Sample records for chronomics human time

  1. Chronomics, human time estimation, and aging

    Directory of Open Access Journals (Sweden)

    Franz Halberg


    Full Text Available Franz Halberg, Robert B Sothern, Germaine Cornélissen, Jerzy Czaplicki1Halberg Chronobiology Center, University of Minnesota, Minneapolis, MN, USA; 1Institut de Pharmacologie et de Biologie Structurale CNRS, Université Paul Sabatier, Toulouse, FranceBackground: Circadian rhythm stage affects many outcomes, including those of mental aging.Methods: Estimations of 1 minute ∼5 times/day for a year, 25 years apart, by a healthy male biomedical scientist (RBS, are analyzed by the extended cosinor.Results: Cycles of a half-week, a week, ∼30 days, a half-year and a year, in self-assessed 1-minute estimation by RBS between 25 and 60 years of age in health, are mapped for the first time, compared and opposite effects are found. For RBS at 60 vs at 25 years of age, it takes less time in the morning around 10:30 (P < 0.001, but not in the evening around 19:30 (P = 0.956, to estimate 1 minute.Discussion: During the intervening decades, the time of estimating 1 minute differed greatly, dependent on circadian stage, being a linear decrease in the morning and increase in the evening, the latter modulated by a ∼33.6-year cycle.Conclusion: Circadian and infradian rhythm mapping is essential for a scrutiny of effects of aging. A ∼30-day and a circannual component apparent at 25 years of age are not found later; cycles longer than a year are detected. Rhythm stages await tests as markers for timing therapy in disease.Keywords: circadian rhythm, mental function, time estimation

  2. Chronomics and ``Glocal'' (Combined Globaland Local) Assessment of Human Life (United States)

    Otsuka, K.; Cornélissen, G.; Norboo, T.; Takasugi, E.; Halberg, F.

    Most organisms, from cyanobacteria to mammals, are known to use circadian mechanisms to coordinate their activities with the natural 24-hour light/dark cycle and/or interacting socio-ecologic schedules. When the human clock gene was discovered in 1997, it was surprising to see that it was very similar in all earthly life. Recent findings suggest that organisms which evolved on Earth acquired many of the visible and invisible cycles of their habitat and/or of their cosmos. While circadian systems are well documented both time-macroscopically and time-microscopically, the temporal organization of physiological function is much more extensive. Long-term physiological quasi-ambulatory monitoring of blood pressure and heart rate, among other variables, such as those of the ECG and other tools of the neuroendocrinologic armamentarium, have already yielded information, among others, on circaseptan (about 7-day), transyears and cisyears (with periods slightly longer or shorter tha n one year, respectively), and circadecennian (about 10-year) cycles; the nervous system displays rhythms, chaos and trends, mapped as chronomes. Chronomes are time structures consisting of multifrequency rhythms covering frequencies over 18 orders of magnitude, elements of chaos, trends in chaotic and rhythmic endpoints, and other, as-yet unresolved variability. These resolvable time structures, chronomes, in us have counterparts around us, also consisting of rhythms, trends and chaos, as is increasingly being recognized. In 2000, we began a community-based study, relying on 7-day/24-hour monitoring of blood pressure as a public service. Our goal was the prevention of stroke and myocardial infarction and of the decline in cognitive function of the elderly in a community. Chronomic detection of elevated illness-risks aim at the prevention of diseases of individuals, such as myocardial infarctions and strokes, and, equally important, chronomics resolves illness of societies, such as crime and war

  3. Computer analysis of environmental temperature, light and noise in intensive care: chaos or chronome nurseries? (United States)

    Ardura, J; Andrés, J; Aldana, J; Revilla, M A; Cornélissen, G; Halberg, F


    Lighting, noise and temperature were monitored in two perinatal nurseries. Rhythms of several frequencies were found, including prominent 24-hour rhythms with acrophases around 13:00 (light intensity) and 16:00 (noise). For light and noise, the ratio formed by dividing the amplitude of a 1-week (circaseptan) or half-week (circasemiseptan) fitted cosine curve by the amplitude of a 24-hour fitted cosine curve is smaller than unity, since 24-hour rhythms are prominent for these variables. The amplitude ratios are larger than unity for temperature in the newborns' unit but not in the infants' unit. Earlier, the origin of the about-7-day rhythms of neonatal physiologic variables was demonstrated to have, in addition to a major endogenous, also a minor exogenous component. Hence, the possibility of optimizing maturation by manipulating environmental changes can be considered, using, as gauges of development, previously mapped chronomes (time structures of biologic multifrequency rhythms, trends and noise).

  4. Are human interactivity times lognormal?

    CERN Document Server

    Blenn, Norbert


    In this paper, we are analyzing the interactivity time, defined as the duration between two consecutive tasks such as sending emails, collecting friends and followers and writing comments in online social networks (OSNs). The distributions of these times are heavy tailed and often described by a power-law distribution. However, power-law distributions usually only fit the heavy tail of empirical data and ignore the information in the smaller value range. Here, we argue that the durations between writing emails or comments, adding friends and receiving followers are likely to follow a lognormal distribution. We discuss the similarities between power-law and lognormal distributions, show that binning of data can deform a lognormal to a power-law distribution and propose an explanation for the appearance of lognormal interactivity times. The historical debate of similarities between lognormal and power-law distributions is reviewed by illustrating the resemblance of measurements in this paper with the historical...

  5. Who creates the Time: Nature or Human?

    CERN Document Server

    Kulikov, Sergey


    The paper defends the thesis that analysis of time meaning in a context of philosophy of physical and mathematical natural sciences and philosophical anthropology allows to clear basis of human being and to construct special model of general understanding of time as a creation of nature or creation of human. Regulations on discretization and virtual nature of cultural interaction, mutual tension of limits of cultural and historical process allow connecting philosophy of the nature and philosophical anthropology with system of categories (energy, weight, distance, etc.). It finds application both in the physical and mathematical sphere and in the field of humanitarian studies. We can make a conclusion that neither nature nor human create the time. Time is an imaginary phenomenon connecting human activity and natural processes in the limits of human consciousness.

  6. Visualizing Human Migration Trhough Space and Time (United States)

    Zambotti, G.; Guan, W.; Gest, J.


    Human migration has been an important activity in human societies since antiquity. Since 1890, approximately three percent of the world's population has lived outside of their country of origin. As globalization intensifies in the modern era, human migration persists even as governments seek to more stringently regulate flows. Understanding this phenomenon, its causes, processes and impacts often starts from measuring and visualizing its spatiotemporal patterns. This study builds a generic online platform for users to interactively visualize human migration through space and time. This entails quickly ingesting human migration data in plain text or tabular format; matching the records with pre-established geographic features such as administrative polygons; symbolizing the migration flow by circular arcs of varying color and weight based on the flow attributes; connecting the centroids of the origin and destination polygons; and allowing the user to select either an origin or a destination feature to display all flows in or out of that feature through time. The method was first developed using ArcGIS Server for world-wide cross-country migration, and later applied to visualizing domestic migration patterns within China between provinces, and between states in the United States, all through multiple years. The technical challenges of this study include simplifying the shapes of features to enhance user interaction, rendering performance and application scalability; enabling the temporal renderers to provide time-based rendering of features and the flow among them; and developing a responsive web design (RWD) application to provide an optimal viewing experience. The platform is available online for the public to use, and the methodology is easily adoptable to visualizing any flow, not only human migration but also the flow of goods, capital, disease, ideology, etc., between multiple origins and destinations across space and time.

  7. Interactively human: Sharing time, constructing materiality. (United States)

    Roepstorff, Andreas


    Predictive processing models of cognition are promising an elegant way to unite action, perception, and learning. However, in the current formulations, they are species-unspecific and have very little particularly human about them. I propose to examine how, in this framework, humans can be able to massively interact and to build shared worlds that are both material and symbolic.

  8. Human response times in a graphic environment

    CERN Document Server

    Yule, A


    A summary of the results obtained from measuring the response times of the users of an interactive graphics system available on the CERN central computers is presented. These results are then used to find an optimum time to wait before rolling the user's program to disc.

  9. Time trends in human fecundability in Sweden

    DEFF Research Database (Denmark)

    Scheike, Thomas H; Rylander, Lars; Carstensen, Lisbeth


    increased with age, except that for women in their late 1930s, an apparent decrease was observed, particularly among the early cohorts. CONCLUSION: We found decreasing subfertility over time. We speculate that these patterns might be related to a Sweden-specific decrease over time in sexually transmitted...

  10. 'Human paced' walking: Followers adopt stride time dynamics of leaders

    NARCIS (Netherlands)

    Marmelat, V.C.M.; Delignières, D.; Torre, K.; Beek, P.J.; Daffertshofer, A.


    Isochronous cueing is widely used in gait rehabilitation even though it alters the stride-time dynamics toward anti-persistent rather than the persistent, fractal fluctuations characteristic of human walking. In the present experiment we tested an alternative cueing method: pacing by a human. To thi

  11. Resolving human object recognition in space and time. (United States)

    Cichy, Radoslaw Martin; Pantazis, Dimitrios; Oliva, Aude


    A comprehensive picture of object processing in the human brain requires combining both spatial and temporal information about brain activity. Here we acquired human magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) responses to 92 object images. Multivariate pattern classification applied to MEG revealed the time course of object processing: whereas individual images were discriminated by visual representations early, ordinate and superordinate category levels emerged relatively late. Using representational similarity analysis, we combined human fMRI and MEG to show content-specific correspondence between early MEG responses and primary visual cortex (V1), and later MEG responses and inferior temporal (IT) cortex. We identified transient and persistent neural activities during object processing with sources in V1 and IT. Finally, we correlated human MEG signals to single-unit responses in monkey IT. Together, our findings provide an integrated space- and time-resolved view of human object categorization during the first few hundred milliseconds of vision.

  12. 24 Hours chronomics of ambulatory blood pressure and its relation with circadian rhythm of 6-sulfatoxy melatonin in night shift health care workers

    Directory of Open Access Journals (Sweden)

    B. Anjum


    Results: Ambulatory BP and HR were recorded at every 30 min intervals in day time and each hour in night time synchronically with circadian pattern of 6 sulfatoxy melatonin during shift duties. Highly Significant difference was found in double amplitude (2DA of blood pressure between night and day shift (p<0.001. In night shift, hyperbaric index (HBI of mean systolic blood pressure was found to be increased at 00-03 am (midnight while during day shift, peak was found at 06-09 am. Peak melatonin was to be found in early morning as compared to mid night in both the shift. Conclusions: The present study concluded that the desynchronization was appeared during night shift and entrainment of circadian rhythm in the day shift. [Int J Res Med Sci 2015; 3(8.000: 1922-1931

  13. Time-varying priority queuing models for human dynamics. (United States)

    Jo, Hang-Hyun; Pan, Raj Kumar; Kaski, Kimmo


    Queuing models provide insight into the temporal inhomogeneity of human dynamics, characterized by the broad distribution of waiting times of individuals performing tasks. We theoretically study the queuing model of an agent trying to execute a task of interest, the priority of which may vary with time due to the agent's "state of mind." However, its execution is disrupted by other tasks of random priorities. By considering the priority of the task of interest either decreasing or increasing algebraically in time, we analytically obtain and numerically confirm the bimodal and unimodal waiting time distributions with power-law decaying tails, respectively. These results are also compared to the updating time distribution of papers in and the processing time distribution of papers in Physical Review journals. Our analysis helps to understand human task execution in a more realistic scenario.

  14. Time-Varying Priority Queuing Models for Human Dynamics

    CERN Document Server

    Jo, Hang-Hyun; Kaski, Kimmo


    Queuing models provide insight into the temporal inhomogeneity of human dynamics, characterized by the broad distribution of waiting times of individuals performing tasks. We study the queuing model of an agent trying to execute a task of interest, the priority of which may vary with time due to the agent's "state of mind." However, its execution can be disrupted by other tasks of random priorities. By considering the priority of the task of interest either decreasing or increasing algebraically in time, we analytically obtain and numerically confirm the bimodal and unimodal waiting time distributions with power-law decaying tails, respectively. These results are also compared to the updating time distribution of papers in the arXiv and the processing time distribution of papers in Physical Review journals. Our analysis helps to understand the human task execution behavior in a more realistic scenario.

  15. Noise-induced transition in human reaction times (United States)

    Medina, José M.; Díaz, José A.


    The human reaction/response time can be defined as the time elapsed from the onset of stimulus presentation until a response occurs in many sensory and cognitive processes. A reaction time model based on Piéron’s law is investigated. The model shows a noise-induced transition in the moments of reaction time distributions due to the presence of strong additive noise. The model also demonstrates that reaction times do not follow fluctuation scaling between the mean and the variance but follow a generalized version between the skewness and the kurtosis. The results indicate that noise-induced transitions in the moments govern fluctuations in sensory-motor transformations and open an insight into the macroscopic effects of noise in human perception and action. The conditions that lead to extreme reaction times are discussed based on the transfer of information in neurons.

  16. The beginning of human life under time-laps Cinematography


    Mio, Yasuyuki


    Background and Purpose: The aim of this study was to follow and record the early stages of development of a human embryo using time-lapse cinematography, and to discuss the beginning of human life. Materials and Methods: Human ova were incubated in thermo-stabilized and pH controlled chambers and observed using an inverted microscope fitted with a CCD digital camera. Images were taken at 2-minute intervals for 5–6 days. A total of 30 consecutive images, corresponding to an hour of incubat...

  17. Space, time and the limits of human understanding

    CERN Document Server

    Ghirardi, Giancarlo


    In this compendium of essays, some of the world’s leading thinkers discuss their conceptions of space and time, as viewed through the lens of their own discipline. With an epilogue on the limits of human understanding, this volume hosts contributions from six or more diverse fields. It presumes only rudimentary background knowledge on the part of the reader. Time and again, through the prism of intellect, humans have tried to diffract reality into various distinct, yet seamless, atomic, yet holistic, independent, yet interrelated disciplines and have attempted to study it contextually. Philosophers debate the paradoxes, or engage in meditations, dialogues and reflections on the content and nature of space and time. Physicists, too, have been trying to mold space and time to fit their notions concerning micro- and macro-worlds. Mathematicians focus on the abstract aspects of space, time and measurement. While cognitive scientists ponder over the perceptual and experiential facets of our consciousness of spac...

  18. Time and temporality: linguistic distribution in human life-games

    DEFF Research Database (Denmark)

    Cowley, Stephen


    While clock-time can be used to clarify facts, all living systems construct their own temporalities. Having illustrated the claim for foxtail grasses, it is argued that, with motility and brains, organisms came to use temporalities that build flexibility into behavior. With the rise of human...... culture, individuals developed a knack of using linguistic distribution to link metabolism with collective ways of assessing and managing experience. Of human temporal management, the best known case is the mental time travel enabled by, among other functions, autobiographical memory. One contribution...

  19. Extreme reaction times determine fluctuation scaling in human color vision (United States)

    Medina, José M.; Díaz, José A.


    In modern mental chronometry, human reaction time defines the time elapsed from stimulus presentation until a response occurs and represents a reference paradigm for investigating stochastic latency mechanisms in color vision. Here we examine the statistical properties of extreme reaction times and whether they support fluctuation scaling in the skewness-kurtosis plane. Reaction times were measured for visual stimuli across the cardinal directions of the color space. For all subjects, the results show that very large reaction times deviate from the right tail of reaction time distributions suggesting the existence of dragon-kings events. The results also indicate that extreme reaction times are correlated and shape fluctuation scaling over a wide range of stimulus conditions. The scaling exponent was higher for achromatic than isoluminant stimuli, suggesting distinct generative mechanisms. Our findings open a new perspective for studying failure modes in sensory-motor communications and in complex networks.

  20. Forming Human-Robot Teams Across Time and Space (United States)

    Hambuchen, Kimberly; Burridge, Robert R.; Ambrose, Robert O.; Bluethmann, William J.; Diftler, Myron A.; Radford, Nicolaus A.


    NASA pushes telerobotics to distances that span the Solar System. At this scale, time of flight for communication is limited by the speed of light, inducing long time delays, narrow bandwidth and the real risk of data disruption. NASA also supports missions where humans are in direct contact with robots during extravehicular activity (EVA), giving a range of zero to hundreds of millions of miles for NASA s definition of "tele". . Another temporal variable is mission phasing. NASA missions are now being considered that combine early robotic phases with later human arrival, then transition back to robot only operations. Robots can preposition, scout, sample or construct in advance of human teammates, transition to assistant roles when the crew are present, and then become care-takers when the crew returns to Earth. This paper will describe advances in robot safety and command interaction approaches developed to form effective human-robot teams, overcoming challenges of time delay and adapting as the team transitions from robot only to robots and crew. The work is predicated on the idea that when robots are alone in space, they are still part of a human-robot team acting as surrogates for people back on Earth or in other distant locations. Software, interaction modes and control methods will be described that can operate robots in all these conditions. A novel control mode for operating robots across time delay was developed using a graphical simulation on the human side of the communication, allowing a remote supervisor to drive and command a robot in simulation with no time delay, then monitor progress of the actual robot as data returns from the round trip to and from the robot. Since the robot must be responsible for safety out to at least the round trip time period, the authors developed a multi layer safety system able to detect and protect the robot and people in its workspace. This safety system is also running when humans are in direct contact with the robot

  1. A Circuit Model of Real Time Human Body Hydration. (United States)

    Asogwa, Clement Ogugua; Teshome, Assefa K; Collins, Stephen F; Lai, Daniel T H


    Changes in human body hydration leading to excess fluid losses or overload affects the body fluid's ability to provide the necessary support for healthy living. We propose a time-dependent circuit model of real-time human body hydration, which models the human body tissue as a signal transmission medium. The circuit model predicts the attenuation of a propagating electrical signal. Hydration rates are modeled by a time constant τ, which characterizes the individual specific metabolic function of the body part measured. We define a surrogate human body anthropometric parameter θ by the muscle-fat ratio and comparing it with the body mass index (BMI), we find theoretically, the rate of hydration varying from 1.73 dB/min, for high θ and low τ to 0.05 dB/min for low θ and high τ. We compare these theoretical values with empirical measurements and show that real-time changes in human body hydration can be observed by measuring signal attenuation. We took empirical measurements using a vector network analyzer and obtained different hydration rates for various BMI, ranging from 0.6 dB/min for 22.7 [Formula: see text] down to 0.04 dB/min for 41.2 [Formula: see text]. We conclude that the galvanic coupling circuit model can predict changes in the volume of the body fluid, which are essential in diagnosing and monitoring treatment of body fluid disorder. Individuals with high BMI would have higher time-dependent biological characteristic, lower metabolic rate, and lower rate of hydration.

  2. Jet-Ricci Geometry of Time-Dependent Human Biomechanics

    CERN Document Server

    Ivancevic, Tijana T


    We propose the time-dependent generalization of an `ordinary' autonomous human biomechanics, in which total mechanical + biochemical energy is not conserved. We introduce a general framework for time-dependent biomechanics in terms of jet manifolds derived from the extended musculo-skeletal configuration manifold. The corresponding Riemannian geometrical evolution follows the Ricci flow diffusion. In particular, we show that the exponential-like decay of total biomechanical energy (due to exhaustion of biochemical resources) is closely related to the Ricci flow on the biomechanical configuration manifold. Keywords: Time-dependent biomechanics, extended configuration manifold, configuration bundle, jet manifolds, Ricci flow diffusion

  3. Understanding human activity patterns based on space-time-semantics (United States)

    Huang, Wei; Li, Songnian


    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.

  4. Dispersal time for ancient human migrations: Americas and Europe colonization (United States)

    Flores, J. C.


    I apply the recently proposed intermittence strategy to investigate the ancient human migrations in the world. That is, the Americas colonization (Bering-bridge and Pacific-coast theories) and Neanderthal replacement in Europe around 45000 years before the present. Using a mathematical equation related to diffusion and ballistic motion, I calculate the colonization time in all these cases in good agreement with archeological data (including Neolithic transition in Europe). Moreover, to support these calculations, I obtain analytically the effective speed of colonization in Europe veff=0.62 [km/yr] and related to the Aurignacian culture propagation.

  5. Good vibrations: human interval timing in the vibrotactile modality. (United States)

    Jones, Luke A; Poliakoff, Ellen; Wells, Jill


    This article reports a detailed examination of timing in the vibrotactile modality and comparison with that of visual and auditory modalities. Three experiments investigated human timing in the vibrotactile modality. In Experiment 1, a staircase threshold procedure with a standard duration of 1,000 ms revealed a difference threshold of 160.35 ms for vibrotactile stimuli, which was significantly higher than that for auditory stimuli (103.25 ms) but not significantly lower than that obtained for visual stimuli (196.76 ms). In Experiment 2, verbal estimation revealed a significant slope difference between vibrotactile and auditory timing, but not between vibrotactile and visual timing. That is, both vibrations and lights were judged as shorter than sounds, and this comparative difference was greater at longer durations than at shorter ones. In Experiment 3, performance on a temporal generalization task showed characteristics consistent with the predications of scalar expectancy theory (SET: Gibbon, 1977) with both mean accuracy and scalar variance exhibited. The results were modelled using the modified Church and Gibbon model (MCG; derived by Wearden, 1992, from Church & Gibbon 1982). The model was found to give an excellent fit to the data, and the parameter values obtained were compared with those for visual and auditory temporal generalization. The pattern of results suggest that timing in the vibrotactile modality conforms to SET and that the internal clock speed for vibrotactile stimuli is significantly slower than that for auditory stimuli, which is logically consistent with the significant differences in difference threshold that were obtained.

  6. Fetal growth and timing of parturition in humans. (United States)

    Zhang, Jun; Sundaram, Rajeshwari; Sun, Wenyu; Troendle, James


    Animal studies indicate that either the fetus or the intrauterine environment, both of which set the pattern for fetal growth, may affect the timing of parturition. The authors examined the association between fetal growth and timing of spontaneous onset of labor in humans among low-risk white US women with singleton pregnancies (1987-1991). They restricted the data to pregnancies which had a reliable date of the last menstrual period, normal fetal growth in the first half of pregnancy, and no history of or current pregnancy complications that might have impaired fetal growth (n = 3,360). Subjects received ultrasound examinations at 15-22 and 31-35 weeks' gestation. Fetal growth was adjusted for parity, fetal sex, and maternal prepregnancy weight and height. Results showed that slower or faster fetal growth in the second half of pregnancy resulted in substantially lower or higher birth weight, respectively. However, fetal growth in the second half of pregnancy, even at extremes (2 standard deviations below or above the mean), did not have a meaningful impact on the timing of parturition; neither did fetal growth acceleration or deceleration in late pregnancy. Thus, in low-risk pregnancies where fetal growth is normal in early gestation, fetal growth in the second half of pregnancy does not affect the timing of normal parturition.

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

    Directory of Open Access Journals (Sweden)

    Mario Munoz-Organero


    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

  8. Restyling the Humanities Curriculum of Higher Education for Posthuman Times (United States)

    Siddiqui, Jamila R.


    The future viability of the humanities in higher education has been broadly debated. Yet, most of these debates are missing an important consideration. The humanities' object of study is the human, an object that some would argue has been replaced in our onto-epistemological systems by the posthuman. In her 2013 book, "The Posthuman,"…

  9. The Cell Cycle Timing of Human Papillomavirus DNA Replication. (United States)

    Reinson, Tormi; Henno, Liisi; Toots, Mart; Ustav, Mart; Ustav, Mart


    Viruses manipulate the cell cycle of the host cell to optimize conditions for more efficient viral genome replication. One strategy utilized by DNA viruses is to replicate their genomes non-concurrently with the host genome; in this case, the viral genome is amplified outside S phase. This phenomenon has also been described for human papillomavirus (HPV) vegetative genome replication, which occurs in G2-arrested cells; however, the precise timing of viral DNA replication during initial and stable replication phases has not been studied. We developed a new method to quantitate newly synthesized DNA levels and used this method in combination with cell cycle synchronization to show that viral DNA replication is initiated during S phase and is extended to G2 during initial amplification but follows the replication pattern of cellular DNA during S phase in the stable maintenance phase. E1 and E2 protein overexpression changes the replication time from S only to both the S and G2 phases in cells that stably maintain viral episomes. These data demonstrate that the active synthesis and replication of the HPV genome are extended into the G2 phase to amplify its copy number and the duration of HPV genome replication is controlled by the level of the viral replication proteins E1 and E2. Using the G2 phase for genome amplification may be an important adaptation that allows exploitation of changing cellular conditions during cell cycle progression. We also describe a new method to quantify newly synthesized viral DNA levels and discuss its benefits for HPV research.

  10. The time course of shape discrimination in the human brain. (United States)

    Ales, Justin M; Appelbaum, L Gregory; Cottereau, Benoit R; Norcia, Anthony M


    The lateral occipital cortex (LOC) activates selectively to images of intact objects versus scrambled controls, is selective for the figure-ground relationship of a scene, and exhibits at least some degree of invariance for size and position. Because of these attributes, it is considered to be a crucial part of the object recognition pathway. Here we show that human LOC is critically involved in perceptual decisions about object shape. High-density EEG was recorded while subjects performed a threshold-level shape discrimination task on texture-defined figures segmented by either phase or orientation cues. The appearance or disappearance of a figure region from a uniform background generated robust visual evoked potentials throughout retinotopic cortex as determined by inverse modeling of the scalp voltage distribution. Contrasting responses from trials containing shape changes that were correctly detected (hits) with trials in which no change occurred (correct rejects) revealed stimulus-locked, target-selective activity in the occipital visual areas LOC and V4 preceding the subject's response. Activity that was locked to the subjects' reaction time was present in the LOC. Response-locked activity in the LOC was determined to be related to shape discrimination for several reasons: shape-selective responses were silenced when subjects viewed identical stimuli but their attention was directed away from the shapes to a demanding letter discrimination task; shape-selectivity was present across four different stimulus configurations used to define the figure; LOC responses correlated with participants' reaction times. These results indicate that decision-related activity is present in the LOC when subjects are engaged in threshold-level shape discriminations.

  11. A Real-Time Model-Based Human Motion Tracking and Analysis for Human-Computer Interface Systems

    Directory of Open Access Journals (Sweden)

    Chung-Lin Huang


    Full Text Available This paper introduces a real-time model-based human motion tracking and analysis method for human computer interface (HCI. This method tracks and analyzes the human motion from two orthogonal views without using any markers. The motion parameters are estimated by pattern matching between the extracted human silhouette and the human model. First, the human silhouette is extracted and then the body definition parameters (BDPs can be obtained. Second, the body animation parameters (BAPs are estimated by a hierarchical tritree overlapping searching algorithm. To verify the performance of our method, we demonstrate different human posture sequences and use hidden Markov model (HMM for posture recognition testing.

  12. [The human embryo after Dolly: new practices for new times]. (United States)

    de Miguel Beriain, Iñigo


    The possiblity of cloning human beings introduced a lot of issues in our ethical and legal frameworks. In this paper, we will put the focus into the necessary changes in the concept of embryo that our legal systems will have to implement in order to face the new situation. The description of the embryo as a group of cells able to develop into a human being will be defended here as the best way of doing so.

  13. Human movement analysis with image processing in real time (United States)

    Fauvet, Eric; Paindavoine, Michel; Cannard, F.


    In the field of the human sciences, a lot of applications needs to know the kinematic characteristics of the human movements Psycology is associating the characteristics with the control mechanism, sport and biomechariics are associating them with the performance of the sportman or of the patient. So the trainers or the doctors can correct the gesture of the subject to obtain a better performance if he knows the motion properties. Roherton's studies show the children motion evolution2 . Several investigations methods are able to measure the human movement But now most of the studies are based on image processing. Often the systems are working at the T.V. standard (50 frame per secund ). they permit only to study very slow gesture. A human operator analyses the digitizing sequence of the film manually giving a very expensive, especially long and unprecise operation. On these different grounds many human movement analysis systems were implemented. They consist of: - markers which are fixed to the anatomical interesting points on the subject in motion, - Image compression which is the art to coding picture data. Generally the compression Is limited to the centroid coordinates calculation tor each marker. These systems differ from one other in image acquisition and markers detection.

  14. Real-time Animation of Interactive Virtual Humans

    NARCIS (Netherlands)

    Egges, A.


    Over the last years, there has been a lot of interest in the area of Interactive Virtual Humans (IVHs). Virtual characters who interact naturally with users in mixed realities have many different applications, such as interactive video games, virtual training and rehabilitation, or virtual heritage.

  15. Real-time human walking estimation with radar

    NARCIS (Netherlands)

    Dorp, Ph. van; Groen, F.C.A.


    Radars can be used to observe persons. Animation of an observed human on the basis of Frequency Modulated Continuous Wave (FMCW) radar measurements in virtual reality considerably facilitates the interpretation of the radar measurements. These radar measurements give detailed information of the moti

  16. Human time perception in temporal isolation : Effects of illumination intensity

    NARCIS (Netherlands)

    Aschoff, J; Daan, S


    Living in isolation from time cues under relatively high and low light intensities for a total (on average) of 24 days, 18 subjects estimated the passage of time by ''producing'' short (10 to 120 seconds) and long (1h) intervals throughout the experiments. The 1h productions were independent of ligh

  17. Trends in puberty timing in humans and environmental modifiers

    DEFF Research Database (Denmark)

    Toppari, Jorma; Juul, Anders


    Secular trends in timing of puberty appear to continue although under-nutrition has not been any longer a limiting factor for pubertal development. Now obesity and other environmental reasons have been suspected to cause this trend, and endocrine disrupting chemicals have become into focus...... as possible contributors. Epidemiological studies on endocrine disrupters are still scarce and show only weak associations between exposures and timing of puberty. Since genetic background explains 50-80% of variability in the timing of puberty, it is not surprising that the observed environmental effects...... are rather modest when individual exposures are assessed. Despite that, some exposures have been reported to be associated to early (e.g., polybrominated biphenyls) or delayed (e.g., lead) puberty. Here we shortly review the available data on recent trends in timing of puberty and the possible role...

  18. Human Activity Recognition as Time-Series Analysis

    Directory of Open Access Journals (Sweden)

    Hyesuk Kim


    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.

  19. Human time perception in temporal isolation: effects of illumination intensity. (United States)

    Aschoff, J; Daan, S


    Living in isolation from time cues under relatively high and low light intensities for a total (on average) of 24 days, 18 subjects estimated the passage of time by "producing" short (10 to 120 seconds) and long (1h) intervals throughout the experiments. The 1h productions were independent of light intensity and highly positively correlated with the duration of wake times. The short-interval productions were markedly increased under high light intensity. In a subsample of 6 subjects, the interaction between effects of body temperature and light condition on 10-second production was analyzed. Productions were negatively correlated with body temperature. In both dim and bright light, productions decreased by a factor of 0.7 per degree C. In bright light, production was increased by a factor of 1.2 relative to dim light. This effect was not mediated by body temperature, which itself was on average slightly increased in bright light. Since subjective time is slowed by bright light, objective time seems to pass faster in bright light.

  20. Human learning: Power laws or multiple characteristic time scales?

    Directory of Open Access Journals (Sweden)

    Gottfried Mayer-Kress


    Full Text Available The central proposal of A. Newell and Rosenbloom (1981 was that the power law is the ubiquitous law of learning. This proposition is discussed in the context of the key factors that led to the acceptance of the power law as the function of learning. We then outline the principles of an epigenetic landscape framework for considering the role of the characteristic time scales of learning and an approach to system identification of the processes of performance dynamics. In this view, the change of performance over time is the product of a superposition of characteristic exponential time scales that reflect the influence of different processes. This theoretical approach can reproduce the traditional power law of practice – within the experimental resolution of performance data sets - but we hypothesize that this function may prove to be a special and perhaps idealized case of learning.

  1. Investing in early human development: timing and economic efficiency. (United States)

    Doyle, Orla; Harmon, Colm P; Heckman, James J; Tremblay, Richard E


    Policy discussions to ameliorate socioeconomic (SES) inequalities are increasingly focused on investments in early childhood. Yet such interventions are costly to implement, and clear evidence on the optimal time to intervene to yield a high economic and social return in the future is meagre. The majority of successful early childhood interventions start in the preschool years. However socioeconomic gradients in cognitive skills, socio-emotional functioning and health can be observed by age three, suggesting that preventative programmes starting earlier in childhood may be even more effective. We discuss the optimal timing of early childhood intervention with reference to recent research in developmental neuroscience. We motivate the need for early intervention by providing an overview of the impact of adverse risk factors during the antenatal and early childhood periods on outcomes later in life. We provide a brief review of the economic rationale for investing early in life and propose the "antenatal investment hypothesis". We conclude by discussing a suite of new European interventions that will inform this optimal timing debate.

  2. Time-dependent histamine release from stored human blood products

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Edvardsen, L; Vangsgaard, K;


    storage. Whole blood (six units), plasma-reduced whole blood (six units), and plasma- and buffy coat-reduced (saline-adenine-glucose-mannitol) (SAGM) blood (six units) from unpaid healthy donors were stored in the blood bank for 35 days at 4 degrees C. Plasma histamine and total cell-bound histamine......Perioperative transfusion of whole blood has been shown to amplify trauma-induced immunosuppression, which could be attenuated by perioperative administration of histamine2 receptor antagonists. Supernatants from different blood products were, therefore, analysed for histamine content during.......0 (range 176.0-910.0) nmol/l in whole blood and 475.0 (range 360.0-1560.0) nmol/l in plasma-reduced whole blood, while it was undetectable in SAGM blood. Spontaneous histamine release increased in a time-dependent manner from a median of 6.7 (range 2.2-17.4) nmol/l at the time of storage to 175.0 (range 33...

  3. Time is on my side: time, general mental ability, human capital, and extrinsic career success. (United States)

    Judge, Timothy A; Klinger, Ryan L; Simon, Lauren S


    The present study linked general mental ability (GMA) to extrinsic career success using a multilevel framework that included time and 3 possible time-based mediators of the GMA-career success relationship. Results, based on a large national sample, revealed that over a 28-year period, GMA affected growth in 2 indicators of extrinsic career success (income and occupational prestige), such that the careers of high-GMA individuals ascended more steeply over time than those of low-GMA individuals. Part of the reason high-GMA individuals had steeper growth in extrinsic success over time was because they attained more education, completed more job training, and gravitated toward more complex jobs. GMA also moderated the degree to which within-individual variation in the mediating variables affected within-individual variation in extrinsic career success over time: Education, training, and job complexity were much more likely to translate into career success for more intelligent individuals.

  4. Determining Human Clot Lysis Time (in vitro with Plasminogen/Plasmin from Four Species (Human, Bovine, Goat, and Swine

    Directory of Open Access Journals (Sweden)

    Omaira Cañas Bermúdez


    Full Text Available Cardiovascular disease is the leading cause of death worldwide, including failures in the plasminogen/plasmin system which is an important factor in poor lysis of blood clots. This article studies the fibrinolytic system in four species of mammals, and it identifies human plasminogen with highest thrombolysis efficiency. It examines plasminogen from four species (human, bovine, goat, and swine and identifies the most efficient one in human clot lysis in vitro. All plasminogens were identically purified by affinity chromatography. Human fibrinogen was purified by fractionation with ethanol. The purification of both plasminogen and fibrinogen was characterized by one-dimensional SDS-PAGE (10%. Human clot formation in vitro and its dissolution by plasminogen/plasmin consisted of determining lysis time from clot formation to its dilution. Purification of proteins showed greater than 95% purity, human plasminogen showed greater ability to lyse clot than animal plasminogen. The article concludes that human plasminogen/plasmin has the greatest catalysis and efficiency, as it dissolves human clot up to three times faster than that of irrational species.

  5. Real-time monitoring for human clinical trials

    Energy Technology Data Exchange (ETDEWEB)

    Harker, Y.D. [Idaho National Engineering Lab., Idaho Falls, ID (United States)


    On August 3-4, 1994, an INEL team made measurements related to a real-time monitoring system for use on the epithermal beam facility at the BMRR. BNL has installed two fission chambers in front of the beam collimator, which are to monitor the beam coming from the reactor. These two monitors are located with one just above the 16-cm dia. front aperture and the other is just below. The fission chambers contain depleted uranium, but because of the small amount of U-235 present, they respond to thermal and near thermal neutrons rather than fast neutrons. This feature combined with their relatively small size (0.6 cm dia x 4 cm long) makes them very good monitors in the BMRR epithermal neutron beam. The INEL team worked with H.B. Lui (BNL) in performing initial tests of these monitors and established the settings to achieve stable operation. The main purpose of the measurement studies was to establish a basis for a monitoring method that tracks the dose the patient is receiving rather than the neutron fluence being delivered down the beam line.

  6. Double loop control strategy with different time steps based on human characteristics. (United States)

    Gu, Gwang Min; Lee, Jinoh; Kim, Jung


    This paper proposes a cooperative control strategy in consideration of the force sensitivity of human. The strategy consists of two loops: one is the intention estimation loop whose sampling time can be variable in order to investigate the effect of the sampling time; the other is the position control loop with fixed time step. A high sampling rate is not necessary for the intention estimation loop due to the bandwidth of the mechanoreceptors in humans. In addition, the force sensor implemented in the robot is sensitive to the noise induced from the sensor itself and tremor of the human. Multiple experiments were performed with the experimental protocol using various time steps of the intention estimation loop to find the suitable sampling times in physical human robot interaction. The task involves pull-and-push movement with a two-degree-of-freedom robot, and the norm of the interaction force was obtained for each experiment as the measure of the cooperative control performance.

  7. An Augmented Discrete-Time Approach for Human-Robot Collaboration

    Directory of Open Access Journals (Sweden)

    Peidong Liang


    Full Text Available Human-robot collaboration (HRC is a key feature to distinguish the new generation of robots from conventional robots. Relevant HRC topics have been extensively investigated recently in academic institutes and companies to improve human and robot interactive performance. Generally, human motor control regulates human motion adaptively to the external environment with safety, compliance, stability, and efficiency. Inspired by this, we propose an augmented approach to make a robot understand human motion behaviors based on human kinematics and human postural impedance adaptation. Human kinematics is identified by geometry kinematics approach to map human arm configuration as well as stiffness index controlled by hand gesture to anthropomorphic arm. While human arm postural stiffness is estimated and calibrated within robot empirical stability region, human motion is captured by employing a geometry vector approach based on Kinect. A biomimetic controller in discrete-time is employed to make Baxter robot arm imitate human arm behaviors based on Baxter robot dynamics. An object moving task is implemented to validate the performance of proposed methods based on Baxter robot simulator. Results show that the proposed approach to HRC is intuitive, stable, efficient, and compliant, which may have various applications in human-robot collaboration scenarios.

  8. Real-time estimation of 3D human arm motion from markerless images for human-machine interaction (United States)

    Verma, Siddharth; Kofman, Jonathan


    Vision-based motion tracking is commonly used in surveillance, human-machine interfaces in robotics and automation, virtual and augmented reality applications and biomechanics. Most techniques require markers, use a predefined motion sequence or user-intervention for initialization, and do not process in real-time. This paper describes the implementation of a vision-based non-invasive technique for markerless real-time tracking of human-arm motion. Human-arm motion is tracked by processing images from two calibrated cameras in real-time to estimate the position of the 3D joint centers of the wrist and elbow, and determine the orientation of the hand from the 3D positions of the index finger and thumb. Tracking of the hand and arm was carried out without any prior knowledge of subject's arm length, texture, width and distance from the camera.

  9. Do monkeys think in metaphors? Representations of space and time in monkeys and humans


    Merritt, D.; Casasanto, D; Brannon, E.


    Research on the relationship between the representation of space and time has produced two contrasting proposals. ATOM, posits that space and time are represented via a common magnitude system, suggesting a symmetrical relationship between space and time. According to metaphor theory, however, representations of time depend on representations of space asymmetrically. Previous findings in humans have supported metaphor theory. Here, we investigate the relationship between time and space in a n...

  10. Real Time Detection and Tracking of Human Face using Skin Color Segmentation and Region Properties

    Directory of Open Access Journals (Sweden)

    Prashanth Kumar G.


    Full Text Available Real time faces detection and face tracking is one of the challenging problems in application like computer human interaction, video surveillance, biometrics etc. In this paper we are presenting an algorithm for real time face detection and tracking using skin color segmentation and region properties. First segmentation of skin regions from an image is done by using different color models. Skin regions are separated from the image by using thresholding. Then to decide whether these regions contain human face or not we used face features. Our procedure is based on skin color segmentation and human face features (knowledge-based approach. We have used RGB, YCbCr, and HSV color models for skin color segmentation. These color models with thresholds, help to remove non skin like pixel from an image. Each segmented skin regions are tested to know whether region is human face or not, by using human face features based on knowledge of geometrical properties of human face.

  11. Human perception of short and long time intervals: its correlation with body temperature and the duration of wake time. (United States)

    Aschoff, J


    Time estimation was studied in seven human subjects during prolonged sojourn is isolation from time cues. They wore rectal temperature probes throughout the experiments, and during wakefulness recorded each time they thought one hour had passed. At the end of each of these subjective hours they produced a subjective 5 or 10 sec interval. The produced intervals on the 1-h task were not related to body temperature but were correlated with and proportional to the duration of waketime in all subjects. The produced 5 and 10 sec intervals were in all subjects negatively correlated with rectal temperature, but were not associated with wake time. Brief and long time intervals are subjectively experienced via different mechanisms.

  12. Separating timing, movement conditions and individual differences in the analysis of human movement

    DEFF Research Database (Denmark)

    Raket, Lars Lau; Grimme, Britta; Schöner, Gregor


    A central task in the analysis of human movement behavior is to determine systematic patterns and differences across experimental conditions, participants and repetitions. This is possible because human movement is highly regular, being constrained by invariance principles. Movement timing......-effects model for analyzing temporally continuous signals that contain systematic effects in both timing and path. Identifiability issues of path relative to timing are overcome by using maximum likelihood estimation in which the most likely separation of space and time is chosen given the variation found...

  13. Time to smell: a cascade model of human olfactory perception based on response-time (RT) measurement. (United States)

    Olofsson, Jonas K


    The timing of olfactory behavioral decisions may provide an important source of information about how the human olfactory-perceptual system is organized. This review integrates results from olfactory response-time (RT) measurements from a perspective of mental chronometry. Based on these findings, a new cascade model of human olfaction is presented. Results show that main perceptual decisions are executed with high accuracy within about 1~s of sniff onset. The cascade model proposes the existence of distinct processing stages within this brief time-window. According to the cascade model, different perceptual features become accessible to the perceiver at different time-points, and the output of earlier processing stages provides the input for later processing stages. The olfactory cascade starts with detecting the odor, which is followed by establishing an odor object. The odor object, in turn, triggers systems for determining odor valence and edibility. Evidence for the cascade model comes from studies showing that RTs for odor valence and edibility assessment are predicted by the shorter RTs needed to establish the odor object. Challenges for future research include innovative task designs for olfactory RT experiments and the integration of the behavioral processing sequence into the underlying cortical processes using complementary RT measures and neuroimaging methods.

  14. Mental time travel : A conceptual overview of social psychological perspectives on a fundamental human capacity

    NARCIS (Netherlands)

    Epstude, K.; Peetz, J.


