work shift. The standard curve of the human operator activity performance is based on the extensive research experience of functional activity of the human operator with the help of photos of the day, his action timing and ergonomic generalizations. Main Results. The apparatus of regular finite Markov chains gave the possibility to evaluate correctly the human operator activity performance in a quasi-static functional environment with the use of the main information component of these chains as a vector of final probabilities. In addition, we managed to build an algorithmic basis for estimating the stationary time (time study for transit of human operator from arbitrary initial functional state into a state corresponding to a vector of final probabilities for a used chain after it reaches the final state based on the analysis of the eigenvalues spectrum of the matrix of transition probabilities for a regular (recurrent finite Markov chain. Practical Relevance. Obtained theoretical results are confirmed by illustrative examples, which

  20. Experiment-model interaction for analysis of epicardial activation during human ventricular fibrillation with global myocardial ischaemia.

    Science.gov (United States)

    Clayton, R H; Nash, M P; Bradley, C P; Panfilov, A V; Paterson, D J; Taggart, P

    2011-10-01

    We describe a combined experiment-modelling framework to investigate the effects of ischaemia on the organisation of ventricular fibrillation in the human heart. In a series of experimental studies epicardial activity was recorded from 10 patients undergoing routine cardiac surgery. Ventricular fibrillation was induced by burst pacing, and recording continued during 2.5 min of global cardiac ischaemia followed by 30 s of coronary reflow. Modelling used a 2D description of human ventricular tissue. Global cardiac ischaemia was simulated by (i) decreased intracellular ATP concentration and subsequent activation of an ATP sensitive K⁺ current, (ii) elevated extracellular K⁺ concentration, and (iii) acidosis resulting in reduced magnitude of the L-type Ca²⁺ current I(Ca,L). Simulated ischaemia acted to shorten action potential duration, reduce conduction velocity, increase effective refractory period, and flatten restitution. In the model, these effects resulted in slower re-entrant activity that was qualitatively consistent with our observations in the human heart. However, the flattening of restitution also resulted in the collapse of many re-entrant waves to several stable re-entrant waves, which was different to the overall trend we observed in the experimental data. These findings highlight a potential role for other factors, such as structural or functional heterogeneity in sustaining wavebreak during human ventricular fibrillation with global myocardial ischaemia.

  1. Active immunotherapy of allergic asthma with a recombinant human interleukin-5 protein as vaccine in a murine model

    Institute of Scientific and Technical Information of China (English)

    TAN Guang-hong; WANG Cai-chun; HUANG Feng-ying; WANG Hua; HUANG Yong-hao; LIN Ying-ying

    2007-01-01

    Background Eosinophils are highly related to allergic asthma inflammation. Interleukin (IL)-5 is the major chemokine of eosinophils, inhibition of the activity of IL-5 thus seems to be a potential approach to asthma therapy. The current study was performed to determine whether a recombinant human IL-5 protein as a xenogeneic vaccine has the capability of inducing anti-asthma activities.Methods Recombinant human IL-5 was used as a protein vaccine. Mouse asthma model was established to observe the anti-asthma activities. Lung histology was observed; eosinophils in blood and bronchoalveolar lavage were stained and counted. Airway hyperresponsiveness was determined by whole body plethysmograph. Antibody characters and cytokines were detected with enzyme linked immunosorbent assay (ELISA) and Western blot assay.Results Vaccination with recombinant human IL-5 protein as vaccine significantly reduced airway inflammation and airway hyperresponsiveness, and shifted the cytokine production from Th2 (IL-4) to Th1 (INF-γ) in mice allergic-asthma model. Immunization with recombinant human IL-5 protein vaccine bypassed the immunological tolerance and induced production of polyclonal antibodies that were cross-reactive with murine IL-5.Conclusions Active immunization with xenogeneic homologous IL-5 may be a possible therapeutic approach to the treatment of asthma and potentially of other eosinophilic disorders.

  2. Telomere Lengths and Telomerase Activity in Dog Tissues: A Potential Model System to Study Human Telomere and Telomerase Biology

    Directory of Open Access Journals (Sweden)

    Lubna Nasir

    2001-01-01

    Full Text Available Studies on telomere and telomerase biology are fundamental to the understanding of aging and age-related diseases such as cancer. However, human studies have been hindered by differences in telomere biology between humans and the classical murine animal model system. In this paper, we describe basic studies of telomere length and telomerase activity in canine normal and neoplastic tissues and propose the dog as an alternative model system. Briefly, telomere lengths were measured in normal canine peripheral blood mononuclear cells (PBMCs, a range of normal canine tissues, and in a panel of naturally occurring soft tissue tumours by terminal restriction fragment (TRF analysis. Further, telomerase activity was measured in canine cell lines and multiple canine tissues using a combined polymerase chain reaction/enzyme-linked immunosorbent assay method. TRF analysis in canine PBMCs and tissues demonstrated mean TRF lengths to range between 12 and 23 kbp with heterogeneity in telomere lengths being observed in a range of normal somatic tissues. In soft tissue sarcomas, two subgroups were identified with mean TRFs of 22.2 and 18.2 kbp. Telomerase activity in canine tissue was present in tumour tissue and testis with little or no activity in normal somatic tissues. These results suggest that the dog telomere biology is similar to that in humans and may represent an alternative model system for studying telomere biology and telomerase-targeted anticancer therapies.

  3. Sepsis and Inflammatory Response Mechanisms: An Activity Stress Model in Humans

    Science.gov (United States)

    2001-01-31

    Suzui M, Zamecnik 1, Sabiston BH, Shek PN, Shephard RJ. B- endorphin and natural killer cell activity during prolonged exercise. Is there a connection? Am...A.A. and Wilmore, D.W. 1996. The systemic inflammatory response: Perspective of human endotoxemia. Shock 6: S50-S56. Shek, P.N., Sabiston , B.H...Gannon, G., Rhind, S.G., Suzui, M., Zamecnik, J., Sabiston , B.H., Shek, P.N. & Shephard, R.J. (1998). B-endorphin and natural killer cell cytolytic

  4. Identification of FGFR4-activating mutations in human rhabdomyosarcomas that promote metastasis in xenotransplanted models.

    Science.gov (United States)

    Taylor, James G; Cheuk, Adam T; Tsang, Patricia S; Chung, Joon-Yong; Song, Young K; Desai, Krupa; Yu, Yanlin; Chen, Qing-Rong; Shah, Kushal; Youngblood, Victoria; Fang, Jun; Kim, Su Young; Yeung, Choh; Helman, Lee J; Mendoza, Arnulfo; Ngo, Vu; Staudt, Louis M; Wei, Jun S; Khanna, Chand; Catchpoole, Daniel; Qualman, Stephen J; Hewitt, Stephen M; Merlino, Glenn; Chanock, Stephen J; Khan, Javed

    2009-11-01

    Rhabdomyosarcoma (RMS) is a childhood cancer originating from skeletal muscle, and patient survival is poor in the presence of metastatic disease. Few determinants that regulate metastasis development have been identified. The receptor tyrosine kinase FGFR4 is highly expressed in RMS tissue, suggesting a role in tumorigenesis, although its functional importance has not been defined. Here, we report the identification of mutations in FGFR4 in human RMS tumors that lead to its activation and present evidence that it functions as an oncogene in RMS. Higher FGFR4 expression in RMS tumors was associated with advanced-stage cancer and poor survival, while FGFR4 knockdown in a human RMS cell line reduced tumor growth and experimental lung metastases when the cells were transplanted into mice. Moreover, 6 FGFR4 tyrosine kinase domain mutations were found among 7 of 94 (7.5%) primary human RMS tumors. The mutants K535 and E550 increased autophosphorylation, Stat3 signaling, tumor proliferation, and metastatic potential when expressed in a murine RMS cell line. These mutants also transformed NIH 3T3 cells and led to an enhanced metastatic phenotype. Finally, murine RMS cell lines expressing the K535 and E550 FGFR4 mutants were substantially more susceptible to apoptosis in the presence of a pharmacologic FGFR inhibitor than the control cell lines expressing the empty vector or wild-type FGFR4. Together, our results demonstrate that mutationally activated FGFR4 acts as an oncogene, and these are what we believe to be the first known mutations in a receptor tyrosine kinase in RMS. These findings support the potential therapeutic targeting of FGFR4 in RMS.

  5. QGP-1 cells release 5-HT via TRPA1 activation; a model of human enterochromaffin cells.

    Science.gov (United States)

    Doihara, Hitoshi; Nozawa, Katsura; Kojima, Ryosuke; Kawabata-Shoda, Eri; Yokoyama, Toshihide; Ito, Hiroyuki

    2009-11-01

    Recently, we discovered that transient receptor potential ankyrin1 channel (TRPA1) is highly expressed in human and rat enterochromaffin (EC) cells, and those TRPA1 agonists such as allyl isothiocyanates (AITC) and cinnamaldehyde (CA) enhance the release of serotonin (5-hydroxytryptamine; 5-HT) from EC cells in vitro. In this study, QGP-1 cells, a human pancreatic endocrine cell line, were found to highly express TRPA1 and EC cell marker genes, such as tryptophan hydroxylase 1 (TPH1), chromogranin A (CgA), synaptophysin, ATP-dependent vesicular monoamine transporter 1 (VMAT1), metabotropic glutamate receptor 4 (mGluR4), beta1-adrenergic receptor (ADB1), muscarinic 4 acetylcholine receptor (ACM4), substance P, serotonin transporter (SERT), and guanylin. Furthermore, the TRPA1 agonists AITC, CA, and acrolein concentration dependently evoked an increase in intracellular Ca(2+) influx and the release of 5-HT in QGP-1 cells. The effects of these TRPA1 agonists were inhibited by ruthenium red, a TRPA1 antagonist, and TRPA1-specific siRNA. These results indicate that the Ca(2+) influx increase and 5-HT release induced by AITC, CA and acrolein in QGP-1 cells were mediated by TRPA1, and that the QGP-1 cell line could be a new model for the investigation of TRPA1 function in the human EC cell.

  6. Research and Application of Fire Forecasting Model for Electric Transmission Lines Incorporating Meteorological Data and Human Activities

    Directory of Open Access Journals (Sweden)

    Jiazheng Lu

    2016-01-01

    Full Text Available Recently, there is a rise in frequency of fires which pose a serious threat to the safety operation of electric transmission lines. Several ultrahigh voltage (UHV electric transmission lines, including Fufeng line, Jinsu line, Longzheng line, and Changnan line, showed many times tripping or bipolar latching caused by fire disasters. Fire disasters have tended to be the biggest threat to the safety operation of electric transmission lines and even can cause power grid collapse in some severe situations. Researchers have made much research on fires forecasting. However, these studies are mainly concentrated on predicting fires based on measured or forecasting meteorological data and do not take into account the effect of human activities. In fact, fire disasters have a very close relationship with human activities. In our research, a fire prediction model is proposed incorporating meteorological data as well as human activities. And this model is applied in Hunan province and Anhui province, which seriously suffer from fire disasters. The results show that the model has good prediction precision and can be a powerful tool for practical application.

  7. Valproic Acid Induces Hair Regeneration in Murine Model and Activates Alkaline Phosphatase Activity in Human Dermal Papilla Cells

    Science.gov (United States)

    Lee, Soung-Hoon; Yoon, Juyong; Shin, Seung Ho; Zahoor, Muhamad; Kim, Hyoung Jun; Park, Phil June; Park, Won-Seok; Min, Do Sik; Kim, Hyun-Yi; Choi, Kang-Yell

    2012-01-01

    Background Alopecia is the common hair loss problem that can affect many people. However, current therapies for treatment of alopecia are limited by low efficacy and potentially undesirable side effects. We have identified a new function for valproic acid (VPA), a GSK3β inhibitor that activates the Wnt/β-catenin pathway, to promote hair re-growth in vitro and in vivo. Methodology/ Principal Findings Topical application of VPA to male C3H mice critically stimulated hair re-growth and induced terminally differentiated epidermal markers such as filaggrin and loricrin, and the dermal papilla marker alkaline phosphatase (ALP). VPA induced ALP in human dermal papilla cells by up-regulating the Wnt/β-catenin pathway, whereas minoxidil (MNX), a drug commonly used to treat alopecia, did not significantly affect the Wnt/β-catenin pathway. VPA analogs and other GSK3β inhibitors that activate the Wnt/β-catenin pathway such as 4-phenyl butyric acid, LiCl, and BeCl2 also exhibited hair growth-promoting activities in vivo. Importantly, VPA, but not MNX, successfully stimulate hair growth in the wounds of C3H mice. Conclusions/ Significance Our findings indicate that small molecules that activate the Wnt/β-catenin pathway, such as VPA, can potentially be developed as drugs to stimulate hair re-growth. PMID:22506014

  8. Valproic acid induces hair regeneration in murine model and activates alkaline phosphatase activity in human dermal papilla cells.

    Directory of Open Access Journals (Sweden)

    Soung-Hoon Lee

    Full Text Available BACKGROUND: Alopecia is the common hair loss problem that can affect many people. However, current therapies for treatment of alopecia are limited by low efficacy and potentially undesirable side effects. We have identified a new function for valproic acid (VPA, a GSK3β inhibitor that activates the Wnt/β-catenin pathway, to promote hair re-growth in vitro and in vivo. METHODOLOGY/ PRINCIPAL FINDINGS: Topical application of VPA to male C3H mice critically stimulated hair re-growth and induced terminally differentiated epidermal markers such as filaggrin and loricrin, and the dermal papilla marker alkaline phosphatase (ALP. VPA induced ALP in human dermal papilla cells by up-regulating the Wnt/β-catenin pathway, whereas minoxidil (MNX, a drug commonly used to treat alopecia, did not significantly affect the Wnt/β-catenin pathway. VPA analogs and other GSK3β inhibitors that activate the Wnt/β-catenin pathway such as 4-phenyl butyric acid, LiCl, and BeCl(2 also exhibited hair growth-promoting activities in vivo. Importantly, VPA, but not MNX, successfully stimulate hair growth in the wounds of C3H mice. CONCLUSIONS/ SIGNIFICANCE: Our findings indicate that small molecules that activate the Wnt/β-catenin pathway, such as VPA, can potentially be developed as drugs to stimulate hair re-growth.

  9. Phoneme restoration and empirical coverage of interactive activation and adaptive resonance models of human speech processing.

    Science.gov (United States)

    Magnuson, James S

    2015-03-01

    Grossberg and Kazerounian [(2011). J. Acoust. Soc. Am. 130, 440-460] present a model of sequence representation for spoken word recognition, the cARTWORD model, which simulates essential aspects of phoneme restoration. Grossberg and Kazerounian also include simulations with the TRACE model presented by McClelland and Elman [(1986). Cognit. Psychol. 18, 1-86] that seem to indicate that TRACE cannot simulate phoneme restoration. Grossberg and Kazerounian also claim cARTWORD should be preferred to TRACE because of TRACE's implausible approach to sequence representation (reduplication of time-specific units) and use of non-modulatory feedback (i.e., without position-specific bottom-up support). This paper responds to Grossberg and Kazerounian first with TRACE simulations that account for phoneme restoration when appropriately constructed noise is used (and with minor changes to TRACE phoneme definitions), then reviews the case for reduplicated units and feedback as implemented in TRACE, as well as TRACE's broad and deep coverage of empirical data. Finally, it is argued that cARTWORD is not comparable to TRACE because cARTWORD cannot represent sequences with repeated elements, has only been implemented with small phoneme and lexical inventories, and has been applied to only one phenomenon (phoneme restoration). Without evidence that cARTWORD captures a similar range and detail of human spoken language processing as alternative models, it is premature to prefer cARTWORD to TRACE.

  10. 1,25D3 enhances antitumor activity of gemcitabine and cisplatin in human bladder cancer models

    Science.gov (United States)

    Ma, Yingyu; Yu, Wei-Dong; Trump, Donald L.; Johnson, Candace S.

    2010-01-01

    Background 1,25 dihydroxyvitamin D3 (1,25D3) potentiates the cytotoxic effects of several common chemotherapeutic agents. The combination of gemcitabine and cisplatin (GC) is a current standard chemotherapy regimen for bladder cancer. We investigated whether 1,25D3 could enhance the antitumor activity of GC in bladder cancer model systems. Methods Human bladder cancer T24 and UMUC3 cells were pretreated with 1,25D3 followed by GC. Apoptosis were assessed by annexin V staining. Caspase activation was examined by immunoblot analysis and substrate-based caspase activity assay. The cytotoxic effects were examined using MTT and in vitro clonogenic assay. p73 protein levels were assessed by immunoblot analysis. Knockdown of p73 was achieved by siRNA. The in vivo antitumor activity was assessed by in vivo excision clonogenic assay and tumor regrowth delay in the T24 xenograft model. Results 1,25D3 pretreatment enhanced GC-induced apoptosis and the activities of caspases- 8, 9 and 3 in T24 and UMUC3 cells. 1,25D3 synergistically reduced GC-suppressed surviving fraction in T24 cells. 1,25D3, gemcitabine, or cisplatin induced p73 accumulation, which was enhanced by GC or 1,25D3 and GC. p73 expression was lower in human primary bladder tumor tissue compared with adjacent normal tissue. Knockdown of p73 increased clonogenic capacity of T24 cells treated with 1,25D3, GC or 1,25D3 and GC. 1,25D3 and GC combination enhanced tumor regression compared with 1,25D3 or GC alone. Conclusions 1,25D3 potentiates GC-mediated growth inhibition in human bladder cancer models in vitro and in vivo, which involves p73 induction and apoptosis. PMID:20564622

  11. Interactive production planning and ergonomic assessment with Digital Human Models--introducing the Editor for Manual Work Activities (ema).

    Science.gov (United States)

    Fritzsche, Lars; Leidholdt, Wolfgang; Bauer, Sebastian; Jäckel, Thomas; Moreno, Adrian

    2012-01-01

    The aging workforce is a risk factor for manufacturing industries that contain many jobs with high physical workloads. Thus, ergonomic risk factors have to be avoided in early phases of production planning. This paper introduces a new tool for simulating manual work activities with 3D human models, the so-called emaΦ. For the most part, the emaΦ software is based on a unique modular approach including a number of complex operations that were theoretically developed and empirically validated by means of motion capturing technologies. Using these modules for defining the digital work process enables the production planner to compile human simulations more accurately and much quicker compared to any of the existing modeling tools. Features of the emaΦ software implementation, such as ergonomic evaluation and MTM-time analyses, and the workflow for practical application are presented.

  12. Antitumor Activity of Human Hydatid Cyst Fluid in a Murine Model of Colon Cancer

    Directory of Open Access Journals (Sweden)

    Edgardo Berriel

    2013-01-01

    Full Text Available This study evaluates the antitumor immune response induced by human hydatic cyst fluid (HCF in an animal model of colon carcinoma. We found that anti-HCF antibodies were able to identify cell surface and intracellular antigens in CT26 colon cancer cells. In prophylactic tumor challenge experiments, HCF vaccination was found to be protective against tumor formation for 40% of the mice (P=0.01. In the therapeutic setting, HCF vaccination induced tumor regression in 40% of vaccinated mice (P=0.05. This vaccination generated memory immune responses that protected surviving mice from tumor rechallenge, implicating the development of an adaptive immune response in this process. We performed a proteomic analysis of CT26 antigens recognized by anti-HCF antibodies to analyze the immune cross-reactivity between E. granulosus (HCF and CT26 colon cancer cells. We identified two proteins: mortalin and creatine kinase M-type. Interestingly, CT26 mortalin displays 60% homology with E. granulosus hsp70. In conclusion, our data demonstrate the capacity of HCF vaccination to induce antitumor immunity which protects from tumor growth in an animal model. This new antitumor strategy could open new horizons in the development of highly immunogenic anticancer vaccines.

  13. Antitumor Activity of Human Hydatid Cyst Fluid in a Murine Model of Colon Cancer

    Science.gov (United States)

    Russo, Sofía; Berois, Nora; Fernández, Gabriel; Freire, Teresa; Osinaga, Eduardo

    2013-01-01

    This study evaluates the antitumor immune response induced by human hydatic cyst fluid (HCF) in an animal model of colon carcinoma. We found that anti-HCF antibodies were able to identify cell surface and intracellular antigens in CT26 colon cancer cells. In prophylactic tumor challenge experiments, HCF vaccination was found to be protective against tumor formation for 40% of the mice (P = 0.01). In the therapeutic setting, HCF vaccination induced tumor regression in 40% of vaccinated mice (P = 0.05). This vaccination generated memory immune responses that protected surviving mice from tumor rechallenge, implicating the development of an adaptive immune response in this process. We performed a proteomic analysis of CT26 antigens recognized by anti-HCF antibodies to analyze the immune cross-reactivity between E. granulosus (HCF) and CT26 colon cancer cells. We identified two proteins: mortalin and creatine kinase M-type. Interestingly, CT26 mortalin displays 60% homology with E. granulosus hsp70. In conclusion, our data demonstrate the capacity of HCF vaccination to induce antitumor immunity which protects from tumor growth in an animal model. This new antitumor strategy could open new horizons in the development of highly immunogenic anticancer vaccines. PMID:24023528

  14. Abnormal network activity in a targeted genetic model of human double cortex.

    Science.gov (United States)

    Ackman, James B; Aniksztejn, Laurent; Crépel, Valérie; Becq, Hélène; Pellegrino, Christophe; Cardoso, Carlos; Ben-Ari, Yehezkel; Represa, Alfonso

    2009-01-14

    In human patients, cortical dysplasia produced by Doublecortin (DCX) mutations lead to mental retardation and intractable infantile epilepsies, but the underlying mechanisms are not known. DCX(-/-) mice have been generated to investigate this issue. However, they display no neocortical abnormality, lessening their impact on the field. In contrast, in utero knockdown of DCX RNA produces a morphologically relevant cortical band heterotopia in rodents. On this preparation we have now compared the neuronal and network properties of ectopic, overlying, and control neurons in an effort to identify how ectopic neurons generate adverse patterns that will impact cortical activity. We combined dynamic calcium imaging and anatomical and electrophysiological techniques and report now that DCX(-/-)EGFP(+)-labeled ectopic neurons that fail to migrate develop extensive axonal subcortical projections and retain immature properties, and most of them display a delayed maturation of GABA-mediated signaling. Cortical neurons overlying the heterotopia, in contrast, exhibit a massive increase of ongoing glutamatergic synaptic currents reflecting a strong reactive plasticity. Neurons in both experimental fields are more frequently coactive in coherent synchronized oscillations than control cortical neurons. In addition, both fields displayed network-driven oscillations during evoked epileptiform burst. These results show that migration disorders produce major alterations not only in neurons that fail to migrate but also in their programmed target areas. We suggest that this duality play a major role in cortical dysfunction of DCX brains.

  15. Calcitriol enhances gemcitabine antitumor activity in vitro and in vivo by promoting apoptosis in a human pancreatic carcinoma model system

    Science.gov (United States)

    Yu, Wei-Dong; Ma, Yingyu; Flynn, Geraldine; Muindi, Josephia R; Kong, Rui-Xian; Trump, Donald L

    2010-01-01

    Gemcitabine is the standard care chemotherapeutic agent to treat pancreatic cancer. Previously we demonstrated that calcitriol (1, 25-dihydroxycholecalciferol) has significant anti-proliferative effects in vitro and in vivo in multiple tumor models and enhances the activity of a variety of chemotherapeutic agents. We therefore investigated whether calcitriol could potentiate the cytotoxic activity of gemcitabine in the human pancreatic cancer Capan-1 model system. Isobologram analysis revealed that calcitriol and gemcitabine had synergistic antiproliferative effect over a wide range of drug concentrations. Calcitriol did not reduce the cytidine deaminase activity in Capan-1 tumors nor in the livers of Capan-1 tumor bearing mice. Calcitriol and gemcitabine combination promoted apoptosis in Capan-1 cells compared with either agent alone. The combination treatment also increased the activation of caspases-8, -9, -6 and -3 in Capan-1 cells. This result was confirmed by substrate-based caspase activity assay. Akt phosphorylation was reduced by calcitriol and gemcitabine combination treatment compared to single agent treatment. However, ERK1/2 phosphorylation was not modulated by either agent alone or by the combination. Tumor regrowth delay studies showed that calcitriol in combination with gemcitabine resulted in a significant reduction of Capan-1 tumor volume compared to single agent treatment. Our study suggests that calcitriol and gemcitabine in combination promotes caspase-dependent apoptosis, which may contribute to increased anti-tumor activity compared to either agent alone. PMID:20699664

  16. Turbulent electrical activity at sharp-edged inexcitable obstacles in a model for human cardiac tissue.

    Science.gov (United States)

    Majumder, Rupamanjari; Pandit, Rahul; Panfilov, A V

    2014-10-01

    Wave propagation around various geometric expansions, structures, and obstacles in cardiac tissue may result in the formation of unidirectional block of wave propagation and the onset of reentrant arrhythmias in the heart. Therefore, we investigated the conditions under which reentrant spiral waves can be generated by high-frequency stimulation at sharp-edged obstacles in the ten Tusscher-Noble-Noble-Panfilov (TNNP) ionic model for human cardiac tissue. We show that, in a large range of parameters that account for the conductance of major inward and outward ionic currents of the model [fast inward Na(+) current (INa), L-type slow inward Ca(2+) current (ICaL), slow delayed-rectifier current (IKs), rapid delayed-rectifier current (IKr), inward rectifier K(+) current (IK1)], the critical period necessary for spiral formation is close to the period of a spiral wave rotating in the same tissue. We also show that there is a minimal size of the obstacle for which formation of spirals is possible; this size is ∼2.5 cm and decreases with a decrease in the excitability of cardiac tissue. We show that other factors, such as the obstacle thickness and direction of wave propagation in relation to the obstacle, are of secondary importance and affect the conditions for spiral wave initiation only slightly. We also perform studies for obstacle shapes derived from experimental measurements of infarction scars and show that the formation of spiral waves there is facilitated by tissue remodeling around it. Overall, we demonstrate that the formation of reentrant sources around inexcitable obstacles is a potential mechanism for the onset of cardiac arrhythmias in the presence of a fast heart rate.

  17. Improved experimental model for measuring skin degerming activity on the human hand.

    Science.gov (United States)

    Michaud, R N; McGrath, M B; Goss, W A

    1972-07-01

    A gloved-hand method is presented for evaluating the interaction of antimicrobial agents with the normal resident bacterial flora of human skin. One of the key features of the experimental model is a simplified technique for sampling the skin, which involves the addition of eluting fluid to the gloved hand. As with other skin sampling techniques, the number of bacteria recovered from the hands showed considerable variation from subject to subject. However, no significant differences were observed between the numbers of bacteria recovered from the right and left hands of individual subjects. The mean number of bacteria recovered from the hand before and after washing with nonmedicated soap was consistent and reproducible over a period of at least 5 consecutive days. The number of recoverable bacteria from the hand was greatly reduced by a single treatment with a surgical scrub preparation containing hexachlorophene. The extent of skin degerming achieved was little affected by the use of a surgical brush, and was maximal at approximately 30 min after contact with the hexachlorophene-containing formulation. It was determined that the level of transient bacteria on the hands could be controlled by a simple wash with nonmedicated soap, resulting in a stabilized base-line level from which treatment interactions with the resident microflora could be measured more precisely. The basic elements of the method presented fulfill the requirements of a satisfactory experimental model for the in vivo evaluation of skin-degerming agents on the hand. The selection of appropriate experimental designs allows treatment comparisons to be made with a high degree of statistical confidence.

  18. Cognitive improvement by activation of alpha7 nicotinic acetylcholine receptors: from animal models to human pathophysiology

    DEFF Research Database (Denmark)

    Thomsen, Morten S; Hansen, Henrik H; Timmerman, Daniel B

    2010-01-01

    Agonists and positive allosteric modulators of the alpha(7) nicotinic acetylcholine receptor (nAChR) are currently being developed for the treatment of cognitive disturbances in patients with schizophrenia or Alzheimer's disease. This review describes the neurobiological properties of the alpha n......AChR and the cognitive effects of alpha(7) nAChR activation, focusing on the translational aspects in the development of these drugs. The functional properties and anatomical localization of the alpha(7) nAChR makes it well suited to modulate cognitive function. Accordingly, systemic administration of alpha(7) n......AChR agonists improves learning, memory, and attentional function in variety of animal models, and pro-cognitive effects of alpha(7) nAChR agonists have recently been demonstrated in patients with schizophrenia or Alzheimer's disease. The alpha(7) nAChR desensitizes rapidly in vitro, and this has been a major...

  19. Formulation development of transdermal dosage forms: quantitative structure-activity relationship model for predicting activities of terpenes that enhance drug penetration through human skin.

    Science.gov (United States)

    Kang, L; Yap, C W; Lim, P F C; Chen, Y Z; Ho, P C; Chan, Y W; Wong, G P; Chan, S Y

    2007-07-31

    Terpenes and terpenoids have been used as enhancers in transdermal formulations for facilitating penetration of drugs into human skin. Knowledge of the correlation between the human skin penetration effect (HSPE) and the physicochemical properties of these enhancers is important for facilitating the discovery and development of more enhancers. In this work, the HSPE of 49 terpenes and terpenoids were compared by the in vitro permeability coefficients of haloperidol (HP) through excised human skin. A first-order multiple linear regression (MLR) model was constructed to link the permeability coefficient of the drug to the lipophilicity, molecular weight, boiling point, the terpene type and the functional group of each enhancer. The Quantitative Structure-Activity Relationship (QSAR) model was derived from our data generated by using standardized experimental protocols, which include: HP in propylene glycol (PG) of 3 mg/ml as the donor solution containing 5% (w/v) of the respective terpene, the same composition and volume of receptor solution, similar human skin samples, in the same set of automated flow-through diffusion cells. The model provided a simple method to predict the enhancing effects of terpenes for drugs with physicochemical properties similar to HP. Our study suggested that an ideal terpene enhancer should possess at least one or combinations of the following properties: hydrophobic, in liquid form at room temperature, with an ester or aldehyde but not acid functional group, and is neither a triterpene nor tetraterpene. Possible mechanisms revealed by the QSAR model were discussed.

  20. Modulation of antioxidant enzymatic activities by certain antiepileptic drugs (valproic acid, oxcarbazepine, and topiramate): evidence in humans and experimental models.

    Science.gov (United States)

    Cárdenas-Rodríguez, Noemí; Coballase-Urrutia, Elvia; Rivera-Espinosa, Liliana; Romero-Toledo, Arantxa; Sampieri, Aristides; Ortega-Cuellar, Daniel; Montesinos-Correa, Hortencia; Floriano-Sánchez, Esaú; Carmona-Aparicio, Liliana

    2013-01-01

    It is estimated that at least 100 million people worldwide will suffer from epilepsy at some point in their lives. This neurological disorder induces brain death due to the excessive liberation of glutamate, which activates the postsynaptic N-methyl-D-aspartic acid (NMDA) receptors, which in turn cause the reuptake of intracellular calcium (excitotoxicity). This excitotoxicity elicits a series of events leading to nitric oxide synthase (NOS) activation and the generation of reactive oxygen species (ROS). Several studies in experimental models and in humans have demonstrated that certain antiepileptic drugs (AEDs) exhibit antioxidant effects by modulating the activity of various enzymes associated with this type of stress. Considering the above-mentioned data, we aimed to compile evidence elucidating how AEDs such as valproic acid (VPA), oxcarbazepine (OXC), and topiramate (TPM) modulate oxidative stress.

  1. Modulation of Antioxidant Enzymatic Activities by Certain Antiepileptic Drugs (Valproic Acid, Oxcarbazepine, and Topiramate): Evidence in Humans and Experimental Models

    Science.gov (United States)

    Cárdenas-Rodríguez, Noemí; Coballase-Urrutia, Elvia; Rivera-Espinosa, Liliana; Romero-Toledo, Arantxa; Sampieri, Aristides III; Ortega-Cuellar, Daniel; Montesinos-Correa, Hortencia; Floriano-Sánchez, Esaú; Carmona-Aparicio, Liliana

    2013-01-01

    It is estimated that at least 100 million people worldwide will suffer from epilepsy at some point in their lives. This neurological disorder induces brain death due to the excessive liberation of glutamate, which activates the postsynaptic N-methyl-D-aspartic acid (NMDA) receptors, which in turn cause the reuptake of intracellular calcium (excitotoxicity). This excitotoxicity elicits a series of events leading to nitric oxide synthase (NOS) activation and the generation of reactive oxygen species (ROS). Several studies in experimental models and in humans have demonstrated that certain antiepileptic drugs (AEDs) exhibit antioxidant effects by modulating the activity of various enzymes associated with this type of stress. Considering the above-mentioned data, we aimed to compile evidence elucidating how AEDs such as valproic acid (VPA), oxcarbazepine (OXC), and topiramate (TPM) modulate oxidative stress. PMID:24454986

  2. Modulation of Antioxidant Enzymatic Activities by Certain Antiepileptic Drugs (Valproic Acid, Oxcarbazepine, and Topiramate: Evidence in Humans and Experimental Models

    Directory of Open Access Journals (Sweden)

    Noemí Cárdenas-Rodríguez

    2013-01-01

    Full Text Available It is estimated that at least 100 million people worldwide will suffer from epilepsy at some point in their lives. This neurological disorder induces brain death due to the excessive liberation of glutamate, which activates the postsynaptic N-methyl-D-aspartic acid (NMDA receptors, which in turn cause the reuptake of intracellular calcium (excitotoxicity. This excitotoxicity elicits a series of events leading to nitric oxide synthase (NOS activation and the generation of reactive oxygen species (ROS. Several studies in experimental models and in humans have demonstrated that certain antiepileptic drugs (AEDs exhibit antioxidant effects by modulating the activity of various enzymes associated with this type of stress. Considering the above-mentioned data, we aimed to compile evidence elucidating how AEDs such as valproic acid (VPA, oxcarbazepine (OXC, and topiramate (TPM modulate oxidative stress.

  3. Modulation of protease activated receptor 1 influences human metapneumovirus disease severity in a mouse model.

    Directory of Open Access Journals (Sweden)

    Laetitia Aerts

    Full Text Available Human metapneumovirus (hMPV infection causes acute respiratory tract infections (RTI which can result in hospitalization of both children and adults. To date, no antiviral or vaccine is available for this common viral infection. Immunomodulators could represent an interesting strategy for the treatment of severe viral infection. Recently, the role of protease-activated receptors (PAR in inflammation, coagulation and infection processes has been of growing interest. Herein, the effects of a PAR1 agonist and a PAR1 antagonist on hMPV infection were investigated in BALB/c mice. Intranasal administration of the PAR1 agonist resulted in increased weight loss and mortality of infected mice. Conversely, the PAR1 antagonist was beneficial to hMPV infection by decreasing weight loss and clinical signs and by significantly reducing pulmonary inflammation, pro-inflammatory cytokine levels (including IL-6, KC and MCP-1 and recruitment of immune cells to the lungs. In addition, a significant reduction in pulmonary viral titers was also observed in the lungs of PAR1 antagonist-treated mice. Despite no apparent direct effect on virus replication during in vitro experiments, an important role for PAR1 in the regulation of furin expression in the lungs was shown for the first time. Further experiments indicated that the hMPV fusion protein can be cleaved by furin thus suggesting that PAR1 could have an effect on viral infectivity in addition to its immunomodulatory properties. Thus, inhibition of PAR1 by selected antagonists could represent an interesting strategy for decreasing the severity of paramyxovirus infections.

  4. Membrane-dependent Activities of Human 15-LOX-2 and Its Murine Counterpart: IMPLICATIONS FOR MURINE MODELS OF ATHEROSCLEROSIS.

    Science.gov (United States)

    Bender, Gunes; Schexnaydre, Erin E; Murphy, Robert C; Uhlson, Charis; Newcomer, Marcia E

    2016-09-01

    The enzyme encoded by the ALOX15B gene has been linked to the development of atherosclerotic plaques in humans and in a mouse model of hypercholesterolemia. In vitro, these enzymes, which share 78% sequence identity, generate distinct products from their substrate arachidonic acid: the human enzyme, a 15-S-hydroperoxy product; and the murine enzyme, an 8-S-product. We probed the activities of these enzymes with nanodiscs as membrane mimics to determine whether they can access substrate esterified in a bilayer and characterized their activities at the membrane interface. We observed that both enzymes transform phospholipid-esterified arachidonic acid to a 15-S-product. Moreover, when expressed in transfected HEK cells, both enzymes result in significant increases in the amounts of 15-hydroxyderivatives of eicosanoids detected. In addition, we show that 15-LOX-2 is distributed at the plasma membrane when the HEK293 cells are stimulated by the addition Ca(2+) ionophore and that cellular localization is dependent upon the presence of a putative membrane insertion loop. We also report that sequence differences between the human and mouse enzymes in this loop appear to confer distinct mechanisms of enzyme-membrane interaction for the homologues.

  5. Additive reductions in zebrafish PRPS1 activity result in a spectrum of deficiencies modeling several human PRPS1-associated diseases

    Science.gov (United States)

    Pei, Wuhong; Xu, Lisha; Varshney, Gaurav K.; Carrington, Blake; Bishop, Kevin; Jones, MaryPat; Huang, Sunny C.; Idol, Jennifer; Pretorius, Pamela R.; Beirl, Alisha; Schimmenti, Lisa A.; Kindt, Katie S.; Sood, Raman; Burgess, Shawn M.

    2016-01-01

    Phosphoribosyl pyrophosphate synthetase-1 (PRPS1) is a key enzyme in nucleotide biosynthesis, and mutations in PRPS1 are found in several human diseases including nonsyndromic sensorineural deafness, Charcot-Marie-Tooth disease-5, and Arts Syndrome. We utilized zebrafish as a model to confirm that mutations in PRPS1 result in phenotypic deficiencies in zebrafish similar to those in the associated human diseases. We found two paralogs in zebrafish, prps1a and prps1b and characterized each paralogous mutant individually as well as the double mutant fish. Zebrafish prps1a mutants and prps1a;prps1b double mutants showed similar morphological phenotypes with increasingly severe phenotypes as the number of mutant alleles increased. Phenotypes included smaller eyes and reduced hair cell numbers, consistent with the optic atrophy and hearing impairment observed in human patients. The double mutant also showed abnormal development of primary motor neurons, hair cell innervation, and reduced leukocytes, consistent with the neuropathy and recurrent infection of the human patients possessing the most severe reductions of PRPS1 activity. Further analyses indicated the phenotypes were associated with a prolonged cell cycle likely resulting from reduced nucleotide synthesis and energy production in the mutant embryos. We further demonstrated the phenotypes were caused by delays in the tissues most highly expressing the prps1 genes. PMID:27425195

  6. Consolidated Human Activities Database (CHAD)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Consolidated Human Activity Database (CHAD) contains data obtained from human activity studies that were collected at city, state, and national levels. CHAD is...

  7. Brain connections of words, perceptions and actions: A neurobiological model of spatio-temporal semantic activation in the human cortex.

    Science.gov (United States)

    Tomasello, Rosario; Garagnani, Max; Wennekers, Thomas; Pulvermüller, Friedemann

    2017-04-01

    Neuroimaging and patient studies show that different areas of cortex respectively specialize for general and selective, or category-specific, semantic processing. Why are there both semantic hubs and category-specificity, and how come that they emerge in different cortical regions? Can the activation time-course of these areas be predicted and explained by brain-like network models? In this present work, we extend a neurocomputational model of human cortical function to simulate the time-course of cortical processes of understanding meaningful concrete words. The model implements frontal and temporal cortical areas for language, perception, and action along with their connectivity. It uses Hebbian learning to semantically ground words in aspects of their referential object- and action-related meaning. Compared with earlier proposals, the present model incorporates additional neuroanatomical links supported by connectivity studies and downscaled synaptic weights in order to control for functional between-area differences purely due to the number of in- or output links of an area. We show that learning of semantic relationships between words and the objects and actions these symbols are used to speak about, leads to the formation of distributed circuits, which all include neuronal material in connector hub areas bridging between sensory and motor cortical systems. Therefore, these connector hub areas acquire a role as semantic hubs. By differentially reaching into motor or visual areas, the cortical distributions of the emergent 'semantic circuits' reflect aspects of the represented symbols' meaning, thus explaining category-specificity. The improved connectivity structure of our model entails a degree of category-specificity even in the 'semantic hubs' of the model. The relative time-course of activation of these areas is typically fast and near-simultaneous, with semantic hubs central to the network structure activating before modality-preferential areas carrying

  8. Pyranoxanthones: Synthesis, growth inhibitory activity on human tumor cell lines and determination of their lipophilicity in two membrane models

    DEFF Research Database (Denmark)

    Goncalves de Azavedo, Carlos M. B. P.; Afonso, C. M.; Soares, J. X.;

    2013-01-01

    The benzopyran and dihydrobenzopyran moieties can be considered as "privileged motifs" in drug discovery being good platforms for the search of new bioactive compounds. These moieties are commonly found fused to the xanthonic scaffold belonging to the biologically important family of the generally...... hard to be established. Accordingly, with the aim of rationalizing the importance of the fused ring orientation and oxygenation pattern in pyranoxanthones, this study describes the synthesis of 14 new pyranoxanthones and evaluation of their cell growth inhibitory activity in four human tumor cell lines...... as well as their lipophilicity in two membrane models. This systematic approach allowed establishing structure-activity and structure-lipophilicity relationships for the obtained compounds in combination with 6 previously described compounds. From this work an angular pyranoxanthone scaffold emerged...

  9. Chemical form of selenium affects its uptake, transport, and glutathione peroxidase activity in the human intestinal Caco-2 cell model.

    Science.gov (United States)

    Zeng, Huawei; Jackson, Matthew I; Cheng, Wen-Hsing; Combs, Gerald F

    2011-11-01

    Determining the effect of selenium (Se) chemical form on uptake, transport, and glutathione peroxidase activity in human intestinal cells is critical to assess Se bioavailability at nutritional doses. In this study, we found that two sources of L-selenomethionine (SeMet) and Se-enriched yeast each increased intracellular Se content more effectively than selenite or methylselenocysteine (SeMSC) in the human intestinal Caco-2 cell model. Interestingly, SeMSC, SeMet, and digested Se-enriched yeast were transported at comparable efficacy from the apical to basolateral sides, each being about 3-fold that of selenite. In addition, these forms of Se, whether before or after traversing from apical side to basolateral side, did not change the potential to support glutathione peroxidase (GPx) activity. Although selenoprotein P has been postulated to be a key Se transport protein, its intracellular expression did not differ when selenite, SeMSC, SeMet, or digested Se-enriched yeast was added to serum-contained media. Taken together, our data show, for the first time, that the chemical form of Se at nutritional doses can affect the absorptive (apical to basolateral side) efficacy and retention of Se by intestinal cells; but that, these effects are not directly correlated to the potential to support GPx activity.

  10. Borrelia burgdorferi Induces TLR2-Mediated Migration of Activated Dendritic Cells in an Ex Vivo Human Skin Model

    Science.gov (United States)

    Wagemakers, Alex; van ‘t Veer, Cornelis; Oei, Anneke; van der Pot, Wouter J.; Ahmed, Kalam; van der Poll, Tom; Geijtenbeek, Teunis B. H.; Hovius, Joppe W. R.

    2016-01-01

    Borrelia burgdorferi is transmitted into the skin of the host where it encounters and interacts with two dendritic cell (DC) subsets; Langerhans cells (LCs) and dermal DCs (DDCs). These cells recognize pathogens via pattern recognition receptors, mature and migrate out of the skin into draining lymph nodes, where they orchestrate adaptive immune responses. In order to investigate the response of skin DCs during the early immunopathogenesis of Lyme borreliosis, we injected B. burgdorferi intradermally into full-thickness human skin and studied the migration of DCs out of the skin, the activation profile and phenotype of migrated cells. We found a significant increase in the migration of LCs and DDCs in response to B. burgdorferi. Notably, migration was prevented by blocking TLR2. DCs migrated from skin inoculated with higher numbers of spirochetes expressed significantly higher levels of CD83 and produced pro-inflammatory cytokines. No difference was observed in the expression of HLA-DR, CD86, CD38, or CCR7. To conclude, we have established an ex vivo human skin model to study DC-B. burgdorferi interactions. Using this model, we have demonstrated that B. burgdorferi-induced DC migration is mediated by TLR2. Our findings underscore the utility of this model as a valuable tool to study immunity to spirochetal infections. PMID:27695100

  11. Evaluation of an active multi-body human model for braking and frontal crash events

    NARCIS (Netherlands)

    Meijer, R.; Elrofai, H.B.H.; Broos, W.J.C.; Hassel, E. van

    2013-01-01

    Active safety systems that start to act moments before the crash might be capable of anticipating the occupant’s position, either by correcting it, or by taking the out-of-position into account. For the development and evaluation of such active safety systems, recently a run-time efficient

  12. In Silico Structure Prediction of Human Fatty Acid Synthase-Dehydratase: A Plausible Model for Understanding Active Site Interactions.

    Science.gov (United States)

    John, Arun; Umashankar, Vetrivel; Samdani, A; Sangeetha, Manoharan; Krishnakumar, Subramanian; Deepa, Perinkulam Ravi

    2016-01-01

    Fatty acid synthase (FASN, UniProt ID: P49327) is a multienzyme dimer complex that plays a critical role in lipogenesis. Consequently, this lipogenic enzyme has gained tremendous biomedical importance. The role of FASN and its inhibition is being extensively researched in several clinical conditions, such as cancers, obesity, and diabetes. X-ray crystallographic structures of some of its domains, such as β-ketoacyl synthase, acetyl transacylase, malonyl transacylase, enoyl reductase, β-ketoacyl reductase, and thioesterase, (TE) are already reported. Here, we have attempted an in silico elucidation of the uncrystallized dehydratase (DH) catalytic domain of human FASN. This theoretical model for DH domain was predicted using comparative modeling methods. Different stand-alone tools and servers were used to validate and check the reliability of the predicted models, which suggested it to be a highly plausible model. The stereochemical analysis showed 92.0% residues in favorable region of Ramachandran plot. The initial physiological substrate β-hydroxybutyryl group was docked into active site of DH domain using Glide. The molecular dynamics simulations carried out for 20 ns in apo and holo states indicated the stability and accuracy of the predicted structure in solvated condition. The predicted model provided useful biochemical insights into the substrate-active site binding mechanisms. This model was then used for identifying potential FASN inhibitors using high-throughput virtual screening of the National Cancer Institute database of chemical ligands. The inhibitory efficacy of the top hit ligands was validated by performing molecular dynamics simulation for 20 ns, where in the ligand NSC71039 exhibited good enzyme inhibition characteristics and exhibited dose-dependent anticancer cytotoxicity in retinoblastoma cancer cells in vitro.

  13. Modelling Landscape Dynamics in a Highland Mediterranean Catchment: Establishing the impact of Climate Variation and Human Activity

    Science.gov (United States)

    van Beek, L. P. H.; Feiken, H.; van Asch, T. W. J.; Bierkens, M. F. P.

    2012-04-01

    The close link between human occupancy and the Mediterranean landscape has long been recognized. Through the exploitation of the various but fragmented resources that these landscapes have to offer, man has been able to secure a living. However, these activities are often marginal and small shifts in population pressure, corresponding land use patterns or climatic variability can have large consequences on the redistribution of water and sediment in these areas. The meso-scale landscape dynamics model, CALEROS, has been developed to simulate the interactions between climate, soil production and erosion, vegetation and land use on geomorphological to human time scales in Mediterranean environments. Starting from an initial landscape consisting of a DTM, soil distribution and underlying lithology, the landscape is free to develop in response to the imposed climate variability and seismicity. In addition to changes in soil distribution and bedrock lowering, this includes the establishment of vegetation as conditioned by a selection of plant functional types and, optionally, population and land use dynamics as conditioned by land use scenarios specifying technological and dietary constraints for different periods. As such CALEROS is well-suited to investigate the relative impacts of climate, land cover and human activities on the hydrological catchment response and the associated sediment fluxes due to soil erosion and mass movements. Within the context of a geo-archeological study on the conservation potential of settlement history in the Contrada Maddalena (~14km2, Calabria, Italy), we apply CALEROS to investigate the relative contributions of climate and man from Neolithic times onwards (5000 BP-present). Model results allow to establish when human impacts become significant over natural variations and to discern shifts in catchment functioning as a result of sudden or climatic variations (e.g., Little Ice Age) as reflected in vegetation patterns and water and

  14. Mycoplasma genitalium Infection Activates Cellular Host Defense and Inflammation Pathways in a 3-Dimensional Human Endocervical Epithelial Cell Model

    Science.gov (United States)

    McGowin, Chris L.; Radtke, Andrea L.; Abraham, Kyle; Martin, David H.; Herbst-Kralovetz, Melissa

    2013-01-01

    Background. Because Mycoplasma genitalium is a prevalent and emerging cause of sexually transmitted infections, understanding the mechanisms by which M. genitalium elicits mucosal inflammation is an essential component to managing lower and upper reproductive tract disease syndromes in women. Methods. We used a rotating wall vessel bioreactor system to create 3-dimensional (3-D) epithelial cell aggregates to model and assess endocervical infection by M. genitalium. Results. Attachment of M. genitalium to the host cell's apical surface was observed directly and confirmed using immunoelectron microscopy. Bacterial replication was observed from 0 to 72 hours after inoculation, during which time host cells underwent ultrastructural changes, including reduction of microvilli, and marked increases in secretory vesicle formation. Using genome-wide transcriptional profiling, we identified a host defense and inflammation signature activated by M. genitalium during acute infection (48 hours after inoculation) that included cytokine and chemokine activity and secretion of factors for antimicrobial defense. Multiplex bead-based protein assays confirmed secretion of proinflammatory cytokines, several of which are involved in leukocyte recruitment and hypothesized to enhance susceptibility to human immunodeficiency type 1 infection. Conclusions. These findings provide insight into key molecules and pathways involved in innate recognition of M. genitalium and the response to acute infection in the human endocervix. PMID:23493725

  15. Modeling Forces on the Human Body.

    Science.gov (United States)

    Pagonis, Vasilis; Drake, Russel; Morgan, Michael; Peters, Todd; Riddle, Chris; Rollins, Karen

    1999-01-01

    Presents five models of the human body as a mechanical system which can be used in introductory physics courses: human arms as levers, humans falling from small heights, a model of the human back, collisions during football, and the rotating gymnast. Gives ideas for discussions and activities, including Interactive Physics (TM) simulations. (WRM)

  16. Preclinical Evidence of Anti-Tumor Activity Induced by EZH2 Inhibition in Human Models of Synovial Sarcoma.

    Directory of Open Access Journals (Sweden)

    Satoshi Kawano

    Full Text Available The catalytic activities of covalent and ATP-dependent chromatin remodeling are central to regulating the conformational state of chromatin and the resultant transcriptional output. The enzymes that catalyze these activities are often contained within multiprotein complexes in nature. Two such multiprotein complexes, the polycomb repressive complex 2 (PRC2 methyltransferase and the SWItch/Sucrose Non-Fermentable (SWI/SNF chromatin remodeler have been reported to act in opposition to each other during development and homeostasis. An imbalance in their activities induced by mutations/deletions in complex members (e.g. SMARCB1 has been suggested to be a pathogenic mechanism in certain human cancers. Here we show that preclinical models of synovial sarcoma-a cancer characterized by functional SMARCB1 loss via its displacement from the SWI/SNF complex through the pathognomonic SS18-SSX fusion protein-display sensitivity to pharmacologic inhibition of EZH2, the catalytic subunit of PRC2. Treatment with tazemetostat, a clinical-stage, selective and orally bioavailable small-molecule inhibitor of EZH2 enzymatic activity reverses a subset of synovial sarcoma gene expression and results in concentration-dependent cell growth inhibition and cell death specifically in SS18-SSX fusion-positive cells in vitro. Treatment of mice bearing either a cell line or two patient-derived xenograft models of synovial sarcoma leads to dose-dependent tumor growth inhibition with correlative inhibition of trimethylation levels of the EZH2-specific substrate, lysine 27 on histone H3. These data demonstrate a dependency of SS18-SSX-positive, SMARCB1-deficient synovial sarcomas on EZH2 enzymatic activity and suggests the potential utility of EZH2-targeted drugs in these genetically defined cancers.

  17. STAT3 signaling is activated preferentially in tumor-initiating cells in claudin-low models of human breast cancer.

    Science.gov (United States)

    Wei, Wei; Tweardy, David J; Zhang, Mei; Zhang, Xiaomei; Landua, John; Petrovic, Ivana; Bu, Wen; Roarty, Kevin; Hilsenbeck, Susan G; Rosen, Jeffrey M; Lewis, Michael T

    2014-10-01

    In breast cancer, a subset of tumor-initiating cells (TIC) or "cancer stem cells" are thought to be responsible for tumor maintenance, treatment resistance, and disease recurrence. While current breast cancer stem cell markers (e.g., CD44(high) /CD24(low/neg) , ALDH positive) have allowed enrichment for such cells, they are not universally expressed and may actually identify distinct TIC subpopulations in the same tumor. Thus, additional markers of functional stem cells are needed. The STAT3 pathway is a critical regulator of the function of normal stem cells, and evidence is accumulating for its important role in breast cancer stem cells. However, due to the lack of a method for separating live cells based on their level of STAT3 activity, it remains unknown whether STAT3 functions in the cancer stem cells themselves, or in surrounding niche cells, or in both. To approach this question, we constructed a series of lentiviral fluorescent (enhanced green fluorescent protein, EGFP) reporters that enabled flow cytometric enrichment of cells differing in STAT3-mediated transcriptional activity, as well as in vivo/in situ localization of STAT3 responsive cells. Using in vivo claudin-low cell line xenograft models of human breast cancer, we found that STAT3 signaling reporter activity (EGFP(+) ) is associated with a subpopulation of cancer cells enriched for mammosphere-forming efficiency, as well as TIC function in limiting dilution transplantation assays compared to negative or unsorted populations. Our results support STAT3 signaling activity as another functional marker for human breast cancer stem cells thus making it an attractive therapeutic target for stem-cell-directed therapy in some breast cancer subtypes. © AlphaMed Press.

  18. Hypolipemic and hypoglycaemic activity of bergamot polyphenols: from animal models to human studies.

    Science.gov (United States)

    Mollace, Vincenzo; Sacco, Iolanda; Janda, Elzbieta; Malara, Claudio; Ventrice, Domenica; Colica, Carmen; Visalli, Valeria; Muscoli, Saverio; Ragusa, Salvatore; Muscoli, Carolina; Rotiroti, Domenicantonio; Romeo, Franco

    2011-04-01

    Bergamot juice produces hypolipemic activity in rats though the mechanism remains unclear. Here we investigated on the effect of bergamot extract (BPF) in diet-induced hyperlipemia in Wistar rats and in 237 patients suffering from hyperlipemia either associated or not with hyperglycaemia. BPF, given orally for 30 days to both rats and patients, reduces total and LDL cholesterol levels (an effect accompanied by elevation of cHDL), triglyceride levels and by a significant decrease in blood glucose. Moreover, BPF inhibited HMG-CoA reductase activity and enhanced reactive vasodilation thus representing an efficient phytotherapeutic approach in combating hyperlipemic and hyperglycaemic disorders.

  19. Human intestinal P-glycoprotein activity estimated by the model substrate digoxin

    DEFF Research Database (Denmark)

    Larsen, U L; Hyldahl Olesen, L; Nyvold, Charlotte Guldborg;

    2007-01-01

    P-glycoprotein (Pgp) plays a part in the intestinal uptake of xenobiotics and has been associated with susceptibility to ulcerative colitis. The aim of this study was to examine Pgp activity in relation to age, gender, medical treatment (rifampicin or ketoconazole) and the multidrug resistance (M...

  20. Testing the Role of p21-Activated Kinases in Schwannoma Formation Using a Novel Genetically Engineered Murine Model that Closely Phenocopies Human NF2 Disease

    Science.gov (United States)

    2015-06-01

    Kinases in Schwannoma Formation Using a Novel Genetically Engineered Murine Model that Closely Phenocopies Human NF2 Disease The views, opinions and...TITLE AND SUBTITLE Testing the Role of p21-Activated Kinases in Schwannoma Formation Using a Novel Genetically Engineered Murine Model that Closely...1.20 calendar Testing the Role of p21 Activated Kinases in Schwannoma Formation Using a Novel Genetically Engineered Murine Model that Closely

  1. Pharmacokinetics of human recombinant tissue-type plasminogen activator, administered intra-abdominally, in a rat peritonitis model

    NARCIS (Netherlands)

    van Goor, Harry; Bom, VJJ; van der Meer, J; Sluiter, WJ; Geerards, S; de Graaf, JS; Bleichrodt, RP; van der Schaaf, W

    1996-01-01

    Human recombinant tissue-type plasminogen activator (rtPA), administered intraperitoneally, may promote intraabdominal fibrinolysis in peritonitis, thereby preventing adhesion and abscess formation. The pharmacokinetics of a single intraperitoneal dose of 0.5 or 2.0 mg/ml human rtPA were assessed in

  2. Pharmacokinetics of human recombinant tissue-type plasminogen activator, administered intra-abdominally, in a rat peritonitis model

    NARCIS (Netherlands)

    van Goor, Harry; Bom, VJJ; van der Meer, J; Sluiter, WJ; Geerards, S; de Graaf, JS; Bleichrodt, RP; van der Schaaf, W

    1996-01-01

    Human recombinant tissue-type plasminogen activator (rtPA), administered intraperitoneally, may promote intraabdominal fibrinolysis in peritonitis, thereby preventing adhesion and abscess formation. The pharmacokinetics of a single intraperitoneal dose of 0.5 or 2.0 mg/ml human rtPA were assessed in

  3. Mathematical models of human behavior

    DEFF Research Database (Denmark)

    Møllgaard, Anders Edsberg

    data set, along with work on other behavioral data. The overall goal is to contribute to a quantitative understanding of human behavior using big data and mathematical models. Central to the thesis is the determination of the predictability of different human activities. Upper limits are derived......, thereby implying that interactions between spreading processes are driving forces of attention dynamics. Overall, the thesis contributes to a quantitative understanding of a wide range of different human behaviors by applying mathematical modeling to behavioral data. There can be no doubt......During the last 15 years there has been an explosion in human behavioral data caused by the emergence of cheap electronics and online platforms. This has spawned a whole new research field called computational social science, which has a quantitative approach to the study of human behavior. Most...

  4. Human activity recognition and prediction

    CERN Document Server

    2016-01-01

    This book provides a unique view of human activity recognition, especially fine-grained human activity structure learning, human-interaction recognition, RGB-D data based action recognition, temporal decomposition, and causality learning in unconstrained human activity videos. The techniques discussed give readers tools that provide a significant improvement over existing methodologies of video content understanding by taking advantage of activity recognition. It links multiple popular research fields in computer vision, machine learning, human-centered computing, human-computer interaction, image classification, and pattern recognition. In addition, the book includes several key chapters covering multiple emerging topics in the field. Contributed by top experts and practitioners, the chapters present key topics from different angles and blend both methodology and application, composing a solid overview of the human activity recognition techniques. .

  5. Marked antitumor activity of cat's whiskers tea (Orthosiphon stamineus extract in orthotopic model of human colon tumor in nude mice

    Directory of Open Access Journals (Sweden)

    Foaud Saleih R Al-Suede

    2012-08-01

    Full Text Available Orthosiphon stamineus is used to treat kidney ailments including angiogenesis-dependent diseases. O. stamineus has shown to possess strong anti-angiogenic activity. In present study, an orthotopic nude mouse model of colon cancer was employed to study the factors that influence suppression of tumor by standardized 50% ethanol extract of O. stamineus leaves (EOS. Human colorectal cancer cells (HCT116 were surgically injected into the cecal wall of mice. Two different oral doses (100 and 200 mg/kg/day were given for 5 weeks. EOS suppressed 61.62±3.7% and 82.8±1.5% tumor growth at 100 and 200 mg/kg, respectively. Tumor histology revealed significant reduction in vascularization. Anti-angiogenic efficacy of EOS was investigated in human endothelial cells (HUVEC. In vitro, EOS inhibited migration and tube formation of HUVECs. HPLC data showed high content of rosmarinic acid in EOS. This work supports previous anti-tumor works on the plant in which suppression of VEGFR phosphorylation is thought to be involved.