    Humans have the unique capacity to mentally travel through time, that is, to reflect on the past, anticipate the future, and construct alternate realities in their minds. The ability to mentally travel through time affects a variety of social psychological topics. Representations of events can diffe

  15. [Study on real-time wearable monitoring system for human heat and cold stresses]. (United States)

    Shen, Yuhong; Wang, Tianhao; Li, Chenming


    In order to study the way of evaluating human performance under heat and cold stresses, we developed a wearable physiological monitoring system-intelligent belt system, capable of providing real-time, continuous and dynamic monitoring of multiple physiological parameters. The system has following features: multiuser communication, high integration, strong environment adaptability, dynamic features and real time physiological monitoring ability. The system uses sensing belts and elastic belts to acquire physiological parameters, uses WIFI to build wireless network monitoring for multiuser, and uses Delphi to develop data processing software capable of real-time viewing, storagng, processing, and alerting. With four different intensity-activity trials on six subjects and compared with standard laboratory human physiological acquisition instruments, the system was proved to be able to acquire accu-rate physiological parameters such as ECG, respiration, multi-point body temperatures, and body movement. The system worked steadily and reliably. This wearable real-time monitoring system for human heat and cold stresses can solve the problem facing our country that human heat stress and cold stress monitoring technology is insufficient, provide new methods and new ways for monitoring and evaluation of human heat and cold stresses under real task or stress environment, and provide technical platform for the study on human ergonomics.

  16. Time-invariant person-specific frequency templates in human brain activity

    CERN Document Server

    Doron, I; Baruchi, I; Towle, V L; Ben-Jacob, E; Doron, Itai; Hulata, Eyal; Baruchi, Itay; Towle, Vernon L.; Ben-Jacob, Eshel


    The various human brain tasks are performed at different locations and time scales. Yet, we discovered the existence of time-invariant (above an essential time scale) partitioning of the brain activity into person-specific frequency bands. For that, we perform temporal and ensemble averaging of best wavelet packet bases from multi-electrode EEG recordings. These personal frequency-bands provide new templates for quantitative analyses of brain function, e.g., normal vs. epileptic activity.

  17. Remote detection of human toxicants in real time using a human-optimized, bioluminescent bacterial luciferase gene cassette bioreporter (United States)

    Close, Dan; Webb, James; Ripp, Steven; Patterson, Stacey; Sayler, Gary


    Traditionally, human toxicant bioavailability screening has been forced to proceed in either a high throughput fashion using prokaryotic or lower eukaryotic targets with minimal applicability to humans, or in a more expensive, lower throughput manner that uses fluorescent or bioluminescent human cells to directly provide human bioavailability data. While these efforts are often sufficient for basic scientific research, they prevent the rapid and remote identification of potentially toxic chemicals required for modern biosecurity applications. To merge the advantages of high throughput, low cost screening regimens with the direct bioavailability assessment of human cell line use, we re-engineered the bioluminescent bacterial luciferase gene cassette to function autonomously (without exogenous stimulation) within human cells. Optimized cassette expression provides for fully endogenous bioluminescent production, allowing continuous, real time monitoring of the bioavailability and toxicology of various compounds in an automated fashion. To access the functionality of this system, two sets of bioluminescent human cells were developed. The first was programed to suspend bioluminescent production upon toxicological challenge to mimic the non-specific detection of a toxicant. The second induced bioluminescence upon detection of a specific compound to demonstrate autonomous remote target identification. These cells were capable of responding to μM concentrations of the toxicant n-decanal, and allowed for continuous monitoring of cellular health throughout the treatment process. Induced bioluminescence was generated through treatment with doxycycline and was detectable upon dosage at a 100 ng/ml concentration. These results demonstrate that leveraging autonomous bioluminescence allows for low-cost, high throughput direct assessment of toxicant bioavailability.

  18. Domesticated animals and human infectious diseases of zoonotic origins: domestication time matters. (United States)

    Morand, Serge; McIntyre, K Marie; Baylis, Matthew


    The rate of emergence for emerging infectious diseases has increased dramatically over the last century, and research findings have implicated wildlife as an importance source of novel pathogens. However, the role played by domestic animals as amplifiers of pathogens emerging from the wild could also be significant, influencing the human infectious disease transmission cycle. The impact of domestic hosts on human disease emergence should therefore be ascertained. Here, using three independent datasets we showed positive relationships between the time since domestication of the major domesticated mammals and the total number of parasites or infectious diseases they shared with humans. We used network analysis, to better visualize the overall interactions between humans and domestic animals (and amongst animals) and estimate which hosts are potential sources of parasites/pathogens for humans (and for all other hosts) by investigating the network architecture. We used centrality, a measure of the connection amongst each host species (humans and domestic animals) in the network, through the sharing of parasites/pathogens, where a central host (i.e. high value of centrality) is the one that is infected by many parasites/pathogens that infect many other hosts in the network. We showed that domesticated hosts that were associated a long time ago with humans are also the central ones in the network and those that favor parasites/pathogens transmission not only to humans but also to all other domesticated animals. These results urge further investigation of the diversity and origin of the infectious diseases of domesticated animals in their domestication centres and the dispersal routes associated with human activities. Such work may help us to better understand how domesticated animals have bridged the epidemiological gap between humans and wildlife.

  19. Real-time multiple human perception with color-depth cameras on a mobile robot. (United States)

    Zhang, Hao; Reardon, Christopher; Parker, Lynne E


    The ability to perceive humans is an essential requirement for safe and efficient human-robot interaction. In real-world applications, the need for a robot to interact in real time with multiple humans in a dynamic, 3-D environment presents a significant challenge. The recent availability of commercial color-depth cameras allow for the creation of a system that makes use of the depth dimension, thus enabling a robot to observe its environment and perceive in the 3-D space. Here we present a system for 3-D multiple human perception in real time from a moving robot equipped with a color-depth camera and a consumer-grade computer. Our approach reduces computation time to achieve real-time performance through a unique combination of new ideas and established techniques. We remove the ground and ceiling planes from the 3-D point cloud input to separate candidate point clusters. We introduce the novel information concept, depth of interest, which we use to identify candidates for detection, and that avoids the computationally expensive scanning-window methods of other approaches. We utilize a cascade of detectors to distinguish humans from objects, in which we make intelligent reuse of intermediary features in successive detectors to improve computation. Because of the high computational cost of some methods, we represent our candidate tracking algorithm with a decision directed acyclic graph, which allows us to use the most computationally intense techniques only where necessary. We detail the successful implementation of our novel approach on a mobile robot and examine its performance in scenarios with real-world challenges, including occlusion, robot motion, nonupright humans, humans leaving and reentering the field of view (i.e., the reidentification challenge), human-object and human-human interaction. We conclude with the observation that the incorporation of the depth information, together with the use of modern techniques in new ways, we are able to create an

  20. The Human Placenta Project: Placental Structure, Development, and Function in Real Time (United States)

    Guttmacher, Alan E.; Maddox, Yvonne T.; Spong, Catherine Y.


    Despite its crucial role in the health of both the fetus and the pregnant woman, the placenta is the least understood human organ. Since a growing body of evidence also underscores the importance of placental development in the lifelong health of both mother and offspring, this lack of knowledge about placental structure and function is particularly concerning. Given modern approaches and technologies and the ability to develop new methods, we propose a coordinated “Human Placenta Project,” with the ultimate goal of understanding human placental structure, development, and function in real time. PMID:24661567

  1. The Human Placenta Project: placental structure, development, and function in real time. (United States)

    Guttmacher, A E; Maddox, Y T; Spong, C Y


    Despite its crucial role in the health of both the fetus and the pregnant woman, the placenta is the least understood human organ. Since a growing body of evidence also underscores the importance of placental development in the lifelong health of both mother and offspring, this lack of knowledge about placental structure and function is particularly concerning. Given modern approaches and technologies and the ability to develop new methods, we propose a coordinated "Human Placenta Project", with the ultimate goal of understanding human placental structure, development, and function in real time.

  2. Human factors in continuous time-concerned cooperative systems represented by NΣ-labeled calculus

    Institute of Scientific and Technical Information of China (English)

    Tetsuya MIZUTANI; Shigeru IGARASH; Masayuki SHIO; Yasuwo IKEDA


    N-E-labeled calculus is a generalization of N-labeled calculus so as to describe time-concerned recog-nition, knowledge, belief and decision of humans or com-puter programs together with related external physical or logical phenomena. N-labeled calculus is the smallest for-mal system applicable to verification and analysis of coop-erative real-timing systems on natural number time introduced as an adaptation of tense arithmetic (TA). A merging problem of vehicles with misunderstanding or incorrect recognition is discussed as an example of coop-erating systems controlling continuously changing objects including human factor. Euler's approximation is intro-duced in order to represent the continuously changing objects. Through this example, relationship among arti-ficial intelligence, external environment and human fac-tors is investigated.

  3. Feature integration with random forests for real-time human activity recognition (United States)

    Kataoka, Hirokatsu; Hashimoto, Kiyoshi; Aoki, Yoshimitsu


    This paper presents an approach for real-time human activity recognition. Three different kinds of features (flow, shape, and a keypoint-based feature) are applied in activity recognition. We use random forests for feature integration and activity classification. A forest is created at each feature that performs as a weak classifier. The international classification of functioning, disability and health (ICF) proposed by WHO is applied in order to set the novel definition in activity recognition. Experiments on human activity recognition using the proposed framework show - 99.2% (Weizmann action dataset), 95.5% (KTH human actions dataset), and 54.6% (UCF50 dataset) recognition accuracy with a real-time processing speed. The feature integration and activity-class definition allow us to accomplish high-accuracy recognition match for the state-of-the-art in real-time.

  4. WiFi-Based Real-Time Calibration-Free Passive Human Motion Detection. (United States)

    Gong, Liangyi; Yang, Wu; Man, Dapeng; Dong, Guozhong; Yu, Miao; Lv, Jiguang


    With the rapid development of WLAN technology, wireless device-free passive human detection becomes a newly-developing technique and holds more potential to worldwide and ubiquitous smart applications. Recently, indoor fine-grained device-free passive human motion detection based on the PHY layer information is rapidly developed. Previous wireless device-free passive human detection systems either rely on deploying specialized systems with dense transmitter-receiver links or elaborate off-line training process, which blocks rapid deployment and weakens system robustness. In the paper, we explore to research a novel fine-grained real-time calibration-free device-free passive human motion via physical layer information, which is independent of indoor scenarios and needs no prior-calibration and normal profile. We investigate sensitivities of amplitude and phase to human motion, and discover that phase feature is more sensitive to human motion, especially to slow human motion. Aiming at lightweight and robust device-free passive human motion detection, we develop two novel and practical schemes: short-term averaged variance ratio (SVR) and long-term averaged variance ratio (LVR). We realize system design with commercial WiFi devices and evaluate it in typical multipath-rich indoor scenarios. As demonstrated in the experiments, our approach can achieve a high detection rate and low false positive rate.

  5. An evolutionary genomic approach to identify genes involved in human birth timing.

    Directory of Open Access Journals (Sweden)

    Jevon Plunkett


    Full Text Available Coordination of fetal maturation with birth timing is essential for mammalian reproduction. In humans, preterm birth is a disorder of profound global health significance. The signals initiating parturition in humans have remained elusive, due to divergence in physiological mechanisms between humans and model organisms typically studied. Because of relatively large human head size and narrow birth canal cross-sectional area compared to other primates, we hypothesized that genes involved in parturition would display accelerated evolution along the human and/or higher primate phylogenetic lineages to decrease the length of gestation and promote delivery of a smaller fetus that transits the birth canal more readily. Further, we tested whether current variation in such accelerated genes contributes to preterm birth risk. Evidence from allometric scaling of gestational age suggests human gestation has been shortened relative to other primates. Consistent with our hypothesis, many genes involved in reproduction show human acceleration in their coding or adjacent noncoding regions. We screened >8,400 SNPs in 150 human accelerated genes in 165 Finnish preterm and 163 control mothers for association with preterm birth. In this cohort, the most significant association was in FSHR, and 8 of the 10 most significant SNPs were in this gene. Further evidence for association of a linkage disequilibrium block of SNPs in FSHR, rs11686474, rs11680730, rs12473870, and rs1247381 was found in African Americans. By considering human acceleration, we identified a novel gene that may be associated with preterm birth, FSHR. We anticipate other human accelerated genes will similarly be associated with preterm birth risk and elucidate essential pathways for human parturition.

  6. Effects of a pretarget distractor on saccade reaction times across space and time in monkeys and humans. (United States)

    Khan, Aarlenne Z; Munoz, Douglas P; Takahashi, Naomi; Blohm, Gunnar; McPeek, Robert M


    Previous studies have shown that the influence of a behaviorally irrelevant distractor on saccade reaction times (SRTs) varies depending on the temporal and spatial relationship between the distractor and the saccade target. We measured distractor influence on SRTs to a subsequently presented target, varying the spatial location and the timing between the distractor and the target. The distractor appeared at one of four equally eccentric locations, followed by a target (either 50 ms or 200 ms after) at one of 136 different locations encompassing an area of 20° square. We extensively tested two humans and two monkeys on this task to determine interspecies similarities and differences, since monkey neurophysiology is often used to interpret human behavioral findings. Results were similar across species; for the short interval (50 ms), SRTs were shortest to a target presented close to or at the distractor location and increased primarily as a function of the distance from the distractor. There was also an effect of distractor-target direction and visual field. For the long interval (200 ms) the results were inverted; SRTs were longest for short distances between the distractor and target and decreased as a function of distance from distractor. Both SRT patterns were well captured by a two-dimensional dynamic field model with short-distance excitation and long-distance inhibition, based upon known functional connectivity found in the superior colliculus that includes wide-spread excitation and inhibition. Based on these findings, we posit that the different time-dependent patterns of distractor-related SRTs can emerge from the same underlying neuronal mechanisms common to both species.

  7. Saline obtaining and time standardization of prothrombin using thromboplastin of human placenta.

    Directory of Open Access Journals (Sweden)

    María de Jesús Sánchez Bouza


    Full Text Available Background: Determining prothombine ‘s time is an important lab test in the study of coagulation disorders. To develop this essay the main reactive was thromboplastin , a substance that is presented in tissue and that has been obtained habitually from the human brain or certain animals but its extraction in labs or its commercial acquisition is difficult at present. Objective: To obtain Thromboplastin throughout the extraction of human placenta and to standardise the determination of pro-time into the obtained reactive Method: Placenta from normal delivery was used from which thromboplastin was obtained using a saline extraction. The reactive was compared with thromboplastin from human brain from ¨Dr. Hermanos Ameijeiras¨ Hospital in Havana City in a group of patients with and without anticoagulant treatment . With the extracted thromplastin similar or compatible results were obtained than with the habitual reactives by using easier and cheaper process.

  8. Interevent time distributions of human multi-level activity in a virtual world (United States)

    Mryglod, O.; Fuchs, B.; Szell, M.; Holovatch, Yu.; Thurner, S.


    Studying human behavior in virtual environments provides extraordinary opportunities for a quantitative analysis of social phenomena with levels of accuracy that approach those of the natural sciences. In this paper we use records of player activities in the massive multiplayer online game Pardus over 1238 consecutive days, and analyze dynamical features of sequences of actions of players. We build on previous work where temporal structures of human actions of the same type were quantified, and provide an empirical understanding of human actions of different types. This study of multi-level human activity can be seen as a dynamic counterpart of static multiplex network analysis. We show that the interevent time distributions of actions in the Pardus universe follow highly non-trivial distribution functions, from which we extract action-type specific characteristic 'decay constants'. We discuss characteristic features of interevent time distributions, including periodic patterns on different time scales, bursty dynamics, and various functional forms on different time scales. We comment on gender differences of players in emotional actions, and find that while males and females act similarly when performing some positive actions, females are slightly faster for negative actions. We also observe effects on the age of players: more experienced players are generally faster in making decisions about engaging in and terminating enmity and friendship, respectively.

  9. Time-related contact angle measurements with human plasma on biomaterial surfaces

    NARCIS (Netherlands)

    Rakhorst, G; Van der Mei, HC; Van Oeveren, W; Spijker, HT; Busscher, HJ


    Axisymmetric drop shape analysis by profile (ADSA-P) was used to assess in time contact angle changes of human plasma drops placed on four different biomaterials. Results were related with conventional blood compatibility measurements: albumin adsorption, fibrinogen adsorption and platelet adhesion.


    Institute of Scientific and Technical Information of China (English)

    沈启宏; 魏俊杰


    The stability and bifurcation of the trivial solution in the two-dimensional differential equation of a model describing human respiratory system with time delay were investigated. Formulas about the stability of bifurcating periodic solution and the direction of Hopf bifurcation were exhibited by applying the normal form theory and the center manifold theorem. Furthermore, numerical simulation was carried out.

  11. Dating the time of birth: A radiocarbon calibration curve for human eye-lens crystallines

    DEFF Research Database (Denmark)

    Kjeldsen, Henrik; Heinemeier, Jan; Heegaard, Steffen;


    Radiocarbon bomb-pulse dating has been used to measure the formation age of human eye-lens crystallines. Lens crystallines are special proteins in the eye-lens that consist of virtually inert tissue. The experimental data show that the radiocarbon ages to a large extent reflect the time of birth...

  12. Real-time trace gas sensing of ethylene, propanal and acetaldehyde from human skin in vivo.

    NARCIS (Netherlands)

    Moeskops, B.W.M.; Steeghs, M.M.L.; Swam, K. van; Cristescu, S.M.; Scheepers, P.T.J.; Harren, F.J.M.


    Trace gases emitted by human skin in vivo are monitored non-invasively and in real time using laser-based photoacoustic detection and proton-transfer reaction mass spectrometry. A small quartz cuvette is placed on the skin to create a headspace from which a carrier gas transports the skin emissions

  13. Colonic transit time relates to bacterial metabolism and mucosal turnover in the human gut

    DEFF Research Database (Denmark)

    Roager, Henrik Munch; Hansen, Lea Benedicte Skov; Bahl, Martin Iain

    transit time and the gut microbial composition and metabolism, we assessed the colonic transit time of 98 subjects using radiopaque markers, and profiled their gut microbiota by16S rRNA gene sequencingand their urine metabolome by ultra performance liquid chromatography mass spectrometry. Based......Little is known about how colonic transit time relates to human colonic metabolism, and its importance for host health, although stool consistency, a proxy for colonic transit time, has recently been negatively associated with gut microbial richness. To address the relationships between colonic...... on correlation analyses,we show that colonic transit time is associated with overall gutmicrobial composition, diversity and metabolism. A relatively prolonged colonic transit time associates with high microbial species richness and a shift in colonic metabolismfrom carbohydrate fermentation to protein...

  14. Colonic transit time is related to bacterial metabolism and mucosal turnover in the human gut

    DEFF Research Database (Denmark)

    Roager, Henrik Munch; Hansen, Lea Benedicte Skov; Bahl, Martin Iain

    transit time and the gut microbial composition and metabolism, we assessed the colonic transit time of 98 subjects using radiopaque markers, and profiled their gut microbiota by16S rRNA gene sequencing and their urine metabolome by ultra performance liquid chromatography mass spectrometry. Based......Little is known about how colonic transit time relates to human colonic metabolism, and its importance for host health, although stool consistency, a proxy for colonic transit time, has recently been negatively associated with gut microbial richness. To address the relationships between colonic...... on correlation analyses, we show that colonic transit time is associated with overall gut microbial composition, diversity and metabolism. A relatively prolonged colonic transit time associates with high microbial species richness and a shift in colonic metabolism from carbohydrate fermentation to protein...

  15. Ultrasonication and the quality of human milk: variation of power and time of exposure. (United States)

    Christen, Lukas; Lai, Ching Tat; Hartmann, Peter E


    Donor human milk is pasteurized to prevent the potential risk of the transmission of pathogens to preterm infants. Currently, Holder pasteurization (human milk held at 62·5°C for 30 min) is used in most human milk banks, but has the disadvantage that it results in excessive inactivation of important bioactive components. Power-ultrasound (20-100 kHz) is an emerging technology for the preservation of foods and could be an alternative method for the treatment of human milk. The aim of this study was to investigate the effect of different ultrasound settings on the elimination of Escherichia coli and the retention of bile salt stimulated lipase (BSSL) activity. Ultrasonication with a constant power decreased Esch. coli viability exponentially over time until the processing temperature increased to sub-pasteurization level to between 51·4 and 58·5°C, then a log10 1·3 decrease was observed (Phuman milk using high ultrasound power over a short exposure time to ensure that the temperature remains below the critical level for protein denaturation. Alternatively, the use of lower power settings such as the 26 W used in the present studies would require a cooling system to ensure the human milk BSSL was protected against temperature denaturation.

  16. Real-time face and gesture analysis for human-robot interaction (United States)

    Wallhoff, Frank; Rehrl, Tobias; Mayer, Christoph; Radig, Bernd


    Human communication relies on a large number of different communication mechanisms like spoken language, facial expressions, or gestures. Facial expressions and gestures are one of the main nonverbal communication mechanisms and pass large amounts of information between human dialog partners. Therefore, to allow for intuitive human-machine interaction, a real-time capable processing and recognition of facial expressions, hand and head gestures are of great importance. We present a system that is tackling these challenges. The input features for the dynamic head gestures and facial expressions are obtained from a sophisticated three-dimensional model, which is fitted to the user in a real-time capable manner. Applying this model different kinds of information are extracted from the image data and afterwards handed over to a real-time capable data-transferring framework, the so-called Real-Time DataBase (RTDB). In addition to the head and facial-related features, also low-level image features regarding the human hand - optical flow, Hu-moments are stored into the RTDB for the evaluation process of hand gestures. In general, the input of a single camera is sufficient for the parallel evaluation of the different gestures and facial expressions. The real-time capable recognition of the dynamic hand and head gestures are performed via different Hidden Markov Models, which have proven to be a quick and real-time capable classification method. On the other hand, for the facial expressions classical decision trees or more sophisticated support vector machines are used for the classification process. These obtained results of the classification processes are again handed over to the RTDB, where other processes (like a Dialog Management Unit) can easily access them without any blocking effects. In addition, an adjustable amount of history can be stored by the RTDB buffer unit.

  17. Continuous, real-time bioimaging of chemical bioavailability and toxicology using autonomously bioluminescent human cell lines (United States)

    Xu, Tingting; Close, Dan M.; Webb, James D.; Price, Sarah L.; Ripp, Steven A.; Sayler, Gary S.


    Bioluminescent imaging is an emerging biomedical surveillance strategy that uses external cameras to detect in vivo light generated in small animal models of human physiology or in vitro light generated in tissue culture or tissue scaffold mimics of human anatomy. The most widely utilized of reporters is the firefly luciferase (luc) gene; however, it generates light only upon addition of a chemical substrate, thus only generating intermittent single time point data snapshots. To overcome this disadvantage, we have demonstrated substrate-independent bioluminescent imaging using an optimized bacterial bioluminescence (lux) system. The lux reporter produces bioluminescence autonomously using components found naturally within the cell, thereby allowing imaging to occur continuously and in real-time over the lifetime of the host. We have validated this technology in human cells with demonstrated chemical toxicological profiling against exotoxin exposures at signal strengths comparable to existing luc systems (~1.33 × 107 photons/second). As a proof-in-principle demonstration, we have engineered breast carcinoma cells to express bioluminescence for real-time screening of endocrine disrupting chemicals and validated detection of 17β-estradiol (EC50 = ~ 10 pM). These and other applications of this new reporter technology will be discussed as potential new pathways towards improved models of target chemical bioavailability, toxicology, efficacy, and human safety.

  18. Continuous, real-time bioimaging of chemical bioavailability and toxicology using autonomously bioluminescent human cell lines (United States)

    Xu, Tingting; Close, Dan M.; Webb, James D.; Price, Sarah L.; Ripp, Steven A.; Sayler, Gary S.


    Bioluminescent imaging is an emerging biomedical surveillance strategy that uses external cameras to detect in vivo light generated in small animal models of human physiology or in vitro light generated in tissue culture or tissue scaffold mimics of human anatomy. The most widely utilized of reporters is the firefly luciferase (luc) gene; however, it generates light only upon addition of a chemical substrate, thus only generating intermittent single time point data snapshots. To overcome this disadvantage, we have demonstrated substrate-independent bioluminescent imaging using an optimized bacterial bioluminescence (lux) system. The lux reporter produces bioluminescence autonomously using components found naturally within the cell, thereby allowing imaging to occur continuously and in real-time over the lifetime of the host. We have validated this technology in human cells with demonstrated chemical toxicological profiling against exotoxin exposures at signal strengths comparable to existing luc systems (~1.33 × 107 photons/second). As a proof-in-principle demonstration, we have engineered breast carcinoma cells to express bioluminescence for real-time screening of endocrine disrupting chemicals and validated detection of 17β-estradiol (EC50 = ~ 10 pM). These and other applications of this new reporter technology will be discussed as potential new pathways towards improved models of target chemical bioavailability, toxicology, efficacy, and human safety. PMID:26516295

  19. Detection of human bocavirus and human metapneumovirus by real-time PCR from patients with respiratory symptoms in Southern Brazil

    Directory of Open Access Journals (Sweden)

    Diogo André Pilger


    Full Text Available The introduction of newer molecular methods has led to the discovery of new respiratory viruses, such as human metapneumovirus (hMPV and human bocavirus (hBoV, in respiratory tract specimens. We have studied the occurrence of hMPV and hBoV in the Porto Alegre (PA metropolitan area, one of the southernmost cities of Brazil, evaluating children with suspected lower respiratory tract infection from May 2007-June 2008. A real-time polymerase chain reaction method was used for amplification and detection of hMPV and hBoV and to evaluate coinfections with respiratory syncytial virus (RSV, influenza A and B, parainfluenza 1, 2 and 3, human rhinovirus and human adenovirus. Of the 455 nasopharyngeal aspirates tested, hMPV was detected in 14.5% of samples and hBoV in 13.2%. A unique causative viral agent was identified in 46.2% samples and the coinfection rate was 43.7%. For hBoV, 98.3% of all positive samples were from patients with mixed infections. Similarly, 84.8% of all hMPV-positive results were also observed in mixed infections. Both hBoV and hMPV usually appeared with RSV. In summary, this is the first confirmation that hMPV and hBoV circulate in PA; this provides evidence of frequent involvement of both viruses in children with clinical signs of acute viral respiratory tract infection, although they mainly appeared as coinfection agents.

  20. Circadian variation of the human metabolome captured by real-time breath analysis.

    Directory of Open Access Journals (Sweden)

    Pablo Martinez-Lozano Sinues

    Full Text Available Circadian clocks play a significant role in the correct timing of physiological metabolism, and clock disruption might lead to pathological changes of metabolism. One interesting method to assess the current state of metabolism is metabolomics. Metabolomics tries to capture the entirety of small molecules, i.e. the building blocks of metabolism, in a given matrix, such as blood, saliva or urine. Using mass spectrometric approaches we and others have shown that a significant portion of the human metabolome in saliva and blood exhibits circadian modulation; independent of food intake or sleep/wake rhythms. Recent advances in mass spectrometry techniques have introduced completely non-invasive breathprinting; a method to instantaneously assess small metabolites in human breath. In this proof-of-principle study, we extend these findings about the impact of circadian clocks on metabolomics to exhaled breath. As previously established, our method allows for real-time analysis of a rich matrix during frequent non-invasive sampling. We sampled the breath of three healthy, non-smoking human volunteers in hourly intervals for 24 hours during total sleep deprivation, and found 111 features in the breath of all individuals, 36-49% of which showed significant circadian variation in at least one individual. Our data suggest that real-time mass spectrometric "breathprinting" has high potential to become a useful tool to understand circadian metabolism, and develop new biomarkers to easily and in real-time assess circadian clock phase and function in experimental and clinical settings.

  1. Separating timing, movement conditions and individual differences in the analysis of human movement

    DEFF Research Database (Denmark)

    Raket, Lars Lau; Grimme, Britta; Schöner, Gregor;


    mixed-effects models as viable alternatives to conventional analysis frameworks. The model is then combined with a novel factor-analysis model that estimates the low-dimensional subspace within which movements vary when the task demands vary. Our framework enables us to visualize different dimensions......A central task in the analysis of human movement behavior is to determine systematic patterns and differences across experimental conditions, participants and repetitions. This is possible because human movement is highly regular, being constrained by invariance principles. Movement timing...... of movement variation and to test hypotheses about the effect of obstacle placement and height on the movement path. We demonstrate that the approach can be used to uncover new properties of human movement....

  2. Tolerance of disturbance by humans in long-time resident and recent colonist urban doves

    Institute of Scientific and Technical Information of China (English)

    Jemma; Gendall; Alan; Lill; Juliey; Beckman


    Background: A critical trait for successful urban dwelling by birds is the ability to tolerate high levels of disturbing stimulation by humans. If such tolerance is partly acquired gradually after colonization, species with a long history of residence in cities are likely to be more tolerant of such stimulation than recent urban colonists, but this has not often been tested.Methods: We tested whether introduced Rock(Columba livia) and Spotted(Streptopelis chinensis) Doves, historically long-term residents of Melbourne, Australia, were more tolerant of disturbance by humans than the very recent colonist, the native Crested Pigeon(Ochyphaps lophotes) by comparing the Flight Initiation Distances(FID) and time allocations to vigilance during foraging of all three species in urban Melbourne. That all three species are members of the Columbiformes reduces the possibility that any species differences in tolerance are simply phylogenetic in origin.Results: Flight initiation distance was shorter in Rock Doves than in the other two species, which did not differ in approachability by a human. Rock Doves retreated from an approaching human mainly by walking a relatively short distance, Crested Pigeons mainly by running a relatively short distance and Spotted Doves primarily by flying a comparatively long distance. The time allocation to anti-predator vigilance of Rock Doves was smaller than that of the other two species, whose allocations were similar.Conclusions: The very recent colonist of eastern Melbourne, the Crested Pigeon, was not the least tolerant of disturbance by humans of the three related species. Natural selection for tolerance therefore probably cannot entirely explain the pattern of tolerance evident among these urban dove species and behavioural flexibility is probably involved. Length of residency in a city is not an infallible guide to a species’ level of tolerance of disturbance by humans.

  3. Tolerance of disturbance by humans in long-time resident and recent colonist urban doves

    Institute of Scientific and Technical Information of China (English)

    Jemma Gendall; Alan Lill; Juliey Beckman


    Background:A critical trait for successful urban dwelling by birds is the ability to tolerate high levels of disturbing stimulation by humans. If such tolerance is partly acquired gradually after colonization, species with a long history of residence in cities are likely to be more tolerant of such stimulation than recent urban colonists, but this has not often been tested. Methods:We tested whether introduced Rock (Columba livia) and Spotted (Streptopelis chinensis) Doves, historically long-term residents of Melbourne, Australia, were more tolerant of disturbance by humans than the very recent colonist, the native Crested Pigeon (Ochyphaps lophotes) by comparing the Flight Initiation Distances (FID) and time allocations to vigilance during foraging of all three species in urban Melbourne. That al three species are members of the Columbiformes reduces the possibility that any species differences in tolerance are simply phylogenetic in origin. Results:Flight initiation distance was shorter in Rock Doves than in the other two species, which did not differ in approachability by a human. Rock Doves retreated from an approaching human mainly by walking a relatively short distance, Crested Pigeons mainly by running a relatively short distance and Spotted Doves primarily by flying a comparatively long distance. The time allocation to anti-predator vigilance of Rock Doves was smaller than that of the other two species, whose allocations were similar. Conclusions:The very recent colonist of eastern Melbourne, the Crested Pigeon, was not the least tolerant of disturbance by humans of the three related species. Natural selection for tolerance therefore probably cannot entirely explain the pattern of tolerance evident among these urban dove species and behavioural flexibility is probably involved. Length of residency in a city is not an infallible guide to a species’ level of tolerance of disturbance by humans.

  4. Amplified Immunoassay of Human IgG Using Real-time Biomolecular Interaction Analysis (BIA) Technology

    Institute of Scientific and Technical Information of China (English)

    PEI,Ren-Jun(裴仁军); CUI,Xiao-Qiang(崔小强); YANG,Xiu-Rong(杨秀荣); WANG,Er-Kang(汪尔康)


    An automated biomolecular interaction analysis instrument (BIAcore) based on surface plasmon resonance (SPR) has been used to determine human immunoglobulin G (IgG) in real time. Polyclonal anti-human IgG antibody was covalently immobilized to a carboxymethyldextran-modified gold film surface. The samples of human IgG prepared in HBS buffer were poured over the immobilized surface. The signal amplification antibody was applied to amplify the response signal. After each measurement, the surface was regenerated with 0.1 mol/L H3PO4. The assay was rapid, requiring only 30 min for antibody immobilization and 20 min for each subsequent process of immune binding, antibody amplification and regeneration. The antibody immobilized surface had good response to human IgG in the range of 0.12-60 nmol/L with a detection limit of 60 pmoL/L. The same antibody immobilized surface could be used for more than 110 cycles of binding, amplificafion and regeneration. The results demonstrate that the sensitivity, specificity and reproducibility of amplified immunoassay using real-time BIA technology are satisfactory.

  5. Evidence for a time-invariant phase variable in human ankle control.

    Directory of Open Access Journals (Sweden)

    Robert D Gregg

    Full Text Available Human locomotion is a rhythmic task in which patterns of muscle activity are modulated by state-dependent feedback to accommodate perturbations. Two popular theories have been proposed for the underlying embodiment of phase in the human pattern generator: a time-dependent internal representation or a time-invariant feedback representation (i.e., reflex mechanisms. In either case the neuromuscular system must update or represent the phase of locomotor patterns based on the system state, which can include measurements of hundreds of variables. However, a much simpler representation of phase has emerged in recent designs for legged robots, which control joint patterns as functions of a single monotonic mechanical variable, termed a phase variable. We propose that human joint patterns may similarly depend on a physical phase variable, specifically the heel-to-toe movement of the Center of Pressure under the foot. We found that when the ankle is unexpectedly rotated to a position it would have encountered later in the step, the Center of Pressure also shifts forward to the corresponding later position, and the remaining portion of the gait pattern ensues. This phase shift suggests that the progression of the stance ankle is controlled by a biomechanical phase variable, motivating future investigations of phase variables in human locomotor control.

  6. A Novel Bioinspired Vision System: A Step toward Real-Time Human-Robot Interactions

    Directory of Open Access Journals (Sweden)

    Abdul Rahman Hafiz


    Full Text Available Building a human-like robot that could be involved in our daily lives is a dream of many scientists. Achieving a sophisticated robot's vision system, which can enhance the robot's real-time interaction ability with the human, is one of the main keys toward realizing such an autonomous robot. In this work, we are suggesting a bioinspired vision system that helps to develop an advanced human-robot interaction in an autonomous humanoid robot. First, we enhance the robot's vision accuracy online by applying a novel dynamic edge detection algorithm abstracted from the rules that the horizontal cells play in the mammalian retina. Second, in order to support the first algorithm, we improve the robot's tracking ability by designing a variant photoreceptors distribution corresponding to what exists in the human vision system. The experimental results verified the validity of the model. The robot could have a clear vision in real time and build a mental map that assisted it to be aware of the frontal users and to develop a positive interaction with them.

  7. Time-dependent biphasic modulation of human BDNF by antidepressants in neuroblastoma cells

    Directory of Open Access Journals (Sweden)

    Musazzi Laura


    Full Text Available Abstract Background Recent rodent studies reported that antidepressant treatments affect the expression of brain-derived neurotrophic factor (BDNF mRNA in a way that is dependent on treatment duration, by selective modulation of different BDNF transcripts. However, no data are available for the human BDNF gene. We studied the effect of different antidepressants on BDNF mRNA expression in human neuroblastoma SH-SY5Y cells. Results Cultured cells were treated with the antidepressants fluoxetine, reboxetine and desipramine for different time lengths (6, 24, 48 hours. Expression of total BDNF mRNA was analyzed by reverse transcription PCR and levels of different BDNF transcripts were detected by hemi-nested PCR with specific primers. Short-term treatment (6 hours with reboxetine or desipramine reduced total BDNF, whereas long-term treatment (48 hours significantly increased total BDNF mRNA levels. These changes were accounted for by differential regulation of BDNF IV and VIa/b transcripts. Fluoxetine showed no significant effects. Conclusion This is the first study showing biphasic changes in the expression of total and specific BDNF transcripts in human cells following antidepressant treatments. These findings suggest that biphasic induction of BDNF by antidepressants could be a feature common to rodents and humans and encourage the use of SH-SY5Y cells as a tool for investigation of drug effects on human genes.

  8. Plasticity resembling spike-timing dependent synaptic plasticity: the evidence in human cortex

    Directory of Open Access Journals (Sweden)

    Florian Müller-Dahlhaus


    Full Text Available Spike-timing dependent plasticity (STDP has been studied extensively in a variety of animal models during the past decade but whether it can be studied at the systems level of the human cortex has been a matter of debate. Only recently newly developed non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS have made it possible to induce and assess timing dependent plasticity in conscious human subjects. This review will present a critical synopsis of these experiments, which suggest that several of the principal characteristics and molecular mechanisms of TMS-induced plasticity correspond to those of STDP as studied at a cellular level. TMS combined with a second phasic stimulation modality can induce bidirectional long-lasting changes in the excitability of the stimulated cortex, whose polarity depends on the order of the associated stimulus-evoked events within a critical time window of tens of milliseconds. Pharmacological evidence suggests an NMDA receptor mediated form of synaptic plasticity. Studies in human motor cortex demonstrated that motor learning significantly modulates TMS-induced timing dependent plasticity, and, conversely, may be modulated bidirectionally by prior TMS-induced plasticity, providing circumstantial evidence that long-term potentiation-like mechanisms may be involved in motor learning. In summary, convergent evidence is being accumulated for the contention that it is now possible to induce STDP-like changes in the intact human central nervous system by means of TMS to study and interfere with synaptic plasticity in neural circuits in the context of behaviour such as learning and memory.

  9. Constitutive Modeling of Time-Dependent Response of Human Plantar Aponeurosis


    Pavan, P. G.; Pachera, P.; Stecco, C.; Natali, A. N.


    The attention is focused on the viscoelastic behavior of human plantar aponeurosis tissue. At this purpose, stress relaxation tests were developed on samples taken from the plantar aponeurosis of frozen adult donors with age ranging from 67 to 78 years, imposing three levels of strain in the physiological range (4%, 6%, and 8%) and observing stress decay for 240 s. A viscohyperelastic fiber-reinforced constitutive model with transverse isotropy was assumed to describe the time-dependent behav...

  10. MRI is unable to illustrate the absorption time of the absorbable TIGR mesh in humans

    DEFF Research Database (Denmark)

    Öberg, Stina; Andresen, Kristoffer; Møller, Jakob M;


    3 years in sheep. The patient was therefore followed for 3 years by annual magnetic resonance imagings (MRIs) to illustrate the absorption time in humans. During follow-up, the thickness of the absorbable mesh slightly decreased, and at the last clinical examination, the patient was without...... a recurrence. However, MRI failed to illustrate absorption of the TIGR mesh, perhaps since new connective tissue and the mesh material had the same appearance on the images. In conclusion, MRI was unable to confirm an absorption time of 3 years for the TIGR mesh, and further studies are needed to investigate...

  11. Optimal time for human umbilical cord blood cell transplantation in rats with myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    XING Yun-li; SHEN Lu-hua; LI Hong-wei; ZHANG Yu-chen; ZHAO Lin; ZHAO Shu-mei; XU Qing


    Background Cell therapy for cardiac regeneration is still under investigation. To date there have been a limited number of studies describing the optimal time for cell injection. The present study aimed to examine the optimal time for human umbilical cord blood cells (HUCBCs) transplantation after myocardial infarction (MI).Methods The animals underwent MI by ligation of the left anterior descending coronary artery and received an intravenous injection of equal volumes of HUCBCs or phosphate buffered saline at days 1,5,10 and 30 after MI. HUCBCs were detected by immunostaining against human human leucocyte antigen (HLA). Cardiac function, histological analysis and measurement of vascular endothelial growth factor (VEGF) were performed 4 weeks after cell transplantation. Results HUCBCs transplantation could improve cardiac function in rats that received transplantation at 5 and 10 days after MI. The best benefit was achieved in rats that received cells at 10-day after MI. Survival of engrafted HUCBCs, angiogenesis and VEGF expression were more obvious in the 10-day transplantation group than in the other transplantation groups. No evidence of cardiomyocyte regeneration was detected in any transplanted rats. Conclusions HUCBCs transplantation could improve cardiac function in rats that received HUCBCs at days 5 and 10 after MI with the optimal time for transplantation being 10 days post MI. Angiogenesis, but not cardiomyocyte regeneration, played a key role in the cardiac function improvement.

  12. UWB micro-doppler radar for human gait analysis using joint range-time-frequency representation (United States)

    Wang, Yazhou; Fathy, Aly E.


    In this paper, we present a novel, standalone ultra wideband (UWB) micro-Doppler radar sensor that goes beyond simple range or micro-Doppler detection to combined range-time-Doppler frequency analysis. Moreover, it can monitor more than one human object in both line-of-sight (LOS) and through wall scenarios, thus have full human objects tracking capabilities. The unique radar design is based on narrow pulse transceiver, high speed data acquisition module, and wideband antenna array. For advanced radar post-data processing, joint range-time-frequency representation has been performed. Characteristics of human walking activity have been analyzed using the radar sensor by precisely tracking the radar object and acquiring range-time-Doppler information simultaneously. The UWB micro-Doppler radar prototype is capable of detecting Doppler frequency range from -180 Hz to +180 Hz, which allows a maximum target velocity of 9 m/s. The developed radar sensor can also be extended for many other applications, such as respiration and heartbeat detection of trapped survivors under building debris.

  13. Time-course regulation of quercetin on cell survival/proliferation pathways in human hepatoma cells. (United States)

    Granado-Serrano, Ana Belén; Angeles Martín, María; Bravo, Laura; Goya, Luis; Ramos, Sonia


    Quercetin, a dietary flavonoid, has been shown to possess anticarcinogenic properties, but the precise molecular mechanisms of action are not thoroughly elucidated. This study was aimed at investigating the time-course regulation effect of quercetin on survival/proliferation pathways in a human hepatoma cell line (HepG2). Quercetin induced a significant time-dependent inactivation of the major survival signaling proteins, i. e., phosphatidylinositol 3-kinase (PI 3-kinase)/protein kinase B (AKT), extracellular regulated kinase (ERK), protein kinase C-alpha (PKC-alpha), in concert with a time-dependent activation of key death-related signals: c-jun amino-terminal kinase (JNK) and PKC-delta. These data suggest that quercetin exerts a tight regulation of survival/proliferation pathways that requires the integration of different signals and persists over time, being the balance of these regulatory signals what determines the fate of HepG2 cells.

  14. Influence of Power Delivery Timing on the Energetics and Biomechanics of Humans Wearing a Hip Exoskeleton (United States)

    Young, Aaron J.; Foss, Jessica; Gannon, Hannah; Ferris, Daniel P.


    A broad goal in the field of powered lower limb exoskeletons is to reduce the metabolic cost of walking. Ankle exoskeletons have successfully achieved this goal by correctly timing a plantarflexor torque during late stance phase. Hip exoskeletons have the potential to assist with both flexion and extension during walking gait, but the optimal timing for maximally reducing metabolic cost is unknown. The focus of our study was to determine the best assistance timing for applying hip assistance through a pneumatic exoskeleton on human subjects. Ten non-impaired subjects walked with a powered hip exoskeleton, and both hip flexion and extension assistance were separately provided at different actuation timings using a simple burst controller. The largest average across-subject reduction in metabolic cost for hip extension was at 90% of the gait cycle (just prior to heel contact) and for hip flexion was at 50% of the gait cycle; this resulted in an 8.4 and 6.1% metabolic reduction, respectively, compared to walking with the unpowered exoskeleton. However, the ideal timing for both flexion and extension assistance varied across subjects. When selecting the assistance timing that maximally reduced metabolic cost for each subject, average metabolic cost for hip extension was 10.3% lower and hip flexion was 9.7% lower than the unpowered condition. When taking into account user preference, we found that subject preference did not correlate with metabolic cost. This indicated that user feedback was a poor method of determining the most metabolically efficient assistance power timing. The findings of this study are relevant to developers of exoskeletons that have a powered hip component to assist during human walking gait. PMID:28337434

  15. Real-time functional near-infrared imager and imaging of human brain activity (United States)

    Luo, Qingming; Zeng, Shaoqun; Gong, Hui; Chen, Weiguo; Zhang, Zhi; Chance, Britton


    A real time functional near infrared imager (fNIRI) was introduced. The imager was controlled by a computer and the signals from the detectors were converted and processed in real time. A user-friendly software was programmed with Visual C++ language. Relative changes of oxy - Hb, Hb, and total blood concentration in 16 channels and the corresponding images can be displayed in real time on the computer. The imager was used as a real time monitor in psychological tests to record the response of the frontal cortex of human subjects. In mental work and pattern recognition tests, we recorded oxygen consumption and blood flow changes of volunteers' frontal cortex. The psychological results showed that the lower part of the left frontal gyres had intensive relation to pattern recognition and has definite boundaries. However, the mental work involved more zones of the frontal gyres and may be a complex conceptual model. The results also suggested that the human brain has an precise and complicated adjustability. The oxygen supplement in the stimulated area increased as the neuron stimulation.

  16. Critical time delay of the pineal melatonin rhythm in humans due to weak electromagnetic exposure. (United States)

    Halgamuge, Malka N


    Electromagnetic fields (EMFs) can increase free radicals, activate the stress response and alter enzyme reactions. Intracellular signalling is mediated by free radicals and enzyme kinetics is affected by radical pair recombination rates. The magnetic field component of an external EMF can delay the "recombination rate" of free radical pairs. Magnetic fields thus increase radical life-times in biological systems. Although measured in nanoseconds, this extra time increases the potential to do more damage. Melatonin regulates the body's sleep-wake cycle or circadian rhythm. The World Health Organization (WHO) has confirmed that prolonged alterations in sleep patterns suppress the body's ability to make melatonin. Considerable cancer rates have been attributed to the reduction of melatonin production as a result of jet lag and night shift work. In this study, changes in circadian rhythm and melatonin concentration are observed due to the external perturbation of chemical reaction rates. We further analyze the pineal melatonin rhythm and investigate the critical time delay or maturation time of radical pair recombination rates, exploring the impact of the mRNA degradation rate on the critical time delay. The results show that significant melatonin interruption and changes to the circadian rhythm occur due to the perturbation of chemical reaction rates, as also reported in previous studies. The results also show the influence of the mRNA degradation rate on the circadian rhythm's critical time delay or maturation time. The results support the hypothesis that exposure to weak EMFs via melatonin disruption can adversely affect human health.

  17. DNA methylation dynamics in human induced pluripotent stem cells over time.

    Directory of Open Access Journals (Sweden)

    Koichiro Nishino


    Full Text Available Epigenetic reprogramming is a critical event in the generation of induced pluripotent stem cells (iPSCs. Here, we determined the DNA methylation profiles of 22 human iPSC lines derived from five different cell types (human endometrium, placental artery endothelium, amnion, fetal lung fibroblast, and menstrual blood cell and five human embryonic stem cell (ESC lines, and we followed the aberrant methylation sites in iPSCs for up to 42 weeks. The iPSCs exhibited distinct epigenetic differences from ESCs, which were caused by aberrant methylation at early passages. Multiple appearances and then disappearances of random aberrant methylation were detected throughout iPSC reprogramming. Continuous passaging of the iPSCs diminished the differences between iPSCs and ESCs, implying that iPSCs lose the characteristics inherited from the parent cells and adapt to very closely resemble ESCs over time. Human iPSCs were gradually reprogrammed through the "convergence" of aberrant hyper-methylation events that continuously appeared in a de novo manner. This iPS reprogramming consisted of stochastic de novo methylation and selection/fixation of methylation in an environment suitable for ESCs. Taken together, random methylation and convergence are driving forces for long-term reprogramming of iPSCs to ESCs.

  18. Enhanced homology-directed human genome engineering by controlled timing of CRISPR/Cas9 delivery. (United States)

    Lin, Steven; Staahl, Brett T; Alla, Ravi K; Doudna, Jennifer A


    The CRISPR/Cas9 system is a robust genome editing technology that works in human cells, animals and plants based on the RNA-programmed DNA cleaving activity of the Cas9 enzyme. Building on previous work (Jinek et al., 2013), we show here that new genetic information can be introduced site-specifically and with high efficiency by homology-directed repair (HDR) of Cas9-induced site-specific double-strand DNA breaks using timed delivery of Cas9-guide RNA ribonucleoprotein (RNP) complexes. Cas9 RNP-mediated HDR in HEK293T, human primary neonatal fibroblast and human embryonic stem cells was increased dramatically relative to experiments in unsynchronized cells, with rates of HDR up to 38% observed in HEK293T cells. Sequencing of on- and potential off-target sites showed that editing occurred with high fidelity, while cell mortality was minimized. This approach provides a simple and highly effective strategy for enhancing site-specific genome engineering in both transformed and primary human cells.

  19. Quantifying the Human Impacts on Papua New Guinea Reef Fish Communities across Space and Time. (United States)

    Drew, Joshua A; Amatangelo, Kathryn L; Hufbauer, Ruth A


    Describing the drivers of species loss and of community change are important goals in both conservation and ecology. However, it is difficult to determine whether exploited species decline due to direct effects of harvesting or due to other environmental perturbations brought about by proximity to human populations. Here we quantify differences in species richness of coral reef fish communities along a human population gradient in Papua New Guinea to understand the relative impacts of fishing and environmental perturbation. Using data from published species lists we categorize the reef fishes as either fished or non-fished based on their body size and reports from the published literature. Species diversity for both fished and non-fished groups decreases as the size of the local human population increases, and this relationship is stronger in species that are fished. Additionally, comparison of modern and museum collections show that modern reef communities have proportionally fewer fished species relative to 19th century ones. Together these findings show that the reef fish communities of Papua New Guinea experience multiple anthropogenic stressors and that even at low human population levels targeted species experience population declines across both time and space.

  20. Automatic Tracking and Motility Analysis of Human Sperm in Time-Lapse Images. (United States)

    Urbano, Leonardo F; Masson, Puneet; VerMilyea, Matthew; Kam, Moshe


    We present a fully automated multi-sperm tracking algorithm. It has the demonstrated capability to detect and track simultaneously hundreds of sperm cells in recorded videos while accurately measuring motility parameters over time and with minimal operator intervention. Algorithms of this kind may help in associating dynamic swimming parameters of human sperm cells with fertility and fertilization rates. Specifically, we offer an image processing method, based on radar tracking algorithms, that detects and tracks automatically the swimming paths of human sperm cells in timelapse microscopy image sequences of the kind that is analyzed by fertility clinics. Adapting the well-known joint probabilistic data association filter (JPDAF), we automatically tracked hundreds of human sperm simultaneously and measured their dynamic swimming parameters over time. Unlike existing CASA instruments, our algorithm has the capability to track sperm swimming in close proximity to each other and during apparent cell-to-cell collisions. Collecting continuously parameters for each sperm tracked without sample dilution (currently impossible using standard CASA systems) provides an opportunity to compare such data with standard fertility rates. The use of our algorithm thus has the potential to free the clinician from having to rely on elaborate motility measurements obtained manually by technicians, speed up semen processing, and provide medical practitioners and researchers with more useful data than are currently available.

  1. Real Time Multiple Hand Gesture Recognition System for Human Computer Interaction

    Directory of Open Access Journals (Sweden)

    Siddharth S. Rautaray


    Full Text Available With the increasing use of computing devices in day to day life, the need of user friendly interfaces has lead towards the evolution of different types of interfaces for human computer interaction. Real time vision based hand gesture recognition affords users the ability to interact with computers in more natural and intuitive ways. Direct use of hands as an input device is an attractive method which can communicate much more information by itself in comparison to mice, joysticks etc allowing a greater number of recognition system that can be used in a variety of human computer interaction applications. The gesture recognition system consist of three main modules like hand segmentation, hand tracking and gesture recognition from hand features. The designed system further integrated with different applications like image browser, virtual game etc. possibilities for human computer interaction. Computer Vision based systems has the potential to provide more natural, non-contact solutions. The present research work focuses on to design and develops a practical framework for real time hand gesture.

  2. The impact of communication on human behaviour in times of crisis. (United States)

    MacLeod, Andrew

    Decision makers have constantly sought to find the most appropriate ways to use communication to influence behaviour during times of crises to assist in their recovery. This paper will investigate why policy makers wish to utilise effective crisis communications and explore the importance of crisis communication on influencing human behaviour in a time of crisis as well as the influence that the medium of communication can have. It will be noted that the medium of the message is important to ensure that the correct audience has been reached. This paper will suggest that, for decision makers to maximise the impact of crisis communications during a crisis, they must utilise rhetoric and cognitive response theory. It will also be suggested that the most importance factor in influencing behaviour in a time of crisis is that communications are provided from a credible source and are empathic in nature.

  3. Real-time detection of acetylcholine release from the human endocrine pancreas. (United States)

    Rodriguez-Diaz, Rayner; Dando, Robin; Huang, Y Anthony; Berggren, Per-Olof; Roper, Stephen D; Caicedo, Alejandro


    Neurons, sensory cells and endocrine cells secrete neurotransmitters and hormones to communicate with other cells and to coordinate organ and system function. Validation that a substance is used as an extracellular signaling molecule by a given cell requires a direct demonstration of its secretion. In this protocol we describe the use of biosensor cells to detect neurotransmitter release from endocrine cells in real-time. Chinese hamster ovary cells expressing the muscarinic acetylcholine (ACh) receptor M3 were used as ACh biosensors to record ACh release from human pancreatic islets. We show how ACh biosensors loaded with the Ca(2+) indicator Fura-2 and pressed against isolated human pancreatic islets allow the detection of ACh release. The biosensor approach is simple; the Ca(2+) signal generated in the biosensor cell reflects the presence (release) of a neurotransmitter. The technique is versatile because biosensor cells expressing a variety of receptors can be used in many applications. The protocol takes ∼3 h.

  4. Real-time estimation of small-area populations with human biomarkers in sewage

    Energy Technology Data Exchange (ETDEWEB)

    Daughton, Christian G., E-mail:


    A new approach is conceptualized for measuring small-area human populations by using biomarkers in sewage. The basis for the concept (SCIM: Sewage Chemical-Information Mining) is supported by a comprehensive examination and synthesis of data published across several disciplines, including medicine, microbiology, clinical chemistry, and environmental science. Accurate measures of human populations are fundamental to numerous disciplines, including economics, marketing, politics, sociology, public health and safety (e.g., disease management; assessment of natural hazards; disaster prevention and response), quality of life, and the environment. Knowing the size, distribution, and flow of a small-area (local) population facilitates understanding the numerous and complex linkages and interactions between humans and the environment. Examples include material-flow (substance-flow) analysis, determining the magnitude of per capita contribution of pollutant loadings to watersheds, or forecasting future impacts of local populations on the environment or a population's demands on resources. While no definitive approach exists for measuring small-area populations, census-taking is a long-established convention. No approach exists, however, for gauging small-area populations in real-time, as none is able to capture population dynamics, which involve transient changes (e.g., daily influx and efflux) and lasting changes (e.g., births, deaths, change in residence). Accurate measurement of small-area populations in real time has never been possible but is essential for facilitating the design of more sustainable communities. Real-time measurement would provide communities the capability of testing what-if scenarios in design and policy decisions. After evaluation of a range of biomarkers (including the nitrogenous waste product creatinine, which has been long used in clinical chemistry as a parameter to normalize the concentrations of other urinary excretion products to

  5. Human hippocampus represents space and time during retrieval of real-world memories. (United States)

    Nielson, Dylan M; Smith, Troy A; Sreekumar, Vishnu; Dennis, Simon; Sederberg, Per B


    Memory stretches over a lifetime. In controlled laboratory settings, the hippocampus and other medial temporal lobe brain structures have been shown to represent space and time on the scale of meters and seconds. It remains unclear whether the hippocampus also represents space and time over the longer scales necessary for human episodic memory. We recorded neural activity while participants relived their own experiences, cued by photographs taken with a custom lifelogging device. We found that the left anterior hippocampus represents space and time for a month of remembered events occurring over distances of up to 30 km. Although previous studies have identified similar drifts in representational similarity across space or time over the relatively brief time scales (seconds to minutes) that characterize individual episodic memories, our results provide compelling evidence that a similar pattern of spatiotemporal organization also exists for organizing distinct memories that are distant in space and time. These results further support the emerging view that the anterior, as opposed to posterior, hippocampus integrates distinct experiences, thereby providing a scaffold for encoding and retrieval of autobiographical memories on the scale of our lives.

  6. Physiological and Molecular Genetic Effects of Time-Varying Electromagnetic Fields on Human Neuronal Cells (United States)

    Goodwin, Thomas J.


    The present investigation details the development of model systems for growing two- and three-dimensional human neural progenitor cells within a culture medium facilitated by a time-varying electromagnetic field (TVEMF). The cells and culture medium are contained within a two- or three-dimensional culture vessel, and the electromagnetic field is emitted from an electrode or coil. These studies further provide methods to promote neural tissue regeneration by means of culturing the neural cells in either configuration. Grown in two dimensions, neuronal cells extended longitudinally, forming tissue strands extending axially along and within electrodes comprising electrically conductive channels or guides through which a time-varying electrical current was conducted. In the three-dimensional aspect, exposure to TVEMF resulted in the development of three-dimensional aggregates, which emulated organized neural tissues. In both experimental configurations, the proliferation rate of the TVEMF cells was 2.5 to 4.0 times the rate of the non-waveform cells. Each of the experimental embodiments resulted in similar molecular genetic changes regarding the growth potential of the tissues as measured by gene chip analyses, which measured more than 10,000 human genes simultaneously.

  7. Human Activity Recognition in Real-Times Environments using Skeleton Joints

    Directory of Open Access Journals (Sweden)

    Ajay Kumar


    Full Text Available In this research work, we proposed a most effective noble approach for Human activity recognition in real-time environments. We recognize several distinct dynamic human activity actions using kinect. A 3D skeleton data is processed from real-time video gesture to sequence of frames and getter skeleton joints (Energy Joints, orientation, rotations of joint angles from selected setof frames. We are using joint angle and orientations, rotations information from Kinect therefore less computation required. However, after extracting the set of frames we implemented several classification techniques Principal Component Analysis (PCA with several distance based classifiers and Artificial Neural Network (ANN respectively with some variants for classify our all different gesture models. However, we conclude that use very less number of frame (10-15% for train our system efficiently from the entire set of gesture frames. Moreover, after successfully completion of our classification methods we clinch an excellent overall accuracy 94%, 96% and 98% respectively. We finally observe that our proposed system is more useful than comparing to other existing system, therefore our model is best suitable for real-time application such as in video games for player action/gesture recognition.

  8. Gene expression time course in the human skin during elicitation of allergic contact dermatitis

    DEFF Research Database (Denmark)

    Pedersen, Malene; Skov, Lone; Menné, Torkil


    Genes involved in the inflammatory response resulting in allergic contact dermatitis (ACD) are only partly known. In this study, we introduce the use of high-density oligonucleotide arrays for gene expression profiling in human skin during the elicitation of ACD. Skin biopsies from normal...... and nickel-exposed skin were obtained from seven nickel-allergic patients and five nonallergic controls at four different time points during elicitation of eczema. Each gene expression profile was analyzed by hybridization to high-density oligonucleotide arrays. Cluster analysis of 74 genes found...

  9. Evolution of human posture and bipedal locomotion within a provisional time frame of harsh climate changes


    Kurbel, Sven; Rapan, Saša


    In this review paper several emerging issues related to development of human posture and locomotion are arranged in a provisional time frame. Accumulated evidences show that the Eurasian climate was often cold and arid with abundant dust in the atmosphere during the last 500 Ky. These dusty periods of cold, aridity and low insolation lasted from 360 to 340 Kya, 270 to 255 Kya, 170 to 130 Kya, 80 to 60 and finally 40 to 10 Kya. They coincide with migrations of Neanderthals a...

  10. A real time study of the human equilibrium using an instrumented insole with 3 pressure sensors. (United States)

    Abou Ghaida, Hussein; Mottet, Serge; Goujon, Jean-Marc


    The present work deals with the study of the human equilibrium using an ambulatory e-health system. One of the point on which we focus is the fall risk, when losing equilibrium control. A specific postural learning model is presented, and an ambulatory instrumented insole is developed using 3 pressures sensors per foot, in order to determine the real-time displacement and the velocity of the centre of pressure (CoP). The increase of these parameters signals a loss of physiological sensation, usually of vision or of the inner ear. The results are compared to those obtained from classical more complex systems.

  11. Real-time Human Pose Estimation from Video with Convolutional Neural Networks


    Linna, Marko; Kannala, Juho; Rahtu, Esa


    In this paper, we present a method for real-time multi-person human pose estimation from video by utilizing convolutional neural networks. Our method is aimed for use case specific applications, where good accuracy is essential and variation of the background and poses is limited. This enables us to use a generic network architecture, which is both accurate and fast. We divide the problem into two phases: (1) pre-training and (2) finetuning. In pre-training, the network is learned with highly...

  12. Modular Sampling and Analysis Techniques for the Real-Time Analysis of Human Breath

    Energy Technology Data Exchange (ETDEWEB)

    Frank, M; Farquar, G; Adams, K; Bogan, M; Martin, A; Benner, H; Spadaccini, C; Steele, P; Davis, C; Loyola, B; Morgan, J; Sankaran, S


    At LLNL and UC Davis, we are developing several techniques for the real-time sampling and analysis of trace gases, aerosols and exhaled breath that could be useful for a modular, integrated system for breath analysis. Those techniques include single-particle bioaerosol mass spectrometry (BAMS) for the analysis of exhaled aerosol particles or droplets as well as breath samplers integrated with gas chromatography mass spectrometry (GC-MS) or MEMS-based differential mobility spectrometry (DMS). We describe these techniques and present recent data obtained from human breath or breath condensate, in particular, addressing the question of how environmental exposure influences the composition of breath.

  13. A real-time system for biomechanical analysis of human movement and muscle function. (United States)

    van den Bogert, Antonie J; Geijtenbeek, Thomas; Even-Zohar, Oshri; Steenbrink, Frans; Hardin, Elizabeth C


    Mechanical analysis of movement plays an important role in clinical management of neurological and orthopedic conditions. There has been increasing interest in performing movement analysis in real-time, to provide immediate feedback to both therapist and patient. However, such work to date has been limited to single-joint kinematics and kinetics. Here we present a software system, named human body model (HBM), to compute joint kinematics and kinetics for a full body model with 44 degrees of freedom, in real-time, and to estimate length changes and forces in 300 muscle elements. HBM was used to analyze lower extremity function during gait in 12 able-bodied subjects. Processing speed exceeded 120 samples per second on standard PC hardware. Joint angles and moments were consistent within the group, and consistent with other studies in the literature. Estimated muscle force patterns were consistent among subjects and agreed qualitatively with electromyography, to the extent that can be expected from a biomechanical model. The real-time analysis was integrated into the D-Flow system for development of custom real-time feedback applications and into the gait real-time analysis interactive lab system for gait analysis and gait retraining.

  14. Design for interaction between humans and intelligent systems during real-time fault management (United States)

    Malin, Jane T.; Schreckenghost, Debra L.; Thronesbery, Carroll G.


    Initial results are reported to provide guidance and assistance for designers of intelligent systems and their human interfaces. The objective is to achieve more effective human-computer interaction (HCI) for real time fault management support systems. Studies of the development of intelligent fault management systems within NASA have resulted in a new perspective of the user. If the user is viewed as one of the subsystems in a heterogeneous, distributed system, system design becomes the design of a flexible architecture for accomplishing system tasks with both human and computer agents. HCI requirements and design should be distinguished from user interface (displays and controls) requirements and design. Effective HCI design for multi-agent systems requires explicit identification of activities and information that support coordination and communication between agents. The effects are characterized of HCI design on overall system design and approaches are identified to addressing HCI requirements in system design. The results include definition of (1) guidance based on information level requirements analysis of HCI, (2) high level requirements for a design methodology that integrates the HCI perspective into system design, and (3) requirements for embedding HCI design tools into intelligent system development environments.

  15. Ultrasensitive PCR and real-time detection from human genomic samples using a bidirectional flow microreactor. (United States)

    Chen, Lin; West, Jonathan; Auroux, Pierre-Alain; Manz, Andreas; Day, Philip J R


    In this paper we present a reliable bidirectional flow DNA amplification microreactor for processing real-world genomic samples. This system shares the low-power thermal responsiveness of a continuous flow reactor with the low surface area to volume ratio character of stationary reactors for reducing surface inhibitory effects. Silanization with dimethyldichlorosilane in combination with dynamic surface passivation was used to enhance PCR compatibility and enable efficient amplification. For real-time fragment amplification monitoring we have implemented an epimodal fluorescent detection capability. The passivated bidirectional flow system was ultrasensitive, achieving an RNase P gene detection limit of 24 human genome copies with a reaction efficiency of 77%. This starts to rival the performance of a conventional real-time PCR instrument with a reaction efficiency of 93% and revitalizes flow-through PCR as a viable component of lab on a chip DNA analysis formats.

  16. An ultrasensitive time-resolved immunofluorometric assay of human epidermal growth factor. (United States)

    Pesonen, K; Alfthan, H; Stenman, U H; Viinikka, L; Perheentupa, J


    We have developed a sandwich-type time-resolved immunofluorometric assay (TR-IFMA) for human epidermal growth factor (hEGF) in body fluids. A two-step solid-phase technique was used. The assay utilizes a polyclonal anti-hEGF attached to the solid phase, and a monoclonal anti-hEGF labeled with Europium (III) as a tracer. The sensitivity of the assay (2.5 pg/ml) is at least 20 times better than what has been achieved by radioimmunoassay (RIA), and the measuring range is much wider: 2.5-5000 pg/ml. The feasibility of TR-IFMA was tested by assaying urine containing large amounts and amniotic fluid containing small amounts (mostly undetectable by RIA) of immunoreactive hEGF. The correlation between urine hEGF concentrations (1-100 ng/ml) measured by RIA and TR-IFMA was good: r = 0.96.

  17. Steady state and time-resolved autofluorescence studies of human colonic tissues

    Institute of Scientific and Technical Information of China (English)

    Buhong Li; Zhenxi Zhang; Shusen Xie


    Steady state and time-resolved autofluorescence spectroscopies are employed to study the autofluorescence characteristics of human colonic tissues in vitro. The excitation wavelength varies from 260 to 540 nm, and the corresponding fluorescence emission spectra are acquired from 280 to 800 nm. Significant difference in fluorescence intensity of excitation-emission matrices (EEMs) is observed between normal and tumor colonic tissues. Compared with normal colonic tissue, low nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD), and high amino acids and protoporphyrin Ⅸ (PpⅨ) fluorescences characterize high-grade malignant tissue. Moreover, the autofluorescence lifetimes of normal and carcinomatous colonic tissues at 635 nm under 397-nm excitation are about 4.32±0.12 and 18.45±0.05 ns, respectively. The high accumulation of endogenous PpⅨ in colonic cancers is demonstrated in both steady state and time-resolved autofluorescence spectroscopies.

  18. Time-dependent mechanical behavior of human amnion: macroscopic and microscopic characterization. (United States)

    Mauri, Arabella; Perrini, Michela; Ehret, Alexander E; De Focatiis, Davide S A; Mazza, Edoardo


    Characterizing the mechanical response of the human amnion is essential to understand and to eventually prevent premature rupture of fetal membranes. In this study, a large set of macroscopic and microscopic mechanical tests have been carried out on fresh unfixed amnion to gain insight into the time-dependent material response and the underlying mechanisms. Creep and relaxation responses of amnion were characterized in macroscopic uniaxial tension, biaxial tension and inflation configurations. For the first time, these experiments were complemented by microstructural information from nonlinear laser scanning microscopy performed during in situ uniaxial relaxation tests. The amnion showed large tension reduction during relaxation and small inelastic strain accumulation in creep. The short-term relaxation response was related to a concomitant in-plane and out-of-plane contraction, and was dependent on the testing configuration. The microscopic investigation revealed a large volume reduction at the beginning, but no change of volume was measured long-term during relaxation. Tension-strain curves normalized with respect to the maximum strain were highly repeatable in all configurations and allowed the quantification of corresponding characteristic parameters. The present data indicate that dissipative behavior of human amnion is related to two mechanisms: (i) volume reduction due to water outflow (up to ∼20 s) and (ii) long-term dissipative behavior without macroscopic deformation and no systematic global reorientation of collagen fibers.

  19. Distortion effects in a switch array UWB radar for time-lapse imaging of human heartbeats (United States)

    Brovoll, Sverre; Berger, Tor; Aardal, Åyvind; Lande, Tor S.; Hamran, Svein-Erik


    Cardiovascular diseases (CVD) are a major cause of deaths all over the world. Microwave radar can be an alternative sensor for heart diagnostics and monitoring in modern healthcare that aids early detection of CVD symptoms. In this paper measurements from a switch array radar system are presented. This UWB system operates below 3 GHz and does time-lapse imaging of the beating heart inside the human body. The array consists of eight fat dipole elements. With a switch system, every possible sequence of transmit/receive element pairs can be selected to build a radar image from the recordings. To make the radar waves penetrate the human tissue, the antenna array is placed in contact with the body. Removal of the direct signal leakage through the antennas and body surface are done by high-pass (HP) filtering of the data prior to image processing. To analyze the results, measurements of moving spheres in air and simulations are carried out. We see that removal of the direct signal introduces amplitude distortion in the images. In addition, the effect of small target motion between the collection times of data from the individual elements is analyzed. With low pulse repetition frequency (PRF) this motion will distort the image. By using data from real measurements of heart motion in simulations, we analyze how the PRF and the antenna geometry influence this distortions.

  20. Processing Time Reduction: an Application in Living Human High-Resolution Diffusion Magnetic Resonance Imaging Data. (United States)

    Lori, Nicolás F; Ibañez, Augustin; Lavrador, Rui; Fonseca, Lucia; Santos, Carlos; Travasso, Rui; Pereira, Artur; Rossetti, Rosaldo; Sousa, Nuno; Alves, Victor


    High Angular Resolution Diffusion Imaging (HARDI) is a type of brain imaging that collects a very large amount of data, and if many subjects are considered then it amounts to a big data framework (e.g., the human connectome project has 20 Terabytes of data). HARDI is also becoming increasingly relevant for clinical settings (e.g., detecting early cerebral ischemic changes in acute stroke, and in pre-clinical assessment of white matter-WM anatomy using tractography). Thus, this method is becoming a routine assessment in clinical settings. In such settings, the computation time is critical, and finding forms of reducing the processing time in high computation processes such as Diffusion Spectrum Imaging (DSI), a form of HARDI data, is very relevant to increase data-processing speed. Here we analyze a method for reducing the computation time of the dMRI-based axonal orientation distribution function h by using Monte Carlo sampling-based methods for voxel selection. Results evidenced a robust reduction in required data sampling of about 50 % without losing signal's quality. Moreover, we show that the convergence to the correct value in this type of Monte Carlo HARDI/DSI data-processing has a linear improvement in data-processing speed of the ODF determination. Although further improvements are needed, our results represent a promissory step for future processing time reduction in big data.

  1. Time pattern locking scheme for secure multimedia contents in human-centric device. (United States)

    Kim, Hyun-Woo; Kim, Jun-Ho; Park, Jong Hyuk; Jeong, Young-Sik


    Among the various smart multimedia devices, multimedia smartphones have become the most widespread due to their convenient portability and real-time information sharing, as well as various other built-in features. Accordingly, since personal and business activities can be carried out using multimedia smartphones without restrictions based on time and location, people have more leisure time and convenience than ever. However, problems such as loss, theft, and information leakage because of convenient portability have also increased proportionally. As a result, most multimedia smartphones are equipped with various built-in locking features. Pattern lock, personal identification numbers, and passwords are the most used locking features on current smartphones, but these are vulnerable to shoulder surfing and smudge attacks, allowing malicious users to bypass the security feature easily. In particular, the smudge attack technique is a convenient way to unlock multimedia smartphones after they have been stolen. In this paper, we propose the secure locking screen using time pattern (SLSTP) focusing on improved security and convenience for users to support human-centric multimedia device completely. The SLSTP can provide a simple interface to users and reduce the risk factors pertaining to security leakage to malicious third parties.

  2. Real-Time Hand Posture Recognition for Human-Robot Interaction Tasks. (United States)

    Hernandez-Belmonte, Uriel Haile; Ayala-Ramirez, Victor


    In this work, we present a multiclass hand posture classifier useful for human-robot interaction tasks. The proposed system is based exclusively on visual sensors, and it achieves a real-time performance, whilst detecting and recognizing an alphabet of four hand postures. The proposed approach is based on the real-time deformable detector, a boosting trained classifier. We describe a methodology to design the ensemble of real-time deformable detectors (one for each hand posture that can be classified). Given the lack of standard procedures for performance evaluation, we also propose the use of full image evaluation for this purpose. Such an evaluation methodology provides us with a more realistic estimation of the performance of the method. We have measured the performance of the proposed system and compared it to the one obtained by using only the sampled window approach. We present detailed results of such tests using a benchmark dataset. Our results show that the system can operate in real time at about a 10-fps frame rate.

  3. Malnutrition has no effect on the timing of human tooth formation. (United States)

    Elamin, Fadil; Liversidge, Helen M


    The effect of nutrition on the timing of human tooth formation is poorly understood. Delays and advancements in dental maturation have all been reported as well as no effect. We investigated the effect of severe malnutrition on the timing of human tooth formation in a large representative sample of North Sudanese children. The sample (1102 males, 1013 females) consisted of stratified randomly selected healthy individuals in Khartoum, Sudan, aged 2-22 years using a cross-sectional design following the STROBE statement. Nutritional status was defined using WHO criteria of height and weight. Body mass index Z-scores and height for age Z-scores of ≤-2 (cut-off) were used to identify the malnourished group (N = 474) while the normal was defined by Z-scores of ≥0 (N = 799). Clinical and radiographic examination of individuals, with known ages of birth was performed including height and weight measurements. Mandibular left permanent teeth were assessed using eight crown and seven root established tooth formation stages. Mean age at entry and mean age within tooth stages were calculated for each available tooth stage in each group and compared using a t-test. Results show the mean age at entry and mean age within tooth stages were not significantly different between groups affected by severe malnutrition and normal children (p>0.05). This remarkable finding was evident across the span of dental development. We demonstrate that there is little measurable effect of sustained malnutrition on the average timing of tooth formation. This noteworthy finding supports the notion that teeth have substantial biological stability and are insulated from extreme nutritional conditions compared to other maturing body systems.

  4. Malnutrition has no effect on the timing of human tooth formation.

    Directory of Open Access Journals (Sweden)

    Fadil Elamin

    Full Text Available The effect of nutrition on the timing of human tooth formation is poorly understood. Delays and advancements in dental maturation have all been reported as well as no effect. We investigated the effect of severe malnutrition on the timing of human tooth formation in a large representative sample of North Sudanese children. The sample (1102 males, 1013 females consisted of stratified randomly selected healthy individuals in Khartoum, Sudan, aged 2-22 years using a cross-sectional design following the STROBE statement. Nutritional status was defined using WHO criteria of height and weight. Body mass index Z-scores and height for age Z-scores of ≤-2 (cut-off were used to identify the malnourished group (N = 474 while the normal was defined by Z-scores of ≥0 (N = 799. Clinical and radiographic examination of individuals, with known ages of birth was performed including height and weight measurements. Mandibular left permanent teeth were assessed using eight crown and seven root established tooth formation stages. Mean age at entry and mean age within tooth stages were calculated for each available tooth stage in each group and compared using a t-test. Results show the mean age at entry and mean age within tooth stages were not significantly different between groups affected by severe malnutrition and normal children (p>0.05. This remarkable finding was evident across the span of dental development. We demonstrate that there is little measurable effect of sustained malnutrition on the average timing of tooth formation. This noteworthy finding supports the notion that teeth have substantial biological stability and are insulated from extreme nutritional conditions compared to other maturing body systems.


    Directory of Open Access Journals (Sweden)

    H. Miyazaki


    Full Text Available Methodology of automated human settlement mapping is highly needed for utilization of historical satellite data archives for urgent issues of urban growth in global scale, such as disaster risk management, public health, food security, and urban management. As development of global data with spatial resolution of 10-100 m was achieved by some initiatives using ASTER, Landsat, and TerraSAR-X, next goal has targeted to development of time-series data which can contribute to studies urban development with background context of socioeconomy, disaster risk management, public health, transport and other development issues. We developed an automated algorithm to detect human settlement by classification of built-up and non-built-up in time-series Landsat images. A machine learning algorithm, Local and Global Consistency (LLGC, was applied with improvements for remote sensing data. The algorithm enables to use MCD12Q1, a MODIS-based global land cover map with 500-m resolution, as training data so that any manual process is not required for preparation of training data. In addition, we designed the method to composite multiple results of LLGC into a single output to reduce uncertainty. The LLGC results has a confidence value ranging 0.0 to 1.0 representing probability of built-up and non-built-up. The median value of the confidence for a certain period around a target time was expected to be a robust output of confidence to identify built-up or non-built-up areas against uncertainties in satellite data quality, such as cloud and haze contamination. Four scenes of Landsat data for each target years, 1990, 2000, 2005, and 2010, were chosen among the Landsat archive data with cloud contamination less than 20%.We developed a system with the algorithms on the Data Integration and Analysis System (DIAS in the University of Tokyo and processed 5200 scenes of Landsat data for cities with more than one million people worldwide.

  6. Development of Time-Series Human Settlement Mapping System Using Historical Landsat Archive (United States)

    Miyazaki, H.; Nagai, M.; Shibasaki, R.


    Methodology of automated human settlement mapping is highly needed for utilization of historical satellite data archives for urgent issues of urban growth in global scale, such as disaster risk management, public health, food security, and urban management. As development of global data with spatial resolution of 10-100 m was achieved by some initiatives using ASTER, Landsat, and TerraSAR-X, next goal has targeted to development of time-series data which can contribute to studies urban development with background context of socioeconomy, disaster risk management, public health, transport and other development issues. We developed an automated algorithm to detect human settlement by classification of built-up and non-built-up in time-series Landsat images. A machine learning algorithm, Local and Global Consistency (LLGC), was applied with improvements for remote sensing data. The algorithm enables to use MCD12Q1, a MODIS-based global land cover map with 500-m resolution, as training data so that any manual process is not required for preparation of training data. In addition, we designed the method to composite multiple results of LLGC into a single output to reduce uncertainty. The LLGC results has a confidence value ranging 0.0 to 1.0 representing probability of built-up and non-built-up. The median value of the confidence for a certain period around a target time was expected to be a robust output of confidence to identify built-up or non-built-up areas against uncertainties in satellite data quality, such as cloud and haze contamination. Four scenes of Landsat data for each target years, 1990, 2000, 2005, and 2010, were chosen among the Landsat archive data with cloud contamination less than 20%.We developed a system with the algorithms on the Data Integration and Analysis System (DIAS) in the University of Tokyo and processed 5200 scenes of Landsat data for cities with more than one million people worldwide.

  7. Time trends of human papillomavirus types in invasive cervical cancer, from 1940 to 2007. (United States)

    Alemany, Laia; de Sanjosé, Silvia; Tous, Sara; Quint, Wim; Vallejos, Carlos; Shin, Hai-Rim; Bravo, Luis E; Alonso, Patricia; Lima, Marcus A; Guimerà, Núria; Klaustermeier, Joellen; Llombart-Bosch, Antonio; Kasamatsu, Elena; Tatti, Silvio A; Felix, Ana; Molina, Carla; Velasco, Julio; Lloveras, Belen; Clavero, Omar; Lerma, Enrique; Laco, Jan; Bravo, Ignacio G; Guarch, Rosa; Pelayo, Adela; Ordi, Jaume; Andújar, Miguel; Sanchez, Gloria I; Castellsagué, Xavier; Muñoz, Nubia; Bosch, F Xavier


    Contribution over time of human papillomavirus (HPV) types in human cancers has been poorly documented. Such data is fundamental to measure current HPV vaccines impact in the years to come. We estimated the HPV type-specific distribution in a large international series of invasive cervical cancer (ICC) over 70 years prior to vaccination. Paraffin embedded ICC cases diagnosed between 1940 and 2007 were retrieved from eleven countries in Central-South America, Asia and Europe. Included countries reported to have low-medium cervical cancer screening uptake. Information on age at and year of diagnosis was collected from medical records. After histological confirmation, HPV DNA detection was performed by SPF-10/DEIA/LiPA25 (version1). Logistic regression models were used for estimating the adjusted relative contributions (RC) of HPV16 and of HPV18 over time. Among 4,771 HPV DNA positive ICC cases, HPV16 and HPV18 were the two most common HPVs in all the decades with no statistically significant variations of their adjusted-RC from 1940-59 to 2000-07 (HPV16-from 61.5 to 62.1%, and HPV18-from 6.9 to 7.2%). As well, the RC of other HPV types did not varied over time. In the stratified analysis by histology, HPV16 adjusted-RC significantly increased across decades in adenocarcinomas. Regarding age, cases associated to either HPV16, 18 or 45 were younger than those with other HPV types in all the evaluated decades. The observed stability on the HPV type distribution predicts a high and stable impact of HPV vaccination in reducing the cervical cancer burden in future vaccinated generations.

  8. Time-Resolved Autofluorescence Imaging of Human Donor Retina Tissue from Donors with Significant Extramacular Drusen (United States)

    Schweitzer, Dietrich; Gaillard, Elizabeth R.; Dillon, James; Mullins, Robert F.; Russell, Stephen; Hoffmann, Birgit; Peters, Sven; Hammer, Martin; Biskup, Christoph


    Purpose. Time and spectrally resolved measurements of autofluorescence have the potential to monitor metabolism at the cellular level. Fluorophores that emit with the same fluorescence intensity can be discriminated from each other by decay time of fluorescence intensity after pulsed excitation. We performed time-resolved autofluorescence measurements on fundus samples from a donor with significant extramacular drusen. Methods. Tissue sections from two human donors were prepared and imaged with a laser scanning microscope. The sample was excited with a titanium-sapphire laser, which was tuned to 860 nm, and frequency doubled by a BBO crystal to 430 nm. The repetition rate was 76 MHz and the pulse width was 170 femtoseconds (fs). The time-resolved autofluorescence was recorded simultaneously in 16 spectral channels (445–605 nm) and bi-exponentially fitted. Results. RPE can be discriminated clearly from Bruch's membrane, drusen, and choroidal connective tissue by fluorescence lifetime. In RPE, bright fluorescence of lipofuscin could be detected with a maximum at 510 nm and extending beyond 600 nm. The lifetime was 385 ps. Different types of drusen were found. Most of them did not contain lipofuscin and exhibited a weak fluorescence, with a maximum at 470 nm. The lifetime was 1785 picoseconds (ps). Also, brightly emitting lesions, presumably representing basal laminar deposits, with fluorescence lifetimes longer than those recorded in RPE could be detected. Conclusions. The demonstrated differentiation of fluorescent structures by their fluorescence decay time is important for interpretation of in vivo measurements by the new fluorescence lifetime imaging (FLIM) ophthalmoscopy on healthy subjects as well as on patients. PMID:22511622

  9. Effects of psilocybin on time perception and temporal control of behaviour in humans. (United States)

    Wittmann, Marc; Carter, Olivia; Hasler, Felix; Cahn, B Rael; Grimberg, Ulrike; Spring, Philipp; Hell, Daniel; Flohr, Hans; Vollenweider, Franz X


    Hallucinogenic psilocybin is known to alter the subjective experience of time. However, there is no study that systematically investigated objective measures of time perception under psilocybin. Therefore, we studied dose-dependent effects of the serotonin (5-HT)2A/1A receptor agonist psilocybin (4-phosphoryloxy-N, N-dimethyltryptamine) on temporal processing, employing tasks of temporal reproduction, sensorimotor synchronization and tapping tempo. To control for cognitive and subjective changes, we assessed spatial working memory and conscious experience. Twelve healthy human volunteers were tested under placebo, medium (115 microg/kg), and high (250 microg/kg) dose conditions, in a double-blind experimental design. Psilocybin was found to significantly impair subjects' ability to (1) reproduce interval durations longer than 2.5 sec, (2) to synchronize to inter-beat intervals longer than 2 sec and (3) caused subjects to be slower in their preferred tapping rate. These objective effects on timing performance were accompanied by working-memory deficits and subjective changes in conscious state, namely increased reports of 'depersonalization' and 'derealization' phenomena including disturbances in subjective 'time sense.' Our study is the first to systematically assess the impact of psilocybin on timing performance on standardized measures of temporal processing. Results indicate that the serotonin system is selectively involved in duration processing of intervals longer than 2 to 3 seconds and in the voluntary control of the speed of movement. We speculate that psilocybin's selective disruption of longer intervals is likely to be a product of interactions with cognitive dimensions of temporal processing -presumably via 5-HT2A receptor stimulation.

  10. Time resolved dosimetry of human brain exposed to low frequency pulsed magnetic fields (United States)

    Paffi, Alessandra; Camera, Francesca; Lucano, Elena; Apollonio, Francesca; Liberti, Micaela


    An accurate dosimetry is a key issue to understanding brain stimulation and related interaction mechanisms with neuronal tissues at the basis of the increasing amount of literature revealing the effects on human brain induced by low-level, low frequency pulsed magnetic fields (PMFs). Most literature on brain dosimetry estimates the maximum E field value reached inside the tissue without considering its time pattern or tissue dispersivity. Nevertheless a time-resolved dosimetry, accounting for dispersive tissues behavior, becomes necessary considering that the threshold for an effect onset may vary depending on the pulse waveform and that tissues may filter the applied stimulatory fields altering the predicted stimulatory waveform’s size and shape. In this paper a time-resolved dosimetry has been applied on a realistic brain model exposed to the signal presented in Capone et al (2009 J. Neural Transm. 116 257-65), accounting for the broadband dispersivity of brain tissues up to several kHz, to accurately reconstruct electric field and current density waveforms inside different brain tissues. The results obtained by exposing the Duke’s brain model to this PMF signal show that the E peak in the brain is considerably underestimated if a simple monochromatic dosimetry is carried out at the pulse repetition frequency of 75 Hz.