  6. Computational human body models

    NARCIS (Netherlands)

    Wismans, J.S.H.M.; Happee, R.; Dommelen, J.A.W. van

    2005-01-01

    Computational human body models are widely used for automotive crashsafety research and design and as such have significantly contributed to a reduction of traffic injuries and fatalities. Currently crash simulations are mainly performed using models based on crash-dummies. However crash dummies dif

  7. Computational human body models

    NARCIS (Netherlands)

    Wismans, J.S.H.M.; Happee, R.; Dommelen, J.A.W. van

    2005-01-01

    Computational human body models are widely used for automotive crashsafety research and design and as such have significantly contributed to a reduction of traffic injuries and fatalities. Currently crash simulations are mainly performed using models based on crash-dummies. However crash dummies

  8. Towards a Self-Consistent Physical Framework for Modeling Coupled Human and Physical Activities during the Anthropocene

    Science.gov (United States)

    Garrett, T. J.

    2014-12-01

    Studies of the response of global climate to anthropogenic activities rely upon scenarios for future human activity to provide a range of possible trajectories for greenhouse gases emissions over the coming century. Sophisticated integrated models are used to explore not only what will happen, but what should happen in order to optimize societal well-being. Hundreds of equations might be used to account for the interplay between human decisions, technological change, and macroeconomic priniciples. In contrast, the model equations used to describe geophysical phenomena look very different because they are a) purely deterministic and b) consistent with basic thermodynamic laws. This inconsistency between macroeconomics and physics suggests a rather unhappy marriage. During the Anthropocene the evolution of humanity and our environment will become increasingly intertwined. Representing such a coupling suggests a need for a common theoretical basis. To this end, the approach that is described here is to treat civilization like any other physical process, that is as an open, non-equilibrium thermodynamic system that dissipates energy and diffuses matter in order to sustain existing circulations and to further its material growth. Theoretical arguments and over 40 years of measurements show that a very general representation of global economic wealth (not GDP) has been tied to rates of global primary energy consumption through a constant 7.1 ± 0.1 mW per year 2005 USD. This link between physics and economics leads to very simple expressions for how fast civilization and its rate of energy consumption grow. These are expressible as a function of rates of energy and material resource discovery and depletion, and of the magnitude of externally imposed decay. The equations are validated through hindcasts that show, for example, that economic conditions in the 1950s can be invoked to make remarkably accurate forecasts of present rates of global GDP growth and primary energy

  9. Event-Based Activity Modeling

    DEFF Research Database (Denmark)

    Bækgaard, Lars

    2004-01-01

    We present and discuss a modeling approach that supports event-based modeling of information and activity in information systems. Interacting human actors and IT-actors may carry out such activity. We use events to create meaningful relations between information structures and the related activit...

  10. Gaussian mixture models and semantic gating improve reconstructions from human brain activity

    Directory of Open Access Journals (Sweden)

    Sanne eSchoenmakers

    2015-01-01

    Full Text Available Better acquisition protocols and analysis techniques are making it possible to use fMRI to obtain highly detailed visualizations of brain processes. In particular we focus on the reconstruction of natural images from BOLD responses in visual cortex. We expand our linear Gaussian framework for percept decoding with Gaussian mixture models to better represent the prior distribution of natural images. Reconstruction of such images then boils down to probabilistic inference in a hybrid Bayesian network. In our set-up, different mixture components correspond to different character categories. Our framework can automatically infer higher-order semantic categories from lower-level brain areas. Furthermore the framework can gate semantic information from higher-order brain areas to enforce the correct category during reconstruction. When categorical information is not available, we show that automatically learned clusters in the data give a similar improvement in reconstruction. The hybrid Bayesian network leads to highly accurate reconstructions in both supervised and unsupervised settings.

  11. Determination of structure-activity relationships between fentanyl analogs and human μ-opioid receptors based on active binding site models

    Institute of Scientific and Technical Information of China (English)

    Ming Liu; Xiaoli Liu; Ping Wan; Qiangsan Wu; Wenxiang Hu

    2011-01-01

    Fentanyl is a potent and widely used clinical narcotic analgesic, as well as a highly selective μ-opioid agonist. The present study established a homologous model of the human μ-opioid receptor; an intercomparison of three types of μ-opioid receptor protein sequence homologous rates was made. The secondary receptor structure was predicted, the model reliability was assessed and verified using the Ramachandran plot and ProTab analysis. The predictive ability of the CoMFA model was further validated using an external test set. Using the Surflex-Dock program, a series of fentanyl analog molecules were docked to the receptor, the calculation results from Biopolymer/SiteID showed that the receptor had a deep binding area situated in the extracellular side of the transmembrane domains (TM) among TM3, TM5, TM6, and TM7. Results suggested that there might be 5 active areas in the receptor. The important residues were Asp147, Tyr148, and Tyr149 in TM3, Trp293, and His297 in TM6, and Trp318, His319, Ile322, and Tyr326 in TM7, which were located at the 5 active areas. The best fentanyl docking orientation position was the piperidine ring, which was nearly perpendicular to the membrane surface in the 7 TM domains. Molecular dynamic simulations were applied to evaluate potential relationships between ligand conformation and fentanyl substitution.

  12. Modeling the effects of human activity on Katmai brown bears (Ursus arctos) through the use of survival analysis

    Science.gov (United States)

    Smith, T.S.; Johnson, B.A.

    2004-01-01

    Brown bear-human interactions were observed in 1993, 1995, and 1997 at Kulik River in Katmai National Park and Preserve, Alaska. We analyzed these interactions using survival analysis, creating survival curves for the time that bears remained on the river in the presence, and absence, of human activity. Bear-only survival curves did not vary significantly between years (p = 0.067). Ninety-seven percent of bears left the river within 70 minutes of arrival in all years. Temporal patterns of bear activity were unaffected by the presence of humans as long as the bears did not share river zones with humans (p = 0.062 to p = 0.360). When people and bears did not share river zones, 38.6% (1993), 36.0% (1995), and 37.0% (1997) of bears remained on the river for at least 10 minutes after arrival. In contrast, when people and bears shared river zones, fewer bears remained on the river after the first 10 minutes, with 28.6% (1993), 25.0% (1995), and 32.6% (1997) observed in each year. We conclude that human activity displaced 26.0% (1993), 30.5% (1995), and 12.0% (1997) of the bears using the river, which otherwise would likely have remained longer. Over the three years of study, habituation to human activity may account for observed changes in bears' use of the river.

  13. Mathematical models of human behavior

    DEFF Research Database (Denmark)

    Møllgaard, Anders Edsberg

    During the last 15 years there has been an explosion in human behavioral data caused by the emergence of cheap electronics and online platforms. This has spawned a whole new research field called computational social science, which has a quantitative approach to the study of human behavior. Most...... studies have considered data sets with just one behavioral variable such as email communication. The Social Fabric interdisciplinary research project is an attempt to collect a more complete data set on human behavior by providing 1000 smartphones with pre-installed data collection software to students...... data set, along with work on other behavioral data. The overall goal is to contribute to a quantitative understanding of human behavior using big data and mathematical models. Central to the thesis is the determination of the predictability of different human activities. Upper limits are derived...

  14. The Effects of Vandetanib on Paclitaxel Tumor Distribution and Antitumor Activity in a Xenograft Model of Human Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    Marta Cesca

    2009-11-01

    Full Text Available This study was designed to determine the effects of vandetanib, a small-molecule receptor tyrosine kinase inhibitor of vascular endothelial growth factor and epidermal growth factor receptor, on paclitaxel (PTX tumor distribution and antitumor activity in xenograft models of human ovarian carcinoma. Nude mice bearing A2780-1A9 xenografts received daily (5, 10, or 15 days doses of vandetanib (50 mg/kg per os, combined with PTX (20 mg/kg intravenously. Morphologic and functional modifications associated with the tumor vasculature (CD31 and α-smooth muscle actin staining and Hoechst 33342 perfusion and PTX concentrations in plasma and tumor tissues were analyzed. Activity was evaluated as inhibition of tumor growth subcutaneously and spreading into the peritoneal cavity. Vandetanib treatment produced no significant change in tumor vessel density, although a reduced number of large vessels, an increased percentage of mature vessels, and diminished tumor perfusion were evident. Pretreatment with vandetanib led to decreased tumor PTX levels within 1 hour of PTX injection, although 24 hours later, tumor PTX levels were comparable with controls. In efficacy studies, the combination of vandetanib plus PTX improved antitumor activity compared with vandetanib or PTX alone, with greater effects being obtained when PTX was administered before vandetanib. The combination of PTX plus vandetanib reduced tumor burden in the peritoneal cavity of mice and significantly increased their survival. Analysis of vascular changes and PTX tumor uptake in vandetanib-treated tumors may help to guide the scheduling of vandetanib plus PTX combinations and may have implications for the design of clinical trials with these drugs.

  15. Steroid receptor RNA activator (SRA modification by the human pseudouridine synthase 1 (hPus1p: RNA binding, activity, and atomic model.

    Directory of Open Access Journals (Sweden)

    Tiphaine Huet

    Full Text Available The most abundant of the modified nucleosides, and once considered as the "fifth" nucleotide in RNA, is pseudouridine, which results from the action of pseudouridine synthases. Recently, the mammalian pseudouridine synthase 1 (hPus1p has been reported to modulate class I and class II nuclear receptor responses through its ability to modify the Steroid receptor RNA Activator (SRA. These findings highlight a new level of regulation in nuclear receptor (NR-mediated transcriptional responses. We have characterised the RNA association and activity of the human Pus1p enzyme with its unusual SRA substrate. We validate that the minimal RNA fragment within SRA, named H7, is necessary for both the association and modification by hPus1p. Furthermore, we have determined the crystal structure of the catalytic domain of hPus1p at 2.0 Å resolution, alone and in a complex with several molecules present during crystallisation. This model shows an extended C-terminal helix specifically found in the eukaryotic protein, which may prevent the enzyme from forming a homodimer, both in the crystal lattice and in solution. Our biochemical and structural data help to understand the hPus1p active site architecture, and detail its particular requirements with regard to one of its nuclear substrates, the non-coding RNA SRA.

  16. Steroid receptor RNA activator (SRA) modification by the human pseudouridine synthase 1 (hPus1p): RNA binding, activity, and atomic model.

    Science.gov (United States)

    Huet, Tiphaine; Miannay, François-Alexandre; Patton, Jeffrey R; Thore, Stéphane

    2014-01-01

    The most abundant of the modified nucleosides, and once considered as the "fifth" nucleotide in RNA, is pseudouridine, which results from the action of pseudouridine synthases. Recently, the mammalian pseudouridine synthase 1 (hPus1p) has been reported to modulate class I and class II nuclear receptor responses through its ability to modify the Steroid receptor RNA Activator (SRA). These findings highlight a new level of regulation in nuclear receptor (NR)-mediated transcriptional responses. We have characterised the RNA association and activity of the human Pus1p enzyme with its unusual SRA substrate. We validate that the minimal RNA fragment within SRA, named H7, is necessary for both the association and modification by hPus1p. Furthermore, we have determined the crystal structure of the catalytic domain of hPus1p at 2.0 Å resolution, alone and in a complex with several molecules present during crystallisation. This model shows an extended C-terminal helix specifically found in the eukaryotic protein, which may prevent the enzyme from forming a homodimer, both in the crystal lattice and in solution. Our biochemical and structural data help to understand the hPus1p active site architecture, and detail its particular requirements with regard to one of its nuclear substrates, the non-coding RNA SRA.

  17. Pollen indicators of human activity

    Institute of Scientific and Technical Information of China (English)

    LI YiYin; ZHOU LiPing; CUI HaiTing

    2008-01-01

    The study of past human activities and their environmental effect is high in the agenda of global change research. A record of pollen assemblages is one of the most common proxies employed for detecting the impact of human activities on the landscape. In this review, we provide a summary and discussion on the recent progress on the use of pollen as indicators of human activity. For most of the studies related to human impact, the following features have been focused on: (1) decline of certain tree pollen; (2) flourishing of pioneer plant pollen; (3) concomitant occurrence of cereal-type pollen and cropland weed pollen; (4) abrupt changes in pollen concentration and richness; and (5) occurrence of nitrophilous plants and pastoral weed. Pollen of anthropogenic plants (weeds and cereal-type plants) is ideal indicators of human activities. Different types of human activities will result in different pollen assem-blages. Patterns of human-impacted pollen spectra would vary between forested areas and grassland. In the study of human impact with pollen data, high resolution in both time and space must be consid-ered. High resolution in space will help to inform the complexity of the landscape. More importantly, it can help to reveal the interference of human activities on the landscape, hence avoiding the bias cre-ated by the limited data points. Fine resolution in time will make accurate recording of short-lived events possible, hence avoiding the exclusion of events related to human activities. The combination of palynology with other proxies will help to decipher more accurately landscape changes through time. Charcoal is a particularly useful proxy for recording the disturbance of humans on vegetation. Its peak values usually occur with pronounced drop of tree pollen and significant rise of anthropogenic pollen.

  18. Activation of Src and Src-associated signaling pathways in relation to hypoxia in human cancer xenograft models.

    Science.gov (United States)

    Pham, Nhu-An; Magalhaes, Joao M M M; Do, Trevor; Schwock, Joerg; Dhani, Neesha; Cao, Ping-Jiang; Hill, Richard P; Hedley, David W

    2009-01-15

    The hypoxic response in vitro involves alterations in signaling proteins, including Src, STAT3 and AKT that are considered to be broadly pro-survival. The involvement of these signaling proteins in the hypoxic microenviroments that occur in solid tumors was investigated by the use of multicolor fluorescence image analysis to colocalize signaling proteins and regions of hypoxia in 4 human tumor xenografts, pancreatic carcinoma BxPC3 and PANC1 and cervical squamous cell carcinoma ME180 and SiHa. Expression levels of total Src protein (mean intensity x labeled region fraction) were higher in hypoxic regions, identified using the nitroimidazole probe EF5, relative to non-EF5 regions in all 4 tumor models. This was associated with higher levels of phosphorylated (p-) Y419p-Src and its substrate Y861p-FAK in EF5 positive regions of BxPC3 tumors. This effect was also seen in tumor-bearing mice continuously breathing 7% oxygen for 3 hr which markedly increased the extent of EF5 positive labeling. In contrast, the hypoxia treatment resulted in a significant decrease in S727p-STAT3 in BxPC3 xenografts and suggested that STAT3 activity is responsive to acute hypoxia, whereas Src-FAK signaling is associated with predominantly chronically hypoxic EF5 positive regions. Src activity in both hypoxic and nonhypoxic BxPC3 tumor regions was suppressed when mice were treated with the Src inhibitor AZD0530 (25 mg/kg/day, 5 days), suggesting that both hypoxic and normoxic tumor regions are accessible to pharmacological Src inhibition. These results show that signaling pathways are responsive to tumor hypoxia in vivo, although the effects appear to differ between individual tumor types. Copyright (c) 2008 Wiley-Liss, Inc.

  19. Modelling Landscape Dynamics in a Highland Mediterranean Catchment: Establishing the impact of Climate Variation and Human Activity

    NARCIS (Netherlands)

    Beek, L.P.H. van; Feiken, H.; Asch, Th.W.J. van; Bierkens, M.F.P.

    2012-01-01

    The close link between human occupancy and the Mediterranean landscape has long been recognized. Through the exploitation of the various but fragmented resources that these landscapes have to offer, man has been able to secure a living. However, these activities are often marginal and small shifts i

  20. Human Factors Model

    Science.gov (United States)

    1993-01-01

    Jack is an advanced human factors software package that provides a three dimensional model for predicting how a human will interact with a given system or environment. It can be used for a broad range of computer-aided design applications. Jack was developed by the computer Graphics Research Laboratory of the University of Pennsylvania with assistance from NASA's Johnson Space Center, Ames Research Center and the Army. It is the University's first commercial product. Jack is still used for academic purposes at the University of Pennsylvania. Commercial rights were given to Transom Technologies, Inc.

  1. Toxicity challenges in environmental chemicals: Prediction of human plasma protein binding through quantitative structure-activity relationship (QSAR) models

    Science.gov (United States)

    The present study explores the merit of utilizing available pharmaceutical data to construct a quantitative structure-activity relationship (QSAR) for prediction of the fraction of a chemical unbound to plasma protein (Fub) in environmentally relevant compounds. Independent model...

  2. Agouti Related Peptide Secreted Via Human Mesenchymal Stem Cells Upregulates Proteasome Activity in an Alzheimer’s Disease Model

    Science.gov (United States)

    Lee, Na Kyung; Park, Sang Eon; Kwon, Soo Jin; Shim, Sangmi; Byeon, Yeji; Kim, Jong-Hwa; Na, Duk L.; Chang, Jong Wook

    2017-01-01

    The activity of the ubiquitin proteasome system (UPS) is downregulated in aggregation diseases such as Alzheimer’s disease (AD). In this study, we investigated the therapeutic potential of the Agouti-related peptide (AgRP), which is secreted by human mesenchymal stem cells (MSCs), in terms of its effect on the regulation of proteasome activity in AD. When SH-SY5Y human neuroblastoma cells were co-cultured with MSCs isolated from human Wharton’s Jelly (WJ-MSC), their proteasome activity was significantly upregulated. Further analysis of the conditioned media after co-culture allowed us to identify significant concentrations of a neuropeptide, called AgRP. The stereotactic delivery of either WJ-MSCs or AgRP into the hippocampi of C57BL6/J and 5XFAD mice induced a significant increase of proteasome activity and suppressed the accumulation of ubiquitin-conjugated proteins. Collectively, these findings suggest strong therapeutic potential for WJ-MSCs and AgRP to enhance proteasome activity, thereby potentially reducing abnormal protein aggregation and delaying the clinical progression of various neurodegenerative diseases. PMID:28051110

  3. Inhibition of C5a-induced inflammation with preserved C5b-9-mediated bactericidal activity in a human whole blood model of meningococcal sepsis.

    NARCIS (Netherlands)

    Sprong, T.; Brandtzaeg, P.; Fung, M.; Pharo, A.M.; Hoiby, E.A.; Michaelsen, T.E.; Aase, A.; Meer, J.W.M. van der; Deuren, M. van; Mollnes, T.E.

    2003-01-01

    The complement system plays an important role in the initial defense against Neisseria meningitidis. In contrast, uncontrolled activation in meningococcal sepsis contributes to the development of tissue damage and shock. In a novel human whole blood model of meningococcal sepsis, we studied the effe

  4. Effect of gene modified mesenchymal stem cells overexpression human receptor activity modified protein 1 on inflammation and cardiac repair in a rabbit model of myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    赵然尊

    2012-01-01

    Objective To investigate the effect of mesenchymal stem cells(MSCs) overexpressing human receptor activity modified protein 1(hRAMP1) by adenovirus vector on infarction related inflammation and cardiac repair in a rabbit model of myocardial infarction(MI)

  5. Inhibition of C5a-induced inflammation with preserved C5b-9-mediated bactericidal activity in a human whole blood model of meningococcal sepsis.

    NARCIS (Netherlands)

    Sprong, T.; Brandtzaeg, P.; Fung, M.; Pharo, A.M.; Hoiby, E.A.; Michaelsen, T.E.; Aase, A.; Meer, J.W.M. van der; Deuren, M. van; Mollnes, T.E.

    2003-01-01

    The complement system plays an important role in the initial defense against Neisseria meningitidis. In contrast, uncontrolled activation in meningococcal sepsis contributes to the development of tissue damage and shock. In a novel human whole blood model of meningococcal sepsis, we studied the

  6. Human neutrophil antimicrobial activity.

    Science.gov (United States)

    Thomas, E L; Lehrer, R I; Rest, R F

    1988-01-01

    Polymorphonuclear neutrophilic leukocytes (PMNs) take up opsonized microorganisms into phagosomes that fuse with secretory granules in the PMN cytoplasm to form phagolysosomes. Killing and digestion of microorganisms take place within phagolysosomes. Antimicrobial activities in phagolysosomes are divided into two classes. Oxygen (O2)-dependent mechanisms are expressed when PMNs undergo the "respiratory burst." An NADPH oxidase in the phagolysosome membrane is activated and reduces O2 to superoxide (O2-). O2 reduction is the first step in a series of reactions that produce toxic oxidants. For example, .O2- dismutases to hydrogen peroxide (H2O2), and the azurophil granule enzyme myeloperoxidase catalyzes the oxidation of Cl- by H2O2 to yield hypochlorous acid (HOCl). The reaction of HOCl with ammonia and amines modulates the toxicity of this oxidant. O2-independent antimicrobial mechanisms include the activities of lysosomal proteases, other hydrolytic enzymes, and proteins and peptides that bind to microorganisms and disrupt essential processes or structural components. For example, the bactericidal/permeability-increasing protein, cathepsin G, and the defensins are released into phagolysosomes from the azurophil granules. Proposed mechanisms of action of neutrophil antimicrobial agents, their range of microbial targets, and their possible interactions within phagolysosomes are discussed.

  7. Glucuronidation does not suppress the estrogenic activity of quercetin in yeast and human breast cancer cell model systems.

    Science.gov (United States)

    Ruotolo, Roberta; Calani, Luca; Brighenti, Furio; Crozier, Alan; Ottonello, Simone; Del Rio, Daniele

    2014-10-01

    Several plant-derived molecules, referred to as phytoestrogens, are thought to mimic the actions of endogenous estrogens. Among these, quercetin, one of the most widespread flavonoids in the plant kingdom, has been reported as estrogenic in some occasions. However, quercetin occurs in substantial amounts as glycosides such as quercetin-3-O-glucoside (isoquercitrin) and quercetin-3-O-rutinoside (rutin) in dietary sources. It is now well established that quercetin undergoes substantial phase II metabolism after ingestion by humans, with plasma metabolites after a normal dietary intake rarely exceeding nmol/L concentrations. Therefore, attributing phytoestrogenic activity to flavonoids without taking into account the fact that it is their phase II metabolites that enter the circulatory system, will almost certainly lead to misleading conclusions. With the aim of clarifying the above issue, the goal of the present study was to determine if plant-associated quercetin glycosides and human phase II quercetin metabolites, actually found in human biological fluids after intake of quercetin containing foods, are capable of interacting with the estrogen receptors (ER). To this end, we used a yeast-based two-hybrid system and an estrogen response element-luciferase reporter assay in an ER-positive human cell line (MCF-7) to probe the ER interaction capacities of quercetin and its derivatives. Our results show that quercetin-3-O-glucuronide, one of the main human phase II metabolites produced after intake of dietary quercetin, displays ERα- and ERβ-dependent estrogenic activity, the functional consequences of which might be related to the protective activity of diets rich in quercetin glycosides.

  8. Modelling Landscape Dynamics in a Highland Mediterranean Catchment: Establishing the impact of Climate Variation and Human Activity

    OpenAIRE

    L. P. H. van Beek; (Rik) Feiken, H.; Asch, Th. W. J. van; Bierkens, M.F.P.

    2012-01-01

    The close link between human occupancy and the Mediterranean landscape has long been recognized. Through the exploitation of the various but fragmented resources that these landscapes have to offer, man has been able to secure a living. However, these activities are often marginal and small shifts in population pressure, corresponding land use patterns or climatic variability can have large consequences on the redistribution of water and sediment in these areas.

  9. The transgenic rabbit as model for human diseases and as a source of biologically active recombinant proteins.

    Science.gov (United States)

    Bosze, Zs; Hiripi, L; Carnwath, J W; Niemann, H

    2003-10-01

    Until recently, transgenic rabbits were produced exclusively by pronuclear microinjection which results in additive random insertional transgenesis; however, progress in somatic cell cloning based on nuclear transfer will soon make it possible to produce rabbits with modifications to specific genes by the combination of homologous recombination and subsequent prescreening of nuclear donor cells. Transgenic rabbits have been found to be excellent animal models for inherited and acquired human diseases including hypertrophic cardiomyopathy, perturbed lipoprotein metabolism and atherosclerosis. Transgenic rabbits have also proved to be suitable bioreactors for the production of recombinant protein both on an experimental and a commercial scale. This review summarizes recent research based on the transgenic rabbit model.

  10. Human IgG1 monoclonal antibody against human collagen 17 noncollagenous 16A domain induces blisters via complement activation in experimental bullous pemphigoid model.

    Science.gov (United States)

    Li, Qiang; Ujiie, Hideyuki; Shibaki, Akihiko; Wang, Gang; Moriuchi, Reine; Qiao, Hong-jiang; Morioka, Hiroshi; Shinkuma, Satoru; Natsuga, Ken; Long, Heather A; Nishie, Wataru; Shimizu, Hiroshi

    2010-12-15

    Bullous pemphigoid (BP) is an autoimmune blistering disease caused by IgG autoantibodies targeting the noncollagenous 16A (NC16A) domain of human collagen 17 (hCOL17), which triggers blister formation via complement activation. Previous in vitro analysis demonstrated that IgG1 autoantibodies showed much stronger pathogenic activity than IgG4 autoantibodies; however, the exact pathogenic role of IgG1 autoantibodies has not been fully demonstrated in vivo. We constructed a recombinant IgG1 mAb against hCOL17 NC16A from BP patients. In COL17-humanized mice, this mAb effectively reproduced a BP phenotype that included subepidermal blisters, deposition of IgG1, C1q and C3, neutrophil infiltration, and mast cell degranulation. Subsequently, alanine substitutions at various C1q binding sites were separately introduced to the Fc region of the IgG1 mAb. Among these mutated mAbs, the one that was mutated at the P331 residue completely failed to activate the complement in vitro and drastically lost pathogenic activity in COL17-humanized mice. These findings indicate that P331 is a key residue required for complement activation and that IgG1-dependent complement activation is essential for blister formation in BP. This study is, to our knowledge, the first direct evidence that IgG1 Abs to hCOL17 NC16A can induce blister formation in vivo, and it raises the possibility that IgG1 mAbs with Fc modification may be used to block pathogenic epitopes in autoimmune diseases.

  11. Effects of endothelial cells on human mesenchymal stem cell activity in a three-dimensional in vitro model

    Directory of Open Access Journals (Sweden)

    FA Saleh

    2011-10-01

    Full Text Available An increasing body of data suggest that mesenchymal stem cells (MSCs reside in a perivascular niche. To more closely mimic this in vivo microenvironment and for better understanding of its complexity, and the factors that regulate the MSC activity, human umbilical vein endothelial cells (HUVECs were co-cultured with human bone marrow MSCs – using a novel three-dimensional (3D spheroid co-culture system. Using confocal microscopy of fluorescently labelled cells, we observed HUVECs and MSCs to self-assemble and form organised structures with segregated cell-type partitioning. Under osteogenic conditions, the rate and extent of differentiation in MSC/HUVEC spheroids was significantly elevated compared to 3D co-cultures of MSCs and human dermal fibroblast controls as shown by alkaline phosphatase staining. Conversely, HUVECs inhibited adipogenic differentiation and the proliferation of MSCs in 3D co-cultures indicating that HUVECs suppressed MSC cycling and selectively promoted osteogenic differentiation in 3D. We have also shown that HUVECs enhanced activation of endogenous Wnt signalling and bone morphogenetic protein (BMP signalling as shown by increased levels of active nuclear β-catenin and pSmad 1/5/8 immunopositivity respectively. These data suggest strongly that endothelial cells regulate the MSC activity in simulated in vivo conditions, by maintaining quiescence and facilitating niche exit via osteogenic differentiation following appropriate cues. Our findings also underline the importance of 3D heterotypic cell-cell interactions in the regulation of MSC behaviour, suggesting that multicellular cocktails and/or 3D-based delivery strategies may be beneficial for bone repair.

  12. 3D models of MBP, a biologically active metabolite of bisphenol A, in human estrogen receptor α and estrogen receptor β.

    Directory of Open Access Journals (Sweden)

    Michael E Baker

    Full Text Available Bisphenol A [BPA] is a widely dispersed environmental chemical that is of much concern because the BPA monomer is a weak transcriptional activator of human estrogen receptor α [ERα] and ERβ in cell culture. A BPA metabolite, 4-methyl-2,4-bis(4-hydroxyphenylpent-1-ene [MBP], has transcriptional activity at nM concentrations, which is 1000-fold lower than the concentration for estrogenic activity of BPA, suggesting that MBP may be an environmental estrogen. To investigate the structural basis for the activity of MBP at nM concentrations and the lower activity of BPA for human ERα and ERβ, we constructed 3D models of human ERα and ERβ with MBP and BPA for comparison with estradiol in these ERs. These 3D models suggest that MBP, but not BPA, has key contacts with amino acids in human ERα and ERβ that are important in binding of estradiol by these receptors. Metabolism of BPA to MBP increases the spacing between two phenolic rings, resulting in contacts between MBP and ERα and ERβ that mimic those of estradiol with these ERs. Mutagenesis of residues on these ERs that contact the phenolic hydroxyls will provide a test for our 3D models. Other environmental chemicals containing two appropriately spaced phenolic rings and an aliphatic spacer instead of an estrogenic B and C ring also may bind to ERα or ERβ and interfere with normal estrogen physiology. This analysis also may be useful in designing novel chemicals for regulating the actions of human ERα and ERβ.

  13. Antitumor Activity of Lenvatinib (E7080: An Angiogenesis Inhibitor That Targets Multiple Receptor Tyrosine Kinases in Preclinical Human Thyroid Cancer Models

    Directory of Open Access Journals (Sweden)

    Osamu Tohyama

    2014-01-01

    Full Text Available Inhibition of tumor angiogenesis by blockading the vascular endothelial growth factor (VEGF signaling pathway is a promising therapeutic strategy for thyroid cancer. Lenvatinib mesilate (lenvatinib is a potent inhibitor of VEGF receptors (VEGFR1–3 and other prooncogenic and prooncogenic receptor tyrosine kinases, including fibroblast growth factor receptors (FGFR1–4, platelet derived growth factor receptor α (PDGFRα, KIT, and RET. We examined the antitumor activity of lenvatinib against human thyroid cancer xenograft models in nude mice. Orally administered lenvatinib showed significant antitumor activity in 5 differentiated thyroid cancer (DTC, 5 anaplastic thyroid cancer (ATC, and 1 medullary thyroid cancer (MTC xenograft models. Lenvatinib also showed antiangiogenesis activity against 5 DTC and 5 ATC xenografts, while lenvatinib showed in vitro antiproliferative activity against only 2 of 11 thyroid cancer cell lines: that is, RO82-W-1 and TT cells. Western blot analysis showed that cultured RO82-W-1 cells overexpressed FGFR1 and that lenvatinib inhibited the phosphorylation of FGFR1 and its downstream effector FRS2. Lenvatinib also inhibited the phosphorylation of RET with the activated mutation C634W in TT cells. These data demonstrate that lenvatinib provides antitumor activity mainly via angiogenesis inhibition but also inhibits FGFR and RET signaling pathway in preclinical human thyroid cancer models.

  14. Human platelets produced in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice upon transplantation of human cord blood CD34(+) cells are functionally active in an ex vivo flow model of thrombosis.

    Science.gov (United States)

    Salles, Isabelle I; Thijs, Tim; Brunaud, Christine; De Meyer, Simon F; Thys, Johan; Vanhoorelbeke, Karen; Deckmyn, Hans

    2009-12-01

    Xenotransplantation systems have been used with increasing success to better understand human hematopoiesis and thrombopoiesis. In this study, we demonstrate that production of human platelets in nonobese diabetic/severe combined immunodeficient mice after transplantation of unexpanded cord-blood CD34(+) cells was detected within 10 days after transplantation, with the number of circulating human platelets peaking at 2 weeks (up to 87 x 10(3)/microL). This rapid human platelet production was followed by a second wave of platelet formation 5 weeks after transplantation, with a population of 5% still detected after 8 weeks, attesting for long-term engraftment. Platelets issued from human hematopoietic stem cell progenitors are functional, as assessed by increased CD62P expression and PAC1 binding in response to collagen-related peptide and thrombin receptor-activating peptide activation and their ability to incorporate into thrombi formed on a collagen-coated surface in an ex vivo flow model of thrombosis. This interaction was abrogated by addition of inhibitory monoclonal antibodies against human glycoprotein Ibalpha (GPIbalpha) and GPIIb/IIIa. Thus, our mouse model with production of human platelets may be further explored to study the function of genetically modified platelets, but also to investigate the effect of stimulators or inhibitors of human thrombopoiesis in vivo.

  15. A single dose of neuron-binding human monoclonal antibody improves spontaneous activity in a murine model of demyelination.

    Directory of Open Access Journals (Sweden)

    Aleksandar Denic

    Full Text Available Our laboratory demonstrated that a natural human serum antibody, sHIgM12, binds to neurons in vitro and promotes neurite outgrowth. We generated a recombinant form, rHIgM12, with identical properties. Intracerebral infection with Theiler's Murine Encephalomyelitis Virus (TMEV of susceptible mouse strains results in chronic demyelinating disease with progressive axonal loss and neurologic dysfunction similar to progressive forms of multiple sclerosis. To study the effects of rHIgM12 on the motor function of TMEV-infected mice, we monitored spontaneous nocturnal activity over many weeks. Nocturnal behavior is a sensitive measure of rodent neurologic function because maximal activity changes are expected to occur during the normally active night time monitoring period. Mice were placed in activity boxes eight days prior to treatment to collect baseline spontaneous activity. After treatment, activity in each group was continuously recorded over 8 weeks. We chose a long 8-week monitoring period for two reasons: (1 we previously demonstrated that IgM induced remyelination is present by 5 weeks post treatment, and (2 TMEV-induced demyelinating disease in this strain progresses very slowly. Due to the long observation periods and large data sets, differences among treatment groups may be difficult to appreciate studying the original unfiltered recordings. To clearly delineate changes in the highly fluctuating original data we applied three different methods: (1 binning, (2 application of Gaussian low-pass filters (GF and (3 polynomial fitting. Using each of the three methods we showed that compared to control IgM and saline, early treatment with rHIgM12 induced improvement in both horizontal and vertical motor function, whereas later treatment improved only horizontal activity. rHIgM12 did not alter activity of normal, uninfected mice. This study supports the hypothesis that treatment with a neuron-binding IgM not only protects neurons in vitro, but

  16. Integrated Extravehicular Activity Human Research Plan: 2017

    Science.gov (United States)

    Abercromby, Andrew

    2017-01-01

    Multiple organizations within NASA as well as industry and academia fund and participate in research related to extravehicular activity (EVA). In October 2015, representatives of the EVA Office, the Crew and Thermal Systems Division (CTSD), and the Human Research Program (HRP) at NASA Johnson Space Center agreed on a formal framework to improve multi-year coordination and collaboration in EVA research. At the core of the framework is an Integrated EVA Human Research Plan and a process by which it will be annually reviewed and updated. The over-arching objective of the collaborative framework is to conduct multi-disciplinary cost-effective research that will enable humans to perform EVAs safely, effectively, comfortably, and efficiently, as needed to enable and enhance human space exploration missions. Research activities must be defined, prioritized, planned and executed to comprehensively address the right questions, avoid duplication, leverage other complementary activities where possible, and ultimately provide actionable evidence-based results in time to inform subsequent tests, developments and/or research activities. Representation of all appropriate stakeholders in the definition, prioritization, planning and execution of research activities is essential to accomplishing the over-arching objective. A formal review of the Integrated EVA Human Research Plan will be conducted annually. Coordination with stakeholders outside of the EVA Office, CTSD, and HRP is already in effect on a study-by-study basis; closer coordination on multi-year planning with other EVA stakeholders including academia is being actively pursued. Details of the preliminary Integrated EVA Human Research Plan are presented including description of ongoing and planned research activities in the areas of: physiological and performance capabilities; suit design parameters; EVA human health and performance modeling; EVA tasks and concepts of operations; EVA informatics; human-suit sensors; suit

  17. Amylase activity in human bile.

    Science.gov (United States)

    Donaldson, L A; Joffe, S N; McIntosh, W; Brodie, M J

    1979-03-01

    The mean amylase level in 42 human bile samples was 154 IU/l and there was no significant difference in the amylase activity of 32 paired serum and bile samples. Estimation of the amylase thermolability of bile showed it to be similar to that of serum. This suggests that the amylase activity in bile may have filtered through the liver from the hepatic circulation rather than refluxed from the pancreatic duct. The presence of amylase in human bile provides further evidence that the liver might have a role in the regulation of serum amylase.

  18. Patch-occupancy models indicate human activity as major determinant of forest elephant Loxodonta cyclotis seasonal distribution in an industrial corridor in Gabon

    Science.gov (United States)

    Buij, R.; McShea, W.J.; Campbell, P.; Lee, M.E.; Dallmeier, F.; Guimondou, S.; Mackaga, L.; Guisseougou, N.; Mboumba, S.; Hines, J.E.; Nichols, J.D.; Alonso, A.

    2007-01-01

    The importance of human activity and ecological features in influencing African forest elephant ranging behaviour was investigated in the Rabi-Ndogo corridor of the Gamba Complex of Protected Areas in southwest Gabon. Locations in a wide geographical area with a range of environmental variables were selected for patch-occupancy surveys using elephant dung to assess seasonal presence and absence of elephants. Patch-occupancy procedures allowed for covariate modelling evaluating hypotheses for both occupancy in relation to human activity and ecological features, and detection probability in relation to vegetation density. The best fitting models for old and fresh dung data sets indicate that (1) detection probability for elephant dung is negatively related to the relative density of the vegetation, and (2) human activity, such as presence and infrastructure, are more closely associated with elephant distribution patterns than are ecological features, such as the presence of wetlands and preferred fresh fruit. Our findings emphasize the sensitivity of elephants to human disturbance, in this case infrastructure development associated with gas and oil production. Patch-occupancy methodology offers a viable alternative to current transect protocols for monitoring programs with multiple covariates.

  19. Plectasin shows intracellular activity against Staphylococcus aureus in human THP-1 monocytes and in a mouse peritonitis model

    DEFF Research Database (Denmark)

    Brinch, Karoline Sidelmann; Sandberg, Anne; Baudoux, Pierre

    2009-01-01

    was maintained (maximal relative efficacy [E(max)], 1.0- to 1.3-log reduction in CFU) even though efficacy was inferior to that of extracellular killing (E(max), >4.5-log CFU reduction). Animal studies included a novel use of the mouse peritonitis model, exploiting extra- and intracellular differentiation assays...... concentration. These findings stress the importance of performing studies of extra- and intracellular activity since these features cannot be predicted from traditional MIC and killing kinetic studies. Application of both the THP-1 and the mouse peritonitis models showed that the in vitro results were similar...

  20. INPO Assistance Activities: Human Resources

    Energy Technology Data Exchange (ETDEWEB)

    Wheelock, J.T.

    1999-11-14

    The Institute of Nuclear Power Operations (INPO) has a number of ongoing activities designed to provide assistance to our members in the human resources area. These include the Educational Assistance Program and the ongoing facilitation of information exchange through Nuclear Network and INPO publications. INPO will continue to seek ways to assist its member utilities.

  1. Intrinsic Patterns of Human Activity

    Science.gov (United States)

    Hu, Kun; Ivanov, Plamen Ch.; Chen, Zhi; Hilton, Michael; Stanley, H. Eugene; Shea, Steven

    2003-03-01

    Activity is one of the defining features of life. Control of human activity is complex, being influenced by many factors both extrinsic and intrinsic to the body. The most obvious extrinsic factors that affect activity are the daily schedule of planned events, such as work and recreation, as well as reactions to unforeseen or random events. These extrinsic factors may account for the apparently random fluctuations in human motion observed over short time scales. The most obvious intrinsic factors are the body clocks including the circadian pacemaker that influences our sleep/wake cycle and ultradian oscillators with shorter time scales [2, 3]. These intrinsic rhythms may account for the underlying regularity in average activity level over longer periods of up to 24 h. Here we ask if the known extrinsic and intrinsic factors fully account for all complex features observed in recordings of human activity. To this end, we measure activity over two weeks from forearm motion in subjects undergoing their regular daily routine. Utilizing concepts from statistical physics, we demonstrate that during wakefulness human activity possesses previously unrecognized complex dynamic patterns. These patterns of activity are characterized by robust fractal and nonlinear dynamics including a universal probability distribution and long-range power-law correlations that are stable over a wide range of time scales (from minutes to hours). Surprisingly, we find that these dynamic patterns are unaffected by changes in the average activity level that occur within individual subjects throughout the day and on different days of the week, and between subjects. Moreover, we find that these patterns persist when the same subjects undergo time-isolation laboratory experiments designed to account for the phase of the circadian pacemaker, and control the known extrinsic factors by restricting behaviors and manipulating scheduled events including the sleep/wake cycle. We attribute these newly

  2. On the Use of Hydrological Models and Satellite Data to Study the Water Budget of River Basins Affected by Human Activities: Examples from the Garonne Basin of France

    Science.gov (United States)

    Martin, Eric; Gascoin, Simon; Grusson, Youen; Murgue, Clément; Bardeau, Mélanie; Anctil, François; Ferrant, Sylvain; Lardy, Romain; Le Moigne, Patrick; Leenhardt, Delphine; Rivalland, Vincent; Sánchez Pérez, José-Miguel; Sauvage, Sabine; Therond, Olivier

    2016-03-01

    Natural and anthropogenic forcing factors and their changes significantly impact water resources in many river basins around the world. Information on such changes can be derived from fine scale in situ and satellite observations, used in combination with hydrological models. The latter need to account for hydrological changes caused by human activities to correctly estimate the actual water resource. In this study, we consider the catchment area of the Garonne river (in France) to investigate the capabilities of space-based observations and up-to-date hydrological modeling in estimating water resources of a river basin modified by human activities and a changing climate. Using the ISBA-MODCOU and SWAT hydrological models, we find that the water resources of the Garonne basin display a negative climate trend since 1960. The snow component of the two models is validated using the moderate-resolution imaging spectroradiometer snow cover extent climatology. Crop sowing dates based on remote sensing studies are also considered in the validation procedure. Use of this dataset improves the simulated evapotranspiration and river discharge amounts when compared to conventional data. Finally, we investigate the benefit of using the MAELIA multi-agent model that accounts for a realistic agricultural and management scenario. Among other results, we find that changes in crop systems have significant impacts on water uptake for agriculture. This work constitutes a basis for the construction of a future modeling framework of the sociological and hydrological system of the Garonne river region.

  3. Human filarial Wolbachia lipopeptide directly activates human neutrophils in vitro.

    Science.gov (United States)

    Tamarozzi, F; Wright, H L; Johnston, K L; Edwards, S W; Turner, J D; Taylor, M J

    2014-10-01

    The host inflammatory response to the Onchocerca volvulus endosymbiont, Wolbachia, is a major contributing factor in the development of chronic pathology in humans (onchocerciasis/river blindness). Recently, the toll-like pattern recognition receptor motif of the major inflammatory ligands of filarial Wolbachia, membrane-associated diacylated lipoproteins, was functionally defined in murine models of pathology, including mediation of neutrophil recruitment to the cornea. However, the extent to which human neutrophils can be activated in response to this Wolbachia pattern recognition motif is not known. Therefore, the responses of purified peripheral blood human neutrophils to a synthetic N-terminal diacylated lipopeptide (WoLP) of filarial Wolbachia peptidoglycan-associated lipoprotein (PAL) were characterized. WoLP exposure led to a dose-dependent activation of healthy, human neutrophils that included gross morphological alterations and modulation of surface expressed integrins involved in tethering, rolling and extravasation. WoLP exposure induced chemotaxis but not chemokinesis of neutrophils, and secretion of the major neutrophil chemokine, interleukin 8. WoLP also induced and primed the respiratory burst, and enhanced neutrophil survival by delay of apoptosis. These results indicate that the major inflammatory motif of filarial Wolbachia lipoproteins directly activates human neutrophils in vitro and promotes a molecular pathway by which human neutrophils are recruited to sites of Onchocerca parasitism.

  4. Subtoxic Concentrations of Hepatotoxic Drugs Lead to Kupffer Cell Activation in a Human In Vitro Liver Model: An Approach to Study DILI

    Directory of Open Access Journals (Sweden)

    Victoria Kegel

    2015-01-01

    Full Text Available Drug induced liver injury (DILI is an idiosyncratic adverse drug reaction leading to severe liver damage. Kupffer cells (KC sense hepatic tissue stress/damage and therefore could be a tool for the estimation of consequent effects associated with DILI. Aim of the present study was to establish a human in vitro liver model for the investigation of immune-mediated signaling in the pathogenesis of DILI. Hepatocytes and KC were isolated from human liver specimens. The isolated KC yield was 1.2±0.9×106 cells/g liver tissue with a purity of >80%. KC activation was investigated by the measurement of reactive oxygen intermediates (ROI, DCF assay and cell activity (XTT assay. The initial KC activation levels showed broad donor variability. Additional activation of KC using supernatants of hepatocytes treated with hepatotoxic drugs increased KC activity and led to donor-dependent changes in the formation of ROI compared to KC incubated with supernatants from untreated hepatocytes. Additionally, a compound- and donor-dependent increase in proinflammatory cytokines or in anti-inflammatory cytokines was detected. In conclusion, KC related immune signaling in hepatotoxicity was successfully determined in a newly established in vitro liver model. KC were able to detect hepatocyte stress/damage and to transmit a donor- and compound-dependent immune response via cytokine production.

  5. Subtoxic Concentrations of Hepatotoxic Drugs Lead to Kupffer Cell Activation in a Human In Vitro Liver Model: An Approach to Study DILI.

    Science.gov (United States)

    Kegel, Victoria; Pfeiffer, Elisa; Burkhardt, Britta; Liu, Jia L; Zeilinger, Katrin; Nüssler, Andreas K; Seehofer, Daniel; Damm, Georg

    2015-01-01

    Drug induced liver injury (DILI) is an idiosyncratic adverse drug reaction leading to severe liver damage. Kupffer cells (KC) sense hepatic tissue stress/damage and therefore could be a tool for the estimation of consequent effects associated with DILI. Aim of the present study was to establish a human in vitro liver model for the investigation of immune-mediated signaling in the pathogenesis of DILI. Hepatocytes and KC were isolated from human liver specimens. The isolated KC yield was 1.2 ± 0.9 × 10(6) cells/g liver tissue with a purity of >80%. KC activation was investigated by the measurement of reactive oxygen intermediates (ROI, DCF assay) and cell activity (XTT assay). The initial KC activation levels showed broad donor variability. Additional activation of KC using supernatants of hepatocytes treated with hepatotoxic drugs increased KC activity and led to donor-dependent changes in the formation of ROI compared to KC incubated with supernatants from untreated hepatocytes. Additionally, a compound- and donor-dependent increase in proinflammatory cytokines or in anti-inflammatory cytokines was detected. In conclusion, KC related immune signaling in hepatotoxicity was successfully determined in a newly established in vitro liver model. KC were able to detect hepatocyte stress/damage and to transmit a donor- and compound-dependent immune response via cytokine production.

  6. Anti-leukemia activity of in vitro-expanded human gamma delta T cells in a xenogeneic Ph+ leukemia model.

    Directory of Open Access Journals (Sweden)

    Gabrielle M Siegers

    Full Text Available Gamma delta T cells (GDTc lyse a variety of hematological and solid tumour cells in vitro and in vivo, and are thus promising candidates for cellular immunotherapy. We have developed a protocol to expand human GDTc in vitro, yielding highly cytotoxic Vgamma9/Vdelta2 CD27/CD45RA double negative effector memory cells. These cells express CD16, CD45RO, CD56, CD95 and NKG2D. Flow cytometric, clonogenic, and chromium release assays confirmed their specific cytotoxicity against Ph(+ cell lines in vitro. We have generated a fluorescent and bioluminescent Ph(+ cell line, EM-2eGFPluc, and established a novel xenogeneic leukemia model. Intravenous injection of EM-2eGFPluc into NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG mice resulted in significant dose-dependent bone marrow engraftment; lower levels engrafted in blood, lung, liver and spleen. In vitro-expanded human GDTc injected intraperitoneally were found at higher levels in blood and organs compared to those injected intravenously; GDTc survived at least 33 days post-injection. In therapy experiments, we documented decreased bone marrow leukemia burden in mice treated with GDTc. Live GDTc were found in spleen and bone marrow at endpoint, suggesting the potential usefulness of this therapy.

  7. Physical activity and human health

    Directory of Open Access Journals (Sweden)

    Paulina Wojciechowska

    2015-01-01

    Full Text Available Introduction: The dynamic development of the automotive industry, transport, and the media means that human life has become much easier. At the same time, the comfortable living conditions have decreased physical activity. Biologically conditioned, the need of activity has been minimised by the ever-increasing pace of life. As a result, it may lead to the loss of physical and mental health. Active recreation is not only an excellent source of activity, but also a source of satisfaction. Youths and adults should therefore spend their free time primarily on various forms of physical activity. Aim of the research : To evaluate the physical fitness of students who regularly practice physical exercise, those who occasionally practice, and those not practicing any form of physical activity. Material and methods : In the research we used a questionnaire of the Ruffier test and an orthostatic test. The study involved a group of 15 people aged 20–25 years. Participation in the study was entirely voluntary and anonymous. The study group consisted only of women. Results obtained from the questionnaire survey were fully reflected during exercise tests performed. Results and conclusions: Only regularly practiced physical activity has an effect on our body. Regular exercise increases our body’s physical capacity. Activity is the best means of prevention of lifestyle diseases. Youths and adults should spend their free time mainly doing various forms of physical activity.

  8. A discrete electromechanical model for human cardiac tissue: effects of stretch-activated currents and stretch conditions on restitution properties and spiral wave dynamics.

    Directory of Open Access Journals (Sweden)

    Louis D Weise

    Full Text Available We introduce an electromechanical model for human cardiac tissue which couples a biophysical model of cardiac excitation (Tusscher, Noble, Noble, Panfilov, 2006 and tension development (adjusted Niederer, Hunter, Smith, 2006 model with a discrete elastic mass-lattice model. The equations for the excitation processes are solved with a finite difference approach, and the equations of the mass-lattice model are solved using Verlet integration. This allows the coupled problem to be solved with high numerical resolution. Passive mechanical properties of the mass-lattice model are described by a generalized Hooke's law for finite deformations (Seth material. Active mechanical contraction is initiated by changes of the intracellular calcium concentration, which is a variable of the electrical model. Mechanical deformation feeds back on the electrophysiology via stretch-activated ion channels whose conductivity is controlled by the local stretch of the medium. We apply the model to study how stretch-activated currents affect the action potential shape, restitution properties, and dynamics of spiral waves, under constant stretch, and dynamic stretch caused by active mechanical contraction. We find that stretch conditions substantially affect these properties via stretch-activated currents. In constantly stretched medium, we observe a substantial decrease in conduction velocity, and an increase of action potential duration; whereas, with dynamic stretch, action potential duration is increased only slightly, and the conduction velocity restitution curve becomes biphasic. Moreover, in constantly stretched medium, we find an increase of the core size and period of a spiral wave, but no change in rotation dynamics; in contrast, in the dynamically stretching medium, we observe spiral drift. Our results may be important to understand how altered stretch conditions affect the heart's functioning.

  9. Human Centered Hardware Modeling and Collaboration

    Science.gov (United States)

    Stambolian Damon; Lawrence, Brad; Stelges, Katrine; Henderson, Gena

    2013-01-01

    In order to collaborate engineering designs among NASA Centers and customers, to in clude hardware and human activities from multiple remote locations, live human-centered modeling and collaboration across several sites has been successfully facilitated by Kennedy Space Center. The focus of this paper includes innovative a pproaches to engineering design analyses and training, along with research being conducted to apply new technologies for tracking, immersing, and evaluating humans as well as rocket, vehic le, component, or faci lity hardware utilizing high resolution cameras, motion tracking, ergonomic analysis, biomedical monitoring, wor k instruction integration, head-mounted displays, and other innovative human-system integration modeling, simulation, and collaboration applications.

  10. Evaluating the effect of human activity patterns on air pollution exposure using an integrated field-based and agent-based modelling framework

    Science.gov (United States)

    Schmitz, Oliver; Beelen, Rob M. J.; de Bakker, Merijn P.; Karssenberg, Derek

    2015-04-01

    Constructing spatio-temporal numerical models to support risk assessment, such as assessing the exposure of humans to air pollution, often requires the integration of field-based and agent-based modelling approaches. Continuous environmental variables such as air pollution are best represented using the field-based approach which considers phenomena as continuous fields having attribute values at all locations. When calculating human exposure to such pollutants it is, however, preferable to consider the population as a set of individuals each with a particular activity pattern. This would allow to account for the spatio-temporal variation in a pollutant along the space-time paths travelled by individuals, determined, for example, by home and work locations, road network, and travel times. Modelling this activity pattern requires an agent-based or individual based modelling approach. In general, field- and agent-based models are constructed with the help of separate software tools, while both approaches should play together in an interacting way and preferably should be combined into one modelling framework, which would allow for efficient and effective implementation of models by domain specialists. To overcome this lack in integrated modelling frameworks, we aim at the development of concepts and software for an integrated field-based and agent-based modelling framework. Concepts merging field- and agent-based modelling were implemented by extending PCRaster (http://www.pcraster.eu), a field-based modelling library implemented in C++, with components for 1) representation of discrete, mobile, agents, 2) spatial networks and algorithms by integrating the NetworkX library (http://networkx.github.io), allowing therefore to calculate e.g. shortest routes or total transport costs between locations, and 3) functions for field-network interactions, allowing to assign field-based attribute values to networks (i.e. as edge weights), such as aggregated or averaged

  11. In vitro and in vivo models for the evaluation of new inhibitors of human steroid sulfatase, devoid of residual estrogenic activity.

    Science.gov (United States)

    Shields-Botella, J; Bonnet, P; Duc, I; Duranti, E; Meschi, S; Cardinali, S; Prouheze, P; Chaigneau, A M; Duranti, V; Gribaudo, S; Rivière, A; Mengual, L; Carniato, D; Cecchet, L; Lafay, J; Rondot, B; Sandri, J; Pascal, J C; Delansorne, R

    2003-02-01

    The goal of our research project is to develop a new class of orally active drugs, estrone sulfatase inhibitors, for the treatment of estrogen-dependent (receptor positive) breast cancer. Several compounds were synthesized and their pharmacological potencies explored. Based on encouraging preliminary results, three of them, TX 1299, TX 1492 and TX 1506 were further studied in vitro as well as in vivo. They proved to be strong inhibitors of estrone sulfatase when measured on the whole human JEG-3 choriocarcinoma and MCF-7 breast cancer cells and their IC(50)s found to be in the range of known standard inhibitors. Their residual estrogenic activity was checked as negative in the test of induction of alkaline phosphatase (APase) activity in whole human endometrial adenocarcinoma Ishikawa cells. In addition, their effect on aromatase activity in JEG-3 cells was also examined, since the goal of inhibiting both sulfatase and aromatase activities appears very attractive. However, it has been unsuccessful so far. Then, in vivo potencies of TX 1299, the lead compound in our chemical series, were evaluated in comparison with 6,6,7-COUMATE, a non-steroidal standard, in two different rat models and by oral route. First, the absence of any residual estrogenic activity for these compounds was checked in the uterotrophic model in prepubescent female rats. Second, antiuterotrophic activity in adult ovariectomized rat supplemented with estrone sulfate (E(1)S), showed that both compounds were potent inhibitors, the power of TX 1299 relative to 6,6,7-COUMATE being around 80%. This assay was combined with uterine sulfatase level determination and confirmed the complete inhibition of this enzyme within the target organ. Preliminary studies indicated that other non-steroid compounds in the Théramex series were potent in vitro and in vivo inhibitors of estrone sulfatase in rats and further studies are in progress.

  12. Modeling human color categorization

    NARCIS (Netherlands)

    van den Broek, Egon; Schouten, Th.E.; Kisters, P.M.F.

    2008-01-01

    A unique color space segmentation method is introduced. It is founded on features of human cognition, where 11 color categories are used in processing color. In two experiments, human subjects were asked to categorize color stimuli into these 11 color categories, which resulted in markers for a Colo

  13. Modeling human color categorization

    NARCIS (Netherlands)

    van den Broek, Egon; Schouten, Th.E.; Kisters, P.M.F.

    A unique color space segmentation method is introduced. It is founded on features of human cognition, where 11 color categories are used in processing color. In two experiments, human subjects were asked to categorize color stimuli into these 11 color categories, which resulted in markers for a

  14. Antitumor activity of Herceptin in combination with STEALTH liposomal cisplatin or nonliposomal cisplatin in a HER2 positive human breast cancer model.

    Science.gov (United States)

    Colbern, G T; Hiller, A J; Musterer, R S; Working, P K; Henderson, I C

    1999-10-01

    Single agent antitumor activity of Herceptin, a humanized monoclonal antibody directed against HER2, has been demonstrated in numerous preclinical and clinical studies. Additionally, combination therapy with Herceptin and chemotherapy (CRx) has demonstrated additive antitumor activity in both preclinical models and early clinical trials. STEALTH (pegylated) liposomal (PL) cisplatin, also known as SPI-077, is currently in clinical trials for a variety of solid tumors. The three studies reported here discuss the antitumor activity of the combination of Herceptin and nonliposomal cisplatin or PL-cisplatin in two xenograft tumor models, initiated from the cell lines, BT474 and MDA453, that overexpress the oncogene, HER2. Herceptin alone had significant antitumor activity in all three experiments (p cisplatin and PL-cisplatin were both effective antitumor agents but, at tolerable dose levels, PL-cisplatin was superior to nonliposomal cisplatin (p cisplatin or PL-cisplatin, was most significant at moderate doses of H (0.5 mg/kg, p cisplatin with Herceptin had statistically similar antitumor activity to that of nonliposomal cisplatin with Herceptin in all experiments. We conclude that combination therapy with PL-cisplatin and Herceptin results in significant antitumor activity with the potential for reducing toxicity in metastatic breast cancer patients.

  15. DNA repair in modeled microgravity: Double strand break rejoining activity in human lymphocytes irradiated with {gamma}-rays

    Energy Technology Data Exchange (ETDEWEB)

    Mognato, Maddalena, E-mail: maddalena.mognato@unipd.it [Dipartimento di Biologia, Universita di Padova, via U. Bassi 58 B, 35121 Padova (Italy); Girardi, Cristina; Fabris, Sonia [Dipartimento di Biologia, Universita di Padova, via U. Bassi 58 B, 35121 Padova (Italy); Celotti, Lucia [Dipartimento di Biologia, Universita di Padova, via U. Bassi 58 B, 35121 Padova (Italy); Laboratori Nazionali di Legnaro, INFN, Padova (Italy)

    2009-04-26

    Cell response to ionising radiation depends, besides on genetic and physiological features of the biological systems, on environmental conditions occurring during DNA repair. Many data showed that microgravity, experienced by astronauts during space flights or modeled on Earth, causes apoptosis, cytoskeletal alteration, cell growth inhibition, increased frequency of mutations and chromosome aberrations. In this study, we analysed the progression of the rejoining of double strand breaks (DSBs) in human peripheral blood lymphocytes (PBLs) irradiated with {gamma}-rays and incubated in static condition (1g) or in modeled microgravity (MMG). {gamma}-H2AX foci formation and disappearance, monitored during the repair incubation, showed that the kinetics of DSBs rejoining was different in the two gravity conditions. The fraction of foci-positive cells decreased slower in MMG than in 1g at 6 and 24 h after irradiation (P < 0.01) and the mean number of {gamma}-H2AX foci per nucleus was significantly higher in MMG than in 1g at the same time-points (P < 0.001). In the same samples we determined apoptotic level and the rate of DSB rejoining during post-irradiation incubation. A significant induction of apoptosis was observed in MMG at 24 h after irradiation (P < 0.001), whereas at shorter times the level of apoptosis was slightly higher in MMG respect to 1g. In accordance with the kinetics of {gamma}-H2AX foci, the slower rejoining of radiation-induced DSBs in MMG was observed by DNA fragmentation analyses during the repair incubation; the data of pulsed-field gel electrophoresis assay showed that the fraction of DNA released in the gel was significantly higher in PBL incubated in MMG after irradiation with respect to cells maintained in 1g. Our results provide evidences that MMG incubation during DNA repair delayed the rate of radiation-induced DSB rejoining, and increased, as a consequence, the genotoxic effects of ionising radiation.