  11. Time course of the angiogenic response during normotrophic and hypertrophic scar formation in humans. (United States)

    van der Veer, Willem M; Niessen, Frank B; Ferreira, José A; Zwiers, Peter J; de Jong, Etty H; Middelkoop, Esther; Molema, Grietje


    Previous research suggests that in hypertrophic scars (HSs), an excess of microvessels is present compared with normotrophic scars (NSs). The aim of our study was to quantify vascular densities in HSs and normotrophic scars and to provide an insight into the kinetics of changes in the expression of angiogenic factors in time during wound healing and HS formation. Human presternal wound healing after cardiothoracic surgery through a sternotomy incision was investigated in a standardized manner. Skin biopsies were collected at consecutive time points, i.e., during surgery and 2, 4, 6, 12, and 52 weeks postoperatively. The expression levels of angiopoietin-1, angiopoietin-2, Tie-2, vascular endothelial growth factor, and urokinase-type plasminogen activator were measured by real-time reverse transcription-polymerase chain reaction. Quantification of angiogenesis and cellular localization of the proteins of interest were based on immunohistochemical analysis. Microvessel densities were higher in the HSs compared with the normotrophic scars 12 weeks (p=0.017) and 52 weeks (p=0.030) postoperatively. Angiopoietin-1 expression was lower in the hypertrophic group (pdecrease in the angiopoietin-1/angiopoietin-2 ratio in the hypertrophic group 4 weeks (p=0.053), 12 weeks (pscars.

  12. A human fecal contamination index for ranking impaired recreational watersusing the HF183 quantitative real-time PCR method (United States)

    Human fecal pollution of surface water remains a public health concern worldwide. As a result, there is a growing interest in the application of human-associated fecal source identification quantitative real-time PCR (qPCR) technologies for recreational water quality risk managem...

  13. Improved HF183 quantitative real-time PCR assay for characterization of human fecal pollution in ambient surface water samples (United States)

    Real-time quantitative PCR assays that target the human-associated HF183 bacterial cluster have been found to be some of the top performing methods for the characterization of human fecal pollution in ambient surface waters. The United States Environmental Protection Agency is planning to conduct a ...

  14. Real-time sweat analysis via alternating current conductivity of artificial and human sweat (United States)

    Liu, Gengchen; Alomari, Mahmoud; Sahin, Bunyamin; Snelgrove, Samuel E.; Edwards, Jeffrey; Mellinger, Axel; Kaya, Tolga


    Dehydration is one of the most profound physiological challenges that significantly affects athletes and soldiers if not detected early. Recently, a few groups have focused on dehydration detection using sweat as the main biomarker. Although there are some proposed devices, the electrical and chemical characteristics of sweat have yet to be incorporated into the validations. In this work, we have developed a simple test setup to analyze artificial sweat that is comprised the main components of human sweat. We provide theoretical and experimental details on the electrical and chemical behavior of the artificial sweat for various concentration values within a temperature range of 5 °C to 50 °C. We have also developed an efficient sweat collecting and detection system based on 3D printing. Human studies were conducted and this particular protocol has shown that dehydration starts to take effect as early as 40 min into the physical activity if there is no fluid intake during the exercise. We believe that our device will lead to developing viable real-time sweat analysis systems.

  15. Dose- and Time-Dependent Response of Human Leukemia (HL-60 Cells to Arsenic Trioxide Treatment

    Directory of Open Access Journals (Sweden)

    Paul B. Tchounwou


    Full Text Available The treatment of acute promyelocytic leukemia (APL has been based on the administration of all-trans retinoic acid plus anthracycline chemotherapy, which is very effective as first line therapy; however 25 to 30% of patients will relapse with their disease becoming refractory to conventional therapy. Recently, studies have shown arsenic trioxide to be effective in the treatment of acute promyelocytic leukemia. In this study, we used the human leukemia (HL-60 cell line as a model to evaluate the cytoxicity of arsenic trioxide based on the MTT assay. Data obtained from this assay indicated that arsenic trioxide significantly reduced the viability of HL-60 cells, showing LD50 values of 14.26 + 0.5μg/mL, 12.54 + 0.3μg/mL, and 6.4 + 0.6μg/mL upon 6, 12, and 24 hours of exposure, respectively; indicating a dose- and time-dependent response relationship. Findings from the present study indicate that arsenic trioxide is highly cytotoxic to human leukemia (HL-60 cells, supporting its use as an effective therapeutic agent in the management of acute promyelocytic leukemia.

  16. Human exposure to acrolein: Time-dependence and individual variation in eye irritation. (United States)

    Claeson, Anna-Sara; Lind, Nina


    The aim of the study was to examine the time dependence on sensory irritation detection following exposure to threshold levels of acrolein, in humans. The exposures occurred in an exposure chamber and the subjects were breathing fresh air through a mask that covered the nose and mouth. All participants participated in four exposure conditions, of which three consisted of a mixture of acrolein and heptane and one of only heptane. Exposure to acrolein at a concentration half of the TLV-C lead to sensory irritation. The perceived sensory irritation resulted in both increased detectability and sensory irritation after about 6.8min of exposure in 58% of the participants. The study confirm the previously suggested LOAEL of about 0.34mg/m(3) for eye irritation due to acrolein exposure. The sensory irritation was still significant 10min after exposure. These results have implications for risk assessment and limit setting in occupational hygiene.

  17. Constitutive modeling of time-dependent response of human plantar aponeurosis. (United States)

    Pavan, P G; Pachera, P; Stecco, C; Natali, A N


    The attention is focused on the viscoelastic behavior of human plantar aponeurosis tissue. At this purpose, stress relaxation tests were developed on samples taken from the plantar aponeurosis of frozen adult donors with age ranging from 67 to 78 years, imposing three levels of strain in the physiological range (4%, 6%, and 8%) and observing stress decay for 240 s. A viscohyperelastic fiber-reinforced constitutive model with transverse isotropy was assumed to describe the time-dependent behavior of the aponeurotic tissue. This model is consistent with the structural conformation of the tissue where collagen fibers are mainly aligned with the proximal-distal direction. Constitutive model fitting to experimental data was made by implementing a stochastic-deterministic procedure. The stress relaxation was found close to 40%, independently of the level of strain applied. The agreement between experimental data and numerical results confirms the suitability of the constitutive model to describe the viscoelastic behaviour of the plantar aponeurosis.

  18. Reaction time as a measure of binocular interaction in human vision. (United States)

    Blake, R; Martens, W; Di Gianfilippo, A


    In a series of psychophysical experiments monocular and binocular reaction times (RTs) were measured in response to the presentation of sinusoidal grating patterns. Over a wide range of contrast values, binocular RT was consistently faster than monocular RT, even at high-contrast levels where RT had reached asymptotic levels. For observers with good stereopsis this binocular summation effect was greater than that expected on the basis of probability summation alone, whereas observers with deficient stereopsis performed at the level of probability summation. For normal observers broadband random noise presented to one eye produced an elevation in RT to gratings presented to the other eye; no such dichoptic masking effect was found in a stereoblind observer. These results validate the use of RT as an efficient, reliable measure of binocular interaction in human vision.

  19. Health and Disease Imprinted in the Time Variability of the Human Microbiome (United States)

    Rubio, Teresa; Gracia, César; Peña, Manuel; Latorre, Amparo


    ABSTRACT The animal microbiota (including the human microbiota) plays an important role in keeping the physiological status of the host healthy. Research seeks greater insight into whether changes in the composition and function of the microbiota are associated with disease. We analyzed published 16S rRNA and shotgun metagenomic sequencing (SMS) data pertaining to the gut microbiotas of 99 subjects monitored over time. Temporal fluctuations in the microbial composition revealed significant differences due to factors such as dietary changes, antibiotic intake, age, and disease. This article shows that a fluctuation scaling law can describe the temporal changes in the gut microbiota. This law estimates the temporal variability of the microbial population and quantitatively characterizes the path toward disease via a noise-induced phase transition. Estimation of the systemic parameters may be of clinical utility in follow-up studies and have more general applications in fields where it is important to know whether a given community is stable or not. IMPORTANCE The human microbiota correlates closely with the health status of its host. This article analyzes the microbial composition of several subjects under different conditions over time spans that ranged from days to months. Using the Langevin equation as the basis of our mathematical framework to evaluate microbial temporal stability, we proved that stable microbiotas can be distinguished from unstable microbiotas. This initial step will help us to determine how temporal microbiota stability is related to a subject’s health status and to develop a more comprehensive framework that will provide greater insight into this complex system. PMID:28345059

  20. Human Exploration Using Real-Time Robotic Operations (HERRO)- Crew Telerobotic Control Vehicle (CTCV) Design (United States)

    Oleson, Steven R.; McGuire, Melissa L.; Burke, Laura; Chato, David; Fincannon, James; Landis, Geoff; Sandifer, Carl; Warner, Joe; Williams, Glenn; Colozza, Tony; Fittje, Jim; Martini, Mike; Packard, Tom; McCurdy, Dave; Gyekenyesi, John


    The HERRO concept allows real time investigation of planets and small bodies by sending astronauts to orbit these targets and telerobotically explore them using robotic systems. Several targets have been put forward by past studies including Mars, Venus, and near Earth asteroids. A conceptual design study was funded by the NASA Innovation Fund to explore what the HERRO concept and it's vehicles would look like and what technological challenges need to be met. This design study chose Mars as the target destination. In this way the HERRO studies can define the endpoint design concepts for an all-up telerobotic exploration of the number one target of interest Mars. This endpoint design will serve to help planners define combined precursor telerobotics science missions and technology development flights. A suggested set of these technologies and demonstrator missions is shown in Appendix B. The HERRO concept includes a crewed telerobotics orbit vehicle as well three Truck rovers, each supporting two teleoperated geologist robots Rockhounds (each truck/Rockhounds set is landed using a commercially launched aeroshell landing system.) Options include a sample ascent system teamed with an orbital telerobotic sample rendezvous and return spacecraft (S/C) (yet to be designed). Each truck rover would be landed in a science location with the ability to traverse a 100 km diameter area, carrying the Rockhounds to 100 m diameter science areas for several week science activities. The truck is not only responsible for transporting the Rockhounds to science areas, but also for relaying telecontrol and high-res communications to/from the Rockhound and powering/heating the Rockhound during the non-science times (including night-time). The Rockhounds take the place of human geologists by providing an agile robotic platform with real-time telerobotics control to the Rockhound from the crew telerobotics orbiter. The designs of the Truck rovers and Rockhounds will be described in other

  1. Assimilation of Real-Time Satellite And Human Sensor Networks for Modeling Natural Disasters (United States)

    Aulov, O.; Halem, M.; Lary, D. J.


    We describe the development of underlying technologies needed to address the merging of a web of real time satellite sensor Web (SSW) and Human Sensor Web (HSW) needed to augment the US response to extreme events. As an initial prototyping step and use case scenario, we consider the development of two major system tools that can be transitioned from research to the responding operational agency for mitigating coastal oil spills. These tools consist of the capture of Situation Aware (SA) Social Media (SM) Data, and assimilation of the processed information into forecasting models to provide incident decision managers with interactive virtual spatial temporal animations superimposed with probabilistic data estimates. The system methodologies are equally applicable to the wider class of extreme events such as plume dispersions from volcanoes or massive fires, major floods, hurricane impacts, radioactive isotope dispersions from nuclear accidents, etc. A successful feasibility demonstration of this technology has been shown in the case of the Deepwater Horizon Oil Spill where Human Sensor Networks have been combined with a geophysical model to perform parameter assessments. Flickr images of beached oil were mined from the spill area, geolocated and timestamped and converted into geophysical data. This data was incorporated into General NOAA Operational Modeling Environment (GNOME), a Lagrangian forecast model that uses near real-time surface winds, ocean currents, and satellite shape profiles of oil to generate a forecast of plume movement. As a result, improved estimates of diffusive coefficients and rates of oil spill were determined. Current approaches for providing satellite derived oil distributions are collected from a satellite sensor web of operational and research sensors from many countries, and a manual analysis is performed by NESDIS. A real time SA HSW processing system based on geolocated SM data from sources such as Twitter, Flickr, YouTube etc., greatly

  2. The cardiac cycle time effect revisited: Temporal dynamics of the central-vagal modulation of heart rate in human reaction time tasks.

    NARCIS (Netherlands)

    R.J.M. Somsen; J.R. Jennings; M.W. van der Molen


    Lacey and Lacey (1974) suggested that during reaction time tasks higher brain centers dynamically adjust efferent vagal nerve pulses to the sino-atrial node of the heart, inducing phase-dependent heart rate changes. Since then, animal and human neuro-physiological results have provided evidence for

  3. Time scales of representation in the human brain: weighing past information to predict future events

    Directory of Open Access Journals (Sweden)

    Lee eHarrison


    Full Text Available The estimates that humans make of statistical dependencies in the environment and therefore their representation of uncertainty crucially depend on the integration of data over time. As such, the extent to which past events are used to represent uncertainty has been postulated to vary over the cortex. For example, primary visual cortex responds to rapid perturbations in the environment, while frontal cortices involved in executive control encode the longer term contexts within which these perturbations occur. Here we tested whether primary and executive regions can be distinguished by the number of past observations they represent. This was based on a decay-dependent model that weights past observations from a Markov process and Bayesian Model Selection (BMS to test the prediction that neuronal responses are characterised by different decay half-lives depending on location in the brain. We show distributions of brain responses for short and long term decay functions in primary and secondary visual and frontal cortices, respectively. We found that visual and parietal responses are released from the burden of the past, enabling an agile response to fluctuations in events as they unfold. In contrast, frontal regions are more concerned with average trends over longer time scales within which local variations are embedded. Specifically, we provide evidence for a temporal gradient for representing context within the prefrontal cortex and possibly beyond to include primary sensory and association areas.

  4. A blueprint for real-time functional mapping via human intracranial recordings.

    Directory of Open Access Journals (Sweden)

    Jean-Philippe Lachaux

    Full Text Available BACKGROUND: The surgical treatment of patients with intractable epilepsy is preceded by a pre-surgical evaluation period during which intracranial EEG recordings are performed to identify the epileptogenic network and provide a functional map of eloquent cerebral areas that need to be spared to minimize the risk of post-operative deficits. A growing body of research based on such invasive recordings indicates that cortical oscillations at various frequencies, especially in the gamma range (40 to 150 Hz, can provide efficient markers of task-related neural network activity. PRINCIPAL FINDINGS: Here we introduce a novel real-time investigation framework for mapping human brain functions based on online visualization of the spectral power of the ongoing intracranial activity. The results obtained with the first two implanted epilepsy patients who used the proposed online system illustrate its feasibility and utility both for clinical applications, as a complementary tool to electrical stimulation for presurgical mapping purposes, and for basic research, as an exploratory tool used to detect correlations between behavior and oscillatory power modulations. Furthermore, our findings suggest a putative role for high gamma oscillations in higher-order auditory processing involved in speech and music perception. CONCLUSION/SIGNIFICANCE: The proposed real-time setup is a promising tool for presurgical mapping, the investigation of functional brain dynamics, and possibly for neurofeedback training and brain computer interfaces.

  5. Time course of human motoneuron recovery after sustained low-level voluntary activity. (United States)

    Héroux, Martin E; Butler, Annie A; Gandevia, Simon C; Taylor, Janet L; Butler, Jane E


    Motoneurons often fire repetitively and for long periods. In sustained voluntary contractions the excitability of motoneurons declines. We provide the first detailed description of the time course of human motoneuron recovery after sustained activity at a constant discharge rate. We recorded the discharge of single motor units (MUs, n = 30) with intramuscular wire electrodes inserted in triceps brachii during weak isometric contractions. Subjects (n = 15) discharged single MUs at a constant frequency (∼10 Hz) with visual feedback for prolonged durations (3-7 min) until rectified surface electromyogram (sEMG) of triceps brachii increased by ∼100%. After a rest of 1-2, 15, 30, 60, 120, or 240 s, subjects briefly resumed the contraction with the target MU at the same discharge rate. Each MU was tested with three to four rest periods. The magnitude of sEMG was increased when contractions were resumed, and the target motoneuron discharged at the test frequency following rest intervals of 2-60 s (P = 0.001-0.038). The increased sEMG indicates that greater excitatory drive was needed to discharge the motoneuron at the test rate. The increase in EMG recovered exponentially with a time constant of 28 s but did not return to baseline even after a rest period of ∼240 s. Thus the decline in motoneuron excitability from a weak contraction takes several minutes to recover fully.

  6. Influence of Breastfeeding Time on Levels of Organochlorine Pesticides in Human Milk of a Mexican Population. (United States)

    Chávez-Almazán, Luis A; Diaz-Ortiz, Jesús; Alarcón-Romero, Mario; Davila-Vazquez, Gustavo; Saldarriaga-Noreña, Hugo; Sampedro-Rosas, Laura; López-Silva, Saúl; Santiago-Moreno, Agustín; Rosas-Acevedo, José L; Waliszewski, Stefan M


    This study was conducted with the objective of determining whether there is a depuration of organochlorine pesticides in breast milk according to breastfeeding time. In total, 171 samples from mothers that lived in the State of Guerrero, Mexico were analyzed. There was a weak negative relationship between pp'DDE (r = -0.216) and Σ-DDT (r = -0.222) concentrations with the days of lactation. In a comparison analysis, a statistically significant decrease of pp'DDT and pp'DDE levels was observed, as well as the Σ-DDT from the first to the fifth week of lactation. A reduction of 0.188 mg/kg lipid of pp'DDE and 0.181 mg/kg lipid of Σ-DDT per week was obtained. HCB, β-HCH and op'DDT concentrations were low and had no major fluctuations between subgroups. The low levels found and the observed reduction in time involve less exposure to the infant to these pollutants. Through this methodology changes in levels of certain organochlorine pesticides in various stages of human milk production may be shown.

  7. Collaborative Science: Human Sensor Networks for Real-time Natural Disaster Prediction (United States)

    Halem, M.; Yesha, Y.; Aulov, O.; Martineau, J.; Brown, S.; Conte, T.; CenterHybrid Multicore Productivity Research


    We have implemented a ‘Human Sensor Network’ as a real time collaborative science data observing system by collecting and integrating the vast untapped information potential of digital social media data sources occurring during the oil spill situation arising from the Macondo well in the Gulf of Mexico. We collected, and archived blogs, Twitter status updates (aka tweets), photographs posted to Flicker, and videos posted to YouTube related to the Gulf oil spill and processed the meta data, text, and photos to extract quantitative physical data such as locations and estimates of the severity and dispersion of oil being collected on the beaches and marshes, frequencies of observations of tar ball sightings, correlations of sightings from different media, numbers of dead or distressed animals, trends, etc. These data were then introduced into the NOAA operational Gnome oil spill predictive model as time dependent boundary conditions employing a 2-D variational data assimilation scheme. The three participating institutions employed a distributed cloud computing system for the processing and model executions. In this presentation, we conducted preliminary forecast impact tests of the Gnome model with and without the use of social media data using a 2-D variational data assimilation technique. The 2-D VAR is used to adjust the state variables of the model by recursively minimizing the differences between oil spill predictions reaching locations across the entire coastlines of the Gulf of Mexico and the estimated positions of oil derived from analyzed social media data. Ensemble forecasts will be performed to provide estimates of the rates of oil and surface oil distributions emanating from the Deepwater Horizon. We display the derived predictions from the photos and animations from Flicker, YouTube, and extracted content from tweets and blogs in a dynamic representation on very large tiled walls of LCDs at the UCSD Cal IT2 visualization facility. We describe the

  8. Evaluating the Human Damage of Tsunami at Each Time Frame in Aggregate Units Based on GPS data (United States)

    Ogawa, Y.; Akiyama, Y.; Kanasugi, H.; Shibasaki, R.; Kaneda, H.


    Assessments of the human damage caused by the tsunami are required in order to consider disaster prevention at such a regional level. Hence, there is an increasing need for the assessments of human damage caused by earthquakes. However, damage assessments in japan currently usually rely on static population distribution data, such as statistical night time population data obtained from national census surveys. Therefore, human damage estimation that take into consideration time frames have not been assessed yet. With these backgrounds, the objectives of this study are: to develop a method for estimating the population distribution of the for each time frame, based on location positioning data observed with mass GPS loggers of mobile phones, to use a evacuation and casualties models for evaluating human damage due to the tsunami, and evaluate each time frame by using the data developed in the first objective, and 3) to discuss the factors which cause the differences in human damage for each time frame. By visualizing the results, we clarified the differences in damage depending on time frame, day and area. As this study enables us to assess damage for any time frame in and high resolution, it will be useful to consider provision for various situations when an earthquake may hit, such as during commuting hours or working hours and week day or holiday.

  9. Predicting decisions in human social interactions using real-time fMRI and pattern classification.

    Directory of Open Access Journals (Sweden)

    Maurice Hollmann

    Full Text Available Negotiation and trade typically require a mutual interaction while simultaneously resting in uncertainty which decision the partner ultimately will make at the end of the process. Assessing already during the negotiation in which direction one's counterpart tends would provide a tremendous advantage. Recently, neuroimaging techniques combined with multivariate pattern classification of the acquired data have made it possible to discriminate subjective states of mind on the basis of their neuronal activation signature. However, to enable an online-assessment of the participant's mind state both approaches need to be extended to a real-time technique. By combining real-time functional magnetic resonance imaging (fMRI and online pattern classification techniques, we show that it is possible to predict human behavior during social interaction before the interacting partner communicates a specific decision. Average accuracy reached approximately 70% when we predicted online the decisions of volunteers playing the ultimatum game, a well-known paradigm in economic game theory. Our results demonstrate the successful online analysis of complex emotional and cognitive states using real-time fMRI, which will enable a major breakthrough for social fMRI by providing information about mental states of partners already during the mutual interaction. Interestingly, an additional whole brain classification across subjects confirmed the online results: anterior insula, ventral striatum, and lateral orbitofrontal cortex, known to act in emotional self-regulation and reward processing for adjustment of behavior, appeared to be strong determinants of later overt behavior in the ultimatum game. Using whole brain classification we were also able to discriminate between brain processes related to subjective emotional and motivational states and brain processes related to the evaluation of objective financial incentives.

  10. Evidence for high-fidelity timing-dependent synaptic plasticity of human motor cortex. (United States)

    Cash, R F H; Mastaglia, F L; Thickbroom, G W


    A single transcranial magnetic stimulation (TMS) pulse typically evokes a short series of spikes in corticospinal neurons [known as indirect (I)-waves] which are thought to arise from transynaptic input. Delivering a second pulse at inter-pulse intervals (IPIs) corresponding to the timing of these I-waves leads to a facilitation of the response, and if stimulus pairs are delivered repeatedly, a persistent LTP-like increase in excitability can occur. This has been demonstrated at an IPI of 1.5 ms, which corresponds to the first I-wave interval, in an intervention referred to as ITMS (I-wave TMS), and it has been argued that this may have similarities with timing-dependent plasticity models. Consequently, we hypothesized that if the second stimulus is delivered so as not to coincide with I-wave timing, it should lead to LTD. We performed a crossover study in 10 subjects in which TMS doublets were timed to coincide (1.5-ms IPI, ITMS(1.5)) or not coincide (2-ms IPI, ITMS(2)) with I-wave firing. Single pulse motor-evoked potential (MEP) amplitude, resting motor threshold (RMT), and short-interval cortical inhibition (SICI) were measured from the first dorsal interosseous (FDI) muscle. After ITMS(1.5) corticomotor excitability was increased by ~60% for 15 min (P < 0.05) and returned to baseline by 20 min. Increasing the IPI by just 500 μs to 2 ms reversed the aftereffect, and MEP amplitude was significantly reduced (~35%, P < 0.05) for 15 min before returning to baseline. This reduction was not associated with an increase in SICI, suggesting a reduction in excitatory transmission rather than an increase in inhibitory efficacy. RMT also remained unchanged, suggesting that these changes were not due to changes in membrane excitability. Amplitude-matching ITMS(2) did not modulate excitability. The results are consistent with timing-dependent synaptic LTP/D-like effects and suggest that there are plasticity mechanisms operating in the human motor cortex with a temporal

  11. Time, human being and mental health care: an introduction to Gilles Deleuze. (United States)

    Roberts, Marc


    The French philosopher, Gilles Deleuze, is emerging as one of the most important and influential philosophers of the 20th century, having published widely on philosophy, literature, language, psychoanalysis, art, politics, and cinema. However, because of the 'experimental' nature of certain works, combined with the manner in which he draws upon a variety of sources from various disciplines, his work can seem difficult, obscure, and even 'willfully obstructive'. In an attempt to resist such impressions, this paper will seek to provide an accessible introduction to Deleuze's work, and to begin to discuss how it can be employed to provide a significant critique and reconceptualization of the theoretical foundations and therapeutic practices of psychiatry, psychotherapy, and mental health nursing. In order to do this, the paper will focus upon Deleuze's masterwork, and the cornerstone to his philosophy as a whole, Difference and Repetition; in particular, it will discuss how his innovative and challenging account of time can be employed to provide a conception of human life as a 'continuity', rather than as a series of distinct 'moments' or 'events'. As well as discussing the manner in which his work can provide us with an understanding of how life is different and significant for each human being, this paper will also highlight the potential importance of Deleuze's work for logotherapy, for the recent 'turn' to 'narrative' as a psychotherapeutic approach and for contemporary mental health care's growing interest in 'social constructionism'. As such, this paper also seeks to stimulate further discussion and research into the importance and the relevance of Deleuze's work for the theory and practice of psychiatry, psychotherapy, and mental health nursing.

  12. Performance Assessment of Human and Cattle Associated Quantitative Real-time PCR Assays - slides (United States)

    The presentation overview is (1) Single laboratory performance assessment of human- and cattle associated PCR assays and (2) A Field Study: Evaluation of two human fecal waste management practices in Ohio watershed.

  13. In vivo measurements of T1 relaxation times of 31P-metabolites in human skeletal muscle

    DEFF Research Database (Denmark)

    Thomsen, C; Jensen, K E; Henriksen, O


    The T1 relaxation times were estimated for 31P-metabolites in human skeletal muscle. Five healthy volunteers were examined in a 1.5 Tesla wholebody imaging system using an inversion recovery pulse sequence. The calculated T1 relaxation times ranged from 5.517 sec for phosphocreatine to 3.603 sec...

  14. Education in Responsibility in Order to Secure Human Rights in Times of Crisis (United States)

    Merrigan, Michaël


    Education in and awareness about human rights is generally seen as one of the less contentious elements of citizenship education. However, it would seem that, for the concept of human rights to have a real impact in today's world, theoretical knowledge of human rights standards should be complemented by an understanding of the ethical concept of…

  15. Human transformations of the Wadden Sea ecosystem through time : a synthesis

    NARCIS (Netherlands)

    Lotze, HK; Reise, K; Worm, B; van Beusekom, J; Busch, M; Ehlers, A; Heinrich, D; Hoffmann, RC; Holm, P; Jensen, C; Knottnerus, OS; Langhanki, N; Prummel, W; Vollmer, M; Wolff, WJ


    Todays Wadden Sea is a heavily human-altered ecosystem. Shaped by natural forces since its origin 7,500 years ago, humans gradually gained dominance in influencing ecosystem structure and functioning. Here, we reconstruct the timeline of human impacts and the history of ecological changes in the Wad

  16. Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells

    Directory of Open Access Journals (Sweden)

    van Erk Marjan J


    Full Text Available Abstract Background Curcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an anti-oxidant and it can act as an anti-inflammatory agent. The aim of this study was to elucidate mechanisms and effect of curcumin in colon cancer cells using gene expression profiling. Methods Gene expression changes in response to curcumin exposure were studied in two human colon cancer cell lines, using cDNA microarrays with four thousand human genes. HT29 cells were exposed to two different concentrations of curcumin and gene expression changes were followed in time (3, 6, 12, 24 and 48 hours. Gene expression changes after short-term exposure (3 or 6 hours to curcumin were also studied in a second cell type, Caco-2 cells. Results Gene expression changes (>1.5-fold were found at all time points. HT29 cells were more sensitive to curcumin than Caco-2 cells. Early response genes were involved in cell cycle, signal transduction, DNA repair, gene transcription, cell adhesion and xenobiotic metabolism. In HT29 cells curcumin modulated a number of cell cycle genes of which several have a role in transition through the G2/M phase. This corresponded to a cell cycle arrest in the G2/M phase as was observed by flow cytometry. Functional groups with a similar expression profile included genes involved in phase-II metabolism that were induced by curcumin after 12 and 24 hours. Expression of some cytochrome P450 genes was downregulated by curcumin in HT29 and Caco-2 cells. In addition, curcumin affected expression of metallothionein genes, tubulin genes, p53 and other genes involved in colon carcinogenesis. Conclusions This study has extended knowledge on pathways or processes already reported to be affected by curcumin (cell cycle arrest, phase

  17. A Human Sensor Network Framework in Support of Near Real Time Situational Geophysical Modeling (United States)

    Aulov, O.; Price, A.; Smith, J. A.; Halem, M.


    The area of Disaster Management is well established among Federal Agencies such as FEMA, EPA, NOAA and NASA. These agencies have well formulated frameworks for response and mitigation based on near real time satellite and conventional observing networks for assimilation into geophysical models. Forecasts from these models are used to communicate with emergency responders and the general public. More recently, agencies have started using social media to broadcast warnings and alerts to potentially affected communities. In this presentation, we demonstrate the added benefits of mining and assimilating the vast amounts of social media data available from heterogeneous hand held devices and social networks into established operational geophysical modeling frameworks as they apply to the five cornerstones of disaster management - Prevention, Mitigation, Preparedness, Response and Recovery. Often, in situations of extreme events, social media provide the earliest notification of adverse extreme events. However, various forms of social media data also can provide useful geolocated and time stamped in situ observations, complementary to directly sensed conventional observations. We use the concept of a Human Sensor Network where one views social media users as carrying field deployed "sensors" whose posts are the remotely "sensed instrument measurements.' These measurements can act as 'station data' providing the resolution and coverage needed for extreme event specific modeling and validation. Here, we explore the use of social media through the use of a Human Sensor Network (HSN) approach as another data input source for assimilation into geophysical models. Employing the HSN paradigm can provide useful feedback in near real-time, but presents software challenges for rapid access, quality filtering and transforming massive social media data into formats consistent with the operational models. As a use case scenario, we demonstrate the value of HSN for disaster management

  18. Timing of Initiation of Antiretroviral Therapy in Human Immunodeficiency Virus (HIV)–Associated Tuberculous Meningitis (United States)

    Török, M. Estee; Yen, Nguyen Thi Bich; Chau, Tran Thi Hong; Mai, Nguyen Thi Hoang; Phu, Nguyen Hoan; Mai, Pham Phuong; Dung, Nguyen Thi; Van Vinh Chau, Nguyen; Bang, Nguyen Duc; Tien, Nguyen Anh; Minh, N. H.; Hien, Nguyen Quang; Thai, Phan Vuong Khac; Dong, Doan The; Anh, Do Thi Tuong; Thoa, Nguyen Thi Cam; Hai, Nguyen Ngoc; Lan, Nguyen Ngoc; Lan, Nguyen Thi Ngoc; Quy, Hoang Thi; Dung, Nguyen Huy; Hien, Tran Tinh; Chinh, Nguyen Tran; Simmons, Cameron Paul; de Jong, Menno; Wolbers, Marcel; Farrar, Jeremy James


    Background The optimal time to initiate antiretroviral therapy (ART) in human immunodeficiency virus (HIV)–associated tuberculous meningitis is unknown. Methods We conducted a randomized, double-blind, placebo-controlled trial of immediate versus deferred ART in patients with HIV-associated tuberculous meningitis to determine whether immediate ART reduced the risk of death. Antiretroviral drugs (zidovudine, lamivudine, and efavirenz) were started either at study entry or 2 months after randomization. All patients were treated with standard antituberculosis treatment, adjunctive dexamethasone, and prophylactic co-trimoxazole and were followed up for 12 months. We conducted intention-to-treat, per-protocol, and prespecified subgroup analyses. Results A total of 253 patients were randomized, 127 in the immediate ART group and 126 in the deferred ART group; 76 and 70 patients died within 9 months in the immediate and deferred ART groups, respectively. Immediate ART was not significantly associated with 9-month mortality (hazard ratio [HR], 1.12; 95% confidence interval [CI], .81–1.55; P = .50) or the time to new AIDS events or death (HR, 1.16; 95% CI, .87–1.55; P = .31). The percentage of patients with severe (grade 3 or 4) adverse events was high in both arms (90% in the immediate ART group and 89% in the deferred ART group; P = .84), but there were significantly more grade 4 adverse events in the immediate ART arm (102 in the immediate ART group vs 87 in the deferred ART group; P = .04). Conclusions Immediate ART initiation does not improve outcome in patients presenting with HIV-associated tuberculous meningitis. There were significantly more grade 4 adverse events in the immediate ART arm, supporting delayed initiation of ART in HIV-associated tuberculous meningitis. Clinical Trials Registration ISRCTN63659091. PMID:21596680

  19. Real-time determination of human telomerase reverse transcriptase mRNA in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Li-Hua Hu; Feng-Hua Chen; Yi-Rong Li; Lin Wang


    AIM: To set up a real-time fluorescent quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay,to detect human telomerase reverse transcriptase (hTERT)messenger RNA in gastric carcinomas, and to evaluate quantitative determination of hTERT mRNA in the diagnostic value of gastric carcinomas, and to analyze the correlation between the expression level of hTERT mRNA and dinicopathological parameters in patients with gastric cancer.METHODS: A real-time quantitative RT-PCR (RQ-PCR)based on TaqMan fluorescence methodoloogy and the LightCyder system was used to quantify the full range of hTERT mRNA copy numbers in 35 samples of gastric carcinomas and corresponding adjacent non-cancerous tissues. The normalized hTERT (NhTERT) was standardized by quantifying the number of GAPDH transcripts as internal control and expressed as 100× (hTERT/GAPDH) ratio. Variables were analyzed by the Student's t-test, χ2 test and Fisher's exact test.RESULTS: NhTERT from gastric carcinomas and corresponding adjacent non-cancerous tissues was 6.27±0.89 and 0.93±0.18,respectively (t= 12.76, P<0.001). There was no significant association between gastric cancer hTERT mRNA expression level and patient's age, gender, tumor size, location and stage (pTNM), but a significant correlation was found between hTERT mRNA expression level in gastric carcinomas and the degree of differentiation.CONCLUSION: Quantitative determination of hTERT mRNA by RQ-PCR is a rapid and sensitive method. hTERT might be a potential biomarker for the early detection of gastric cancer.

  20. Ultrasensitive quantitation of human papillomavirus type 16 E6 oncogene sequences by nested real time PCR

    Directory of Open Access Journals (Sweden)

    López-Revilla Rubén


    Full Text Available Abstract Background We have developed an ultrasensitive method based on conventional PCR preamplification followed by nested amplification through real time PCR (qPCR in the presence of the DNA intercalating agent EvaGreen. Results Amplification mixtures calibrated with a known number of pHV101 copies carrying a 645 base pair (bp-long insert of the human papillomavirus type 16 (HPV16 E6 oncogene were used to generate the E6-1 amplicon of 645 bp by conventional PCR and then the E6-2 amplicon of 237 bp by nested qPCR. Direct and nested qPCR mixtures for E6-2 amplification corresponding to 2.5 × 102-2.5 × 106 initial pHV101 copies had threshold cycle (Ct values in the ranges of 18.7-29.0 and 10.0-25.0, respectively. The Ct of qPCR mixtures prepared with 1/50 volumes of preamplified mixtures containing 50 ng of DNA of the SiHa cell line (derived from an invasive cervical cancer with one HPV16 genome per cell was 19.9. Thermal fluorescence extinction profiles of E6-2 amplicons generated from pHV101 and SiHa DNA were identical, with a peak at 85.5°C. Conclusions Our method based on conventional preamplification for 15 cycles increased 10,750 times the sensitivity of nested qPCR for the quantitation of the E6 viral oncogene and confirmed that the SiHa cell line contains one E6-HPV16 copy per cell.

  1. The public’s belief in climate change and its human cause are increasing over time (United States)

    Milfont, Taciano L.; Wilson, Marc S.; Sibley, Chris G.


    Polls examining public opinion on the subject of climate change are now commonplace, and one-off public opinion polls provide a snapshot of citizen's opinions that can inform policy and communication strategies. However, cross-sectional polls do not track opinions over time, thus making it impossible to ascertain whether key climate change beliefs held by the same group of individuals are changing or not. Here we examine the extent to which individual's level of agreement with two key beliefs ("climate change is real" and "climate change is caused by humans") remain stable or increase/decrease over a six-year period in New Zealand using latent growth curve modelling (n = 10,436). Data were drawn from the New Zealand Attitudes and Values Study, a probabilistic national panel study, and indicated that levels of agreement to both beliefs have steadily increased over the 2009–2015 period. Given that climate change beliefs and concerns are key predictors of climate change action, our findings suggest that a combination of targeted endeavors, as well as serendipitous events, may successfully convey the emergency of the issue. PMID:28319190

  2. Forecasting Human African Trypanosomiasis Prevalences from Population Screening Data Using Continuous Time Models (United States)

    Hasker, Epco; Lumbala, Crispin; Lutumba, Pascal; de Vlas, Sake J.; van de Klundert, Joris


    To eliminate and eradicate gambiense human African trypanosomiasis (HAT), maximizing the effectiveness of active case finding is of key importance. The progression of the epidemic is largely influenced by the planning of these operations. This paper introduces and analyzes five models for predicting HAT prevalence in a given village based on past observed prevalence levels and past screening activities in that village. Based on the quality of prevalence level predictions in 143 villages in Kwamouth (DRC), and based on the theoretical foundation underlying the models, we consider variants of the Logistic Model—a model inspired by the SIS epidemic model—to be most suitable for predicting HAT prevalence levels. Furthermore, we demonstrate the applicability of this model to predict the effects of planning policies for screening operations. Our analysis yields an analytical expression for the screening frequency required to reach eradication (zero prevalence) and a simple approach for determining the frequency required to reach elimination within a given time frame (one case per 10000). Furthermore, the model predictions suggest that annual screening is only expected to lead to eradication if at least half of the cases are detected during the screening rounds. This paper extends knowledge on control strategies for HAT and serves as a basis for further modeling and optimization studies. PMID:27657937

  3. Self-Organizing Wearable Device Platform for Assisting and Reminding Humans in Real Time

    Directory of Open Access Journals (Sweden)

    Yu Jin Park


    Full Text Available Most older persons would prefer “aging in my place,” that is, to remain in good health and live independently in their own home as long as possible. For assisting the independent living of older people, the ability to gather and analyze a user’s daily activity data would constitute a significant technical advance, enhancing their quality of life. However, the general approach based on centralized server has several problems such as the usage complexity, the high price of deployment and expansion, and the difficulty in identifying an individual person. To address these problems, we propose a wearable device platform for the life assistance of older persons that automatically records and analyzes their daily activity without intentional human intervention or a centralized server (i.e., cloud server. The proposed platform contains self-organizing protocols, Delay-Tolerant Messaging system, knowledge-based analysis and alerting for daily activities, and a hardware platform that provides low power consumption. We implemented a prototype smart watch, called Personal Activity Assisting and Reminding (PAAR, as a testbed for the proposed platform, and evaluated the power consumption and the service time of example scenarios.

  4. Time course of pharmacokinetic and hormonal effects of inhaled high-dose salvinorin A in humans. (United States)

    Johnson, Matthew W; MacLean, Katherine A; Caspers, Michael J; Prisinzano, Thomas E; Griffiths, Roland R


    Salvinorin A is a kappa opioid agonist and the principal psychoactive constituent of the Salvia divinorum plant, which has been used for hallucinogenic effects. Previous research on salvinorin A pharmacokinetics likely underestimated plasma levels typically resulting from the doses administered due to inefficient vaporization and not collecting samples during peak drug effects. Six healthy adults inhaled a single high dose of vaporized salvinorin A (n = 4, 21 mcg/kg; n = 2, 18 mcg/kg). Participant- and monitor-rated effects were assessed every 2 min for 60 min post-inhalation. Blood samples were collected at 13 time points up to 90 min post-inhalation. Drug levels peaked at 2 min and then rapidly decreased. Drug levels were significantly, positively correlated with participant and monitor drug effect ratings. Significant elevations in prolactin were observed beginning 5 min post-inhalation and peaking at 15 min post-inhalation. Cortisol showed inconsistent increases across participants. Hormonal responses were not well correlated with drug levels. This is the first study to demonstrate a direct relationship between changes in plasma levels of salvinorin A and drug effects in humans. The results confirm the efficacy of an inhalation technique for salvinorin A.

  5. Constitutive Modeling of Time-Dependent Response of Human Plantar Aponeurosis

    Directory of Open Access Journals (Sweden)

    P. G. Pavan


    Full Text Available The attention is focused on the viscoelastic behavior of human plantar aponeurosis tissue. At this purpose, stress relaxation tests were developed on samples taken from the plantar aponeurosis of frozen adult donors with age ranging from 67 to 78 years, imposing three levels of strain in the physiological range (4%, 6%, and 8% and observing stress decay for 240 s. A viscohyperelastic fiber-reinforced constitutive model with transverse isotropy was assumed to describe the time-dependent behavior of the aponeurotic tissue. This model is consistent with the structural conformation of the tissue where collagen fibers are mainly aligned with the proximal-distal direction. Constitutive model fitting to experimental data was made by implementing a stochastic-deterministic procedure. The stress relaxation was found close to 40%, independently of the level of strain applied. The agreement between experimental data and numerical results confirms the suitability of the constitutive model to describe the viscoelastic behaviour of the plantar aponeurosis.

  6. Trial frequency effects in human temporal bisection: implications for theories of timing. (United States)

    Jozefowiez, Jeremie; Polack, Cody W; Machado, Armando; Miller, Ralph R


    To contrast the classic version of the Scalar Expectancy Theory (SET) with the Behavioral Economic Model (BEM), we examined the effects of trial frequency on human temporal judgments. Mathematical analysis showed that, in a temporal bisection task, SET predicts that participants should show almost exclusive preference for the response associated with the most frequent duration, whereas BEM predicts that, even though participants will be biased, they will still display temporal control. Participants learned to emit one response (R[S]) after a 1.0-s stimulus and another (R[L]) after a 1.5-s stimulus. Then the effects of varying the frequencies of the 1.0-s and 1.5-s stimuli were assessed. Results were more consistent with BEM than with SET. Overall, this research illustrates how the impact of non-temporal factors on temporal discrimination may help us to contrast associative models such as BEM with cognitive models such as SET. Deciding between these two classes of models has important implications regarding the relations between associative learning and timing. This article is part of a Special Issue entitled: Associative and Temporal Learning.

  7. Studying the replication history of human B lymphocytes by real-time quantitative (RQ)-PCR. (United States)

    van Zelm, Menno C; Berkowska, Magdalena A; van Dongen, Jacques J M


    The cells of the adaptive immune system, B and T lymphocytes, each generate a unique antigen receptor through V(D)J recombination of their immunoglobulin (Ig) and T cell receptor (TCR) loci, respectively. Such rearrangements join coding elements to form a coding joint and delete the intervening DNA as circular excision products containing the signal joint. These excision circles are stable structures that cannot replicate and have no function in the cell. Since the coding joint in the genome is replicated with each cell division, the ratio between coding joints and signal joints in a population of B cells can be used as a measure for proliferation. This chapter describes a real-time quantitative (RQ-)PCR-based approach to quantify proliferation through calculating the ratio between coding joints and signal joints of the frequently occurring intronRSS-Kde rearrangements in the IGK light chain locus. The approach is useful to study basic B-cell biology as well as abnormal proliferation in human diseases.

  8. Time to accelerate integration of human factors and ergonomics in patient safety. (United States)

    Gurses, Ayse P; Ozok, A Ant; Pronovost, Peter J


    Progress toward improving patient safety has been slow despite engagement of the health care community in improvement efforts. A potential reason for this sluggish pace is the inadequate integration of human factors and ergonomics principles and methods in these efforts. Patient safety problems are complex and rarely caused by one factor or component of a work system. Thus, health care would benefit from human factors and ergonomics evaluations to systematically identify the problems, prioritize the right ones, and develop effective and practical solutions. This paper gives an overview of the discipline of human factors and ergonomics and describes its role in improving patient safety. We provide examples of how human factors and ergonomics principles and methods have improved both care processes and patient outcomes. We provide five major recommendations to better integrate human factors and ergonomics in patient safety improvement efforts: build capacity among health care workers to understand human factors and ergonomics, create market forces that demand the integration of human factors and ergonomics design principles into medical technologies, increase the number of human factors and ergonomic practitioners in health care organizations, expand investments in improvement efforts informed by human factors and ergonomics, and support interdisciplinary research to improve patient safety. In conclusion, human factors and ergonomics must play a more prominent role in health care if we want to increase the pace in improving patient safety.

  9. Human Rights in Times of Terror - Is Collective Security the Enemy of Individual Freedom?

    Directory of Open Access Journals (Sweden)

    Jutta Limbach


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    I have chosen a subject that concerns our two states - Israel and Germany - and that time and again poses a challenge to our courts: the respect of human rights in times of terrorism. In Israel as in Germany there exists a firm consensus on the need to fight terror. In both states there is much controversy regarding the best way to conduct this fight. The question is raised whether collective security is the enemy of individual freedom. As Aharon Barak rightly stated: “Fighting against terrorism in an effective manner entails finding the right balance between security and public interests, on one hand, and the need to safeguard human rights

  10. Real-time PCR quantification of human complement C4A and C4B genes

    Directory of Open Access Journals (Sweden)

    Fust George


    Full Text Available Abstract Background The fourth component of human complement (C4, an essential factor of the innate immunity, is represented as two isoforms (C4A and C4B in the genome. Although these genes differ only in 5 nucleotides, the encoded C4A and C4B proteins are functionally different. Based on phenotypic determination, unbalanced production of C4A and C4B is associated with several diseases, such as systemic lupus erythematosus, type 1 diabetes, several autoimmune diseases, moreover with higher morbidity and mortality of myocardial infarction and increased susceptibility for bacterial infections. Despite of this major clinical relevance, only low throughput, time and labor intensive methods have been used so far for the quantification of C4A and C4B genes. Results A novel quantitative real-time PCR (qPCR technique was developed for rapid and accurate quantification of the C4A and C4B genes applying a duplex, TaqMan based methodology. The reliable, single-step analysis provides the determination of the copy number of the C4A and C4B genes applying a wide range of DNA template concentration (0.3–300 ng genomic DNA. The developed qPCR was applied to determine C4A and C4B gene dosages in a healthy Hungarian population (N = 118. The obtained data were compared to the results of an earlier study of the same population. Moreover a set of 33 samples were analyzed by two independent methods. No significant difference was observed between the gene dosages determined by the employed techniques demonstrating the reliability of the novel qPCR methodology. A Microsoft Excel worksheet and a DOS executable are also provided for simple and automated evaluation of the measured data. Conclusion This report describes a novel real-time PCR method for single-step quantification of C4A and C4B genes. The developed technique could facilitate studies investigating disease association of different C4 isotypes.

  11. Clinical applications of a real-time scanning-slit confocal microscope designed for real-time observations of the in-vivo human cornea (United States)

    Masters, Barry R.


    We describe a new, real-time, flying slit confocal microscope, that has unique features and imaging characteristics for in vivo human ocular imaging. In vivo real-time confocal microscopy is currently used to investigate the tear film, renewal of the ocular surface, the role of epithelial innervation in epithelial cell proliferation, wound healing, kinetics of drug penetration, the effects of laser refractive surgery on the keratocyte activation and distribution in the stroma, and the nature of endothelial defects. The following clinical examples will be presented and discussed: confocal microscopy of normal human basal and wing cells in the epithelium, confocal microscopy of lamellar and penetrating corneal grafts, confocal microscopy of corneal ulcer, confocal microscopy of scar formation after herpes keratitis, and confocal microscopy of corneal innervation. The use of scanning slit confocal microscopes has unique advantages over other instrumental systems based on pinhole-containing Nipkow disks (tandem-scanning confocal microscopes) for clinical in vivo confocal microscopy.

  12. It is time to talk about people: a human-centered healthcare system

    Directory of Open Access Journals (Sweden)

    Borgi Lea


    Full Text Available Abstract Examining vulnerabilities within our current healthcare system we propose borrowing two tools from the fields of engineering and design: a Reason's system approach 1 and b User-centered design 23. Both approaches are human-centered in that they consider common patterns of human behavior when analyzing systems to identify problems and generate solutions. This paper examines these two human-centered approaches in the context of healthcare. We argue that maintaining a human-centered orientation in clinical care, research, training, and governance is critical to the evolution of an effective and sustainable healthcare system.

  13. It is time to talk about people: a human-centered healthcare system. (United States)

    Searl, Meghan M; Borgi, Lea; Chemali, Zeina


    Examining vulnerabilities within our current healthcare system we propose borrowing two tools from the fields of engineering and design: a) Reason's system approach 1 and b) User-centered design 23. Both approaches are human-centered in that they consider common patterns of human behavior when analyzing systems to identify problems and generate solutions. This paper examines these two human-centered approaches in the context of healthcare. We argue that maintaining a human-centered orientation in clinical care, research, training, and governance is critical to the evolution of an effective and sustainable healthcare system.

  14. Genomic relationships and speciation times of human, chimpanzee, and gorilla inferred from a coalescent hidden Markov model.

    Directory of Open Access Journals (Sweden)

    Asger Hobolth


    Full Text Available The genealogical relationship of human, chimpanzee, and gorilla varies along the genome. We develop a hidden Markov model (HMM that incorporates this variation and relate the model parameters to population genetics quantities such as speciation times and ancestral population sizes. Our HMM is an analytically tractable approximation to the coalescent process with recombination, and in simulations we see no apparent bias in the HMM estimates. We apply the HMM to four autosomal contiguous human-chimp-gorilla-orangutan alignments comprising a total of 1.9 million base pairs. We find a very recent speciation time of human-chimp (4.1 +/- 0.4 million years, and fairly large ancestral effective population sizes (65,000 +/- 30,000 for the human-chimp ancestor and 45,000 +/- 10,000 for the human-chimp-gorilla ancestor. Furthermore, around 50% of the human genome coalesces with chimpanzee after speciation with gorilla. We also consider 250,000 base pairs of X-chromosome alignments and find an effective population size much smaller than 75% of the autosomal effective population sizes. Finally, we find that the rate of transitions between different genealogies correlates well with the region-wide present-day human recombination rate, but does not correlate with the fine-scale recombination rates and recombination hot spots, suggesting that the latter are evolutionarily transient.

  15. Real-time monitoring of ethane in human breath using mid-infrared cavity leak-out spectroscopy (United States)

    Dahnke, H.; Kleine, D.; Hering, P.; Mürtz, M.


    We report on spectroscopic real-time analysis of ethane traces in exhaled human breath. Ethane is considered the most important volatile marker of free-radical induced lipid peroxidation and cell damage in the human body. Our measurements were carried out by means of mid-infrared cavity leak-out spectroscopy in the 3 μm region, a cw variant of cavity ring-down spectroscopy. The spectrometer is based on a CO overtone laser with tunable microwave sidebands. The resulting system proved to be an unique tool with high sensitivity and selectivity for rapid and precise breath testing. With a 5 s integration time, we achieved a detection limit on the order of 100 parts per trillion ethane in human breath. Thus, sample preconcentration is unnecessary. Time-resolved monitoring of the decaying ethane fraction in breath after smoking a cigarette is demonstrated.

  16. Effect of time pressure and human judgment on decision making in three public sector organizations of Pakistan

    Directory of Open Access Journals (Sweden)

    Rizwan Saleem


    Full Text Available This study attempts to widen the effect of time pressure and human judgment on decision making. A census of three organizations named Project Management Organization (PMO, Accountant General Pakistan Revenues (AGPR and Controller General of Accountant (CGA was occupied. To demeanor this study a questionnaire tagged Decision Making, Time Pressure and Human Judgment was used for the assortment of data. The questionnaire was predominantly designed to accomplish the objectives of the study. The total number of observations was eighty two and the Arithmetic Mean Score of decision making, time pressure and human judgment were 2.532, 2.527 and 2.395 respectively. The significance level of the model was 0.000 which illustrates maximum significant level. As p-value is less than .05 so it can be assumed that the variables elected for the study are decidedly significant.

  17. DNA-Based Sensor for Real-Time Measurement of the Enzymatic Activity of Human Topoisomerase I

    DEFF Research Database (Denmark)

    Marcussen, Lærke Bay; Jepsen, Morten Leth; Kristoffersen, Emil Laust;


    . The basic design of the sensor relies on two DNA strands that hybridize to form a hairpin structure with a fluorophore-quencher pair. The quencher moiety is released from the sensor upon reaction with human topoisomerase I thus enabling real-time optical measurement of enzymatic activity. The sensor......Sensors capable of quantitative real-time measurements may present the easiest and most accurate way to study enzyme activities. Here we present a novel DNA-based sensor for specific and quantitative real-time measurement of the enzymatic activity of the essential human enzyme, topoisomerase I...... is specific for topoisomerase I even in raw cell extracts and presents a simple mean of following enzyme kinetics using standard laboratory equipment such as a qPCR machine or fluorimeter. Human topoisomerase I is a well-known target for the clinically used anti-cancer drugs of the camptothecin family...

  18. Real-time Quantitative RT-PCR for CT9 Level in Human Cancer

    Institute of Scientific and Technical Information of China (English)


    CT9 is a recently cloned cancer-testis antigen, which is a member of the bromodomain and extraterminal family.Each member of this protein family contains two N-terminal bromodomain motifs. We investigated the distribution of CT9 in different tissues and the possibility for it to be used as a potential therapeutic target in cancer treament. By using the real-time RT-PCR method and 18SrRNA as an internal standard, we analyzed the CT9 expression in several normal human tissues and in the tissues of patients suffering from cancer. The result of this study shows that the highest level of mRNA is only present in testis tissue because the CT9 expression has not been detected in other normal tissues. In 6 of 10 cases of gastric adenocarcinoma, in 3 of 10 cases of esophageal squamous cell carcinoma, in 2 of 9 cases of endometrial carcinoma and only in 1 of 12 cases of brain cancer, the low level expression of CT9 was detected. In none of the 12 cases of cervical squamous cell carcinoma, the expression of CT9 was detected. Since the high level expression of CT9 is only found in the normal testis tissue, but the low expression in cancer tissues, for example tissues of cervical squamous cell carcinoma, brain cancer, endometrial adenocarcinoma, esophageal squamous cell carcinoma, we conclude that CT9 cannot be used as a cancer therapeutic target molecule for cervical squamous cell carcinoma, brain cancer, endometrial adenocarcinoma, esophageal squamous cell carcinoma.

  19. Baseflow mean transit times in natural and human-altered catchments (United States)

    Boll, J.; Sanchez-Murillo, R.; Brooks, E. S.; Elliot, W. E.


    Baseflow is one of the most important components of the ecosystem since it provides continuous habitat to aquatic biota; regulates water chemistry, temperature, and dissolved oxygen during summer; and functions as an essential supply for drinking water and food production worldwide. This study will evaluate baseflow mean transit times (MTTs) in five natural (i.e. pristine forest) and human-altered (i.e. agricultural, urban, and mining) catchments in eastern Washington and northern Idaho during 2011-2013. Drainage area ranges from small (6.35 km2) to meso scale (342 km2) and mean annual precipitation varies from 670 mm to 1,313 mm. MTTs were evaluated by applying d18O input precipitation and output stream waters to a lumped parameter model (FlowPC 3.2) using four main theoretical distribution models: piston flow, exponential, dispersion, and piston-exponential. Precipitation samples (N=307) were collected on weekly to biweekly basis and stream samples (N=690) were collected weekly using automated samplers. Precipitation showed a strong seasonal periodicity with a sine-wave modeled amplitude of 3.03‰ and a mean annual average of d18O= -15.13‰. Mean annual stream d18O ranged from -14.87‰ to -15.80‰ across the study catchments. Our modeling results will show information for examining solute transport and water availability under current and future land use practices and climate variability within a variety of watersheds in the inland Pacific Northwest that share similar underlying geology and climate attributes.

  20. Near Real Time Analytics of Human Sensor Networks in the Realm of Big Data (United States)

    Aulov, O.; Halem, M.


    With the prolific development of social media, emergency responders have an increasing interest in harvesting social media from outlets such as Flickr, Twitter, and Facebook, in order to assess the scale and specifics of extreme events including wild fires, earthquakes, terrorist attacks, oil spills, etc. A number of experimental platforms have successfully been implemented to demonstrate the utilization of social media data in extreme events, including Twitter Earthquake Detector, which relied on tweets for earthquake monitoring; AirTwitter, which used tweets for air quality reporting; and our previous work, using Flickr data as boundary value forcings to improve the forecast of oil beaching in the aftermath of the Deepwater Horizon oil spill. The majority of these platforms addressed a narrow, specific type of emergency and harvested data from a particular outlet. We demonstrate an interactive framework for monitoring, mining and analyzing a plethora of heterogeneous social media sources for a diverse range of extreme events. Our framework consists of three major parts: a real time social media aggregator, a data processing and analysis engine, and a web-based visualization and reporting tool. The aggregator gathers tweets, Facebook comments from fan pages, Google+ posts, forum discussions, blog posts (such as LiveJournal and, images from photo-sharing platforms (such as Flickr, Picasa), videos from video-sharing platforms (youtube, Vimeo), and so forth. The data processing and analysis engine pre-processes the aggregated information and annotates it with geolocation and sentiment information. In many cases, the metadata of the social media posts does not contain geolocation information—-however, a human reader can easily guess from the body of the text what location is discussed. We are automating this task by use of Named Entity Recognition (NER) algorithms and a gazetteer service. The visualization and reporting tool provides a web-based, user

  1. Dynamics and flexibility of human aromatase probed by FTIR and time resolved fluorescence spectroscopy.

    Directory of Open Access Journals (Sweden)

    Giovanna Di Nardo

    Full Text Available Human aromatase (CYP19A1 is a steroidogenic cytochrome P450 converting androgens into estrogens. No ligand-free crystal structure of the enzyme is available to date. The crystal structure in complex with the substrate androstenedione and the steroidal inhibitor exemestane shows a very compact conformation of the enzyme, leaving unanswered questions on the conformational changes that must occur to allow access of the ligand to the active site. As H/D exchange kinetics followed by FTIR spectroscopy can provide information on the conformational changes in proteins where solvent accessibility is affected, here the amide I region was used to measure the exchange rates of the different elements of the secondary structure for aromatase in the ligand-free form and in the presence of the substrate androstenedione and the inhibitor anastrozole. Biphasic exponential functions were found to fit the H/D exchange data collected as a function of time. Two exchange rates were assigned to two populations of protons present in different flexible regions of the protein. The addition of the substrate androstenedione and the inhibitor anastrozole lowers the H/D exchange rates of the α-helices of the enzyme when compared to the ligand-free form. Furthermore, the presence of the inhibitor anastrozole lowers exchange rate constant (k1 for β-sheets from 0.22±0.06 min(-1 for the inhibitor-bound enzyme to 0.12±0.02 min(-1 for the free protein. Dynamics effects localised in helix F were studied by time resolved fluorescence. The data demonstrate that the fluorescence lifetime component associated to Trp224 emission undergoes a shift toward longer lifetimes (from ≈5.0 to ≈5.5 ns when the substrate or the inhibitor are present, suggesting slower dynamics in the presence of ligands. Together the results are consistent with different degrees of flexibility of the access channel and therefore different conformations adopted by the enzyme in the free, substrate- and

  2. Dynamics and flexibility of human aromatase probed by FTIR and time resolved fluorescence spectroscopy. (United States)

    Di Nardo, Giovanna; Breitner, Maximilian; Sadeghi, Sheila J; Castrignanò, Silvia; Mei, Giampiero; Di Venere, Almerinda; Nicolai, Eleonora; Allegra, Paola; Gilardi, Gianfranco


    Human aromatase (CYP19A1) is a steroidogenic cytochrome P450 converting androgens into estrogens. No ligand-free crystal structure of the enzyme is available to date. The crystal structure in complex with the substrate androstenedione and the steroidal inhibitor exemestane shows a very compact conformation of the enzyme, leaving unanswered questions on the conformational changes that must occur to allow access of the ligand to the active site. As H/D exchange kinetics followed by FTIR spectroscopy can provide information on the conformational changes in proteins where solvent accessibility is affected, here the amide I region was used to measure the exchange rates of the different elements of the secondary structure for aromatase in the ligand-free form and in the presence of the substrate androstenedione and the inhibitor anastrozole. Biphasic exponential functions were found to fit the H/D exchange data collected as a function of time. Two exchange rates were assigned to two populations of protons present in different flexible regions of the protein. The addition of the substrate androstenedione and the inhibitor anastrozole lowers the H/D exchange rates of the α-helices of the enzyme when compared to the ligand-free form. Furthermore, the presence of the inhibitor anastrozole lowers exchange rate constant (k1) for β-sheets from 0.22±0.06 min(-1) for the inhibitor-bound enzyme to 0.12±0.02 min(-1) for the free protein. Dynamics effects localised in helix F were studied by time resolved fluorescence. The data demonstrate that the fluorescence lifetime component associated to Trp224 emission undergoes a shift toward longer lifetimes (from ≈5.0 to ≈5.5 ns) when the substrate or the inhibitor are present, suggesting slower dynamics in the presence of ligands. Together the results are consistent with different degrees of flexibility of the access channel and therefore different conformations adopted by the enzyme in the free, substrate- and inhibitor

  3. Learning dictionaries of sparse codes of 3D movements of body joints for real-time human activity understanding.

    Directory of Open Access Journals (Sweden)

    Jin Qi

    Full Text Available Real-time human activity recognition is essential for human-robot interactions for assisted healthy independent living. Most previous work in this area is performed on traditional two-dimensional (2D videos and both global and local methods have been used. Since 2D videos are sensitive to changes of lighting condition, view angle, and scale, researchers begun to explore applications of 3D information in human activity understanding in recently years. Unfortunately, features that work well on 2D videos usually don't perform well on 3D videos and there is no consensus on what 3D features should be used. Here we propose a model of human activity recognition based on 3D movements of body joints. Our method has three steps, learning dictionaries of sparse codes of 3D movements of joints, sparse coding, and classification. In the first step, space-time volumes of 3D movements of body joints are obtained via dense sampling and independent component analysis is then performed to construct a dictionary of sparse codes for each activity. In the second step, the space-time volumes are projected to the dictionaries and a set of sparse histograms of the projection coefficients are constructed as feature representations of the activities. Finally, the sparse histograms are used as inputs to a support vector machine to recognize human activities. We tested this model on three databases of human activities and found that it outperforms the state-of-the-art algorithms. Thus, this model can be used for real-time human activity recognition in many applications.

  4. Preliminary study on the time-related changes of the infrared thermal images of the human body (United States)

    Li, Ziru; Zhang, Xusheng; Lin, Gang; Chen, Zhigang


    It is of great importance to study the manifestations and the influencing factors of the time-related changes of infrared thermal images (ITI) of human body since the variable body surface temperature distribution seriously affected the application of ITI in medicine. In this paper, manifestations of time-related changes of the ITI of human body from three double-blind randomized trials and their correlation with meteorological factors (e.g. temperature, pressure, humidity, cold front passage and tropical cyclone landing) were studied. The trials were placebo or drug controlled studying the influences of Chinese medicine health food (including Shengsheng capsule with immunity adjustment function, Shengan capsule with sleep improvement function and Shengyi capsule with the function of helping to decrease serum lipid) on the ITI of human body. In the first thirty-six days of the trials images were scanned every six days and image data in the seven observation time spots (including the 0, 6, 12, 18, 24, 30, 36 day of the trial) were used for the time-related study. For every subject the scanned time was fixed in the day within two hours. The ITI features which could reflect the functions of the health foods were studied. The indexes of the features were relative magnitude (temperature difference between the viewing area and the reference area). Results showed that the variation tendencies of the trial group and control group were basically the same in placebo controlled trials and some of the long-term effects of Chinese medicine health food could be reflected significantly in certain time spots in the first thirty-six days. Time-related changes of the ITI of human body were closely related with meteorological factors but there were other influencing factors still need to be studied. As the ITI of human body could reflect the influences of Chinese medicine health foods and are closely related with meteorology, there are bright prospects for the application of ITI in

  5. Reconstructing the Distribution of Archaic and Modern Humans in Time and Space in Relation to the Last Glacial Climate Change (United States)

    Yoneda, Minoru; Abe-Ouchi, Ayako; Oguchi, Takashi; Kawahata, Hodaka; Yokoyama, Yusuke


    The impact of climate change is an intriguing focus to invest the replacement of archaic humans, including Neanderthals in Europe, by the modern humans. On the other hand, our ancestor survived in the same/similar environmental settings sharing with archaic human species. The reason why only homo sapience can survive is the important but still challenging task for anthropologists and archaeologists. In the project "Replacement of Neanderthal by Modern Humans: Testing Evolutionary Models of Learning" supported by MEXT, Japan, we have tried to establish more reliable maps of human distribution and climatic zones by developing some new techniques. New data-set for calibrating conventional radiocarbon dates, IntCAl09, makes it possible to compare the archaeological events dated by radiocarbon and the history of climate changes recorded in annual rings in ice cores from the Antarctic and Greenland. Because the replacement was a process ongoing in time and space, however, it is not easy to evaluate the impact of climate change on the extinction of archaic humans. Hence, we are applying several different methods to extract quantitative relationship between the changes in human activities and past climate. Our methods include (1) the development of geoscientific and informatics methodology such as the meta-analysis of large data-set of radiocarbon dating, (2) the reconstruction of climate and vegetation maps in higher resolution based on a global circulation model, (3) reconstructing history of regional environments based on geochemical proxies from land, and (4) the combination and comparison between environmental factors and human distribution using the eco-cultural niche modeling. Each branch of our project has established methods to evaluate the more concrete distribution of past climate and human species in time and space. We would like to discuss the current status of our project and the problems we have to overcome.

  6. Robust Real-time Vision-based Human Detection and Tracking


    Leu, Adrian


    In the last couple of decades technology has made its way into our everyday lives including our homes, our offices and the vehicles we use for travelling. Many modern devices interact with humans in a more or less intuitive way and some of them use cameras for observing or interacting with humans. Nevertheless, teaching a machine to detect humans in an image or a video is a very difficult task. There are many aspects that contribute to the complexity of this task, such as the many variations ...

  7. Time-resolved fluoroimmunoassays of the complete set of secreted phospholipases A2 in human serum. (United States)

    Nevalainen, Timo J; Eerola, Leena I; Rintala, Esa; Laine, V Jukka O; Lambeau, Gérard; Gelb, Michael H


    Time-resolved fluoroimmunoassays (TR-FIA) were developed for all human secreted phospholipases A(2) (PLA(2)), viz. group (G) IB, GIIA, GIID, GIIE, GIIF, GIII, GV, GX and GXIIA PLA(2) and the GXIIB PLA(2)-like protein. Antibodies were raised in rabbits against recombinant human PLA(2) proteins and used in sandwich-type TR-FIAs as both catching and detecting antibodies, the latter after labeling with Europium. The antibodies were non-cross-reactive. The analytical sensitivities were 1 microg/L for the TR-FIA for GIB PLA(2), 1 microg/L (GIIA), 35 microg/L (GIID), 3 microg/L (GIIE), 4 microg/L (GIIF), 14 microg/L (GIII), 11 microg/L (GV), 2 microg/L (GX), 92 microg/L (GXIIA) and 242 microg/L (GXIIB). All secreted PLA(2)s were assayed by these TR-FIAs in serum samples from 34 patients (23 men and 11 women, mean age 53.2 years) treated in an intensive care unit for septic infections, and in control samples from 28 volunteer blood donors (14 men and 14 women, mean age 57.0 years). Five serum samples (3 in the sepsis group and 2 in the blood donor group) gave high TR-FIA signals that were reduced to background (blank) levels by the addition of non-immune rabbit IgG to the sera. This reactivity was assumed to be due to the presence of heterophilic antibodies in these subjects. In all other subjects, including septic patients and healthy blood donors, the TR-FIA signals for GIID, GIIE, GIIF, GIII, GV, GX and GXIIA PLA(2) and the GXIIB PLA(2)-like protein were at background (blank) levels. Four patients in the sepsis group had pancreatic involvement and elevated concentration of GIB PLA(2) in serum (median 19.0 microg/L, range 13.1-33.7 microg/L, n = 4) as compared to the healthy blood donors (median 1.8 microg/L, range 0.8-3.4 microg/L, n = 28, P < 0.0001). The concentration of GIIA PLA(2) in the sera of septic patients (median 315.7 microg/L, range 15.9-979.6 microg/L, n = 34) was highly elevated as compared to that of the blood donors (median 1.8 microg/L, range 0

  8. Comparing the Impact of Topical Application of Human Milk and Chlorhexidine on Cord Separation Time in Newborns


    Abbaszadeh, Fatemeh; Hajizadeh, Zanab; Mohammad JAHANGIRI


    Objectives: The best umbilical cord care after birth is a controversial issue. Aim of this research was to compare the effect of topical application of human milk and chlorhexidin on cord separation time in newborns. Methods: One hundred seventy four neonates attending from hospitals affiliated to Kashan University of Medical Sciences were included. Newborns from birth were randomized to two groups. In group mother’s milk, mother will rub her own milk to cord stump two times a day. chlorhexid...

  9. Some aspects of oxidative metabolism in human endometrium after long time of applying the intrauterine contraceptive device. (United States)

    Bausic, V; Ionescu, N


    The paper intends to study the variation of oxidative metabolism of human endometrium (all the components) after applying the intrauterine contraceptive device for a long period of time. The results of the study show that modifications "in situ" of the oxidative enzymes vary according to the: type of the enzymes (NADH2-cytochrome-c-reductase, Lactatdehydrogenase), the hormonal cyclic stage (proliferative phase, or luteal phase), epithelial or connective tissue structures, time of resting the intrauterine contraceptive device (DIU) in uterus.

  10. Do Monkeys Think in Metaphors? Representations of Space and Time in Monkeys and Humans (United States)

    Merritt, Dustin J.; Casasanto, Daniel; Brannon, Elizabeth M.


    Research on the relationship between the representation of space and time has produced two contrasting proposals. ATOM posits that space and time are represented via a common magnitude system, suggesting a symmetrical relationship between space and time. According to metaphor theory, however, representations of time depend on representations of…


    Method standardization or the formal development of a protocol that establishes uniform performance benchmarks and practices is necessary for widespread adoption of a fecal source identification approach. Standardization of a human-associated fecal identification method has been...

  12. Human Fecal Source Identification: Real-Time Quantitative PCR Method Standardization (United States)

    Method standardization or the formal development of a protocol that establishes uniform performance benchmarks and practices is necessary for widespread adoption of a fecal source identification approach. Standardization of a human-associated fecal identification method has been...

  13. Climate and humans set the place and time of Proboscidean extinction in late Quaternary of South America

    DEFF Research Database (Denmark)

    Lima-Ribeiro, Matheus Souza; Nogues, David Bravo; Terribile, Levi Carina


    (ENMs) and modeled the timing for extinction under human hunting scenario, and both variables were used to explain the extinction dynamics of Proboscideans during a full interglacial/glacial cycle (from 126 ka to 6 ka) in South America. We found a large contraction in the geographic range size of two...... Proboscidean species studied (Cuvieronius hyodon and Notiomastodon platensis) across time. The largest contractions of their geographical ranges occurred in the northern part of South America, where we previously reported no evidence of coexistence among earliest humans and non-sloth megafauna, including...... on scattered patches of suitable habitats (i.e., refugia) around 11 ka, period in which the earliest humans potentially arrived in South America, increasing the population density thereafter. Under this overall unsuitable climatic condition at 11 ka, both Proboscideans would be extinct after around 550 years...

  14. Time to Separate the Men From the Beasts: Symbolic Anticipation as the Typically Human Subjective Dimension (United States)

    De Grave, Dieter


    In this paper it is argued that the dividing line that runs between the human psyche as opposed to any other complex system is made up by symbolic anticipation. The functionality of the human mind as an anticipatory system is entirely caught up in the crucial role that finiteness, shortage or lack plays for human beings. Anticipation for us is the way by which this negative finiteness or lack is translated into a positive longing, want or desire. We take a look at the three dimensional view of Jacques Lacan regarding these matters in a sophistical example and we illustrate how anticipation as a Symbolic phenomenon is distinct from the Imaginary or the Real register. As Lacan points out anticipation creates a symbolic social link which binds two or more interacting humans together in an anticipatory relationship. Beliefs, expectations and convictions are the typically human social links which ground human interaction and set it apart from other forms of social interaction we can observe in other complex biological entities.

  15. Data Acceptance Criteria for Standardized Human-Associated Fecal Source Identification Quantitative Real-Time PCR Methods (United States)

    There is a growing interest in the application of human-associated fecal sourceidentification quantitative real-time PCR (qPCR) technologies for water quality management. The transition from a research tool to a standardized protocol requires a high degree of confidence in data q...

  16. STR analysis of human DNA from maggots fed on decomposing bodies: Assessment of the time period for successful analysis

    Directory of Open Access Journals (Sweden)

    Daniel Gachuiri Njau


    Full Text Available Frequently, forensic entomology is applied in the use of insect maggots for the identification of specimens or remains of humans. Maggot crop analysis could be valuable in criminal investigations when maggots are found at a crime scene and a corpse is absent. Human short tandem repeat (STR has previously been used to support the association of maggots to a specific corpse but not in the period at which the body has been decomposing. The aim of this research was to assess the time period for successful STR analyses of human DNA from third instar maggots (Protophormia terraenovae obtained from decomposing human corpses as well as to investigate the human DNA turnover and degradation in the maggot crop after they are removed from food and/or are fed on a beef (a new/different food source. Results showed that the amount of human DNA recovered from maggots decreased with time in all cases. For maggots fed on beef, the human DNA could only be recovered up to day two and up to day four for the starved maggots. STR analyses of human DNA from maggots’ crop content using 16 loci generated profiles that matched those of reference samples although some of the alleles were not amplifiable therefore generating partial profiles for the samples starved for 4 days and those fed on beef. This may be due to nuclease activity present in the gut of larvae that may have caused degradation of DNA and consequently reduction in DNA yield. It was possible to identify the decomposing body using STRs as markers.

  17. Accurate measurement of circulating mitochondrial DNA content from human blood samples using real-time quantitative PCR. (United States)

    Ajaz, Saima; Czajka, Anna; Malik, Afshan


    We describe a protocol to accurately measure the amount of human mitochondrial DNA (MtDNA) in peripheral blood samples which can be modified to quantify MtDNA from other body fluids, human cells, and tissues. This protocol is based on the use of real-time quantitative PCR (qPCR) to quantify the amount of MtDNA relative to nuclear DNA (designated the Mt/N ratio). In the last decade, there have been increasing numbers of studies describing altered MtDNA or Mt/N in circulation in common nongenetic diseases where mitochondrial dysfunction may play a role (for review see Malik and Czajka, Mitochondrion 13:481-492, 2013). These studies are distinct from those looking at genetic mitochondrial disease and are attempting to identify acquired changes in circulating MtDNA content as an indicator of mitochondrial function. However, the methodology being used is not always specific and reproducible. As more than 95 % of the human mitochondrial genome is duplicated in the human nuclear genome, it is important to avoid co-amplification of nuclear pseudogenes. Furthermore, template preparation protocols can also affect the results because of the size and structural differences between the mitochondrial and nuclear genomes. Here we describe how to (1) prepare DNA from blood samples; (2) pretreat the DNA to prevent dilution bias; (3) prepare dilution standards for absolute quantification using the unique primers human mitochondrial genome forward primer (hMitoF3) and human mitochondrial genome reverse primer(hMitoR3) for the mitochondrial genome, and human nuclear genome forward primer (hB2MF1) and human nuclear genome reverse primer (hB2MR1) primers for the human nuclear genome; (4) carry out qPCR for either relative or absolute quantification from test samples; (5) analyze qPCR data; and (6) calculate the sample size to adequately power studies. The protocol presented here is suitable for high-throughput use.

  18. Education in Responsibility in Order to Secure Human Rights in Times of Crisis

    Directory of Open Access Journals (Sweden)

    Michaël Merrigan


    Full Text Available Education in and awareness about human rights is generally seen as one of the less contentious elements of citizenship education. However, it would seem that, for the concept of human rights to have a real impact in today's world, theoretical knowledge of human rights standards should be complemented by an understanding of the ethical concept of individual responsibility. This concept could, moreover, prove to be a valuable tool in conceiving creative answers to some of the consequences of the crisis Europe has been facing. This crisis has affected especially the protection and realisation of socio-economic rights, as many States were left with increasingly less budgetary space to meet increasingly urgent societal demands. Over the last few decades, and already prior to the current crisis, many have called for a greater stress on ‘duties and responsibilities’, as it was perceived that ‘rights-talk’ alone did not provide all the answers. From a legal perspective, as well as from the side of human rights advocacy groups, however, these appeals were often met with scepticism and hostility. In answer to the often justified criticism, it is essential to make a distinction between the ‘legal’, the ‘moral’ and the ‘ethical’ realms. While an unnuanced greater focus on moral duties is potentially dangerous, education based on the proposed notion of ethical ‘responsibility’ would seem, on the contrary, essential for the survival of human rights and, hence, of the democratic society.

  19. R/S analysis of reaction time in Neuron Type Test for human activity in civil aviation (United States)

    Zhang, Hong-Yan; Kang, Ming-Cui; Li, Jing-Qiang; Liu, Hai-Tao


    Human factors become the most serious problem leading to accidents of civil aviation, which stimulates the design and analysis of Neuron Type Test (NTT) system to explore the intrinsic properties and patterns behind the behaviors of professionals and students in civil aviation. In the experiment, normal practitioners' reaction time sequences, collected from NTT, exhibit log-normal distribution approximately. We apply the χ2 test to compute the goodness-of-fit by transforming the time sequence with Box-Cox transformation to cluster practitioners. The long-term correlation of different individual practitioner's time sequence is represented by the Hurst exponent via Rescaled Range Analysis, also named by Range/Standard deviation (R/S) Analysis. The different Hurst exponent suggests the existence of different collective behavior and different intrinsic patterns of human factors in civil aviation.

  20. Strong Memory in Time Series of Human Magnetoencephalograms Can Identify Photosensitive Epilepsy

    CERN Document Server

    Yulmetyev, R M; Hänggi, P; Khusaenova, E V; Shimojo, S; Yulmetyeva, D G


    o discuss the salient role of the statistical memory effects in the human brain functioning we have analyzed a set of stochastic memory quantifiers that reflects the dynamical characteristics of neuromagnetic brain responses to a flickering stimulus of different color combinations from a group of control subjects which is contrasted with those from a patient with photosensitive epilepsy (PSE). We have discovered the emergence of strong memory and the accompanying transition to a regular and robust regime of chaotic behavior of the signals in the separate areas for a patient with PSE. This finding most likely identifies the regions of the location the protective mechanism in a human organism against occurrence of PSE.

  1. Quantitative real-time PCR (qPCR) assay for human-dog-cat species identification and nuclear DNA quantification. (United States)

    Kanthaswamy, S; Premasuthan, A; Ng, J; Satkoski, J; Goyal, V


    In the United States, human forensic evidence collected from crime scenes is usually comingled with biomaterial of canine and feline origins. Knowledge of the concentration of nuclear DNA extracted from a crime scene biological sample and the species from which the sample originated is essential for DNA profiling. The ability to accurately detect and quantify target DNA in mixed-species samples is crucial when target DNA may be overwhelmed by non-target DNA. We have designed and evaluated a species-specific (human, dog and cat) nuclear DNA identification assay based on the TaqMan(®) quantitative real-time PCR (qPCR) technology that can simultaneously detect and measure minute quantities of DNA specific to either humans, dogs and/or cats. The fluorogenic triplex assay employs primers and hydrolysis probes that target the human TH01 locus as well as the dog and cat Melanocortin 1 Receptor (MC1R) sequences in a species-specific manner. We also demonstrate that the assay is a highly sensitive, reliable and robust method for identifying and quantifying mixed-species templates of human-dog-cat origin with as little as 0.4 pg of human and cat nuclear DNA, respectively, and 4.0 pg of dog nuclear DNA.

  2. Quantification of Hydrological Responses Due to Climate Change and Human Activities over Various Time Scales in South Korea

    Directory of Open Access Journals (Sweden)

    Sangho Lee


    Full Text Available Hydrological responses are being impacted by both climate change and human activities. In particular, climate change and regional human activities have accelerated significantly during the last three decades in South Korea. The variation in runoff due to the two types of factors should be quantitatively investigated to aid effective water resources’ planning and management. In water resources’ planning, analysis using various time scales is useful where rainfall is unevenly distributed. However, few studies analyzed the impacts of these two factors over different time scales. In this study, hydrologic model-based approach and hydrologic sensitivity were used to separate the relative impacts of these two factors at monthly, seasonal and annual time scales in the Soyang Dam upper basin and the Seom River basin in South Korea. After trend analysis using the Mann–Kendall nonparametric test to identify the causes of gradual change, three techniques, such as the double mass curve method, Pettitt’s test and the BCP (Bayesian change point analysis, were used to detect change points caused by abrupt changes in the collected observed runoff. Soil and Water Assessment Tool (SWAT models calibrated from the natural periods were used to calculate the impacts of human activities. Additionally, six Budyko-based methods were used to verify the results obtained from the hydrological-based approach. The results show that impacts of climate change have been stronger than those of human activities in the Soyang Dam upper basin, while the impacts of human activities have been stronger than those of climate change in the Seom River basin. Additionally, the quantitative characteristics of relative impacts due to these two factors were identified at the monthly, seasonal and annual time scales. Finally, we suggest that the procedure used in this study can be used as a reference for regional water resources’ planning and management.

  3. The Reallocation of Human Resources to Improve Student Achievement in a Time of Fiscal Constraints (United States)

    Behar, Steve


    This study compared the allocation of human resources of a K-12 unified school district in Southern California to the Evidence-Based model (Odden & Picus, 2008). Using document analysis and interviews of key administrators of the district, data was input into a spreadsheet to identify gaps between current practice and the Evidence-Based model.…

  4. From "Time Pass" to Transformative Force: School-Based Human Rights Education in Tamil Nadu, India (United States)

    Bajaj, Monisha


    This article presents data collected at the level of practice to highlight one non-governmental organization's approach to human rights education and how household-, school-, and community-level factors mediated student impact. Findings suggest that a variety of factors at the three levels contribute to the program's successful implementation in…

  5. Forecasting Human African Trypanosomiasis Prevalences from Population Screening Data Using Continuous Time Models

    NARCIS (Netherlands)

    H. de Vries (Harwin); A.P.M. Wagelmans (Albert); E.C. Hasker (Epco C.); C. Lumbala (Crispin); P. Lutumba (Pascal); S.J. de Vlas (Sake); J. van de Klundert (Joris)


    textabstractTo eliminate and eradicate gambiense human African trypanosomiasis (HAT), maximizing the effectiveness of active case finding is of key importance. The progression of the epidemic is largely influenced by the planning of these operations. This paper introduces and analyzes five models fo

  6. Replication timing of human telomeres is chromosome arm-specific, influenced by subtelomeric structures and connected to nuclear localization.

    Directory of Open Access Journals (Sweden)

    Nausica Arnoult


    Full Text Available The mechanisms governing telomere replication in humans are still poorly understood. To fill this gap, we investigated the timing of replication of single telomeres in human cells. Using in situ hybridization techniques, we have found that specific telomeres have preferential time windows for replication during the S-phase and that these intervals do not depend upon telomere length and are largely conserved between homologous chromosomes and between individuals, even in the presence of large subtelomeric segmental polymorphisms. Importantly, we show that one copy of the 3.3 kb macrosatellite repeat D4Z4, present in the subtelomeric region of the late replicating 4q35 telomere, is sufficient to confer both a more peripheral localization and a later-replicating property to a de novo formed telomere. Also, the presence of beta-satellite repeats next to a newly created telomere is sufficient to delay its replication timing. Remarkably, several native, non-D4Z4-associated, late-replicating telomeres show a preferential localization toward the nuclear periphery, while several early-replicating telomeres are associated with the inner nuclear volume. We propose that, in humans, chromosome arm-specific subtelomeric sequences may influence both the spatial distribution of telomeres in the nucleus and their replication timing.

  7. A methodology to condition distorted acoustic emission signals to identify fracture timing from human cadaver spine impact tests. (United States)

    Arun, Mike W J; Yoganandan, Narayan; Stemper, Brian D; Pintar, Frank A


    While studies have used acoustic sensors to determine fracture initiation time in biomechanical studies, a systematic procedure is not established to process acoustic signals. The objective of the study was to develop a methodology to condition distorted acoustic emission data using signal processing techniques to identify fracture initiation time. The methodology was developed from testing a human cadaver lumbar spine column. Acoustic sensors were glued to all vertebrae, high-rate impact loading was applied, load-time histories were recorded (load cell), and fracture was documented using CT. Compression fracture occurred to L1 while other vertebrae were intact. FFT of raw voltage-time traces were used to determine an optimum frequency range associated with high decibel levels. Signals were bandpass filtered in this range. Bursting pattern was found in the fractured vertebra while signals from other vertebrae were silent. Bursting time was associated with time of fracture initiation. Force at fracture was determined using this time and force-time data. The methodology is independent of selecting parameters a priori such as fixing a voltage level(s), bandpass frequency and/or using force-time signal, and allows determination of force based on time identified during signal processing. The methodology can be used for different body regions in cadaver experiments.