  16. Integrated Environmental Modelling: human decisions, human challenges

    Science.gov (United States)

    Glynn, Pierre D.

    2015-01-01

    Integrated Environmental Modelling (IEM) is an invaluable tool for understanding the complex, dynamic ecosystems that house our natural resources and control our environments. Human behaviour affects the ways in which the science of IEM is assembled and used for meaningful societal applications. In particular, human biases and heuristics reflect adaptation and experiential learning to issues with frequent, sharply distinguished, feedbacks. Unfortunately, human behaviour is not adapted to the more diffusely experienced problems that IEM typically seeks to address. Twelve biases are identified that affect IEM (and science in general). These biases are supported by personal observations and by the findings of behavioural scientists. A process for critical analysis is proposed that addresses some human challenges of IEM and solicits explicit description of (1) represented processes and information, (2) unrepresented processes and information, and (3) accounting for, and cognizance of, potential human biases. Several other suggestions are also made that generally complement maintaining attitudes of watchful humility, open-mindedness, honesty and transparent accountability. These suggestions include (1) creating a new area of study in the behavioural biogeosciences, (2) using structured processes for engaging the modelling and stakeholder communities in IEM, and (3) using ‘red teams’ to increase resilience of IEM constructs and use.

  17. Adapted Active Appearance Models

    Directory of Open Access Journals (Sweden)

    Renaud Séguier

    2009-01-01

    Full Text Available Active Appearance Models (AAMs are able to align efficiently known faces under duress, when face pose and illumination are controlled. We propose Adapted Active Appearance Models to align unknown faces in unknown poses and illuminations. Our proposal is based on the one hand on a specific transformation of the active model texture in an oriented map, which changes the AAM normalization process; on the other hand on the research made in a set of different precomputed models related to the most adapted AAM for an unknown face. Tests on public and private databases show the interest of our approach. It becomes possible to align unknown faces in real-time situations, in which light and pose are not controlled.

  18. Integrated Extravehicular Activity Human Research Plan: 2016

    Science.gov (United States)

    Abercromby, Andrew F. J.; Ross, Amy J.; Cupples, J. Scott; Rajulu, Sudhakar; Norcross, Jason R.; Chappell, Steven P.

    2016-01-01

    Multiple organizations within NASA and outside of NASA fund and participate in research related to extravehicular activity (EVA). In October 2015, representatives of the EVA Office, the Crew and Thermal Systems Division (CTSD), and the Human Research Program (HRP) at NASA Johnson Space Center agreed on a formal framework to improve multi-year coordination and collaboration in EVA research. At the core of the framework is an Integrated EVA Human Research Plan and a process by which it will be annually reviewed and updated. The over-arching objective of the collaborative framework is to conduct multi-disciplinary cost-effective research that will enable humans to perform EVAs safely, effectively, comfortably, and efficiently, as needed to enable and enhance human space exploration missions. Research activities must be defined, prioritized, planned and executed to comprehensively address the right questions, avoid duplication, leverage other complementary activities where possible, and ultimately provide actionable evidence-based results in time to inform subsequent tests, developments and/or research activities. Representation of all appropriate stakeholders in the definition, prioritization, planning and execution of research activities is essential to accomplishing the over-arching objective. A formal review of the Integrated EVA Human Research Plan will be conducted annually. External peer review of all HRP EVA research activities including compilation and review of published literature in the EVA Evidence Report is will also continue at a frequency determined by HRP management. Coordination with stakeholders outside of the EVA Office, CTSD, and HRP is already in effect on a study-by-study basis; closer coordination on multi-year planning with other EVA stakeholders including academia is being actively pursued. Details of the current Integrated EVA Human Research Plan are presented including description of ongoing and planned research activities in the areas of

  19. Pro-apoptotic activity of α-bisabolol in preclinical models of primary human acute leukemia cells

    Directory of Open Access Journals (Sweden)

    Fato Romana

    2011-04-01

    Full Text Available Abstract Background We previously demonstrated that the plant-derived agent α-bisabolol enters cells via lipid rafts, binds to the pro-apoptotic Bcl-2 family protein BID, and may induce apoptosis. Here we studied the activity of α-bisabolol in acute leukemia cells. Methods We tested ex vivo blasts from 42 acute leukemias (14 Philadelphia-negative and 14 Philadelphia-positive B acute lymphoid leukemias, Ph-/Ph+B-ALL; 14 acute myeloid leukemias, AML for their sensitivity to α-bisabolol in 24-hour dose-response assays. Concentrations and time were chosen based on CD34+, CD33+my and normal peripheral blood cell sensitivity to increasing α-bisabolol concentrations for up to 120 hours. Results A clustering analysis of the sensitivity over 24 hours identified three clusters. Cluster 1 (14 ± 5 μM α-bisabolol IC50 included mainly Ph-B-ALL cells. AML cells were split into cluster 2 and 3 (45 ± 7 and 65 ± 5 μM IC50. Ph+B-ALL cells were scattered, but mainly grouped into cluster 2. All leukemias, including 3 imatinib-resistant cases, were eventually responsive, but a subset of B-ALL cells was fairly sensitive to low α-bisabolol concentrations. α-bisabolol acted as a pro-apoptotic agent via a direct damage to mitochondrial integrity, which was responsible for the decrease in NADH-supported state 3 respiration and the disruption of the mitochondrial membrane potential. Conclusion Our study provides the first evidence that α-bisabolol is a pro-apoptotic agent for primary human acute leukemia cells.

  20. Selective Activation of Resting-State Networks following Focal Stimulation in a Connectome-Based Network Model of the Human Brain

    Science.gov (United States)

    2016-01-01

    Abstract When the brain is stimulated, for example, by sensory inputs or goal-oriented tasks, the brain initially responds with activities in specific areas. The subsequent pattern formation of functional networks is constrained by the structural connectivity (SC) of the brain. The extent to which information is processed over short- or long-range SC is unclear. Whole-brain models based on long-range axonal connections, for example, can partly describe measured functional connectivity dynamics at rest. Here, we study the effect of SC on the network response to stimulation. We use a human whole-brain network model comprising long- and short-range connections. We systematically activate each cortical or thalamic area, and investigate the network response as a function of its short- and long-range SC. We show that when the brain is operating at the edge of criticality, stimulation causes a cascade of network recruitments, collapsing onto a smaller space that is partly constrained by SC. We found both short- and long-range SC essential to reproduce experimental results. In particular, the stimulation of specific areas results in the activation of one or more resting-state networks. We suggest that the stimulus-induced brain activity, which may indicate information and cognitive processing, follows specific routes imposed by structural networks explaining the emergence of functional networks. We provide a lookup table linking stimulation targets and functional network activations, which potentially can be useful in diagnostics and treatments with brain stimulation. PMID:27752540

  1. Phenyl valerate esterase activity of human butyrylcholinesterase.

    Science.gov (United States)

    Mangas, Iris; Vilanova, Eugenio; Estévez, Jorge

    2017-03-15

    Phenyl valerate is used for detecting and measuring neuropathy target esterase (NTE) and has been used for discriminating esterases as potential target in hen model of organophosphorus delayed neuropathy. In previous studies we observed that phenyl valerate esterase (PVase) activity of an enzymatic fraction in chicken brain might be due to a butyrylcholinesterase protein (BuChE), and it was suggested that this enzymatic fraction could be related to the potentiation/promotion phenomenon of the organophosphate-induced delayed neuropathy (OPIDN). In this work, PVase activity of purified human butyrylcholinesterase (hBuChE) is demonstrated and confirms the novel observation that a relationship of BuChE with PVase activities is also relevant for humans, as is, therefore the potential role in toxicity for humans. The KM and catalytic constant (kcat) were estimated as 0.52/0.72 µM and 45,900/49,200 min(-1) respectively. Furthermore, this work studies the inhibition by preincubation of PVase and cholinesterase activities of hBuChE with irreversible inhibitors (mipafox, iso-OMPA or PMSF), showing that these inhibitors interact similarly in both activities with similar second-order inhibition constants. Acethylthiocholine and phenyl valerate partly inhibit PVase and cholinesterase activities, respectively. All these observations suggest that both activities occur in the same active center. The interaction with a reversible inhibitor (ethopropazine) showed that the cholinesterase activity was more sensitive than the PVase activity, showing that the sensitivity for this reversible inhibitor is affected by the nature of the substrate. The present work definitively establishes the capacity of BuChE to hydrolyze the carboxylester phenyl valerate using a purified enzyme (hBuChE). Therefore, BuChE should be considered in the research of organophosphorus targets of toxicity related with PVase proteins.

  2. Antitumor activity and prolonged survival by carbon-nanotube-mediated therapeutic siRNA silencing in a human lung xenograft model.

    Science.gov (United States)

    Podesta, Jennifer E; Al-Jamal, Khuloud T; Herrero, M Antonia; Tian, Bowen; Ali-Boucetta, Hanene; Hegde, Vikas; Bianco, Alberto; Prato, Maurizio; Kostarelos, Kostas

    2009-05-01

    Carbon nanotubes are novel nanomaterials that are thought to offer potential benefits to a variety of biomedical and clinical applications. In this study, the treatment of a human lung carcinoma model in vivo using siRNA sequences leading to cytotoxicity and cell death is carried out using either cationic liposomes (DOTAP:cholesterol) or amino-functionalized multi-walled carbon nanotubes (MWNT - NH(+)(3)). Validation for the most cytotoxic siRNA sequence using a panel of human carcinoma and murine cells reveals that the proprietary siTOX sequence is human specific and can lead to significant cytotoxic activities delivered both by liposome or MWNT - NH(+)(3) in vitro. A comparative study using both types of vector indicates that only MWNT - NH(+)(3):siRNA complexes administered intratumorally can elicit delayed tumor growth and increased survival of xenograft-bearing animals. siTOX delivery via the cationic MWNT - NH(+)(3) is biologically active in vivo by triggering an apoptotic cascade, leading to extensive necrosis of the human tumor mass. This suggests that carbon-nanotube-mediated delivery of siRNA by intratumoral administration leads to successful and statistically significant suppression of tumor volume, followed by a concomitant prolongation of survival of human lung tumor-bearing animals. The direct comparison between carbon nanotubes and liposomes demonstrates the potential advantages offered by carbon nanotubes for the intracellular delivery of therapeutic agents in vivo. The present work may act as the impetus for further studies to explore the therapeutic capacity of chemically functionalized carbon nanotubes to deliver siRNA directly into the cytoplasm of target cells and achieve effective therapeutic silencing in various disease indications where local delivery is feasible or desirable.

  3. Human Activity Detection from RGBD Images

    CERN Document Server

    Sung, Jaeyong; Selman, Bart; Saxena, Ashutosh

    2011-01-01

    Being able to detect and recognize human activities is important for making personal assistant robots useful in performing assistive tasks. The challenge is to develop a system that is low-cost, reliable in unstructured home settings, and also straightforward to use. In this paper, we use a RGBD sensor (Microsoft Kinect) as the input sensor, and present learning algorithms to infer the activities. Our algorithm is based on a hierarchical maximum entropy Markov model (MEMM). It considers a person's activity as composed of a set of sub-activities, and infers the two-layered graph structure using a dynamic programming approach. We test our algorithm on detecting and recognizing twelve different activities performed by four people in different environments, such as a kitchen, a living room, an office, etc., and achieve an average performance of 84.3% when the person was seen before in the training set (and 64.2% when the person was not seen before).

  4. Chemically synthesized glycosides of hydroxylated flavylium ions as suitable models of anthocyanins: binding to iron ions and human serum albumin, antioxidant activity in model gastric conditions.

    Science.gov (United States)

    Al Bittar, Sheiraz; Mora, Nathalie; Loonis, Michèle; Dangles, Olivier

    2014-12-11

    Polyhydroxylated flavylium ions, such as 3',4',7-trihydroxyflavylium chloride (P1) and its more water-soluble 7-O-β-d-glucopyranoside (P2), are readily accessible by chemical synthesis and suitable models of natural anthocyanins in terms of color and species distribution in aqueous solution. Owing to their catechol B-ring, they rapidly bind FeIII, weakly interact with FeII and promote its autoxidation to FeIII. Both pigments inhibit heme-induced lipid peroxidation in mildly acidic conditions (a model of postprandial oxidative stress in the stomach), the colorless (chalcone) forms being more potent than the colored forms. Finally, P1 and P2 are moderate ligands of human serum albumin (HSA), their likely carrier in the blood circulation, with chalcones having a higher affinity for HSA than the corresponding colored forms.

  5. Chemically Synthesized Glycosides of Hydroxylated Flavylium Ions as Suitable Models of Anthocyanins: Binding to Iron Ions and Human Serum Albumin, Antioxidant Activity in Model Gastric Conditions

    Directory of Open Access Journals (Sweden)

    Sheiraz Al Bittar

    2014-12-01

    Full Text Available Polyhydroxylated flavylium ions, such as 3',4',7-trihydroxyflavylium chloride (P1 and its more water-soluble 7-O-β-d-glucopyranoside (P2, are readily accessible by chemical synthesis and suitable models of natural anthocyanins in terms of color and species distribution in aqueous solution. Owing to their catechol B-ring, they rapidly bind FeIII, weakly interact with FeII and promote its autoxidation to FeIII. Both pigments inhibit heme-induced lipid peroxidation in mildly acidic conditions (a model of postprandial oxidative stress in the stomach, the colorless (chalcone forms being more potent than the colored forms. Finally, P1 and P2 are moderate ligands of human serum albumin (HSA, their likely carrier in the blood circulation, with chalcones having a higher affinity for HSA than the corresponding colored forms.

  6. Plasma-derived human C1-esterase inhibitor does not prevent mechanical ventilation-induced pulmonary complement activation in a rat model of Streptococcus pneumoniae pneumonia.

    Science.gov (United States)

    de Beer, F M; Aslami, H; Hoeksma, J; van Mierlo, G; Wouters, D; Zeerleder, S; Roelofs, J J T H; Juffermans, N P; Schultz, M J; Lagrand, W K

    2014-11-01

    Mechanical ventilation has the potential to cause lung injury, and the role of complement activation herein is uncertain. We hypothesized that inhibition of the complement cascade by administration of plasma-derived human C1-esterase inhibitor (C1-INH) prevents ventilation-induced pulmonary complement activation, and as such attenuates lung inflammation and lung injury in a rat model of Streptococcus pneumoniae pneumonia. Forty hours after intratracheal challenge with S. pneumoniae causing pneumonia rats were subjected to ventilation with lower tidal volumes and positive end-expiratory pressure (PEEP) or high tidal volumes without PEEP, after an intravenous bolus of C1-INH (200 U/kg) or placebo (saline). After 4 h of ventilation blood, broncho-alveolar lavage fluid and lung tissue were collected. Non-ventilated rats with S. pneumoniae pneumonia served as controls. While ventilation with lower tidal volumes and PEEP slightly amplified pneumonia-induced complement activation in the lungs, ventilation with higher tidal volumes without PEEP augmented local complement activation more strongly. Systemic pre-treatment with C1-INH, however, failed to alter ventilation-induced complement activation with both ventilation strategies. In accordance, lung inflammation and lung injury were not affected by pre-treatment with C1-INH, neither in rats ventilated with lower tidal volumes and PEEP, nor rats ventilated with high tidal volumes without PEEP. Ventilation augments pulmonary complement activation in a rat model of S. pneumoniae pneumonia. Systemic administration of C1-INH, however, does not attenuate ventilation-induced complement activation, lung inflammation, and lung injury.

  7. Synthesis and antiproliferative activity of conformationally restricted 1,2,3-triazole analogues of combretastatins in the sea urchin embryo model and against human cancer cell lines.

    Science.gov (United States)

    Demchuk, Dmitry V; Samet, Alexander V; Chernysheva, Natalia B; Ushkarov, Vladimir I; Stashina, Galina A; Konyushkin, Leonid D; Raihstat, Mikhail M; Firgang, Sergei I; Philchenkov, Alex A; Zavelevich, Michael P; Kuiava, Ludmila M; Chekhun, Vasyl F; Blokhin, Dmitry Yu; Kiselyov, Alex S; Semenova, Marina N; Semenov, Victor V

    2014-01-15

    A series of 1,5-diaryl- and 4,5-diaryl-1,2,3-triazole derivatives of combretastatin A4 were synthesized and evaluated as antimitotic microtubule destabilizing agents using the sea urchin embryo model. Structure-activity relationship studies identified compounds substituted with 3,4,5-trimethoxyphenyl and 3,4-methylenedioxy-5-methoxyphenyl ring A and 4-methoxyphenyl ring B as potent antiproliferative agents with high cytotoxicity against a panel of human cancer cell lines including multi-drug resistant cells. 4,5-Diaryl-1,2,3-triazoles (C-C geometry) were found to be considerably more active than the respective 1,5-diaryl-1,2,3-triazoles (N-C geometry). Compound 10ad' induced G2/M cell cycle arrest and apoptosis in human T-leukemia Jurkat cells via caspase 2/3/9 activation and downregulation of the antiapoptotic protein XIAP. A mitotic catastrophe has been evaluated as another possible cell death mode.

  8. A model of the effects of land-based, human activities on the health of coral reefs in the Great Barrier Reef and in Fouha Bay, Guam, Micronesia

    Science.gov (United States)

    Wolanski, Eric; Richmond, Robert H.; McCook, Laurence

    2004-05-01

    A model is proposed to explain coral and algal abundance on coastal coral reefs as a function of spike-like natural disturbances from tropical cyclones and turbid river floods, followed by long recovery periods where the rate of reef recovery depends on ambient water and substratum quality. The model includes competition for space between corals and algae, coral recruitment and reef connectivity. The model is applied to a 400-km stretch of Australia's Great Barrier Reef and to the 200-m-long reef tract at Fouha Bay, in Guam, Micronesia. For these two sites and at these two scales, the model appears successful at reproducing the observed distribution of algae and coral. For both sites, it is suggested that the reefs have been degraded by human activities on land and that they will recover provided remedial measures are implemented on land to restore the water and substrate conditions. We suggest ways to improve the model and to use the model to guide future ecological research and management efforts on coastal coral reefs.

  9. Human Adaptive Mechatronics and Human-System Modelling

    Directory of Open Access Journals (Sweden)

    Satoshi Suzuki

    2013-03-01

    Full Text Available Several topics in projects for mechatronics studies, which are 'Human Adaptive Mechatronics (HAM' and 'Human-System Modelling (HSM', are presented in this paper. The main research theme of the HAM project is a design strategy for a new intelligent mechatronics system, which enhances operators' skills during machine operation. Skill analyses and control system design have been addressed. In the HSM project, human modelling based on hierarchical classification of skills was studied, including the following five types of skills: social, planning, cognitive, motion and sensory-motor skills. This paper includes digests of these research topics and the outcomes concerning each type of skill. Relationships with other research activities, knowledge and information that will be helpful for readers who are trying to study assistive human-mechatronics systems are also mentioned.

  10. Anti-tumor activity of the TRA-8 anti-DR5 antibody in combination with cisplatin in an ex vivo human cervical cancer model.

    Science.gov (United States)

    Kendrick, James E; Straughn, J Michael; Oliver, Patsy G; Wang, Wenquan; Nan, Li; Grizzle, William E; Stockard, Cecil R; Alvarez, Ronald D; Buchsbaum, Donald J

    2008-03-01

    To investigate the cytotoxicity of TRA-8, an antibody that specifically binds death receptor 5 (DR5), alone and in combination with cisplatin, using an ex vivo human cervical cancer model. Fifteen cervical cancer specimens were obtained at the time of radical hysterectomy and tumor slices were prepared with the Krumdieck tissue slicer. Tumor slices were exposed to varying concentrations of TRA-8, cisplatin, or the combination of TRA-8 and cisplatin. Using non-linear modeling, dose response curves and IC50 values were generated for each specimen treated with TRA-8. The additive cytotoxic effect of combination treatment was evaluated as well. In addition to ATP viability assays, treated and untreated slices were assessed by immunohistochemistry (IHC) and western blot analysis to confirm apoptosis induction via the extrinsic pathway. Eleven patient specimens yielded TRA-8-induced IC50 values. Sixty-four percent were found to be sensitive to TRA-8-induced cytotoxicity at IC50 doses less than 1000 ng/ml. Seven patient specimens underwent combination treatment with TRA-8 and cisplatin. Of these specimens, 86% exhibited additive cytotoxicity in comparison to treatment with either agent alone. IHC revealed an increase in DR5 expression in tumor slices treated with cisplatin for 24 h. IHC and Western blotting demonstrated TRA-8-induced cell death via apoptosis and activation of caspase 3 and 8. This study confirms the utility of an ex vivo human cervical cancer model, to evaluate the anti-tumor activity of TRA-8 and cisplatin. This model may be a useful pre-clinical tool to assess cytotoxicity and mechanistic properties of novel agents in cervical cancer.

  11. MODELING ENERGY EXPENDITURE AND OXYGEN CONSUMPTION IN HUMAN EXPOSURE MODELS: ACCOUNTING FOR FATIGUE AND EPOC

    Science.gov (United States)

    Human exposure and dose models often require a quantification of oxygen consumption for a simulated individual. Oxygen consumption is dependent on the modeled Individual's physical activity level as described in an activity diary. Activity level is quantified via standardized val...

  12. MODELING ENERGY EXPENDITURE AND OXYGEN CONSUMPTION IN HUMAN EXPOSURE MODELS: ACCOUNTING FOR FATIGUE AND EPOC

    Science.gov (United States)

    Human exposure and dose models often require a quantification of oxygen consumption for a simulated individual. Oxygen consumption is dependent on the modeled Individual's physical activity level as described in an activity diary. Activity level is quantified via standardized val...

  13. Telomerase activity in human cancer

    Energy Technology Data Exchange (ETDEWEB)

    Griffith, J.

    2000-10-01

    The overall goal of this collaborative project was to investigate the role in malignant cells of both chromosome telomeres, and telomerase, the enzyme that replicates telomeres. Telomeres are highly conserved nucleoprotein complexes located at the ends of eucaryotic chromosomes. Telomere length in somatic cells is reduced by 40--50 nucleotide pairs with every cell division due to incomplete replication of terminal DNA sequences and the absence of telomerase, the ribonucleoprotein that adds telomere DNA to chromosome ends. Although telomerase is active in cells with extended proliferative capacities, including more than 85% of tumors, work performed under this contract demonstrated that the telomeres of human cancer cells are shorter than those of paired normal cells, and that the length of the telomeres is characteristic of particular types of cancers. The extent of telomere shortening ostensibly is related to the number of cell divisions the tumor has undergone. It is believed that ongoing cell proliferation leads to the accumulation and fixation of new mutations in tumor cell lineages.Therefore, it is not unreasonable to assume that the degree of phenotypic variability is related to the proliferative history of the tumor, and therefore to telomere length, implying a correlation with prognosis. In some human tumors, short telomeres are also correlated with genomic instabilities, including interstitial chromosome translocation, loss of heterozygosity, and aneuoploidy. Moreover, unprotected chromosome ends are highly recombinogenic and telomere shortening in cultured human cells correlates with the formation of dicentric chromosomes, suggesting that critically short telomeres not only identify, but also predispose, cells to genomic instability, again implying a correlation with prognosis. Therefore, telomere length or content could be an important predictor of metastatic potential or responsiveness to various therapeutic modalities.

  14. A Spatiotemporal Robust Approach for Human Activity Recognition

    Directory of Open Access Journals (Sweden)

    Md. Zia Uddin

    2013-11-01

    Full Text Available Nowadays, human activity recognition is considered to be one of the fundamental topics in computer vision research areas, including human-robot interaction. In this work, a novel method is proposed utilizing the depth and optical flow motion information of human silhouettes from video for human activity recognition. The recognition method utilizes enhanced independent component analysis (EICA on depth silhouettes, optical flow motion features, and hidden Markov models (HMMs for recognition. The local features are extracted from the collection of the depth silhouettes exhibiting various human activities. Optical flow- based motion features are also extracted from the depth silhouette area and used in an augmented form to form the spatiotemporal features. Next, the augmented features are enhanced by generalized discriminant analysis (GDA for better activity representation. These features are then fed into HMMs to model human activities and recognize them. The experimental results show the superiority of the proposed approach over the conventional ones.

  15. Physical Human Activity Recognition Using Wearable Sensors

    Directory of Open Access Journals (Sweden)

    Ferhat Attal

    2015-12-01

    Full Text Available This paper presents a review of different classification techniques used to recognize human activities from wearable inertial sensor data. Three inertial sensor units were used in this study and were worn by healthy subjects at key points of upper/lower body limbs (chest, right thigh and left ankle. Three main steps describe the activity recognition process: sensors’ placement, data pre-processing and data classification. Four supervised classification techniques namely, k-Nearest Neighbor (k-NN, Support Vector Machines (SVM, Gaussian Mixture Models (GMM, and Random Forest (RF as well as three unsupervised classification techniques namely, k-Means, Gaussian mixture models (GMM and Hidden Markov Model (HMM, are compared in terms of correct classification rate, F-measure, recall, precision, and specificity. Raw data and extracted features are used separately as inputs of each classifier. The feature selection is performed using a wrapper approach based on the RF algorithm. Based on our experiments, the results obtained show that the k-NN classifier provides the best performance compared to other supervised classification algorithms, whereas the HMM classifier is the one that gives the best results among unsupervised classification algorithms. This comparison highlights which approach gives better performance in both supervised and unsupervised contexts. It should be noted that the obtained results are limited to the context of this study, which concerns the classification of the main daily living human activities using three wearable accelerometers placed at the chest, right shank and left ankle of the subject.

  16. Computational Intelligence in a Human Brain Model

    Directory of Open Access Journals (Sweden)

    Viorel Gaftea

    2016-06-01

    Full Text Available This paper focuses on the current trends in brain research domain and the current stage of development of research for software and hardware solutions, communication capabilities between: human beings and machines, new technologies, nano-science and Internet of Things (IoT devices. The proposed model for Human Brain assumes main similitude between human intelligence and the chess game thinking process. Tactical & strategic reasoning and the need to follow the rules of the chess game, all are very similar with the activities of the human brain. The main objective for a living being and the chess game player are the same: securing a position, surviving and eliminating the adversaries. The brain resolves these goals, and more, the being movement, actions and speech are sustained by the vital five senses and equilibrium. The chess game strategy helps us understand the human brain better and easier replicate in the proposed ‘Software and Hardware’ SAH Model.

  17. Computational Intelligence in a Human Brain Model

    Directory of Open Access Journals (Sweden)

    Viorel Gaftea

    2016-06-01

    Full Text Available This paper focuses on the current trends in brain research domain and the current stage of development of research for software and hardware solutions, communication capabilities between: human beings and machines, new technologies, nano-science and Internet of Things (IoT devices. The proposed model for Human Brain assumes main similitude between human intelligence and the chess game thinking process. Tactical & strategic reasoning and the need to follow the rules of the chess game, all are very similar with the activities of the human brain. The main objective for a living being and the chess game player are the same: securing a position, surviving and eliminating the adversaries. The brain resolves these goals, and more, the being movement, actions and speech are sustained by the vital five senses and equilibrium. The chess game strategy helps us understand the human brain better and easier replicate in the proposed ‘Software and Hardware’ SAH Model.

  18. Analysis of Gait Pattern to Recognize the Human Activities

    Directory of Open Access Journals (Sweden)

    Jay Prakash Gupta

    2014-09-01

    Full Text Available Human activity recognition based on the computer vision is the process of labelling image sequences with action labels. Accurate systems for this problem are applied in areas such as visual surveillance, human computer interaction and video retrieval. The challenges are due to variations in motion, recording settings and gait differences. Here we propose an approach to recognize the human activities through gait. Activity recognition through Gait is the process of identifying an activity by the manner in which they walk. The identification of human activities in a video, such as a person is walking, running, jumping, jogging etc are important activities in video surveillance. We contribute the use of Model based approach for activity recognition with the help of movement of legs only. Experimental results suggest that our method are able to recognize the human activities with a good accuracy rate and robust to shadows present in the videos.

  19. Human cord blood progenitors with high aldehyde dehydrogenase activity improve vascular density in a model of acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Creer Michael H

    2010-03-01

    Full Text Available Abstract Human stem cells from adult sources have been shown to contribute to the regeneration of muscle, liver, heart, and vasculature. The mechanisms by which this is accomplished are, however, still not well understood. We tested the engraftment and regenerative potential of human umbilical cord blood-derived ALDHhiLin-, and ALDHloLin- cells following transplantation to NOD/SCID or NOD/SCID β2m null mice with experimentally induced acute myocardial infarction. We used combined nanoparticle labeling and whole organ fluorescent imaging to detect human cells in multiple organs 48 hours post transplantation. Engraftment and regenerative effects of cell treatment were assessed four weeks post transplantation. We found that ALDHhiLin- stem cells specifically located to the site of injury 48 hours post transplantation and engrafted the infarcted heart at higher frequencies than ALDHloLin- committed progenitor cells four weeks post transplantation. We found no donor derived cardiomyocytes and few endothelial cells of donor origin. Cell treatment was not associated with any detectable functional improvement at the four week endpoint. There was, however, a significant increase in vascular density in the central infarct zone of ALDHhiLin- cell-treated mice, as compared to PBS and ALDHloLin- cell-treated mice. Conclusions Our data indicate that adult human stem cells do not become a significant part of the regenerating tissue, but rapidly home to and persist only temporarily at the site of hypoxic injury to exert trophic effects on tissue repair thereby enhancing vascular recovery.

  20. A natural human hand model

    NARCIS (Netherlands)

    Van Nierop, O.A.; Van der Helm, A.; Overbeeke, K.J.; Djajadiningrat, T.J.P.

    2007-01-01

    We present a skeletal linked model of the human hand that has natural motion. We show how this can be achieved by introducing a new biology-based joint axis that simulates natural joint motion and a set of constraints that reduce an estimated 150 possible motions to twelve. The model is based on obs

  1. In vitro and in vivo activities of 2-aminopyrazines and 2-aminopyridines in experimental models of human African trypanosomiasis.

    Science.gov (United States)

    Vodnala, Suman K; Lundbäck, Thomas; Sjöberg, Birger; Svensson, Richard; Rottenberg, Martin E; Hammarström, Lars G J

    2013-02-01

    New drugs for the treatment of human African trypanosomiasis are urgently needed. A number of 2-aminopyrazines/2-aminopyridines were identified as promising leads following a focused screen of 5,500 compounds for Trypanosoma brucei subsp. brucei viability. Described compounds are trypanotoxic in the submicromolar range and show comparably low cytotoxicity on representative mammalian cell lines. Specifically, 6-([6-fluoro-3,4-dihydro-2H-1-benzopyran-4-yl)]oxy)-N-(piperidin-4-yl)pyrazin-2-amine (CBK201352) is trypanotoxic for T. brucei subsp. brucei, T. brucei subsp. gambiense, and T. brucei subsp. rhodesiense and is nontoxic to mammalian cell lines, and in vitro preclinical assays predict promising pharmacokinetic parameters. Mice inoculated intraperitoneally (i.p.) with 25 mg/kg CBK201352 twice daily for 10 days, starting on the day of infection with T. brucei subsp. brucei, show complete clearance of parasites for more than 90 days. Thus, CBK201352 and related analogs are promising leads for the development of novel treatments for human African trypanosomiasis.

  2. Therapeutic Effects of CUR-Activated Human Umbilical Cord Mesenchymal Stem Cells on 1-Methyl-4-phenylpyridine-Induced Parkinson's Disease Cell Model.

    Science.gov (United States)

    Jinfeng, Li; Yunliang, Wang; Xinshan, Liu; Yutong, Wang; Shanshan, Wang; Peng, Xue; Xiaopeng, Yang; Zhixiu, Xu; Qingshan, Lu; Honglei, Yin; Xia, Cao; Hongwei, Wang; Bingzhen, Cao

    2016-01-01

    The purpose of this study is to evaluate the therapeutic effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSC) activated by curcumin (CUR) on PC12 cells induced by 1-methyl-4-phenylpyridinium ion (MPP+), a cell model of Parkinson's disease (PD). The supernatant of hUC-MSC and hUC-MSC activated by 5 µmol/L CUR (hUC-MSC-CUR) were collected in accordance with the same concentration. The cell proliferation and differentiation potential to dopaminergic neuronal cells and antioxidation were observed in PC12 cells after being treated with the above two supernatants and 5 µmol/L CUR. The results showed that the hUC-MSC-CUR could more obviously promote the proliferation and the expression of tyrosine hydroxylase (TH) and microtubule associated protein-2 (MAP2) and significantly decreased the expression of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) in PC12 cells. Furtherly, cytokines detection gave a clue that the expression of IL-6, IL-10, and NGF was significantly higher in the group treated with the hUC-MSC-CUR compared to those of other two groups. Therefore, the hUC-MSC-CUR may be a potential strategy to promote the proliferation and differentiation of PD cell model, therefore providing new insights into a novel therapeutic approach in PD.

  3. Therapeutic Effects of CUR-Activated Human Umbilical Cord Mesenchymal Stem Cells on 1-Methyl-4-phenylpyridine-Induced Parkinson’s Disease Cell Model

    Directory of Open Access Journals (Sweden)

    Li Jinfeng

    2016-01-01

    Full Text Available The purpose of this study is to evaluate the therapeutic effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSC activated by curcumin (CUR on PC12 cells induced by 1-methyl-4-phenylpyridinium ion (MPP+, a cell model of Parkinson’s disease (PD. The supernatant of hUC-MSC and hUC-MSC activated by 5 µmol/L CUR (hUC-MSC-CUR were collected in accordance with the same concentration. The cell proliferation and differentiation potential to dopaminergic neuronal cells and antioxidation were observed in PC12 cells after being treated with the above two supernatants and 5 µmol/L CUR. The results showed that the hUC-MSC-CUR could more obviously promote the proliferation and the expression of tyrosine hydroxylase (TH and microtubule associated protein-2 (MAP2 and significantly decreased the expression of nitric oxide (NO and inducible nitric oxide synthase (iNOS in PC12 cells. Furtherly, cytokines detection gave a clue that the expression of IL-6, IL-10, and NGF was significantly higher in the group treated with the hUC-MSC-CUR compared to those of other two groups. Therefore, the hUC-MSC-CUR may be a potential strategy to promote the proliferation and differentiation of PD cell model, therefore providing new insights into a novel therapeutic approach in PD.

  4. A δ38 deletion variant of human transketolase as a model of transketolase-like protein 1 exhibits no enzymatic activity.

    Directory of Open Access Journals (Sweden)

    Stefan Schneider

    Full Text Available Besides transketolase (TKT, a thiamin-dependent enzyme of the pentose phosphate pathway, the human genome encodes for two closely related transketolase-like proteins, which share a high sequence identity with TKT. Transketolase-like protein 1 (TKTL1 has been implicated in cancerogenesis as its cellular expression levels were reported to directly correlate with invasion efficiency of cancer cells and patient mortality. It has been proposed that TKTL1 exerts its function by catalyzing an unusual enzymatic reaction, a hypothesis that has been the subject of recent controversy. The most striking difference between TKTL1 and TKT is a deletion of 38 consecutive amino acids in the N-terminal domain of the former, which constitute part of the active site in authentic TKT. Our structural and sequence analysis suggested that TKTL1 might not possess transketolase activity. In order to test this hypothesis in the absence of a recombinant expression system for TKTL1 and resilient data on its biochemical properties, we have engineered and biochemically characterized a "pseudo-TKTL1" Δ38 deletion variant of human TKT (TKTΔ38 as a viable model of TKTL1. Although the isolated protein is properly folded under in vitro conditions, both thermal stability as well as stability of the TKT-specific homodimeric assembly are markedly reduced. Circular dichroism and NMR spectroscopic analysis further indicates that TKTΔ38 is unable to bind the thiamin cofactor in a specific manner, even at superphysiological concentrations. No transketolase activity of TKTΔ38 can be detected for conversion of physiological sugar substrates thus arguing against an intrinsically encoded enzymatic function of TKTL1 in tumor cell metabolism.

  5. On Activity modelling in process modeling

    Directory of Open Access Journals (Sweden)

    Dorel Aiordachioaie

    2001-12-01

    Full Text Available The paper is looking to the dynamic feature of the meta-models of the process modelling process, the time. Some principles are considered and discussed as main dimensions of any modelling activity: the compatibility of the substances, the equipresence of phenomena and the solvability of the model. The activity models are considered and represented at meta-level.

  6. In vitro and in vivo activity of 4-thio-uridylate against JY cells, a model for human acute lymphoid leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Berenyi, Erika [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary); Benko, Ilona [Department of Pharmacology and Pharmacotherapy, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary); Vamosi, Gyoergy [Cell Biology and Signaling Research Group of the Hungarian Academy of Sciences, Department of Biophysics and Cell Biology, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary); Research Center for Molecular Medicine, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary); Geresi, Krisztina [Department of Pharmacology and Pharmacotherapy, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary); Tarkanyi, Ilona [3rd Department of Internal Medicine, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary); Szegedi, Istvan [Department of Pediatrics, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary); Lukacs, Levente [Coordinating Department of Surgical Techniques, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary); Juhasz, Istvan [Department of Dermatology, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary); Kiss, Csongor [Department of Pediatrics, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary); Fesues, Laszlo [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary); Research Center for Molecular Medicine, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary); and others

    2011-07-08

    Highlights: {yields} s{sup 4}UMP a naturally occurring thiolated nucleotide, effectively inhibited the proliferation of JY cells in vitro and in vivo. {yields} s{sup 4}UMP decreased the cell number and colony forming activity of leukemia cells in SCID mice. {yields} The effect of s{sup 4}UMP was undetectable on the bone marrow of healthy mice. {yields} The biochemical changes of the treated cells suggested that s{sup 4}UMP induced apoptosis. -- Abstract: We have previously reported the in vitro anti-proliferative effect of 4-thio-uridylate (s{sup 4}UMP) on OCM-1 uveal melanoma cells. Here, we assessed the efficacy of s{sup 4}UMP on JY cells. Treatment of JY cells with s{sup 4}UMP suppressed their colony forming activity and induced apoptosis; healthy human bone marrow granulocyte-macrophage progenitor cells were 14-fold less sensitive to the nucleotide. In vivo effectiveness of s{sup 4}UMP was determined using xenograft SCID mouse model. s{sup 4}UMP decreased the cell number and colony forming activity of the total cell content of the femur of SCID mice transplanted with JY cells without affecting the bone marrow of healthy mice. These results suggest that s{sup 4}UMP alone or in combination with other clinically approved anti-leukemic remedies should be further explored as a potential novel therapeutic agent.

  7. Complement activation in experimental human malaria infection.

    NARCIS (Netherlands)

    Roestenberg, M.; McCall, M.B.B.; Mollnes, T.E.; Deuren, M. van; Sprong, T.; Klasen, I.S.; Hermsen, C.C.; Sauerwein, R.W.; Ven, A.J.A.M. van der

    2007-01-01

    The objective of this study was to investigate complement activation in uncomplicated, early phases of human malaria. Fifteen healthy volunteers were experimentally infected with Plasmodium falciparum malaria. Parasitemia and complement activation products were assessed. During blood stage parasitem

  8. Changes in dissolved iron deposition to the oceans driven by human activity: a 3-D global modelling study

    Science.gov (United States)

    Myriokefalitakis, S.; Daskalakis, N.; Mihalopoulos, N.; Baker, A. R.; Nenes, A.; Kanakidou, M.

    2015-07-01

    The global atmospheric iron (Fe) cycle is parameterized in the global 3-D chemical transport model TM4-ECPL to simulate the proton- and the organic ligand-promoted mineral-Fe dissolution as well as the aqueous-phase photochemical reactions between the oxidative states of Fe (III/II). Primary emissions of total (TFe) and dissolved (DFe) Fe associated with dust and combustion processes are also taken into account, with TFe mineral emissions calculated to amount to ~ 35 Tg-Fe yr-1 and TFe emissions from combustion sources of ~ 2 Tg-Fe yr-1. The model reasonably simulates the available Fe observations, supporting the reliability of the results of this study. Proton- and organic ligand-promoted Fe dissolution in present-day TM4-ECPL simulations is calculated to be ~ 0.175 Tg-Fe yr-1, approximately half of the calculated total primary DFe emissions from mineral and combustion sources in the model (~ 0.322 Tg-Fe yr-1). The atmospheric burden of DFe is calculated to be ~ 0.024 Tg-Fe. DFe deposition presents strong spatial and temporal variability with an annual flux of ~ 0.496 Tg-Fe yr-1, from which about 40 % (~ 0.191 Tg-Fe yr-1) is deposited over the ocean. The impact of air quality on Fe deposition is studied by performing sensitivity simulations using preindustrial (year 1850), present (year 2008) and future (year 2100) emission scenarios. These simulations indicate that about a 3 times increase in Fe dissolution may have occurred in the past 150 years due to increasing anthropogenic emissions and thus atmospheric acidity. Air-quality regulations of anthropogenic emissions are projected to decrease atmospheric acidity in the near future, reducing to about half the dust-Fe dissolution relative to the present day. The organic ligand contribution to Fe dissolution shows an inverse relationship to the atmospheric acidity, thus its importance has decreased since the preindustrial period but is projected to increase in the future. The calculated changes also show that the

  9. Changes in dissolved iron deposition to the oceans driven by human activity: a 3-D global modelling study

    Directory of Open Access Journals (Sweden)

    S. Myriokefalitakis

    2015-03-01

    Full Text Available The global atmospheric iron (Fe cycle is parameterized in the global 3-D chemical transport model TM4-ECPL to simulate the proton- and the organic ligand-promoted mineral Fe dissolution as well as the aqueous-phase photochemical reactions between the oxidative states of Fe(III/II. Primary emissions of total (TFe and dissolved (DFe Fe associated with dust and combustion processes are also taken into account. TFe emissions are calculated to amount to ~35 Tg Fe yr−1. The model reasonably simulates the available Fe observations, supporting the reliability of the results of this study. Accounting for proton- and organic ligand-promoted Fe-dissolution in present-day TM4-ECPL simulations, the total Fe-dissolution is calculated to be ~0.163 Tg Fe yr−1 that accounts for up to ~50% of the calculated total DFe emissions. The atmospheric burden of DFe is calculated to be ~0.012 Tg Fe. DFe deposition presents strong spatial and temporal variability with an annual deposition flux ~0.489 Tg Fe yr−1 from which about 25% (~0.124 Tg Fe yr−1 are deposited over the ocean. The impact of air-quality on Fe deposition is studied by performing sensitivity simulations using preindustrial (year 1850, present (year 2008 and future (year 2100 emission scenarios. These simulations indicate that an increase (~2 times in Fe-dissolution may have occurred in the past 150 years due to increasing anthropogenic emissions and thus atmospheric acidity. On the opposite, a decrease (~2 times of Fe-dissolution is projected for near future, since atmospheric acidity is expected to be lower than present-day due to air-quality regulations of anthropogenic emissions. The organic ligand contribution to Fe dissolution shows inverse relationship to the atmospheric acidity thus its importance has decreased since the preindustrial period but is projected to increase in the future. The calculated changes also show that the atmospheric DFe supply to High-Nutrient-Low-Chlorophyll oceanic

  10. Pharmacology of DB844, an orally active aza analogue of pafuramidine, in a monkey model of second stage human African trypanosomiasis.

    Directory of Open Access Journals (Sweden)

    John K Thuita

    Full Text Available Novel drugs to treat human African trypanosomiasis (HAT are still urgently needed despite the recent addition of nifurtimox-eflornithine combination therapy (NECT to WHO Model Lists of Essential Medicines against second stage HAT, where parasites have invaded the central nervous system (CNS. The pharmacology of a potential orally available lead compound, N-methoxy-6-{5-[4-(N-methoxyamidino phenyl]-furan-2-yl}-nicotinamidine (DB844, was evaluated in a vervet monkey model of second stage HAT, following promising results in mice. DB844 was administered orally to vervet monkeys, beginning 28 days post infection (DPI with Trypanosoma brucei rhodesiense KETRI 2537. DB844 was absorbed and converted to the active metabolite 6-[5-(4-phenylamidinophenyl-furanyl-2-yl]-nicotinamide (DB820, exhibiting plasma C(max values of 430 and 190 nM for DB844 and DB820, respectively, after the 14th dose at 6 mg/kg qd. A 100-fold reduction in blood trypanosome counts was observed within 24 h of the third dose and, at the end of treatment evaluation performed four days post the last drug dose, trypanosomes were not detected in the blood or cerebrospinal fluid of any monkey. However, some animals relapsed during the 300 days of post treatment monitoring, resulting in a cure rate of 3/8 (37.5% and 3/7 (42.9% for the 5 mg/kg×10 days and the 6 mg/kg×14 days dose regimens respectively. These DB844 efficacy data were an improvement compared with pentamidine and pafuramidine both of which were previously shown to be non-curative in this model of CNS stage HAT. These data show that synthesis of novel diamidines with improved activity against CNS-stage HAT was possible.

  11. Flexible Bayesian Human Fecundity Models.

    Science.gov (United States)

    Kim, Sungduk; Sundaram, Rajeshwari; Buck Louis, Germaine M; Pyper, Cecilia

    2012-12-01

    Human fecundity is an issue of considerable interest for both epidemiological and clinical audiences, and is dependent upon a couple's biologic capacity for reproduction coupled with behaviors that place a couple at risk for pregnancy. Bayesian hierarchical models have been proposed to better model the conception probabilities by accounting for the acts of intercourse around the day of ovulation, i.e., during the fertile window. These models can be viewed in the framework of a generalized nonlinear model with an exponential link. However, a fixed choice of link function may not always provide the best fit, leading to potentially biased estimates for probability of conception. Motivated by this, we propose a general class of models for fecundity by relaxing the choice of the link function under the generalized nonlinear model framework. We use a sample from the Oxford Conception Study (OCS) to illustrate the utility and fit of this general class of models for estimating human conception. Our findings reinforce the need for attention to be paid to the choice of link function in modeling conception, as it may bias the estimation of conception probabilities. Various properties of the proposed models are examined and a Markov chain Monte Carlo sampling algorithm was developed for implementing the Bayesian computations. The deviance information criterion measure and logarithm of pseudo marginal likelihood are used for guiding the choice of links. The supplemental material section contains technical details of the proof of the theorem stated in the paper, and contains further simulation results and analysis.

  12. The Shigella human challenge model.

    Science.gov (United States)

    Porter, C K; Thura, N; Ranallo, R T; Riddle, M S

    2013-02-01

    Shigella is an important bacterial cause of infectious diarrhoea globally. The Shigella human challenge model has been used since 1946 for a variety of objectives including understanding disease pathogenesis, human immune responses and allowing for an early assessment of vaccine efficacy. A systematic review of the literature regarding experimental shigellosis in human subjects was conducted. Summative estimates were calculated by strain and dose. While a total of 19 studies evaluating nine strains at doses ranging from 10 to 1 × 1010 colony-forming units were identified, most studies utilized the S. sonnei strain 53G and the S. flexneri strain 2457T. Inoculum solution and pre-inoculation buffering has varied over time although diarrhoea attack rates do not appear to increase above 75-80%, and dysentery rates remain fairly constant, highlighting the need for additional dose-ranging studies. Expansion of the model to include additional strains from different serotypes will elucidate serotype and strain-specific outcome variability.

  13. Multilevel depth and image fusion for human activity detection.

    Science.gov (United States)

    Ni, Bingbing; Pei, Yong; Moulin, Pierre; Yan, Shuicheng

    2013-10-01

    Recognizing complex human activities usually requires the detection and modeling of individual visual features and the interactions between them. Current methods only rely on the visual features extracted from 2-D images, and therefore often lead to unreliable salient visual feature detection and inaccurate modeling of the interaction context between individual features. In this paper, we show that these problems can be addressed by combining data from a conventional camera and a depth sensor (e.g., Microsoft Kinect). We propose a novel complex activity recognition and localization framework that effectively fuses information from both grayscale and depth image channels at multiple levels of the video processing pipeline. In the individual visual feature detection level, depth-based filters are applied to the detected human/object rectangles to remove false detections. In the next level of interaction modeling, 3-D spatial and temporal contexts among human subjects or objects are extracted by integrating information from both grayscale and depth images. Depth information is also utilized to distinguish different types of indoor scenes. Finally, a latent structural model is developed to integrate the information from multiple levels of video processing for an activity detection. Extensive experiments on two activity recognition benchmarks (one with depth information) and a challenging grayscale + depth human activity database that contains complex interactions between human-human, human-object, and human-surroundings demonstrate the effectiveness of the proposed multilevel grayscale + depth fusion scheme. Higher recognition and localization accuracies are obtained relative to the previous methods.

  14. Human neural stem cell transplantation rescues cognitive defects in APP/PS1 model of Alzheimer's disease by enhancing neuronal connectivity and metabolic activity

    Directory of Open Access Journals (Sweden)

    Xueyuan Li

    2016-11-01

    Full Text Available Alzheimer’s disease (AD, the most frequent type of dementia, is featured by Aβ pathology, neural degeneration and cognitive decline. To date, there is no cure for this disease. Neural stem cell (NSC transplantation provides new promise for treating AD. Many studies report that intra-hippocampal transplantation of murine NSCs improved cognition in rodents with AD by alleviating neurodegeneration via neuronal complement or replacement. However, few reports examined the potential of human NSC transplantation for AD. In this study, we implanted human brain-derived NSCs (hNSCs into bilateral hippocampus of an APP/PS1 transgenic mouse model of AD to test the effects of hNSC transplantation on Alzheimer’s behavior and neuropathology. Six weeks later, transplanted hNSCs engrafted into the brains of AD mice, migrated dispersedly in broad brain regions, and some of them differentiated into neural cell types of central nervous system. The hNSC transplantation restored the recognition, learning and memory deficits but not anxiety tasks in AD mice. Although Aβ plaques were not significantly reduced, the neuronal, synaptic and nerve fiber density was significantly increased in the frontal cortex and hippocampus of hNSC-treated AD mice, suggesting of improved neuronal connectivity in AD brains after hNSC transplantation. Ultrastructural analysis confirmed that synapses and nerve fibers maintained relatively well-structured shapes in these mice. Furthermore, in-vivo magnetic resonance spectroscopy showed that hNSC-treated mice had notably increased levels of NAA and Glu in the frontal cortex and hippocampus, suggesting that neuronal metabolic activity was improved in AD brains after hNSC transplantation. These results suggest that transplanted hNSCs rescued Alzheimer’s cognition by enhancing neuronal connectivity and metabolic activity through a compensation mechanism in APP/PS1 mice. This study provides preclinical evidence that hNSC transplantation

  15. Methanolic extract of white asparagus shoots activates TRAIL apoptotic death pathway in human cancer cells and inhibits colon carcinogenesis in a preclinical model.

    Science.gov (United States)

    Bousserouel, Souad; Le Grandois, Julie; Gossé, Francine; Werner, Dalal; Barth, Stephan W; Marchioni, Eric; Marescaux, Jacques; Raul, Francis

    2013-08-01

    Shoots of white asparagus are a popular vegetable dish, known to be rich in many bioactive phytochemicals reported to possess antioxidant, and anti-inflammatory and antitumor activities. We evaluated the anticancer mechanisms of a methanolic extract of Asparagus officinalis L. shoots (Asp) on human colon carcinoma cells (SW480) and their derived metastatic cells (SW620), and Asp chemopreventive properties were also assessed in a model of colon carcinogenesis. SW480 and SW620 cell proliferation was inhibited by 80% after exposure to Asp (80 µg/ml). We demonstrated that Asp induced cell death through the activation of TRAIL DR4/DR5 death receptors leading to the activation of caspase-8 and caspase-3 and to cell apoptosis. By specific blocking agents of DR4/DR5 receptors we were able to prevent Asp-triggered cell death confirming the key role of DR4/DR5 receptors. We found also that Asp (80 µg/ml) was able to potentiate the effects of the cytokine TRAIL on cell death even in the TRAIL-resistant metastatic SW620 cells. Colon carcinogenesis was initiated in Wistar rats by intraperitoneal injections of azoxymethane (AOM), once a week for two weeks. One week after (post-initiation) rats received daily Asp (0.01%, 14 mg/kg body weight) in drinking water. After 7 weeks of Asp-treatment the colon of rats exhibited a 50% reduction of the number of preneoplastic lesions (aberrant crypt foci). In addition Asp induced inhibition of several pro-inflammatory mediators, in association with an increased expression of host-defense mediators. In the colonic mucosa of Asp-treated rats we also confirmed the pro-apoptotic effects observed in vitro including the activation of the TRAIL death‑receptor signaling pathway. Taken together, our data highlight the chemopreventive effects of Asp on colon carcinogenesis and its ability to promote normal cellular homeostasis.

  16. Universal activity pattern in human interactive dynamics

    CERN Document Server

    Formentin, Marco; Maritan, Amos; Zanzotto, Giovanni

    2014-01-01

    We investigate the response function of human agents as demonstrated by written correspondence, uncovering a new universal pattern for how the reactive dynamics of individuals is distributed across the set of each agent's contacts. In long-term empirical data on email, we find that the set of response times considered separately for the messages to each different correspondent of a given writer, generate a family of heavy-tailed distributions, which have largely the same features for all agents, and whose characteristic times grow exponentially with the rank of each correspondent. We show this universal behavioral pattern emerges robustly by considering weighted moving averages of the priority-conditioned response-time probabilities generated by a basic prioritization model. Our findings clarify how the range of priorities in the inputs from one's environment underpin and shape the dynamics of agents embedded in a net of reactive relations. These newly revealed activity patterns constrain future models of com...

  17. Metabolic activity of tree saps of different origin towards cultured human cells in the light of grade correspondence analysis and multiple regression modeling

    Directory of Open Access Journals (Sweden)

    Artur Wnorowski

    2017-06-01

    Full Text Available Tree saps are nourishing biological media commonly used for beverage and syrup production. Although the nutritional aspect of tree saps is widely acknowledged, the exact relationship between the sap composition, origin, and effect on the metabolic rate of human cells is still elusive. Thus, we collected saps from seven different tree species and conducted composition-activity analysis. Saps from trees of Betulaceae, but not from Salicaceae, Sapindaceae, nor Juglandaceae families, were increasing the metabolic rate of HepG2 cells, as measured using tetrazolium-based assay. Content of glucose, fructose, sucrose, chlorides, nitrates, sulphates, fumarates, malates, and succinates in sap samples varied across different tree species. Grade correspondence analysis clustered trees based on the saps’ chemical footprint indicating its usability in chemotaxonomy. Multiple regression modeling showed that glucose and fumarate present in saps from silver birch (Betula pendula Roth., black alder (Alnus glutinosa Gaertn., and European hornbeam (Carpinus betulus L. are positively affecting the metabolic activity of HepG2 cells.

  18. Human rights education (HRE) and transnational activism

    NARCIS (Netherlands)

    Mihr, A.; Schmitz, Hans-Peter

    2007-01-01

    Transnational human rights activism occupies today a significant place in the practice and scholarship of current global affairs. This article reviews the past successes and limits of this activism and suggests Human Rights Education (HRE) as a strategic tool currently underutilized by activists and

  19. Human Adaptive Mechatronics and Human-System Modelling

    Directory of Open Access Journals (Sweden)

    Satoshi Suzuki

    2013-03-01

    Full Text Available Several topics in projects for mechatronics studies, which are ʹHuman Adaptive Mechatronics (HAMʹ and ʹHuman‐System Modelling (HSMʹ, are presented in this paper. The main research theme of the HAM project is a design strategy for a new intelligent mechatronics system, which enhances operatorsʹ skills during machine operation. Skill analyses and control system design have been addressed. In the HSM project, human modelling based on hierarchical classification of skills was studied, including the following five types of skills: social, planning, cognitive, motion and sensory‐motor skills. This paper includes digests of these research topics and the outcomes concerning each type of skill. Relationships with other research activities, knowledge and information that will be helpful for readers who are trying to study assistive human‐mechatronics systems are also mentioned.

  20. GDF-15 secreted from human umbilical cord blood mesenchymal stem cells delivered through the cerebrospinal fluid promotes hippocampal neurogenesis and synaptic activity in an Alzheimer's disease model.

    Science.gov (United States)

    Kim, Dong Hyun; Lee, Dahm; Chang, Eun Hyuk; Kim, Ji Hyun; Hwang, Jung Won; Kim, Ju-Yeon; Kyung, Jae Won; Kim, Sung Hyun; Oh, Jeong Su; Shim, Sang Mi; Na, Duk Lyul; Oh, Wonil; Chang, Jong Wook

    2015-10-15

    Our previous studies demonstrated that transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) into the hippocampus of a transgenic mouse model of Alzheimer's disease (AD) reduced amyloid-β (Aβ) plaques and enhanced cognitive function through paracrine action. Due to the limited life span of hUCB-MSCs after their transplantation, the extension of hUCB-MSC efficacy was essential for AD treatment. In this study, we show that repeated cisterna magna injections of hUCB-MSCs activated endogenous hippocampal neurogenesis and significantly reduced Aβ42 levels. To identify the paracrine factors released from the hUCB-MSCs that stimulated endogenous hippocampal neurogenesis in the dentate gyrus, we cocultured adult mouse neural stem cells (NSCs) with hUCB-MSCs and analyzed the cocultured media with cytokine arrays. Growth differentiation factor-15 (GDF-15) levels were significantly increased in the media. GDF-15 suppression in hUCB-MSCs with GDF-15 small interfering RNA reduced the proliferation of NSCs in cocultures. Conversely, recombinant GDF-15 treatment in both in vitro and in vivo enhanced hippocampal NSC proliferation and neuronal differentiation. Repeated administration of hUBC-MSCs markedly promoted the expression of synaptic vesicle markers, including synaptophysin, which are downregulated in patients with AD. In addition, in vitro synaptic activity through GDF-15 was promoted. Taken together, these results indicated that repeated cisterna magna administration of hUCB-MSCs enhanced endogenous adult hippocampal neurogenesis and synaptic activity through a paracrine factor of GDF-15, suggesting a possible role of hUCB-MSCs in future treatment strategies for AD.

  1. Antitumor Activities and Apoptosis-regulated Mechanisms of Fermented Wheat Germ Extract in the Transplantation Tumor Model of Human HT-29 Cells in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jia Yan; XIAO Xiang; DONG Ying; WU Jing; ZHOU Xing Hua

    2015-01-01

    Objective A subcutaneous transplantation tumor model of human HT-29 cells in nude mice was established to evaluate anticarcinogenic activities, and the apoptosis-regulated mechanism effect of aqueous extract of fermented wheat germ with Lactobacillus plantarum dy-1 (LFWGE). Methods The HT-29 cells were transplanted via subcutaneous injection of 1×107 cells into the right flank of each nude mouse. Then, nude mice were treated for 30 d with LFWGE (high-dose 2 g/kg/d;low-dose 1 g/kg/d) and for 7 d with 5-fluorouracil (5-FU, 25 mg/kg/d) by gavage and intraperitoneal injection, respectively. An inhibition of tumor growth was observed. Results Tumor volume and weights decreased significantly in both groups of nude mice treated with LFWGE. In addition, the cell apoptosis rate of the LFWGE group (2 g/kg/d, 60.1%±4.4%; 1 g/kg/d, 58.6%±6.9%) was significantly higher than that of the control group (11.5%±1.6%) and 5-FU group (32.1%±3.5%) as measured by the TUNEL assay. Moreover, the real-time fluorescent quantitative PCR and Western blot method further confirmed these enhancing apoptosis and growth inhibition effects. The involvement of LFWGE in inducing apoptosis was confirmed by the expression of Bax, Bcl-2, Caspase-3, and CyclinD1. Conclusion The results showed that LFWGE could induce subcutaneous transplantation tumor apoptosis in nude mice and could be as a natural nutrient supplements or chemopreventive agent in the treatment of human colon cancer.