  8. Reliability of the interval death rate analysis for estimating the time course of the motoneurone afterhyperpolarization in humans. (United States)

    MacDonell, Christopher William; Ivanova, Tanya Dimitrova; Garland, S Jayne


    The reliability of the afterhyperpolarization (AHP) time course, as estimated by the interval death rate (IDR) analysis was evaluated both within and between investigators. The IDR analysis uses the firing history of a single motor unit train at low tonic firing rates to calculate an estimate of the AHP time course [Matthews PB. Relationship of firing intervals of human motor units to the trajectory of post-spike after-hyperpolarization and synaptic noise. J Physiol 1996;492:597-628]. Single motor unit trains were collected from the tibialis anterior (TA) to determine intra-rater reliability (within investigator). Data from the first dorsal interosseus (FDI), collected in a previous investigation [Gossen ER, Ivanova TD, Garland SJ. The time course of the motoneurone afterhyperpolarization is related to motor unit twitch speed in human skeletal muscle. J Physiol 2003;552:657-64], were used to examine the inter-rater reliability (between investigators). The lead author was blinded to the original time constants and file identities for the re-analysis. The intra-rater reliability of the AHP time constant in the TA data was high (r(2)=0.88; pFDI data was also strong (r(2)=0.92; pFDI. It is concluded that the interval death rate analysis is a reliable tool for estimating the AHP time course with experienced investigators.

  9. Relaxational Singularities of Human Motor System at Aging Due to Short-Range and Long-Range Time Correlations

    CERN Document Server

    Yulmetyev, Renat M; Gafarov, Fail M; Demin, Sergey A; Panischev, Oleg Yu; Hänggi, Peter


    In this paper we study the relaxation singularities of human motor system at aging. Our purpose is to examine the structure of force output variability as a function of human aging in the time and frequency domains. For analysis of experimental data we have developed here the statistical theory of relaxation of force output fluctuation with taking into account the effects of two relaxation channels. The first of them contains the contribution of short-range correlation whereas other relaxation component reflects the effect of long-range correlation. The analysis of experimental data shows, that the general behavior of relaxation processes at human aging is determined by a complicated combination and nonlinear interactions two above stated relaxation processes as a whole.

  10. A Study on Human Oriented Autonomous Distributed Manufacturing System —Real-time Scheduling Method Based on Preference of Human Operators (United States)

    Iwamura, Koji; Kuwahara, Shinya; Tanimizu, Yoshitaka; Sugimura, Nobuhiro

    Recently, new distributed architectures of manufacturing systems are proposed, aiming at realizing more flexible control structures of the manufacturing systems. Many researches have been carried out to deal with the distributed architectures for planning and control of the manufacturing systems. However, the human operators have not yet been discussed for the autonomous components of the distributed manufacturing systems. A real-time scheduling method is proposed, in this research, to select suitable combinations of the human operators, the resources and the jobs for the manufacturing processes. The proposed scheduling method consists of following three steps. In the first step, the human operators select their favorite manufacturing processes which they will carry out in the next time period, based on their preferences. In the second step, the machine tools and the jobs select suitable combinations for the next machining processes. In the third step, the automated guided vehicles and the jobs select suitable combinations for the next transportation processes. The second and third steps are carried out by using the utility value based method and the dispatching rule-based method proposed in the previous researches. Some case studies have been carried out to verify the effectiveness of the proposed method.

  11. The human circadian clock's seasonal adjustment is disrupted by daylight saving time

    NARCIS (Netherlands)

    Kantermann, Thomas; Juda, Myriam; Merrow, Martha; Roenneberg, Till


    A quarter of the world's population is subjected to a 1 hr time change twice a year (daylight saving time, DST). This reflects a change in social clocks, not environmental ones (e.g., dawn). The impact of DST is poorly understood. Circadian clocks use daylight to synchronize (entrain) to the organis

  12. Techniques for optimizing human-machine information transfer related to real-time interactive display systems (United States)

    Granaas, Michael M.; Rhea, Donald C.


    The requirements for the development of real-time displays are reviewed. Of particular interest are the psychological aspects of design such as the layout, color selection, real-time response rate, and the interactivity of displays. Some existing Western Aeronautical Test Range displays are analyzed.

  13. A non linear analysis of human gait time series based on multifractal analysis and cross correlations

    Energy Technology Data Exchange (ETDEWEB)

    Munoz-Diosdado, A [Department of Mathematics, Unidad Profesional Interdisciplinaria de Biotecnologia, Instituto Politecnico Nacional, Av. Acueducto s/n, 07340, Mexico City (Mexico)


    We analyzed databases with gait time series of adults and persons with Parkinson, Huntington and amyotrophic lateral sclerosis (ALS) diseases. We obtained the staircase graphs of accumulated events that can be bounded by a straight line whose slope can be used to distinguish between gait time series from healthy and ill persons. The global Hurst exponent of these series do not show tendencies, we intend that this is because some gait time series have monofractal behavior and others have multifractal behavior so they cannot be characterized with a single Hurst exponent. We calculated the multifractal spectra, obtained the spectra width and found that the spectra of the healthy young persons are almost monofractal. The spectra of ill persons are wider than the spectra of healthy persons. In opposition to the interbeat time series where the pathology implies loss of multifractality, in the gait time series the multifractal behavior emerges with the pathology. Data were collected from healthy and ill subjects as they walked in a roughly circular path and they have sensors in both feet, so we have one time series for the left foot and other for the right foot. First, we analyzed these time series separately, and then we compared both results, with direct comparison and with a cross correlation analysis. We tried to find differences in both time series that can be used as indicators of equilibrium problems.

  14. Time allocation in social networks: correlation between social structure and human communication dynamics

    CERN Document Server

    Miritello, Giovanna; Moro, Esteban


    Recent research has shown the deep impact of the dynamics of human interactions (or temporal social networks) on the spreading of information, opinion formation, etc. In general, the bursty nature of human interactions lowers the interaction between people to the extent that both the speed and reach of information diffusion are diminished. Using a large database of 20 million users of mobile phone calls we show evidence this effect is not homogeneous in the social network but in fact, there is a large correlation between this effect and the social topological structure around a given individual. In particular, we show that social relations of hubs in a network are relatively weaker from the dynamical point than those that are poorer connected in the information diffusion process. Our results show the importance of the temporal patterns of communication when analyzing and modeling dynamical process on social networks.

  15. Time Allocation in Social Networks: Correlation Between Social Structure and Human Communication Dynamics (United States)

    Miritello, Giovanna; Lara, Rubén; Moro, Esteban

    Recent research has shown the deep impact of the dynamics of human interactions (or temporal social networks) on the spreading of information, opinion formation, etc. In general, the bursty nature of human interactions lowers the interaction between people to the extent that both the speed and reach of information diffusion are diminished. Using a large database of 20 million users of mobile phone calls we show evidence this effect is not homogeneous in the social network but in fact, there is a large correlation between this effect and the social topological structure around a given individual. In particular, we show that social relations of hubs in a network are relatively weaker from the dynamical point than those that are poorer connected in the information diffusion process. Our results show the importance of the temporal patterns of communication when analyzing and modeling dynamical process on social networks.

  16. Losses of Humanity in Times of War: The Actions of Alternative Subjects of Justice

    Directory of Open Access Journals (Sweden)

    Julia Estela Monárrez


    Full Text Available This article discusses loss of humanity due to violence in Ciudad Juarez (2008–2014 and the actions of alternative subjects of justice – the organized civil society – seeking to address it. This paper resonates with theoretical currents of feminism and humanism, both of which have created a critical apparatus for thinking about social inequality in the context of life, death, and injustice. The discussion draws on the theoretical concepts of discourse societies, necropolitics, private government and actions. With this theoretical structure, the paper seeks to understand the political actions of eight civil society organizations aiming to recover the right to the body, to space and to be a political subject for a community shattered by violence. The paper argues that, through these actions, they helped to prevent crime, enhance public safety and stabilise a society suffering from continued violence due in large part to the war on drugs.

  17. Time dependent human hip joint lubrication for periodic motion with stochastic asymmetric density function. (United States)

    Wierzcholski, Krzysztof


    The present paper is concerned with the calculation of the human hip joint parameters for periodic, stochastic unsteady, motion with asymmetric probability density function for gap height. The asymmetric density function indicates that the stochastic probabilities of gap height decreasing are different in comparison with the probabilities of the gap height increasing. The models of asymmetric density functions are considered on the grounds of experimental observations. Some methods are proposed for calculation of pressure distributions and load carrying capacities for unsteady stochastic conditions in a super thin layer of biological synovial fluid inside the slide biobearing gap limited by a spherical bone acetabulum. Numerical calculations are performed in Mathcad 12 Professional Program, by using the method of finite differences. This method assures stability of numerical solutions of partial differential equations and gives proper values of pressure and load carrying capacity forces occurring in human hip joints.

  18. Timing of human protein evolution as revealed by massively parallel capture of Neandertal nuclear DNA sequences (United States)

    Burbano, Hernán A.; Hodges, Emily; Green, Richard E.; Briggs, Adrian W.; Krause, Johannes; Meyer, Matthias; Good, Jeffrey M.; Maricic, Tomislav; Johnson, Philipp L.F.; Xuan, Zhenyu; Rooks, Michelle; Bhattacharjee, Arindam; Brizuela, Leonardo; Albert, Frank W.; de la Rasilla, Marco; Fortea, Javier; Rosas, Antonio; Lachmann, Michael; Hannon, Gregory J.; Pääbo, Svante


    Whole genome shotgun sequencing is now possible for extinct organisms, as well as the targeted capture of specific regions. However, targeted resequencing of megabase sized parts of nuclear genomes has yet to be demonstrated for ancient DNA. Here we show that hybridization capture on microarrays can be used to generate large scale targeted data from Neandertal DNA even in the presence of ~99.8% microbial DNA. It is thus now possible to generate high quality data from large regions of the nuclear genome from Neandertals and other extinct organisms. Using this approach we have sequenced ~14,000 protein coding positions that have been inferred to have changed on the human lineage since the last common ancestor shared with chimpanzees. We identify 88 amino acid substitutions that have become fixed in all humans since the divergence from the Neandertals. PMID:20448179

  19. Rapid Increase in Neural Conduction Time in the Adult Human Auditory Brainstem Following Sudden Unilateral Deafness. (United States)

    Maslin, M R D; Lloyd, S K; Rutherford, S; Freeman, S; King, A; Moore, D R; Munro, K J


    Individuals with sudden unilateral deafness offer a unique opportunity to study plasticity of the binaural auditory system in adult humans. Stimulation of the intact ear results in increased activity in the auditory cortex. However, there are no reports of changes at sub-cortical levels in humans. Therefore, the aim of the present study was to investigate changes in sub-cortical activity immediately before and after the onset of surgically induced unilateral deafness in adult humans. Click-evoked auditory brainstem responses (ABRs) to stimulation of the healthy ear were recorded from ten adults during the course of translabyrinthine surgery for the removal of a unilateral acoustic neuroma. This surgical technique always results in abrupt deafferentation of the affected ear. The results revealed a rapid (within minutes) reduction in latency of wave V (mean pre = 6.55 ms; mean post = 6.15 ms; p < 0.001). A latency reduction was also observed for wave III (mean pre = 4.40 ms; mean post = 4.13 ms; p < 0.001). These reductions in response latency are consistent with functional changes including disinhibition or/and more rapid intra-cellular signalling affecting binaurally sensitive neurons in the central auditory system. The results are highly relevant for improved understanding of putative physiological mechanisms underlying perceptual disorders such as tinnitus and hyperacusis.

  20. Control of Dog Mediated Human Rabies in Haiti: No Time to Spare.

    Directory of Open Access Journals (Sweden)

    Max F Millien

    Full Text Available The American region has pledged to eliminate dog-mediated human rabies by 2015. As part of these efforts, we describe the findings of a desk and field mission review of Haiti's rabies situation by the end of 2013. While government officials recognize the importance of dog-mediated rabies control, and the national rabies plan adequately contemplates the basic capacities to that effect, regular and sufficient implementation, for example, of dog vaccination, is hampered by limited funding. Compounding insufficient funding and human resources, official surveillance figures do not accurately reflect the risk to the population, as evidenced by the large number of rabid dogs detected by focalized and enhanced surveillance activities conducted by the Ministry of Agriculture, Natural Resources and Rural Development (MARNDR and the Health and Population Ministry (MSPP with the technical assistance of the United States Centers for Disease Control and Prevention. Although international support is common, either in the form of on-the-ground technical support or donations of immunobiologicals, it is not comprehensive. In addition, there is limited coordination with MARNDR/MSPP and with other actors at the strategic or operational level due to human resources limitations. Given these findings, the 2015 elimination goal in the region is compromised by the situation in Haiti where control of the disease is not yet in sight despite the best efforts of the resolute national officials. More importantly, dog-mediated rabies is still a threat to the Haitian population.

  1. Control of Dog Mediated Human Rabies in Haiti: No Time to Spare. (United States)

    Millien, Max F; Pierre-Louis, Jocelyne B; Wallace, Ryan; Caldas, Eduardo; Rwangabgoba, Jean M; Poncelet, Jean L; Cosivi, Ottorino; Del Rio Vilas, Victor J


    The American region has pledged to eliminate dog-mediated human rabies by 2015. As part of these efforts, we describe the findings of a desk and field mission review of Haiti's rabies situation by the end of 2013. While government officials recognize the importance of dog-mediated rabies control, and the national rabies plan adequately contemplates the basic capacities to that effect, regular and sufficient implementation, for example, of dog vaccination, is hampered by limited funding. Compounding insufficient funding and human resources, official surveillance figures do not accurately reflect the risk to the population, as evidenced by the large number of rabid dogs detected by focalized and enhanced surveillance activities conducted by the Ministry of Agriculture, Natural Resources and Rural Development (MARNDR) and the Health and Population Ministry (MSPP) with the technical assistance of the United States Centers for Disease Control and Prevention. Although international support is common, either in the form of on-the-ground technical support or donations of immunobiologicals, it is not comprehensive. In addition, there is limited coordination with MARNDR/MSPP and with other actors at the strategic or operational level due to human resources limitations. Given these findings, the 2015 elimination goal in the region is compromised by the situation in Haiti where control of the disease is not yet in sight despite the best efforts of the resolute national officials. More importantly, dog-mediated rabies is still a threat to the Haitian population.

  2. Nutrigenetics and Nutrimiromics of the Circadian System: The Time for Human Health. (United States)

    Micó, Víctor; Díez-Ricote, Laura; Daimiel, Lidia


    Even though the rhythmic oscillations of life have long been known, the precise molecular mechanisms of the biological clock are only recently being explored. Circadian rhythms are found in virtually all organisms and affect our lives. Thus, it is not surprising that the correct running of this clock is essential for cellular functions and health. The circadian system is composed of an intricate network of genes interwined in an intrincated transcriptional/translational feedback loop. The precise oscillation of this clock is controlled by the circadian genes that, in turn, regulate the circadian oscillations of many cellular pathways. Consequently, variations in these genes have been associated with human diseases and metabolic disorders. From a nutrigenetics point of view, some of these variations modify the individual response to the diet and interact with nutrients to modulate such response. This circadian feedback loop is also epigenetically modulated. Among the epigenetic mechanisms that control circadian rhythms, microRNAs are the least studied ones. In this paper, we review the variants of circadian-related genes associated to human disease and nutritional response and discuss the current knowledge about circadian microRNAs. Accumulated evidence on the genetics and epigenetics of the circadian system points to important implications of chronotherapy in the clinical practice, not only in terms of pharmacotherapy, but also for dietary interventions. However, interventional studies (especially nutritional trials) that include chronotherapy are scarce. Given the importance of chronobiology in human health such studies are warranted in the near future.

  3. Development and validation of a real-time PCR for Chlamydia suis diagnosis in swine and humans.

    Directory of Open Access Journals (Sweden)

    Kristien De Puysseleyr

    Full Text Available Pigs are the natural host for Chlamydia suis, a pathogen which is phylogenetically highly related to the human pathogen C. trachomatis. Chlamydia suis infections are generally treated with tetracyclines. In 1998, tetracyline resistant C. suis strains emerged on U.S. pig farms and they are currently present in the Belgian, Cypriote, German, Israeli, Italian and Swiss pig industry. Infections with tetracycline resistant C. suis strains are mainly associated with severe reproductive failure leading to marked economical loss. We developed a sensitive and specific TaqMan probe-based C. suis real-time PCR for examining clinical samples of both pigs and humans. The analytical sensitivity of the real-time PCR is 10 rDNA copies/reaction without cross-amplifying DNA of other Chlamydia species. The PCR was successfully validated using conjunctival, pharyngeal and stool samples of slaughterhouse employees, as well as porcine samples from two farms with evidence of reproductive failure and one farm without clinical disease. Chlamydia suis was only detected in diseased pigs and in the eyes of humans. Positive humans had no clinical complaints. PCR results were confirmed by culture in McCoy cells. In addition, Chlamydia suis isolates were also examined by the tet(C PCR, designed for demonstrating the tetracycline resistance gene tet(C. The tet(C gene was only present in porcine C. suis isolates.

  4. Development and validation of a real-time PCR for Chlamydia suis diagnosis in swine and humans. (United States)

    De Puysseleyr, Kristien; De Puysseleyr, Leentje; Geldhof, Julie; Cox, Eric; Vanrompay, Daisy


    Pigs are the natural host for Chlamydia suis, a pathogen which is phylogenetically highly related to the human pathogen C. trachomatis. Chlamydia suis infections are generally treated with tetracyclines. In 1998, tetracyline resistant C. suis strains emerged on U.S. pig farms and they are currently present in the Belgian, Cypriote, German, Israeli, Italian and Swiss pig industry. Infections with tetracycline resistant C. suis strains are mainly associated with severe reproductive failure leading to marked economical loss. We developed a sensitive and specific TaqMan probe-based C. suis real-time PCR for examining clinical samples of both pigs and humans. The analytical sensitivity of the real-time PCR is 10 rDNA copies/reaction without cross-amplifying DNA of other Chlamydia species. The PCR was successfully validated using conjunctival, pharyngeal and stool samples of slaughterhouse employees, as well as porcine samples from two farms with evidence of reproductive failure and one farm without clinical disease. Chlamydia suis was only detected in diseased pigs and in the eyes of humans. Positive humans had no clinical complaints. PCR results were confirmed by culture in McCoy cells. In addition, Chlamydia suis isolates were also examined by the tet(C) PCR, designed for demonstrating the tetracycline resistance gene tet(C). The tet(C) gene was only present in porcine C. suis isolates.

  5. Time allocation shifts and pollutant exposure due to traffic congestion: an analysis using the national human activity pattern survey. (United States)

    Zhang, Kai; Batterman, Stuart A


    Traffic congestion increases air pollutant exposures of commuters and urban populations due to the increased time spent in traffic and the increased vehicular emissions that occur in congestion, especially "stop-and-go" traffic. Increased time in traffic also decreases time in other microenvironments, a trade-off that has not been considered in previous time activity pattern (TAP) analyses conducted for exposure assessment purposes. This research investigates changes in time allocations and exposures that result from traffic congestion. Time shifts were derived using data from the National Human Activity Pattern Survey (NHAPS), which was aggregated to nine microenvironments (six indoor locations, two outdoor locations and one transport location). After imputing missing values, handling outliers, and conducting other quality checks, these data were stratified by respondent age, employment status and period (weekday/weekend). Trade-offs or time-shift coefficients between time spent in vehicles and the eight other microenvironments were then estimated using robust regression. For children and retirees, congestion primarily reduced the time spent at home; for older children and working adults, congestion shifted the time spent at home as well as time in schools, public buildings, and other indoor environments. Changes in benzene and PM(2.5) exposure were estimated for the current average travel delay in the U.S. (9 min day(-1)) and other scenarios using the estimated time shifts coefficients, concentrations in key microenvironments derived from the literature, and a probabilistic analysis. Changes in exposures depended on the duration of the congestion and the pollutant. For example, a 30 min day(-1) travel delay was determined to account for 21+/-12% of current exposure to benzene and 14+/-8% of PM(2.5) exposure. The time allocation shifts and the dynamic approach to TAPs improve estimates of exposure impacts from congestion and other recurring events.

  6. Associative stimulation of the supraorbital nerve fails to induce timing-specific plasticity in the human blink reflex

    DEFF Research Database (Denmark)

    Zeuner, Kirsten E; Knutzen, Arne; Al-Ali, Asmaa;


    Associative high-frequency electrical stimulation (HFS) of the supraorbital nerve in five healthy individuals induced long-term potentiation (LTP)-like or depression (LTD)-like changes in the human blink reflex circuit according to the rules of spike timing-dependent plasticity (Mao and Evinger...... the orbicularis oculi muscles, HFS(LTP) induced excessive LTP-like associative plasticity relative to healthy controls, which was normalized after botulinum toxin (BTX) injections (Quartarone et al, 2006)....

  7. Biological properties of differently-aged human keratinocytes:population doubling time growth curve and cell cycle analysis

    Institute of Scientific and Technical Information of China (English)


    Objective To explore the biological properties of keratinocytes from differently-aged healthy human beings. Methods Keratinocytes from fetus,teenager and middle-aged groups were separated and cultured. The population doubling time (PDT) and cell growth curve in different cells were compared,and the cell cycles were analyzed by flow cytometry. Results ① In primary culture of keratinocytes,the adherence time in middle-aged group was longer than that in fetus and teenager groups. However,all cell morphology sh...

  8. Angiographic Features and Cardiovascular Risk Factors in Human Immunodeficiency Virus-Infected Patients With First-Time Acute Coronary Syndrome

    DEFF Research Database (Denmark)

    Knudsen, Andreas; Mathiasen, Anders B; Worck, R.H.;


    A matched cohort study was conducted comparing patients with first-time acute coronary syndromes infected with human immunodeficiency virus (HIV) to non-HIV-infected patients with and without diabetes matched for smoking, gender, and type of acute coronary syndrome who underwent first-time coronary...... angiography. A total of 48 HIV-infected patients were identified from a national database. Coronary angiography showed that the HIV-infected patients had significantly fewer lesions with classification B2/C than the 2 control groups (p...

  9. Effects of varied doses of psilocybin on time interval reproduction in human subjects. (United States)

    Wackermann, Jirí; Wittmann, Marc; Hasler, Felix; Vollenweider, Franz X


    Action of a hallucinogenic substance, psilocybin, on internal time representation was investigated in two double-blind, placebo-controlled studies: Experiment 1 with 12 subjects and graded doses, and Experiment 2 with 9 subjects and a very low dose. The task consisted in repeated reproductions of time intervals in the range from 1.5 to 5s. The effects were assessed by parameter kappa of the 'dual klepsydra' model of internal time representation, fitted to individual response data and intra-individually normalized with respect to initial values. The estimates kappa were in the same order of magnitude as in earlier studies. In both experiments, kappa was significantly increased by psilocybin at 90 min from the drug intake, indicating a higher loss rate of the internal duration representation. These findings are tentatively linked to qualitative alterations of subjective time in altered states of consciousness.

  10. Effects of alpha-glucosidase inhibitors on mouth to caecum transit time in humans.


    Ladas, S D; Frydas, A; Papadopoulos, A.; S. A. Raptis


    The alpha-glucosidase inhibitors acarbose and miglitol have been successfully used to control postprandial hyperglycaemia in diabetics. They probably work by slowing carbohydrate digestion and absorption, but their effect on mouth to caecum transit time has not been studied. The effect acarbose (100 mg), miglitol (100 mg), and placebo on mouth to caecum transit time (380 kcal breakfast with 20 g of lactulose) was investigated in 18 normal volunteers using breath hydrogen analysis. Both miglit...

  11. Effects of alpha-glucosidase inhibitors on mouth to caecum transit time in humans. (United States)

    Ladas, S D; Frydas, A; Papadopoulos, A; Raptis, S A


    The alpha-glucosidase inhibitors acarbose and miglitol have been successfully used to control postprandial hyperglycaemia in diabetics. They probably work by slowing carbohydrate digestion and absorption, but their effect on mouth to caecum transit time has not been studied. The effect acarbose (100 mg), miglitol (100 mg), and placebo on mouth to caecum transit time (380 kcal breakfast with 20 g of lactulose) was investigated in 18 normal volunteers using breath hydrogen analysis. Both miglitol and acarbose significantly increased breath hydrogen excretion (F2,34 = 6.31, p = 0.005) and shortened the mouth to caecum transit time (F2,34 = 3.49, p = 0.04) after breakfast compared with placebo. There was a significant negative correlation between breath hydrogen excretion and mouth to caecum transit time suggesting that with shorter transit times significantly more carbohydrates were spilled into the colon. These results indicate that alpha-glucosidase inhibitors accelerate mouth to caecum transit time by inducing carbohydrate malabsorption.

  12. Nanoparticle Albumin Bound Paclitaxel in the Treatment of Human Cancer: Nanodelivery Reaches Prime-Time?

    Directory of Open Access Journals (Sweden)

    Iole Cucinotto


    Full Text Available Nanoparticle albumin bound paclitaxel (nab-paclitaxel represents the first nanotechnology-based drug in cancer treatment. We discuss the development of this innovative compound and report the recent changing-practice results in breast and pancreatic cancer. A ground-breaking finding is the demonstration that nab-paclitaxel can not only enhance the activity and reduce the toxicity of chromophore-diluted compound, but also exert activity in diseases considered refractory to taxane-based treatment. This is the first clinical demonstration of major activity of nanotechnologically modified drugs in the treatment of human neoplasms.

  13. Nanoparticle Albumin Bound Paclitaxel in the Treatment of Human Cancer: Nanodelivery Reaches Prime-Time? (United States)

    Cucinotto, Iole; Fiorillo, Lucia; Gualtieri, Simona; Arbitrio, Mariamena; Ciliberto, Domenico; Staropoli, Nicoletta; Grimaldi, Anna; Luce, Amalia; Tassone, Pierfrancesco; Caraglia, Michele; Tagliaferri, Pierosandro


    Nanoparticle albumin bound paclitaxel (nab-paclitaxel) represents the first nanotechnology-based drug in cancer treatment. We discuss the development of this innovative compound and report the recent changing-practice results in breast and pancreatic cancer. A ground-breaking finding is the demonstration that nab-paclitaxel can not only enhance the activity and reduce the toxicity of chromophore-diluted compound, but also exert activity in diseases considered refractory to taxane-based treatment. This is the first clinical demonstration of major activity of nanotechnologically modified drugs in the treatment of human neoplasms. PMID:23738077

  14. Time-Dependent Electrical Properties of Human Nail Upon Hydration In Vivo



    The objectives of this study were to investigate the effects of hydration and solution ion concentration on the electrical properties of human nail in vivo and compare these in vivo results with those in vitro. In vivo electrical resistance measurements on the nail were conducted with a three-electrode system in phosphate buffered saline of 0.01–0.6 M. The effect of electric current on nail resistance and possible adverse effects were studied under 1.5- and 9-V iontophoresis in vivo. The elec...

  15. Model cortical association fields account for the time course and dependence on target complexity of human contour perception.

    Directory of Open Access Journals (Sweden)

    Vadas Gintautas


    Full Text Available Can lateral connectivity in the primary visual cortex account for the time dependence and intrinsic task difficulty of human contour detection? To answer this question, we created a synthetic image set that prevents sole reliance on either low-level visual features or high-level context for the detection of target objects. Rendered images consist of smoothly varying, globally aligned contour fragments (amoebas distributed among groups of randomly rotated fragments (clutter. The time course and accuracy of amoeba detection by humans was measured using a two-alternative forced choice protocol with self-reported confidence and variable image presentation time (20-200 ms, followed by an image mask optimized so as to interrupt visual processing. Measured psychometric functions were well fit by sigmoidal functions with exponential time constants of 30-91 ms, depending on amoeba complexity. Key aspects of the psychophysical experiments were accounted for by a computational network model, in which simulated responses across retinotopic arrays of orientation-selective elements were modulated by cortical association fields, represented as multiplicative kernels computed from the differences in pairwise edge statistics between target and distractor images. Comparing the experimental and the computational results suggests that each iteration of the lateral interactions takes at least [Formula: see text] ms of cortical processing time. Our results provide evidence that cortical association fields between orientation selective elements in early visual areas can account for important temporal and task-dependent aspects of the psychometric curves characterizing human contour perception, with the remaining discrepancies postulated to arise from the influence of higher cortical areas.

  16. Rapid telomere motions in live human cells analyzed by highly time-resolved microscopy

    Directory of Open Access Journals (Sweden)

    Wang Xueying


    Full Text Available Abstract Background Telomeres cap chromosome ends and protect the genome. We studied individual telomeres in live human cancer cells. In capturing telomere motions using quantitative imaging to acquire complete high-resolution three-dimensional datasets every second for 200 seconds, telomere dynamics were systematically analyzed. Results The motility of individual telomeres within the same cancer cell nucleus was widely heterogeneous. One class of internal heterochromatic regions of chromosomes analyzed moved more uniformly and showed less motion and heterogeneity than telomeres. The single telomere analyses in cancer cells revealed that shorter telomeres showed more motion, and the more rapid telomere motions were energy dependent. Experimentally increasing bulk telomere length dampened telomere motion. In contrast, telomere uncapping, but not a DNA damaging agent, methyl methanesulfonate, significantly increased telomere motion. Conclusion New methods for seconds-scale, four-dimensional, live cell microscopic imaging and data analysis, allowing systematic tracking of individual telomeres in live cells, have defined a previously undescribed form of telomere behavior in human cells, in which the degree of telomere motion was dependent upon telomere length and functionality.

  17. From time series analysis to a biomechanical multibody model of the human eye

    Energy Technology Data Exchange (ETDEWEB)

    Pascolo, P. [Dipartimento di Ingegneria Civile, Universita di Udine, Udine (Italy); Dipartimento di Bioingegneria, CISM, Udine (Italy)], E-mail:; Carniel, R. [Dipartimento di Georisorse e Territorio, Universita di Udine, Udine (Italy)], E-mail:


    A mechanical model of the human eye is presented aimed at estimating the level of muscular activation. The applicability of the model in the biomedical field is discussed. Human eye movements studied in the laboratory are compared with the ones produced by a virtual eye described in kinematical terms and subject to the dynamics of six actuators, as many as the muscular systems devoted to the eye motion control. The definition of an error function between the experimental and the numerical response and the application of a suitable law that links activation and muscular force are at the base of the proposed methodology. The aim is the definition of a simple conceptual tool that could help the specialist in the diagnosis of potential physiological disturbances of saccadic and nystagmic movements but can also be extended in a second phase when more sophisticated data become available. The work is part of a collaboration between the Functional Mechanics Laboratory of the University and the Neurophysiopatology Laboratory of the 'S. Maria della Misericordia' Hospital in Udine, Italy.

  18. Timing of human preimplantation embryonic development is confounded by embryo origin

    DEFF Research Database (Denmark)

    Kirkegaard, Kirstine Kjær; Sundvall Germeys, Linda Karin M; Erlandsen, M.


    embryos from one patient as independent observations, and only very few studies that evaluate the influence from patient- and treatment-related factors on timing of development or time-lapse parameters as predictors of viability have controlled for confounding, which implies a high risk of overestimating...... these results may not be generalized to all infertile women. Not all patient-related factors were investigated. WIDER IMPLICATIONS OF THE FINDINGS Our findings underline the importance of treating embryos as dependent observations and suggest a high risk of patient-based confounding in retrospective studies....... The impact of confounders and the embryo origin needs to be addressed in order to apply appropriate statistical models in observational studies. Furthermore, this observation emphasizes the need for RCTs for evaluating use of time-lapse parameters for embryo selection. STUDY FUNDING/COMPETING INTERESTS...

  19. Real-time Human Activity Recognition using a Body Sensor Network

    DEFF Research Database (Denmark)

    Wang, Liang; Gu, Tao; Chen, Hanhua


    . In this model, we first use a fast, lightweight template matching algorithm to detect gestures at the sensor node level, and then use a discriminative pattern based real-time algorithm to recognize high-level activities at the portable device level. We evaluate our algorithms over a real-world dataset......Real-time activity recognition using body sensor networks is an important and challenging task and it has many potential applications. In this paper, we propose a realtime, hierarchical model to recognize both simple gestures and complex activities using a wireless body sensor network....... The results show that the proposed system not only achieves good performance (an average precision of 94.9%, an average recall of 82.5%, and an average real-time delay of 5.7 seconds), but also significantly reduces the network communication cost by 60.2%....

  20. Human mobility and time spent at destination: Impact on spatial epidemic spreading

    CERN Document Server

    Poletto, Chiara; Colizza, Vittoria


    Host mobility plays a fundamental role in the spatial spread of infectious diseases. Previous theoretical works based on the integration of network theory into the metapopulation framework have shown that the heterogeneities that characterize real mobility networks favor the propagation of epidemics. Nevertheless, the studies conducted so far assumed the mobility process to be either Markovian or non-Markovian with a fixed traveling time scale. Available statistics however show that the time spent by travelers at destination is characterized by wide fluctuations, ranging between a single day up to several months. Such varying length of stay crucially affects the chance and duration of mixing events among hosts and may therefore have a strong impact on the spread of an emerging disease. Here, we present an analytical and computational study of epidemic processes on a complex subpopulation network where travelers have memory of their origin and spend a heterogeneously distributed time interval at their destinat...

  1. Long-Time Autocorrelation Function of ECG Signal for Healthy versus Diseased Human Heart (United States)

    Kulessa, B.; Srokowski, T.; Drozdz, S.


    Long-time ECG time series for healthy subjects and diseased patients are analysed. In the first case, the power spectrum has the 1/f shape in a broad frequency range. However, its behaviour for very low and very high frequency is different and the entire spectrum is integrable. For patients with post-ictal heart rate oscillation in partial epilepsy the 1/f noise is not present. We determine the power spectrum by evaluating the Fourier transform of the signal in both cases and calculate the signal autocorrelation function. It falls with time faster for diseased patients then for healthy people. The presented method can serve as a diagnostic tool of some heart diseases.

  2. Development of real-time PCR array for simultaneous detection of eight human blood-borne viral pathogens.

    Directory of Open Access Journals (Sweden)

    Natalia Pripuzova

    Full Text Available BACKGROUND: Real-time PCR array for rapid detection of multiple viral pathogens should be highly useful in cases where the sample volume and the time of testing are limited, i.e. in the eligibility testing of tissue and organ donors. FINDINGS: We developed a real-time PCR array capable of simultaneously detecting eight human viral pathogens: human immunodeficiency virus types 1 and 2 (HIV-1 and -2, hepatitis B virus (HBV, hepatitis C virus (HCV, human T-cell leukemia virus-1 and -2 (HTLV-1 and -2, vaccinia virus (VACV and West Nile virus (WNV. One hundred twenty (120 primers were designed using a combination of bioinformatics approaches, and, after experimental testing, 24 primer sets targeting eight viral pathogens were selected to set up the array with SYBR Green chemistry. The specificity and sensitivity of the virus-specific primer sets selected for the array were evaluated using analytical panels with known amounts of viruses spiked into human plasma. The array detected: 10 genome equivalents (geq/ml of HIV-2 and HCV, 50 geq of HIV-1 (subtype B, HBV (genotype A and WNV. It detected 100-1,000 geq/ml of plasma of HIV-1 subtypes (A - G, group N and CRF (AE and AG isolates. Further evaluation with a panel consisting of 28 HIV-1 and HIV-2 clinical isolates revealed no cross-reactivity of HIV-1 or HIV-2 specific primers with another type of HIV. All 28 viral isolates were identified with specific primer sets targeting the most conserved genome areas. The PCR array correctly identified viral infections in a panel of 17 previously quantified clinical plasma samples positive for HIV-1, HCV or HBV at as low as several geq per PCR reaction. CONCLUSIONS: The viral array described here demonstrated adequate performance in the testing of donors' clinical samples. Further improvement in its sensitivity for the broad spectrum of HIV-1 subtypes is under development.

  3. Refining Time-Activity Classification of Human Subjects Using the Global Positioning System (United States)

    Hu, Maogui; Li, Wei; Li, Lianfa; Houston, Douglas; Wu, Jun


    Background Detailed spatial location information is important in accurately estimating personal exposure to air pollution. Global Position System (GPS) has been widely used in tracking personal paths and activities. Previous researchers have developed time-activity classification models based on GPS data, most of them were developed for specific regions. An adaptive model for time-location classification can be widely applied to air pollution studies that use GPS to track individual level time-activity patterns. Methods Time-activity data were collected for seven days using GPS loggers and accelerometers from thirteen adult participants from Southern California under free living conditions. We developed an automated model based on random forests to classify major time-activity patterns (i.e. indoor, outdoor-static, outdoor-walking, and in-vehicle travel). Sensitivity analysis was conducted to examine the contribution of the accelerometer data and the supplemental spatial data (i.e. roadway and tax parcel data) to the accuracy of time-activity classification. Our model was evaluated using both leave-one-fold-out and leave-one-subject-out methods. Results Maximum speeds in averaging time intervals of 7 and 5 minutes, and distance to primary highways with limited access were found to be the three most important variables in the classification model. Leave-one-fold-out cross-validation showed an overall accuracy of 99.71%. Sensitivities varied from 84.62% (outdoor walking) to 99.90% (indoor). Specificities varied from 96.33% (indoor) to 99.98% (outdoor static). The exclusion of accelerometer and ambient light sensor variables caused a slight loss in sensitivity for outdoor walking, but little loss in overall accuracy. However, leave-one-subject-out cross-validation showed considerable loss in sensitivity for outdoor static and outdoor walking conditions. Conclusions The random forests classification model can achieve high accuracy for the four major time

  4. Refined Assessment of Human PM2.5 Exposure in Chinese city by Incorporating Time-activity Data (United States)

    Zhu, W.; Wang, H.


    Since urban residents tend to spend a majority of time indoors throughout a day, it has been widely discussed in recent years, whether fixed-site monitoring PM2.5 ambient concentration is feasible as a surrogate of human PM2.5 exposure. Comprehensive understanding of residents' daily time-activity patterns (TAP) and possible indoor behavior are urgently needed to perform a more accurate estimate of human PM2.5exposure, especially in China, where is experiencing rapid urbanization.Field surveys of TAP were carried out in a Chinese city of Suzhou from 2014 to 2015 to evaluate PM2.5 exposure in various micro-environments (ME, e.g., residence, outdoors and in-transit). We gathered and analyzed urban residents' seasonal time-activity data using 24h retrospective time-location diaries, as well as diversified exposure-related indoor information (e.g. ventilation, environment tobacco smoke and cooking). PM2.5exposure is calculated through the incorporation of ambient concentration data, modified indoor/outdoor empirical functions and TAP. The spatial distributions of TAP-based exposure and static-population based exposure are also compared.Residents in Suzhou urban area spend over 65% of time at home and 90% indoors. There are significant temporal (season, day type) and socioeconomic differences (gender, age, education, living alone, having children at home, employment status, etc.) of time-activity distributions, which makes the sum of PM2.5 ME exposure differs notably from static-population based ambient exposure. People prefer to spend more time at home both in winter (Pinverse distance squared weighting method is not ideally performed and may be less representative of the ambient PM2.5characteristics than satellite data.

  5. Effect of oxygen concentration on human embryo development evaluated by time-lapse monitoring

    DEFF Research Database (Denmark)

    Ingerslev, Hans Jakob; Hindkjær, Johnny Juhl; Kirkegaard, Kirstine


    by using a statistical programme (STATA) to random choose half of the embryos from each patient, generating group 2 consisting of 98 IVF embryos from 21 patients and group 3 consisting of 109 ICSI embryos from 38 patients. Automated image recording was performed every 20 min. Key events such as time...

  6. Modeling Real-Time Human-Automation Collaborative Scheduling of Unmanned Vehicles (United States)


    situation with unbounded indeterminacy (Russell & Norvig , 2003), depending on the problem formulation, where the set of possible preconditions or...find an optimal solution in polynomial time (Russell & Norvig , 2003). Also, the objective function for this optimization may be non-convex, meaning...environments are likely situations with unbounded indeterminacy (Russell & Norvig , 2003). The set of possible preconditions or effects either is unknown

  7. Linguistic embodiment and verbal constraints: human cognition and the scales of time

    DEFF Research Database (Denmark)

    Cowley, Stephen


    Using radical embodied cognitive science, the paper offers the hypothesis that language is symbiotic: its agent-environment dynamics arise as linguistic embodiment is managed under verbal constraints. As a result, co-action grants human agents the ability to use a unique form of phenomenal...... experience. In defense of the hypothesis, I stress how linguistic embodiment enacts thinking: accordingly, I present auditory and acoustic evidence from 750 ms of mother-daughter talk, first, in fine detail and, then, in narrative mode. As the parties attune, they use a dynamic field to co-embody speech......, linguistic symbiosis grants access to diachronic resources. On this distributed-ecological view, language can thus be redefined as: “activity in which wordings play a part.”...

  8. The impact of early human data on clinical development: there is time to win. (United States)

    Swart, Piet; Lozac'h, Frederic; Simon, Marjorie; van Duijn, Esther; Vaes, Wouter H J


    Modern accelerator mass spectrometry (AMS) methods enable the routine application of this technology in drug development. By the administration of a (14)C-labelled microdose or microtrace, pharmacokinetic (PK) data, such as mass balance, metabolite profiling, and absolute bioavailability (AB) data, can be generated easier, faster, and at lower costs. Here, we emphasize the advances and impact of this technology for pharmaceutical companies. The availability of accurate intravenous (iv) PK and human absorption, distribution, metabolism, and excretion (ADME) information, even before or during Phase I trials, can improve the clinical development plan. Moreover, applying the microtrace approach during early clinical development might impact the number of clinical pharmacology and preclinical safety pharmacology studies required, and shorten the overall drug discovery program.

  9. Failed drug discovery in psychiatry: time for human genome-guided solutions. (United States)

    Papassotiropoulos, Andreas; de Quervain, Dominique J F


    Our knowledge about the molecular and neural mechanisms of emotional and cognitive processes has increased exponentially in the past decades. Unfortunately, there has been no translation of this knowledge into the development of novel and improved pharmacological treatments for psychiatric disorders. We comment on some of the reasons for failed drug discovery in psychiatry, particularly on the use of ill-suited disease models and on the use of diagnostic constructs unrelated to the underlying biological mechanisms. Furthermore, we argue that the use of human genetic findings together with biologically informed phenotypes and advanced data-mining methodology will catalyze the identification of promising drug targets and, finally, will lead to improved therapeutic outcomes.

  10. Electronic tracking of human resource skills and knowledge, just in time training, manageable due diligence

    Energy Technology Data Exchange (ETDEWEB)

    Kolodziej, M.A. [Quick Test International Inc., (Canada). Canadian Technology Human Resource Board; Baker, O. [KeySpan Energy Canada, Calgary, AB (Canada)


    KeySpan Energy Canada is in the process of obtaining recognition of various occupational profiles including pipeline operators, inspectors, and field and plant operators from various certifying organizations. The process of allowing individuals to obtain certification is recognized by Canadian Technology Human Resources Board as a step towards national standards for technologists and technicians. Proven competency is a must for workers in todays oil industry in response to increasingly stringent government safety regulations, environmental concerns and high public scrutiny. Quick Test international Inc. has developed a management tool in collaboration with end users at KeySpan Energy Canada. It is an electronic, Internet based competency tool for tracking personal competencies and maintaining continued competency. Response to the tool has been favourable. 2 refs., 4 figs.

  11. Sleep deprivation influences diurnal variation of human time perception with prefrontal activity change: a functional near-infrared spectroscopy study.

    Directory of Open Access Journals (Sweden)

    Takahiro Soshi

    Full Text Available Human short-time perception shows diurnal variation. In general, short-time perception fluctuates in parallel with circadian clock parameters, while diurnal variation seems to be modulated by sleep deprivation per se. Functional imaging studies have reported that short-time perception recruits a neural network that includes subcortical structures, as well as cortical areas involving the prefrontal cortex (PFC. It has also been reported that the PFC is vulnerable to sleep deprivation, which has an influence on various cognitive functions. The present study is aimed at elucidating the influence of PFC vulnerability to sleep deprivation on short-time perception, using the optical imaging technique of functional near-infrared spectroscopy. Eighteen participants performed 10-s time production tasks before (at 21:00 and after (at 09:00 experimental nights both in sleep-controlled and sleep-deprived conditions in a 4-day laboratory-based crossover study. Compared to the sleep-controlled condition, one-night sleep deprivation induced a significant reduction in the produced time simultaneous with an increased hemodynamic response in the left PFC at 09:00. These results suggest that activation of the left PFC, which possibly reflects functional compensation under a sleep-deprived condition, is associated with alteration of short-time perception.

  12. Time course and spacial distribution of UV effects on human skin in organ culture. (United States)

    Mori, Eiichiro; Takahashi, Akihisa; Kitagawa, Kou; Kakei, Saki; Tsujinaka, Daiki; Unno, Megumi; Nishikawa, Shoko; Ohnishi, Ken; Hatoko, Mitsuo; Murata, Norio; Watanabe, Masakatsu; Furusawa, Yoshiya; Ohnishi, Takeo


    Apoptosis plays an important role in eliminating cells from populations when cells have been exposed to UV irradiation and damaged. Studies of cells in culture have provided some details of the mechanisms involved when stress response genes act after exposure to UV irradiation and other environmental stresses. However, little is known about the responses of intact sections of human skin growing in organ culture to UV irradiation. In the work reported here, it was found that the response of organ-cultured human skin after exposure to UV irradiation is different than the response of cultured cells. At wavelengths below 300 nm, the action spectrum obtained from organ-cultured skin samples showed a lower sensitivity than that observed at 300 nm, indicating that the overlying stratum corneum and upper epidermal cell layers had probably caused a selective absorption of incident UV radiation at some wavelengths. At 3 hours after UV irradiation, p53 was phosphorylated at Ser 15 and Ser 46, and accumulated in the cell nuclei, notably after exposure to 280-320 nm wavelengths. Accumulations of Bax, active Caspase-3 and cleaved PARP were detected in apoptotic cells at 24 hours post-exposure, along with a reduction of Bcl-2 levels, notably after exposure to 300-365 nm light. This difference in apoptotic responses may result from the characteristics of the different irradiation wavelengths used, and from details in the skin's structure. The data obtained in this study using an organ-culture system utilized direct measurements of the biological effects of different wavelengths of UV lights.

  13. Measurement of vascular water transport in human subjects using time-resolved pulsed arterial spin labelling. (United States)

    Bibic, Adnan; Knutsson, Linda; Schmidt, Anders; Henningsson, Erik; Månsson, Sven; Abul-Kasim, Kasim; Åkeson, Jonas; Gunther, Matthias; Ståhlberg, Freddy; Wirestam, Ronnie


    Most approaches to arterial spin labelling (ASL) data analysis aim to provide a quantitative measure of the cerebral blood flow (CBF). This study, however, focuses on the measurement of the transfer time of blood water through the capillaries to the parenchyma (referred to as the capillary transfer time, CTT) as an alternative parameter to characterise the haemodynamics of the system. The method employed is based on a non-compartmental model, and no measurements need to be added to a common time-resolved ASL experiment. Brownian motion of labelled spins in a potential was described by a one-dimensional general Langevin equation as the starting point, and as a Fokker-Planck differential equation for the averaged distribution of labelled spins at the end point, which takes into account the effects of flow and dispersion of labelled water by the pseudorandom nature of the microvasculature and the transcapillary permeability. Multi-inversion time (multi-TI) ASL data were acquired in 14 healthy subjects on two occasions in a test-retest design, using a pulsed ASL sequence and three-dimensional gradient and spin echo (3D-GRASE) readout. Based on an error analysis to predict the size of a region of interest (ROI) required to obtain reasonably precise parameter estimates, data were analysed in two relatively large ROIs, i.e. the occipital lobe (OC) and the insular cortex (IC). The average values of CTT in OC were 260 ± 60 ms in the first experiment and 270 ± 60 ms in the second experiment. The corresponding IC values were 460 ± 130 ms and 420 ± 139 ms, respectively. Information related to the water transfer time may be important for diagnostics and follow-up of cerebral conditions or diseases characterised by a disrupted blood-brain barrier or disturbed capillary blood flow.

  14. Timing and causes of North African wet phases during the last glacial period and implications for modern human migration (United States)

    Hoffmann, Dirk L.; Rogerson, Mike; Spötl, Christoph; Luetscher, Marc; Vance, Derek; Osborne, Anne H.; Fello, Nuri M.; Moseley, Gina E.


    We present the first speleothem-derived central North Africa rainfall record for the last glacial period. The record reveals three main wet periods at 65-61 ka, 52.5-50.5 ka and 37.5-33 ka that lead obliquity maxima and precession minima. We find additional minor wet episodes that are synchronous with Greenland interstadials. Our results demonstrate that sub-tropical hydrology is forced by both orbital cyclicity and North Atlantic moisture sources. The record shows that after the end of a Saharan wet phase around 70 ka ago, North Africa continued to intermittently receive substantially more rainfall than today, resulting in favourable environmental conditions for modern human expansion. The encounter and subsequent mixture of Neanderthals and modern humans – which, on genetic evidence, is considered to have occurred between 60 and 50 ka – occurred synchronously with the wet phase between 52.5 and 50.5 ka. Based on genetic evidence the dispersal of modern humans into Eurasia started less than 55 ka ago. This may have been initiated by dry conditions that prevailed in North Africa after 50.5 ka. The timing of a migration reversal of modern humans from Eurasia into North Africa is suggested to be coincident with the wet period between 37.5 and 33 ka.

  15. Functional high-resolution time-course expression analysis of human embryonic stem cells undergoing cardiac induction

    Directory of Open Access Journals (Sweden)

    Ilaria Piccini


    Full Text Available Cardiac induction of human embryonic stem cells (hESCs is a process bearing increasing medical relevance, yet it is poorly understood from a developmental biology perspective. Anticipated technological progress in deriving stably expandable cardiac precursor cells or in advancing cardiac subtype specification protocols will likely require deeper insights into this fascinating system. Recent improvements in controlling hESC differentiation now enable a near-homogeneous induction of the cardiac lineage. This is based on an optimized initial stimulation of mesoderm-inducing signaling pathways such as Activin and/or FGF, BMP, and WNT, followed by WNT inhibition as a secondary requirement. Here, we describe a comprehensive data set based on varying hESC differentiation conditions in a systematic manner and recording high-resolution differentiation time-courses analyzed by genome-wide expression profiling (GEO accession number GSE67154. As a baseline, hESCs were differentiated into cardiomyocytes under optimal conditions. Moreover, in additional time-series, individual signaling factors were withdrawn from the initial stimulation cocktail to reveal their specific roles via comparison to the standard condition. Hence, this data set presents a rich resource for hypothesis generation in studying human cardiac induction, as we reveal numbers of known as well as uncharacterized genes prominently marking distinct intermediate stages in the process. These data will also be useful for identifying putative cardiac master regulators in the human system as well as for characterizing expandable cardiac stem cells.

  16. Far-infrared in vivo signature of human skin by terahertz time-domain spectroscopy using waveform rebuilding technology (United States)

    Li, Xiangjun; Liu, Jianjun; Hong, Zhi


    We present terahertz time-domain spectroscopy characterization of human thumb skin in reflection measurement mode with waveform rebuilding technology. The thumb skin contacts one side of a high resistive silicon wafer with 3 mm thick, and here is an orthogonal incidence of the THz pulse putting on the other side of the wafer. We rebuild the time domain signal from silicon-skin interface as a sample signal by the signal from the air-silicon interface as a reference and a Fresnel transform function between them. Material parameters were calculated by minimizing the difference between the measured sample waveform and a rebuilt one in time domain. The double Debye model parameters for the thumb skin were fitted. The method has potential to research complex layer-structures in skin if a precise model is built.

  17. A New Profile Shape Matching Stereovision Algorithm for Real-time Human Pose and Hand Gesture Recognition

    Directory of Open Access Journals (Sweden)

    Dong Zhang


    Full Text Available This paper presents a new profile shape matching stereovision algorithm that is designed to extract 3D information in real time. This algorithm obtains 3D information by matching profile intensity shapes of each corresponding row of the stereo image pair. It detects the corresponding matching patterns of the intensity profile rather than the intensity values of individual pixels or pixels in a small neighbourhood. This approach reduces the effect of the intensity and colour variations caused by lighting differences. As with all real-time vision algorithms, there is always a trade-off between accuracy and processing speed. This algorithm achieves a balance between the two to produce accurate results for real-time applications. To demonstrate its performance, the proposed algorithm is tested for human pose and hand gesture recognition to control a smart phone and an entertainment system.

  18. Large-scale time-lapse microscopy of Oct4 expression in human embryonic stem cell colonies. (United States)

    Bhadriraju, Kiran; Halter, Michael; Amelot, Julien; Bajcsy, Peter; Chalfoun, Joe; Vandecreme, Antoine; Mallon, Barbara S; Park, Kye-Yoon; Sista, Subhash; Elliott, John T; Plant, Anne L


    Identification and quantification of the characteristics of stem cell preparations is critical for understanding stem cell biology and for the development and manufacturing of stem cell based therapies. We have developed image analysis and visualization software that allows effective use of time-lapse microscopy to provide spatial and dynamic information from large numbers of human embryonic stem cell colonies. To achieve statistically relevant sampling, we examined >680 colonies from 3 different preparations of cells over 5days each, generating a total experimental dataset of 0.9 terabyte (TB). The 0.5 Giga-pixel images at each time point were represented by multi-resolution pyramids and visualized using the Deep Zoom Javascript library extended to support viewing Giga-pixel images over time and extracting data on individual colonies. We present a methodology that enables quantification of variations in nominally-identical preparations and between colonies, correlation of colony characteristics with Oct4 expression, and identification of rare events.

  19. The Hybrid Design: Integrating the Human and Technical Components of Just-In-Time Knowledge Management Systems

    Directory of Open Access Journals (Sweden)

    Nabie Y. Conteh


    Full Text Available This paper explores the right balance of human and technical resources in the design of Just-in-Time knowledge delivery. It also examines and analyzes the case study: “Teltech: The business of Knowledge Management” by Davenport. It further attempts to depict the characteristics of the hybrid. The paper describes how the hybrid can be applied to Just-In-Time knowledge delivery. It also seeks to analyze and explore its interplay with knowledge splits with a view to designing Just-In- Time Knowledge Management. These include: “tacit versus explicit knowledge”, “in-process” versus “after action” documentation, “process-centered versus product-centered approach”, “knowledge versus information” and the “culture of sharing versus hoarding.”

  20. Prostitution in times of economic crisis: effects, human agency and societal responses


    Persak, Nina


    In times of economic hardship both formal and informal economy are affected. The paper begins by inspecting the characteristics of the informal economy, some of which may act as disadvantages as well as advantages, addressing prostitution as one type of informal economic activity. Looking at the available data, we then observe in which way and to what extent the current global financial crisis has affected the informal economy, in general, and prostitution, in particular. Next, we examine the...

  1. Time course production of urolithins from ellagic acid by human gut microbiota. (United States)

    García-Villalba, Rocío; Beltrán, David; Espín, Juan Carlos; Selma, María Victoria; Tomás-Barberán, Francisco A


    Ellagic acid (EA) is converted to urolithins by gut microbiota. Urolithins have beneficial biological effects in humans, but differences in urolithin production capacity among individuals have been shown. Therefore, the identification of the urolithin production pathways and the microorganisms implicated is of high interest. EA was incubated with gut microbiota from two volunteers able to produce urolithins but with different in vivo urolithin profiles (urolithin A and isourolithin A producers). The metabolic capabilities observed in vivo were retained in vitro. Both individuals showed a much higher abundance of Clostridium leptum group of Firmicutes phylum than Bacteroides / Prevotella . EA was either dissolved in DMSO or suspended in water. DMSO increased EA solubility but decreased urolithin production rate due to a delay in growth of some microbial groups, principally, Clostridium coccoides . This allowed the detection of catabolic intermediates [urolithins M-5, M-6, M-7, C, and 2,3,8,10-tetrahydroxy urolithin (urolithin E)]. Bacteria from C. coccoides group (or genera co-occurring in vivo with this group) seem to be involved in production of different urolithins.

  2. Progressive human immunodeficiency virus-associated vasculopathy: time to revise antiretroviral therapy guidelines? (United States)

    Ntusi, N B A; Taylor, D; Naidoo, N G; Mendelson, M


    Cardiovascular abnormalities were appreciated early in the epidemic of the acquired immunodeficiency syndrome (AIDS), even before the aetiological agent, human immunodeficiency virus (HIV) was isolated and characterised. The aetiology and pathogenesis of cardiovascular disease in HIV infection is still the subject of intense speculation, and is likely multi-factorial. HIV affects every aspect of the cardiac axis, causing pericarditis, myocarditis, cardiomyopathy, coronary artery disease and microvascular dysfunction, valvular heart disease, pulmonary vascular disease and pulmonary hypertension, stroke and peripheral vascular disease. HIV-associated vasculopathy is an increasingly recognised clinical entity, causing high morbidity and increasing mortality in southern Africa, particularly from stroke and cardiovascular disease. HIV causes disease of the vascular tree, either by a direct effect on vascular or perivascular tissue, or indirectly via immune complex-mediated mechanisms, associated opportunistic infections and malignancies. As a result, highly active antiretroviral therapy (HAART) may have an important role in controlling disease progression. We report a case of histologically defined primary HIV vasculopathy in which the chance to start HAART was initially missed and in which the patient progressed to require bilateral amputations, but obtained disease quiescence upon commencement of HAART.

  3. Molecular study on human tuberculosis in three geographically distinct and time delineated populations from ancient Egypt. (United States)

    Zink, A R; Grabner, W; Reischl, U; Wolf, H; Nerlich, A G


    We describe the molecular identification of human tuberculosis (TB) from vertebral bone tissue samples from three different populations of ancient Egypt. The specimens were obtained from the predynastic to early dynastic necropolis of Abydos (7 individuals, c. 3500-2650 B.C.), from a Middle Kingdom to Second Intermediate Period tomb of the necropolis of Thebes-West (37. c. 2100-1550 B.C.) and from five further Theban tombs used in the New Kingdom and the Late Period (39, c. 1450-500 B.C.). A total of 18 cases tested positive for the presence of ancient DNA (aDNA) of the M. tuberculosis complex. Out of the 9 cases with typical macromorphological signs of tuberculous spondylitis, 6 were positive for mycobacterial aDNA (66.7%). Of 24 cases with non-specific pathological alterations, 5 provided a positive result (20.8%). In 50 cases of normally appearing vertebral bones 7 tested positive (14.0%). There were only minor differences in the frequencies between the three populations. These data strongly support the notion that tuberculosis was present and prevalent in ancient Egypt since very early periods of this civilization. The unexpectedly high rate of mycobacterial aDNA in normal bone samples is presumably due to a pre- to perimortal systemic spread of the bacteria and indicates a generalized infection by M. tuberculosis.

  4. ASAR15, A cis-acting locus that controls chromosome-wide replication timing and stability of human chromosome 15.

    Directory of Open Access Journals (Sweden)

    Nathan Donley


    Full Text Available DNA replication initiates at multiple sites along each mammalian chromosome at different times during each S phase, following a temporal replication program. We have used a Cre/loxP-based strategy to identify cis-acting elements that control this replication-timing program on individual human chromosomes. In this report, we show that rearrangements at a complex locus at chromosome 15q24.3 result in delayed replication and structural instability of human chromosome 15. Characterization of this locus identified long, RNA transcripts that are retained in the nucleus and form a "cloud" on one homolog of chromosome 15. We also found that this locus displays asynchronous replication that is coordinated with other random monoallelic genes on chromosome 15. We have named this locus ASynchronous replication and Autosomal RNA on chromosome 15, or ASAR15. Previously, we found that disruption of the ASAR6 lincRNA gene results in delayed replication, delayed mitotic condensation and structural instability of human chromosome 6. Previous studies in the mouse found that deletion of the Xist gene, from the X chromosome in adult somatic cells, results in a delayed replication and instability phenotype that is indistinguishable from the phenotype caused by disruption of either ASAR6 or ASAR15. In addition, delayed replication and chromosome instability were detected following structural rearrangement of many different human or mouse chromosomes. These observations suggest that all mammalian chromosomes contain similar cis-acting loci. Thus, under this scenario, all mammalian chromosomes contain four distinct types of essential cis-acting elements: origins, telomeres, centromeres and "inactivation/stability centers", all functioning to promote proper replication, segregation and structural stability of each chromosome.

  5. Human short-term exposure to electromagnetic fields emitted by mobile phones decreases computer-assisted visual reaction time. (United States)

    Mortazavi, S M J; Rouintan, M S; Taeb, S; Dehghan, N; Ghaffarpanah, A A; Sadeghi, Z; Ghafouri, F


    The worldwide dramatic increase in mobile phone use has generated great concerns about the detrimental effects of microwave radiations emitted by these communication devices. Reaction time plays a critical role in performing tasks necessary to avoid hazards. As far as we know, this study is the first survey that reports decreased reaction time after exposure to electromagnetic fields generated by a high specific absorption rate mobile phone. It is also the first study in which previous history of mobile phone use is taken into account. The aim of this study was to assess both the acute and chronic effects of electromagnetic fields emitted by mobile phones on reaction time in university students. Visual reaction time (VRT) of young university students was recorded with a simple blind computer-assisted-VRT test, before and after a 10 min real/sham exposure to electromagnetic fields of mobile phones. Participants were 160 right-handed university students aged 18-31. To assess the effect of chronic exposures, the reaction time in sham-exposed phases were compared among low level, moderate and frequent users of mobile phones. The mean ± SD reaction time after real exposure and sham exposure were 286.78 ± 31.35 ms and 295.86 ± 32.17 ms (P students did not significantly alter the reaction time either in talk or in standby mode. The reaction time either in talk or in standby mode was shorter in male students. The students' VRT was significantly affected by exposure to electromagnetic fields emitted by a mobile phone. It can be concluded that these exposures cause decreased reaction time, which may lead to a better response to different hazards. In this light, this phenomenon might decrease the chances of human errors and fatal accidents.

  6. Time and motion, experiment M151. [human performance and space flight stress (United States)

    Kubis, J. F.; Elrod, J. T.; Rusnak, R.; Mcbride, G. H.; Barnes, J. E.; Saxon, S. C.


    Astronaut work performance during the preparation and execution of experiments in simulated Skylab tests was analyzed according to time and motion in order to evaluate the efficiency and consistency of performance (adaptation function) for several different types of activity over the course of the mission; to evaluate the procedures to be used by the same experiment in Skylab; to generate characteristic adaptation functions for later comparison with Skylab data; and to examine astronaut performance for any behavioral stress due to the environment. The overall results indicate that the anticipated adaptation function was obtained both for individual and for averaged data.

  7. Timing of postexercise protein intake is important for muscle hypertrophy with resistance training in elderly humans

    DEFF Research Database (Denmark)

    Esmarck, Birgitte; Olsen, Steen Schytte


    1. Age-associated loss of skeletal muscle mass and strength can partly be counteracted by resistance training, causing a net synthesis of muscular proteins. Protein synthesis is influenced synergistically by postexercise amino acid supplementation, but the importance of the timing of protein intake...... remains unresolved. 2. The study investigated the importance of immediate (P0) or delayed (P2) intake of an oral protein supplement upon muscle hypertrophy and strength over a period of resistance training in elderly males. 3. Thirteen men (age, 74 ± 1 years; body mass index (BMI), 25 ± 1 kg m−2 (means...... %, respectively (P important...

  8. Nuclear magnetic resonance relaxation times for human lung cancer and lung tissues

    Energy Technology Data Exchange (ETDEWEB)

    Matsuura, Yoshifumi; Shioya, Sumie; Kurita, Daisaku; Ohta, Takashi; Haida, Munetaka; Ohta, Yasuyo [Tokai Univ., Isehara, Kanagawa (Japan). School of Medicine; Suda, Syuichi; Fukuzaki, Minoru


    We investigated the nuclear magnetic resonance (NMR) relaxation times, T{sub 1} and T{sub 2}, for lung cancer tissue, and other samples of lung tissue obtained from surgical specimens. The samples were nine squamous cell carcinomas, five necrotic squamous cell carcinomas, 15 adenocarcinomas, two benign mesotheliomas, and 13 fibrotic lungs. The relaxation times were measured with a 90 MHz NMR spectrometer and the results were correlated with histological changes. The values of T{sub 1} and T{sub 2} for squamous cell carcinoma and mesothelioma were significantly longer than those of adenocarcinoma and fibrotic lung tissue. There were no significant differences in values of T{sub 1} and T{sub 2} between adenocarcinoma and lung tissue. The values of T{sub 1} and T{sub 2} for benign mesothelioma were similar to those of squamous cell carcinoma, which suggested that increases in T{sub 1} and T{sub 2} are not specific to malignant tissues. (author).

  9. Transitional B cells in early human B cell development - time to revisit the paradigm?

    Directory of Open Access Journals (Sweden)

    Victoria G Martin


    Full Text Available The B cell repertoire is generated in the adult bone marrow by an ordered series of gene rearrangement processes that result in massive diversity of immunoglobulin (Ig genes, and consequently an equally large number of potential specificities for antigen. As the process is essentially random, then cells exhibiting excess reactivity with self-antigens are generated and need to be removed from the repertoire before the cells are fully mature. Some of the cells are deleted, and some will undergo receptor editing to see if changing the light chain can rescue an autoreactive antibody. As a consequence, the binding properties of the B cell receptor are changed as development progresses through pre-B>>immature>>transitional>>naïve phenotypes. Using long-read, high-throughput, sequencing we have produced a unique set of sequences from these four cell types in human bone marrow and matched peripheral blood and our results describe the effects of tolerance selection on the B cell repertoire at the Ig gene level. Most strong effects of selection are seen within the heavy chain repertoire, and can be seen both in gene usage and in CDR-H3 characteristics. Age-related changes are small and only the size of the CDR-H3 shows constant and significant change in these data. The paucity of significant changes in either kappa or lambda light chain repertoires implies that either the heavy chain has more influence over autoreactivity than light chain and/or that switching between kappa and lambda light chains, as opposed to switching within the light chain loci, may effect a more successful autoreactive rescue by receptor editing. Our results show that the transitional cell population contains cells other than those that are part of the pre-B>>immature>>transitional>>naïve development pathway, since the population often shows a repertoire that is outside the trajectory of gene loss/gain between pre-B and naïve stages.

  10. Human strategies for solving a time-place learning task: the role of counting and following verbal cues. (United States)

    García-Gallardo, Daniel; Aguilar, Francisco; Armenta, Benjamín; Carpio, Claudio


    Two experiments were conducted to assess the emergence of time-place learning in humans. In experiment 1, a computer based software was designed in which participants had to choose to enter one of four rooms in an abandoned house search for a zombie every 3-15s. Zombies could be found in only one of these rooms every trial in 3 min periods during the 12 min sessions. After 4 training sessions, participants were exposed to a probe session in which zombies could be found in any room on every trial. Almost all participants behaved as if they were timing the availability intervals: they anticipated the changes in the location of the zombie and they persisted in their performance patterns during the probe session; however, verbal reports revealed that they were counting the number of trials in each period in order to decide when to switch between rooms. In the second experiment, the task was modified in two ways: counting was made harder by using three different intertrial ranges within each session: 2-6s, 2-11s and 2-16s. Second, labels were displaced during the final session to assess whether participants learned to click on a given place or to follow a set of verbal cues. We found that participants did not notice the label changes suggesting that they learned to click on a given place, and that a win/stay-lose/shift strategy was clearly used to decide when to switch rooms in the second experiment. The implications of verbal behavior when assessing time-place learning with humans and the possible differences in this process between humans and animals are discussed.

  11. Explaining the highly enantiomeric photocyclodimerization of 2-anthracenecarboxylate bound to human serum albumin using time-resolved anisotropy studies. (United States)

    Fuentealba, Denis; Kato, Hanako; Nishijima, Masaki; Fukuhara, Gaku; Mori, Tadashi; Inoue, Yoshihisa; Bohne, Cornelia


    The mechanism for the high enantiomeric excess (ee) (80-90%) observed in the photocyclodimerization of 2-anthracenecarboxylate (AC) in the chiral binding sites of human serum albumin (HSA) was studied using fluorescence anisotropy. A long rotational correlation time of 36 ns was observed for the excited states of the ACs bound to the HSA site responsible for the high ee, suggesting that the ACs have restricted rotational mobility in this site. The ACs in this site have the same prochiral face protected by the protein, and this protection is responsible for the high ee observed. These insights provide a strategy for the rational design of supramolecular photochirogenic systems.

  12. Comparison of Real-Time Multiplex Human Papillomavirus (HPV) PCR Assays with INNO-LiPA HPV Genotyping Extra Assay▿


    Else, Elizabeth A.; Swoyer, Ryan; Zhang, Yuhua; Taddeo, Frank J.; Bryan, Janine T.; Lawson, John; Van Hyfte, Inez; Roberts, Christine C.


    Real-time type-specific multiplex human papillomavirus (HPV) PCR assays were developed to detect HPV DNA in samples collected for the efficacy determination of the quadrivalent HPV (type 6, 11, 16, and 18) L1 virus-like particle (VLP) vaccine (Gardasil). Additional multiplex (L1, E6, and E7 open reading frame [ORF]) or duplex (E6 and E7 ORF) HPV PCR assays were developed to detect high-risk HPV types, including HPV type 31 (HPV31), HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV56, HPV58, and H...

  13. On the space and time evolution of regular or irregular human heart or brain signals

    CERN Document Server

    Tuncay, Caglar


    A coupled map is suggested to investigate various spatial or temporal designs in biology: Several cells (or tissues) in an organ are considered as connected to each other in terms of some molecular diffusions or electrical potential differences and so on. The biological systems (groups of cells) start from various initial conditions for spatial designs (or initial signals for temporal designs) and they evolve in time in terms of the mentioned interactions (connections) besides some individual feedings. The basic aim of the present contribution is to mimic various empirical data for the heart (in normal, quasi-stable, unstable and post operative physiological conditions) or brain (regular or irregular; for epilepsy) signals. The mentioned empirical data are borrowed from various literatures which are cited. The suggested model (to be used besides or instead of the artificial network models) involves simple mathematics and the related software is easy. The results may be considered as in good agreement with the...

  14. Timing of postexercise protein intake is important for muscle hypertrophy with resistance training in elderly humans

    DEFF Research Database (Denmark)

    Esmarck, Birgitte; Olsen, Steen Schytte


    remains unresolved. 2. The study investigated the importance of immediate (P0) or delayed (P2) intake of an oral protein supplement upon muscle hypertrophy and strength over a period of resistance training in elderly males. 3. Thirteen men (age, 74 ± 1 years; body mass index (BMI), 25 ± 1 kg m−2 (means...... ± S.E.M.)) completed a 12 week resistance training programme (3 times per week) receiving oral protein in liquid form (10 g protein, 7 g carbohydrate, 3 g fat) immediately after (P0) or 2 h after (P2) each training session. Muscle hypertrophy was evaluated by magnetic resonance imaging (MRI) and from...... for the development of hypertrophy in skeletal muscle of elderly men in response to resistance training....

  15. Transitional B Cells in Early Human B Cell Development – Time to Revisit the Paradigm? (United States)

    Martin, Victoria G.; Wu, Yu-Chang Bryan; Townsend, Catherine L.; Lu, Grace H. C.; O’Hare, Joselli Silva; Mozeika, Alexander; Coolen, Anthonius C. C.; Kipling, David; Fraternali, Franca; Dunn-Walters, Deborah K.


    The B cell repertoire is generated in the adult bone marrow by an ordered series of gene rearrangement processes that result in massive diversity of immunoglobulin (Ig) genes and consequently an equally large number of potential specificities for antigen. As the process is essentially random, the cells exhibiting excess reactivity with self-antigens are generated and need to be removed from the repertoire before the cells are fully mature. Some of the cells are deleted, and some will undergo receptor editing to see if changing the light chain can rescue an autoreactive antibody. As a consequence, the binding properties of the B cell receptor are changed as development progresses through pre-B ≫ immature ≫ transitional ≫ naïve phenotypes. Using long-read, high-throughput, sequencing we have produced a unique set of sequences from these four cell types in human bone marrow and matched peripheral blood, and our results describe the effects of tolerance selection on the B cell repertoire at the Ig gene level. Most strong effects of selection are seen within the heavy chain repertoire and can be seen both in gene usage and in CDRH3 characteristics. Age-related changes are small, and only the size of the CDRH3 shows constant and significant change in these data. The paucity of significant changes in either kappa or lambda light chain repertoires implies that either the heavy chain has more influence over autoreactivity than light chain and/or that switching between kappa and lambda light chains, as opposed to switching within the light chain loci, may effect a more successful autoreactive rescue by receptor editing. Our results show that the transitional cell population contains cells other than those that are part of the pre-B ≫ immature ≫ transitional ≫ naïve development pathway, since the population often shows a repertoire that is outside the trajectory of gene loss/gain between pre-B and naïve stages. PMID:27994589

  16. Identification of time-varying dynamics of the human triceps surae stretch reflex. I. Rapid isometric contraction. (United States)

    Kirsch, R F; Kearney, R E; MacNeil, J B


    We have examined the time variations of stretch reflex dynamics throughout rapid voluntary changes in the isometric contraction level of the human triceps surae muscles. This was achieved by superimposing a small stochastic displacement upon many such changing contractions and then identifying the time-varying relationship between the perturbation and the evoked electromyograms (EMGs). An "ensemble" time-varying system identification technique was used to estimate these input-output dynamics as a set of impulse response functions, one for each time before, during, and after the change in contraction level, with a temporal resolution equal to the data acquisition rate. Three main findings resulted. First, stretch reflex gain (relating joint velocity to EMG) was significantly modulated during changes in voluntary contraction level, increasing as the subject contracted the muscles and decreasing as the subject relaxed. Second, stretch reflex dynamics did not change with contraction level, even when its gain varied substantially. Third, the time course of the gain changes closely followed the level of the EMG, even though the subjects used rather different activation and deactivation patterns. These results suggest that, for the behavior studied (i.e., rapid changes in isometric contraction level), stretch reflex gain and motoneuron pool activation level were controlled by a common descending command rather than being independently specified.

  17. Human chorionic gonadotropin administration is associated with high pregnancy rates during ovarian stimulation and timed intercourse or intrauterine insemination

    Directory of Open Access Journals (Sweden)

    Abdel-Razeq Sonya


    Full Text Available Abstract Background There are different factors that influence treatment outcome after ovarian stimulation and timed-intercourse or intrauterine insemination (IUI. After patient age, it has been suggested that timing of insemination in relation to ovulation is probably the most important variable affecting the success of treatment. The objective of this study is to study the value of human chorionic gonadotropin (hCG administration and occurrence of luteinizing hormone (LH surge in timing insemination on the treatment outcome after follicular monitoring with timed-intercourse or intrauterine insemination, with or without ovarian stimulation. Methods Retrospective analysis of 2000 consecutive completed treatment cycles (637 timed-intercourse and 1363 intrauterine insemination cycles. Stimulation protocols included clomiphene alone or with FSH injection, letrozole (an aromatase inhibitor alone or with FSH, and FSH alone. LH-surge was defined as an increase in LH level ≥200% over mean of preceding two days. When given, hCG was administered at a dose of 10,000 IU. The main outcome was clinical pregnancy rate per cycle. Results Higher pregnancy rates occurred in cycles in which hCG was given. Occurrence of an LH-surge was associated with a higher pregnancy rate with clomiphene treatment, but a lower pregnancy rate with FSH treatment. Conclusions hCG administration is associated with a favorable outcome during ovarian stimulation. Awaiting occurrence of LH-surge is associated with a better outcome with CC but not with FSH treatment.

  18. Model for interevent times with long tails and multifractality in human communications: An application to financial trading (United States)

    Perelló, Josep; Masoliver, Jaume; Kasprzak, Andrzej; Kutner, Ryszard


    Social, technological, and economic time series are divided by events which are usually assumed to be random, albeit with some hierarchical structure. It is well known that the interevent statistics observed in these contexts differs from the Poissonian profile by being long-tailed distributed with resting and active periods interwoven. Understanding mechanisms generating consistent statistics has therefore become a central issue. The approach we present is taken from the continuous-time random-walk formalism and represents an analytical alternative to models of nontrivial priority that have been recently proposed. Our analysis also goes one step further by looking at the multifractal structure of the interevent times of human decisions. We here analyze the intertransaction time intervals of several financial markets. We observe that empirical data describe a subtle multifractal behavior. Our model explains this structure by taking the pausing-time density in the form of a superstatistics where the integral kernel quantifies the heterogeneous nature of the executed tasks. A stretched exponential kernel provides a multifractal profile valid for a certain limited range. A suggested heuristic analytical profile is capable of covering a broader region.

  19. Divergent selection on, but no genetic conflict over, female and male timing and rate of reproduction in a human population. (United States)

    Bolund, Elisabeth; Bouwhuis, Sandra; Pettay, Jenni E; Lummaa, Virpi


    The sexes often have different phenotypic optima for important life-history traits, and because of a largely shared genome this can lead to a conflict over trait expression. In mammals, the obligate costs of reproduction are higher for females, making reproductive timing and rate especially liable to conflict between the sexes. While studies from wild vertebrates support such sexual conflict, it remains unexplored in humans. We used a pedigreed human population from preindustrial Finland to estimate sexual conflict over age at first and last reproduction, reproductive lifespan and reproductive rate. We found that the phenotypic selection gradients differed between the sexes. We next established significant heritabilities in both sexes for all traits. All traits, except reproductive rate, showed strongly positive intersexual genetic correlations and were strongly genetically correlated with fitness in both sexes. Moreover, the genetic correlations with fitness were almost identical in men and women. For reproductive rate, the intersexual correlation and the correlation with fitness were weaker but again similar between the sexes. Thus, in this population, an apparent sexual conflict at the phenotypic level did not reflect an underlying genetic conflict over the studied reproductive traits. These findings emphasize the need for incorporating genetic perspectives into studies of human life-history evolution.

  20. Noncontacting diffuse VIS-NIR spectroscopy of human skin for evaluation of skin type and time-dependent microcirculation (United States)

    Schmidt, Wolf-Dieter; Fassler, Dieter; Zimmermann, Gabi; Liebold, Kristin; Wollina, Uwe


    Spectroscopic investigations of the VIS-NIR range allow the objective determination of pigmentation, blood microcirculation and water content of human skin. Non- contacting in vivo measurements of the human skin of 50 volunteers reflect the clinical skin type well. Our correlation analysis yields that the red/infrared spectral range can be used for a determination of skin type. The observed strong spectral variations within the same group of skin type are likely based on the high biological variability of human skin and subjective clinically observed skin type. Therefore it can be useful to measure the full spectral range and to calculate a non-observed skin score with multivariate spectral methods. By multivariate analysis a correct classification of remittance spectra can be obtained. Time- depending spectral variations of dermal microcirculation can be measured at defined locations of the body, for instance the dynamics of oxygenation or blood volume in the skin of the fingertip. The cardial, pulmonal and vasomotoric waves of the micro- and macrocirculation are clearly visible at different wavelengths. The spectroscopic informations are important as an objective measure for the skin type evaluation, the penetration behavior of pharmaca, laser surgery, and therapy.

  1. What neuropsychology tells us about human tool use? The four constraints theory (4CT): mechanics, space, time, and effort. (United States)

    Osiurak, François


    Our understanding of human tool use comes mainly from neuropsychology, particularly from patients with apraxia or action disorganization syndrome. However, there is no integrative, theoretical framework explaining what these neuropsychological syndromes tell us about the cognitive/neural bases of human tool use. The goal of the present article is to fill this gap, by providing a theoretical framework for the study of human tool use: The Four Constraints Theory (4CT). This theory rests on two basic assumptions. First, everyday tool use activities can be formalized as multiple problem situations consisted of four distinct constraints (mechanics, space, time, and effort). Second, each of these constraints can be solved by the means of a specific process (technical reasoning, semantic reasoning, working memory, and simulation-based decision-making, respectively). Besides presenting neuropsychological evidence for 4CT, this article shall address epistemological, theoretical and methodological issues I will attempt to resolve. This article will discuss how 4CT diverges from current cognitive models about several widespread hypotheses (e.g., notion of routine, direct and automatic activation of tool knowledge, simulation-based tool knowledge).

  2. Development of energy and time parameters in the walking of healthy human infants. (United States)

    Kimura, Tasuku; Yaguramaki, Naoko; Fujita, Masaki; Ogiue-Ikeda, Mari; Nishizawa, Satoshi; Ueda, Yutaka


    Sixteen infants were analyzed longitudinally from the onset of independent walking to 3 years of age using time parameters, speed and energy recovery. Considerable variation and irregularities were observed in many parameters of infant walking, especially until 13 months of age when infants had difficulty in walking steadily step by step. Infant walking until 3 years of age was characterized by a small braking duration, caused mainly by the forward inclination of the trunk, a large relative stance phase duration, which maintained static balance, short stride length, due to the small range of the lower limb joint angle, and a small recovery of external energy. These characteristics were also predominantly evident until 13 months of age. The small recovery characteristic of infants was caused by flexed lower limb joints, pronounced irregularities in energy output, and in younger infants, slow speed. The maximum recovery up until 2 years of age, though smaller than in adults, appeared at about 0.45 dimensionless speed, which is about the same speed that adults in particular naturally and at which their maximum recovery appeared. The forward inclination of the trunk and the lower limb joint angle, influenced the development of many characteristics of bipedal walking.

  3. A real-time human-perception interface for task-level control of a robot in unfamiliar environments (United States)

    Miles, Eric Scott

    Recent advances in the development of semi-autonomous robotic systems offer numerous potential advantages in many engineering and science endeavors. Significant reductions in cost, time and risk, as well as increased capability, can be obtained by utilizing intelligent machines to assist humans. However, the use of robots also introduces many challenging issues, including the need for high-bandwidth stable control despite communication delays and operator fatigue. In response to these challenges, the Stanford Aerospace Robotics Laboratory has pioneered the Task-Level Control architecture, which enables humans to direct, from a strategic level, sophisticated tasks that a robot then executes autonomously. The research reported here is intended to extend the Task-Level Control architecture significantly--by using human perception in a natural way--to work well in unfamiliar environments. An unfamiliar environment is defined to be one about which it is impossible to have perfect and complete knowledge before developing and deploying a robotic system. Clearly, every work environment is, to some extent, unfamiliar. This research has shown that drawing intimately, in real time, upon a human's deep visual perception is extremely effective in overcoming such unfamiliarity. A novel interactive vision-based operator interface for directing a highly autonomous robot operating in an unfamiliar environment is presented. Intuitive interaction with a live-video display from cameras on board the robot is used in combination with stereo-vision algorithms to maintain the operator's attention at the overall object-level during the modeling process. With this interface, the human's remarkable ability to discern entire object-level constructs is utilized to produce quick, cogent and robust models of unexpected and unknown objects in the environment. Once unfamiliar objects have been suitably modeled, tasks involving those objects can be directed via the Task-Level Control architecture

  4. Comparing the Effect of Topical Application of Human Milk and Dry Cord Care on Umbilical Cord Separation Time in Healthy Newborn Infants


    Aghamohammadi, Azar; Zafari, Mandana; Moslemi, Leila


    Objective Comparing the effect of topical human milk application and dry cord care on cord separation time. Methods This research was a randomized clinical trial study on 130 singleton and mature newborns. Newborns were placed randomly in groups of topical application of human milk and dry cord care. The umbilical separation time was compared in the two groups. Data was analyzed by SPSS software. Independent Samples t-Test, χ2, Fisher were used in this study. Findings Median time of cord sepa...

  5. Differential regulation of circadian melatonin rhythm and sleep-wake cycle by bright lights and nonphotic time cues in humans. (United States)

    Yamanaka, Yujiro; Hashimoto, Satoko; Masubuchi, Satoru; Natsubori, Akiyo; Nishide, Shin-Ya; Honma, Sato; Honma, Ken-Ichi


    Our previous study demonstrated that physical exercise under dim lights (cycle but not the circadian melatonin rhythm to an 8-h phase-advanced sleep schedule, indicating differential effects of physical exercise on the human circadian system. The present study examined the effects of bright light (>5,000 lux) on exercise-induced acceleration of reentrainment because timed bright lights are known to reset the circadian pacemaker. Fifteen male subjects spent 12 days in temporal isolation. The sleep schedule was advanced from habitual sleep times by 8 h for 4 days, which was followed by a free-run session. In the shift session, bright lights were given during the waking time. Subjects in the exercise group performed 2-h bicycle running twice a day. Subjects in the control kept quiet. As a result, the sleep-wake cycle was fully entrained by the shift schedule in both groups. Bright light may strengthen the resetting potency of the shift schedule. By contrast, the circadian melatonin rhythm was phase-advanced by 6.9 h on average in the exercise group but only by 2.0 h in the control. Thus physical exercise prevented otherwise unavoidable internal desynchronization. Polysomnographical analyses revealed that deterioration of sleep quality by shift schedule was protected by physical exercise under bright lights. These findings indicate differential regulation of sleep-wake cycle and circadian melatonin rhythm by physical exercise in humans. The melatonin rhythm is regulated primarily by bright lights, whereas the sleep-wake cycle is by nonphotic time cues, such as physical exercise and shift schedule.

  6. Preliminary observations on polar body extrusion and pronuclear formation in human oocytes using time-lapse video cinematography. (United States)

    Payne, D; Flaherty, S P; Barry, M F; Matthews, C D


    In this study, we have used time-lapse video cinematography to study fertilization in 50 human oocytes that had undergone intracytoplasmic sperm injection (ICSI). Time-lapse recording commenced shortly after ICSI and proceeded for 17-20 h. Oocytes were cultured in an environmental chamber which was maintained under standard culture conditions. Overall, 38 oocytes (76%) were fertilized normally, and the fertilization rate and embryo quality were not significantly different from 487 sibling oocytes cultured in a conventional incubator. Normal fertilization followed a defined course of events, although the timing of these events varied markedly between oocytes. In 35 of the 38 fertilized oocytes (92%), there were circular waves of granulation within the ooplasm which had a periodicity of 20-53 min. The sperm head decondensed during this granulation phase. The second polar body was then extruded, and this was followed by the central formation of the male pronucleus. The female pronucleus formed in the cytoplasm adjacent to the second polar body at the same time as, or slightly after, the male pronucleus, and was subsequently drawn towards the male pronucleus until the two abutted. Both pronuclei then increased in size, the nucleoli moved around within the pronuclei and some nucleoli coalesced. During pronuclear growth, the organelles contracted from the cortex towards the centre of the oocyte, leaving a clear cortical zone. The oocyte decreased in diameter from 112 to 106 microm (P cinematography is an excellent tool for studying fertilization and early embryo development, and have demonstrated that human fertilization comprises numerous complex dynamic events.