  2. Modeling of Human Joint Structures.

    Science.gov (United States)

    1982-09-01

    Radial Lateral " epicondyle Olecranon Radius Ulna Figure 3. Lateral aspect of the right elbow joint. -17- Annular Ligament This strong band encircles... elbow joint, knee joint, human joints, shoulder joint, ankle joint, joint models, hip joint, ligaments. 20. ABSTRACT (Continue on reverse side If...ligaments. -A rather extended discussion of the articulations and anatomical descriptions of the elbow , shoulder, hip, knee and ankle joints are

  3. Generic active appearance models revisited

    NARCIS (Netherlands)

    Tzimiropoulos, Georgios; Alabort-i-Medina, Joan; Zafeiriou, Stefanos; Pantic, Maja

    2012-01-01

    The proposed Active Orientation Models (AOMs) are gen- erative models of facial shape and appearance. Their main dierences with the well-known paradigm of Active Appearance Models (AAMs) are (i) they use a dierent statistical model of appearance, (ii) they are accompanied by a robust algorithm for m

  4. Modeling bursts and heavy tails in human dynamics

    OpenAIRE

    Vazquez, A.; Oliveira, J. Gama; Dezso, Z.; Goh, K. -I.; Kondor, I.; Barabasi, A. -L.

    2005-01-01

    Current models of human dynamics, used from risk assessment to communications, assume that human actions are randomly distributed in time and thus well approximated by Poisson processes. We provide direct evidence that for five human activity patterns the timing of individual human actions follow non-Poisson statistics, characterized by bursts of rapidly occurring events separated by long periods of inactivity. We show that the bursty nature of human behavior is a consequence of a decision ba...

  5. Pharmacokinetic Modeling and Monte Carlo Simulation to Predict Interindividual Variability in Human Exposure to Oseltamivir and Its Active Metabolite, Ro 64-0802.

    Science.gov (United States)

    Ito, Mototsugu; Kusuhara, Hiroyuki; Ose, Atsushi; Kondo, Tsunenori; Tanabe, Kazunari; Nakayama, Hideki; Horita, Shigeru; Fujita, Takuya; Sugiyama, Yuichi

    2017-01-01

    Oseltamivir (Tamiflu®) is a prodrug of Ro 64-0802, a selective inhibitor of influenza virus neuraminidase. There is a possible relationship between oseltamivir treatment and neuropsychiatric adverse events; although this has not been established, close monitoring is recommended on the prescription label. The objective of this study was to predict interindividual variability of human exposure to oseltamivir and its active metabolite Ro 64-0802. By leveraging mathematical models and computations, physiological parameters in virtual subjects were generated with population means and coefficient of variations collected from the literature or produced experimentally. Postulated functional changes caused by genetic mutations in four key molecules, carboxylesterase 1A1, P-glycoprotein, organic anion transporter 3, and multidrug resistance-associated protein 4, were also taken into account. One hundred thousand virtual subjects were generated per simulation, which was iterated 20 times with different random number generator seeds. Even in the most exaggerated case, the systemic areas under the concentration-time curve (AUCs) of oseltamivir and Ro 64-0802 were increased by at most threefold compared with the population mean. By contrast, the brain AUCs of oseltamivir and Ro 64-0802 were increased up to about sevenfold and 40-fold, respectively, compared with the population means. This unexpectedly high exposure to oseltamivir or Ro 64-0802, which occurs extremely rarely, might trigger adverse central nervous system effects in the clinical setting.

  6. Antioxidant activity of pomegranate juice reduces emphysematous changes and injury secondary to cigarette smoke in an animal model and human alveolar cells

    Directory of Open Access Journals (Sweden)

    Husari A

    2016-02-01

    Full Text Available Ahmad Husari,1,* Yasmine Hashem,1 Hala Bitar,1 Ghassan Dbaibo,2,3 Ghazi Zaatari,4 Marwan El Sabban5,* 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, 2Department of Pediatrics and Adolescent Medicine, Division of Pediatric Infectious Diseases, 3Department of Biochemistry and Molecular Genetics, 4Department of Pathology and Laboratory Medicine, 5Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon *These authors contributed equally to this work Background: Cigarette smoke (CS increases oxidative stress (OS in the lungs. Pomegranate juice (PJ possesses potent antioxidant activities, attributed to its polyphenols. This study investigates the effects of PJ on the damaging effects of CS in an animal model and on cultured human alveolar cells (A549. Methods: Male C57BL/6J mice were divided into the following groups: Control, CS, CS + PJ, and PJ. Acute CS exposure was for 3 days, while chronic exposure was for 1 and 3 months (5 days of exposure/week. PJ groups received daily 80 µmol/kg via bottle, while other groups received distilled water. At the end of the experiments, different parameters were studied: 1 expression levels of inflammatory markers, 2 apoptosis, 3 OS, and 4 histopathological changes. In vitro, A549 cells were pretreated for 48 hours with either PJ (0.5 µM or vehicle. Cells were then exposed to increasing concentrations of CS extracted from collected filters. Cell viability was assessed by counting of live and dead cells with trypan blue staining. Results: Acutely, a significant increase in interleukin (IL-1β, IL-6, and tumor necrosis factor (TNF-α expression, apoptosis, and OS was noted in CS when compared to Control. PJ significantly attenuated the expression of inflammatory mediators, apoptosis, and OS. Chronically (at 1 and 3 months, increased expression of TNF-α was observed, and lung sections

  7. Recovery of motor spontaneous activity after intranasal delivery of human recombinant erythropoietin in a focal brain hypoxia model induced by CoCl2 in rats.

    Science.gov (United States)

    Merelli, Amalia; Caltana, Laura; Girimonti, Patricia; Ramos, Alberto Javier; Lazarowski, Alberto; Brusco, Alicia

    2011-08-01

    Stroke is a major human health problem inducing long-term disability without any efficient therapeutic option being currently available. Under hypoxia, hypoxia-inducible factor-1α (HIF-1α) activates several genes as erythropoietin receptor (Epo-R) related with O(2) supply, and the multidrug-resistance gene (MDR-1) related with drug-refractory phenotype. Brain cortical injection of CoCl(2) produces focal hypoxia-like lesion with neuronal and glial alterations, as well as HIF-1α stabilization and MDR-1 overexpression. Intranasal (IN) drug delivery can by-pass blood-brain barrier (BBB) where MDR-1 is normally expressed. We evaluated the effects of IN-rHu-Epo administration on spontaneous motor activity (SMA) and the brain pattern expression of HIF-1α, MDR-1, and Epo-R in our cobalt-induced hypoxia model. Adult male Wistar rats were injected by stereotaxic surgery in frontoparietal cortex, with CoCl(2) (2 μl-50 mM; n = 20) or saline (controls; n = 20). Ten rats of each group were treated with IN-rHu-Epo 24 U or IN-saline. In addition, erythropoietic stimulation was evaluated by reticulocytes (Ret) account during three consecutive days, after intraperitoneal (i.p.)-recombinant-human Epo (rHu-Epo) (950 U; n = 6) or IN-rHu-Epo (24 U; n = 6) administration. SMA was evaluated by open field and rotarod tests, before and after surgical procedures during five consecutive days. Histological and immunostaining studies of HIF-1α, MDR-1, and Epo-R were performed on brain slides. A significant difference in SMA was observed in the hypoxic rats of IN-rHu-Epo-administered group as compared with Co-Saline-treated subjects and controls (p < 0.001). HIF-1α, EPO-R, and MDR-1 were overexpressed in the hypoxic cortex areas, while in contralateral hemisphere or controls, they were negatives. Reticulocytes were only increased in intraperitoneal (i.p.)-rHu-Epo-administered group. In spite of MDR-1 overexpression being detected in neurons, the coexpression of Epo-R could

  8. Recognition of human activities with wearable sensors

    Science.gov (United States)

    He, Weihua; Guo, Yongcai; Gao, Chao; Li, Xinke

    2012-12-01

    A novel approach for recognizing human activities with wearable sensors is investigated in this article. The key techniques of this approach include the generalized discriminant analysis (GDA) and the relevance vector machines (RVM). The feature vectors extracted from the measured signal are processed by GDA, with its dimension remarkably reduced from 350 to 12 while fully maintaining the most discriminative information. The reduced feature vectors are then classified by the RVM technique according to an extended multiclass model, which shows good convergence characteristic. Experimental results on the Wearable Action Recognition Dataset demonstrate that our approach achieves an encouraging recognition rate of 99.2%, true positive rate of 99.18% and false positive rate of 0.07%. Although in most cases, the support vector machines model has more than 70 support vectors, the number of relevance vectors related to different activities is always not more than 4, which implies a great simplicity in the classifier structure. Our approach is expected to have potential in real-time applications or solving problems with large-scale datasets, due to its perfect recognition performance, strong ability in feature reduction, and simple classifier structure.

  9. Human activity understanding for robot-assisted living

    NARCIS (Netherlands)

    N. Hu

    2016-01-01

    This thesis investigated the problem of understanding human activities, at different levels of granularity and taking into account both the variability in activities and annotator disagreement. To be able to capture the large variations within each of the action classes, we propose a model that uses

  10. The Human-Artifact Model

    DEFF Research Database (Denmark)

    Bødker, Susanne; Klokmose, Clemens Nylandsted

    2011-01-01

    Although devices of all shapes and sizes currently dominate the technological landscape, human–computer interaction (HCI) as a field is not yet theoretically equipped to match this reality. In this article we develop the human–artifact model, which has its roots in activity theoretical HCI....... By reinterpreting the activity theoretical foundation, we present a framework that helps addressing the analysis of individual interactive artifacts while embracing that they are part of a larger ecology of artifacts. We show how the human–artifact model helps structuring the understanding of an artifact's action......-possibilities in relation to the artifact ecology surrounding it. Essential to the model is that it provides four interconnected levels of analysis and addresses the possibilities and problems at these four levels. Artifacts and their use are constantly developing, and we address development in, and of, use. The framework...

  11. Human Thermal Model Evaluation Using the JSC Human Thermal Database

    Science.gov (United States)

    Bue, Grant; Makinen, Janice; Cognata, Thomas

    2012-01-01

    Human thermal modeling has considerable long term utility to human space flight. Such models provide a tool to predict crew survivability in support of vehicle design and to evaluate crew response in untested space environments. It is to the benefit of any such model not only to collect relevant experimental data to correlate it against, but also to maintain an experimental standard or benchmark for future development in a readily and rapidly searchable and software accessible format. The Human thermal database project is intended to do just so; to collect relevant data from literature and experimentation and to store the data in a database structure for immediate and future use as a benchmark to judge human thermal models against, in identifying model strengths and weakness, to support model development and improve correlation, and to statistically quantify a model s predictive quality. The human thermal database developed at the Johnson Space Center (JSC) is intended to evaluate a set of widely used human thermal models. This set includes the Wissler human thermal model, a model that has been widely used to predict the human thermoregulatory response to a variety of cold and hot environments. These models are statistically compared to the current database, which contains experiments of human subjects primarily in air from a literature survey ranging between 1953 and 2004 and from a suited experiment recently performed by the authors, for a quantitative study of relative strength and predictive quality of the models.

  12. Activated sludge model No. 3

    DEFF Research Database (Denmark)

    Gujer, W.; Henze, M.; Mino, T.

    1999-01-01

    The Activated Sludge Model No. 3 (ASM3) can predict oxygen consumption, sludge production, nitrification and denitrification of activated sludge systems. It relates to the Activated Sludge Model No. 1 (ASM1) and corrects for some defects of ASM I. In addition to ASM1, ASM3 includes storage...

  13. Diet drives quick changes in the metabolic activity and composition of human gut microbiota in a validated in vitro gut model

    NARCIS (Netherlands)

    Aguirre, M.; Eck, A.; Koenen, M.E.; Savelkoul, P.H.M.; Budding, A.E.; Venema, K.

    2016-01-01

    The aim of this study was to screen how rapidly the human gut microbiota responds to diet in an in vitro model of the proximal colon (TIM-system). Two experimental diets were provided to the gut bacteria: a high carbohydrate and a high protein diet. The metabolic response and the composition of the

  14. Diet drives quick changes in the metabolic activity and composition of human gut microbiota in a validated in vitro gut model

    NARCIS (Netherlands)

    Aguirre, M.; Eck, A.; Koenen, M.E.; Savelkoul, P.H.M.; Budding, A.E.; Venema, K.

    2016-01-01

    The aim of this study was to screen how rapidly the human gut microbiota responds to diet in an in vitro model of the proximal colon (TIM-system). Two experimental diets were provided to the gut bacteria: a high carbohydrate and a high protein diet. The metabolic response and the composition of the

  15. Diffusion Based Modeling of Human Brain Response to External Stimuli

    CERN Document Server

    Namazi, Hamidreza

    2012-01-01

    Human brain response is the overall ability of the brain in analyzing internal and external stimuli in the form of transferred energy to the mind/brain phase-space and thus, making the proper decisions. During the last decade scientists discovered about this phenomenon and proposed some models based on computational, biological, or neuropsychological methods. Despite some advances in studies related to this area of the brain research there was less effort which have been done on the mathematical modeling of the human brain response to external stimuli. This research is devoted to the modeling of human EEG signal, as an alert state of overall human brain activity monitoring, due to receiving external stimuli, based on fractional diffusion equation. The results of this modeling show very good agreement with the real human EEG signal and thus, this model can be used as a strong representative of the human brain activity.

  16. Closed-loop feedback control and bifurcation analysis of epileptiform activity via optogenetic stimulation in a mathematical model of human cortex

    Science.gov (United States)

    Selvaraj, Prashanth; Sleigh, Jamie W.; Kirsch, Heidi E.; Szeri, Andrew J.

    2016-01-01

    Optogenetics provides a method of neuron stimulation that has high spatial, temporal, and cell-type specificity. Here we present a model of optogenetic feedback control that targets the inhibitory population, which expresses light-sensitive channelrhodopsin-2 channels, in a mean-field model of undifferentiated cortex that is driven to seizures. The inhibitory population is illuminated with an intensity that is a function of electrode measurements obtained via the cortical model. We test the efficacy of this control method on seizurelike activity observed in two parameter spaces of the cortical model that most closely correspond to seizures observed in patients. We also compare the effect of closed-loop and open-loop control on seizurelike activity using a less-complicated ordinary differential equation model of the undifferentiated cortex in parameter space. Seizurelike activity is successfully suppressed in both parameter planes using optimal illumination intensities less likely to have adverse effects on cortical tissue.

  17. Understanding human activity patterns based on space-time-semantics

    Science.gov (United States)

    Huang, Wei; Li, Songnian

    2016-11-01

    Understanding human activity patterns plays a key role in various applications in an urban environment, such as transportation planning and traffic forecasting, urban planning, public health and safety, and emergency response. Most existing studies in modeling human activity patterns mainly focus on spatiotemporal dimensions, which lacks consideration of underlying semantic context. In fact, what people do and discuss at some places, inferring what is happening at the places, cannot be simple neglected because it is the root of human mobility patterns. We believe that the geo-tagged semantic context, representing what individuals do and discuss at a place and a specific time, drives a formation of specific human activity pattern. In this paper, we aim to model human activity patterns not only based on space and time but also with consideration of associated semantics, and attempt to prove a hypothesis that similar mobility patterns may have different motivations. We develop a spatiotemporal-semantic model to quantitatively express human activity patterns based on topic models, leading to an analysis of space, time and semantics. A case study is conducted using Twitter data in Toronto based on our model. Through computing the similarities between users in terms of spatiotemporal pattern, semantic pattern and spatiotemporal-semantic pattern, we find that only a small number of users (2.72%) have very similar activity patterns, while the majority (87.14%) show different activity patterns (i.e., similar spatiotemporal patterns and different semantic patterns, similar semantic patterns and different spatiotemporal patterns, or different in both). The population of users that has very similar activity patterns is decreased by 56.41% after incorporating semantic information in the corresponding spatiotemporal patterns, which can quantitatively prove the hypothesis.

  18. Liver immune-pathogenesis and therapy of human liver tropic virus infection in humanized mouse models.

    Science.gov (United States)

    Bility, Moses T; Li, Feng; Cheng, Liang; Su, Lishan

    2013-08-01

    Hepatitis B virus (HBV) and hepatitis C virus (HCV) infect and replicate primarily in human hepatocytes. Few reliable and easy accessible animal models are available for studying the immune system's contribution to the liver disease progression during hepatitis virus infection. Humanized mouse models reconstituted with human hematopoietic stem cells (HSCs) have been developed to study human immunology, human immunodeficiency virus 1 infection, and immunopathogenesis. However, a humanized mouse model engrafted with both human immune and human liver cells is needed to study infection and immunopathogenesis of HBV/HCV infection in vivo. We have recently developed the humanized mouse model with both human immune and human liver cells (AFC8-hu HSC/Hep) to study immunopathogenesis and therapy of HCV infection in vivo. In this review, we summarize the current models of HBV/HCV infection and their limitations in immunopathogenesis. We will then present our recent findings of HCV infection and immunopathogenesis in the AFC8-hu HSC/Hep mouse, which supports HCV infection, human T-cell response and associated liver pathogenesis. Inoculation of humanized mice with primary HCV isolates resulted in long-term HCV infection. HCV infection induced elevated infiltration of human immune cells in the livers of HCV-infected humanized mice. HCV infection also induced HCV-specific T-cell immune response in lymphoid tissues of humanized mice. Additionally, HCV infection induced liver fibrosis in humanized mice. Anti-human alpha smooth muscle actin (αSMA) staining showed elevated human hepatic stellate cell activation in HCV-infected humanized mice. We discuss the limitation and future improvements of the AFC8-hu HSC/Hep mouse model and its application in evaluating novel therapeutics, as well as studying both HCV and HBV infection, human immune responses, and associated human liver fibrosis and cancer.

  19. Estimating an Activity Driven Hidden Markov Model

    OpenAIRE

    Meyer, David A.; Shakeel, Asif

    2015-01-01

    We define a Hidden Markov Model (HMM) in which each hidden state has time-dependent $\\textit{activity levels}$ that drive transitions and emissions, and show how to estimate its parameters. Our construction is motivated by the problem of inferring human mobility on sub-daily time scales from, for example, mobile phone records.

  20. Anticipating Human Activities Using Object Affordances for Reactive Robotic Response.

    Science.gov (United States)

    Koppula, Hema S; Saxena, Ashutosh

    2016-01-01

    An important aspect of human perception is anticipation, which we use extensively in our day-to-day activities when interacting with other humans as well as with our surroundings. Anticipating which activities will a human do next (and how) can enable an assistive robot to plan ahead for reactive responses. Furthermore, anticipation can even improve the detection accuracy of past activities. The challenge, however, is two-fold: We need to capture the rich context for modeling the activities and object affordances, and we need to anticipate the distribution over a large space of future human activities. In this work, we represent each possible future using an anticipatory temporal conditional random field (ATCRF) that models the rich spatial-temporal relations through object affordances. We then consider each ATCRF as a particle and represent the distribution over the potential futures using a set of particles. In extensive evaluation on CAD-120 human activity RGB-D dataset, we first show that anticipation improves the state-of-the-art detection results. We then show that for new subjects (not seen in the training set), we obtain an activity anticipation accuracy (defined as whether one of top three predictions actually happened) of 84.1, 74.4 and 62.2 percent for an anticipation time of 1, 3 and 10 seconds respectively. Finally, we also show a robot using our algorithm for performing a few reactive responses.

  1. Modelling the evolution of human trail systems

    Science.gov (United States)

    Helbing, Dirk; Keltsch, Joachim; Molnár, Péter

    1997-07-01

    Many human social phenomena, such as cooperation, the growth of settlements, traffic dynamics and pedestrian movement, appear to be accessible to mathematical descriptions that invoke self-organization. Here we develop a model of pedestrian motion to explore the evolution of trails in urban green spaces such as parks. Our aim is to address such questions as what the topological structures of these trail systems are, and whether optimal path systems can be predicted for urban planning. We use an `active walker' model that takes into account pedestrian motion and orientation and the concomitant feedbacks with the surrounding environment. Such models have previously been applied to the study of complex structure formation in physical, chemical and biological systems. We find that our model is able to reproduce many of the observed large-scale spatial features of trail systems.

  2. New activity pattern in human interactive dynamics

    Science.gov (United States)

    Formentin, Marco; Lovison, Alberto; Maritan, Amos; Zanzotto, Giovanni

    2015-09-01

    We investigate the response function of human agents as demonstrated by written correspondence, uncovering a new pattern for how the reactive dynamics of individuals is distributed across the set of each agent’s contacts. In long-term empirical data on email, we find that the set of response times considered separately for the messages to each different correspondent of a given writer, generate a family of heavy-tailed distributions, which have largely the same features for all agents, and whose characteristic times grow exponentially with the rank of each correspondent. We furthermore show that this new behavioral pattern emerges robustly by considering weighted moving averages of the priority-conditioned response-time probabilities generated by a basic prioritization model. Our findings clarify how the range of priorities in the inputs from one’s environment underpin and shape the dynamics of agents embedded in a net of reactive relations. These newly revealed activity patterns might be universal, being present in other general interactive environments, and constrain future models of communication and interaction networks, affecting their architecture and evolution.

  3. Modelling the scaling properties of human mobility

    Science.gov (United States)

    Song, Chaoming; Koren, Tal; Wang, Pu; Barabási, Albert-László

    2010-10-01

    Individual human trajectories are characterized by fat-tailed distributions of jump sizes and waiting times, suggesting the relevance of continuous-time random-walk (CTRW) models for human mobility. However, human traces are barely random. Given the importance of human mobility, from epidemic modelling to traffic prediction and urban planning, we need quantitative models that can account for the statistical characteristics of individual human trajectories. Here we use empirical data on human mobility, captured by mobile-phone traces, to show that the predictions of the CTRW models are in systematic conflict with the empirical results. We introduce two principles that govern human trajectories, allowing us to build a statistically self-consistent microscopic model for individual human mobility. The model accounts for the empirically observed scaling laws, but also allows us to analytically predict most of the pertinent scaling exponents.

  4. Environment sensitive fluorescent analogue of biologically active oxazoles differentially recognizes human serum albumin and bovine serum albumin: Photophysical and molecular modeling studies

    Science.gov (United States)

    Maiti, Jyotirmay; Biswas, Suman; Chaudhuri, Ankur; Chakraborty, Sandipan; Chakraborty, Sibani; Das, Ranjan

    2017-03-01

    An environment sensitive fluorophore, 4-(5-(4-(dimethylamino)phenyl)oxazol-2-yl)benzoic acid (DMOBA), that closely mimics biologically active 2,5-disubstituited oxazoles has been designed to probe two homologous serum proteins, human serum albumin (HSA) and bovine serum albumin (BSA) by means of photophysical and molecular modeling studies. This fluorescent analogue exhibits solvent polarity sensitive fluorescence due to an intramolecular charge transfer in the excited state. In comparison to water, the steady state emission spectra of DMOBA in BSA is characterized by a greater blue shift ( 10 nm) and smaller Stokes' shift ( 5980 cm- 1) in BSA than HSA (Stokes'shift 6600 cm- 1), indicating less polar and more hydrophobic environment of the dye in the former than the latter. The dye-protein binding interactions are remarkably stronger for BSA than HSA which is evident from higher value of the association constant for the DMOBA-BSA complex (Ka 5.2 × 106 M- 1) than the DMOBA-HSA complex (Ka 1.0 × 106 M- 1). Fӧrster resonance energy transfer studies revealed remarkably less efficient energy transfer (8%) between the donor tryptophans in BSA and the acceptor DMOBA dye than that (30%) between the single tryptophan moiety in HSA and the dye, which is consistent with a much larger distance between the donor (tryptophan)-acceptor (dye) pair in BSA (34.5 Å) than HSA (25.4 Å). Site specific competitive binding assays have confirmed on the location of the dye in Sudlow's site II of BSA and in Sudlow's site I of HSA, respectively. Molecular modeling studies have shown that the fluorescent analogue is tightly packed in the binding site of BSA due to strong steric complementarity, where, binding of DMOBA to BSA is primarily dictated by the van der Waals and hydrogen bonding interactions. In contrast, in HSA the steric complementarity is less significant and binding is primarily guided by polar interactions and van der Waals interactions appear to be less significant in the

  5. Deep Human Parsing with Active Template Regression.

    Science.gov (United States)

    Liang, Xiaodan; Liu, Si; Shen, Xiaohui; Yang, Jianchao; Liu, Luoqi; Dong, Jian; Lin, Liang; Yan, Shuicheng

    2015-12-01

    In this work, the human parsing task, namely decomposing a human image into semantic fashion/body regions, is formulated as an active template regression (ATR) problem, where the normalized mask of each fashion/body item is expressed as the linear combination of the learned mask templates, and then morphed to a more precise mask with the active shape parameters, including position, scale and visibility of each semantic region. The mask template coefficients and the active shape parameters together can generate the human parsing results, and are thus called the structure outputs for human parsing. The deep Convolutional Neural Network (CNN) is utilized to build the end-to-end relation between the input human image and the structure outputs for human parsing. More specifically, the structure outputs are predicted by two separate networks. The first CNN network is with max-pooling, and designed to predict the template coefficients for each label mask, while the second CNN network is without max-pooling to preserve sensitivity to label mask position and accurately predict the active shape parameters. For a new image, the structure outputs of the two networks are fused to generate the probability of each label for each pixel, and super-pixel smoothing is finally used to refine the human parsing result. Comprehensive evaluations on a large dataset well demonstrate the significant superiority of the ATR framework over other state-of-the-arts for human parsing. In particular, the F1-score reaches 64.38 percent by our ATR framework, significantly higher than 44.76 percent based on the state-of-the-art algorithm [28].

  6. Enhanced anti-tumor activity of the glycoengineered type II CD20 antibody obinutuzumab (GA101) in combination with chemotherapy in xenograft models of human lymphoma

    OpenAIRE

    Herting, Frank; Friess, Thomas; Bader, Sabine; Muth, Gunter; Hölzlwimmer, Gabriele; Rieder, Natascha; Umana, Pablo; Klein, Christian

    2013-01-01

    Obinutuzumab (GA101) is a novel glycoengineered type II CD20 antibody in development for non-Hodgkin lymphoma. We compared the anti-tumor activity of obinutuzumab and rituximab in preclinical studies using subcutaneous Z138 and WSU-DLCL2 xenograft mouse models. Obinutuzumab and rituximab were assessed alone and in combination with bendamustine, fludarabine, chlorambucil, doxorubicin and cyclophosphamide/vincristine. Owing to strong single-agent efficacy in these models, suboptimal doses of ob...

  7. Computer Modeling of Human Delta Opioid Receptor

    Directory of Open Access Journals (Sweden)

    Tatyana Dzimbova

    2013-04-01

    Full Text Available The development of selective agonists of δ-opioid receptor as well as the model of interaction of ligands with this receptor is the subjects of increased interest. In the absence of crystal structures of opioid receptors, 3D homology models with different templates have been reported in the literature. The problem is that these models are not available for widespread use. The aims of our study are: (1 to choose within recently published crystallographic structures templates for homology modeling of the human δ-opioid receptor (DOR; (2 to evaluate the models with different computational tools; and (3 to precise the most reliable model basing on correlation between docking data and in vitro bioassay results. The enkephalin analogues, as ligands used in this study, were previously synthesized by our group and their biological activity was evaluated. Several models of DOR were generated using different templates. All these models were evaluated by PROCHECK and MolProbity and relationship between docking data and in vitro results was determined. The best correlations received for the tested models of DOR were found between efficacy (erel of the compounds, calculated from in vitro experiments and Fitness scoring function from docking studies. New model of DOR was generated and evaluated by different approaches. This model has good GA341 value (0.99 from MODELLER, good values from PROCHECK (92.6% of most favored regions and MolProbity (99.5% of favored regions. Scoring function correlates (Pearson r = -0.7368, p-value = 0.0097 with erel of a series of enkephalin analogues, calculated from in vitro experiments. So, this investigation allows suggesting a reliable model of DOR. Newly generated model of DOR receptor could be used further for in silico experiments and it will give possibility for faster and more correct design of selective and effective ligands for δ-opioid receptor.

  8. Modeling Nonalcoholic Fatty Liver Disease with Human Pluripotent Stem Cell-Derived Immature Hepatocyte-Like Cells Reveals Activation of PLIN2 and Confirms Regulatory Functions of Peroxisome Proliferator-Activated Receptor Alpha

    Science.gov (United States)

    Graffmann, Nina; Ring, Sarah; Kawala, Marie-Ann; Wruck, Wasco; Ncube, Audrey; Trompeter, Hans-Ingo

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD/steatosis) is a metabolic disease characterized by the incorporation of fat into hepatocytes. In this study, we developed an in vitro model for NAFLD based on hepatocyte-like cells (HLCs) differentiated from human pluripotent stem cells. We induced fat storage in these HLCs and detected major expression changes of metabolism-associated genes, as well as an overall reduction of liver-related microRNAs. We observed an upregulation of the lipid droplet coating protein Perilipin 2 (PLIN2), as well as of numerous genes of the peroxisome proliferator-activated receptor (PPAR) pathway, which constitutes a regulatory hub for metabolic processes. Interference with PLIN2 and PPARα resulted in major alterations in gene expression, especially affecting lipid, glucose, and purine metabolism. Our model recapitulates many metabolic changes that are characteristic for NAFLD. It permits the dissection of disease-promoting molecular pathways and allows us to investigate the influences of distinct genetic backgrounds on disease progression. PMID:27308945

  9. Human Performance Modeling for Dynamic Human Reliability Analysis

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-08-01

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

  10. Human telomerase: biogenesis, trafficking, recruitment, and activation.

    Science.gov (United States)

    Schmidt, Jens C; Cech, Thomas R

    2015-06-01

    Telomerase is the ribonucleoprotein enzyme that catalyzes the extension of telomeric DNA in eukaryotes. Recent work has begun to reveal key aspects of the assembly of the human telomerase complex, its intracellular trafficking involving Cajal bodies, and its recruitment to telomeres. Once telomerase has been recruited to the telomere, it appears to undergo a separate activation step, which may include an increase in its repeat addition processivity. This review covers human telomerase biogenesis, trafficking, and activation, comparing key aspects with the analogous events in other species.

  11. Active control: Wind turbine model

    DEFF Research Database (Denmark)

    Bindner, H.

    1999-01-01

    This report is a part of the reporting of the work done in the project 'Active Control of Wind Turbines'. This project aim is to develop a simulation model for design of control systems for turbines with pitch control and to use that model to designcontrollers. This report describes the model...... developed for controller design and analysis. Emphasis has been put on establishment of simple models describing the dynamic behavior of the wind turbine in adequate details for controller design. This hasbeen done with extensive use of measurements as the basis for selection of model complexity and model...... validation as well as parameter estimation. The model includes a simple model of the structure of the turbine including tower and flapwise blade bending,a detailed model of the gear box and induction generator, a linearized aerodynamic model including modelling of induction lag and actuator and sensor models...

  12. Zebrafish Models for Human Acute Organophosphorus Poisoning.

    Science.gov (United States)

    Faria, Melissa; Garcia-Reyero, Natàlia; Padrós, Francesc; Babin, Patrick J; Sebastián, David; Cachot, Jérôme; Prats, Eva; Arick Ii, Mark; Rial, Eduardo; Knoll-Gellida, Anja; Mathieu, Guilaine; Le Bihanic, Florane; Escalon, B Lynn; Zorzano, Antonio; Soares, Amadeu M V M; Raldúa, Demetrio

    2015-10-22

    Terrorist use of organophosphorus-based nerve agents and toxic industrial chemicals against civilian populations constitutes a real threat, as demonstrated by the terrorist attacks in Japan in the 1990 s or, even more recently, in the Syrian civil war. Thus, development of more effective countermeasures against acute organophosphorus poisoning is urgently needed. Here, we have generated and validated zebrafish models for mild, moderate and severe acute organophosphorus poisoning by exposing zebrafish larvae to different concentrations of the prototypic organophosphorus compound chlorpyrifos-oxon. Our results show that zebrafish models mimic most of the pathophysiological mechanisms behind this toxidrome in humans, including acetylcholinesterase inhibition, N-methyl-D-aspartate receptor activation, and calcium dysregulation as well as inflammatory and immune responses. The suitability of the zebrafish larvae to in vivo high-throughput screenings of small molecule libraries makes these models a valuable tool for identifying new drugs for multifunctional drug therapy against acute organophosphorus poisoning.

  13. Clouds caused by human activities: the anthropoclouds

    Science.gov (United States)

    Mazon, Jordi; Costa, Marcel; Pino, David; Lorente, Jeroni

    2013-04-01

    The classification of clouds is based on the pioneering classification carried out by Howard (1804). In this classification, and also in the successive editions of the International Classification of Clouds published by the World Meteorological Organization (WMO, 1975, 1987) 10 basic cloud genera are included and described. In all cases, the cause that leads to the formation of clouds remains as a secondary issue. It is assumed that all of them are exclusively produced by natural mechanisms without any human intervention. However, aerosol and water vapour emissions produced by human activity may increase cloud formation having an increasing importance in the atmospheric energy budget and consequently in the earth's climate. Effectively, since the end of the Nineteenth century, human activity has been injecting large amounts of water vapour into the atmosphere, cloud condensation nuclei and hot air mainly generated in the combustion processes that under certain spatial and temporal conditions can enhance cloud formation. These anthropogenic aerosols are linked to the climate and the water cycle (Kaufman et al, 2002). The aim of this communication is to point out the anthropic origin of some clouds in the cloud classification. Several cases of the 7 basic genera cloud caused by human activities will be shown to discuss the importance of differentiating the origin of clouds in weather observations. This differentiation would improve the understanding the contribution of these clouds to climate change. To differentiate the clouds formed by human activity, we propose to use the prefix anthropo- before the scientific name (and a- before the abbreviation) in some of the 10 basic clouds defined by the International Classification of Clouds, those which could have an anthropic origin, and thus begin new data of cloud observations that could help future research to improve the effect of human activity in the troposphere.

  14. Model human heart or brain signals

    CERN Document Server

    Tuncay, Caglar

    2008-01-01

    A new model is suggested and used to mimic various spatial or temporal designs in biological or non biological formations where the focus is on the normal or irregular electrical signals coming from human heart (ECG) or brain (EEG). The electrical activities in several muscles (EMG) or neurons or other organs of human or various animals, such as lobster pyloric neuron, guinea pig inferior olivary neuron, sepia giant axon and mouse neocortical pyramidal neuron and some spatial formations are also considered (in Appendix). In the biological applications, several elements (cells or tissues) in an organ are taken as various entries in a representative lattice (mesh) where the entries are connected to each other in terms of some molecular diffusions or electrical potential differences. The biological elements evolve in time (with the given tissue or organ) in terms of the mentioned connections (interactions) besides some individual feedings. The anatomical diversity of the species (or organs) is handled in terms o...

  15. DEVELOPMENT OF 2D HUMAN BODY MODELING USING THINNING ALGORITHM

    Directory of Open Access Journals (Sweden)

    K. Srinivasan

    2010-11-01

    Full Text Available Monitoring the behavior and activities of people in Video surveillance has gained more applications in Computer vision. This paper proposes a new approach to model the human body in 2D view for the activity analysis using Thinning algorithm. The first step of this work is Background subtraction which is achieved by the frame differencing algorithm. Thinning algorithm has been used to find the skeleton of the human body. After thinning, the thirteen feature points like terminating points, intersecting points, shoulder, elbow, and knee points have been extracted. Here, this research work attempts to represent the body model in three different ways such as Stick figure model, Patch model and Rectangle body model. The activities of humans have been analyzed with the help of 2D model for the pre-defined poses from the monocular video data. Finally, the time consumption and efficiency of our proposed algorithm have been evaluated.

  16. Metalloprotein-inhibitor binding: human carbonic anhydrase II as a model for probing metal-ligand interactions in a metalloprotein active site.

    Science.gov (United States)

    Martin, David P; Hann, Zachary S; Cohen, Seth M

    2013-11-01

    An ever-increasing number of metalloproteins are being discovered that play essential roles in physiological processes. Inhibitors of these proteins have significant potential for the treatment of human disease, but clinical success of these compounds has been limited. Herein, zinc(II)-dependent metalloprotein inhibitors in clinical use are reviewed, and the potential for using novel metal-binding groups (MBGs) in the design of these inhibitors is discussed. By using human carbonic anhydrase II as a model system, the nuances of MBG-metal interactions in the context of a protein environment can be probed. Understanding how metal coordination influences inhibitor binding may help in the design of new therapeutics targeting metalloproteins.

  17. Scaling behavior of online human activity

    Science.gov (United States)

    Zhao, Zhi-Dan; Cai, Shi-Min; Huang, Junming; Fu, Yan; Zhou, Tao

    2012-11-01

    The rapid development of the Internet technology enables humans to explore the web and record the traces of online activities. From the analysis of these large-scale data sets (i.e., traces), we can get insights about the dynamic behavior of human activity. In this letter, the scaling behavior and complexity of human activity in the e-commerce, such as music, books, and movies rating, are comprehensively investigated by using the detrended fluctuation analysis technique and the multiscale entropy method. Firstly, the interevent time series of rating behaviors of these three types of media show similar scaling properties with exponents ranging from 0.53 to 0.58, which implies that the collective behaviors of rating media follow a process embodying self-similarity and long-range correlation. Meanwhile, by dividing the users into three groups based on their activities (i.e., rating per unit time), we find that the scaling exponents of the interevent time series in the three groups are different. Hence, these results suggest that a stronger long-range correlations exist in these collective behaviors. Furthermore, their information complexities vary in the three groups. To explain the differences of the collective behaviors restricted to the three groups, we study the dynamic behavior of human activity at the individual level, and find that the dynamic behaviors of a few users have extremely small scaling exponents associated with long-range anticorrelations. By comparing the interevent time distributions of four representative users, we can find that the bimodal distributions may bring forth the extraordinary scaling behaviors. These results of the analysis of the online human activity in the e-commerce may not only provide insight into its dynamic behaviors but may also be applied to acquire potential economic interest.

  18. Humanized in vivo Model for Autoimmune Diabetes

    Science.gov (United States)

    2009-02-01

    AWARD NUMBER: W81XWH-07-1-0121 TITLE: Humanized in vivo Model for Autoimmune Diabetes PRINCIPAL INVESTIGATOR: Gerald T Nepom, M.D., Ph.D...4. TITLE AND SUBTITLE Sa. CONTRACT NUMBER Humanized in vivo Model for Autoimmune Diabetes Sb. GRANT NUMBER W81XWH-07-1-0121 Sc. PROGRAM ELEMENT...therapies. This research study entails using humanized mice manifesting type 1 diabetes (T1 D)-associated human HLA molecules to address the fate and

  19. Food & Fitness. Directory. Human Nutrition Activities.

    Science.gov (United States)

    Department of Agriculture, Washington, DC.

    Activities of the following regulatory and food service agencies of the Department of Agriculture are described: (1) Agricultural Research Service; (2) Cooperative State Research Service; (3) Economic Research Service; (4) Human Nutrition Information Service; (5) Office of Grants and Program Systems; (6) Office of International Cooperation and…

  20. MEASURING CHOLINESTERASE ACTIVITY IN HUMAN SALIVA.

    Science.gov (United States)

    To assess the potential for using saliva in pesticide biomonitoring, the consistency of cholinesterase activity in human saliva collected over time was examined. In this pilot study, saliva was collected from 20 healthy adults once per week for 5 consecutive weeks using 2 differe...

  1. MEASURING CHOLINESTERASE ACTIVITY IN HUMAN SALIVA.

    Science.gov (United States)

    To assess the potential for using saliva in pesticide biomonitoring, the consistency of cholinesterase activity in human saliva collected over time was examined. In this pilot study, saliva was collected from 20 healthy adults once per week for 5 consecutive weeks using 2 differe...

  2. Identification of essential residues for binding and activation in the human 5-HT7(a) serotonin receptor by molecular modeling and site-directed mutagenesis.

    Science.gov (United States)

    Impellizzeri, Agata Antonina Rita; Pappalardo, Matteo; Basile, Livia; Manfra, Ornella; Andressen, Kjetil Wessel; Krobert, Kurt Allen; Messina, Angela; Levy, Finn Olav; Guccione, Salvatore

    2015-01-01

    The human 5-HT7 receptor is expressed in both the central nervous system and peripheral tissues and is a potential drug target in behavioral and psychiatric disorders. We examined molecular determinants of ligand binding and G protein activation by the human 5-HT7(a) receptor. The role of several key residues in the 7th transmembrane domain (TMD) and helix 8 were elucidated combining in silico and experimental mutagenesis. Several single and two double point mutations of the 5-HT7(a) wild type receptor were made (W7.33V, E7.35T, E7.35R, E7.35D, E7.35A, R7.36V, Y7.43A, Y7.43F, Y7.43T, R8.52D, D8.53K; E7.35T-R7.36V, R8.52D-D8.53K), and their effects upon ligand binding were assessed by radioligand binding using a potent agonist (5-CT) and a potent antagonist (SB269970). In addition, the ability of the mutated 5-HT7(a) receptors to activate G protein after 5-HT-stimulation was determined through activation of adenylyl cyclase. In silico investigation on mutated receptors substantiated the predicted importance of TM7 and showed critical roles of residues E7.35, W7.33, R7.36 and Y7.43 in agonist and antagonist binding and conformational changes of receptor structure affecting adenylyl cyclase activation. Experimental data showed that mutants E7.35T and E7.35R were incapable of ligand binding and adenylyl cyclase activation, consistent with a requirement for a negatively charged residue at this position. The mutant R8.52D was unable to activate adenylyl cyclase, despite unaffected ligand binding, consistent with the R8.52 residue playing an important role in the receptor-G protein interface. The mutants Y7.43A and Y7.43T displayed reduced agonist binding and AC agonist potency, not seen in Y7.43F, consistent with a requirement for an aromatic residue at this position. Knowledge of the molecular interactions important in h5-HT7 receptor ligand binding and G protein activation will aid the design of selective h5-HT7 receptor ligands for potential pharmacological use.

  3. Identification of essential residues for binding and activation in the human 5-HT7(a receptor by molecular modeling and site-directed mutagenesis

    Directory of Open Access Journals (Sweden)

    Agata Antonina Rita eImpellizzeri

    2015-05-01

    Full Text Available The human 5-HT7 receptor is expressed in both the central nervous system and peripheral tissues and is a potential drug target in behavioral and psychiatric disorders.We examined molecular determinants of ligand binding and G protein activation by the human 5-HT7(a receptor. The role of several key residues in the 7th transmembrane domain and helix 8 were elucidated combining in silico and experimental mutagenesis. Several single and two double point mutations of the 5-HT7(a wild type receptor were made (W7.33V, E7.35T, E7.35R, E7.35D, E7.35A, R7.36V, Y7.43A, Y7.43F, Y7.43T, R8.52D, D8.53K; E7.35T-R7.36V, R8.52D-D8.53K, and their effects upon ligand binding were assessed by radioligand binding using a potent agonist (5-CT and a potent antagonist (SB269970. In addition, the ability of the mutated 5-HT7(a receptors to activate G protein after 5-HT-stimulation was determined through activation of adenylyl cyclase. In silico investigation on mutated receptors substantiated the predicted importance of TM7 and showed critical roles of residues E7.35, W7.33, R7.36 and Y7.43 in agonist and antagonist binding and conformational changes of receptor structure affecting adenylyl cyclase activation. Experimental data showed that mutants E7.35T and E7.35R were incapable of ligand binding and adenylyl cyclase activation, consistent with a requirement for a negatively charged residue at this position. The mutant R8.52D was unable to activate adenylyl cyclase, despite unaffected ligand binding, consistent with the R8.52 residue playing an important role in the receptor-G protein interface. The mutants Y7.43A and Y7.43T displayed reduced agonist binding and AC agonist potency, not seen in Y7.43F, consistent with a requirement for an aromatic residue at this position. Knowledge of the molecular interactions important in h5-HT7 receptor ligand binding and G protein activation will aid the design of selective h5-HT7 receptor ligands for potential pharmacological use.

  4. NET amyloidogenic backbone in human activated neutrophils.

    Science.gov (United States)

    Pulze, L; Bassani, B; Gini, E; D'Antona, P; Grimaldi, A; Luini, A; Marino, F; Noonan, D M; Tettamanti, G; Valvassori, R; de Eguileor, M

    2016-03-01

    Activated human neutrophils produce a fibrillar DNA network [neutrophil extracellular traps (NETs)] for entrapping and killing bacteria, fungi, protozoa and viruses. Our results suggest that the neutrophil extracellular traps show a resistant amyloidogenic backbone utilized for addressing reputed proteins and DNA against the non-self. The formation of amyloid fibrils in neutrophils is regulated by the imbalance of reactive oxygen species (ROS) in the cytoplasm. The intensity and source of the ROS signal is determinant for promoting stress-associated responses such as amyloidogenesis and closely related events: autophagy, exosome release, activation of the adrenocorticotrophin hormone/α-melanocyte-stimulating hormone (ACTH/α-MSH) loop and synthesis of specific cytokines. These interconnected responses in human activated neutrophils, that have been evaluated from a morphofunctional and quantitative viewpoint, represent primitive, but potent, innate defence mechanisms. In invertebrates, circulating phagocytic immune cells, when activated, show responses similar to those described previously for activated human neutrophils. Invertebrate cells within endoplasmic reticulum cisternae produce a fibrillar material which is then assembled into an amyloidogenic scaffold utilized to convey melanin close to the invader. These findings, in consideration to the critical role played by NET in the development of several pathologies, could explain the structural resistance of these scaffolds and could provide the basis for developing new diagnostic and therapeutic approaches in immunomediated diseases in which the innate branch of the immune system has a pivotal role.

  5. Active control: Wind turbine model

    Energy Technology Data Exchange (ETDEWEB)

    Bindner, Henrik

    1999-07-01

    This report is a part of the reporting of the work done in the project `Active Control of Wind Turbines`. This project aim is to develop a simulation model for design of control systems for turbines with pitch control and to use that model to design controllers. This report describes the model developed for controller design and analysis. Emphasis has been put on establishment of simple models describing the dynamic behavior of the wind turbine in adequate details for controller design. This has been done with extensive use of measurements as the basis for selection of model complexity and model validation as well as parameter estimation. The model includes a simple model of the structure of the turbine including tower and flapwise blade bending, a detailed model of the gear box and induction generator, a linearized aerodynamic model including modelling of induction lag and actuator and sensor models. The models are all formulated as linear differential equations. The models are validated through comparisons with measurements performed on a Vestas WD 34 400 kW wind turbine. It is shown from a control point of view simple linear models can be used to describe the dynamic behavior of a pitch controlled wind turbine. The model and the measurements corresponds well in the relevant frequency range. The developed model is therefore applicable for controller design. (au) EFP-91. 18 ills., 22 refs.

  6. Human mammary microenvironment better regulates the biology of human breast cancer in humanized mouse model.

    Science.gov (United States)

    Zheng, Ming-Jie; Wang, Jue; Xu, Lu; Zha, Xiao-Ming; Zhao, Yi; Ling, Li-Jun; Wang, Shui

    2015-02-01

    During the past decades, many efforts have been made in mimicking the clinical progress of human cancer in mouse models. Previously, we developed a human breast tissue-derived (HB) mouse model. Theoretically, it may mimic the interactions between "species-specific" mammary microenvironment of human origin and human breast cancer cells. However, detailed evidences are absent. The present study (in vivo, cellular, and molecular experiments) was designed to explore the regulatory role of human mammary microenvironment in the progress of human breast cancer cells. Subcutaneous (SUB), mammary fat pad (MFP), and HB mouse models were developed for in vivo comparisons. Then, the orthotopic tumor masses from three different mouse models were collected for primary culture. Finally, the biology of primary cultured human breast cancer cells was compared by cellular and molecular experiments. Results of in vivo mouse models indicated that human breast cancer cells grew better in human mammary microenvironment. Cellular and molecular experiments confirmed that primary cultured human breast cancer cells from HB mouse model showed a better proliferative and anti-apoptotic biology than those from SUB to MFP mouse models. Meanwhile, primary cultured human breast cancer cells from HB mouse model also obtained the migratory and invasive biology for "species-specific" tissue metastasis to human tissues. Comprehensive analyses suggest that "species-specific" mammary microenvironment of human origin better regulates the biology of human breast cancer cells in our humanized mouse model of breast cancer, which is more consistent with the clinical progress of human breast cancer.

  7. Enhanced anti-tumor activity of the glycoengineered type II CD20 antibody obinutuzumab (GA101) in combination with chemotherapy in xenograft models of human lymphoma.

    Science.gov (United States)

    Herting, Frank; Friess, Thomas; Bader, Sabine; Muth, Gunter; Hölzlwimmer, Gabriele; Rieder, Natascha; Umana, Pablo; Klein, Christian

    2014-09-01

    Obinutuzumab (GA101) is a novel glycoengineered type II CD20 antibody in development for non-Hodgkin lymphoma. We compared the anti-tumor activity of obinutuzumab and rituximab in preclinical studies using subcutaneous Z138 and WSU-DLCL2 xenograft mouse models. Obinutuzumab and rituximab were assessed alone and in combination with bendamustine, fludarabine, chlorambucil, doxorubicin and cyclophosphamide/vincristine. Owing to strong single-agent efficacy in these models, suboptimal doses of obinutuzumab were applied to demonstrate a combination effect. Obinutuzumab plus bendamustine achieved superior tumor growth inhibition versus rituximab plus bendamustine and showed a statistically significant effect versus the respective single treatments. Combinations of obinutuzumab with fludarabine, chlorambucil or cyclophosphamide/vincristine demonstrated significantly superior activity to rituximab-based treatment. Obinutuzumab monotherapy was at least as effective as rituximab plus chemotherapy in vivo, and obinutuzumab plus chemotherapy was superior to the respective monotherapies. These data support further clinical investigation of obinutuzumab plus chemotherapy.

  8. Activity of lysosomal exoglycosidases in human gliomas.

    Science.gov (United States)

    Wielgat, P; Walczuk, U; Szajda, S; Bień, M; Zimnoch, L; Mariak, Z; Zwierz, K

    2006-12-01

    There is a lot of data suggesting that modifications of cell glycoconjugates may be important in progression of cancer. In the present work we studied activities of lysosomal exoglycosidases: beta-hexosaminidase and its isoenzymes A and B, beta-galactosidase and alpha-mannosidase, in human gliomas. Enzyme activity was determined spectrophotometrically based on the release of p-nitrophenol from p-nitrophenyl-derivative of appropriate sugars. The activities of the exoglycosidases tested were significantly higher in malignant glial tumors than in control tissue (normal brain tissue) and non-glial tumors. The highest activities of exoglycosidases were observed in high-grade gliomas, and a positive correlation of enzyme activities and degree of malignancy was noted. Our results suggest that lysosomal exoglycosidases may participate in the progression and dynamical development of glial tumors.

  9. Utilizing Model Eliciting Activities (MEA's) to engage middle school teachers and students in storm water management practices to mitigate human impacts of land development

    Science.gov (United States)

    Tazaz, A.; Wilson, R. M.; Schoen, R.; Blumsack, S.; King, L.; Dyehouse, M.

    2013-12-01

    'The Integrating STEM Project' engaged 6-8 grade teachers through activities incorporating mathematics, science and technology incorporating both Next Generation Science Standards (NGSS) and Common Core State Standards-Mathematics (CCSS-Math). A group of researchers from Oceanography, Mathematics, and Education set out to provide middle school teachers with a 2 year intensive STEM integration professional development with a focus on environmental topics and to monitor the achievement outcomes in their students. Over the course of 2 years the researchers created challenging professional development sessions to expand teacher knowledge and teachers were tasked to transform the information gained during the professional development sessions for classroom use. One lesson resource kit presented to the teachers, which was directly applicable to the classroom, included Model Eliciting Activities (MEA's) to explore the positive and negative effects land development has on climate and the environment, and how land development impacts storm water management. MEA's were developed to encourage students to create models to solve complex problems and to allow teachers to investigate students thinking. MEA's are a great curriculum technique used in engineering fields to help engage students by providing hands on activities using real world data and problems. We wish to present the Storm Water Management Resource toolkit including the MEA and present the outcomes observed from student engagement in this activity.

  10. Fast Newton active appearance models

    NARCIS (Netherlands)

    Kossaifi, Jean; Tzimiropoulos, Georgios; Pantic, Maja

    2014-01-01

    Active Appearance Models (AAMs) are statistical models of shape and appearance widely used in computer vision to detect landmarks on objects like faces. Fitting an AAM to a new image can be formulated as a non-linear least-squares problem which is typically solved using iterative methods. Owing to i

  11. Scaling behavior of online human activity

    CERN Document Server

    Zhao, Zhi-Dan; Huang, Junming; Fu, Yan; Zhou, Tao; 10.1209/0295-5075/100/48004

    2013-01-01

    The rapid development of Internet technology enables human explore the web and record the traces of online activities. From the analysis of these large-scale data sets (i.e. traces), we can get insights about dynamic behavior of human activity. In this letter, the scaling behavior and complexity of human activity in the e-commerce, such as music, book, and movie rating, are comprehensively investigated by using detrended fluctuation analysis technique and multiscale entropy method. Firstly, the interevent time series of rating behaviors of these three type medias show the similar scaling property with exponents ranging from 0.53 to 0.58, which implies that the collective behaviors of rating media follow a process embodying self-similarity and long-range correlation. Meanwhile, by dividing the users into three groups based their activities (i.e., rating per unit time), we find that the scaling exponents of interevent time series in three groups are different. Hence, these results suggest the stronger long-rang...

  12. In vivo functional brain mapping in a conditional mouse model of human tauopathy (taup301l reveals reduced neural activity in memory formation structures

    Directory of Open Access Journals (Sweden)

    Perez Pablo D

    2013-02-01

    Full Text Available Abstract Background Tauopathies are characterized by intracellular deposition of the microtubule-associated protein tau as filamentous aggregates. The rTg4510 mouse conditionally expresses mutant human tau protein in various forebrain areas under the Tet-off expression system. Mice develop neurofibrillary tangles, with significant neuronal loss and cognitive deficits by 6 months of age. Previous behavioral and biochemical work has linked the expression and aggregates of mutant tau to functional impairments. The present work used manganese-enhanced magnetic resonance imaging (MEMRI to investigate basal levels of brain activity in the rTg4510 and control mice. Results Our results show an unmistakable curtailment of neural activity in the amygdala and hippocampus, two regions known for their role in memory formation, but not the cortex, cerebellum, striatum and hypothalamus in tau expressing mice. Conclusion Behavioral impairments associated with changes in activity in these areas may correspond to age progressive mutant tauP301L-induced neurodegeneration.

  13. Genetically Modified Pig Models for Human Diseases

    Institute of Scientific and Technical Information of China (English)

    Nana Fan; Liangxue Lai

    2013-01-01

    Genetically modified animal models are important for understanding the pathogenesis of human disease and developing therapeutic strategies.Although genetically modified mice have been widely used to model human diseases,some of these mouse models do not replicate important disease symptoms or pathology.Pigs are more similar to humans than mice in anatomy,physiology,and genome.Thus,pigs are considered to be better animal models to mimic some human diseases.This review describes genetically modified pigs that have been used to model various diseases including neurological,cardiovascular,and diabetic disorders.We also discuss the development in gene modification technology that can facilitate the generation of transgenic pig models for human diseases.

  14. Modeling interdisciplinary activities involving Mathematics

    DEFF Research Database (Denmark)

    Iversen, Steffen Møllegaard

    2006-01-01

    In this paper a didactical model is presented. The goal of the model is to work as a didactical tool, or conceptual frame, for developing, carrying through and evaluating interdisciplinary activities involving the subject of mathematics and philosophy in the high schools. Through the terms...... of Horizontal Intertwining, Vertical Structuring and Horizontal Propagation the model consists of three phases, each considering different aspects of the nature of interdisciplinary activities. The theoretical modelling is inspired by work which focuses on the students abilities to concept formation in expanded...... domains (Michelsen, 2001, 2005a, 2005b). Furthermore the theoretical description rest on a series of qualitative interviews with teachers from the Danish high school (grades 9-11) conducted recently. The special case of concrete interdisciplinary activities between mathematics and philosophy is also...

  15. Optimal Control of Active Suspension in Consideration of Human Body Sitting Posture Model%考虑人体坐姿模型的汽车主动悬架最优控制

    Institute of Scientific and Technical Information of China (English)

    叶光湖; 盛云; 吴光强

    2013-01-01

    根据IS05982:2001 (E)推荐使用的人体坐姿低频振动模型,基于1/4汽车垂向振动模型,建立了车辆-人体振动系统的力学与数学模型.采用最优控制理论,设计了汽车主动悬架线性二次型调节控制器.在Matlab/Simulink环境下分别对被动悬架与主动悬架的性能进行仿真,时域和频域仿真结果对比表明,所建立的车辆-人体振动系统动力学模型能很好地反映人体振动特性,设计的主动悬架线性二次型调节控制器使汽车平顺性得到明显改善.%Based on the biodynamic model of the seated human body recommended by ISO 5982: 2001 (E) in low frequency vibration, and combined with the quarter automotive vertical vibration model, the mechanical and mathematical models of vehicle-human vibration system are established. Then, an active suspension with Linear Quadratic Regulator (LQR) controller is designed by applying the optimal control theory. The performance of the passive and active suspension systems is simulated in Matlab/Simulink and compared on frequency and time domain. The simulation results show that the vibration property of the human body can be well reflected by vehicle-human dynamics model, and the ride comfort of automobile with the active suspension with LQR is improved obviously.

  16. Classification and modeling of human activities using empirical mode decomposition with S-band and millimeter-wave micro-Doppler radars

    Science.gov (United States)

    Fairchild, Dustin P.; Narayanan, Ram M.

    2012-06-01

    The ability to identify human movements can be an important tool in many different applications such as surveillance, military combat situations, search and rescue operations, and patient monitoring in hospitals. This information can provide soldiers, security personnel, and search and rescue workers with critical knowledge that can be used to potentially save lives and/or avoid a dangerous situation. Most research involving human activity recognition is focused on using the Short-Time Fourier Transform (STFT) as a method of analyzing the micro-Doppler signatures. Because of the time-frequency resolution limitations of the STFT and because Fourier transform-based methods are not well-suited for use with non-stationary and nonlinear signals, we have chosen a different approach. Empirical Mode Decomposition (EMD) has been shown to be a valuable time-frequency method for processing non-stationary and nonlinear data such as micro-Doppler signatures and EMD readily provides a feature vector that can be utilized for classification. For classification, the method of a Support Vector Machine (SVMs) was chosen. SVMs have been widely used as a method of pattern recognition due to their ability to generalize well and also because of their moderately simple implementation. In this paper, we discuss the ability of these methods to accurately identify human movements based on their micro-Doppler signatures obtained from S-band and millimeter-wave radar systems. Comparisons will also be made based on experimental results from each of these radar systems. Furthermore, we will present simulations of micro-Doppler movements for stationary subjects that will enable us to compare our experimental Doppler data to what we would expect from an "ideal" movement.

  17. A human activity approach to User Interfaces

    DEFF Research Database (Denmark)

    Bødker, Susanne

    1989-01-01

    How can we understand why a bank teller has different needs for a user interface than those of casual users of a machine teller, or why a graphic designer needs a different user interface than a secretary? This article presents a framework for the design of user interfaces that originates from...... the work situations in which computer-based artifacts are used: The framework deals with the role of the user interface in purposeful human work. Human activity theory is used in this analysis. The purpose of this article is to make the reader curious and hopefully open his or her eyes to a somewhat...... different way of thinking about the user interface. The article applies examples of real-life interfaces to support this process, but it does not include a systematic presentation of empirical results. I focus on the role of the computer application in use. Thus, it is necessary to consider human...

  18. 3-D Human Modeling and Animation

    CERN Document Server

    Ratner, Peter

    2012-01-01

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

  19. Does human activity widen the tropics?

    CERN Document Server

    Georgieva, Katya

    2008-01-01

    The progress article - Widening of the tropical belt in a changing climate - by Seidel et al. (2008) published in the first issue of Nature Geosciences, summarizes the results of several methods to determine the width of the tropical zone. All they show evidence that the tropics have been expanding over the past few decades. We confirm this widening based on one more indicator - the position of the subtropical centers of high pressure. However, we question the implication of the authors that the tropics widen in response to human activity, and suggest as a more probable cause the increasing solar activity. Consequently, we question their conclusion that this widening may continue into the future in association with anthropogenic climate change, and suggest that whether the tropics will continue widening will depend on the future evolution of solar activity rather than on anthropogenic activity.

  20. Human hand modelling: kinematics, dynamics, applications

    NARCIS (Netherlands)

    Gustus, A.; Stillfried, G.; Visser, J.; Jörntell, H.; Van der Smagt, P.

    2012-01-01

    An overview of mathematical modelling of the human hand is given. We consider hand models from a specific background: rather than studying hands for surgical or similar goals, we target at providing a set of tools with which human grasping and manipulation capabilities can be studied, and hand funct

  1. Modeling the human prothrombinase complex components

    Science.gov (United States)

    Orban, Tivadar

    Thrombin generation is the culminating stage of the blood coagulation process. Thrombin is obtained from prothrombin (the substrate) in a reaction catalyzed by the prothrombinase complex (the enzyme). The prothrombinase complex is composed of factor Xa (the enzyme), factor Va (the cofactor) associated in the presence of calcium ions on a negatively charged cell membrane. Factor Xa, alone, can activate prothrombin to thrombin; however, the rate of conversion is not physiologically relevant for survival. Incorporation of factor Va into prothrombinase accelerates the rate of prothrombinase activity by 300,000-fold, and provides the physiological pathway of thrombin generation. The long-term goal of the current proposal is to provide the necessary support for the advancing of studies to design potential drug candidates that may be used to avoid development of deep venous thrombosis in high-risk patients. The short-term goals of the present proposal are to (1) to propose a model of a mixed asymmetric phospholipid bilayer, (2) expand the incomplete model of human coagulation factor Va and study its interaction with the phospholipid bilayer, (3) to create a homology model of prothrombin (4) to study the dynamics of interaction between prothrombin and the phospholipid bilayer.

  2. Human factors engineering program review model

    Energy Technology Data Exchange (ETDEWEB)

    1994-07-01

    The staff of the Nuclear Regulatory Commission is performing nuclear power plant design certification reviews based on a design process plan that describes the human factors engineering (HFE) program elements that are necessary and sufficient to develop an acceptable detailed design specification and an acceptable implemented design. There are two principal reasons for this approach. First, the initial design certification applications submitted for staff review did not include detailed design information. Second, since human performance literature and industry experiences have shown that many significant human factors issues arise early in the design process, review of the design process activities and results is important to the evaluation of an overall design. However, current regulations and guidance documents do not address the criteria for design process review. Therefore, the HFE Program Review Model (HFE PRM) was developed as a basis for performing design certification reviews that include design process evaluations as well as review of the final design. A central tenet of the HFE PRM is that the HFE aspects of the plant should be developed, designed, and evaluated on the basis of a structured top-down system analysis using accepted HFE principles. The HFE PRM consists of ten component elements. Each element in divided into four sections: Background, Objective, Applicant Submittals, and Review Criteria. This report describes the development of the HFE PRM and gives a detailed description of each HFE review element.

  3. Conditional Lineage Ablation to Model Human Diseases

    Science.gov (United States)

    Lee, Paul; Morley, Gregory; Huang, Qian; Fischer, Avi; Seiler, Stephanie; Horner, James W.; Factor, Stephen; Vaidya, Dhananjay; Jalife, Jose; Fishman, Glenn I.

    1998-09-01

    Cell loss contributes to the pathogenesis of many inherited and acquired human diseases. We have developed a system to conditionally ablate cells of any lineage and developmental stage in the mouse by regulated expression of the diphtheria toxin A (DTA) gene by using tetracycline-responsive promoters. As an example of this approach, we targeted expression of DTA to the hearts of adult mice to model structural abnormalities commonly observed in human cardiomyopathies. Induction of DTA expression resulted in cell loss, fibrosis, and chamber dilatation. As in many human cardiomyopathies, transgenic mice developed spontaneous arrhythmias in vivo, and programmed electrical stimulation of isolated-perfused transgenic hearts demonstrated a strikingly high incidence of spontaneous and inducible ventricular tachycardia. Affected mice showed marked perturbations of cardiac gap junction channel expression and localization, including a subset with disorganized epicardial activation patterns as revealed by optical action potential mapping. These studies provide important insights into mechanisms of arrhythmogenesis and suggest that conditional lineage ablation may have wide applicability for studies of disease pathogenesis.

  4. FE simulation of sound transmission in human ear with an active cochlea model%含主动耳蜗的人耳传声有限元模拟

    Institute of Scientific and Technical Information of China (English)

    王学林; 周健军; 凌玲; 胡于进

    2012-01-01

    采用外耳道、中耳、简化耳蜗耦合的有限元模型,模拟声压从外耳道传入耳蜗和耳蜗液体驱动基底膜振动的过程.耳蜗模型包含正交各向异性材料基底膜并考虑尺寸和材料性质沿长度的变化,在对柯蒂氏器进行微观力学分析的基础上,运用前馈模型实现耳蜗的主动机制.提出外耳道声音激励与耳蜗主动机制联合作用下中耳和耳蜗响应计算方法,结果表明:该模型实现了外耳道激励下基底膜位移与激励水平的非线性、基底膜频率选择等特性的模拟.%A finite element model integrating ear canal, middle ear and cochlea was established and used to simulate a process of sound transmission from ear canal to cochlea, and cochlear fluid driving basilar membrane to vibrate. The cochlea model included an orthotropic basilar membrane with dimensional and material property variation along its length. Based on the micro-mechanic analysis of organ of Corti, a feed-forward mechanism was used to realize the cochlea active amplifier features. A numerical method, combining ear canal stimuli and cochlea active mechanism, was developed to compute the responses in the middle ear and active cochlea. The results showed that the model achieves basilar membrane response level compression and frequency selectivity characteristics with respect to ear canal sound stimuli.

  5. Hidden Markov Models for Human Genes

    DEFF Research Database (Denmark)

    Baldi, Pierre; Brunak, Søren; Chauvin, Yves

    1997-01-01

    We analyse the sequential structure of human genomic DNA by hidden Markov models. We apply models of widely different design: conventional left-right constructs and models with a built-in periodic architecture. The models are trained on segments of DNA sequences extracted such that they cover...

  6. Protease activity, localization and inhibition in the human hair follicle.

    Science.gov (United States)

    Bhogal, R K; Mouser, P E; Higgins, C A; Turner, G A

    2014-02-01

    In humans, the process of hair shedding, referred to as exogen, is believed to occur independently of the other hair cycle phases. Although the actual mechanisms involved in hair shedding are not fully known, it has been hypothesized that the processes leading to the final step of hair shedding may be driven by proteases and/or protease inhibitor activity. In this study, we investigated the presence of proteases and protease activity in naturally shed human hairs and assessed enzyme inhibition activity of test materials. We measured enzyme activity using a fluorescence-based assay and protein localization by indirect immunohistochemistry (IHC). We also developed an ex vivo skin model for measuring the force required to pull hair fibres from skin. Our data demonstrate the presence of protease activity in the tissue material surrounding club roots. We also demonstrated the localization of specific serine protease protein expression in human hair follicle by IHC. These data provide evidence demonstrating the presence of proteases around the hair club roots, which may play a role during exogen. We further tested the hypothesis that a novel protease inhibitor system (combination of Trichogen) and climbazole) could inhibit protease activity in hair fibre club root extracts collected from a range of ethnic groups (U.K., Brazil, China, first-generation Mexicans in the U.S.A., Thailand and Turkey) in both males and females. Furthermore, we demonstrated that this combination is capable of increasing the force required to remove hair in an ex vivo skin model system. These studies indicate the presence of proteolytic activity in the tissue surrounding the human hair club root and show that it is possible to inhibit this activity with a combination of Trichogen and climbazole. This technology may have potential to reduce excessive hair shedding. © 2013 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  7. Kinetic mechanism of the activation of human plasminogen by streptokinase.

    Science.gov (United States)

    Kosow, D P

    1975-10-07

    A method of determining the initial rate of plasminogen activation has been developed. The method has been used to investigate the mechanism of activation of human plasminogen by streptokinase. Plasmin formation follows saturation kinetics. Inhibition of plasmin formation by epsilon-aminocaproic acid is uncompetitive with a Ki of 0.6 mM. A model consistent with the data is that streptokinase induces a conformational change in the plasminogen molecule, producing an active center which cleaves an internal peptide bond to produce plasmin. Thus, streptokinase functions as a catalytic allosteric effector.

  8. Modeling interdisciplinary activities involving Mathematics

    DEFF Research Database (Denmark)

    Iversen, Steffen Møllegaard

    2006-01-01

    In this paper a didactical model is presented. The goal of the model is to work as a didactical tool, or conceptual frame, for developing, carrying through and evaluating interdisciplinary activities involving the subject of mathematics and philosophy in the high schools. Through the terms...... domains (Michelsen, 2001, 2005a, 2005b). Furthermore the theoretical description rest on a series of qualitative interviews with teachers from the Danish high school (grades 9-11) conducted recently. The special case of concrete interdisciplinary activities between mathematics and philosophy is also...

  9. Modeling Cytoskeletal Active Matter Systems

    Science.gov (United States)

    Blackwell, Robert

    Active networks of filamentous proteins and crosslinking motor proteins play a critical role in many important cellular processes. One of the most important microtubule-motor protein assemblies is the mitotic spindle, a self-organized active liquid-crystalline structure that forms during cell division and that ultimately separates chromosomes into two daughter cells. Although the spindle has been intensively studied for decades, the physical principles that govern its self-organization and function remain mysterious. To evolve a better understanding of spindle formation, structure, and dynamics, I investigate course-grained models of active liquid-crystalline networks composed of microtubules, modeled as hard spherocylinders, in diffusive equilibrium with a reservoir of active crosslinks, modeled as hookean springs that can adsorb to microtubules and and translocate at finite velocity along the microtubule axis. This model is investigated using a combination of brownian dynamics and kinetic monte carlo simulation. I have further refined this model to simulate spindle formation and kinetochore capture in the fission yeast S. pombe. I then make predictions for experimentally realizable perturbations in motor protein presence and function in S. pombe.

  10. Inflammatory aetiology of human myometrial activation tested using directed graphs.

    Directory of Open Access Journals (Sweden)

    2005-07-01

    Full Text Available THERE ARE THREE MAIN HYPOTHESES FOR THE ACTIVATION OF THE HUMAN UTERUS AT LABOUR: functional progesterone withdrawal, inflammatory stimulation, and oxytocin receptor activation. To test these alternatives we have taken information and data from the literature to develop causal pathway models for the activation of human myometrium. The data provided quantitative RT-PCR results on key genes from samples taken before and during labour. Principal component analysis showed that pre-labour samples form a homogenous group compared to those during labour. We therefore modelled the alternative causal pathways in non-labouring samples using directed graphs and statistically compared the likelihood of the different models using structural equations and D-separation approaches. Using the computer program LISREL, inflammatory activation as a primary event was highly consistent with the data (p = 0.925, progesterone withdrawal, as a primary event, is plausible (p = 0.499, yet comparatively unlikely, oxytocin receptor mediated initiation is less compatible with the data (p = 0.091. DGraph, a software program that creates directed graphs, produced similar results (p= 0.684, p= 0.280, and p = 0.04, respectively. This outcome supports an inflammatory aetiology for human labour. Our results demonstrate the value of directed graphs in determining the likelihood of causal relationships in biology in situations where experiments are not possible.

  11. Human Activity Recognition as Time-Series Analysis

    Directory of Open Access Journals (Sweden)

    Hyesuk Kim

    2015-01-01

    Full Text Available We propose a system that can recognize daily human activities with a Kinect-style depth camera. Our system utilizes a set of view-invariant features and the hidden state conditional random field (HCRF model to recognize human activities from the 3D body pose stream provided by MS Kinect API or OpenNI. Many high-level daily activities can be regarded as having a hierarchical structure where multiple subactivities are performed sequentially or iteratively. In order to model effectively these high-level daily activities, we utilized a multiclass HCRF model, which is a kind of probabilistic graphical models. In addition, in order to get view-invariant, but more informative features, we extract joint angles from the subject’s skeleton model and then perform the feature transformation to obtain three different types of features regarding motion, structure, and hand positions. Through various experiments using two different datasets, KAD-30 and CAD-60, the high performance of our system is verified.

  12. Integration of Lightning- and Human-Caused Wildfire Occurrence Models

    DEFF Research Database (Denmark)

    Vilar, Lara; Nieto Solana, Hector; Martín, M. Pilar

    2010-01-01

    Fire risk indices are useful tools for fire prevention actions by fire managers. A fire ignition is either the result of lightning or human activities. In European Mediterranean countries most forest fires are due to human activities. However, lightning is still an important fire ignition source...... in some regions. Integration of lightning and human fire occurrence probability into fire risk indices would be necessary to have a complete picture of the causal agents and their relative importance in fire occurrence. We present two methods for the integration of lightning and human fire occurrence...... probability models at 1 × 1 km grid cell resolution in two regions of Spain: Madrid, which presents a high fire incidence due to human activities; and Aragón, one of the most affected regions in Spain by lightning-fires. For validation, independent fire ignition points were used to compute the Receiver...

  13. Ferromagnetic interaction model of activity level in workplace communication

    Science.gov (United States)

    Akitomi, Tomoaki; Ara, Koji; Watanabe, Jun-ichiro; Yano, Kazuo

    2013-03-01

    The nature of human-human interaction, specifically, how people synchronize with each other in multiple-participant conversations, is described by a ferromagnetic interaction model of people’s activity levels. We found two microscopic human interaction characteristics from a real-environment face-to-face conversation. The first characteristic is that people quite regularly synchronize their activity level with that of the other participants in a conversation. The second characteristic is that the degree of synchronization increases as the number of participants increases. Based on these microscopic ferromagnetic characteristics, a “conversation activity level” was modeled according to the Ising model. The results of a simulation of activity level based on this model well reproduce macroscopic experimental measurements of activity level. This model will give a new insight into how people interact with each other in a conversation.

  14. Human Exposure Modeling - Databases to Support Exposure Modeling

    Science.gov (United States)

    Human exposure modeling relates pollutant concentrations in the larger environmental media to pollutant concentrations in the immediate exposure media. The models described here are available on other EPA websites.

  15. Acute activation, desensitization and smoldering activation of human acetylcholine receptors.

    Directory of Open Access Journals (Sweden)

    Barbara G Campling

    Full Text Available The behavioral effects of nicotine and other nicotinic agonists are mediated by AChRs in the brain. The relative contribution of acute activation versus chronic desensitization of AChRs is unknown. Sustained "smoldering activation" occurs over a range of agonist concentrations at which activated and desensitized AChRs are present in equilibrium. We used a fluorescent dye sensitive to changes in membrane potential to examine the effects of acute activation and chronic desensitization by nicotinic AChR agonists on cell lines expressing human α4β2, α3β4 and α7 AChRs. We examined the effects of acute and prolonged application of nicotine and the partial agonists varenicline, cytisine and sazetidine-A on these AChRs. The range of concentrations over which nicotine causes smoldering activation of α4β2 AChRs was centered at 0.13 µM, a level found in smokers. However, nicotine produced smoldering activation of α3β4 and α7 AChRs at concentrations well above levels found in smokers. The α4β2 expressing cell line contains a mixture of two stoichiometries, namely (α4β22β2 and (α4β22α4. The (α4β22β2 stoichiometry is more sensitive to activation by nicotine. Sazetidine-A activates and desensitizes only this stoichiometry. Varenicline, cytisine and sazetidine-A were partial agonists on this mixture of α4β2 AChRs, but full agonists on α3β4 and α7 AChRs. It has been reported that cytisine and varenicline are most efficacious on the (α4β22α4 stoichiometry. In this study, we distinguish the dual effects of activation and desensitization of AChRs by these nicotinic agonists and define the range of concentrations over which smoldering activation can be sustained.

  16. Modelling mutational landscapes of human cancers in vitro

    Science.gov (United States)

    Olivier, Magali; Weninger, Annette; Ardin, Maude; Huskova, Hana; Castells, Xavier; Vallée, Maxime P.; McKay, James; Nedelko, Tatiana; Muehlbauer, Karl-Rudolf; Marusawa, Hiroyuki; Alexander, John; Hazelwood, Lee; Byrnes, Graham; Hollstein, Monica; Zavadil, Jiri

    2014-03-01

    Experimental models that recapitulate mutational landscapes of human cancers are needed to decipher the rapidly expanding data on human somatic mutations. We demonstrate that mutation patterns in immortalised cell lines derived from primary murine embryonic fibroblasts (MEFs) exposed in vitro to carcinogens recapitulate key features of mutational signatures observed in human cancers. In experiments with several cancer-causing agents we obtained high genome-wide concordance between human tumour mutation data and in vitro data with respect to predominant substitution types, strand bias and sequence context. Moreover, we found signature mutations in well-studied human cancer driver genes. To explore endogenous mutagenesis, we used MEFs ectopically expressing activation-induced cytidine deaminase (AID) and observed an excess of AID signature mutations in immortalised cell lines compared to their non-transgenic counterparts. MEF immortalisation is thus a simple and powerful strategy for modelling cancer mutation landscapes that facilitates the interpretation of human tumour genome-wide sequencing data.

  17. Human Operator Control Strategy Model.

    Science.gov (United States)

    1980-04-01

    fashion. HOPE reflects the two-store theory of memory current in the psycho- logical literature ( Atkinson & Shiffrin , 1968; Broadbent, 1971). Two...uncertainty. In P.M.A. Rabbit & S. Dornic (Eds.), Attention and performance V. New York: Academic Press, 1975. Atkinson , R. C., & Shiffrin , R. M. Human...48 2. The Perception Process ... ............... 50 3. The Command Memory and Command Selection Process

  18. Understanding Usability Work as a Human Activity

    DEFF Research Database (Denmark)

    Nørgaard, Mie

    of usability work to include a human perspective, is crucial to downstream utility—how usability work impacts the on-going development process. Our work shows that cross-professional collaboration is subject to challenges that arise from stakeholders having conflicting priorities, procedures and personalities......Three core themes are explored in eight papers: Usability work as a human activity, usability practice and methods, and persuasiveness of evaluation results and feedback. We explore how usability work is much more than methods and work procedures, and argue that maturing our understanding....... Such challenges include evaluation results lacking relevance, poor timing of evaluation results, little respect for other disciplines, and difficulties sharing important information about a design. The studies of practical usability work suggest that user researchers working with computer games and task oriented...

  19. Predicting human brain activity associated with the meanings of nouns.

    Science.gov (United States)

    Mitchell, Tom M; Shinkareva, Svetlana V; Carlson, Andrew; Chang, Kai-Min; Malave, Vicente L; Mason, Robert A; Just, Marcel Adam

    2008-05-30

    The question of how the human brain represents conceptual knowledge has been debated in many scientific fields. Brain imaging studies have shown that different spatial patterns of neural activation are associated with thinking about different semantic categories of pictures and words (for example, tools, buildings, and animals). We present a computational model that predicts the functional magnetic resonance imaging (fMRI) neural activation associated with words for which fMRI data are not yet available. This model is trained with a combination of data from a trillion-word text corpus and observed fMRI data associated with viewing several dozen concrete nouns. Once trained, the model predicts fMRI activation for thousands of other concrete nouns in the text corpus, with highly significant accuracies over the 60 nouns for which we currently have fMRI data.

  20. Active Learning for Player Modeling

    DEFF Research Database (Denmark)

    Shaker, Noor; Abou-Zleikha, Mohamed; Shaker, Mohammad

    2015-01-01

    Learning models of player behavior has been the focus of several studies. This work is motivated by better understanding of player behavior, a knowledge that can ultimately be employed to provide player-adapted or personalized content. In this paper, we propose the use of active learning for player...... experience modeling. We use a dataset from hundreds of players playing Infinite Mario Bros. as a case study and we employ the random forest method to learn mod- els of player experience through the active learning approach. The results obtained suggest that only part of the dataset (up to half the size...... of the full dataset) is necessary for the construction of accu- rate models that are as accurate as those constructed from the full dataset. This indicates the potential of the method and its benefits in cases when obtaining the data is expensive or time, storage or effort consuming. The results also indicate...

  1. Active Learning for Player Modeling

    DEFF Research Database (Denmark)

    Shaker, Noor; Abou-Zleikha, Mohamed; Shaker, Mohammad

    2015-01-01

    Learning models of player behavior has been the focus of several studies. This work is motivated by better understanding of player behavior, a knowledge that can ultimately be employed to provide player-adapted or personalized content. In this paper, we propose the use of active learning for player...... experience modeling. We use a dataset from hundreds of players playing Infinite Mario Bros. as a case study and we employ the random forest method to learn mod- els of player experience through the active learning approach. The results obtained suggest that only part of the dataset (up to half the size...... of the full dataset) is necessary for the construction of accu- rate models that are as accurate as those constructed from the full dataset. This indicates the potential of the method and its benefits in cases when obtaining the data is expensive or time, storage or effort consuming. The results also indicate...

  2. CFTR targeting during activation of human neutrophils.

    Science.gov (United States)

    Ng, Hang Pong; Valentine, Vincent G; Wang, Guoshun

    2016-12-01

    Cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel, plays critical roles in phagocytic host defense. However, how activated neutrophils regulate CFTR channel distribution subcellularly is not well defined. To investigate, we tested multiple Abs against different CFTR domains, to examine CFTR expression in human peripheral blood neutrophils by flow cytometry. The data confirmed that resting neutrophils had pronounced CFTR expression. Activation of neutrophils with soluble or particulate agonists did not significantly increase CFTR expression level, but induced CFTR redistribution to cell surface. Such CFTR mobilization correlated with cell-surface recruitment of formyl-peptide receptor during secretory vesicle exocytosis. Intriguingly, neutrophils from patients with ΔF508-CF, despite expression of the mutant CFTR, showed little cell-surface mobilization upon stimulation. Although normal neutrophils effectively targeted CFTR to their phagosomes, ΔF508-CF neutrophils had impairment in that process, resulting in deficient hypochlorous acid production. Taken together, activated neutrophils regulate CFTR distribution by targeting this chloride channel to the subcellular sites of activation, and ΔF508-CF neutrophils fail to achieve such targeting, thus undermining their host defense function.

  3. Aberrant rel/nfkb genes and activity in human cancer.

    Science.gov (United States)

    Rayet, B; Gélinas, C

    1999-11-22

    Rel/NF-kappaB transcription factors are key regulators of immune, inflammatory and acute phase responses and are also implicated in the control of cell proliferation and apoptosis. Remarkable progress has been made in understanding the signal transduction pathways that lead to the activation of Rel/NF-kappaB factors and the consequent induction of gene expression. Evidence linking deregulated Rel/NF-kappaB activity to oncogenesis in mammalian systems has emerged in recent years, consistent with the acute oncogenicity of the viral oncoprotein v-Rel in animal models. Chromosomal amplification, overexpression and rearrangement of genes coding for Rel/NF-kappaB factors have been noted in many human hematopoietic and solid tumors. Persistent nuclear NF-kappaB activity was also described in several human cancer cell types, as a result of constitutive activation of upstream signaling kinases or mutations inactivating inhibitory IkappaB subunits. Studies point to a correlation between the activation of cellular gene expression by Rel/NF-kappaB factors and their participation in the malignant process. Experiments implicating NF-kappaB in the control of the apoptotic response also support a role in oncogenesis and in the resistance of tumor cells to chemotherapy. This review focuses on the status of the rel, nfkb and ikb genes and their activity in human tumors and their association with the onset or progression of malignancies.

  4. Human body modeling in injury biomechanics

    NARCIS (Netherlands)

    Happee, R.; Morsink, P.L.J.; Horst, M.J. van der; Wismans, J.S.H.M.

    1999-01-01

    Mathematical modelling is widely used for crash-safety research and design. However, most occupant models used in crash simulations are based on crash dummies and thereby inherit their apparent limitations. This paper describes a mathematical model of the real human body for impact loading. A combin

  5. Modeling human operator involvement in robotic systems

    NARCIS (Netherlands)

    Wewerinke, P.H.

    1991-01-01

    A modeling approach is presented to describe complex manned robotic systems. The robotic system is modeled as a (highly) nonlinear, possibly time-varying dynamic system including any time delays in terms of optimal estimation, control and decision theory. The role of the human operator(s) is modeled

  6. Assessment of thermal effects in a model of the human head implanted with a wireless active microvalve for the treatment of glaucoma creating a filtering bleb

    Science.gov (United States)

    Schaumburg, F.; Guarnieri, F. A.

    2017-05-01

    A 3D anatomical computational model is developed to assess thermal effects due to exposure to the electromagnetic field required to power a new investigational active implantable microvalve for the treatment of glaucoma. Such a device, located in the temporal superior eye quadrant, produces a filtering bleb, which is included in the geometry of the model, together with the relevant ocular structures. The electromagnetic field source—a planar coil—as well as the microvalve antenna and casing are also included. Exposure to the electromagnetic field source of an implanted and a non-implanted subject are simulated by solving a magnetic potential formulation, using the finite element method. The maximum SAR10 is reached in the eyebrow and remains within the limits suggested by the IEEE and ICNIRP standards. The anterior chamber, filtering bleb, iris and ciliary body are the ocular structures where more absorption occurs. The temperature rise distribution is also obtained by solving the bioheat equation with the finite element method. The numerical results are compared with the in vivo measurements obtained from four rabbits implanted with the microvalve and exposed to the electromagnetic field source.

  7. Activation of peroxisome proliferator-activated receptor-{alpha} enhances fatty acid oxidation in human adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Joo-Young; Hashizaki, Hikari; Goto, Tsuyoshi; Sakamoto, Tomoya; Takahashi, Nobuyuki [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Kawada, Teruo, E-mail: fat@kais.kyoto-u.ac.jp [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan)

    2011-04-22

    Highlights: {yields} PPAR{alpha} activation increased mRNA expression levels of adipocyte differentiation marker genes and GPDH activity in human adipocytes. {yields} PPAR{alpha} activation also increased insulin-dependent glucose uptake in human adipocytes. {yields} PPAR{alpha} activation did not affect lipid accumulation in human adipocytes. {yields} PPAR{alpha} activation increased fatty acid oxidation through induction of fatty acid oxidation-related genes in human adipocytes. -- Abstract: Peroxisome proliferator-activated receptor-{alpha} (PPAR{alpha}) is a key regulator for maintaining whole-body energy balance. However, the physiological functions of PPAR{alpha} in adipocytes have been unclarified. We examined the functions of PPAR{alpha} using human multipotent adipose tissue-derived stem cells as a human adipocyte model. Activation of PPAR{alpha} by GW7647, a potent PPAR{alpha} agonist, increased the mRNA expression levels of adipocyte differentiation marker genes such as PPAR{gamma}, adipocyte-specific fatty acid-binding protein, and lipoprotein lipase and increased both GPDH activity and insulin-dependent glucose uptake level. The findings indicate that PPAR{alpha} activation stimulates adipocyte differentiation. However, lipid accumulation was not changed, which is usually observed when PPAR{gamma} is activated. On the other hand, PPAR{alpha} activation by GW7647 treatment induced the mRNA expression of fatty acid oxidation-related genes such as CPT-1B and AOX in a PPAR{alpha}-dependent manner. Moreover, PPAR{alpha} activation increased the production of CO{sub 2} and acid soluble metabolites, which are products of fatty acid oxidation, and increased oxygen consumption rate in human adipocytes. The data indicate that activation of PPAR{alpha} stimulates both adipocyte differentiation and fatty acid oxidation in human adipocytes, suggesting that PPAR{alpha} agonists could improve insulin resistance without lipid accumulation in adipocytes. The expected

  8. Cognitive modelling of human temporal reasoning

    NARCIS (Netherlands)

    ter Meulen, AGB

    2003-01-01

    Modelling human reasoning characterizes the fundamental human cognitive capacity to describe our past experience and use it to form expectations as well as plan and direct our future actions. Natural language semantics analyzes dynamic forms of reasoning in which the real-time order determines the

  9. Novel innate cancer killing activity in humans

    Directory of Open Access Journals (Sweden)

    Lovato James

    2011-08-01

    Full Text Available Abstract Background In this study, we pilot tested an in vitro assay of cancer killing activity (CKA in circulating leukocytes of 22 cancer cases and 25 healthy controls. Methods Using a human cervical cancer cell line, HeLa, as target cells, we compared the CKA in circulating leukocytes, as effector cells, of cancer cases and controls. The CKA was normalized as percentages of total target cells during selected periods of incubation time and at selected effector/target cell ratios in comparison to no-effector-cell controls. Results Our results showed that CKA similar to that of our previous study of SR/CR mice was present in human circulating leukocytes but at profoundly different levels in individuals. Overall, males have a significantly higher CKA than females. The CKA levels in cancer cases were lower than that in healthy controls (mean ± SD: 36.97 ± 21.39 vs. 46.28 ± 27.22. Below-median CKA was significantly associated with case status (odds ratio = 4.36; 95% Confidence Interval = 1.06, 17.88 after adjustment of gender and race. Conclusions In freshly isolated human leukocytes, we were able to detect an apparent CKA in a similar manner to that of cancer-resistant SR/CR mice. The finding of CKA at lower levels in cancer patients suggests the possibility that it may be of a consequence of genetic, physiological, or pathological conditions, pending future studies with larger sample size.

  10. Murine models of human wound healing.

    Science.gov (United States)

    Chen, Jerry S; Longaker, Michael T; Gurtner, Geoffrey C

    2013-01-01

    In vivo wound healing experiments remain the most predictive models for studying human wound healing, allowing an accurate representation of the complete wound healing environment including various cell types, environmental cues, and paracrine interactions. Small animals are economical, easy to maintain, and allow researchers to take advantage of the numerous transgenic strains that have been developed to investigate the specific mechanisms involved in wound healing and regeneration. Here we describe three reproducible murine wound healing models that recapitulate the human wound healing process.

  11. Cyberpsychology: a human-interaction perspective based on cognitive modeling.

    Science.gov (United States)

    Emond, Bruno; West, Robert L

    2003-10-01

    This paper argues for the relevance of cognitive modeling and cognitive architectures to cyberpsychology. From a human-computer interaction point of view, cognitive modeling can have benefits both for theory and model building, and for the design and evaluation of sociotechnical systems usability. Cognitive modeling research applied to human-computer interaction has two complimentary objectives: (1) to develop theories and computational models of human interactive behavior with information and collaborative technologies, and (2) to use the computational models as building blocks for the design, implementation, and evaluation of interactive technologies. From the perspective of building theories and models, cognitive modeling offers the possibility to anchor cyberpsychology theories and models into cognitive architectures. From the perspective of the design and evaluation of socio-technical systems, cognitive models can provide the basis for simulated users, which can play an important role in usability testing. As an example of application of cognitive modeling to technology design, the paper presents a simulation of interactive behavior with five different adaptive menu algorithms: random, fixed, stacked, frequency based, and activation based. Results of the simulation indicate that fixed menu positions seem to offer the best support for classification like tasks such as filing e-mails. This research is part of the Human-Computer Interaction, and the Broadband Visual Communication research programs at the National Research Council of Canada, in collaboration with the Carleton Cognitive Modeling Lab at Carleton University.

  12. Prevalence of Telomerase Activity in Human Cancer

    Directory of Open Access Journals (Sweden)

    Chi-Hau Chen

    2011-05-01

    Full Text Available Telomerase activity has been measured in a wide variety of cancerous and non-cancerous tissue types, and the vast majority of clinical studies have shown a direct correlation between it and the presence of cancerous cells. Telomerase plays a key role in cellular immortality and tumorigenesis. Telomerase is activated in 80–90% of human carcinomas, but not in normal somatic cells, therefore, its detection holds promise as a diagnostic marker for cancer. Measurable levels of telomerase have been detected in malignant cells from various samples: tissue from gestational trophoblastic neoplasms; squamous carcinoma cells from oral rinses; lung carcinoma cells from bronchial washings; colorectal carcinoma cells from colonic luminal washings; bladder carcinoma cells from urine or bladder washings; and breast carcinoma or thyroid cancer cells from fine needle aspirations. Such clinical tests for telomerase can be useful as non-invasive and cost-effective methods for early detection and monitoring of cancer. In addition, telomerase activity has been shown to correlate with poor clinical outcome in late-stage diseases such as non-small cell lung cancer, colorectal cancer, and soft tissue sarcomas. In such cases, testing for telomerase activity can be used to identify patients with a poor prognosis and to select those who might benefit from adjuvant treatment. Our review of the latest medical advances in this field reveals that telomerase holds great promise as a biomarker for early cancer detection and monitoring, and has considerable potential as the basis for developing new anticancer therapies.

  13. Model-Based approaches to Human-Automation Systems Design

    DEFF Research Database (Denmark)

    Jamieson, Greg A.; Andersson, Jonas; Bisantz, Ann

    2012-01-01

    Human-automation interaction in complex systems is common, yet design for this interaction is often conducted without explicit consideration of the role of the human operator. Fortunately, there are a number of modeling frameworks proposed for supporting this design activity. However, the framewo......Human-automation interaction in complex systems is common, yet design for this interaction is often conducted without explicit consideration of the role of the human operator. Fortunately, there are a number of modeling frameworks proposed for supporting this design activity. However......, the frameworks are often adapted from other purposes, usually applied to a limited range of problems, sometimes not fully described in the open literature, and rarely critically reviewed in a manner acceptable to proponents and critics alike. The present paper introduces a panel session wherein these proponents...

  14. Concepts of disability: the Activity Space Model.

    Science.gov (United States)

    Kopec, J A

    1995-03-01

    This paper describes a new conceptual framework for functional assessment, the Activity Space Model (ASM). According to this model, functional impairments may lead to restrictions in an individual's activity space, a multidimensional space that represents human potential for activity. For each elementary ability, restrictions in the corresponding dimension of the activity space can be evaluated by deriving a difficulty curve that depicts the relationship between the level of performance and the psychophysical cost of activity. The effect of disease on daily functioning is explained in terms of a tradeoff between the psychophysical cost and the value of each act of behavior to the disabled individual. These two constructs are measured on the same scale and expressed in units of difficulty. The location of each task within the activity space in relation to the difficulty curve determines whether it will be performed or avoided at a given point in time. The ASM has both theoretical and practical implications. It offers a new, integrated perspective on disability and suggests new strategies for developing and evaluating functional assessment measures.

  15. Inferring polymorphism-induced regulatory gene networks active in human lymphocyte cell lines by weighted linear mixed model analysis of multiple RNA-Seq datasets.

    Directory of Open Access Journals (Sweden)

    Wensheng Zhang

    Full Text Available Single-nucleotide polymorphisms (SNPs contribute to the between-individual expression variation of many genes. A regulatory (trait-associated SNP is usually located near or within a (host gene, possibly influencing the gene's transcription or/and post-transcriptional modification. But its targets may also include genes that are physically farther away from it. A heuristic explanation of such multiple-target interferences is that the host gene transfers the SNP genotypic effects to the distant gene(s by a transcriptional or signaling cascade. These connections between the host genes (regulators and the distant genes (targets make the genetic analysis of gene expression traits a promising approach for identifying unknown regulatory relationships. In this study, through a mixed model analysis of multi-source digital expression profiling for 140 human lymphocyte cell lines (LCLs and the genotypes distributed by the international HapMap project, we identified 45 thousands of potential SNP-induced regulatory relationships among genes (the significance level for the underlying associations between expression traits and SNP genotypes was set at FDR < 0.01. We grouped the identified relationships into four classes (paradigms according to the two different mechanisms by which the regulatory SNPs affect their cis- and trans- regulated genes, modifying mRNA level or altering transcript splicing patterns. We further organized the relationships in each class into a set of network modules with the cis- regulated genes as hubs. We found that the target genes in a network module were often characterized by significant functional similarity, and the distributions of the target genes in three out of the four networks roughly resemble a power-law, a typical pattern of gene networks obtained from mutation experiments. By two case studies, we also demonstrated that significant biological insights can be inferred from the identified network modules.

  16. Animal Models of Human Placentation - A Review

    DEFF Research Database (Denmark)

    Carter, Anthony Michael

    2007-01-01

    This review examines the strengths and weaknesses of animal models of human placentation and pays particular attention to the mouse and non-human primates. Analogies can be drawn between mouse and human in placental cell types and genes controlling placental development. There are, however...... and endometrium is similar in macaques and baboons, as is the subsequent lacunar stage. The absence of interstitial trophoblast cells in the monkey is an important difference from human placentation. However, there is a strong resemblance in the way spiral arteries are invaded and transformed in the macaque...

  17. Finite element modeling of the human pelvis

    Energy Technology Data Exchange (ETDEWEB)

    Carlson, B.

    1995-11-01

    A finite element model of the human pelvis was created using a commercial wire frame image as a template. To test the final mesh, the model`s mechanical behavior was analyzed through finite element analysis and the results were displayed graphically as stress concentrations. In the future, this grid of the pelvis will be integrated with a full leg model and used in side-impact car collision simulations.

  18. Individualized Human CAD Models: Anthropmetric Morphing and Body Tissue Layering

    Science.gov (United States)

    2014-07-31

    torso sub-assembly may have more fat in the abdomen than in the chest. A study 18 that could help refine this feature is being developed by the US...responses to various ensembles being developed, taking 3 into account human characteristics (height, weight, body fat , etc.), physical activity levels...model of the human body in a CAD (Computer- Aided Design) format which includes both surface features as well as internal composition, e.g., the fat

  19. Modeling for the Dynamics of Human Innovative Behaviors

    CERN Document Server

    Lin, Ying-Ting; Wang, Bing-Hong

    2013-01-01

    How to promote the innovative activities is an important problem for modern society. In this paper, combining with the evolutionary games and information spreading, we propose a lattice model to investigate dynamics of human innovative behaviors based on benefit-driven assumption. Simulations show several properties in agreement with peoples' daily cognition on innovative behaviors, such as slow diffusion of innovative behaviors, gathering of innovative strategy on "innovative centers", and quasi-localized dynamics. Furthermore, our model also emerges rich non-Poisson properties in the temporal-spacial patterns of the innovative status, including the scaling law in the interval time of innovation releases and the bimodal distributions on the spreading range of innovations, which would be universal in human innovative behaviors. Our model provide a basic framework on the study of the issue relevant to the evolution of human innovative behaviors and the promotion measurement of innovative activities.

  20. Modeling electrically active viscoelastic membranes.

    Directory of Open Access Journals (Sweden)

    Sitikantha Roy

    Full Text Available The membrane protein prestin is native to the cochlear outer hair cell that is crucial to the ear's amplification and frequency selectivity throughout the whole acoustic frequency range. The outer hair cell exhibits interrelated dimensional changes, force generation, and electric charge transfer. Cells transfected with prestin acquire unique active properties similar to those in the native cell that have also been useful in understanding the process. Here we propose a model describing the major electromechanical features of such active membranes. The model derived from thermodynamic principles is in the form of integral relationships between the history of voltage and membrane resultants as independent variables and the charge density and strains as dependent variables. The proposed model is applied to the analysis of an active force produced by the outer hair cell in response to a harmonic electric field. Our analysis reveals the mechanism of the outer hair cell active (isometric force having an almost constant amplitude and phase up to 80 kHz. We found that the frequency-invariance of the force is a result of interplay between the electrical filtering associated with prestin and power law viscoelasticity of the surrounding membrane. Paradoxically, the membrane viscoelasticity boosts the force balancing the electrical filtering effect. We also consider various modes of electromechanical coupling in membrane with prestin associated with mechanical perturbations in the cell. We consider pressure or strains applied step-wise or at a constant rate and compute the time course of the resulting electric charge. The results obtained here are important for the analysis of electromechanical properties of membranes, cells, and biological materials as well as for a better understanding of the mechanism of hearing and the role of the protein prestin in this mechanism.

  1. Mathematical human modelling for impact loading

    NARCIS (Netherlands)

    Happee, R.; Hoof, J.F.A.M. van; Lange, R. de

    2001-01-01

    Mathematical modeling of the human body is widely used for automotive crash-safety research and design. Simulations have contributed to a reduction of injury numbers by optimization of vehicle structures and restraint systems. Currently, such simulations are largely performed using occupant models b

  2. Mathematical human modelling for impact loading

    NARCIS (Netherlands)

    Happee, R.; Hoof, J.F.A.M. van; Lange, R. de

    2001-01-01

    Mathematical modeling of the human body is widely used for automotive crash-safety research and design. Simulations have contributed to a reduction of injury numbers by optimization of vehicle structures and restraint systems. Currently, such simulations are largely performed using occupant models

  3. Mathematical human body modelling for impact loading

    NARCIS (Netherlands)

    Happee, R.; Morsink, P.L.J.; Wismans, J.S.H.M.

    1999-01-01

    Mathematical modelling of the human body is widely used for automotive crash safety research and design. Simulations have contributed to a reduction of injury numbers by optimisation of vehicle structures and restraint systems. Currently such simulations are largely performed using occupant models

  4. Complex Systems and Human Performance Modeling

    Science.gov (United States)

    2013-12-01

    constitute a cognitive architecture or decomposing the work flows and resource constraints that characterize human-system interactions, the modeler...also explored the generation of so-called “ fractal ” series from simple task network models where task times are the calculated by way of a moving

  5. Models of the Human in Tantric Hinduism

    DEFF Research Database (Denmark)

    Olesen, Bjarne Wernicke; Flood, Gavin

    2018-01-01

    This research project explores the origins, developments and transformations of yogic models of the human (e.g. kundalini yoga, the cakra system and ritual sex) in the tantric goddess traditions or what might be called Śāktism of medieval India. These Śākta models of esoteric anatomy originating...

  6. Mathematical human body modelling for impact loading

    NARCIS (Netherlands)

    Happee, R.; Morsink, P.L.J.; Wismans, J.S.H.M.

    1999-01-01

    Mathematical modelling of the human body is widely used for automotive crash safety research and design. Simulations have contributed to a reduction of injury numbers by optimisation of vehicle structures and restraint systems. Currently such simulations are largely performed using occupant models b

  7. Interior Design Research: A Human Ecosystem Model.

    Science.gov (United States)

    Guerin, Denise A.

    1992-01-01

    The interior ecosystems model illustrates effects on the human organism of the interaction of the natural, behavioral, and built environment. Examples of interior lighting and household energy consumption show the model's flexibility for organizing study variables in interior design research. (SK)

  8. A Model of the Human Eye

    Science.gov (United States)

    Colicchia, G.; Wiesner, H.; Waltner, C.; Zollman, D.

    2008-01-01

    We describe a model of the human eye that incorporates a variable converging lens. The model can be easily constructed by students with low-cost materials. It shows in a comprehensible way the functionality of the eye's optical system. Images of near and far objects can be focused. Also, the defects of near and farsighted eyes can be demonstrated.

  9. Interior Design Research: A Human Ecosystem Model.

    Science.gov (United States)

    Guerin, Denise A.

    1992-01-01

    The interior ecosystems model illustrates effects on the human organism of the interaction of the natural, behavioral, and built environment. Examples of interior lighting and household energy consumption show the model's flexibility for organizing study variables in interior design research. (SK)

  10. Peginterferon Beta-1a Shows Antitumor Activity as a Single Agent and Enhances Efficacy of Standard of Care Cancer Therapeutics in Human Melanoma, Breast, Renal, and Colon Xenograft Models.

    Science.gov (United States)

    Boccia, Antonio; Virata, Cyrus; Lindner, Daniel; English, Nicki; Pathan, Nuzhat; Brickelmaier, Margot; Hu, Xiao; Gardner, Jennifer L; Peng, Liaomin; Wang, Xinzhong; Zhang, Xiamei; Yang, Lu; Perron, Keli; Yco, Grace; Kelly, Rebecca; Gamez, James; Scripps, Thomas; Bennett, Donald; Joseph, Ingrid B; Baker, Darren P

    2017-01-01

    Because of its tumor-suppressive effect, interferon-based therapy has been used for the treatment of melanoma. However, limited data are available regarding the antitumor effects of pegylated interferons, either alone or in combination with approved anticancer drugs. We report that treatment of human WM-266-4 melanoma cells with peginterferon beta-1a induced apoptotic markers. Additionally, peginterferon beta-1a significantly inhibited the growth of human SK-MEL-1, A-375, and WM-266-4 melanoma xenografts established in immunocompromised mice. Peginterferon beta-1a regressed large, established WM-266-4 xenografts in nude mice. Treatment of SK-MEL-1 tumor-bearing mice with a combination of peginterferon beta-1a and the MEK inhibitor PD325901 ((R)-N-(2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzamide) significantly improved tumor growth inhibition compared with either agent alone. Examination of the antitumor activity of peginterferon beta-1a in combination with approved anticancer drugs in breast and renal carcinomas revealed improved antitumor activity in these preclinical xenograft models, as did the combination of peginterferon beta-1a and bevacizumab in a colon carcinoma xenograft model.

  11. Human temporal cortical single neuron activity during working memory maintenance.

    Science.gov (United States)

    Zamora, Leona; Corina, David; Ojemann, George

    2016-06-01

    The Working Memory model of human memory, first introduced by Baddeley and Hitch (1974), has been one of the most influential psychological constructs in cognitive psychology and human neuroscience. However the neuronal correlates of core components of this model have yet to be fully elucidated. Here we present data from two studies where human temporal cortical single neuron activity was recorded during tasks differentially affecting the maintenance component of verbal working memory. In Study One we vary the presence or absence of distracting items for the entire period of memory storage. In Study Two we vary the duration of storage so that distractors filled all, or only one-third of the time the memory was stored. Extracellular single neuron recordings were obtained from 36 subjects undergoing awake temporal lobe resections for epilepsy, 25 in Study one, 11 in Study two. Recordings were obtained from a total of 166 lateral temporal cortex neurons during performance of one of these two tasks, 86 study one, 80 study two. Significant changes in activity with distractor manipulation were present in 74 of these neurons (45%), 38 Study one, 36 Study two. In 48 (65%) of those there was increased activity during the period when distracting items were absent, 26 Study One, 22 Study Two. The magnitude of this increase was greater for Study One, 47.6%, than Study Two, 8.1%, paralleling the reduction in memory errors in the absence of distracters, for Study One of 70.3%, Study Two 26.3% These findings establish that human lateral temporal cortex is part of the neural system for working memory, with activity during maintenance of that memory that parallels performance, suggesting it represents active rehearsal. In 31 of these neurons (65%) this activity was an extension of that during working memory encoding that differed significantly from the neural processes recorded during overt and silent language tasks without a recent memory component, 17 Study one, 14 Study two

  12. Human Muscle Fatigue Model in Dynamic Motions

    CERN Document Server

    Ma, Ruina; Bennis, Fouad; Ma, Liang

    2012-01-01

    Human muscle fatigue is considered to be one of the main reasons for Musculoskeletal Disorder (MSD). Recent models have been introduced to define muscle fatigue for static postures. However, the main drawbacks of these models are that the dynamic effect of the human and the external load are not taken into account. In this paper, each human joint is assumed to be controlled by two muscle groups to generate motions such as push/pull. The joint torques are computed using Lagrange's formulation to evaluate the dynamic factors of the muscle fatigue model. An experiment is defined to validate this assumption and the result for one person confirms its feasibility. The evaluation of this model can predict the fatigue and MSD risk in industry production quickly.

  13. ASSESSMENT OF HUMAN RESOURCES FOR REGIONAL INNOVATION ACTIVITY

    Directory of Open Access Journals (Sweden)

    R. R. Lukyanova

    2010-03-01

    Full Text Available The paper deals with the issues of human resource development regarding an innovation activity. Concepts of labor and human resources have been surveyed. An integral index for assessment of human resources for regional innovation activity has been developed and assessment of the Russian regions has been made on the basis of it. Development tendencies of modern human resources for innovation activity in Russia have been revealed.

  14. Planning as a part of human resource management activities

    OpenAIRE

    Kulić, Živko; Milošević, Goran

    2012-01-01

    Human resource management activities are most often grouped, or classified in that they are reduced to some ten basic activities. These activities are considered to be: work analysis; human resource planning; human resource recruitment; human resource selection; employee socialization and orientation; employee training and education; employee performance evaluation; employee rewarding and motivating; employee health and security; career management, and employee degradation and lying off. The ...

  15. Mathematical models of human african trypanosomiasis epidemiology.

    Science.gov (United States)

    Rock, Kat S; Stone, Chris M; Hastings, Ian M; Keeling, Matt J; Torr, Steve J; Chitnis, Nakul

    2015-03-01

    Human African trypanosomiasis (HAT), commonly called sleeping sickness, is caused by Trypanosoma spp. and transmitted by tsetse flies (Glossina spp.). HAT is usually fatal if untreated and transmission occurs in foci across sub-Saharan Africa. Mathematical modelling of HAT began in the 1980s with extensions of the Ross-Macdonald malaria model and has since consisted, with a few exceptions, of similar deterministic compartmental models. These models have captured the main features of HAT epidemiology and provided insight on the effectiveness of the two main control interventions (treatment of humans and tsetse fly control) in eliminating transmission. However, most existing models have overestimated prevalence of infection and ignored transient dynamics. There is a need for properly validated models, evolving with improved data collection, that can provide quantitative predictions to help guide control and elimination strategies for HAT.

  16. Quantitative Modeling of Human-Environment Interactions in Preindustrial Time

    Science.gov (United States)

    Sommer, Philipp S.; Kaplan, Jed O.

    2017-04-01

    Quantifying human-environment interactions and anthropogenic influences on the environment prior to the Industrial revolution is essential for understanding the current state of the earth system. This is particularly true for the terrestrial biosphere, but marine ecosystems and even climate were likely modified by human activities centuries to millennia ago. Direct observations are however very sparse in space and time, especially as one considers prehistory. Numerical models are therefore essential to produce a continuous picture of human-environment interactions in the past. Agent-based approaches, while widely applied to quantifying human influence on the environment in localized studies, are unsuitable for global spatial domains and Holocene timescales because of computational demands and large parameter uncertainty. Here we outline a new paradigm for the quantitative modeling of human-environment interactions in preindustrial time that is adapted to the global Holocene. Rather than attempting to simulate agency directly, the model is informed by a suite of characteristics describing those things about society that cannot be predicted on the basis of environment, e.g., diet, presence of agriculture, or range of animals exploited. These categorical data are combined with the properties of the physical environment in coupled human-environment model. The model is, at its core, a dynamic global vegetation model with a module for simulating crop growth that is adapted for preindustrial agriculture. This allows us to simulate yield and calories for feeding both humans and their domesticated animals. We couple this basic caloric availability with a simple demographic model to calculate potential population, and, constrained by labor requirements and land limitations, we create scenarios of land use and land cover on a moderate-resolution grid. We further implement a feedback loop where anthropogenic activities lead to changes in the properties of the physical

  17. Activity of protease-activated receptors in primary cultured human myenteric neurons

    Directory of Open Access Journals (Sweden)

    Eva Maria Kugler

    2012-09-01

    Full Text Available Activity of the four known protease-activated receptors (PARs has been well studied in rodent enteric nervous system and results in animal models established an important role for neuronal PAR2. We recently demonstrated that, unlike in rodents, PAR1 is the dominant neuronal protease receptor in the human submucous plexus. With this study we investigated whether this also applies to the human myenteric plexus. We used voltage sensitive dye recordings to detect action potential discharge in primary cultures of human myenteric neurons in response to PAR activating peptides (AP. Application of the PAR1-AP (TFLLR or PAR4-AP (GYPGQV evoked spike discharge in 79% or 23% of myenteric neurons, respectively. The PAR1-AP response was mimicked by the endogenous PAR1 activator thrombin and blocked by the PAR1 antagonists SCH79797. Human myenteric neurons did not respond to PAR2-AP. This was not due to culture conditions because all three PAR-APs evoked action potentials in cultured guinea pig myenteric neurons. Consecutive application of PAR-APs revealed coexpression (relative to the population responding to PAR-APs of PAR1/PAR2 in 51%, PAR1/PAR4 in 43% and of PAR2/PAR4 in 29% of guinea pig myenteric neurons. Our study provided further evidence for the prominent role of neuronal PAR1 in the human enteric nervous system.

  18. Knock-in human FGFR3 achondroplasia mutation as a mouse model for human skeletal dysplasia

    Science.gov (United States)

    Lee, Yi-Ching; Song, I-Wen; Pai, Ya-Ju; Chen, Sheng-De; Chen, Yuan-Tsong

    2017-01-01

    Achondroplasia (ACH), the most common genetic dwarfism in human, is caused by a gain-of function mutation in fibroblast growth factor receptor 3 (FGFR3). Currently, there is no effective treatment for ACH. The development of an appropriate human-relevant model is important for testing potential therapeutic interventions before human clinical trials. Here, we have generated an ACH mouse model in which the endogenous mouse Fgfr3 gene was replaced with human FGFR3G380R (FGFR3ACH) cDNA, the most common mutation in human ACH. Heterozygous (FGFR3ACH/+) and homozygous (FGFR3ACH/ACH) mice expressing human FGFR3G380R recapitulate the phenotypes observed in ACH patients, including growth retardation, disproportionate shortening of the limbs, round head, mid-face hypoplasia at birth, and kyphosis progression during postnatal development. We also observed premature fusion of the cranial sutures and low bone density in newborn FGFR3G380R mice. The severity of the disease phenotypes corresponds to the copy number of activated FGFR3G380R, and the phenotypes become more pronounced during postnatal skeletal development. This mouse model offers a tool for assessing potential therapeutic approaches for skeletal dysplasias related to over-activation of human FGFR3, and for further studies of the underlying molecular mechanisms. PMID:28230213

  19. Human models of acute lung injury

    Directory of Open Access Journals (Sweden)

    Alastair G. Proudfoot

    2011-03-01

    Full Text Available Acute lung injury (ALI is a syndrome that is characterised by acute inflammation and tissue injury that affects normal gas exchange in the lungs. Hallmarks of ALI include dysfunction of the alveolar-capillary membrane resulting in increased vascular permeability, an influx of inflammatory cells into the lung and a local pro-coagulant state. Patients with ALI present with severe hypoxaemia and radiological evidence of bilateral pulmonary oedema. The syndrome has a mortality rate of approximately 35% and usually requires invasive mechanical ventilation. ALI can follow direct pulmonary insults, such as pneumonia, or occur indirectly as a result of blood-borne insults, commonly severe bacterial sepsis. Although animal models of ALI have been developed, none of them fully recapitulate the human disease. The differences between the human syndrome and the phenotype observed in animal models might, in part, explain why interventions that are successful in models have failed to translate into novel therapies. Improved animal models and the development of human in vivo and ex vivo models are therefore required. In this article, we consider the clinical features of ALI, discuss the limitations of current animal models and highlight how emerging human models of ALI might help to answer outstanding questions about this syndrome.

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

    Science.gov (United States)

    Gootenberg, D B; Turnbaugh, P J

    2011-05-01

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

  1. Mathematical modeling of the human knee joint

    Energy Technology Data Exchange (ETDEWEB)

    Ricafort, Juliet [Univ. of Southern California, Los Angeles, CA (United States). Dept. of Biomedical Engineering

    1996-05-01

    A model was developed to determine the forces exerted by several flexor and extensor muscles of the human knee under static conditions. The following muscles were studied: the gastrocnemius, biceps femoris, semitendinosus, semimembranosus, and the set of quadricep muscles. The tibia and fibula were each modeled as rigid bodies; muscles were modeled by their functional lines of action in space. Assumptions based on previous data were used to resolve the indeterminacy.

  2. Conceptual Data Modelling of Modern Human Migration

    Directory of Open Access Journals (Sweden)

    Kosta Sotiroski

    2012-12-01

    Full Text Available The processes of human migrations have been present for ages, since the very beginnings of human history on the planet Earth. Nowadays, these are amplified to a large scale due to the modern means of communication, transportation, information and knowledge exchange, as well as the complex processes of globalization. Knowing the social, demographic, ethnical and educational structure of the migrants, as well as their geographical trajectory and temporal dynamics of their spatial moving across territories, countries and continents, is of a crucial meaning for both national governments and international policies. There is an emphasized need for identifying, acquiring, organizing, storing, retrieving and analyzing data related to human migration processes. The relational databases provide an ultimate solution, whilst the E-R diagram represents a common graphical tool for conceptual data modelling and relational database design. Within the paper we develop and propose a logical data model of the modern human migration.

  3. Preclinical and human surrogate models of itch

    DEFF Research Database (Denmark)

    Hoeck, Emil August; Marker, Jens Broch; Gazerani, Parisa;

    2016-01-01

    Pruritus, or simply itch, is a debilitating symptom that significantly decreases the quality of life in a wide range of clinical conditions. While histamine remains the most studied mediator of itch in humans, treatment options for chronic itch, in particular antihistamine-resistant itch, are lim...... currently applied in animals and humans. This article is protected by copyright. All rights reserved.......Pruritus, or simply itch, is a debilitating symptom that significantly decreases the quality of life in a wide range of clinical conditions. While histamine remains the most studied mediator of itch in humans, treatment options for chronic itch, in particular antihistamine-resistant itch......, are limited. Relevant preclinical and human surrogate models of non-histaminergic itch are needed to accelerate the development of novel antipruritics and diagnostic tools. Advances in basic itch research have facilitated the development of diverse models of itch and associated dysesthesiae. While...

  4. Circulating factors induce coronary endothelial cell activation following exposure to inhaled diesel exhaust and nitrogen dioxide in humans: Evidence from a novel translational in vitro model**

    Science.gov (United States)

    The vascular toxicity of inhaled agents may be caused by soluble factors that are released into the systemic circulation. To confirm this in a straightforward manner, we obtained plasma from healthy human volunteers before and after exposure to diesel exhaust (DE) and nitrogen di...

  5. CGRP in human models of primary headaches

    DEFF Research Database (Denmark)

    Ashina, Håkan; Schytz, Henrik Winther; Ashina, Messoud

    2017-01-01

    experiments are likely due to assay variation; therefore, proper validation and standardization of an assay is needed. To what extent CGRP is involved in tension-type headache and cluster headache is unknown. CONCLUSION: Human models of primary headaches have elucidated the role of CGRP in headache......OBJECTIVE: To review the role of CGRP in human models of primary headaches and to discuss methodological aspects and future directions. DISCUSSION: Provocation experiments demonstrated a heterogeneous CGRP migraine response in migraine patients. Conflicting CGRP plasma results in the provocation...... pathophysiology and sparked great interest in developing new treatment strategies using CGRP antagonists and antibodies. Future studies applying more refined human experimental models should identify biomarkers of CGRP-induced primary headache and reveal whether CGRP provocation experiments could be used...

  6. Modeling and percept of transcorneal electrical stimulation in humans.

    Science.gov (United States)

    Xie, John; Wang, Gene-Jack; Yow, Lindy; J Cela, Carlos; Humayun, Mark S; Weiland, James D; Lazzi, Gianluca; Jadvar, Hossein

    2011-07-01

    Retinal activation via transcorneal electrical stimulation (TcES) in normal humans was investigated by comparing subject perception, model predictions, and brain activation patterns. The preferential location of retinal stimulation was predicted from 3-D admittance modeling. Visual cortex activation was measured using positron emission tomography (PET) and (18)F-fluorodeoxyglucose (FDG). Two different corneal electrodes were investigated: DTL-Plus and ERG-Jet. Modeling results predicted preferential stimulation of the peripheral, inferior, nasal retina during right eye TcES using DTL-Plus, but more extensive activation of peripheral, nasal hemiretina using ERG-Jet. The results from human FDG PET study using both corneal electrodes showed areas of visual cortex activation that consistently corresponded with the reported phosphene percept and modeling predictions. ERG-Jet was able to generate brighter phosphene percept than DTL-Plus and elicited retinotopically mapped primary visual cortex activation. This study demonstrates that admittance modeling and PET imaging consistently predict the perceived location of electrically elicited phosphenes produced during TcES.

  7. Animal and human models to understand ageing.

    Science.gov (United States)

    Lees, Hayley; Walters, Hannah; Cox, Lynne S

    2016-11-01

    Human ageing is the gradual decline in organ and tissue function with increasing chronological time, leading eventually to loss of function and death. To study the processes involved over research-relevant timescales requires the use of accessible model systems that share significant similarities with humans. In this review, we assess the usefulness of various models, including unicellular yeasts, invertebrate worms and flies, mice and primates including humans, and highlight the benefits and possible drawbacks of each model system in its ability to illuminate human ageing mechanisms. We describe the strong evolutionary conservation of molecular pathways that govern cell responses to extracellular and intracellular signals and which are strongly implicated in ageing. Such pathways centre around insulin-like growth factor signalling and integration of stress and nutritional signals through mTOR kinase. The process of cellular senescence is evaluated as a possible underlying cause for many of the frailties and diseases of human ageing. Also considered is ageing arising from systemic changes that cannot be modelled in lower organisms and instead require studies either in small mammals or in primates. We also touch briefly on novel therapeutic options arising from a better understanding of the biology of ageing. Copyright © 2016. Published by Elsevier Ireland Ltd.

  8. Early development of synchrony in cortical activations in the human.

    Science.gov (United States)

    Koolen, N; Dereymaeker, A; Räsänen, O; Jansen, K; Vervisch, J; Matic, V; Naulaers, G; De Vos, M; Van Huffel, S; Vanhatalo, S

    2016-05-13

    Early intermittent cortical activity is thought to play a crucial role in the growth of neuronal network development, and large scale brain networks are known to provide the basis for higher brain functions. Yet, the early development of the large scale synchrony in cortical activations is unknown. Here, we tested the hypothesis that the early intermittent cortical activations seen in the human scalp EEG show a clear developmental course during the last trimester of pregnancy, the period of intensive growth of cortico-cortical connections. We recorded scalp EEG from altogether 22 premature infants at post-menstrual age between 30 and 44 weeks, and the early cortical synchrony was quantified using recently introduced activation synchrony index (ASI). The developmental correlations of ASI were computed for individual EEG signals as well as anatomically and mathematically defined spatial subgroups. We report two main findings. First, we observed a robust and statistically significant increase in ASI in all cortical areas. Second, there were significant spatial gradients in the synchrony in fronto-occipital and left-to-right directions. These findings provide evidence that early cortical activity is increasingly synchronized across the neocortex. The ASI-based metrics introduced in our work allow direct translational comparison to in vivo animal models, as well as hold promise for implementation as a functional developmental biomarker in future research on human neonates.

  9. Activity clocks: spreading dynamics on temporal networks of human contact

    CERN Document Server

    Gauvin, Laetitia; Cattuto, Ciro; Barrat, Alain

    2013-01-01

    Dynamical processes on time-varying complex networks are key to un- derstanding and modeling a broad variety of processes in socio-technical systems. Here we focus on empirical temporal networks of human proxim- ity and we aim at understanding the factors that, in simulation, shape the arrival time distribution of simple spreading processes. Abandoning the notion of wall-clock time in favour of node-specific clocks based on activ- ity exposes robust statistical patterns in the arrival times across different social contexts. Using randomization strategies and generative models constrained by data, we show that these patterns can be understood in terms of heterogeneous inter-event time distributions coupled with hetero- geneous numbers of events per edge. We also show, both empirically and by using a synthetic dataset, that significant deviations from the above behavior can be caused by the presence of edge classes with strong activity correlations.

  10. A stochastic model of human gait dynamics

    Science.gov (United States)

    Ashkenazy, Yosef; M. Hausdorff, Jeffrey; Ch. Ivanov, Plamen; Eugene Stanley, H.

    2002-12-01

    We present a stochastic model of gait rhythm dynamics, based on transitions between different “neural centers”, that reproduces distinctive statistical properties of normal human walking. By tuning one model parameter, the transition (hopping) range, the model can describe alterations in gait dynamics from childhood to adulthood-including a decrease in the correlation and volatility exponents with maturation. The model also generates time series with multifractal spectra whose broadness depends only on this parameter. Moreover, we find that the volatility exponent increases monotonically as a function of the width of the multifractal spectrum, suggesting the possibility of a change in multifractality with maturation.

  11. Combining Users' Activity Survey and Simulators to Evaluate Human Activity Recognition Systems

    Science.gov (United States)

    Azkune, Gorka; Almeida, Aitor; López-de-Ipiña, Diego; Chen, Liming

    2015-01-01

    Evaluating human activity recognition systems usually implies following expensive and time-consuming methodologies, where experiments with humans are run with the consequent ethical and legal issues. We propose a novel evaluation methodology to overcome the enumerated problems, which is based on surveys for users and a synthetic dataset generator tool. Surveys allow capturing how different users perform activities of daily living, while the synthetic dataset generator is used to create properly labelled activity datasets modelled with the information extracted from surveys. Important aspects, such as sensor noise, varying time lapses and user erratic behaviour, can also be simulated using the tool. The proposed methodology is shown to have very important advantages that allow researchers to carry out their work more efficiently. To evaluate the approach, a synthetic dataset generated following the proposed methodology is compared to a real dataset computing the similarity between sensor occurrence frequencies. It is concluded that the similarity between both datasets is more than significant. PMID:25856329

  12. Specific activity of radioiodine-labelled human chorionic gonadotropin ligand

    Energy Technology Data Exchange (ETDEWEB)

    Crespi, M. (South African Inst. for Medical Research, Sandringham. National Inst. for Virology); Kay, G.W.; Van der Walt, L.A. (South African Inst. for Medical Research, Johannesburg. Dept. of Pathology)

    1983-10-01

    The article deals with the determination of the specific activity of radioiodine-labelled human chorionic gonadotropin ligand. The iodiation of human chorionic gonadotropin and the counting efficiency of /sup 125/I are discussed.

  13. Exergy Analysis of Human Respiration Under Physical Activity

    Directory of Open Access Journals (Sweden)

    Jurandir Itizo Yanagihara

    2010-09-01

    Full Text Available

    This paper presents an exergy analysis of the human body under physical activity. A model of the respiratory system and a model of the thermal system were used for this purpose. These models consider heat and mass transfers in lungs, tissues and blood. Each component of these models is represented by a uniform compartment governed by equations for diffusion, convection, O2 consumption, CO2/heat generation and heat and mass transfer with the environment. The models allow the calculation of the exergy destruction in the lung and tissues, and the contribution of each entropy generation mechanism in the total generation. Furthermore, a discussion is proposed regarding the efficiency of the human body under physical exercise.

  14. Analisis Model Pengukuran Human Capital dalam Organisasi

    Directory of Open Access Journals (Sweden)

    Cecep Hidayat

    2013-11-01

    Full Text Available Measurement of human capital is not an easy to do because it is dynamic and always changing in accordance with the changing circumstances. Determination of dimensions and indicators of measurement needs to consider various factors such as situations and also the research scopes. This article has objectives to review the concepts, dimensions and measurement models of human capital. The research method used was literature study with a major reference source from current journal articles that discuss the measurement of human capital. Results of the study showed that basically the definition set forth in any dimension containing either explicitly or implicitly. In addition, the result indicated that there are three main categories of equality among researchers regarding the definition of human capital which emphasizes on: economic value/productivity, education, and abilities/competencies. The results also showed that the use of definitions, dimensions, and indicators for measurement of human capital depends on the situation, the scope of research, and the size of the organization. The conclusion of the study indicated that the measurement model and determination of dimensions and indicators of human capital measurement will determine the effectiveness of the measurement, and will have an impact on organizational performance.

  15. Engineering large animal models of human disease.

    Science.gov (United States)

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

    2016-01-01

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

  16. Enhanced casein kinase II activity in human tumour cell cultures

    DEFF Research Database (Denmark)

    Prowald, K; Fischer, H; Issinger, O G

    1984-01-01

    Casein kinase II (CKII) activity is enhanced as much as 2-3 fold in established and 4-5-fold in transformed human cell lines when compared to that of fibroblasts and primary human tumour cell cultures where CKII activity never exceeded a basic level. The high activity of CKII in transformed cells...

  17. Bayesian Modeling of a Human MMORPG Player

    CERN Document Server

    Synnaeve, Gabriel

    2010-01-01

    This paper describes an application of Bayesian programming to the control of an autonomous avatar in a multiplayer role-playing game (the example is based on World of Warcraft). We model a particular task, which consists of choosing what to do and to select which target in a situation where allies and foes are present. We explain the model in Bayesian programming and show how we could learn the conditional probabilities from data gathered during human-played sessions.

  18. Bayesian Modeling of a Human MMORPG Player

    Science.gov (United States)

    Synnaeve, Gabriel; Bessière, Pierre

    2011-03-01

    This paper describes an application of Bayesian programming to the control of an autonomous avatar in a multiplayer role-playing game (the example is based on World of Warcraft). We model a particular task, which consists of choosing what to do and to select which target in a situation where allies and foes are present. We explain the model in Bayesian programming and show how we could learn the conditional probabilities from data gathered during human-played sessions.

  19. Human ex vivo wound healing model.

    Science.gov (United States)

    Stojadinovic, Olivera; Tomic-Canic, Marjana

    2013-01-01

    Wound healing is a spatially and temporally regulated process that progresses through sequential, yet overlapping phases and aims to restore barrier breach. To study this complex process scientists use various in vivo and in vitro models. Here we provide step-by-step instructions on how to perform and employ an ex vivo wound healing model to assess epithelization during wound healing in human skin.

  20. Coupling of the Models of Human Physiology and Thermal Comfort

    Science.gov (United States)

    Pokorny, J.; Jicha, M.

    2013-04-01

    A coupled model of human physiology and thermal comfort was developed in Dymola/Modelica. A coupling combines a modified Tanabe model of human physiology and thermal comfort model developed by Zhang. The Coupled model allows predicting the thermal sensation and comfort of both local and overall from local boundary conditions representing ambient and personal factors. The aim of this study was to compare prediction of the Coupled model with the Fiala model prediction and experimental data. Validation data were taken from the literature, mainly from the validation manual of software Theseus-FE [1]. In the paper validation of the model for very light physical activities (1 met) indoor environment with temperatures from 12 °C up to 48 °C is presented. The Coupled model predicts mean skin temperature for cold, neutral and warm environment well. However prediction of core temperature in cold environment is inaccurate and very affected by ambient temperature. Evaluation of thermal comfort in warm environment is supplemented by skin wettedness prediction. The Coupled model is designed for non-uniform and transient environmental conditions; it is also suitable simulation of thermal comfort in vehicles cabins. The usage of the model is limited for very light physical activities up to 1.2 met only.

  1. Human Communication--A New Model.

    Science.gov (United States)

    McLeish, John

    1978-01-01

    Pavlov's organism-in-the-environment model was adapted to a functional analysis of communication, expecially abstract and symbolic activities. A classification of discrimination response and reinforcement patterns was given. (CP)

  2. Modelling dengue epidemic spreading with human mobility

    Science.gov (United States)

    Barmak, D. H.; Dorso, C. O.; Otero, M.

    2016-04-01

    We explored the effect of human mobility on the spatio-temporal dynamics of Dengue with a stochastic model that takes into account the epidemiological dynamics of the infected mosquitoes and humans, with different mobility patterns of the human population. We observed that human mobility strongly affects the spread of infection by increasing the final size and by changing the morphology of the epidemic outbreaks. When the spreading of the disease is driven only by mosquito dispersal (flight), a main central focus expands diffusively. On the contrary, when human mobility is taken into account, multiple foci appear throughout the evolution of the outbreaks. These secondary foci generated throughout the outbreaks could be of little importance according to their mass or size compared with the largest main focus. However, the coalescence of these foci with the main one generates an effect, through which the latter develops a size greater than the one obtained in the case driven only by mosquito dispersal. This increase in growth rate due to human mobility and the coalescence of the foci are particularly relevant in temperate cities such as the city of Buenos Aires, since they give more possibilities to the outbreak to grow before the arrival of the low-temperature season. The findings of this work indicate that human mobility could be the main driving force in the dynamics of vector epidemics.

  3. AN EFFECTIVE HUMAN LEG MODELING METHOD

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Digital medicine is a new concept in medical field, and the need for digital human body is increasing these years. This paper used Free Form Deformation (FFD) to model the motion of human leg. It presented the motion equations of knee joint on the basis of anatomic structure and motion characters, then transmitted the deformation to the mesh of leg through a simplified FFD that only used two-order B-spline basis function. The experiments prove that this method can simulate the bend of leg and the deformation of muscles fairly well. Compared with the method of curved patches, this method is more convenient and effective. Further more, those equations can be easily applied to other joint models of human body.

  4. Modeling human craniofacial disorders in Xenopus.

    Science.gov (United States)

    Dubey, Aditi; Saint-Jeannet, Jean-Pierre

    2017-03-01

    Craniofacial disorders are among the most common human birth defects and present an enormous health care and social burden. The development of animal models has been instrumental to investigate fundamental questions in craniofacial biology and this knowledge is critical to understand the etiology and pathogenesis of these disorders. The vast majority of craniofacial disorders arise from abnormal development of the neural crest, a multipotent and migratory cell population. Therefore, defining the pathogenesis of these conditions starts with a deep understanding of the mechanisms that preside over neural crest formation and its role in craniofacial development. This review discusses several studies using Xenopus embryos to model human craniofacial conditions, and emphasizes the strength of this system to inform important biological processes as they relate to human craniofacial development and disease.

  5. An Outline Course on Human Performance Modeling

    Science.gov (United States)

    2006-01-01

    complementary or competing tasks: Dario SaIvucci, ??? 46. Bonnie Johns, David Kieras 47. ecological interface design 48. More into modeling human... alarcon 70. Ben Knott 71. Evelyn Rozanski 7.Pete Khooshabeh Optional: If ou would like to be on a mailin list for further seminars lease enter our email

  6. Modeling human muscle disease in zebrafish

    OpenAIRE

    Guyon, Jeffrey R.; Steffen, Leta S; Howell, Melanie H.; Pusack, Timothy J; Lawrence, Chris; Kunkel, Louis M

    2007-01-01

    Modeling human muscle disease in zebrafish correspondence: Corresponding author. Children's Hospital Boston, Enders Bldg, Rm 570, 300 Longwood Ave Boston, MA 02115. Tel.: +1 617 355 7576. (Kunkel, Louis M.) (Kunkel, Louis M.) Program in Genomics and Howard Hughes Medical Institute at Children's Hospital Boston - Boston--> , MA 02115--> - UNITED STATES (Guyon, Jeffrey R.) Program in Genomics a...

  7. Modeling and Simulating Virtual Anatomical Humans

    NARCIS (Netherlands)

    Madehkhaksar, Forough; Luo, Zhiping; Pronost, Nicolas; Egges, Arjan

    2014-01-01

    This chapter presents human musculoskeletal modeling and simulation as a challenging field that lies between biomechanics and computer animation. One of the main goals of computer animation research is to develop algorithms and systems that produce plausible motion. On the other hand, the main chall

  8. Future of human models for crash analysis

    NARCIS (Netherlands)

    Wismans, J.S.H.M.; Happee, R.; Hoof, J.F.A.M. van; Lange, R. de

    2001-01-01

    In the crash safety field mathematical models can be applied in practically all area's of research and development including: reconstruction of actual accidents, design (CAD) of the crash response of vehicles, safety devices and roadside facilities and in support of human impact biomechanical

  9. Future of human models for crash analysis

    NARCIS (Netherlands)

    Wismans, J.S.H.M.; Happee, R.; Hoof, J.F.A.M. van; Lange, R. de

    2001-01-01

    In the crash safety field mathematical models can be applied in practically all area's of research and development including: reconstruction of actual accidents, design (CAD) of the crash response of vehicles, safety devices and roadside facilities and in support of human impact biomechanical studie

  10. The Long and the Short of It: Comments on Multiple Timescale Studies of Human Activity.

    Science.gov (United States)

    Lemke, Jay L.

    2001-01-01

    Comments on four articles in a special issue of the Journal of the Learning Sciences on methodology in learning sciences. Analyzes the articles within a general model seeking to analyze human activity across multiple time scales. (Author/MM)

  11. Intra-urban human mobility and activity transition: evidence from social media check-in data

    National Research Council Canada - National Science Library

    Wu, Lun; Zhi, Ye; Sui, Zhengwei; Liu, Yu

    2014-01-01

    .... In this research, we combine activity-based analysis with a movement-based approach to model the intra-urban human mobility observed from about 15 million check-in records during a yearlong period in Shanghai, China...

  12. 78 FR 8192 - Agency Information Collection Activities: Comment Request; Education and Human Resources Project...

    Science.gov (United States)

    2013-02-05

    ... From the Federal Register Online via the Government Publishing Office NATIONAL SCIENCE FOUNDATION Agency Information Collection Activities: Comment Request; Education and Human Resources Project... study will assess the implementation of resources, models, and technologies to determine how and why...

  13. The effect of agave fructan products on the activity and composition of the microbiota determined in a dynamic in vitro model of the human proximal large intestine

    NARCIS (Netherlands)

    Koenen, M.E.; Cruz Rubio, J.M.; Mueller, M.; Venema, K.

    2016-01-01

    Inulin and trans-galactooligosaccharides have so far fully met the criteria for prebiotics. This study shows the effect of putative prebiotics Metlos and Metlin (short and medium chain branched fructans from agave) on the activity and composition of the gut microbiota compared to the effects of two

  14. The effect of agave fructan products on the activity and composition of the microbiota determined in a dynamic in vitro model of the human proximal large intestine

    NARCIS (Netherlands)

    Koenen, M.E.; Cruz Rubio, J.M.; Mueller, M.; Venema, K.

    2016-01-01

    Inulin and trans-galactooligosaccharides have so far fully met the criteria for prebiotics. This study shows the effect of putative prebiotics Metlos and Metlin (short and medium chain branched fructans from agave) on the activity and composition of the gut microbiota compared to the effects of two

  15. A Review on Video-Based Human Activity Recognition

    Directory of Open Access Journals (Sweden)

    Shian-Ru Ke

    2013-06-01

    Full Text Available This review article surveys extensively the current progresses made toward video-based human activity recognition. Three aspects for human activity recognition are addressed including core technology, human activity recognition systems, and applications from low-level to high-level representation. In the core technology, three critical processing stages are thoroughly discussed mainly: human object segmentation, feature extraction and representation, activity detection and classification algorithms. In the human activity recognition systems, three main types are mentioned, including single person activity recognition, multiple people interaction and crowd behavior, and abnormal activity recognition. Finally the domains of applications are discussed in detail, specifically, on surveillance environments, entertainment environments and healthcare systems. Our survey, which aims to provide a comprehensive state-of-the-art review of the field, also addresses several challenges associated with these systems and applications. Moreover, in this survey, various applications are discussed in great detail, specifically, a survey on the applications in healthcare monitoring systems.

  16. Testing the Role of p21-Activated Kinases in Schwannoma Formation Using a Novel Genetically Engineered Murine Model that Closely Phenocopies Human NF2 Disease

    Science.gov (United States)

    2016-06-01

    Chernoff, Jonathan Remaining Salary Support from Institutional resources. ACTIVE R01 NS066927 (PI: Li, Vanderbilt Univ.) 3/1/2015 - 2/29/ 2020 ...This project is a subcontract to University of New Mexico Cancer Center (UNMCC). The major goals of this project are: 1) To evaluate the functional...Vinyardk, SPO, MSC09 5220 1 University of New Mexico , Albuquerque, NM 87131, 505-272-0159 OVERLAP None COMPLETED None 10 Program Director

  17. Constructing predictive models of human running.

    Science.gov (United States)

    Maus, Horst-Moritz; Revzen, Shai; Guckenheimer, John; Ludwig, Christian; Reger, Johann; Seyfarth, Andre

    2015-02-06

    Running is an essential mode of human locomotion, during which ballistic aerial phases alternate with phases when a single foot contacts the ground. The spring-loaded inverted pendulum (SLIP) provides a starting point for modelling running, and generates ground reaction forces that resemble those of the centre of mass (CoM) of a human runner. Here, we show that while SLIP reproduces within-step kinematics of the CoM in three dimensions, it fails to reproduce stability and predict future motions. We construct SLIP control models using data-driven Floquet analysis, and show how these models may be used to obtain predictive models of human running with six additional states comprising the position and velocity of the swing-leg ankle. Our methods are general, and may be applied to any rhythmic physical system. We provide an approach for identifying an event-driven linear controller that approximates an observed stabilization strategy, and for producing a reduced-state model which closely recovers the observed dynamics. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  18. Model of human visual-motion sensing

    Science.gov (United States)

    Watson, A. B.; Ahumada, A. J., Jr.

    1985-01-01

    A model of how humans sense the velocity of moving images is proposed. The model exploits constraints provided by human psychophysics, notably that motion-sensing elements appear tuned for two-dimensional spatial frequency, and by the frequency spectrum of a moving image, namely, that its support lies in the plane in which the temporal frequency equals the dot product of the spatial frequency and the image velocity. The first stage of the model is a set of spatial-frequency-tuned, direction-selective linear sensors. The temporal frequency of the response of each sensor is shown to encode the component of the image velocity in the sensor direction. At the second stage, these components are resolved in order to measure the velocity of image motion at each of a number of spatial locations and spatial frequencies. The model has been applied to several illustrative examples, including apparent motion, coherent gratings, and natural image sequences. The model agrees qualitatively with human perception.

  19. Space Station crew safety - Human factors model

    Science.gov (United States)

    Cohen, M. M.; Junge, M. K.

    1984-01-01

    A model of the various human factors issues and interactions that might affect crew safety is developed. The first step addressed systematically the central question: How is this Space Station different from all other spacecraft? A wide range of possible issue was identified and researched. Five major topics of human factors issues that interacted with crew safety resulted: Protocols, Critical Habitability, Work Related Issues, Crew Incapacitation and Personal Choice. Second, an interaction model was developed that would show some degree of cause and effect between objective environmental or operational conditions and the creation of potential safety hazards. The intermediary steps between these two extremes of causality were the effects on human performance and the results of degraded performance. The model contains three milestones: stressor, human performance (degraded) and safety hazard threshold. Between these milestones are two countermeasure intervention points. The first opportunity for intervention is the countermeasure against stress. If this countermeasure fails, performance degrades. The second opportunity for intervention is the countermeasure against error. If this second countermeasure fails, the threshold of a potential safety hazard may be crossed.

  20. Development of a realistic human airway model.

    Science.gov (United States)

    Lizal, Frantisek; Elcner, Jakub; Hopke, Philip K; Jedelsky, Jan; Jicha, Miroslav

    2012-03-01

    Numerous models of human lungs with various levels of idealization have been reported in the literature; consequently, results acquired using these models are difficult to compare to in vivo measurements. We have developed a set of model components based on realistic geometries, which permits the analysis of the effects of subsequent model simplification. A realistic digital upper airway geometry except for the lack of an oral cavity has been created which proved suitable both for computational fluid dynamics (CFD) simulations and for the fabrication of physical models. Subsequently, an oral cavity was added to the tracheobronchial geometry. The airway geometry including the oral cavity was adjusted to enable fabrication of a semi-realistic model. Five physical models were created based on these three digital geometries. Two optically transparent models, one with and one without the oral cavity, were constructed for flow velocity measurements, two realistic segmented models, one with and one without the oral cavity, were constructed for particle deposition measurements, and a semi-realistic model with glass cylindrical airways was developed for optical measurements of flow velocity and in situ particle size measurements. One-dimensional phase doppler anemometry measurements were made and compared to the CFD calculations for this model and good agreement was obtained.

  1. A comprehensive model for the humoral coagulation network in humans.

    Science.gov (United States)

    Wajima, T; Isbister, G K; Duffull, S B

    2009-09-01

    Coagulation is an important process in hemostasis and comprises a complicated interaction of multiple enzymes and proteins. We have developed a mechanistic quantitative model of the coagulation network. The model accurately describes the time courses of coagulation factors following in vivo activation as well as in vitro blood coagulation tests of prothrombin time (PT, often reported as international normalized ratio (INR)) and activated partial thromboplastin time (aPTT). The model predicts the concentration-time and time-effect profiles of warfarin, heparins, and vitamin K in humans. The model can be applied to predict the time courses of coagulation kinetics in clinical situations (e.g., hemophilia) and for biomarker identification during drug development. The model developed in this study is the first quantitative description of the comprehensive coagulation network.

  2. Synthesis, biological activity, and three-dimensional quantitative structure-activity relationship model for a series of benzo[c]quinolizin-3-ones, nonsteroidal inhibitors of human steroid 5alpha-reductase 1.

    Science.gov (United States)

    Occhiato, Ernesto G; Ferrali, Alessandro; Menchi, Gloria; Guarna, Antonio; Danza, Giovanna; Comerci, Alessandra; Mancina, Rosa; Serio, Mario; Garotta, Gianni; Cavalli, Andrea; De Vivo, Marco; Recanatini, Maurizio

    2004-07-01

    New 5alpha-reductase 1 (5alphaR-1) inhibitors were designed to complete a consistent set of analogues suitable for a 3D QSAR study. These compounds were synthesized by a modification of the aza-Robinson annulation, further functionalized by Pd-catalyzed cross-coupling processes, and were tested with human 5alphaR-1 expressed in Chinese hamster ovary 1827 cells. It turned out that the potency of the resulting inhibitors was strongly dependent on the type of substitution at the 8 position, with the IC(50) values ranging from 8.1 to 1050 nM. The construction of this homogeneous set of molecules allowed a 3D QSAR study. In particular, comparative molecular field analysis (CoMFA) was used to correlate the potency of the inhibitors with their physicochemical features. Highly accurate evaluations of the atomic point charges were carried out by means of quantum chemical calculations at the DFT/B3LYP level of theory followed by the RESP fitting procedure. It turned out that increasing the reliability of electrostatic parameters greatly affected the statistical results of the QSAR analysis. The 3D QSAR model proposed could be very useful in the further development of 5alphaR-1 inhibitors, which are suitable candidates to be evaluated as drugs in the treatment of 5alphaR-1 related diseases such as acne and alopecia in men and hirsutism in women.

  3. Are animal models relevant to key aspects of human parturition?

    Science.gov (United States)

    Mitchell, Bryan F; Taggart, Michael J

    2009-09-01

    Preterm birth remains the most serious complication of pregnancy and is associated with increased rates of infant death or permanent neurodevelopmental disability. Our understanding of the regulation of parturition remains inadequate. The scientific literature, largely derived from rodent animal models, suggests two major mechanisms regulating the timing of parturition: the withdrawal of the steroid hormone progesterone and a proinflammatory response by the immune system. However, available evidence strongly suggests that parturition in the human has significantly different regulators and mediators from those in most of the animal models. Our objectives are to critically review the data and concepts that have arisen from use of animal models for parturition and to rationalize the use of a new model. Many animal models have contributed to advances in our understanding of the regulation of parturition. However, we suggest that those animals dependent on progesterone withdrawal to initiate parturition clearly have a limitation to their translation to the human. In such models, a linear sequence of events (e.g., luteolysis, progesterone withdrawal, uterine activation, parturition) gives rise to the concept of a "trigger" mechanism. Conversely, we propose that human parturition may arise from the concomitant maturation of several systems in parallel. We have termed this novel concept "modular accumulation of physiological systems" (MAPS). We also emphasize the urgency to determine the precise role of the immune system in the process of parturition in situations other than intrauterine infection. Finally, we accentuate the need to develop a nonprimate animal model whose physiology is more relevant to human parturition. We suggest that the guinea pig displays several key physiological characteristics of gestation that more closely resemble human pregnancy than do currently favored animal models. We conclude that the application of novel concepts and new models are

  4. Simulation Models of Human Decision-Making Processes

    Directory of Open Access Journals (Sweden)

    Nina RIZUN

    2014-10-01

    Full Text Available The main purpose of the paper is presentation of the new concept of human decision-making process modeling via using the analogy with Automatic Control Theory. From the author's point of view this concept allows to develop and improve the theory of decision-making in terms of the study and classification of specificity of the human intellectual processes in different conditions. It was proved that the main distinguishing feature between the Heuristic / Intuitive and Rational Decision-Making Models is the presence of so-called phenomenon of "enrichment" of the input information with human propensity, hobbies, tendencies, expectations, axioms and judgments, presumptions or bias and their justification. In order to obtain additional knowledge about the basic intellectual processes as well as the possibility of modeling the decision results in various parameters characterizing the decision-maker, the complex of the simulation models was developed. These models are based on the assumptions that:  basic intellectual processes of the Rational Decision-Making Model can be adequately simulated and identified by the transient processes of the proportional-integral-derivative controller; basic intellectual processes of the Bounded Rationality and Intuitive Models can be adequately simulated and identified by the transient processes of the nonlinear elements.The taxonomy of the most typical automatic control theory elements and their compliance with certain decision-making models with a point of view of decision-making process specificity and decision-maker behavior during a certain time of professional activity was obtained.

  5. Thermodynamic Modeling and Analysis of Human Stress Response

    Science.gov (United States)

    Boregowda, S. C.; Tiwari, S. N.

    1999-01-01

    A novel approach based on the second law of thermodynamics is developed to investigate the psychophysiology and quantify human stress level. Two types of stresses (thermal and mental) are examined. A Unified Stress Response Theory (USRT) is developed under the new proposed field of study called Engineering Psychophysiology. The USRT is used to investigate both thermal and mental stresses from a holistic (human body as a whole) and thermodynamic viewpoint. The original concepts and definitions are established as postulates which form the basis for thermodynamic approach to quantify human stress level. An Objective Thermal Stress Index (OTSI) is developed by applying the second law of thermodynamics to the human thermal system to quantify thermal stress or dis- comfort in the human body. The human thermal model based on finite element method is implemented. It is utilized as a "Computational Environmental Chamber" to conduct series of simulations to examine the human thermal stress responses under different environmental conditions. An innovative hybrid technique is developed to analyze human thermal behavior based on series of human-environment interaction simulations. Continuous monitoring of thermal stress is demonstrated with the help of OTSI. It is well established that the human thermal system obeys the second law of thermodynamics. Further, the OTSI is validated against the experimental data. Regarding mental stress, an Objective Mental Stress Index (OMSI) is developed by applying the Maxwell relations of thermodynamics to the combined thermal and cardiovascular system in the human body. The OMSI is utilized to demonstrate the technique of monitoring mental stress continuously and is validated with the help of series of experimental studies. Although the OMSI indicates the level of mental stress, it provides a strong thermodynamic and mathematical relationship between activities of thermal and cardiovascular systems of the human body.

  6. Human Activity Recognition Using Heterogeneous Sensors

    NARCIS (Netherlands)

    Shoaib, M.

    Physical activities play an important role in our physical and mental well-being. The lack of such activities can negatively affect our well-being. Though people know the importance of physical activities, still they need regular motivational feedback to remain active in their daily life. In order

  7. Human Activity-Understanding: A Multilayer Approach Combining Body Movements and Contextual Descriptors Analysis

    Directory of Open Access Journals (Sweden)

    Consuelo Granata

    2015-07-01

    Full Text Available A deep understanding of human activity is key to successful human-robot interaction (HRI. The translation of sensed human behavioural signals/cues and context descriptors into an encoded human activity remains a challenge because of the complex nature of human actions. In this paper, we propose a multilayer framework for the understanding of human activity to be implemented in a mobile robot. It consists of a perception layer which exploits a D-RGB-based skeleton tracking output used to simulate a physical model of virtual human dynamics in order to compensate for the inaccuracy and inconsistency of the raw data. A multi-support vector machine (MSVM model trained with features describing the human motor coordination through temporal segments in combination with environment descriptors (object affordance is used to recognize each sub-activity (classification layer. The interpretation of sequences of classified elementary actions is based on discrete hidden Markov models (DHMMs (interpretation layer. The framework assessment was performed on the Cornell Activity Dataset (CAD-120 [1]. The performances of our method are comparable with those presented in [2] and clearly show the relevance of this model-based approach.

  8. Model of the Human Sleep Wake System

    CERN Document Server

    Rogers, Lisa

    2012-01-01

    A model and analysis of the human sleep/wake system is presented. The model is derived using the known neuronal groups, and their various projections, involved with sleep and wake. Inherent in the derivation is the existence of a slow time scale associated with homeostatic regulation, and a faster time scale associated with the dynamics within the sleep phase. A significant feature of the model is that it does not contain a periodic forcing term, common in other models, reflecting the fact that sleep/wake is not dependent upon a diurnal stimulus. Once derived, the model is analyzed using a linearized stability analysis. We then use experimental data from normal sleep-wake systems and orexin knockout systems to verify the physiological validity of the equations.

  9. Depression of cortical activity in humans by mild hypercapnia.

    Science.gov (United States)

    Thesen, Thomas; Leontiev, Oleg; Song, Tao; Dehghani, Nima; Hagler, Donald J; Huang, Mingxiong; Buxton, Richard; Halgren, Eric

    2012-03-01

    The effects of neural activity on cerebral hemodynamics underlie human brain imaging with functional magnetic resonance imaging and positron emission tomography. However, the threshold and characteristics of the converse effects, wherein the cerebral hemodynamic and metabolic milieu influence neural activity, remain unclear. We tested whether mild hypercapnia (5% CO2 ) decreases the magnetoencephalogram response to auditory pattern recognition and visual semantic tasks. Hypercapnia induced statistically significant decreases in event-related fields without affecting behavioral performance. Decreases were observed in early sensory components in both auditory and visual modalities as well as later cognitive components related to memory and language. Effects were distributed across cortical regions. Decreases were comparable in evoked versus spontaneous spectral power. Hypercapnia is commonly used with hemodynamic models to calibrate the blood oxygenation level-dependent response. Modifying model assumptions to incorporate the current findings produce a modest but measurable decrease in the estimated cerebral metabolic rate for oxygen change with activation. Because under normal conditions, low cerebral pH would arise when bloodflow is unable to keep pace with neuronal activity, the cortical depression observed here may reflect a homeostatic mechanism by which neuronal activity is adjusted to a level that can be sustained by available bloodflow. Animal studies suggest that these effects may be mediated by pH-modulating presynaptic adenosine receptors. Although the data is not clear, comparable changes in cortical pH to those induced here may occur during sleep apnea, sleep, and exercise. If so, these results suggest that such activities may in turn have generalized depressive effects on cortical activity.

  10. Acetaminophen induces human neuroblastoma cell death through NFKB activation.

    Directory of Open Access Journals (Sweden)

    Inmaculada Posadas

    Full Text Available Neuroblastoma resistance to apoptosis may contribute to the aggressive behavior of this tumor. Therefore, it would be relevant to activate endogenous cellular death mechanisms as a way to improve neuroblastoma therapy. We used the neuroblastoma SH-SY5Y cell line as a model to study the mechanisms involved in acetaminophen (AAP-mediated toxicity by measuring CYP2E1 enzymatic activity, NFkB p65 subunit activation and translocation to the nucleus, Bax accumulation into the mitochondria, cytochrome c release and caspase activation. AAP activates the intrinsic death pathway in the SH-SY5Y human neuroblastoma cell line. AAP metabolism is partially responsible for this activation, because blockade of the cytochrome CYP2E1 significantly reduced but did not totally prevent, AAP-induced SH-SY5Y cell death. AAP also induced NFkB p65 activation by phosphorylation and its translocation to the nucleus, where NFkB p65 increased IL-1β production. This increase contributed to neuroblastoma cell death through a mechanism involving Bax accumulation into the mitochondria, cytochrome c release and caspase3 activation. Blockade of NFkB translocation to the nucleus by the peptide SN50 prevented AAP-mediated cell death and IL-1β production. Moreover, overexpression of the antiapoptotic protein Bcl-x(L did not decrease AAP-mediated IL-1β production, but prevented both AAP and IL-1β-mediated cell death. We also confirmed the AAP toxic actions on SK-N-MC neuroepithelioma and U87MG glioblastoma cell lines. The results presented here suggest that AAP activates the intrinsic death pathway in neuroblastoma cells through a mechanism involving NFkB and IL-1β.

  11. Efficiency of Human Activity on Information Spreading on Twitter

    CERN Document Server

    Morales, A J; Losada, J C; Benito, R M

    2014-01-01

    Understanding the collective reaction to individual actions is key to effectively spread information in social media. In this work we define efficiency on Twitter, as the ratio between the emergent spreading process and the activity employed by the user. We characterize this property by means of a quantitative analysis of the structural and dynamical patterns emergent from human interactions, and show it to be universal across several Twitter conversations. We found that some influential users efficiently cause remarkable collective reactions by each message sent, while the majority of users must employ extremely larger efforts to reach similar effects. Next we propose a model that reproduces the retweet cascades occurring on Twitter to explain the emergent distribution of the user efficiency. The model shows that the dynamical patterns of the conversations are strongly conditioned by the topology of the underlying network. We conclude that the appearance of a small fraction of extremely efficient users resul...

  12. Human physiologically based pharmacokinetic model for propofol

    Directory of Open Access Journals (Sweden)

    Schnider Thomas W

    2005-04-01

    Full Text Available Abstract Background Propofol is widely used for both short-term anesthesia and long-term sedation. It has unusual pharmacokinetics because of its high lipid solubility. The standard approach to describing the pharmacokinetics is by a multi-compartmental model. This paper presents the first detailed human physiologically based pharmacokinetic (PBPK model for propofol. Methods PKQuest, a freely distributed software routine http://www.pkquest.com, was used for all the calculations. The "standard human" PBPK parameters developed in previous applications is used. It is assumed that the blood and tissue binding is determined by simple partition into the tissue lipid, which is characterized by two previously determined set of parameters: 1 the value of the propofol oil/water partition coefficient; 2 the lipid fraction in the blood and tissues. The model was fit to the individual experimental data of Schnider et. al., Anesthesiology, 1998; 88:1170 in which an initial bolus dose was followed 60 minutes later by a one hour constant infusion. Results The PBPK model provides a good description of the experimental data over a large range of input dosage, subject age and fat fraction. Only one adjustable parameter (the liver clearance is required to describe the constant infusion phase for each individual subject. In order to fit the bolus injection phase, for 10 or the 24 subjects it was necessary to assume that a fraction of the bolus dose was sequestered and then slowly released from the lungs (characterized by two additional parameters. The average weighted residual error (WRE of the PBPK model fit to the both the bolus and infusion phases was 15%; similar to the WRE for just the constant infusion phase obtained by Schnider et. al. using a 6-parameter NONMEM compartmental model. Conclusion A PBPK model using standard human parameters and a simple description of tissue binding provides a good description of human propofol kinetics. The major advantage of a

  13. Immunological characterization of plasminogen activator activities in human tissues and body fluids

    NARCIS (Netherlands)

    Rijken, D.C.; Wijngaards, G.; Welbergen, J.

    1981-01-01

    Human plasminogen activators were compared immunologically in both a double-diffusion technique and quenching experiments on the fibrinolytic activities of the activators. Antisera against HMW and LMW urokinase and an antiserum against highly purified tissue plasminogen activator from human uterus

  14. BACTERICIDAL ACTIVITY OF HUMAN SERA AGAINST ...

    African Journals Online (AJOL)

    hi-tech

    2000-12-12

    Dec 12, 2000 ... Immunoglobulin in the resistance or susceptibility of Salmonella typhi and Salmonella paratyphi A,B,C ... individual to Salmonella typhi and paratyphi infections. Individuals of ..... human immunodeficiency virus. J. Immuno.

  15. Affinity purification of recombinant human plasminogen activator ...

    African Journals Online (AJOL)

    Purpose: To develop processes for effective isolation and purification of recombinant human plasminogen ... three hybridoma strains were superior for producing PR-mAbs (C1, C4, C8). ..... characterization of a polyol- responsive monoclonal.

  16. Human multimedia display interface based on human activity recognition

    Science.gov (United States)

    Shang, Yiting; Lee, Eung-Joo

    2011-06-01

    In this paper, we will propose a Human Multimedia Display Interface. The interface uses the tracking of human hand movements to control the IP-TV. This paper presents an improved CAMSHIFT algorithm to control an IP-TV system. The CAMSHIFT algorithm (Continuously Adaptive MeanShift) is a method of using color information[1]. It can do tracking with a specific color of the target. In some typical environmental constraints, it can obtain good tracking performance. However, as the question of noise, large area similar to the color interference and so on, only by CAM-SHIFT algorithm it is not competent. Against these issues we propose an improved CAMSHIFT algorithm[2].

  17. Identifying and modeling the structural discontinuities of human interactions

    Science.gov (United States)

    Grauwin, Sebastian; Szell, Michael; Sobolevsky, Stanislav; Hövel, Philipp; Simini, Filippo; Vanhoof, Maarten; Smoreda, Zbigniew; Barabási, Albert-László; Ratti, Carlo

    2017-04-01

    The idea of a hierarchical spatial organization of society lies at the core of seminal theories in human geography that have strongly influenced our understanding of social organization. Along the same line, the recent availability of large-scale human mobility and communication data has offered novel quantitative insights hinting at a strong geographical confinement of human interactions within neighboring regions, extending to local levels within countries. However, models of human interaction largely ignore this effect. Here, we analyze several country-wide networks of telephone calls - both, mobile and landline - and in either case uncover a systematic decrease of communication induced by borders which we identify as the missing variable in state-of-the-art models. Using this empirical evidence, we propose an alternative modeling framework that naturally stylizes the damping effect of borders. We show that this new notion substantially improves the predictive power of widely used interaction models. This increases our ability to understand, model and predict social activities and to plan the development of infrastructures across multiple scales.

  18. Activities of Human Gene Nomenclature Committee

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-07-16

    The objective of this project, shared between NIH and DOE, has been and remains to enable the medical genetics communities to use common names for genes that are discovered by different gene hunting groups, in different species. This effort provides consistent gene nomenclature and approved gene symbols to the community at large. This contributes to a uniform and consistent understanding of genomes, particularly the human as well as functional genomics based on comparisons between homologous genes in related species (human and mice).

  19. Human Factors Engineering Program Review Model

    Science.gov (United States)

    2004-02-01

    AA NUREG -0711,Rev. 2 Human Factors Engineering Program Review Model 20081009191 I i m To] Bi U.S. Nuclear Regulatory Commission Office of...Material As of November 1999, you may electronically access NUREG -series publications and other NRC records at NRC’s Public Electronic Reading Room at...http://www.nrc.qov/readinq-rm.html. Publicly released records include, to name a few, NUREG -series publications; Federal Register notices; applicant

  20. Human Plague Risk: Spatial-Temporal Models

    Science.gov (United States)

    Pinzon, Jorge E.

    2010-01-01

    This chpater reviews the use of spatial-temporal models in identifying potential risks of plague outbreaks into the human population. Using earth observations by satellites remote sensing there has been a systematic analysis and mapping of the close coupling between the vectors of the disease and climate variability. The overall result is that incidence of plague is correlated to positive El Nino/Southem Oscillation (ENSO).

  1. Human Immunodeficiency Syndromes Affecting Human Natural Killer Cell Cytolytic Activity

    OpenAIRE

    Ham, Hyoungjun; Billadeau, Daniel D.

    2014-01-01

    Natural killer (NK) cells are lymphocytes of the innate immune system that secrete cytokines upon activation and mediate the killing of tumor cells and virus-infected cells, especially those that escape the adaptive T cell response caused by the down regulation of MHC-I. The induction of cytotoxicity requires that NK cells contact target cells through adhesion receptors, and initiate activation signaling leading to increased adhesion and accumulation of F-actin at the NK cell cytotoxic synaps...

  2. Culture models of human mammary epithelial cell transformation

    Energy Technology Data Exchange (ETDEWEB)

    Stampfer, Martha R.; Yaswen, Paul

    2000-11-10

    Human pre-malignant breast diseases, particularly ductal carcinoma in situ (DCIS)3 already display several of the aberrant phenotypes found in primary breast cancers, including chromosomal abnormalities, telomerase activity, inactivation of the p53 gene and overexpression of some oncogenes. Efforts to model early breast carcinogenesis in human cell cultures have largely involved studies in vitro transformation of normal finite lifespan human mammary epithelial cells (HMEC) to immortality and malignancy. We present a model of HMEC immortal transformation consistent with the know in vivo data. This model includes a recently described, presumably epigenetic process, termed conversion, which occurs in cells that have overcome stringent replicative senescence and are thus able to maintain proliferation with critically short telomeres. The conversion process involves reactivation of telomerase activity, and acquisition of good uniform growth in the absence and presence of TFGB. We propose th at overcoming the proliferative constraints set by senescence, and undergoing conversion, represent key rate-limiting steps in human breast carcinogenesis, and occur during early stage breast cancer progression.

  3. MODELING HUMAN RELIABILITY ANALYSIS USING MIDAS

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-05-01

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

  4. Behavior genetic modeling of human fertility

    DEFF Research Database (Denmark)

    Rodgers, J L; Kohler, H P; Kyvik, K O

    2001-01-01

    Try) and number of children (NumCh). Behavior genetic models were fitted using structural equation modeling and DF analysis. A consistent medium-level additive genetic influence was found for NumCh, equal across genders; a stronger genetic influence was identified for FirstTry, greater for females than for males......Behavior genetic designs and analysis can be used to address issues of central importance to demography. We use this methodology to document genetic influence on human fertility. Our data come from Danish twin pairs born from 1953 to 1959, measured on age at first attempt to get pregnant (First...

  5. Genetically engineered mouse models and human osteosarcoma

    Directory of Open Access Journals (Sweden)

    Ng Alvin JM

    2012-10-01

    Full Text Available Abstract Osteosarcoma is the most common form of bone cancer. Pivotal insight into the genes involved in human osteosarcoma has been provided by the study of rare familial cancer predisposition syndromes. Three kindreds stand out as predisposing to the development of osteosarcoma: Li-Fraumeni syndrome, familial retinoblastoma and RecQ helicase disorders, which include Rothmund-Thomson Syndrome in particular. These disorders have highlighted the important roles of P53 and RB respectively, in the development of osteosarcoma. The association of OS with RECQL4 mutations is apparent but the relevance of this to OS is uncertain as mutations in RECQL4 are not found in sporadic OS. Application of the knowledge or mutations of P53 and RB in familial and sporadic OS has enabled the development of tractable, highly penetrant murine models of OS. These models share many of the cardinal features associated with human osteosarcoma including, importantly, a high incidence of spontaneous metastasis. The recent development of these models has been a significant advance for efforts to improve our understanding of the genetics of human OS and, more critically, to provide a high-throughput genetically modifiable platform for preclinical evaluation of new therapeutics.

  6. Modeling Oxygen Transport in the Human Placenta

    Science.gov (United States)

    Serov, Alexander; Filoche, Marcel; Salafia, Carolyn; Grebenkov, Denis

    Efficient functioning of the human placenta is crucial for the favorable pregnancy outcome. We construct a 3D model of oxygen transport in the placenta based on its histological cross-sections. The model accounts for both diffusion and convention of oxygen in the intervillous space and allows one to estimate oxygen uptake of a placentone. We demonstrate the existence of an optimal villi density maximizing the uptake and explain it as a trade-off between the incoming oxygen flow and the absorbing villous surface. Calculations performed for arbitrary shapes of fetal villi show that only two geometrical characteristics - villi density and the effective villi radius - are required to predict fetal oxygen uptake. Two combinations of physiological parameters that determine oxygen uptake are also identified: maximal oxygen inflow of a placentone and the Damköhler number. An automatic image analysis method is developed and applied to 22 healthy placental cross-sections demonstrating that villi density of a healthy human placenta lies within 10% of the optimal value, while overall geometry efficiency is rather low (around 30-40%). In a perspective, the model can constitute the base of a reliable tool of post partum oxygen exchange efficiency assessment in the human placenta. Also affiliated with Department of Chemistry and Biochemistry, UCLA, Los Angeles, CA 90095, USA.

  7. Biomedical Simulation Models of Human Auditory Processes

    Science.gov (United States)

    Bicak, Mehmet M. A.

    2012-01-01

    Detailed acoustic engineering models that explore noise propagation mechanisms associated with noise attenuation and transmission paths created when using hearing protectors such as earplugs and headsets in high noise environments. Biomedical finite element (FE) models are developed based on volume Computed Tomography scan data which provides explicit external ear, ear canal, middle ear ossicular bones and cochlea geometry. Results from these studies have enabled a greater understanding of hearing protector to flesh dynamics as well as prioritizing noise propagation mechanisms. Prioritization of noise mechanisms can form an essential framework for exploration of new design principles and methods in both earplug and earcup applications. These models are currently being used in development of a novel hearing protection evaluation system that can provide experimentally correlated psychoacoustic noise attenuation. Moreover, these FE models can be used to simulate the effects of blast related impulse noise on human auditory mechanisms and brain tissue.

  8. Optimization of experimental human leukemia models (review

    Directory of Open Access Journals (Sweden)

    D. D. Pankov

    2012-01-01

    Full Text Available Actual problem of assessing immunotherapy prospects including antigenpecific cell therapy using animal models was covered in this review.Describe the various groups of currently existing animal models and methods of their creating – from different immunodeficient mice to severalvariants of tumor cells engraftment in them. The review addresses the possibility of tumor stem cells studying using mouse models for the leukemia treatment with adoptive cell therapy including WT1. Also issues of human leukemia cells migration and proliferation in a mice withdifferent immunodeficiency degree are discussed. To assess the potential immunotherapy efficacy comparison of immunodeficient mouse model with clinical situation in oncology patients after chemotherapy is proposed.

  9. Optimization of experimental human leukemia models (review

    Directory of Open Access Journals (Sweden)

    D. D. Pankov

    2014-07-01

    Full Text Available Actual problem of assessing immunotherapy prospects including antigenpecific cell therapy using animal models was covered in this review.Describe the various groups of currently existing animal models and methods of their creating – from different immunodeficient mice to severalvariants of tumor cells engraftment in them. The review addresses the possibility of tumor stem cells studying using mouse models for the leukemia treatment with adoptive cell therapy including WT1. Also issues of human leukemia cells migration and proliferation in a mice withdifferent immunodeficiency degree are discussed. To assess the potential immunotherapy efficacy comparison of immunodeficient mouse model with clinical situation in oncology patients after chemotherapy is proposed.

  10. Modeling human influenza infection in the laboratory

    Directory of Open Access Journals (Sweden)

    Radigan KA

    2015-08-01

    Full Text Available Kathryn A Radigan,1 Alexander V Misharin,2 Monica Chi,1 GR Scott Budinger11Division of Pulmonary and Critical Care Medicine, 2Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USAAbstract: Influenza is the leading cause of death from an infectious cause. Because of its clinical importance, many investigators use animal models to understand the biologic mechanisms of influenza A virus replication, the immune response to the virus, and the efficacy of novel therapies. This review will focus on the biosafety, biosecurity, and ethical concerns that must be considered in pursuing influenza research, in addition to focusing on the two animal models – mice and ferrets – most frequently used by researchers as models of human influenza infection.Keywords: mice, ferret, influenza, animal model, biosafety

  11. Leveraging Human Brain Activity to Improve Object Classification

    OpenAIRE

    Fong, Ruth Catherine

    2015-01-01

    Today, most object detection algorithms differ drastically from how humans tackle visual problems. In this thesis, I present a new paradigm for improving machine vision algorithms by designing them to better mimic how humans approach these tasks. Specifically, I demonstrate how human brain activity from functional magnetic resonance imaging (fMRI) can be leveraged to improve object classification. Inspired by the graduated manner in which humans learn, I present a novel algorithm that sim...

  12. Computational model of soft tissues in the human upper airway.

    Science.gov (United States)

    Pelteret, J-P V; Reddy, B D

    2012-01-01

    This paper presents a three-dimensional finite element model of the tongue and surrounding soft tissues with potential application to the study of sleep apnoea and of linguistics and speech therapy. The anatomical data was obtained from the Visible Human Project, and the underlying histological data was also extracted and incorporated into the model. Hyperelastic constitutive models were used to describe the material behaviour, and material incompressibility was accounted for. An active Hill three-element muscle model was used to represent the muscular tissue of the tongue. The neural stimulus for each muscle group was determined through the use of a genetic algorithm-based neural control model. The fundamental behaviour of the tongue under gravitational and breathing-induced loading is investigated. It is demonstrated that, when a time-dependent loading is applied to the tongue, the neural model is able to control the position of the tongue and produce a physiologically realistic response for the genioglossus.

  13. TR146 cells grown on filters as a model of human buccal epithelium

    DEFF Research Database (Denmark)

    Mørck Nielsen, H; Rømer Rassing, M; Nielsen, Hanne Mørck

    2000-01-01

    The objective of the present study was to characterise the TR146 cell culture model as an in vitro model of human buccal mucosa with respect to the enzyme activity in the tissues. For this purpose, the contents of aminopeptidase, carboxypeptidase and esterase in homogenate supernatants of the TR146...... cell culture model, and human and porcine buccal epithelium were compared. The esterase activity in the intact cell culture model and in the porcine buccal mucosa was compared. Further, the TR146 cell culture model was used to study the permeability rate and metabolism of leu-enkephalin. The activity...... of the three enzymes in the TR146 homogenate supernatants was in the same range as the activity in homogenate supernatants of human buccal epithelium. In the TR146 cell culture model, the activity of aminopeptidase (13.70+/-2.10 nmol/min per mg protein) was approx. four times the activity of carboxypeptidase...

  14. Modeling learned categorical perception in human vision.

    Science.gov (United States)

    Casey, Matthew C; Sowden, Paul T

    2012-09-01

    A long standing debate in cognitive neuroscience has been the extent to which perceptual processing is influenced by prior knowledge and experience with a task. A converging body of evidence now supports the view that a task does influence perceptual processing, leaving us with the challenge of understanding the locus of, and mechanisms underpinning, these influences. An exemplar of this influence is learned categorical perception (CP), in which there is superior perceptual discrimination of stimuli that are placed in different categories. Psychophysical experiments on humans have attempted to determine whether early cortical stages of visual analysis change as a result of learning a categorization task. However, while some results indicate that changes in visual analysis occur, the extent to which earlier stages of processing are changed is still unclear. To explore this issue, we develop a biologically motivated neural model of hierarchical vision processes consisting of a number of interconnected modules representing key stages of visual analysis, with each module learning to exhibit desired local properties through competition. With this system level model, we evaluate whether a CP effect can be generated with task influence to only the later stages of visual analysis. Our model demonstrates that task learning in just the later stages is sufficient for the model to exhibit the CP effect, demonstrating the existence of a mechanism that requires only a high-level of task influence. However, the effect generalizes more widely than is found with human participants, suggesting that changes to earlier stages of analysis may also be involved in the human CP effect, even if these are not fundamental to the development of CP. The model prompts a hybrid account of task-based influences on perception that involves both modifications to the use of the outputs from early perceptual analysis along with the possibility of changes to the nature of that early analysis itself

  15. A Culture-Behavior-Brain Loop Model of Human Development.

    Science.gov (United States)

    Han, Shihui; Ma, Yina

    2015-11-01

    Increasing evidence suggests that cultural influences on brain activity are associated with multiple cognitive and affective processes. These findings prompt an integrative framework to account for dynamic interactions between culture, behavior, and the brain. We put forward a culture-behavior-brain (CBB) loop model of human development that proposes that culture shapes the brain by contextualizing behavior, and the brain fits and modifies culture via behavioral influences. Genes provide a fundamental basis for, and interact with, the CBB loop at both individual and population levels. The CBB loop model advances our understanding of the dynamic relationships between culture, behavior, and the brain, which are crucial for human phylogeny and ontogeny. Future brain changes due to cultural influences are discussed based on the CBB loop model.

  16. Human Activity Recognition in AAL Environments Using Random Projections

    Directory of Open Access Journals (Sweden)

    Robertas Damaševičius

    2016-01-01

    Full Text Available Automatic human activity recognition systems aim to capture the state of the user and its environment by exploiting heterogeneous sensors attached to the subject’s body and permit continuous monitoring of numerous physiological signals reflecting the state of human actions. Successful identification of human activities can be immensely useful in healthcare applications for Ambient Assisted Living (AAL, for automatic and intelligent activity monitoring systems developed for elderly and disabled people. In this paper, we propose the method for activity recognition and subject identification based on random projections from high-dimensional feature space to low-dimensional projection space, where the classes are separated using the Jaccard distance between probability density functions of projected data. Two HAR domain tasks are considered: activity identification and subject identification. The experimental results using the proposed method with Human Activity Dataset (HAD data are presented.

  17. Aryl hydrocarbon mono-oxygenase activity in human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Griffin, G.D.; Schuresko, D.D.

    1981-06-01

    Aryl hydrocarbon mono-oxygenase (AHM), an enzyme of key importance in metabolism of xenobiotic chemicals such as polynuclear aromatic hydrocarbons (PNA), is present in human lymphocytes. Studies investing the relation of activity of AHM in human lymphocytes to parameters such as disease state, PNA exposure, in vitro mitogen stimulation, etc. have been summarized in this report. Some studies have demonstrated increased AHM activity in lymphocytes from cigarette smokers (compared to nonsmokers), and in lung cancer patients when compared to appropriate control groups. These observations are confused by extreme variability in human lymphocyte AHM activities, such variability arising from factors such as genetic variation in AHM activity, variation in in vitro culture conditions which affect AHM activity, and the problematical relationship of common AHM assays to actual PNA metabolism taking place in lymphocytes. If some of the foregoing problems can be adequately addressed, lymphocyte AHM activity could hold the promise of being a useful biomarker system for human PNA exposure.

  18. Human embryonic stem cell lines model experimental human cytomegalovirus latency.

    Science.gov (United States)

    Penkert, Rhiannon R; Kalejta, Robert F

    2013-05-28

    Herpesviruses are highly successful pathogens that persist for the lifetime of their hosts primarily because of their ability to establish and maintain latent infections from which the virus is capable of productively reactivating. Human cytomegalovirus (HCMV), a betaherpesvirus, establishes latency in CD34(+) hematopoietic progenitor cells during natural infections in the body. Experimental infection of CD34(+) cells ex vivo has demonstrated that expression of the viral gene products that drive productive infection is silenced by an intrinsic immune defense mediated by Daxx and histone deacetylases through heterochromatinization of the viral genome during the establishment of latency. Additional mechanistic details about the establishment, let alone maintenance and reactivation, of HCMV latency remain scarce. This is partly due to the technical challenges of CD34(+) cell culture, most notably, the difficulty in preventing spontaneous differentiation that drives reactivation and renders them permissive for productive infection. Here we demonstrate that HCMV can establish, maintain, and reactivate in vitro from experimental latency in cultures of human embryonic stem cells (ESCs), for which spurious differentiation can be prevented or controlled. Furthermore, we show that known molecular aspects of HCMV latency are faithfully recapitulated in these cells. In total, we present ESCs as a novel, tractable model for studies of HCMV latency.

  19. Computational Models to Synthesize Human Walking

    Institute of Scientific and Technical Information of China (English)

    Lei Ren; David Howard; Laurence Kenney

    2006-01-01

    The synthesis of human walking is of great interest in biomechanics and biomimetic engineering due to its predictive capabilities and potential applications in clinical biomechanics, rehabilitation engineering and biomimetic robotics. In this paper,the various methods that have been used to synthesize humanwalking are reviewed from an engineering viewpoint. This involves a wide spectrum of approaches, from simple passive walking theories to large-scale computational models integrating the nervous, muscular and skeletal systems. These methods are roughly categorized under four headings: models inspired by the concept of a CPG (Central Pattern Generator), methods based on the principles of control engineering, predictive gait simulation using optimisation, and models inspired by passive walking theory. The shortcomings and advantages of these methods are examined, and future directions are discussed in the context of providing insights into the neural control objectives driving gait and improving the stability of the predicted gaits. Future advancements are likely to be motivated by improved understanding of neural control strategies and the subtle complexities of the musculoskeletal system during human locomotion. It is only a matter of time before predictive gait models become a practical and valuable tool in clinical diagnosis, rehabilitation engineering and robotics.

  20. A dynamic model of human physiology

    Science.gov (United States)

    Green, Melissa; Kaplan, Carolyn; Oran, Elaine; Boris, Jay

    2010-11-01

    To study the systems-level transport in the human body, we develop the Computational Man (CMAN): a set of one-dimensional unsteady elastic flow simulations created to model a variety of coupled physiological systems including the circulatory, respiratory, excretory, and lymphatic systems. The model systems are collapsed from three spatial dimensions and time to one spatial dimension and time by assuming axisymmetric vessel geometry and a parabolic velocity profile across the cylindrical vessels. To model the actions of a beating heart or expanding lungs, the flow is driven by user-defined changes to the equilibrium areas of the elastic vessels. The equations are then iteratively solved for pressure, area, and average velocity. The model is augmented with valves and contractions to resemble the biological structure of the different systems. CMAN will be used to track material transport throughout the human body for diagnostic and predictive purposes. Parameters will be adjustable to match those of individual patients. Validation of CMAN has used both higher-dimensional simulations of similar geometries and benchmark measurement from medical literature.

  1. Modeling and simulation of the human eye

    Science.gov (United States)

    Duran, R.; Ventura, L.; Nonato, L.; Bruno, O.

    2007-02-01

    The computational modeling of the human eye has been wide studied for different sectors of the scientific and technological community. One of the main reasons for this increasing interest is the possibility to reproduce eye optic properties by means of computational simulations, becoming possible the development of efficient devices to treat and to correct the problems of the vision. This work explores this aspect still little investigated of the modeling of the visual system, considering a computational sketch that make possible the use of real data in the modeling and simulation of the human visual system. This new approach makes possible the individual inquiry of the optic system, assisting in the construction of new techniques used to infer vital data in medical investigations. Using corneal topography to collect real data from patients, a computational model of cornea is constructed and a set of simulations were build to ensure the correctness of the system and to investigate the effect of corneal abnormalities in retinal image formation, such as Plcido Discs, Point Spread Function, Wave front and the projection of a real image and it's visualization on retina.

  2. Human task-specific somatosensory activation.

    Science.gov (United States)

    Ginsberg, M D; Yoshii, F; Vibulsresth, S; Chang, J Y; Duara, R; Barker, W W; Boothe, T E

    1987-08-01

    We used positron emission tomography to study normal patterns of local cortical metabolic activation induced by somatosensory stimuli. Palpation and sorting of mah-jongg tiles by textured design increased local glucose metabolic rate (lCMRgl), by 18% on average, in contralateral somatosensory cortex. A graphesthesia task gave a similar result. In contrast, vigorous vibrotactile stimulation of fingers, face, or knee did not produce a consistent focus of activation. Our results indicate that lCMRgl activation is best achieved by somatosensory tasks requiring an active perceptual effort.

  3. Modeling of active beam units with Modelica

    DEFF Research Database (Denmark)

    Maccarini, Alessandro; Hultmark, Göran; Vorre, Anders

    2015-01-01

    This paper proposes an active beam model suitable for building energy simulations with the programming language Modelica. The model encapsulates empirical equations derived by a novel active beam terminal unit that operates with low-temperature heating and high-temperature cooling systems....... Measurements from a full-scale experiment are used to compare the thermal behavior of the active beam with the one predicted by simulations. The simulation results show that the model corresponds closely with the actual operation. The model predicts the outlet water temperature of the active beam...... with a maximum mean absolute error of 0.18 °C. In term of maximum mean absolute percentage error, simulation results differ by 0.9%. The methodology presented is general enough to be applied for modeling other active beam units. Modeling of active beam units with Modelica. Available from: https...

  4. Brain activation during human male ejaculation

    NARCIS (Netherlands)

    Holstege, Ger; Georgiadis, Janniko R.; Paans, Anne M.J.; Meiners, Linda C.; Graaf, Ferdinand H.C.E. van der; Reinders, A.A.T.Simone

    2003-01-01

    Brain mechanisms that control human sexual behavior in general, and ejaculation in particular, are poorly understood. We used positron emission tomography to measure increases in regional cerebral blood flow (rCBF) during ejaculation compared with sexual stimulation in heterosexual male volunteers.

  5. Rethinking food anticipatory activity in the activity-based anorexia rat model.

    Science.gov (United States)

    Wu, Hemmings; van Kuyck, Kris; Tambuyzer, Tim; Luyten, Laura; Aerts, Jean-Marie; Nuttin, Bart

    2014-01-29

    When a rat is on a limited fixed-time food schedule with full access to a running wheel (activity-based anorexia model, ABA), its activity level will increase hours prior to the feeding period. This activity, called food-anticipatory activity (FAA), is a hypothesized parallel to the hyperactivity symptom in human anorexia nervosa. To investigate in depth the characteristics of FAA, we retrospectively analyzed the level of FAA and activities during other periods in ABA rats. To our surprise, rats with the most body weight loss have the lowest level of FAA, which contradicts the previously established link between FAA and the severity of ABA symptoms. On the contrary, our study shows that postprandial activities are more directly related to weight loss. We conclude that FAA alone may not be sufficient to reflect model severity, and activities during other periods may be of potential value in studies using ABA model.

  6. Window Size Impact in Human Activity Recognition

    Directory of Open Access Journals (Sweden)

    Oresti Banos

    2014-04-01

    Full Text Available Signal segmentation is a crucial stage in the activity recognition process; however, this has been rarely and vaguely characterized so far. Windowing approaches are normally used for segmentation, but no clear consensus exists on which window size should be preferably employed. In fact, most designs normally rely on figures used in previous works, but with no strict studies that support them. Intuitively, decreasing the window size allows for a faster activity detection, as well as reduced resources and energy needs. On the contrary, large data windows are normally considered for the recognition of complex activities. In this work, we present an extensive study to fairly characterize the windowing procedure, to determine its impact within the activity recognition process and to help clarify some of the habitual assumptions made during the recognition system design. To that end, some of the most widely used activity recognition procedures are evaluated for a wide range of window sizes and activities. From the evaluation, the interval 1–2 s proves to provide the best trade-off between recognition speed and accuracy. The study, specifically intended for on-body activity recognition systems, further provides designers with a set of guidelines devised to facilitate the system definition and configuration according to the particular application requirements and target activities.

  7. A near atomic structure of the active human apoptosome

    Science.gov (United States)

    Cheng, Tat Cheung; Hong, Chuan; Akey, Ildikó V; Yuan, Shujun; Akey, Christopher W

    2016-01-01

    In response to cell death signals, an active apoptosome is assembled from Apaf-1 and procaspase-9 (pc-9). Here we report a near atomic structure of the active human apoptosome determined by cryo-electron microscopy. The resulting model gives insights into cytochrome c binding, nucleotide exchange and conformational changes that drive assembly. During activation an acentric disk is formed on the central hub of the apoptosome. This disk contains four Apaf-1/pc-9 CARD pairs arranged in a shallow spiral with the fourth pc-9 CARD at lower occupancy. On average, Apaf-1 CARDs recruit 3 to 5 pc-9 molecules to the apoptosome and one catalytic domain may be parked on the hub, when an odd number of zymogens are bound. This suggests a stoichiometry of one or at most, two pc-9 dimers per active apoptosome. Thus, our structure provides a molecular framework to understand the role of the apoptosome in programmed cell death and disease. DOI: http://dx.doi.org/10.7554/eLife.17755.001

  8. Learning models of activities involving interacting objects

    DEFF Research Database (Denmark)

    Manfredotti, Cristina; Pedersen, Kim Steenstrup; Hamilton, Howard J.;

    2013-01-01

    We propose the LEMAIO multi-layer framework, which makes use of hierarchical abstraction to learn models for activities involving multiple interacting objects from time sequences of data concerning the individual objects. Experiments in the sea navigation domain yielded learned models that were...... then successfully applied to activity recognition, activity simulation and multi-target tracking. Our method compares favourably with respect to previously reported results using Hidden Markov Models and Relational Particle Filtering....

  9. Sensitivity of the Indian Monsoon to Human Activities

    Institute of Scientific and Technical Information of China (English)

    B. KNOPF; K. ZICKFELD; M. FLECHSIG; V. PETOUKHOV

    2008-01-01

    In this paper the authors perform an extensive sensitivity analysis of the Indian summer monsoon rainfall to changes in parameters and boundary conditions which are influenced by human activities. For this study, the authors use a box model of the Indian monsoon which reproduces key features of the observed monsoon dynamics such as the annual course of precipitation and the transitions between winter and summer regimes. Because of its transparency and computational efficiency, this model is highly suitable for exploring the effects of anthropogenic perturbations such as emissions of greenhouse gases and sulfur dioxide, and land cover changes, on the Indian monsoon. Results of a systematic sensitivity analysis indicate that changes in those parameters which are related to emissions of greenhouse gases lead to an increase in Indian summer rainfall. In contrast, all parameters related to higher atmospheric aerosol concentrations lead to a decrease in Indian rainfall. Similarly, changes in parameters which can be related to forest conversion or desertification, act to decrease the summer precipitation. The results indicate that the sign of precipitation changes over India will be dependent on the direction and relative magnitude of different human perturbations.

  10. HLA-Modeler: Automated Homology Modeling of Human Leukocyte Antigens

    Directory of Open Access Journals (Sweden)

    Shinji Amari

    2013-01-01

    Full Text Available The three-dimensional (3D structures of human leukocyte antigen (HLA molecules are indispensable for the studies on the functions at molecular level. We have developed a homology modeling system named HLA-modeler specialized in the HLA molecules. Segment matching algorithm is employed for modeling and the optimization of the model is carried out by use of the PFROSST force field considering the implicit solvent model. In order to efficiently construct the homology models, HLA-modeler uses a local database of the 3D structures of HLA molecules. The structure of the antigenic peptide-binding site is important for the function and the 3D structure is highly conserved between various alleles. HLA-modeler optimizes the use of this structural motif. The leave-one-out cross-validation using the crystal structures of class I and class II HLA molecules has demonstrated that the rmsds of nonhydrogen atoms of the sites between homology models and crystal structures are less than 1.0 Å in most cases. The results have indicated that the 3D structures of the antigenic peptide-binding sites can be reproduced by HLA-modeler at the level almost corresponding to the crystal structures.

  11. HLA-Modeler: Automated Homology Modeling of Human Leukocyte Antigens.

    Science.gov (United States)

    Amari, Shinji; Kataoka, Ryoichi; Ikegami, Takashi; Hirayama, Noriaki

    2013-01-01

    The three-dimensional (3D) structures of human leukocyte antigen (HLA) molecules are indispensable for the studies on the functions at molecular level. We have developed a homology modeling system named HLA-modeler specialized in the HLA molecules. Segment matching algorithm is employed for modeling and the optimization of the model is carried out by use of the PFROSST force field considering the implicit solvent model. In order to efficiently construct the homology models, HLA-modeler uses a local database of the 3D structures of HLA molecules. The structure of the antigenic peptide-binding site is important for the function and the 3D structure is highly conserved between various alleles. HLA-modeler optimizes the use of this structural motif. The leave-one-out cross-validation using the crystal structures of class I and class II HLA molecules has demonstrated that the rmsds of nonhydrogen atoms of the sites between homology models and crystal structures are less than 1.0 Å in most cases. The results have indicated that the 3D structures of the antigenic peptide-binding sites can be reproduced by HLA-modeler at the level almost corresponding to the crystal structures.

  12. Thrombolytic and pharmacokinetic properties of human tissue-type plasminogen activator variants, obtained by deletion and/or duplication of structural/functional domains, in a hamster pulmonary embolism model.

    Science.gov (United States)

    Collen, D; Lijnen, H R; Vanlinthout, I; Kieckens, L; Nelles, L; Stassen, J M

    1991-02-12

    A pulmonary embolism model in hamsters was used for the quantitative evaluation of the thrombolytic and pharmacokinetic properties of variants of tissue-type plasminogen activator (t-PA). A 25 microliters 125I-fibrin labeled human plasma clot was made in vitro and injected into the jugular vein of heparinized hamsters. The extent of thrombolysis within 90 min was determined as the difference between the radioactivity injected in the jugular vein and that recovered in the heart and lungs. Recombinant t-PA (home-made rt-PA or Activase) infused intravenously over 60 min caused dose-dependent progressive thrombolysis. The results of thrombolytic potency (clot lysis in percent versus dose administered in mg/kg) and of specific thrombolytic activity (clot lysis in percent versus steady state plasma level in microgram/ml) were fitted with an exponentially transformed sigmoidal function y = 100 c/(1 + e-a(ax-eh] and the maximal percent lysis (c), the dose or plasma level at which maximal rate of lysis is achieved (b) and the maximal rate of lysis (z = 1/4 ac.eb) were determined. With rt-PA, these parameters were c = 72 +/- 6% (mean +/- SEM), b = 0.19 +/- 0.08 mg/kg, z = 68 +/- 25% lysis per mg/kg, with corresponding values of 87 +/- 5%, 0.07 +/- 0.03 mg/kg and 150 +/- 38% lysis per mg/kg for Activase (p = NS). Deletion of the finger and growth factor domains in rt-PA (rt-PA-delta FE) was not associated with marked alteration of the thrombolytic potency (c = 90 +/- 30%, b = 0.34 +/- 0.35 mg/kg, and z = 54 +/- 14% per mg/kg), but was associated with a significant reduction of the specific thrombolytic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. The quantitative modelling of human spatial habitability

    Science.gov (United States)

    Wise, J. A.

    1985-01-01

    A model for the quantitative assessment of human spatial habitability is presented in the space station context. The visual aspect assesses how interior spaces appear to the inhabitants. This aspect concerns criteria such as sensed spaciousness and the affective (emotional) connotations of settings' appearances. The kinesthetic aspect evaluates the available space in terms of its suitability to accommodate human movement patterns, as well as the postural and anthrometric changes due to microgravity. Finally, social logic concerns how the volume and geometry of available space either affirms or contravenes established social and organizational expectations for spatial arrangements. Here, the criteria include privacy, status, social power, and proxemics (the uses of space as a medium of social communication).

  14. Robust, synergistic regulation of human gene expression using TALE activators.

    Science.gov (United States)

    Maeder, Morgan L; Linder, Samantha J; Reyon, Deepak; Angstman, James F; Fu, Yanfang; Sander, Jeffry D; Joung, J Keith

    2013-03-01

    Artificial activators designed using transcription activator-like effector (TALE) technology have broad utility, but previous studies suggest that these monomeric proteins often exhibit low activities. Here we demonstrate that TALE activators can robustly function individually or in synergistic combinations to increase expression of endogenous human genes over wide dynamic ranges. These findings will encourage applications of TALE activators for research and therapy, and guide design of monomeric TALE-based fusion proteins.

  15. A Pattern Mining Approach to Sensor-based Human Activity Recognition

    DEFF Research Database (Denmark)

    Gu, Tao; Wang, Liang; Wu, Zhanqing

    2011-01-01

    Recognizing human activities from sensor readings has recently attracted much research interest in pervasive computing due to its potential in many applications such as assistive living and healthcare. This task is particularly challenging because human activities are often performed in not only...... in real life because activities can be interleaved and performed concurrently in many different ways. In this paper, we propose a novel pattern mining approach to recognize sequential, interleaved and concurrent activities in a unified framework. We exploit Emerging Pattern—a discriminative pattern...... that describes significant changes between classes of data—to identify sensor features for classifying activities. Different from existing learning-based approaches which require different training datasets for building activity models, our activity models are built upon the sequential activity trace only...

  16. ActivityNet: A Large-Scale Video Benchmark for Human Activity Understanding

    KAUST Repository

    Heilbron, Fabian Caba

    2015-06-02

    In spite of many dataset efforts for human action recognition, current computer vision algorithms are still severely limited in terms of the variability and complexity of the actions that they can recognize. This is in part due to the simplicity of current benchmarks, which mostly focus on simple actions and movements occurring on manually trimmed videos. In this paper we introduce ActivityNet, a new largescale video benchmark for human activity understanding. Our benchmark aims at covering a wide range of complex human activities that are of interest to people in their daily living. In its current version, ActivityNet provides samples from 203 activity classes with an average of 137 untrimmed videos per class and 1.41 activity instances per video, for a total of 849 video hours. We illustrate three scenarios in which ActivityNet can be used to compare algorithms for human activity understanding: untrimmed video classification, trimmed activity classification and activity detection.

  17. Characterization of ATPase Activity of Recombinant Human Pif1

    Institute of Scientific and Technical Information of China (English)

    Yu HUANG; Deng-Hong ZHANG; Jin-Qiu ZHOU

    2006-01-01

    Saccharomyces cerevisiae Pif1p helicase is the founding member of the Pif1 subfamily that is conserved from yeast to human. The potential human homolog of the yeast PIF1 gene has been cloned from the cDNA library of the Hek293 cell line. Here, we described a purification procedure of glutathione Stransferase (GST)-fused N terminal truncated human Pif1 protein (hPif1△N) from yeast and characterized the enzymatic kinetics of its ATP hydrolysis activity. The ATPase activity of human Pif1 is dependent on divalent cation, such as Mg2+, Ca2+ and single-stranded DNA. Km for ATP for the ATPase activity is approximately 200 μM. As the ATPase activity is essential for hPif1's helicase activity, these results will facilitate the further investigation on hPif1.

  18. Global changes in biogeochemical cycles in response to human activities

    Science.gov (United States)

    Moore, Berrien, III; Melillo, Jerry

    1994-01-01

    The main objective of our research was to characterize biogeochemical cycles at continental and global scales in both terrestrial and aquatic ecosystems. This characterization applied to both natural ecosystems and those disturbed by human activity. The primary elements of interest were carbon and nitrogen and the analysis sought to quantify standing stocks and dynamic cycling processes. The translocation of major nutrients from the terrestrial landscape to the atmosphere (via trace gases) and to fluvial systems (via leaching, erosional losses, and point source pollution) were of particular importance to this study. Our aim was to develop the first generation of Earth System Models. Our research was organized around the construction and testing of component biogeochemical models which treated terrestrial ecosystem processes, aquatic nutrient transport through drainage basins, and trace gas exchanges at the continental and global scale. A suite of three complementary models were defined within this construct. The models were organized to operate at a 1/2 degree latitude by longitude level of spatial resolution and to execute at a monthly time step. This discretization afforded us the opportunity to understand the dynamics of the biosphere down to subregional scales, while simultaneously placing these dynamics into a global context.

  19. The quantitative modelling of human spatial habitability

    Science.gov (United States)

    Wise, James A.

    1988-01-01

    A theoretical model for evaluating human spatial habitability (HuSH) in the proposed U.S. Space Station is developed. Optimizing the fitness of the space station environment for human occupancy will help reduce environmental stress due to long-term isolation and confinement in its small habitable volume. The development of tools that operationalize the behavioral bases of spatial volume for visual kinesthetic, and social logic considerations is suggested. This report further calls for systematic scientific investigations of how much real and how much perceived volume people need in order to function normally and with minimal stress in space-based settings. The theoretical model presented in this report can be applied to any size or shape interior, at any scale of consideration, for the Space Station as a whole to an individual enclosure or work station. Using as a point of departure the Isovist model developed by Dr. Michael Benedikt of the U. of Texas, the report suggests that spatial habitability can become as amenable to careful assessment as engineering and life support concerns.

  20. Modeling Workflow Using UML Activity Diagram

    Institute of Scientific and Technical Information of China (English)

    Wei Yinxing(韦银星); Zhang Shensheng

    2004-01-01

    An enterprise can improve its adaptability in the changing market by means of workflow technologies. In the build time, the main function of Workflow Management System (WFMS) is to model business process. Workflow model is an abstract representation of the real-world business process. The Unified Modeling Language (UML) activity diagram is an important visual process modeling language proposed by the Object Management Group (OMG). The novelty of this paper is representing workflow model by means of UML activity diagram. A translation from UML activity diagram to π-calculus is established. Using π-calculus, the deadlock property of workflow is analyzed.

  1. Lytic efficacy of apoli protein E2 (ApoE2) and recombinant tissue plasminogen activator (rt-PA) treatment with 120 kHz ultrasound in an in-vitro human clot model

    Science.gov (United States)

    Meunier, Jason M.; Cheng, Jason Y.; Clark, Joseph F.; Shaw, George J.

    2005-04-01

    Currently, the only FDA approved therapy for acute ischemic stroke is recombinant tissue plasminogen activator (rt-PA). However rt-PA has substantial side effects such as hemorrhage. This has led to interest in other potential therapies. For example, ultrasound (US) increases the lytic efficacy of rt-PA. Also, apolipoprotein E2 (ApoE2) increases rt-PA activity. This suggests combining US, ApoE2 and rt-PA to improve thrombolysis, but the efficacy is not known. Here, the lytic efficacy of apoE2, rt-PA and 120 kHz US is measured in a human clot model. Whole blood was obtained from volunteers, after local institutional approval. Clots were formed in 1.7 mm micropipettes, and placed in a water tank that allowed microscopic video imaging during US and thrombolytic exposure. Clots were treated with rt-PA ([rt-PA]=3.15 μg/ml), rt-PA and apoE2 ([apoE2]=9.8 μg/ml), or rt-PA, apoE2 and 120 kHz US (0.35 MPa, PRF=1667 Hz, 80% duty cycle) for 15 min at 37°C in human plasma. Clot lysis was visually recorded and the lysis depth (LD) determined from these data using an image analysis algorithm. LD was linear with time for all treatments (R2>=0.81), allowing the determination of a lytic rate (LR). LR was found to be 0.35+/-0.03, 1.55+/-0.11, and 0.75+/-0.04 μm/min for the rt-PA, rt-PA and apoE2, and US treated groups respectively. The thrombolytic efficacy of rt-PA is enhanced by ApoE2. The interaction of 120 kHz with apoE2 and rt-PA showed a reduced lytic efficacy compared with rt-PA and apoE2 treatment alone. It is possible that US interferes with the ApoE2-mediated activation of rt-PA.

  2. Type IV collagen-degrading enzyme activity in human serum.

    OpenAIRE

    Hashimoto, Noriaki; Kobayashi, Michio; Watanabe,Akiharu; Higashi, Toshiro; Tsuji, Takao

    1988-01-01

    Type IV collagen-degrading enzyme activity was detected in human serum. Serum was preincubated with 4-aminophenylmercuric acetate and trypsin to activate the enzyme prior to assay. Type IV collagen, purified from human placentas and radiolabeled with [1-14C] acetic anhydride, was used as the substrate. The enzyme activity was measured at pH 7.5 and inhibited by treatment with ethylenediaminetetraacetic acid or heat. The assay of type IV collagen-degrading enzyme in human serum might be useful...

  3. Type IV collagen-degrading enzyme activity in human serum.

    Directory of Open Access Journals (Sweden)

    Hashimoto,Noriaki

    1988-02-01

    Full Text Available Type IV collagen-degrading enzyme activity was detected in human serum. Serum was preincubated with 4-aminophenylmercuric acetate and trypsin to activate the enzyme prior to assay. Type IV collagen, purified from human placentas and radiolabeled with [1-14C] acetic anhydride, was used as the substrate. The enzyme activity was measured at pH 7.5 and inhibited by treatment with ethylenediaminetetraacetic acid or heat. The assay of type IV collagen-degrading enzyme in human serum might be useful for estimating the degradation of type IV collagen.

  4. Activation of human platelets by misfolded proteins

    NARCIS (Netherlands)

    Herczenik, E.; Bouma, B.; Korporaal, J.A.; Strangi, R.; Zeng, Q.; Gros, P.; van Eck, M.; van Berkel, T.J.C.; Gebbink, M.F.B.G.; Akkerman, J.W.N.

    2007-01-01

    Objective: Protein misfolding diseases result from the deposition of insoluble protein aggregates that often contain fibrils called amyloid. Amyloids are found in Alzheimer disease, atherosclerosis, diabetes mellitus, and systemic amyloidosis,which are diseases where platelet activation might be

  5. Active Learning of Classification Models with Likert-Scale Feedback.

    Science.gov (United States)

    Xue, Yanbing; Hauskrecht, Milos

    2017-01-01

    Annotation of classification data by humans can be a time-consuming and tedious process. Finding ways of reducing the annotation effort is critical for building the classification models in practice and for applying them to a variety of classification tasks. In this paper, we develop a new active learning framework that combines two strategies to reduce the annotation effort. First, it relies on label uncertainty information obtained from the human in terms of the Likert-scale feedback. Second, it uses active learning to annotate examples with the greatest expected change. We propose a Bayesian approach to calculate the expectation and an incremental SVM solver to reduce the time complexity of the solvers. We show the combination of our active learning strategy and the Likert-scale feedback can learn classification models more rapidly and with a smaller number of labeled instances than methods that rely on either Likert-scale labels or active learning alone.

  6. Model of local temperature changes in brain upon functional activation.

    Science.gov (United States)

    Collins, Christopher M; Smith, Michael B; Turner, Robert

    2004-12-01

    Experimental results for changes in brain temperature during functional activation show large variations. It is, therefore, desirable to develop a careful numerical model for such changes. Here, a three-dimensional model of temperature in the human head using the bioheat equation, which includes effects of metabolism, perfusion, and thermal conduction, is employed to examine potential temperature changes due to functional activation in brain. It is found that, depending on location in brain and corresponding baseline temperature relative to blood temperature, temperature may increase or decrease on activation and concomitant increases in perfusion and rate of metabolism. Changes in perfusion are generally seen to have a greater effect on temperature than are changes in metabolism, and hence active brain is predicted to approach blood temperature from its initial temperature. All calculated changes in temperature for reasonable physiological parameters have magnitudes <0.12 degrees C and are well within the range reported in recent experimental studies involving human subjects.

  7. Assessing the impact of climate variability and human activities on streamflow variation

    OpenAIRE

    Chang, Jianxia; Zhang, Hongxue; Wang, Yimin; Zhu, Yuelu

    2016-01-01

    Water resources in river systems have been changing under the impact of both climate variability and human activities. Assessing the respective impact on decadal streamflow variation is important for water resource management. By using an elasticity-based method and calibrated TOPMODEL and VIC hydrological models, we quantitatively isolated the relative contributions that human activities and climate variability made to decadal streamflow changes in the Jinghe basin, located...

  8. Assessing the impact of climate variability and human activity to streamflow variation

    OpenAIRE

    Chang, J.; Zhang, H.; Y. Wang; Zhu, Y.

    2015-01-01

    Water resources in river systems have been changing under the impacts of both climate variability and human activities. Assessing the respective impacts on decadal streamflow variation is important for water resources management. By using an elasticity-based method, calibrated TOPMODEL and VIC hydrologic models, we have quantitatively isolated the relative contributions that human activity and climate variability made to decadal streamflow changes in Jinhe b...

  9. Assessing the impact of climate variability and human activities on streamflow variation

    OpenAIRE

    Chang, J.; Zhang, H.; Y. Wang; Zhu, Y.

    2015-01-01

    Water resources in river systems have been changing under the impact of both climate variability and human activities. Assessing the respective impact on decadal streamflow variation is important for water resource management. By using an elasticity-based method and calibrated TOPMODEL and VIC hydrological models, we quantitatively isolated the relative contributions that human activities and climate variability made to decadal streamflow changes in Jinghe basin, located in ...

  10. POTENT INVITRO ANTI-HUMAN IMMUNODEFICIENCY VIRUS-1 ACTIVITY OF MODIFIED HUMAN SERUM ALBUMINS

    NARCIS (Netherlands)

    JANSEN, RW; MOLEMA, G; PAUWELS, R; SCHOLS, D; DECLERCQ, E; MEIJER, DKF

    1991-01-01

    A series of neoglycoproteins was synthesized by coupling of thiophosgene-activated p-aminophenyl derivatives [Biol. Cell. 47:95-110 (1983); J. Histochem. Cytochem. 32:1091-1094 (1984)] of various sugars to human serum albumin. The compounds were evaluated for their in vitro activity against human im

  11. MODELING HUMAN COMPREHENSION OF DATA VISUALIZATIONS.

    Energy Technology Data Exchange (ETDEWEB)

    Matzen, Laura E.; Haass, Michael Joseph; Divis, Kristin Marie; Wilson, Andrew T.

    2017-09-01

    This project was inspired by two needs. The first is a need for tools to help scientists and engineers to design effective data visualizations for communicating information, whether to the user of a system, an analyst who must make decisions based on complex data, or in the context of a technical report or publication. Most scientists and engineers are not trained in visualization design, and they could benefit from simple metrics to assess how well their visualization's design conveys the intended message. In other words, will the most important information draw the viewer's attention? The second is the need for cognition-based metrics for evaluating new types of visualizations created by researchers in the information visualization and visual analytics communities. Evaluating visualizations is difficult even for experts. However, all visualization methods and techniques are intended to exploit the properties of the human visual system to convey information efficiently to a viewer. Thus, developing evaluation methods that are rooted in the scientific knowledge of the human visual system could be a useful approach. In this project, we conducted fundamental research on how humans make sense of abstract data visualizations, and how this process is influenced by their goals and prior experience. We then used that research to develop a new model, the Data Visualization Saliency Model, that can make accurate predictions about which features in an abstract visualization will draw a viewer's attention. The model is an evaluation tool that can address both of the needs described above, supporting both visualization research and Sandia mission needs.

  12. Mouse Model of Human Hereditary Pancreatitis

    Science.gov (United States)

    2016-09-01

    models that recapitulate the human disease . Therefore, we introduced mutations in the endogenous mouse T7 cationic trypsinogen gene and obtained several...ACCOMPLISHMENTS: What were the major goals of the project? Our original proposal had three specific aims. Aim 1. Identify and biochemically characterize...pancreatitis in mutant mice which do not develop spontaneous disease (strains T7-D23del-Cre, T7-D23del-Neo, T7-K24R-Cre and T7- K24R-Neo), will be

  13. The active metabolite of prasugrel, R-138727, improves cerebral blood flow and reduces cerebral infarction and neurologic deficits in a non-human primate model of acute ischaemic stroke.

    Science.gov (United States)

    Sugidachi, Atsuhiro; Mizuno, Makoto; Ohno, Kousaku; Jakubowski, Joseph A; Tomizawa, Atsuyuki

    2016-10-05

    Previously, we showed preventive effects of prasugrel, a P2Y12 antagonist, in a non-human primate model of thrombotic middle cerebral artery occlusion (MCAO); however, it remains unclear if P2Y12 inhibition after MCAO reduces cerebral injury and dysfunction. Here we investigated the effects of R-138727, the major active metabolite of prasugrel, on ex vivo platelet aggregation at 5min, 15min, 60min, and 24h after administration to non-human primates (n=3). A single intravenous dose of R-138727 (0.03-0.3mg/kg) resulted in significant and sustained dose-related effects on platelets for up to 24h. R-138727 was administered 1h after MCAO induction, and its effects on thrombosis, cerebral infarction, and neurological deficits were determined (n=8-10). R-138727 (0.3mg/kg) significantly increased total patency rate of the MCA (P=0.0211). Although there was no effect on the patency rate before R-138727 dosing (P=0.3975), it increased 1h after dosing (P=0.0114). R-138727 significantly reduced total ischaemic infarction volumes (P=0.0147), including those of basal ganglia (P=0.0028), white matter (P=0.0393), and haemorrhagic infarction (P=0.0235). Additionally, treatment with R-138727 reduced overall neurological deficits (P=0.0019), including the subcategories of consciousness (P=0.0042), sensory system (P=0.0045), motor system (P=0.0079) and musculoskeletal coordination (P=0.0082). These findings support the possible utility of P2Y12 inhibition during early-onset MCAO to limit the progression and degree of cerebral ischaemia and infarction and also associated neurological deficits.

  14. Liver immune-pathogenesis and therapy of human liver tropic virus infection in humanized mouse models

    OpenAIRE

    Bility, Moses T.; Li, Feng; Cheng, Liang; Su, Lishan

    2013-01-01

    Hepatitis B virus (HBV) and hepatitis C virus (HCV) infect and replicate primarily in human hepatocytes. Few reliable and easy accessible animal models are available for studying the immune system’s contribution to the liver disease progression during hepatitis virus infection. Humanized mouse models reconstituted with human hematopoietic stem cells (HSCs) have been developed to study human immunology, human immunodeficiency virus 1 infection, and immunopathogenesis. However, a humanized mous...

  15. Which activation function of cooperation describes human behavior?

    CERN Document Server

    Jarynowski, Andrzej

    2016-01-01

    Properties of cooperation's probability function in Prisoner`s Dilemma have impact on evolution of game. Basic model defines that probability of cooperation depends linearly, both on the player's altruism and the co-player's reputation. I propose modification of activation function to smooth one (hyperbolic tangent with scaling parameter a, which corresponds to its shape) and observe three phases for different range of a. (1) For small a, strategies seem to randomly change in time and situation of mixed choices (one cooperates and second defects) dominate. (2) For medium a, players choose only one strategy for given period of time (the common state can switch to opposite one with some probability). (3) For large a, mixed strategy (once defect, once cooperate) is coexisting with common strategies and no change is allowed. I believe that proposed function characterizes better socio-economical phenomena and especially phase 1 and 2 contain most of human behavior.

  16. Multivariate Models for Prediction of Human Skin Sensitization ...

    Science.gov (United States)

    One of the lnteragency Coordinating Committee on the Validation of Alternative Method's (ICCVAM) top priorities is the development and evaluation of non-animal approaches to identify potential skin sensitizers. The complexity of biological events necessary to produce skin sensitization suggests that no single alternative method will replace the currently accepted animal tests. ICCVAM is evaluating an integrated approach to testing and assessment based on the adverse outcome pathway for skin sensitization that uses machine learning approaches to predict human skin sensitization hazard. We combined data from three in chemico or in vitro assays - the direct peptide reactivity assay (DPRA), human cell line activation test (h-CLAT) and KeratinoSens TM assay - six physicochemical properties and an in silico read-across prediction of skin sensitization hazard into 12 variable groups. The variable groups were evaluated using two machine learning approaches , logistic regression and support vector machine, to predict human skin sensitization hazard. Models were trained on 72 substances and tested on an external set of 24 substances. The six models (three logistic regression and three support vector machine) with the highest accuracy (92%) used: (1) DPRA, h-CLAT and read-across; (2) DPRA, h-CLAT, read-across and KeratinoSens; or (3) DPRA, h-CLAT, read-across, KeratinoSens and log P. The models performed better at predicting human skin sensitization hazard than the murine

  17. Hemagglutinin activity of human plasma fibronectin.

    Science.gov (United States)

    Vuento, M

    1979-09-01

    Purified human plasma fibronectin at concentrations of about 30 microgram/ml was found to agglutinate trypsin-treated erythrocytes from certain species. The hemagglutination reaction was inhibited by specific antibodies to fibronectin, by relatively low concentrations of polyamines and by higher concentrations of basic amino acids and nonacetylated amino sugars. The divalent cations Ca2+ and Mg2+ and the chelating agent ethylenediaminetetraacetate did not affect the reaction. None of the neutral amino acids, neutral sugars or polyanions tested was inhibitory. The results imply that plasma fibronectin is capable of interacting with cell surfaces and support the idea of a similarity between cellular and plasma fibronectins.

  18. Modeling & imaging of bioelectrical activity principles and applications

    CERN Document Server

    He, Bin

    2010-01-01

    Over the past several decades, much progress has been made in understanding the mechanisms of electrical activity in biological tissues and systems, and for developing non-invasive functional imaging technologies to aid clinical diagnosis of dysfunction in the human body. The book will provide full basic coverage of the fundamentals of modeling of electrical activity in various human organs, such as heart and brain. It will include details of bioelectromagnetic measurements and source imaging technologies, as well as biomedical applications. The book will review the latest trends in

  19. A modular approach to numerical human body modeling

    NARCIS (Netherlands)

    Forbes, P.A.; Griotto, G.; Rooij, L. van

    2007-01-01

    The choice of a human body model for a simulated automotive impact scenario must take into account both accurate model response and computational efficiency as key factors. This study presents a "modular numerical human body modeling" approach which allows the creation of a customized human body mod

  20. A modular approach to numerical human body modeling

    NARCIS (Netherlands)

    Forbes, P.A.; Griotto, G.; Rooij, L. van

    2007-01-01

    The choice of a human body model for a simulated automotive impact scenario must take into account both accurate model response and computational efficiency as key factors. This study presents a "modular numerical human body modeling" approach which allows the creation of a customized human body

  1. Pacemaker current inhibition in experimental human cardiac sympathetic activation: a double-blind, randomized, crossover study

    NARCIS (Netherlands)

    Schroeder, C.; Heusser, K.; Zoerner, A.A.; Grosshennig, A.; Wenzel, D.; May, M.; Sweep, F.C.; Mehling, H.; Luft, F.C.; Tank, J.; Jordan, J.

    2014-01-01

    Hyperpolarization-activated, cyclic nucleotide-gated 4 (HCN4) channels comprise the final pathway for autonomic heart rate (HR) regulation. We hypothesized that HCN4 inhibition could reverse autonomic imbalance in a human model of cardiac sympathetic activation. Nineteen healthy men ingested oral me

  2. Generative models: Human embryonic stem cells and multiple modeling relations.

    Science.gov (United States)

    Fagan, Melinda Bonnie

    2016-04-01

    Model organisms are at once scientific models and concrete living things. It is widely assumed by philosophers of science that (1) model organisms function much like other kinds of models, and (2) that insofar as their scientific role is distinctive, it is in virtue of representing a wide range of biological species and providing a basis for generalizations about those targets. This paper uses the case of human embryonic stem cells (hESC) to challenge both assumptions. I first argue that hESC can be considered model organisms, analogous to classic examples such as Escherichia coli and Drosophila melanogaster. I then discuss four contrasts between the epistemic role of hESC in practice, and the assumptions about model organisms noted above. These contrasts motivate an alternative view of model organisms as a network of systems related constructively and developmentally to one another. I conclude by relating this result to other accounts of model organisms in recent philosophy of science. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. A human neurodevelopmental model for Williams syndrome.

    Science.gov (United States)

    Chailangkarn, Thanathom; Trujillo, Cleber A; Freitas, Beatriz C; Hrvoj-Mihic, Branka; Herai, Roberto H; Yu, Diana X; Brown, Timothy T; Marchetto, Maria C; Bardy, Cedric; McHenry, Lauren; Stefanacci, Lisa; Järvinen, Anna; Searcy, Yvonne M; DeWitt, Michelle; Wong, Wenny; Lai, Philip; Ard, M Colin; Hanson, Kari L; Romero, Sarah; Jacobs, Bob; Dale, Anders M; Dai, Li; Korenberg, Julie R; Gage, Fred H; Bellugi, Ursula; Halgren, Eric; Semendeferi, Katerina; Muotri, Alysson R

    2016-08-18

    Williams syndrome is a genetic neurodevelopmental disorder characterized by an uncommon hypersociability and a mosaic of retained and compromised linguistic and cognitive abilities. Nearly all clinically diagnosed individuals with Williams syndrome lack precisely the same set of genes, with breakpoints in chromosome band 7q11.23 (refs 1-5). The contribution of specific genes to the neuroanatomical and functional alterations, leading to behavioural pathologies in humans, remains largely unexplored. Here we investigate neural progenitor cells and cortical neurons derived from Williams syndrome and typically developing induced pluripotent stem cells. Neural progenitor cells in Williams syndrome have an increased doubling time and apoptosis compared with typically developing neural progenitor cells. Using an individual with atypical Williams syndrome, we narrowed this cellular phenotype to a single gene candidate, frizzled 9 (FZD9). At the neuronal stage, layer V/VI cortical neurons derived from Williams syndrome were characterized by longer total dendrites, increased numbers of spines and synapses, aberrant calcium oscillation and altered network connectivity. Morphometric alterations observed in neurons from Williams syndrome were validated after Golgi staining of post-mortem layer V/VI cortical neurons. This model of human induced pluripotent stem cells fills the current knowledge gap in the cellular biology of Williams syndrome and could lead to further insights into the molecular mechanism underlying the disorder and the human social brain.

  4. Integrated Human Futures Modeling in Egypt

    Energy Technology Data Exchange (ETDEWEB)

    Passell, Howard D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Aamir, Munaf Syed [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Bernard, Michael Lewis [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Beyeler, Walter E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Fellner, Karen Marie [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hayden, Nancy Kay [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Jeffers, Robert Fredric [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Keller, Elizabeth James Kistin [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Malczynski, Leonard A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Mitchell, Michael David [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Silver, Emily [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Tidwell, Vincent C. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Villa, Daniel [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Vugrin, Eric D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Engelke, Peter [Atlantic Council, Washington, D.C. (United States); Burrow, Mat [Atlantic Council, Washington, D.C. (United States); Keith, Bruce [United States Military Academy, West Point, NY (United States)

    2016-01-01

    The Integrated Human Futures Project provides a set of analytical and quantitative modeling and simulation tools that help explore the links among human social, economic, and ecological conditions, human resilience, conflict, and peace, and allows users to simulate tradeoffs and consequences associated with different future development and mitigation scenarios. In the current study, we integrate five distinct modeling platforms to simulate the potential risk of social unrest in Egypt resulting from the Grand Ethiopian Renaissance Dam (GERD) on the Blue Nile in Ethiopia. The five platforms simulate hydrology, agriculture, economy, human ecology, and human psychology/behavior, and show how impacts derived from development initiatives in one sector (e.g., hydrology) might ripple through to affect other sectors and how development and security concerns may be triggered across the region. This approach evaluates potential consequences, intended and unintended, associated with strategic policy actions that span the development-security nexus at the national, regional, and international levels. Model results are not intended to provide explicit predictions, but rather to provide system-level insight for policy makers into the dynamics among these interacting sectors, and to demonstrate an approach to evaluating short- and long-term policy trade-offs across different policy domains and stakeholders. The GERD project is critical to government-planned development efforts in Ethiopia but is expected to reduce downstream freshwater availability in the Nile Basin, fueling fears of negative social and economic impacts that could threaten stability and security in Egypt. We tested these hypotheses and came to the following preliminary conclusions. First, the GERD will have an important short-term impact on water availability, food production, and hydropower production in Egypt, depending on the short- term reservoir fill rate. Second, the GERD will have a very small impact on

  5. Velocity profiles in idealized model of human respiratory tract

    Directory of Open Access Journals (Sweden)

    Jicha M.

    2013-04-01

    Full Text Available This article deals with numerical simulation focused on velocity profiles in idealized model of human upper airways during steady inspiration. Three r gimes of breathing were investigated: Resting condition, Deep breathing and Light activity which correspond to most common regimes used for experiments and simulations. Calculation was validated with experimental data given by Phase Doppler Anemometry performed on the model with same geometry. This comparison was made in multiple points which form one cross-section in trachea near first bifurcation of bronchial tree. Development of velocity profile in trachea during steady inspiration was discussed with respect for common phenomenon formed in trachea and for future research of transport of aerosol particles in human respiratory tract.

  6. Human Brain Activity Related to the Tactile Perception of Stickiness.

    Science.gov (United States)

    Yeon, Jiwon; Kim, Junsuk; Ryu, Jaekyun; Park, Jang-Yeon; Chung, Soon-Cheol; Kim, Sung-Phil

    2017-01-01

    While the perception of stickiness serves as one of the fundamental dimensions for tactile sensation, little has been elucidated about the stickiness sensation and its neural correlates. The present study investigated how the human brain responds to perceived tactile sticky stimuli using functional magnetic resonance imaging (fMRI). To evoke tactile perception of stickiness with multiple intensities, we generated silicone stimuli with varying catalyst ratios. Also, an acrylic sham stimulus was prepared to present a condition with no sticky sensation. From the two psychophysics experiments-the methods of constant stimuli and the magnitude estimation-we could classify the silicone stimuli into two groups according to whether a sticky perception was evoked: the Supra-threshold group that evoked sticky perception and the Infra-threshold group that did not. In the Supra-threshold vs. Sham contrast analysis of the fMRI data using the general linear model (GLM), the contralateral primary somatosensory area (S1) and ipsilateral dorsolateral prefrontal cortex (DLPFC) showed significant activations in subjects, whereas no significant result was found in the Infra-threshold vs. Sham contrast. This result indicates that the perception of stickiness not only activates the somatosensory cortex, but also possibly induces higher cognitive processes. Also, the Supra- vs. Infra-threshold contrast analysis revealed significant activations in several subcortical regions, including the pallidum, putamen, caudate and thalamus, as well as in another region spanning the insula and temporal cortices. These brain regions, previously known to be related to tactile discrimination, may subserve the discrimination of different intensities of tactile stickiness. The present study unveils the human neural correlates of the tactile perception of stickiness and may contribute to broadening the understanding of neural mechanisms associated with tactile perception.

  7. Human Brain Activity Related to the Tactile Perception of Stickiness

    Science.gov (United States)

    Yeon, Jiwon; Kim, Junsuk; Ryu, Jaekyun; Park, Jang-Yeon; Chung, Soon-Cheol; Kim, Sung-Phil

    2017-01-01

    While the perception of stickiness serves as one of the fundamental dimensions for tactile sensation, little has been elucidated about the stickiness sensation and its neural correlates. The present study investigated how the human brain responds to perceived tactile sticky stimuli using functional magnetic resonance imaging (fMRI). To evoke tactile perception of stickiness with multiple intensities, we generated silicone stimuli with varying catalyst ratios. Also, an acrylic sham stimulus was prepared to present a condition with no sticky sensation. From the two psychophysics experiments–the methods of constant stimuli and the magnitude estimation—we could classify the silicone stimuli into two groups according to whether a sticky perception was evoked: the Supra-threshold group that evoked sticky perception and the Infra-threshold group that did not. In the Supra-threshold vs. Sham contrast analysis of the fMRI data using the general linear model (GLM), the contralateral primary somatosensory area (S1) and ipsilateral dorsolateral prefrontal cortex (DLPFC) showed significant activations in subjects, whereas no significant result was found in the Infra-threshold vs. Sham contrast. This result indicates that the perception of stickiness not only activates the somatosensory cortex, but also possibly induces higher cognitive processes. Also, the Supra- vs. Infra-threshold contrast analysis revealed significant activations in several subcortical regions, including the pallidum, putamen, caudate and thalamus, as well as in another region spanning the insula and temporal cortices. These brain regions, previously known to be related to tactile discrimination, may subserve the discrimination of different intensities of tactile stickiness. The present study unveils the human neural correlates of the tactile perception of stickiness and may contribute to broadening the understanding of neural mechanisms associated with tactile perception. PMID:28163677

  8. Discursive Positionings and Emotions in Modelling Activities

    Science.gov (United States)

    Daher, Wajeeh

    2015-01-01

    Mathematical modelling is suggested as an activity through which students engage in meaningful mathematics. In the current research, the modelling activity of a group of four seventh-grade students was analysed using the discursive analysis framework. The research findings show that the positionings and emotions of the group members during their…

  9. Antibacterial activity of mangrove leaf extracts against human pathogens

    Digital Repository Service at National Institute of Oceanography (India)

    Sahoo, G.; Mulla, N.S.S.; Ansari, Z.A.; Mohandass, C.

    The antibacterial activity of leaf extract of mangroves, namely, Rhizophora mucronata, Sonneratia alba and Exoecaria agallocha from Chorao island, Goa was investigated against human bacterial pathogens Staphylococcus aureus, Streptococcus sp...

  10. Students’ mathematical learning in modelling activities

    DEFF Research Database (Denmark)

    Kjeldsen, Tinne Hoff; Blomhøj, Morten

    2013-01-01

    Ten years of experience with analyses of students’ learning in a modelling course for first year university students, led us to see modelling as a didactical activity with the dual goal of developing students’ modelling competency and enhancing their conceptual learning of mathematical concepts...... involved. We argue that progress in students’ conceptual learning needs to be conceptualised separately from that of progress in their modelling competency. Findings are that modelling activities open a window to the students’ images of the mathematical concepts involved; that modelling activities can...... create and help overcome hidden cognitive conflicts in students’ understanding; that reflections within modelling can play an important role for the students’ learning of mathematics. These findings are illustrated with a modelling project concerning the world population....

  11. Activation of the Small GTPase Rap1 in Human Neutrophils

    NARCIS (Netherlands)

    M'Rabet, Laura; Coffer, P.J.; Zwartkruis, G.J.T.; Franke, Barbara; Segal, Anthony W.; Koenderman, L.; Bos, J.L.

    2002-01-01

    The small GTPase Rap1 is highly expressed in human neutrophils, but its function is largely unknown. Using the Rap1- binding domain of RalGDS (RalGDS-RBD) as an activationspecific probe for Rap1, we have investigated the regulation of Rap1 activity in primary human neutrophils. We found that a varie

  12. SVM Model for Identification of human GPCRs

    CERN Document Server

    Shrivastava, Sonal; Malik, M M

    2010-01-01

    G-protein coupled receptors (GPCRs) constitute a broad class of cell-surface receptors in eukaryotes and they possess seven transmembrane a-helical domains. GPCRs are usually classified into several functionally distinct families that play a key role in cellular signalling and regulation of basic physiological processes. We can develop statistical models based on these common features that can be used to classify proteins, to predict new members, and to study the sequence-function relationship of this protein function group. In this study, SVM based classification model has been developed for the identification of human gpcr sequences. Sequences of Level 1 subfamilies of Class A rhodopsin is considered as case study. In the present study, an attempt has been made to classify GPCRs on the basis of species. The present study classifies human gpcr sequences with rest of the species available in GPCRDB. Classification is based on specific information derived from the n-terminal and extracellular loops of the sequ...

  13. Human activities change marine ecosystems by altering predation risk.

    Science.gov (United States)

    Madin, Elizabeth M P; Dill, Lawrence M; Ridlon, April D; Heithaus, Michael R; Warner, Robert R

    2016-01-01

    In ocean ecosystems, many of the changes in predation risk - both increases and decreases - are human-induced. These changes are occurring at scales ranging from global to local and across variable temporal scales. Indirect, risk-based effects of human activity are known to be important in structuring some terrestrial ecosystems, but these impacts have largely been neglected in oceans. Here, we synthesize existing literature and data to explore multiple lines of evidence that collectively suggest diverse human activities are changing marine ecosystems, including carbon storage capacity, in myriad ways by altering predation risk. We provide novel, compelling evidence that at least one key human activity, overfishing, can lead to distinct, cascading risk effects in natural ecosystems whose magnitude exceeds that of presumed lethal effects and may account for previously unexplained findings. We further discuss the conservation implications of human-caused indirect risk effects. Finally, we provide a predictive framework for when human alterations of risk in oceans should lead to cascading effects and outline a prospectus for future research. Given the speed and extent with which human activities are altering marine risk landscapes, it is crucial that conservation and management policy considers the indirect effects of these activities in order to increase the likelihood of success and avoid unfortunate surprises. © 2015 John Wiley & Sons Ltd.

  14. Diurnal Human Activity and Introduced Species Affect Occurrence of Carnivores in a Human-Dominated Landscape.

    Directory of Open Access Journals (Sweden)

    Dario Moreira-Arce

    Full Text Available Diurnal human activity and domestic dogs in agro-forestry mosaics should theoretically modify the diurnal habitat use patterns of native carnivores, with these effects being scale-dependent. We combined intensive camera trapping data with Bayesian occurrence probability models to evaluate both diurnal and nocturnal patterns of space use by carnivores in a mosaic of land-use types in southern Chile. A total of eight carnivores species were recorded, including human-introduced dogs. During the day the most frequently detected species were the culpeo fox and the cougar. Conversely, during the night, the kodkod and chilla fox were the most detected species. The best supported models showed that native carnivores responded differently to landscape attributes and dogs depending on both the time of day as well as the spatial scale of landscape attributes. The positive effect of native forest cover at 250 m and 500 m radius buffers was stronger during the night for the Darwin's fox and cougar. Road density at 250 m scale negatively affected the diurnal occurrence of Darwin´s fox, whereas at 500 m scale roads had a stronger negative effect on the diurnal occurrence of Darwin´s foxes and cougars. A positive effect of road density on dog occurrence was evidenced during both night and day. Patch size had a positive effect on cougar occurrence during night whereas it affected negatively the occurrence of culpeo foxes and skunks during day. Dog occurrence had a negative effect on Darwin's fox occurrence during day-time and night-time, whereas its negative effect on the occurrence of cougar was evidenced only during day-time. Carnivore occurrences were not influenced by the proximity to a conservation area. Our results provided support for the hypothesis that diurnal changes to carnivore occurrence were associated with human and dog activity. Landscape planning in our study area should be focused in reducing both the levels of diurnal human activity in

  15. Diurnal Human Activity and Introduced Species Affect Occurrence of Carnivores in a Human-Dominated Landscape.

    Science.gov (United States)

    Moreira-Arce, Dario; Vergara, Pablo M; Boutin, Stan

    2015-01-01

    Diurnal human activity and domestic dogs in agro-forestry mosaics should theoretically modify the diurnal habitat use patterns of native carnivores, with these effects being scale-dependent. We combined intensive camera trapping data with Bayesian occurrence probability models to evaluate both diurnal and nocturnal patterns of space use by carnivores in a mosaic of land-use types in southern Chile. A total of eight carnivores species were recorded, including human-introduced dogs. During the day the most frequently detected species were the culpeo fox and the cougar. Conversely, during the night, the kodkod and chilla fox were the most detected species. The best supported models showed that native carnivores responded differently to landscape attributes and dogs depending on both the time of day as well as the spatial scale of landscape attributes. The positive effect of native forest cover at 250 m and 500 m radius buffers was stronger during the night for the Darwin's fox and cougar. Road density at 250 m scale negatively affected the diurnal occurrence of Darwin´s fox, whereas at 500 m scale roads had a stronger negative effect on the diurnal occurrence of Darwin´s foxes and cougars. A positive effect of road density on dog occurrence was evidenced during both night and day. Patch size had a positive effect on cougar occurrence during night whereas it affected negatively the occurrence of culpeo foxes and skunks during day. Dog occurrence had a negative effect on Darwin's fox occurrence during day-time and night-time, whereas its negative effect on the occurrence of cougar was evidenced only during day-time. Carnivore occurrences were not influenced by the proximity to a conservation area. Our results provided support for the hypothesis that diurnal changes to carnivore occurrence were associated with human and dog activity. Landscape planning in our study area should be focused in reducing both the levels of diurnal human activity in native forest remnants

  16. Antibacterial activity of human cervical mucus.

    Science.gov (United States)

    Zuckerman, H; Kahana, A; Carmel, S

    1975-01-01

    The antimicrobial property of human uterine cervical mucus was tested in three groups of women. Healthy women, using no contraception, women using an intrauterine device and women receiving hormonal treatment for contraception. Cervical mucus was taken on the 10th, 14th, 18th and 22nd day of the menstrual cycle. Cervical mucus had a strong inhibitory effect on the growth of Micrococcus lysodeicticus in all three groups. The strength of the inhibitory effect on the other microorganisms were in the following order: Staphylococcus albus, Staphylococcus aureus, Proteus mirabilis, Escherichia coli, Candida albicans, Streptococcus haemolyticus, Streptococcus faecalis. Use of an intrauterine device did not affect the antimicrobial effect of cervical mucus. The use of hormonal contraceptive canceled the antimicrobial effect on the series of microorganisms, with the exception of M. lysodeicticus. The maximum inhibitory effect occurred on the 14th day and declined toward the end of the menstrual cycle.

  17. Modelling Typical Online Language Learning Activity

    Science.gov (United States)

    Montoro, Carlos; Hampel, Regine; Stickler, Ursula

    2014-01-01

    This article presents the methods and results of a four-year-long research project focusing on the language learning activity of individual learners using online tasks conducted at the University of Guanajuato (Mexico) in 2009-2013. An activity-theoretical model (Blin, 2010; Engeström, 1987) of the typical language learning activity was used to…

  18. Evaluating a Model of Youth Physical Activity

    Science.gov (United States)

    Heitzler, Carrie D.; Lytle, Leslie A.; Erickson, Darin J.; Barr-Anderson, Daheia; Sirard, John R.; Story, Mary

    2010-01-01

    Objective: To explore the relationship between social influences, self-efficacy, enjoyment, and barriers and physical activity. Methods: Structural equation modeling examined relationships between parent and peer support, parent physical activity, individual perceptions, and objectively measured physical activity using accelerometers among a…

  19. Simple models of human brain functional networks.

    Science.gov (United States)

    Vértes, Petra E; Alexander-Bloch, Aaron F; Gogtay, Nitin; Giedd, Jay N; Rapoport, Judith L; Bullmore, Edward T

    2012-04-10

    Human brain functional networks are embedded in anatomical space and have topological properties--small-worldness, modularity, fat-tailed degree distributions--that are comparable to many other complex networks. Although a sophisticated set of measures is available to describe the topology of brain networks, the selection pressures that drive their formation remain largely unknown. Here we consider generative models for the probability of a functional connection (an edge) between two cortical regions (nodes) separated by some Euclidean distance in anatomical space. In particular, we propose a model in which the embedded topology of brain networks emerges from two competing factors: a distance penalty based on the cost of maintaining long-range connections; and a topological term that favors links between regions sharing similar input. We show that, together, these two biologically plausible factors are sufficient to capture an impressive range of topological properties of functional brain networks. Model parameters estimated in one set of functional MRI (fMRI) data on normal volunteers provided a good fit to networks estimated in a second independent sample of fMRI data. Furthermore, slightly detuned model parameters also generated a reasonable simulation of the abnormal properties of brain functional networks in people with schizophrenia. We therefore anticipate that many aspects of brain network organization, in health and disease, may be parsimoniously explained by an economical clustering rule for the probability of functional connectivity between different brain areas.

  20. Hologram QSAR model for the prediction of human oral bioavailability.

    Science.gov (United States)

    Moda, Tiago L; Montanari, Carlos A; Andricopulo, Adriano D

    2007-12-15

    A drug intended for use in humans should have an ideal balance of pharmacokinetics and safety, as well as potency and selectivity. Unfavorable pharmacokinetics can negatively affect the clinical development of many otherwise promising drug candidates. A variety of in silico ADME (absorption, distribution, metabolism, and excretion) models are receiving increased attention due to a better appreciation that pharmacokinetic properties should be considered in early phases of the drug discovery process. Human oral bioavailability is an important pharmacokinetic property, which is directly related to the amount of drug available in the systemic circulation to exert pharmacological and therapeutic effects. In the present work, hologram quantitative structure-activity relationships (HQSAR) were performed on a training set of 250 structurally diverse molecules with known human oral bioavailability. The most significant HQSAR model (q(2)=0.70, r(2)=0.93) was obtained using atoms, bond, connection, and chirality as fragment distinction. The predictive ability of the model was evaluated by an external test set containing 52 molecules not included in the training set, and the predicted values were in good agreement with the experimental values. The HQSAR model should be useful for the design of new drug candidates having increased bioavailability as well as in the process of chemical library design, virtual screening, and high-throughput screening.

  1. Dietary methanol regulates human gene activity.

    Directory of Open Access Journals (Sweden)

    Anastasia V Shindyapina

    Full Text Available Methanol (MeOH is considered to be a poison in humans because of the alcohol dehydrogenase (ADH-mediated conversion of MeOH to formaldehyde (FA, which is toxic. Our recent genome-wide analysis of the mouse brain demonstrated that an increase in endogenous MeOH after ADH inhibition led to a significant increase in the plasma MeOH concentration and a modification of mRNA synthesis. These findings suggest endogenous MeOH involvement in homeostasis regulation by controlling mRNA levels. Here, we demonstrate directly that study volunteers displayed increasing concentrations of MeOH and FA in their blood plasma when consuming citrus pectin, ethanol and red wine. A microarray analysis of white blood cells (WBC from volunteers after pectin intake showed various responses for 30 significantly differentially regulated mRNAs, most of which were somehow involved in the pathogenesis of Alzheimer's disease (AD. There was also a decreased synthesis of hemoglobin mRNA, HBA and HBB, the presence of which in WBC RNA was not a result of red blood cells contamination because erythrocyte-specific marker genes were not significantly expressed. A qRT-PCR analysis of volunteer WBCs after pectin and red wine intake confirmed the complicated relationship between the plasma MeOH content and the mRNA accumulation of both genes that were previously identified, namely, GAPDH and SNX27, and genes revealed in this study, including MME, SORL1, DDIT4, HBA and HBB. We hypothesized that human plasma MeOH has an impact on the WBC mRNA levels of genes involved in cell signaling.

  2. Activation of Raf-1 in human pancreatic adenocarcinoma.

    Science.gov (United States)

    Berger, D H; Jardines, L A; Chang, H; Ruggeri, B

    1997-04-01

    Point mutations in the Ras oncogene cause Ras to remain in its active GTP-bound state sending signals downstream continuously. Since 75 to 90% of all human pancreatic ductal adenocarcinomas harbor activating mutations at codon 12 of the K-ras oncogene it was our belief that Raf-1-MEK-MAPK will be activated in the majority of human pancreatic cancers. The aim of this study was to confirm activation of Raf-1 in K-ras mutant human pancreatic cancer. Additionally, we sought to determine if Raf-1 activation differed in K-ras mutant and nonmutant pancreatic cancer. Furthermore, we were interested in determining if Raf-1 activation in pancreatic cancer led to subsequent activation of downstream effectors such as MAP kinase. The presence of mutations in codon 12 of the K-ras oncogene in 14 human pancreatic adenocarcinoma cell lines was determined by use of mutant allele-specific PCR restriction fragment length polymorphism analysis. Raf-1 expression of quiescent cells was determined by immunoblotting using a rabbit anti-human polyclonal antibody and enhanced chemiluminescence. MAP kinase activity was determined by measuring the incorporation of phosphate into Myelin Basic Protein. Seven cell lines were noted to have mutations in codon 12 of K-ras while seven cell lines did not. There was no difference in expression of the 74 kDa-activated form of Raf-1 in K-ras mutant vs K-ras nonmutant cell lines. However, there was a significant increase in MAP kinase activity in the nonmutant cell lines compared to the cell lines with Ras mutations (P = 0.026). We conclude that Raf-1 is expressed in its active form in human pancreatic cancer regardless of K-ras status. However, signalling downstream of Raf-1 differs in cell lines with K-ras mutations compared to those cell lines without K-ras mutations.

  3. Requirements engineering for human activity systems

    CSIR Research Space (South Africa)

    Erasmus, J

    2014-10-01

    Full Text Available . Office of the Chief Engineer, NASA, 2007. —. Systems Engineering Handbook. Washington, D.C.: National Aeronautics and Space Administration, 2007. Office of the Deputy Under Secretary of Defense for Acquisition and Technology, Systems and Software... and special tools necessary to perform the verification (NASA 2007). This information will also allow for proper planning and scheduling of the verification activities to be performed throughout the development and realisation of the product. Measures...

  4. Delayed Random Walks: Modeling Human Posture Control

    Science.gov (United States)

    Ohira, Toru

    1998-03-01

    We consider a phenomenological description of a noisy trajectory which appears on a stabiliogram platform during human postural sway. We hypothesize that this trajectory arises due to a mixture of uncontrollable noise and a corrective delayed feedback to an upright position. Based on this hypothesis, we model the process with a biased random walk whose transition probability depends on its position at a fixed time delay in the past, which we call a delayed random walk. We first introduce a very simple model (T. Ohira and J. G. Milton, Phys.Rev.E. 52), 3277, (1995), which can nevertheless capture the rough qualitative features of the two--point mean square displacement of experimental data with reasonable estimation of delay time. Then, we discuss two approaches toward better capturing and understanding of the experimental data. The first approach is an extension of the model to include a spatial displacement threshold from the upright position below which no or only weak corrective feedback motion takes place. This can be incorporated into an extended delayed random walk model. Numerical simulations show that this extended model can better capture the three scaling region which appears in the two--point mean square displacement. The other approach studied the autocorrelation function of the experimental data, which shows oscillatory behavior. We recently investigated a delayed random walk model whose autocorrelation function has analytically tractable oscillatory behavior (T. Ohira, Phys.Rev.E. 55), R1255, (1997). We discuss how this analytical understanding and its application to delay estimation (T. Ohira and R. Sawatari, Phys.Rev.E. 55), R2077, (1997) could possibly be used to further understand the postural sway data.

  5. Human suspicious activity recognition in thermal infrared video

    Science.gov (United States)

    Hossen, Jakir; Jacobs, Eddie; Chowdhury, Fahmida K.

    2014-10-01

    Detecting suspicious behaviors is important for surveillance and monitoring systems. In this paper, we investigate suspicious activity detection in thermal infrared imagery, where human motion can be easily detected from the background regardless of the lighting conditions and colors of the human clothing and surfaces. We use locally adaptive regression kernels (LARK) as patch descriptors, which capture the underlying local structure of the data exceedingly well, even in the presence of significant distortions. Patch descriptors are generated for each query patch and for each database patch. A statistical approach is used to match the query activity with the database to make the decision of suspicious activity. Human activity videos in different condition such as, walking, running, carrying a gun, crawling, and carrying backpack in different terrains were acquired using thermal infrared camera. These videos are used for training and performance evaluation of the algorithm. Experimental results show that the proposed approach achieves good performance in suspicious activity recognition.

  6. Automatic Modeling of Virtual Humans and Body Clothing

    Institute of Scientific and Technical Information of China (English)

    Nadia Magnenat-Thalmann; Hyewon Seo; Frederic Cordier

    2004-01-01

    Highly realistic virtual human models are rapidly becoming commonplace in computer graphics.These models, often represented by complex shape and requiring labor-intensive process, challenge the problem of automatic modeling. The problem and solutions to automatic modeling of animatable virtual humans are studied. Methods for capturing the shape of real people, parameterization techniques for modeling static shape (the variety of human body shapes) and dynamic shape (how the body shape changes as it moves) of virtual humans are classified, summarized and compared. Finally, methods for clothed virtual humans are reviewed.

  7. Salt Reduction in a Model High-Salt Akawi Cheese: Effects on Bacterial Activity, pH, Moisture, Potential Bioactive Peptides, Amino Acids, and Growth of Human Colon Cells.

    Science.gov (United States)

    Gandhi, Akanksha; Shah, Nagendra P

    2016-04-01

    This study evaluated the effects of sodium chloride reduction and its substitution with potassium chloride on Akawi cheese during storage for 30 d at 4 °C. Survival of probiotic bacteria (Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium longum) and starter bacteria (Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus), angiotensin-converting enzyme-inhibitory and antioxidant activities, and concentrations of standard amino acids as affected by storage in different brine solutions (10% NaCl, 7.5% NaCl, 7.5% NaCl+KCl [1:1], 5% NaCl, and 5% NaCl+KCl [1:1]) were investigated. Furthermore, viability of human colon cells and human colon cancer cells as affected by the extract showing improved peptide profiles, highest release of amino acids and antioxidant activity (that is, from cheese brined in 7.5% NaCl+KCl) was evaluated. Significant increase was observed in survival of probiotic bacteria in cheeses with low salt after 30 d. Calcium content decreased slightly during storage in all cheeses brined in various solutions. Further, no significant changes were observed in ACE-inhibitory activity and antioxidant activity of cheeses during storage. Interestingly, concentrations of 4 essential amino acids (phenylalanine, tryptophan, valine, and leucine) increased significantly during storage in brine solutions containing 7.5% total salt. Low concentration of cheese extract (100 μg/mL) significantly improved the growth of normal human colon cells, and reduced the growth of human colon cancer cells. Overall, the study revealed that cheese extracts from reduced-NaCl brine improved the growth of human colon cells, and the release of essential amino acids, but did not affect the activities of potential bioactive peptides.

  8. COMMUNICATIVE INTERACTION ACTIVITIES USING HUMAN INTEREST STORIES

    Institute of Scientific and Technical Information of China (English)

    Song Shunling

    1983-01-01

    @@ As an EFL teacher actively engaged in promoting communicative approach in teaching post-intermediate students I have been all the time aware of the risks involved in classroom discussion and debate in the target language. Despite elaborate preparations on thepart of both teacher and students and numerous encouraging cues from the teacher to induce an adequate interaction during the session, the end product is anything but satisfactory: few more able students may hog the show for a few minutes while the rest clamp up, then stony silence dominates and the teacher has recourse to monologue.

  9. Experimental Models in Syrian Golden Hamster Replicate Human Acute Pancreatitis.

    Science.gov (United States)

    Wang, Yunan; Kayoumu, Abudurexiti; Lu, Guotao; Xu, Pengfei; Qiu, Xu; Chen, Liye; Qi, Rong; Huang, Shouxiong; Li, Weiqin; Wang, Yuhui; Liu, George

    2016-06-15

    The hamster has been shown to share a variety of metabolic similarities with humans. To replicate human acute pancreatitis with hamsters, we comparatively studied the efficacy of common methods, such as the peritoneal injections of caerulein, L-arginine, the retrograde infusion of sodium taurocholate, and another novel model with concomitant administration of ethanol and fatty acid. The severity of pancreatitis was evaluated by serum amylase activity, pathological scores, myeloperoxidase activity, and the expression of inflammation factors in pancreas. The results support that the severity of pathological injury is consistent with the pancreatitis induced in mice and rat using the same methods. Specifically, caerulein induced mild edematous pancreatitis accompanied by minimal lung injury, while L-arginine induced extremely severe pancreatic injury including necrosis and neutrophil infiltration. Infusion of Na-taurocholate into the pancreatic duct induced necrotizing pancreatitis in the head of pancreas and lighter inflammation in the distal region. The severity of acute pancreatitis induced by combination of ethanol and fatty acids was between the extent of caerulein and L-arginine induction, with obvious inflammatory cells infiltration. In view of the advantages in lipid metabolism features, hamster models are ideally suited for the studies of pancreatitis associated with altered metabolism in humans.

  10. Human biomonitoring activities--programmes by industry.

    Science.gov (United States)

    Boogaard, Peter J

    2007-05-01

    Biomonitoring of exposure to chemicals has been practiced for over half a century on a regular basis. During the last decade, however, the focus changed from occupational to environmental settings, requiring a different interpretative framework. Under the auspices of the European Centre for Ecology and Ecotoxicology (ECETOC) a framework was developed that allows to assess the relevance of any biomonitoring result to be interpreted reliably. If biomonitoring data is to be used for the evaluation of health risks of a substance, information is required on the analytical integrity of the data, the toxicokinetics of this substance, and its health effects in relation to (low) exposures. In addition, a weight-of-evidence needs to be used. The framework also identifies a number of data-gaps, several of which are addressed through the Long-range Research Initiative (LRI), an initiative of the global chemical industries (EU, USA, and Japan), which aims to help answering important questions in the application of biomonitoring data in human health risk assessment.

  11. Supporting Human Activities - Exploring Activity-Centered Computing

    DEFF Research Database (Denmark)

    Christensen, Henrik Bærbak; Bardram, Jakob

    2002-01-01

    In this paper we explore an activity-centered computing paradigm that is aimed at supporting work processes that are radically different from the ones known from office work. Our main inspiration is healthcare work that is characterized by an extreme degree of mobility, many interruptions, ad...... objects. We also present an exploratory prototype design and first implementation and present some initial results from evaluations in a healthcare environment....

  12. The Application of Humanized Mouse Models for the Study of Human Exclusive Viruses.

    Science.gov (United States)

    Vahedi, Fatemeh; Giles, Elizabeth C; Ashkar, Ali A

    2017-01-01

    The symbiosis between humans and viruses has allowed human tropic pathogens to evolve intricate means of modulating the human immune response to ensure its survival among the human population. In doing so, these viruses have developed profound mechanisms that mesh closely with our human biology. The establishment of this intimate relationship has created a species-specific barrier to infection, restricting the virus-associated pathologies to humans. This specificity diminishes the utility of traditional animal models. Humanized mice offer a model unique to all other means of study, providing an in vivo platform for the careful examination of human tropic viruses and their interaction with human cells and tissues. These types of animal models have provided a reliable medium for the study of human-virus interactions, a relationship that could otherwise not be investigated without questionable relevance to humans.

  13. Humpback Dolphin (Genus Sousa) Behavioural Responses to Human Activities.

    Science.gov (United States)

    Piwetz, Sarah; Lundquist, David; Würsig, Bernd

    2015-01-01

    Humpback dolphins (genus Sousa) use shallow, near-shore waters throughout their range. This coastal distribution makes them vulnerable to recreational and commercial disturbances, especially near heavily populated and industrialized areas. Most research focusing on Sousa and human activities has emphasized direct impacts and threats, involving injury and death, with relatively little focus on indirect effects on dolphins, such as changes in behaviour that may lead to deleterious effects. Understanding behaviour is important in resolving human-wildlife conflict and is an important component of conservation. This chapter gives an overview of animal behavioural responses to human activity with examples from diverse taxa; reviews the scientific literature on behavioural responses of humpback dolphins to human activity throughout their range, including marine vessel traffic, dolphin tourism, cetacean-fishery interactions, noise pollution, and habitat alteration; and highlights information and data gaps for future humpback dolphin research to better inform behaviour-based management decisions that contribute to conservation efforts.

  14. Human Daily Activities Indexing in Videos from Wearable Cameras for Monitoring of Patients with Dementia Diseases

    CERN Document Server

    Karaman, Svebor; Mégret, Rémi; Dovgalecs, Vladislavs; Dartigues, Jean-François; Gaëstel, Yann

    2010-01-01

    Our research focuses on analysing human activities according to a known behaviorist scenario, in case of noisy and high dimensional collected data. The data come from the monitoring of patients with dementia diseases by wearable cameras. We define a structural model of video recordings based on a Hidden Markov Model. New spatio-temporal features, color features and localization features are proposed as observations. First results in recognition of activities are promising.

  15. Animal models for human craniofacial malformations.

    Science.gov (United States)

    Johnston, M C; Bronsky, P T

    1991-01-01

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

  16. Regression-Based Feature Selection on Large Scale Human Activity Recognition

    Directory of Open Access Journals (Sweden)

    Hussein Mazaar

    2016-02-01

    Full Text Available In this paper, we present an approach for regression-based feature selection in human activity recognition. Due to high dimensional features in human activity recognition, the model may have over-fitting and can’t learn parameters well. Moreover, the features are redundant or irrelevant. The goal is to select important discriminating features to recognize the human activities in videos. R-Squared regression criterion can identify the best features based on the ability of a feature to explain the variations in the target class. The features are significantly reduced, nearly by 99.33%, resulting in better classification accuracy. Support Vector Machine with a linear kernel is used to classify the activities. The experiments are tested on UCF50 dataset. The results show that the proposed model significantly outperforms state-of-the-art methods.

  17. ACTIVATION OF HUMAN BLOOD MONONUCLEARS BY LIPOPOLYSACCHARIDE OF DIFFERENT COMPOSITION

    Directory of Open Access Journals (Sweden)

    S. V. Zubova

    2010-01-01

    Full Text Available Influence of lipopolysaccharide (LPS composition upon activation of human blood mononuclears was investigated, by measuring levels of pro-inflammatory TNFα and IL-6 cytokines released by the cells. It is shown that LPS from Rhodobacter capsulatus PG, in contrast to E. coli LPS, did not activate the target cells for synthesis of the cytokines.

  18. Contributions of climate change and human activities to runoff change in seven typical catchments across China.

    Science.gov (United States)

    Zhai, Ran; Tao, Fulu

    2017-12-15

    Climate change and human activities are two major factors affecting water resource change. It is important to understand the roles of the major factors in affecting runoff change in different basins for watershed management. Here, we investigated the trends in climate and runoff in seven typical catchments in seven basins across China from 1961 to 2014. Then we attributed the runoff change to climate change and human activities in each catchment and in three time periods (1980s, 1990s and 2000s), using the VIC model and long-term runoff observation data. During 1961-2014, temperature increased significantly, while the trends in precipitation were insignificant in most of the catchments and inconsistent among the catchments. The runoff in most of the catchments showed a decreasing trend except the Yingluoxia catchment in the northwestern China. The contributions of climate change and human activities to runoff change varied in different catchments and time periods. In the 1980s, climate change contributed more to runoff change than human activities, which was 84%, 59%, -66%, -50%, 59%, 94%, and -59% in the Nianzishan, Yingluoxia, Xiahui, Yangjiaping, Sanjiangkou, Xixian, and Changle catchment, respectively. After that, human activities had played a more essential role in runoff change. In the 1990s and 2000s, human activities contributed more to runoff change than in the 1980s. The contribution by human activities accounted for 84%, -68%, and 67% in the Yingluoxia, Xiahui, and Sanjiangkou catchment, respectively, in the 1990s; and -96%, -67%, -94%, and -142% in the Nianzishan, Yangjiaping, Xixian, and Changle catchment, respectively, in the 2000s. It is also noted that after 2000 human activities caused decrease in runoff in all catchments except the Yingluoxia. Our findings highlight that the effects of human activities, such as increase in water withdrawal, land use/cover change, operation of dams and reservoirs, should be well managed. Copyright © 2017 Elsevier

  19. Prediction limits of mobile phone activity modelling

    Science.gov (United States)

    Kondor, Dániel; Grauwin, Sebastian; Kallus, Zsófia; Gódor, István; Sobolevsky, Stanislav; Ratti, Carlo

    2017-02-01

    Thanks to their widespread usage, mobile devices have become one of the main sensors of human behaviour and digital traces left behind can be used as a proxy to study urban environments. Exploring the nature of the spatio-temporal patterns of mobile phone activity could thus be a crucial step towards understanding the full spectrum of human activities. Using 10 months of mobile phone records from Greater London resolved in both space and time, we investigate the regularity of human telecommunication activity on urban scales. We evaluate several options for decomposing activity timelines into typical and residual patterns, accounting for the strong periodic and seasonal components. We carry out our analysis on various spatial scales, showing that regularity increases as we look at aggregated activity in larger spatial units with more activity in them. We examine the statistical properties of the residuals and show that it can be explained by noise and specific outliers. Also, we look at sources of deviations from the general trends, which we find to be explainable based on knowledge of the city structure and places of attractions. We show examples how some of the outliers can be related to external factors such as specific social events.

  20. Modeling and remodeling of human extraction sockets.

    Science.gov (United States)

    Trombelli, Leonardo; Farina, Roberto; Marzola, Andrea; Bozzi, Leopoldo; Liljenberg, Birgitta; Lindhe, Jan

    2008-07-01

    The available studies on extraction wound repair in humans are affected by significant limitations and have failed to evaluate tissue alterations occurring in all compartments of the hard tissue defect. To monitor during a 6-month period the healing of human extraction sockets and include a semi-quantitative analysis of tissues and cell populations involved in various stages of the processes of modeling/remodeling. Twenty-seven biopsies, representative of the early (2-4 weeks, n=10), intermediate (6-8 weeks, n=6), and late phase (12-24 weeks, n=11) of healing, were collected and analysed. Granulation tissue that was present in comparatively large amounts in the early healing phase of socket healing, was in the interval between the early and intermediate observation phase replaced with provisional matrix and woven bone. The density of vascular structures and macrophages slowly decreased from 2 to 4 weeks over time. The presence of osteoblasts peaked at 6-8 weeks and remained almost stable thereafter; a small number of osteoclasts were present in a few specimens at each observation interval. The present findings demonstrated that great variability exists in man with respect to hard tissue formation within extraction sockets. Thus, whereas a provisional connective tissue consistently forms within the first weeks of healing, the interval during which mineralized bone is laid down is much less predictable.

  1. In Vitro Model of Human Choroidal Neovascular

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Choroidal capillary endothelia cell (CEC) plays a critical role in the development of choroidal neovascularization which is one of the major causes of blindness. An effective method for CEC cultivation was proposed.The isolation of human choroidal CECs using micro dissection followed by the use of superparamagnetic beads (Dynabeads) coated with the CD 31, which selectively binds to the endothelial cell surface. Cells bound to beads were isolated using a magnetic particle concentrator. The CECs were planted into type Ⅳ collagen coated 24 well plates. The results show that the primary cultured CEC is induced to tube formation in collagen Ⅳ coated environment, which can be presented as an in vitro model of choroidal neovascularization.

  2. Molecular Modeling of Prion Transmission to Humans

    Directory of Open Access Journals (Sweden)

    Etienne Levavasseur

    2014-10-01

    Full Text Available Using different prion strains, such as the variant Creutzfeldt-Jakob disease agent and the atypical bovine spongiform encephalopathy agents, and using transgenic mice expressing human or bovine prion protein, we assessed the reliability of protein misfolding cyclic amplification (PMCA to model interspecies and genetic barriers to prion transmission. We compared our PMCA results with in vivo transmission data characterized by attack rates, i.e., the percentage of inoculated mice that developed the disease. Using 19 seed/substrate combinations, we observed that a significant PMCA amplification was only obtained when the mouse line used as substrate is susceptible to the corresponding strain. Our results suggest that PMCA provides a useful tool to study genetic barriers to transmission and to study the zoonotic potential of emerging prion strains.

  3. Brain Activation During Singing: "Clef de Sol Activation" Is the "Concert" of the Human Brain.

    Science.gov (United States)

    Mavridis, Ioannis N; Pyrgelis, Efstratios-Stylianos

    2016-03-01

    Humans are the most complex singers in nature, and the human voice is thought by many to be the most beautiful musical instrument. Aside from spoken language, singing represents a second mode of acoustic communication in humans. The purpose of this review article is to explore the functional anatomy of the "singing" brain. Methodologically, the existing literature regarding activation of the human brain during singing was carefully reviewed, with emphasis on the anatomic localization of such activation. Relevant human studies are mainly neuroimaging studies, namely functional magnetic resonance imaging and positron emission tomography studies. Singing necessitates activation of several cortical, subcortical, cerebellar, and brainstem areas, served and coordinated by multiple neural networks. Functionally vital cortical areas of the frontal, parietal, and temporal lobes bilaterally participate in the brain's activation process during singing, confirming the latter's role in human communication. Perisylvian cortical activity of the right hemisphere seems to be the most crucial component of this activation. This also explains why aphasic patients due to left hemispheric lesions are able to sing but not speak the same words. The term clef de sol activation is proposed for this crucial perisylvian cortical activation due to the clef de sol shape of the topographical distribution of these cortical areas around the sylvian fissure. Further research is needed to explore the connectivity and sequence of how the human brain activates to sing.

  4. Active site similarity between human and Plasmodium falciparum phosphodiesterases: considerations for antimalarial drug design

    Science.gov (United States)

    Howard, Brittany L.; Thompson, Philip E.; Manallack, David T.

    2011-08-01

    The similarity between Plasmodium falciparum phosphodiesterase enzymes ( PfPDEs) and their human counterparts have been examined and human PDE9A was found to be a suitable template for the construction of homology models for each of the four PfPDE isoforms. In contrast, the architecture of the active sites of each model was most similar to human PDE1. Molecular docking was able to model cyclic guanosine monophosphate (cGMP) substrate binding in each case but a docking mode supporting cyclic adenosine monophosphate (cAMP) binding could not be found. Anticipating the potential of PfPDE inhibitors as anti-malarial drugs, a range of reported PDE inhibitors including zaprinast and sildenafil were docked into the model of PfPDEα. The results were consistent with their reported biological activities, and the potential of PDE1/9 inhibitor analogues was also supported by docking.

  5. Dual-induced multifractality of human online activity

    CERN Document Server

    Qin, Yuhao; Cai, Shimin; Gao, Liang

    2014-01-01

    Recent discoveries of human activity reveal the existence of long-term correlation and its relation with the fat-tailed distribution of inter-event times, which imply that there exists the fractality of human activity. However, works further analyzing the type of fractality and its origin still lack. Herein, DFA and MFDFA methods are applied in the analysis of time series of online reviewing activity from Movielens and Netflix. Results show the long-term correlation at individual and whole community level, while the strength of such correlation at individual level is restricted to activity level. Such long-term correlation reveals the fractality of online reviewing activity. In our further investigation of this fractality, we \\emph{first} demonstrate it is multifractality, which results from the dual effect of broad probability density function and long-term correlation of time series in online reviewing activity. This result is also verified by three synthesized series. Therefore, we conclude that the combin...

  6. Design of a Human Reliability Assessment model for structural engineering

    NARCIS (Netherlands)

    De Haan, J.; Terwel, K.C.; Al-Jibouri, S.H.S.

    2013-01-01

    It is generally accepted that humans are the “weakest link” in structural design and construction processes. Despite this, few models are available to quantify human error within engineering processes. This paper demonstrates the use of a quantitative Human Reliability Assessment model within struct

  7. Analysis of rear end impact using mathematical human modelling

    NARCIS (Netherlands)

    Happee, R.; Meijer, R.; Horst, M.J. van der; Ono, K.; Yamazaki, K.

    2000-01-01

    At TNO an omni-directional mathematical human body model has been developed. Until now this human model has been validated for frontal and lateral loading using response data of volunteer and post mortem human subject (PMHS) sled tests. For rearward loading it has been validated for high speed impac

  8. Comparison of fusion methods based on DST and DBN in human activity recognition

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Ambient assistive living environments require sophisticated information fusion and reasoning techniques to accurately identify activities of a person under care. In this paper, we explain, compare and discuss the application of two powerful fusion methods, namely dynamic Bayesian networks (DBN) and Dempster-Shafer theory (DST), for human activity recognition. Both methods are described, the implementation of activity recognition based on these methods is explained, and model acquisition and composition are ...

  9. Selective activation of neuromuscular compartments within the human trapezius muscle

    DEFF Research Database (Denmark)

    Holtermann, A; Roeleveld, K; Mork, P J

    2009-01-01

    was to investigate whether subdivisions within the human trapezius can be independently activated by voluntary command using biofeedback guidance. Bipolar electromyographical electrodes were situated on four subdivisions of the trapezius muscle. The threshold for "active" and "rest" for each subdivision was set...... to >12% and biofeedback from each of the four trapezius subdivisions, 11 of 15 subjects learned selective activation of at least one of the four anatomical subdivisions of the trapezius...

  10. A Competitive Approach for Human Activity Recognition on Smartphones

    OpenAIRE

    Reiss, Attila; Hendeby, Gustaf; Stricker, Didier

    2013-01-01

    This paper describes a competitive approach developed for an activity recognition challenge. The competition was defined on a new and publicly available dataset of human activities, recorded with smartphone sensors. This work investigates different feature sets for the activity recognition task of the competition. Moreover, the focus is also on the introduction of a new, confidence-based boosting algorithm called ConfAda- Boost.M1. Results show that the new classification method outperforms c...

  11. ANTIMICROBIAL ACTIVITIES OF RICINUS COMMUNIS AGAINST SOME HUMAN PATHOGENS

    OpenAIRE

    Kushwah Poonam; Singh Krishan Pratap

    2012-01-01

    The present paper deals with the antimicrobial activities of seed extracts of Ricinus communis against some human pathogenic bacteria namely Bacillus subtilis, Bacillus cereus, Staphylococcus aureus, Escherichia coli and two fungal strains namely Candida albicans and Candida glabrata. The aqueous and methanol extracts of seeds were screened for their antibacterial activity using agar disc diffusion method. The aqueous seed extracts were less active but methanol extracts showed high degree zon...

  12. Effects of Climate Change and Human Activities on Surface Runoff in the Luan River Basin

    Directory of Open Access Journals (Sweden)

    Sidong Zeng

    2015-01-01

    Full Text Available Quantifying the effects of climate change and human activities on runoff changes is the focus of climate change and hydrological research. This paper presents an integrated method employing the Budyko-based Fu model, hydrological modeling, and climate elasticity approaches to separate the effects of the two driving factors on surface runoff in the Luan River basin, China. The Budyko-based Fu model and the double mass curve method are used to analyze runoff changes during the period 1958~2009. Then two types of hydrological models (the distributed Soil and Water Assessment Tool model and the lumped SIMHYD model and seven climate elasticity methods (including a nonparametric method and six Budyko-based methods are applied to estimate the contributions of climate change and human activities to runoff change. The results show that all quantification methods are effective, and the results obtained by the nine methods are generally consistent. During the study period, the effects of climate change on runoff change accounted for 28.3~46.8% while those of human activities contributed with 53.2~71.7%, indicating that both factors have significant effects on the runoff decline in the basin, and that the effects of human activities are relatively stronger than those of climate change.

  13. Development and implication of a human-volcano system model

    Science.gov (United States)

    Bachri, Syamsul; Stötter, Johann; Monreal, Matthias; Sartohadi, Junun

    2014-05-01

    In an attempt to understand the complexity of human-environment systems, models help to define, quantify, describe, or simulate complex interactions. With regards to the human-volcano system, we develop a conceptual model in order to assist analysis of its two basic elements, the physical and the social environment. A field survey of the human environment interaction of two of the most active volcanic areas in Indonesia (Mt. Merapi and Mt. Bromo) and a corresponding literature review from other case studies was carried out. A differentiated understanding of human interaction with hazard potential elements within the human-volcano system is the main focus of the model development. We classified volcanic processes and effects as three pairs of dichotomies: positive or negative impacts, on society or environment in an indirect or direct way. Each volcanically induced process or effect characterized accordingly leads to eight distinct process/effect classes. They are positive direct effects on society (PDS); positive direct effects on natural resources (PDN); positive indirect effects on society (PIS); positive indirect effects on natural resources (PIN); negative direct effects on society (NDS); negative direct effects on natural resources (NDN); negative indirect effects on society (NIS) and lastly negative indirect effects on natural resources (NIN). Such differentiated view of volcanic process/effects bears several advantages. First, whereas volcanic processes have hitherto been viewed as hazards only, it becomes possible now to describe a particular process/effect in a particular context as negative or positive. Secondly, such a categorization makes it possible to account for processes of the human-volcano system that do not have a direct physical expression but are of socio-cultural relevance. Thirdly, the greater degree of differentiation that is made possible when evaluating volcanic processes has significant repercussions on the way volcanic risk must be

  14. Functional Assessment of Pharmacological Telomerase Activators in Human T Cells

    Directory of Open Access Journals (Sweden)

    Rita B. Effros

    2013-01-01

    Full Text Available Telomeres are structures at the ends of chromosomes that shorten during cell division and eventually signal an irreversible state of growth arrest known as cellular senescence. To delay this cellular aging, human T cells, which are critical in the immune control over infections and cancer, activate the enzyme telomerase, which binds and extends the telomeres. Several different extracts from the Astragalus membranaceus root have been documented to activate telomerase activity in human T cells. The objective of this research was to compare two extracts from Astragalus membranaceus, TA-65 and HTA, for their effects on both telomerase and proliferative activity of human CD4 and CD8 T cells. Our results demonstrate that, TA-65 increased telomerase activity significantly (1.3 to 3.3-fold relative to controls in T cell cultures from six donors tested, whereas HTA only increased telomerase levels in two out of six donors. We also demonstrate that TA-65 activates telomerase by a MAPK- specific pathway. Finally, we determine that during a three-day culture period, only the T cells treated with the TA-65 extract showed a statistically significant increase in proliferative activity. Our results underscore the importance of comparing multiple telomerase activators within the same experiment, and of including functional assays in addition to measuring telomerase activity.

  15. Activity-based resource capability modeling

    Institute of Scientific and Technical Information of China (English)

    CHENG Shao-wu; XU Xiao-fei; WANG Gang; SUN Xue-dong

    2008-01-01

    To analyse and optimize a enterprise process in a wide scope, an activity-based method of modeling resource capabilities is presented. It models resource capabilities by means of the same structure as an activity, that is, resource capabilities are defined by input objects, actions and output objects. A set of activity-based re-source capability modeling rules and matching rules between an activity and a resource are introduced. This method can not only be used to describe capability of manufacturing tools, but also capability of persons and applications, etc. It unifies methods of modeling capability of all kinds of resources in an enterprise and supports the optimization of the resource allocation of a process.

  16. Incremental activity modeling in multiple disjoint cameras.

    Science.gov (United States)

    Loy, Chen Change; Xiang, Tao; Gong, Shaogang

    2012-09-01

    Activity modeling and unusual event detection in a network of cameras is challenging, particularly when the camera views are not overlapped. We show that it is possible to detect unusual events in multiple disjoint cameras as context-incoherent patterns through incremental learning of time delayed dependencies between distributed local activities observed within and across camera views. Specifically, we model multicamera activities using a Time Delayed Probabilistic Graphical Model (TD-PGM) with different nodes representing activities in different decomposed regions from different views and the directed links between nodes encoding their time delayed dependencies. To deal with visual context changes, we formulate a novel incremental learning method for modeling time delayed dependencies that change over time. We validate the effectiveness of the proposed approach using a synthetic data set and videos captured from a camera network installed at a busy underground station.

  17. Regulation of IL-17A production is distinct from IL-17F in a primary human cell co-culture model of T cell-mediated B cell activation.

    Directory of Open Access Journals (Sweden)

    Andrew C Melton

    Full Text Available Improper regulation of B cell responses leads to excessive production of antibodies and contributes to the development of autoimmune disease. T helper 17 (Th17 cells also drive the development of autoimmune disease, but the role of B cells in shaping Th17 cell-mediated immune responses, as well as the reciprocal regulation of B cell responses by IL-17 family cytokines, remains unclear. The aim of this study was to characterize the regulation of IL-17A and IL-17F in a model of T cell-dependent B cell activation. Stimulation of primary human B cell and peripheral blood mononuclear cell (BT co-cultures with α-IgM and a non-mitogenic concentration of superantigens for three days promoted a Th17 cell response as evidenced by increased expression of Th17-related gene transcripts, including Il17f, Il21, Il22, and Il23r, in CD4 T cells, as well as the secretion of IL-17A and IL-17F protein. We tested the ability of 144 pharmacologic modulators representing 91 different targets or pathways to regulate IL-17A and IL-17F production in these stimulated BT co-cultures. IL-17A production was found to be preferentially sensitive to inhibition of the PI3K/mTOR pathway, while prostaglandin EP receptor agonists, including PGE2, increased IL-17A concentrations. In contrast, the production of IL-17F was inhibited by PGE2, but selectively increased by TLR2 and TLR5 agonists. These results indicate that IL-17A regulation is distinct from IL-17F in stimulated BT co-cultures and that this co-culture approach can be used to identify pathway mechanisms and novel agents that selectively inhibit production of IL-17A or IL-17F.

  18. Integrated Human Futures Modeling in Egypt

    Energy Technology Data Exchange (ETDEWEB)

    Passell, Howard D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Aamir, Munaf Syed [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Bernard, Michael Lewis [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Beyeler, Walter E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Fellner, Karen Marie [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hayden, Nancy Kay [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Jeffers, Robert Fredric [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Keller, Elizabeth James Kistin [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Malczynski, Leonard A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Mitchell, Michael David [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Silver, Emily [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Tidwell, Vincent C. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Villa, Daniel [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Vugrin, Eric D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Engelke, Peter [Atlantic Council, Washington, D.C. (United States); Burrow, Mat [Atlantic Council, Washington, D.C. (United States); Keith, Bruce [United States Military Academy, West Point, NY (United States)

    2016-01-01

    The Integrated Human Futures Project provides a set of analytical and quantitative modeling and simulation tools that help explore the links among human social, economic, and ecological conditions, human resilience, conflict, and peace, and allows users to simulate tradeoffs and consequences associated with different future development and mitigation scenarios. In the current study, we integrate five distinct modeling platforms to simulate the potential risk of social unrest in Egypt resulting from the Grand Ethiopian Renaissance Dam (GERD) on the Blue Nile in Ethiopia. The five platforms simulate hydrology, agriculture, economy, human ecology, and human psychology/behavior, and show how impacts derived from development initiatives in one sector (e.g., hydrology) might ripple through to affect other sectors and how development and security concerns may be triggered across the region. This approach evaluates potential consequences, intended and unintended, associated with strategic policy actions that span the development-security nexus at the national, regional, and international levels. Model results are not intended to provide explicit predictions, but rather to provide system-level insight for policy makers into the dynamics among these interacting sectors, and to demonstrate an approach to evaluating short- and long-term policy trade-offs across different policy domains and stakeholders. The GERD project is critical to government-planned development efforts in Ethiopia but is expected to reduce downstream freshwater availability in the Nile Basin, fueling fears of negative social and economic impacts that could threaten stability and security in Egypt. We tested these hypotheses and came to the following preliminary conclusions. First, the GERD will have an important short-term impact on water availability, food production, and hydropower production in Egypt, depending on the short- term reservoir fill rate. Second, the GERD will have a very small impact on

  19. A novel in vitro human microglia model: characterization of human monocyte-derived microglia.

    Science.gov (United States)

    Etemad, Samar; Zamin, Rasheeda Mohd; Ruitenberg, Marc J; Filgueira, Luis

    2012-07-30

    Microglia are the innate immune cells of the central nervous system. They help maintaining physiological homeostasis and contribute significantly to inflammatory responses in the course of infection, injury and degenerative processes. To date, there is no standardized simple model available to investigate the biology of human microglia. The aim of this study was to establish a new human microglia model. For that purpose, human peripheral blood monocytes were cultured in serum free medium in the presence of M-CSF, GM-CSF, NGF and CCL2 to generate monocyte-derived microglia (M-MG). M-MG were clearly different in morphology, phenotype and function from freshly isolated monocytes, cultured monocytes in the absence of the cytokines and monocyte-derived dendritic cells (M-DC) cultured in the presence of GM-CSF and IL-4. M-MG acquired a ramified morphology with primary and secondary processes. M-MG displayed a comparable phenotype to the human microglia cell line HMC3, expressing very low levels of CD45, CD14 and HLA-DR, CD11b and CD11c; and undetectable levels of CD40, CD80 and CD83, and a distinct pattern of chemokine receptors (positive for CCR1, CCR2, CCR4, CCR5, CXCR1, CXCR3, CX3CR1; negative for CCR6 and CCR7). In comparison with M-DC, M-MG displayed lower T-lymphocyte stimulatory capacity, as well as lower phagocytosis activity. The described protocol for the generation of human monocyte-derived microglia is feasible, well standardized and reliable, as it uses well defined culture medium and recombinant cytokines, but no serum or conditioned medium. This protocol will certainly be very helpful for future studies investigating the biology and pathology of human microglia.

  20. Human activity recognition based on feature selection in smart home using back-propagation algorithm.

    Science.gov (United States)

    Fang, Hongqing; He, Lei; Si, Hao; Liu, Peng; Xie, Xiaolei

    2014-09-01

    In this paper, Back-propagation(BP) algorithm has been used to train the feed forward neural network for human activity recognition in smart home environments, and inter-class distance method for feature selection of observed motion sensor events is discussed and tested. And then, the human activity recognition performances of neural network using BP algorithm have been evaluated and compared with other probabilistic algorithms: Naïve Bayes(NB) classifier and Hidden Markov Model(HMM). The results show that different feature datasets yield different activity recognition accuracy. The selection of unsuitable feature datasets increases the computational complexity and degrades the activity recognition accuracy. Furthermore, neural network using BP algorithm has relatively better human activity recognition performances than NB classifier and HMM.

  1. Mitigating Insider Threat Using Human Behavior Influence Models

    Science.gov (United States)

    2006-06-01

    Change in Score Versus Time for Both Employees (over 3 years).......................94 45. Distribution of Sensitivity Tests Performed ...Human Behavior Human Behavior is defined as a “collection of activities performed by human beings and influenced by culture, attitudes, emotions...values, ethics, authority, rapport, hypnosis , persuasion, and/or coercion.” [6] The theory behind human behavior is humans react to “definite objective

  2. The Human-Computer Domain Relation in UX Models

    DEFF Research Database (Denmark)

    Clemmensen, Torkil

    This paper argues that the conceptualization of the human, the computer and the domain of use in competing lines of UX research have problematic similarities and superficial differences. The paper qualitatively analyses concepts and models in five research papers that together represent two...... influential lines of UX research: aesthetics and temporal UX, and two use situations: using a website and starting to use a smartphone. The results suggest that the two lines of UX research share a focus on users’ evaluative judgments of technology, both focuses on product qualities rather than activity...... domains, give little details about users, and treat human-computer interaction as perception. The conclusion gives similarities and differences between the approaches to UX. The implications for theory building are indicated....

  3. Activation of GPR119 Stimulates Human β-Cell Replication and Neogenesis in Humanized Mice with Functional Human Islets

    Science.gov (United States)

    Ansarullah; Free, Colette; Christopherson, Jenica; Chen, Quanhai; Gao, Jie; Liu, Chengyang; Naji, Ali; Rabinovitch, Alex; Guo, Zhiguang

    2016-01-01

    Using humanized mice with functional human islets, we investigated whether activating GPR119 by PSN632408, a small molecular agonist, can stimulate human β-cell regeneration in vivo. Human islets were transplanted under the left kidney capsule of immunodeficient mice with streptozotocin- (STZ-) induced diabetes. The recipient mice were treated with PSN632408 or vehicle and BrdU daily. Human islet graft function in the mice was evaluated by nonfasting glucose levels, oral glucose tolerance, and removal of the grafts. Immunostaining for insulin, glucagon, and BrdU or Ki67 was performed in islet grafts to evaluate α- and β-cell replication. Insulin and CK19 immunostaining was performed to evaluate β-cell neogenesis. Four weeks after human islet transplantation, 71% of PSN632408-treated mice achieved normoglycaemia compared with 24% of vehicle-treated mice. Also, oral glucose tolerance was significantly improved in the PSN632408-treated mice. PSN632408 treatment significantly increased both human α- and β-cell areas in islet grafts and stimulated α- and β-cell replication. In addition, β-cell neogenesis was induced from pancreatic duct cells in the islet grafts. Our results demonstrated that activation of GPR119 increases β-cell mass by stimulating human β-cell replication and neogenesis. Therefore, GPR119 activators may qualify as therapeutic agents to increase human β-cell mass in patients with diabetes. PMID:27413754

  4. Human-water interface in hydrological modelling: current status and future directions

    Science.gov (United States)

    Wada, Yoshihide; Bierkens, Marc F. P.; de Roo, Ad; Dirmeyer, Paul A.; Famiglietti, James S.; Hanasaki, Naota; Konar, Megan; Liu, Junguo; Müller Schmied, Hannes; Oki, Taikan; Pokhrel, Yadu; Sivapalan, Murugesu; Troy, Tara J.; van Dijk, Albert I. J. M.; van Emmerik, Tim; Van Huijgevoort, Marjolein H. J.; Van Lanen, Henny A. J.; Vörösmarty, Charles J.; Wanders, Niko; Wheater, Howard

    2017-08-01

    Over recent decades, the global population has been rapidly increasing and human activities have altered terrestrial water fluxes to an unprecedented extent. The phenomenal growth of the human footprint has significantly modified hydrological processes in various ways (e.g. irrigation, artificial dams, and water diversion) and at various scales (from a watershed to the globe). During the early 1990s, awareness of the potential for increased water scarcity led to the first detailed global water resource assessments. Shortly thereafter, in order to analyse the human perturbation on terrestrial water resources, the first generation of large-scale hydrological models (LHMs) was produced. However, at this early stage few models considered the interaction between terrestrial water fluxes and human activities, including water use and reservoir regulation, and even fewer models distinguished water use from surface water and groundwater resources. Since the early 2000s, a growing number of LHMs have incorporated human impacts on the hydrological cycle, yet the representation of human activities in hydrological models remains challenging. In this paper we provide a synthesis of progress in the development and application of human impact modelling in LHMs. We highlight a number of key challenges and discuss possible improvements in order to better represent the human-water interface in hydrological models.

  5. Constrained Total Energy Expenditure and Metabolic Adaptation to Physical Activity in Adult Humans.

    Science.gov (United States)

    Pontzer, Herman; Durazo-Arvizu, Ramon; Dugas, Lara R; Plange-Rhule, Jacob; Bovet, Pascal; Forrester, Terrence E; Lambert, Estelle V; Cooper, Richard S; Schoeller, Dale A; Luke, Amy

    2016-02-08

    Current obesity prevention strategies recommend increasing daily physical activity, assuming that increased activity will lead to corresponding increases in total energy expenditure and prevent or reverse energy imbalance and weight gain [1-3]. Such Additive total energy expenditure models are supported by exercise intervention and accelerometry studies reporting positive correlations between physical activity and total energy expenditure [4] but are challenged by ecological studies in humans and other species showing that more active populations do not have higher total energy expenditure [5-8]. Here we tested a Constrained total energy expenditure model, in which total energy expenditure increases with physical activity at low activity levels but plateaus at higher activity levels as the body adapts to maintain total energy expenditure within a narrow range. We compared total energy expenditure, measured using doubly labeled water, against physical activity, measured using accelerometry, for a large (n = 332) sample of adults living in five populations [9]. After adjusting for body size and composition, total energy expenditure was positively correlated with physical activity, but the relationship was markedly stronger over the lower range of physical activity. For subjects in the upper range of physical activity, total energy expenditure plateaued, supporting a Constrained total energy expenditure model. Body fat percentage and activity intensity appear to modulate the metabolic response to physical activity. Models of energy balance employed in public health [1-3] should be revised to better reflect the constrained nature of total energy expenditure and the complex effects of physical activity on metabolic physiology.

  6. Genomic responses in mouse models poorly mimic human inflammatory diseases.

    Science.gov (United States)

    Seok, Junhee; Warren, H Shaw; Cuenca, Alex G; Mindrinos, Michael N; Baker, Henry V; Xu, Weihong; Richards, Daniel R; McDonald-Smith, Grace P; Gao, Hong; Hennessy, Laura; Finnerty, Celeste C; López, Cecilia M; Honari, Shari; Moore, Ernest E; Minei, Joseph P; Cuschieri, Joseph; Bankey, Paul E; Johnson, Jeffrey L; Sperry, Jason; Nathens, Avery B; Billiar, Timothy R; West, Michael A; Jeschke, Marc G; Klein, Matthew B; Gamelli, Richard L; Gibran, Nicole S; Brownstein, Bernard H; Miller-Graziano, Carol; Calvano, Steve E; Mason, Philip H; Cobb, J Perren; Rahme, Laurence G; Lowry, Stephen F; Maier, Ronald V; Moldawer, Lyle L; Herndon, David N; Davis, Ronald W; Xiao, Wenzhong; Tompkins, Ronald G

    2013-02-26

    A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R(2) between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases.

  7. Genomic responses in mouse models poorly mimic human inflammatory diseases

    Science.gov (United States)

    Seok, Junhee; Warren, H. Shaw; Cuenca, Alex G.; Mindrinos, Michael N.; Baker, Henry V.; Xu, Weihong; Richards, Daniel R.; McDonald-Smith, Grace P.; Gao, Hong; Hennessy, Laura; Finnerty, Celeste C.; López, Cecilia M.; Honari, Shari; Moore, Ernest E.; Minei, Joseph P.; Cuschieri, Joseph; Bankey, Paul E.; Johnson, Jeffrey L.; Sperry, Jason; Nathens, Avery B.; Billiar, Timothy R.; West, Michael A.; Jeschke, Marc G.; Klein, Matthew B.; Gamelli, Richard L.; Gibran, Nicole S.; Brownstein, Bernard H.; Miller-Graziano, Carol; Calvano, Steve E.; Mason, Philip H.; Cobb, J. Perren; Rahme, Laurence G.; Lowry, Stephen F.; Maier, Ronald V.; Moldawer, Lyle L.; Herndon, David N.; Davis, Ronald W.; Xiao, Wenzhong; Tompkins, Ronald G.; Abouhamze, Amer; Balis, Ulysses G. J.; Camp, David G.; De, Asit K.; Harbrecht, Brian G.; Hayden, Douglas L.; Kaushal, Amit; O’Keefe, Grant E.; Kotz, Kenneth T.; Qian, Weijun; Schoenfeld, David A.; Shapiro, Michael B.; Silver, Geoffrey M.; Smith, Richard D.; Storey, John D.; Tibshirani, Robert; Toner, Mehmet; Wilhelmy, Julie; Wispelwey, Bram; Wong, Wing H

    2013-01-01

    A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R2 between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases. PMID:23401516

  8. Modelling elasticity in solids using active cubes - application to simulated operations

    DEFF Research Database (Denmark)

    Bro-Nielsen, Morten

    1995-01-01

    The paper describes an approach to elastic modelling of human tissue based on the use of 3D solid active models-active cubes (M. Bro-Nielsen, 1994)-and a shape description based on the metric tensor in a solid. Active cubes are used because they provide a natural parameterization of the surface a...

  9. Detection of cardiac activity changes from human speech

    Science.gov (United States)

    Tovarek, Jaromir; Partila, Pavol; Voznak, Miroslav; Mikulec, Martin; Mehic, Miralem

    2015-05-01

    Impact of changes in blood pressure and pulse from human speech is disclosed in this article. The symptoms of increased physical activity are pulse, systolic and diastolic pressure. There are many methods of measuring and indicating these parameters. The measurements must be carried out using devices which are not used in everyday life. In most cases, the measurement of blood pressure and pulse following health problems or other adverse feelings. Nowadays, research teams are trying to design and implement modern methods in ordinary human activities. The main objective of the proposal is to reduce the delay between detecting the adverse pressure and to the mentioned warning signs and feelings. Common and frequent activity of man is speaking, while it is known that the function of the vocal tract can be affected by the change in heart activity. Therefore, it can be a useful parameter for detecting physiological changes. A method for detecting human physiological changes by speech processing and artificial neural network classification is described in this article. The pulse and blood pressure changes was induced by physical exercises in this experiment. The set of measured subjects was formed by ten healthy volunteers of both sexes. None of the subjects was a professional athlete. The process of the experiment was divided into phases before, during and after physical training. Pulse, systolic, diastolic pressure was measured and voice activity was recorded after each of them. The results of this experiment describe a method for detecting increased cardiac activity from human speech using artificial neural network.

  10. Antimicrobial activity of Uncaria tomentosa against oral human pathogens

    OpenAIRE

    Renzo Alberto Ccahuana-Vasquez; Silvana Soléo Ferreira dos Santos; Cristiane Yumi Koga-Ito; Antonio Olavo Cardoso Jorge

    2007-01-01

    Uncaria tomentosa is considered a medicinal plant used over centuries by the peruvian population as an alternative treatment for several diseases. Many microorganisms usually inhabit the human oral cavity and under certain conditions can become etiologic agents of diseases. The aim of the present study was to evaluate the antimicrobial activity of different concentrations of Uncaria tomentosa on different strains of microorganisms isolated from the human oral cavity. Micropulverized Uncaria t...

  11. Human DJ-1-specific Transcriptional Activation of Tyrosine Hydroxylase Gene*

    Science.gov (United States)

    Ishikawa, Shizuma; Taira, Takahiro; Takahashi-Niki, Kazuko; Niki, Takeshi; Ariga, Hiroyoshi; Iguchi-Ariga, Sanae M. M.

    2010-01-01

    Loss-of-function mutation in the DJ-1 gene causes a subset of familial Parkinson disease. The mechanism underlying DJ-1-related selective vulnerability in the dopaminergic pathway is, however, not known. DJ-1 has multiple functions, including transcriptional regulation, and one of transcriptional target genes for DJ-1 is the tyrosine hydroxylase (TH) gene, the product of which is a key enzyme for dopamine biosynthesis. It has been reported that DJ-1 is a neuroprotective transcriptional co-activator that sequesters a transcriptional co-repressor polypyrimidine tract-binding protein-associated splicing factor (PSF) from the TH gene promoter. In this study, we found that knockdown of human DJ-1 by small interference RNA in human dopaminergic cell lines attenuated TH gene expression and 4-dihydroxy-l-phenylalanine production but that knockdown or knock-out of mouse DJ-1 in mouse cell lines or in mice did not affect such expression and TH activity. In reporter assays using the human TH gene promoter linked to the luciferase gene, stimulation of TH promoter activity was observed in human cells, but not mouse cells, that had been transfected with DJ-1. Although human DJ-1 and mouse DJ-1 were associated either with human or with mouse PSF, TH promoter activity inhibited by PSF was restored by human DJ-1 but not by mouse DJ-1. Chromatin immunoprecipitation assays revealed that the complex of PSF with DJ-1 bound to the human but not the mouse TH gene promoter. These results suggest a novel species-specific transcriptional regulation of the TH promoter by DJ-1 and one of the mechanisms for no reduction of TH in DJ-1-knock-out mice. PMID:20938049

  12. Carbon-climate-human interactions in an integrated human-Earth system model

    Science.gov (United States)

    Calvin, K. V.; Bond-Lamberty, B. P.; Jones, A. D.; Shi, X.

    2016-12-01

    The C4MIP and CMIP5 results highlighted large uncertainties in climate projections, driven to a large extent by limited understanding of the interactions between terrestrial carbon-cycle and climate feedbacks, and their associated uncertainties. These feedbacks are dominated by uncertainties in soil processes, disturbance dynamics, ecosystem response to climate change, and agricultural productivity, and land-use change. This research addresses three questions: (1) how do terrestrial feedbacks vary across different levels of climate change, (2) what is the relative contribution of CO2 fertilization and climate change, and (3) how robust are the results across different models and methods? We used a coupled modeling framework that integrates an Integrated Assessment Model (modeling economic and energy activity) with an Earth System Model (modeling the natural earth system) to examine how business-as-usual (RCP 8.5) climate change will affect ecosystem productivity, cropland extent, and other aspects of the human-Earth system. We find that higher levels of radiative forcing result in higher productivity growth, that increases in CO2 concentrations are the dominant contributors to that growth, and that our productivity increases fall in the middle of the range when compared to other CMIP5 models and the AgMIP models. These results emphasize the importance of examining both the anthropogenic and natural components of the earth system, and their long-term interactive feedbacks.

  13. The Model of Unreliable Elements (Human Resources) Intellectual Management System on the Basis of Their Psychological and Personal Characteristics

    OpenAIRE

    Ryabtsev, Timofey; Antonova, Elena

    2008-01-01

    The Article suggests a possible approach to creation of the Intellectual Management System for human resources and personnel (during their professional tasks solving), and that could consider personal characteristics and psychological condition of the human resources as an “unreliable” element. The Article describes some elements of the Intellectual Management System: professional activity model and “unreliable” element (human resources) model.

  14. The United Nations Human Space Technology Initiative (HSTI): Science Activities

    CERN Document Server

    Niu, A; Haubold, H J; Doi, T

    2012-01-01

    The United Nations Human Space Technology Initiative (HSTI) aims at promoting international cooperation in human spaceflight and space exploration-related activities; creating awareness among countries on the benefits of utilizing human space technology and its applications; and building capacity in microgravity education and research. HSTI has been conducting various scientific activities to promote microgravity education and research. The primary science activity is called 'Zero-gravity Instrument Distribution Project', in which one-axis clinostats will be distributed worldwide. The distribution project will provide unique opportunities for students and researchers to observe the growth of indigenous plants in their countries in a simulated microgravity condition and is expected to create a huge dataset of plant species with their responses to gravity.

  15. Learning models of activities involving interacting objects

    DEFF Research Database (Denmark)

    Manfredotti, Cristina; Pedersen, Kim Steenstrup; Hamilton, Howard J.;

    2013-01-01

    We propose the LEMAIO multi-layer framework, which makes use of hierarchical abstraction to learn models for activities involving multiple interacting objects from time sequences of data concerning the individual objects. Experiments in the sea navigation domain yielded learned models that were...

  16. Capturing Appearance Variation in Active Appearance Models

    NARCIS (Netherlands)

    Van der Maaten, L.J.P.; Hendriks, E.A.

    2010-01-01

    The paper presents an extension of active appearance models (AAMs) that is better capable of dealing with the large variation in face appearance that is encountered in large multi-person face data sets. Instead of the traditional PCA-based texture model, our extended AAM employs a mixture of probabi

  17. Learning models of activities involving interacting objects

    DEFF Research Database (Denmark)

    Manfredotti, Cristina; Pedersen, Kim Steenstrup; Hamilton, Howard J.

    2013-01-01

    We propose the LEMAIO multi-layer framework, which makes use of hierarchical abstraction to learn models for activities involving multiple interacting objects from time sequences of data concerning the individual objects. Experiments in the sea navigation domain yielded learned models that were t...

  18. Src activity increases and Yes activity decreases during mitosis of human colon carcinoma cells.

    OpenAIRE

    Park, J.; Cartwright, C A

    1995-01-01

    Src and Yes protein-tyrosine kinase activities are elevated in malignant and premalignant tumors of the colon. To determine whether Src activity is elevated throughout the human colon carcinoma cell cycle as it is in polyomavirus middle T antigen- or F527 Src-transformed cells, and whether Yes activity, which is lower than that of Src in the carcinoma cells, is regulated differently, we measured their activities in cycling cells. We observed that the activities of both kinases were higher thr...

  19. Immunology of membranous nephropathy: from animal models to humans.

    Science.gov (United States)

    Sinico, R A; Mezzina, N; Trezzi, B; Ghiggeri, G M; Radice, A

    2016-02-01

    Membranous nephropathy (MN), the leading cause of nephrotic syndrome in adults, is characterized by the deposition of subepithelial immune deposits that consist mainly of immunoglobulin (Ig)G and complement. Most of the cases are primary or idiopathic (iMN), while only approximately 25% of the cases are secondary to some known disease such as systemic lupus erythematosus, hepatitis B, drugs and malignancies. Most of our knowledge on the pathogenesis of iMN has relied upon old experimental models (i.e. Heymann nephritis) that have shown that immune deposits are formed in situ by the reaction of autoantibodies against the respective podocyte antigen. Recent findings indicate that podocyte proteins also act as an autoantigen in human iMN. The M-type phospholipase A2 receptor (PLA2R) has been identified as the main target antigen, as it can be found in approximately 70% of iMN patients but only rarely in other glomerulonephritides. Podocytes damage in the experimental model of Heymann nephritis is complement-mediated. In humans, the presence of complement within the subepithelial deposits is well established, but IgG4, which does not activate complement by classical or alternative pathways, represents the predominant subclass of IgG anti-PLA2R. Some evidence suggests that IgG4 anti-PLA2R autoantibodies can bind mannan-binding lectin (MBL) and activate the lectin complement pathway. A genetic background for iMN has been demonstrated by genome-wide association studies that have shown highly significant associations of the PLA2R1 and the human leucocyte antigen (HLA)-DQA1 loci with iMN. In addition to their diagnostic value, anti-PLA2R antibodies may be useful to monitor disease activity and predict response to treatment.

  20. Modelling the Active Hearing Process in Mosquitoes

    Science.gov (United States)

    Avitabile, Daniele; Homer, Martin; Jackson, Joe; Robert, Daniel; Champneys, Alan

    2011-11-01

    A simple microscopic mechanistic model is described of the active amplification within the Johnston's organ of the mosquito species Toxorhynchites brevipalpis. The model is based on the description of the antenna as a forced-damped oscillator coupled to a set of active threads (ensembles of scolopidia) that provide an impulsive force when they twitch. This twitching is in turn controlled by channels that are opened and closed if the antennal oscillation reaches a critical amplitude. The model matches both qualitatively and quantitatively with recent experiments. New results are presented using mathematical homogenization techniques to derive a mesoscopic model as a simple oscillator with nonlinear force and damping characteristics. It is shown how the results from this new model closely resemble those from the microscopic model as the number of threads approach physiologically correct values.