  7. Human impact on erosion and burial of soil carbon through time (United States)

    Hoffmann, Thomas; Amelung, Wulf; Bornemann, Ludger; Gerlach, Renate; Lang, Andreas


    The effects of soil erosion on atmospheric carbon is governed by three key mechanisms that are i) the replacement of soil organic carbon (SOC) at eroding sites, ii) the mineralization of SOC during erosion and transport and iii) the stability of buried SOC at depositional sites. Markedly different assumptions have been made about the relative importance of the key mechanisms, resulting in a global release of 1 Pg C/a to a global uptake of 1 Pg C/a. Here we present results of a sediment-associated carbon budget in a small headwater catchment in Germany, to highlight the importance of the timescale in controlling the relative importance of the key mechanisms. Therefore, we estimate the loss of SOC through land use change from forests to arable land and compare it with SOC losses at degraded sites and burial of SOC in colluvial deposits. Our results show that the transition of forest to arable land (without erosion and deposition of soils and sediments) resulted in a rapid loss of SOC from 11.8 kg C/m² to 7.2 kg C/m² in our study site. Eroded sites are characterized by carbon stocks of 6.9 kg C/m² compared to depositional sites with 27.9 kg C/m². Thus the combined effect of soil erosion and deposition results in a slow net withdrawal of atmospheric CO2, which compensates land use driven losses. We show that the net effect of SOC degradation and burial depends on the rate of soil erosion and time since the erosion commenced. Given the erosion history in the study site, the removal of SOC through land use change will be compensated after approx. 120 years of erosion and deposition.

  8. The sex ratio distortion in the human head louse is conserved over time

    Directory of Open Access Journals (Sweden)

    Biliński Szczepan M


    Full Text Available Abstract Background At the turn of the 19th century the first observations of a female-biased sex ratio in broods and populations of the head louse, Pediculus humanus capitis, had been reported. A study by Buxton in 1940 on the sex ratio of lice on prisoners in Ceylon is still today the subject of reanalyses. This sex ratio distortion had been detected in ten different countries. In the last sixty years no new data have been collected, especially on scalp infestations under economically and socially more developed conditions. Results Here we report a female bias of head lice in a survey of 480 school children in Argentina. This bias is independent of the intensity of the pediculosis, which makes local mate competition highly unlikely as the source of the aberrant sex ratio; however, other possible adaptive mechanisms cannot be discounted. These lice as well as lice from pupils in Britain were carrying several strains of the endosymbiotic bacterium Wolbachia pipientis, one of the most wide spread intracellular sex ratio distorters. Similar Wolbachia strains are also present in the pig louse, Haematopinus suis, suggesting that this endosymbiont might have a marked influence on the biology of the whole order. The presence of a related obligate nutritional bacterium in lice prevents the investigation of a causal link between sex ratio and endosymbionts. Conclusions Regardless of its origin, this sex ratio distortion in head lice that has been reported world wide, is stable over time and is a remarkable deviation from the stability of frequency-dependent selection of Fisher's sex ratio. A female bias first reported in 1898 is still present over a hundred years and a thousand generations later.

  9. Detection of an extended human volatome with comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry.

    Directory of Open Access Journals (Sweden)

    Michael Phillips

    Full Text Available BACKGROUND: Comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOF MS has been proposed as a powerful new tool for multidimensional analysis of complex chemical mixtures. We investigated GCxGC-TOF MS as a new method for identifying volatile organic compounds (VOCs in normal human breath. METHODS: Samples of alveolar breath VOCs and ambient room air VOC were collected with a breath collection apparatus (BCA onto separate sorbent traps from 34 normal healthy volunteers (mean age = 40 yr, SD = 17 yr, male/female = 19/15. VOCs were separated on two serial capillary columns separated by a cryogenic modulator, and detected with TOF MS. The first and second dimension columns were non-polar and polar respectively. RESULTS: BCA collection combined with GC×GC-TOF MS analysis identified approximately 2000 different VOCs in samples of human breath, many of which have not been previously reported. The 50 VOCs with the highest alveolar gradients (abundance in breath minus abundance in ambient room air mostly comprised benzene derivatives, acetone, methylated derivatives of alkanes, and isoprene. CONCLUSIONS: Collection and analysis of breath VOCs with the BCA-GC×GC-TOF MS system extended the size of the detectable human volatile metabolome, the volatome, by an order of magnitude compared to previous reports employing one-dimensional GC-MS. The size of the human volatome has been under-estimated in the past due to coelution of VOCs in one-dimensional GC analytical systems.

  10. EyeFrame: Real-time memory aid improves human multitasking via domain-general eye tracking procedures

    Directory of Open Access Journals (Sweden)

    P. eTaylor


    Full Text Available OBJECTIVE: We developed an extensively general closed-loop system to improve human interaction in various multitasking scenarios, with semi-autonomous agents, processes, and robots. BACKGROUND: Much technology is converging toward semi-independent processes with intermittent human supervision distributed over multiple computerized agents. Human operators multitask notoriously poorly, in part due to cognitive load and limited working memory. To multitask optimally, users must remember task order, e.g., the most neglected task, since longer times not monitoring an element indicates greater probability of need for user input. The secondary task of monitoring attention history over multiple spatial tasks requires similar cognitive resources as primary tasks themselves. Humans can not reliably make more than ~2 decisions/s. METHODS: Participants managed a range of 4-10 semi-autonomous agents performing rescue tasks. To optimize monitoring and controlling multiple agents, we created an automated short term memory aid, providing visual cues from users' gaze history. Cues indicated when and where to look next, and were derived from an inverse of eye fixation recency. RESULTS: Contingent eye tracking algorithms drastically improved operator performance, increasing multitasking capacity. The gaze aid reduced biases, and reduced cognitive load, measured by smaller pupil dilation. CONCLUSIONS: Our eye aid likely helped by delegating short-term memory to the computer, and by reducing decision making load. Past studies used eye position for gaze-aware control and interactive updating of displays in application-specific scenarios, but ours is the first to successfully implement domain-general algorithms. Procedures should generalize well to: process control, factory operations, robot control, surveillance, aviation, air traffic control, driving, military, mobile search and rescue, and many tasks where probability of utility is predicted by duration since last

  11. Adaptive Fourier series modeling of time-varying evoked potentials: study of human somatosensory evoked response to etomidate anesthetic. (United States)

    Thakor, N V; Vaz, C A; McPherson, R W; Hanley, D F


    Evoked potentials (EPs) have traditionally been analyzed in time domain, with amplitude and latency of various signal components used in clinical interpretation. A new approach, called adaptive Fourier series modeling (FSM), is presented here. Dynamic changes in magnitudes of Fourier coefficients are analyzed for diagnostic purposes. In order to estimate the time-varying changes in the Fourier coefficients of noisy signals, a least mean-square filtering algorithm is applied. Results of computer simulations as well as experimental data are presented. Time-varying trends are presented in a new compressed evoked spectrum format. These techniques are applied to the study of alterations in human somatosensory EPs caused by the intravenous administration of etomidate during neurosurgical procedures. Amplitude increases of the order of 200-500% occurring within a time span of about 100 sec were captured. Due to its superior convergence properties, the adaptive FSM technique estimates more rapid changes in amplitude and latency than exponentially weighted averaging or moving window averaging schemes.

  12. Evidence for sequential and increasing activation of replication origins along replication timing gradients in the human genome. (United States)

    Guilbaud, Guillaume; Rappailles, Aurélien; Baker, Antoine; Chen, Chun-Long; Arneodo, Alain; Goldar, Arach; d'Aubenton-Carafa, Yves; Thermes, Claude; Audit, Benjamin; Hyrien, Olivier


    Genome-wide replication timing studies have suggested that mammalian chromosomes consist of megabase-scale domains of coordinated origin firing separated by large originless transition regions. Here, we report a quantitative genome-wide analysis of DNA replication kinetics in several human cell types that contradicts this view. DNA combing in HeLa cells sorted into four temporal compartments of S phase shows that replication origins are spaced at 40 kb intervals and fire as small clusters whose synchrony increases during S phase and that replication fork velocity (mean 0.7 kb/min, maximum 2.0 kb/min) remains constant and narrowly distributed through S phase. However, multi-scale analysis of a genome-wide replication timing profile shows a broad distribution of replication timing gradients with practically no regions larger than 100 kb replicating at less than 2 kb/min. Therefore, HeLa cells lack large regions of unidirectional fork progression. Temporal transition regions are replicated by sequential activation of origins at a rate that increases during S phase and replication timing gradients are set by the delay and the spacing between successive origin firings rather than by the velocity of single forks. Activation of internal origins in a specific temporal transition region is directly demonstrated by DNA combing of the IGH locus in HeLa cells. Analysis of published origin maps in HeLa cells and published replication timing and DNA combing data in several other cell types corroborate these findings, with the interesting exception of embryonic stem cells where regions of unidirectional fork progression seem more abundant. These results can be explained if origins fire independently of each other but under the control of long-range chromatin structure, or if replication forks progressing from early origins stimulate initiation in nearby unreplicated DNA. These findings shed a new light on the replication timing program of mammalian genomes and provide a general

  13. Quantification of resting myocardial blood flow velocity in normal humans using real-time contrast echocardiography. A feasibility study

    Directory of Open Access Journals (Sweden)

    Slordahl Stig


    Full Text Available Abstract Background Real-time myocardial contrast echocardiography (MCE is a novel method for assessing myocardial perfusion. The aim of this study was to evaluate the feasibility of a very low-power real-time MCE for quantification of regional resting myocardial blood flow (MBF velocity in normal human myocardium. Methods Twenty study subjects with normal left ventricular (LV wall motion and normal coronary arteries, underwent low-power real-time MCE based on color-coded pulse inversion Doppler. Standard apical LV views were acquired during constant IV. infusion of SonoVue®. Following transient microbubble destruction, the contrast replenishment rate (β, reflecting MBF velocity, was derived by plotting signal intensity vs. time and fitting data to the exponential function; y (t =A (1-e-β(t-t0 + C. Results Quantification was feasible in 82%, 49% and 63% of four-chamber, two-chamber and apical long-axis view segments, respectively. The LAD (left anterior descending artery and RCA (right coronary artery territories could potentially be evaluated in most, but contrast detection in the LCx (left circumflex artery bed was poor. Depending on localisation and which frames to be analysed, mean values of were 0.21–0.69 s-1, with higher values in medial than lateral, and in basal compared to apical regions of scan plane (p = 0.03 and p Conclusion Low-power real-time MCE did have the potential to give contrast enhancement for quantification of resting regional MBF velocity. However, the technique is difficult and subjected to several limitations. Significant variability in β suggests that this parameter is best suited for with-in patient changes, comparing values of stress studies to baseline.

  14. Biological properties of differently-aged human keratinocytes:population doubling time growth curve and cell cycle analysis

    Institute of Scientific and Technical Information of China (English)

    Hui-qun Ma; Jie Feng; Lech Chyczewski; Jacek Niklinski


    Objective To explore the biological properties of keratinocytes from differently-aged healthy human beings. Methods Keratinocytes from fetus, teenager and middle-aged groups were separated and cultured. The population doubling time (PDT) and cell growth curve in different cells were compared, and the cell cycles were analyzed by flow cytometry. Results ① In primary culture of keratinocytes, the adherence time in middle-aged group was longer than that in fetus and teenager groups. However, all cell morphology showed no obvioas differences. In subculture of kecatinocytes, with donator's age increasing, time of cell adherence prolonged, passage number decreused and differences in cell morphology were obrioas. ② The average PDT of keratinocytes was shorter in fetus group than in teenager and middle-aged groups. Bat difference in cell growth curve between different passages was not observed. ③ Keratinocytes showed G2/M period in fetus group but G0/G1 period in teenager and middle-aged groups mainly. Conclusion As age increases, the biological properties of keratinocytes change obviously.

  15. Time course of effects of chemotherapy and radiotherapy on a human pancreatic cancer cell line (SUIT-2) in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Wakasugi, Hideyuki; Seo, Yohsuke; Yamada, Yukio; Hata, Kazuo; Higuchi, Kaoru; Kohno, Akira [National Kyushu Cancer Center, Fukuoka (Japan)


    In order to investigate time course of effects of chemotherapy and radiotherapy on pancreatic cancer, we used the monolayer culture of a human pancreatic cancer cell line, SUIT-2 which produces CEA and CA19-9. Into the culture various kinds of anti-cancer drugs (MMC, ADR, FAR, 5FU, FT, CDDP, CPT-11) were administered for a period of 2 days, followed by irradiation with {sup 60}Co. Observation period was 20 days, during which we measured LDH, CEA and Ca19-9 in medium, DNA, protein, CEA and CA19-9 in cells in addition to observation of cells through microscope. Effects of anti-cancer drugs on pancreatic cancer cells were greater than those of irradiation when doses of anti-cancer drugs were enough. By using a lot of anti-cancer drugs, LDH value in medium increased at early time and decreased later. CEA and Ca19-9 values in medium decreased with the lapse of time, while they were increased later when small doses of the drugs had been administered. DNA, protein, CEA and Ca19-9 values in cells showed a decrease in accordance with increased doses of the drugs. Effects of FT and CPT-11 were marginal compared with the other drugs. (author).

  16. Simulating plastic surgery: from human skin tensile tests, through hyperelastic finite element models to real-time haptics. (United States)

    Lapeer, R J; Gasson, P D; Karri, V


    In this paper, we provide a summary of a number of experiments we conducted to arrive at a prototype real-time simulator for plastic surgical interventions such as skin flap repair and inguinal herniotomy. We started our research with a series of in-vitro tensile stress tests on human skin, harvested from female patients undergoing plastic reconstructive surgery. We then used the acquired stress-strain data to fit hyperelastic models. Three models were considered: General Polynomial, Reduced Polynomial and Ogden. Only Reduced Polynomial models were found to be stable, hence they progressed to the next stage to be used in an explicit finite element model aimed at real-time performance in conjunction with a haptic feedback device. A total Lagrangian formulation with the half-step central difference method was employed to integrate the dynamic equation of motion of the mesh. The mesh was integrated into two versions of a real-time skin simulator: a single-threaded version running on a computer's main central processing unit and a multi-threaded version running on the computer's graphics card. The latter was achieved by exploiting recent advances in programmable graphics technology.

  17. Time-course of ventilation, arterial and pulmonary CO(2) tension during CO (2) increase in humans. (United States)

    Satoh, Toru; Okada, Yasumasa; Hara, Yasushi; Sakamaki, Fumio; Kyotani, Shingo; Tomita, Takeshi; Nagaya, Noritoshi; Nakanishi, Norifumi


    A change of ventilation (VE), PaCO( 2 ) (arterial CO( 2 ) tension) and PvCO( 2 ) (pulmonary arterial CO( 2 ) tension) with time was not evaluated precisely during exercise or CO( 2 ) rebreathing in humans. In this study, changes of these variables with time were fitted to exponential curves {y = Exp ( x/ T + A ) + k} and compared. When exercise pulmonary hemodynamics was examined in 15 cardiac patients to decide therapies, we asked the patients to undergo CO( 2 ) rebreathing using air with supplementation of consumed O( 2 ). Arterial and pulmonary blood was drawn every minute. During exercise, T was 28.2 ± 8.4 and 26.8 ± 12.4, and A was 0.80 ± 0.50 and 0.50 ± 0.90 in VE and PvCO( 2 ), respectively, with no statistical differences. During CO( 2 ) rebreathing, T was 18.6 ± 5.8, 41.8 ± 38.0 and 21.6 ± 9.7 and A was 0.39 ± 0.67, 1.64 ± 1.35 and 0.17 ± 0.83 in VE, PaCO( 2 ) and PvCO( 2 ), respectively, with statistical difference of PaCO( 2 ) from other variables, suggesting that VE and PvCO( 2 ) showed same mode of change according to time but PaCO( 2 ) did not.

  18. New Potential Biomarker for Methasterone Misuse in Human Urine by Liquid Chromatography Quadrupole Time of Flight Mass Spectrometry (United States)

    Zhang, Jianli; Lu, Jianghai; Wu, Yun; Wang, Xiaobing; Xu, Youxuan; Zhang, Yinong; Wang, Yan


    In this study, methasterone urinary metabolic profiles were investigated by liquid chromatography quadrupole time of flight mass spectrometry (LC-QTOF-MS) in full scan and targeted MS/MS modes with accurate mass measurement. A healthy male volunteer was asked to take the drug and liquid–liquid extraction was employed to process urine samples. Chromatographic peaks for potential metabolites were hunted out with the theoretical [M − H]− as a target ion in a full scan experiment and actual deprotonated ions were studied in targeted MS/MS experiment. Fifteen metabolites including two new sulfates (S1 and S2), three glucuronide conjugates (G2, G6 and G7), and three free metabolites (M2, M4 and M6) were detected for methasterone. Three metabolites involving G4, G5 and M5 were obtained for the first time in human urine samples. Owing to the absence of helpful fragments to elucidate the steroid ring structure of methasterone phase II metabolites, gas chromatography mass spectrometry (GC-MS) was employed to obtain structural information of the trimethylsilylated phase I metabolite released after enzymatic hydrolysis and the potential structure was inferred using a combined MS method. Metabolite detection times were also analyzed and G2 (18-nor-17β-hydroxymethyl-2α, 17α-dimethyl-androst-13-en-3α-ol-ξ-O-glucuronide) was thought to be new potential biomarker for methasterone misuse which can be detected up to 10 days. PMID:27669235

  19. Continuous time Bayesian networks identify Prdm1 as a negative regulator of TH17 cell differentiation in humans. (United States)

    Acerbi, Enzo; Viganò, Elena; Poidinger, Michael; Mortellaro, Alessandra; Zelante, Teresa; Stella, Fabio


    T helper 17 (TH17) cells represent a pivotal adaptive cell subset involved in multiple immune disorders in mammalian species. Deciphering the molecular interactions regulating TH17 cell differentiation is particularly critical for novel drug target discovery designed to control maladaptive inflammatory conditions. Using continuous time Bayesian networks over a time-course gene expression dataset, we inferred the global regulatory network controlling TH17 differentiation. From the network, we identified the Prdm1 gene encoding the B lymphocyte-induced maturation protein 1 as a crucial negative regulator of human TH17 cell differentiation. The results have been validated by perturbing Prdm1 expression on freshly isolated CD4(+) naïve T cells: reduction of Prdm1 expression leads to augmentation of IL-17 release. These data unravel a possible novel target to control TH17 polarization in inflammatory disorders. Furthermore, this study represents the first in vitro validation of continuous time Bayesian networks as gene network reconstruction method and as hypothesis generation tool for wet-lab biological experiments.

  20. Mechanical diagnosis of human erythrocytes by ultra-high speed manipulation unraveled critical time window for global cytoskeletal remodeling (United States)

    Ito, Hiroaki; Murakami, Ryo; Sakuma, Shinya; Tsai, Chia-Hung Dylan; Gutsmann, Thomas; Brandenburg, Klaus; Pöschl, Johannes M. B.; Arai, Fumihito; Kaneko, Makoto; Tanaka, Motomu


    Large deformability of erythrocytes in microvasculature is a prerequisite to realize smooth circulation. We develop a novel tool for the three-step “Catch-Load-Launch” manipulation of a human erythrocyte based on an ultra-high speed position control by a microfluidic “robotic pump”. Quantification of the erythrocyte shape recovery as a function of loading time uncovered the critical time window for the transition between fast and slow recoveries. The comparison with erythrocytes under depletion of adenosine triphosphate revealed that the cytoskeletal remodeling over a whole cell occurs in 3 orders of magnitude longer timescale than the local dissociation-reassociation of a single spectrin node. Finally, we modeled septic conditions by incubating erythrocytes with endotoxin, and found that the exposure to endotoxin results in a significant delay in the characteristic transition time for cytoskeletal remodeling. The high speed manipulation of erythrocytes with a robotic pump technique allows for high throughput mechanical diagnosis of blood-related diseases. PMID:28233788

  1. Assessment of human embryos by time-lapse videography: A comparison of quantitative and qualitative measures between two independent laboratories. (United States)

    Liu, Yanhe; Copeland, Christopher; Stevens, Adam; Feenan, Katie; Chapple, Vincent; Myssonski, Kim; Roberts, Peter; Matson, Phillip


    A total of 488 Day 3 human embryos with known implantation data from two independent in vitro fertilization laboratories were included for analysis, with 270 from Fertility North (FN) and 218 from Canberra Fertility Centre (CFC). Implanting embryos grew at different rates between FN and CFC as indicated in hours of the time intervals between pronuclear fading and the 4- (13.9 ± 1.1 vs. 14.9 ± 1.8), 5- (25.7 ± 1.9 vs. 28.4 ± 3.7) and 8-cell stages (29.0 ± 3.2 vs. 32.2 ± 4.6), as well as the durations of 2- (10.8 ± 0.8 vs. 11.6 ± 1.1), 3- (0.4 ± 0.5 vs. 0.9 ± 1.2), and 4-cell stages (11.8 ± 1.4 vs. 13.6 ± 2.9), all pqualitative measures including poor conventional morphology, direct cleavage, reverse cleavage and 0.05) or non-implanting embryos (30.4% vs. 38.3%, p>0.05) between FN and CFC. Furthermore, implanting embryos favored lower proportions of the above biological events compared to the non-implanting ones in both laboratories (both pquantitative timing parameters may have reduced inter-laboratory transferability; qualitative measures are independent of cell division timings, with potentially improved inter-laboratory reproducibility.

  2. Understanding Human Development Potentials and Demands for Greenhouse Gas Emissions:with Empirical Analysis using time series and cross-sectional data

    Institute of Scientific and Technical Information of China (English)

    Pan Jiahua


    Based on an investigation of the meaning of development, the neo-dassical economic approach to development, and the post-welfarist theory of development, this paper proposes a conceptual framework for understanding human development potentials, while undertaking empirical analysis using cross-sectional and time series data on human development. Human development is associated with basic necessities for subsistence, the quality of life,and political and civil rights, in addition to income indicators. Our analysis suggests that the concept of human development potentials has two dimensions:the rights of development and limits to human development. Both are largely ignored in the neoclassical theory of development. However, human development is not unbounded, which approaches to a relatively fixed constant at given economic,technological and institutional conditions. This conceptual understanding is supported by results from the empirical examination of the relationships between demands for carbon emissions and other elements of human development.

  3. Expression Levels of RFP in Normal and Cancer Human Tissues via Real-time RT-PCR Detection

    Institute of Scientific and Technical Information of China (English)


    Ret finger protein(RFP) is a member of the tripartite motif family, which is characterized by a conserved RING finger of motif, a B-box, and a coiled-coil domain(they are called RBCC generally). Although RFP was known to be an oncogene when its RBCC moiety was connected with a tyrosine kinase domain by DNA rearrangement, its biological function was not well defined. In this study, by using real-time RT-PCR, the RFP expressions in human and mouse normal tissues, and in the cervical squamous cell carcinoma, endometrial adenocarcinoma, gastric adenocarcinoma, esophageal squamous cell carcinoma, and brain cancer tissues were analyzed. The result of the study proved that the highest level of mRNA reverse transcription appeared in the normal testical tissue, whereas that in other normal tissues of human and mice were low. The mRNA reverse transcription level of RFP was higher in the endometrial adenocarcinoma tissue than in the cervical squamous cell carcinoma tissue; the mRNA reverse transcription level of RFP in the gastric adenocarcinoma tissue was significantly higher than that in the esophageal squamous cell carcinoma tissue. It was also found that the mRNA reverse transcription level of RFP in the brain cancer tissue was higher than that in the normal brain tissue. These results suggested that RFP could possibly be a useful molecular target for the development of new therapeutics for malignant tumors.

  4. Real-time PCR-based identification of Borrelia burgdorferi sensu lato species in ticks collected from humans in Romania. (United States)

    Briciu, Violeta T; Meyer, Fabian; Sebah, Daniela; Tăţulescu, Doina F; Coroiu, Georgiana; Lupşe, Mihaela; Carstina, Dumitru; Mihalca, Andrei D; Hizo-Teufel, Cecilia; Klier, Christiane; Huber, Ingrid; Fingerle, Volker


    The aims of our study were to determine (i) which tick species bite humans in Romania and (ii) the prevalence of Borrelia (B.) burgdorferi genospecies in these ticks. All ticks collected from patients who presented to the Clinic of Infectious Diseases Cluj Napoca in spring/summer 2010 were morphologically identified by an entomologist and tested for B. burgdorferi genospecies prevalence by a real-time PCR assay targeting the hbb gene and melting curve analysis. Out of 532 ticks, 518 were Ixodes ricinus, 10 Dermacentor marginatus, and 3 Haemaphysalis spp. ticks, and one unidentified tick due to destruction. Since evaluation of the hbb PCR revealed that it was not possible to differentiate between B. spielmanii/B. valaisiana and B. garinii/B. bavariensis, sequencing of an 800-bp fragment of the ospA gene was performed in these cases. Out of 389 investigated ticks, 43 were positive by hbb PCR for B. burgdorferi sensu lato. The positive samples were 42 Ixodes ricinus (11.1% B. burgdorferi sensu lato prevalence) and the one unidentified tick. Species identification revealed the presence of mainly B. afzelii, but also of B. garinii, B. burgdorferi sensu stricto, B. valaisiana, and B. lusitaniae. In 4 samples, differentiation between B. spielmanii/B. valaisiana was impossible. Our study shows that the most relevant human pathogenic B. burgdorferi genospecies - predominantly B. afzelii - are present in ticks collected from Romanian patients.

  5. Time-of-flight secondary ion mass spectrometry-based molecular distribution distinguishing healthy and osteoarthritic human cartilage

    CERN Document Server

    Cillero-Pastor, Berta; Kiss, Andras; Blanco, Francisco J; Heeren, Ron M A


    Osteoarthritis (OA) is a pathology that ultimately causes joint destruction. The cartilage is one of the principal affected tissues. Alterations in the lipid mediators and an imbalance in the metabolism of cells that form the cartilage (chondrocytes) have been described as contributors to the OA development. In this study, we have studied the distribution of lipids and chemical elements in healthy and OA human cartilage. Time of flight-secondary ion mass spectrometry (TOF-SIMS) allows us to study the spatial distribution of molecules at a high resolution on a tissue section. TOF-SIMS revealed a specific peak profile that distinguishes healthy from OA cartilages. The spatial distribution of cholesterol-related peaks exhibited a remarkable difference between healthy and OA cartilages. A distinctive colocalization of cholesterol and other lipids in the superficial area of the cartilage was found. A higher intensity of oleic acid and other fatty acids in the OA cartilages exhibited a similar localization. On the ...

  6. Real-time study of shape and thermal fluctuations in the echinocyte transformation of human erythrocytes using defocusing microscopy. (United States)

    Etcheverry, Sebastián; Gallardo, María José; Solano, Pablo; Suwalsky, Mario; Mesquita, Oscar N; Saavedra, Carlos


    We present a real-time method to measure the amplitude of thermal fluctuations in biological membranes by means of a new treatment of the defocusing microscopy (DM) optical technique. This approach was also applied to study the deformation of human erythrocytes to its echinocyte structure. This was carried out by making three-dimensional shape reconstructions of the cell and measuring the thermal fluctuations of its membrane, as the cell is exposed to the anti-inflammatory drug naproxen and as it recovers its original shape, when it is subsequently cleansed of the drug. The results showed biomechanical changes in the membrane even at low naproxen concentration (0.2 mM). Also, we found that when the cell recovered its original shape, the membrane properties were different compared to the nondrugged initial erythrocyte, indicating that the drug administration-recovery process is not completely reversible.

  7. The Humanity Marches into the Low-Carbon Time%人类步入低碳时代

    Institute of Scientific and Technical Information of China (English)



    The low-carbon time's arrival, is international big background making to cause to so, particularly the energy crisis, the climate crisis and financial crisis's superimposed effect, its bright attribute is the iow-carbon which fierce disputes' climate politics,engulfs the entire world economical, the vigorous development low-carbon science and technology, the aware showing low-carbon culture, this indicates the human culture jump.%低碳时代的到来,是国际大背景使然,尤其是能源危机、气候危机和金融危机的叠加效应,其鲜明表征是激烈交锋的气候政治、席卷全球的低/碳经济、蓬勃发展的低碳科技、自觉彰显的低/碳文化,这预示着人类文明的跃迁.

  8. In vivo field dependence of proton relaxation times in human brain, liver and skeletal muscle: a multicenter study

    DEFF Research Database (Denmark)

    Henriksen, O; de Certaines, J D; Spisni, A;


    T1 and T2 relaxation times are fundamental parameters for signal contrast behaviour in MRI. A number of ex vivo relaxometry studies have dealt with the magnetic field dispersion of T1. By means of multicenter study within the frame of the COMAC BME Concerted Action on Tissue Characterization by MRI...... and MRS, the in vivo field dispersion of T1 and T2 has been measured in order to evaluate whether ex vivo data are representative for the in vivo situation. Brain, skeletal muscle, and liver of healthy human volunteers were studied. Fifteen MR units with a field strength ranging from 0.08 T to 1.5 T took...... part in the trial, which comprised 218 volunteers. All the MR systems were tested for measurement accuracy using the Eurospin TO5 test object. The measured relaxation data were subsequently corrected according to the obtained calibration curves. The results showed a clear field dispersion of T1...

  9. Quantification of viral genome in cord blood donors by real time PCR to investigate human herpesvirus type 8 active infection. (United States)

    Golchin, Neda; Kheirandish, Maryam; Sharifi, Zohreh; Samiee, Shahram; Kokhaei, Parviz; Pourpak, Zahra


    Umbilical cord blood (UCB) is one of the most important sources of hematopoietic stem cells which can be used for transplantation. The transplanted CB stem cells might cause infections in recipients. The aim of this study is to evaluate Human Herpes Virus8 (HHV8) as a Rhadinovirus among CB samples in order to assess safety of cord blood stem cells transplantation. To assess this aim, we surveyed 800 cord blood specimens by Real Time PCR.The overall HHV8 incidence in cord blood mononuclear cells was 1.38% and none of them was in lytic phase of HHV8. The authors suggest further HHV8 study on CB samples for transplantation.

  10. Comparing the Effect of Topical Application of Human Milk and Dry Cord Care on Umbilical Cord Separation Time in Healthy Newborn Infants

    Directory of Open Access Journals (Sweden)

    Azar Aghamohammadi


    Full Text Available Objective: Comparing the effect of topical human milk application and dry cord care on cord separation time.Methods: This research was a randomized clinical trial study on 130 singleton and mature newborns.Newborns were placed randomly in groups of topical application of human milk and dry cord care. Theumbilical separation time was compared in the two groups. Data was analyzed by SPSS software. Independent Samples t-Test, χ2, Fisher were used in this study.Findings: Median time of cord separation in human milk application group (150.95±28.68 hours was significantly shorter than dry cord care group (180.93±37.42 hours (P<0.001.Conclusion: Topical application of human milk on the remaining part of the cord reduces the cord separation time and it can be used as an easy, cheap and non invasive way for cord care.

  11. Evaluating genomic DNA extraction methods from human whole blood using endpoint and real-time PCR assays. (United States)

    Koshy, Linda; Anju, A L; Harikrishnan, S; Kutty, V R; Jissa, V T; Kurikesu, Irin; Jayachandran, Parvathy; Jayakumaran Nair, A; Gangaprasad, A; Nair, G M; Sudhakaran, P R


    The extraction of genomic DNA is the crucial first step in large-scale epidemiological studies. Though there are many popular DNA isolation methods from human whole blood, only a few reports have compared their efficiencies using both end-point and real-time PCR assays. Genomic DNA was extracted from coronary artery disease patients using solution-based conventional protocols such as the phenol-chloroform/proteinase-K method and a non-phenolic non-enzymatic Rapid-Method, which were evaluated and compared vis-a-vis a commercially available silica column-based Blood DNA isolation kit. The appropriate method for efficiently extracting relatively pure DNA was assessed based on the total DNA yield, concentration, purity ratios (A260/A280 and A260/A230), spectral profile and agarose gel electrophoresis analysis. The quality of the isolated DNA was further analysed for PCR inhibition using a murine specific ATP1A3 qPCR assay and mtDNA/Y-chromosome ratio determination assay. The suitability of the extracted DNA for downstream applications such as end-point SNP genotyping, was tested using PCR-RFLP analysis of the AGTR1-1166A>C variant, a mirSNP having pharmacogenetic relevance in cardiovascular diseases. Compared to the traditional phenol-chloroform/proteinase-K method, our results indicated the Rapid-Method to be a more suitable protocol for genomic DNA extraction from human whole blood in terms of DNA quantity, quality, safety, processing time and cost. The Rapid-Method, which is based on a simple salting-out procedure, is not only safe and cost-effective, but also has the added advantage of being scaled up to process variable sample volumes, thus enabling it to be applied in large-scale epidemiological studies.

  12. Human resources needs for universal access to antiretroviral therapy in South Africa: a time and motion study

    Directory of Open Access Journals (Sweden)

    Hontelez Jan AC


    Full Text Available Abstract Background Although access to life-saving treatment for patients infected with HIV in South Africa has improved substantially since 2004, treating all eligible patients (universal access remains elusive. As the prices of antiretroviral drugs have dropped over the past years, availability of human resources may now be the most important barrier to achieving universal access to HIV treatment in Africa. We quantify the number of HIV health workers (HHWs required to be added to the current HIV workforce to achieve universal access to HIV treatment in South Africa, under different eligibility criteria. Methods We performed a time and motion study in three HIV clinics in a rural, primary care-based HIV treatment program in KwaZulu-Natal, South Africa, to estimate the average time per patient visit for doctors, nurses, and counselors. We estimated the additional number of HHWs needed to achieve universal access to HIV treatment within one year. Results For universal access to HIV treatment for all patients with a CD4 cell count of ≤350 cells/μl, an additional 2,200 nurses, 3,800 counselors, and 300 doctors would be required, at additional annual salary cost of 929 million South African rand (ZAR, equivalent to US$ 141 million. For universal treatment (‘treatment as prevention’, an additional 6,000 nurses, 11,000 counselors, and 800 doctors would be required, at an additional annual salary cost of ZAR 2.6 billion (US$ 400 million. Conclusions Universal access to HIV treatment for patients with a CD4 cell count of ≤350 cells/μl in South Africa may be affordable, but the number of HHWs available for HIV treatment will need to be substantially increased. Treatment as prevention strategies will require considerable additional financial and human resources commitments.

  13. Time course of the induction of homeostatic plasticity generated by repeated transcranial direct current stimulation of the human motor cortex. (United States)

    Fricke, K; Seeber, A A; Thirugnanasambandam, N; Paulus, W; Nitsche, M A; Rothwell, J C


    Several mechanisms have been proposed that control the amount of plasticity in neuronal circuits and guarantee dynamic stability of neuronal networks. Homeostatic plasticity suggests that the ease with which a synaptic connection is facilitated/suppressed depends on the previous amount of network activity. We describe how such homeostatic-like interactions depend on the time interval between two conditioning protocols and on the duration of the preconditioning protocol. We used transcranial direct current stimulation (tDCS) to produce short-lasting plasticity in the motor cortex of healthy humans. In the main experiment, we compared the aftereffect of a single 5-min session of anodal or cathodal tDCS with the effect of a 5-min tDCS session preceded by an identical 5-min conditioning session administered 30, 3, or 0 min beforehand. Five-minute anodal tDCS increases excitability for about 5 min. The same duration of cathodal tDCS reduces excitability. Increasing the duration of tDCS to 10 min prolongs the duration of the effects. If two 5-min periods of tDCS are applied with a 30-min break between them, the effect of the second period of tDCS is identical to that of 5-min stimulation alone. If the break is only 3 min, then the second session has the opposite effect to 5-min tDCS given alone. Control experiments show that these shifts in the direction of plasticity evolve during the 10 min after the first tDCS session and depend on the duration of the first tDCS but not on intracortical inhibition and facilitation. The results are compatible with a time-dependent "homeostatic-like" rule governing the response of the human motor cortex to plasticity probing protocols.

  14. Real-time in vivo imaging of early mucosal changes during ischemia-reperfusion in human jejunum.

    Directory of Open Access Journals (Sweden)

    Joep Grootjans

    Full Text Available BACKGROUND AND STUDY AIMS: Small intestinal ischemia-reperfusion (IR is a frequent, potentially life threatening phenomenon. There is a lack of non-invasive diagnostic modalities. For many intestinal diseases, visualizing the intestinal mucosa using endoscopy is gold standard. However, limited knowledge exists on small intestinal IR-induced, early mucosal changes. The aims of this study were to investigate endoscopic changes in human jejunum exposed to IR, and to study concordance between endoscopic appearance and histology. PATIENTS AND METHODS: In 23 patients a part of jejunum, to be removed for surgical reasons, was isolated and selectively exposed to ischemia with 0, 30 or 120 minutes of reperfusion. In 3 patients, a videocapsule was inserted in the isolated segment before exposure to IR, to visualize the mucosa. Endoscopic view at several time points was related to histology (Heamatoxylin & Eosin obtained from 20 patients. RESULTS: Ischemia was characterized by loss of villous structure, mucosal whitening and appearance of punctate lesions. This was related to appearance of subepithelial spaces and breaches in the epithelial lining in the histological view. Early during reperfusion, the lumen filled with IR-damaged, shed cells and VCE showed mucosal erosions, hemorrhage and intraluminal debris. At 60 minutes of reperfusion, the only remaining signs of IR were loss of villous structure and small erosions, indicating rapid mucosal healing. CONCLUSIONS: This study shows a unique, real-time in vivo endoscopic view of early mucosal changes during IR of the human small intestine. Future studies should evaluate its usefulness in diagnosis of patients suspected of IR.

  15. The time course of metabolites in human plasma after 6-[(18)F]fluoro-l-m-tyrosine administration. (United States)

    Wahl, L M; Chen, J J; Thompson, M; Chirakal, R; Nahmias, C


    For the investigation of intracerebral dopamine metabolism, 6-[(18)F]fluoro-l-m-tyrosine (FmT) has been proposed as an alternative tracer that, unlike 6-[(18)F]fluoro-l-dopa, is not subjected to O-methylation. We have studied the time course of FmT and its labelled metabolites in plasma after intravenous injection into humans, employing a method that we have developed and validated to analyze labelled metabolites of FmT in plasma. The study population comprised 38 subjects, 14 of whom were taking an aromatic amino acid decarboxylase inhibitor (carbidopa), and obtained arterialized venous blood samples at various times after an intravenous injection of between 185 and 370 MBq of FmT. The major metabolite of FmT present in plasma was 6-[(18)F]fluoro-3-hydroxyphenylacetic acid. The time course of the fraction of radioactivity in plasma attributable to FmT was fitted well by the decay of two exponential functions. The fast component of the decay accounted for 40%-50% of the radioactivity and had a half-life of about 5 min. The slow component of the decay had a half-life of about 6 h in the subjects not taking carbidopa and 20 h in the patients taking carbidopa. When the total available FmT was calculated for each individual subject and expressed as a proportion of total radioactivity, this quantity did not differ significantly from that determined from the corresponding population mean. There was significantly more (15% on average) FmT available over the course of the 2-h experiment in the group pretreated with carbidopa. Our results demonstrate that the major metabolite in plasma after an intravenous injection of FmT is 6-[(18)F]fluoro-3-hydroxyphenylacetic acid. The clearance of FmT from plasma compares well with the clearance of intravenously administered levodopa. Carbidopa increases significantly the availability of FmT in plasma. These results verify, in a large number of human subjects, earlier analyses of FmT metabolism in other species. We validate a

  16. Time of correlation of low-frequency fluctuations in the regional laser Doppler flow signal from human skin (United States)

    Folgosi-Correa, M. S.; Nogueira, G. E. C.


    The laser Doppler flowmetry allows the non-invasive assessment of the skin perfusion in real-time, being an attractive technique to study the human microcirculation in clinical settings. Low-frequency oscillations in the laser Doppler blood flow signal from the skin have been related to the endothelial, endothelial-metabolic, neurogenic and myogenic mechanisms of microvascular flow control, in the range 0.005-0.0095 Hz, 0.0095-0.021 Hz, 0.021-0.052 Hz and 0.052- 0.145 Hz respectively. The mean Amplitude (A) of the periodic fluctuations in the laser Doppler blood flow signal, in each frequency range, derived from the respective wavelet-transformed coefficients, has been used to assess the function and dysfunctions of each mechanism of flow control. Known sources of flow signal variances include spatial and temporal variability, diminishing the discriminatory capability of the technique. Here a new time domain method of analysis is proposed, based on the Time of Correlation (TC) of flow fluctuations between two adjacent sites. Registers of blood flow from two adjacent regions, for skin temperature at 32 0C (basal) and thermally stimulated (42 0C) of volar forearms from 20 healthy volunteers were collected and analyzed. The results obtained revealed high time of correlation between two adjacent regions when thermally stimulated, for signals in the endothelial, endothelial-metabolic, neurogenic and myogenic frequency ranges. Experimental data also indicate lower variability for TC when compared to A, when thermally stimulated, suggesting a new promising parameter for assessment of the microvascular flow control.

  17. Detection and identification of human Plasmodium species with real-time quantitative nucleic acid sequence-based amplification

    Directory of Open Access Journals (Sweden)

    Kager Piet A


    Full Text Available Abstract Background Decisions concerning malaria treatment depend on species identification causing disease. Microscopy is most frequently used, but at low parasitaemia (Plasmodium antigen detection do often not allow for species discrimination as microscopy does, but also become insensitive at Methods This paper reports the development of a sensitive and specific real-time Quantitative Nucleic Acid Sequence Based Amplification (real-time QT-NASBA assays, based on the small-subunit 18S rRNA gene, to identify the four human Plasmodium species. Results The lower detection limit of the assay is 100 – 1000 molecules in vitro RNA for all species, which corresponds to 0.01 – 0.1 parasite per diagnostic sample (i.e. 50 μl of processed blood. The real-time QT-NASBA was further evaluated using 79 clinical samples from malaria patients: i.e. 11 Plasmodium. falciparum, 37 Plasmodium vivax, seven Plasmodium malariae, four Plasmodium ovale and 20 mixed infections. The initial diagnosis of 69 out of the 79 samples was confirmed with the developed real-time QT-NASBA. Re-analysis of seven available original slides resolved five mismatches. Three of those were initially identified as P. malariae mono-infection, but after re-reading the slides P. falciparum was found, confirming the real-time QT-NASBA result. The other two slides were of poor quality not allowing true species identification. The remaining five discordant results could not be explained by microscopy, but may be due to extreme low numbers of parasites present in the samples. In addition, 12 Plasmodium berghei isolates from mice and 20 blood samples from healthy donors did not show any reaction in the assay. Conclusion Real-time QT-NASBA is a very sensitive and specific technique with a detection limit of 0.1 Plasmodium parasite per diagnostic sample (50 μl of blood and can be used for the detection, identification and quantitative measurement of low parasitaemia of Plasmodium species, thus

  18. Development and assessment of a multiplex real-time PCR assay for quantification of human immunodeficiency virus type 1 DNA. (United States)

    Beloukas, A; Paraskevis, D; Haida, C; Sypsa, V; Hatzakis, A


    Previous studies showed that high levels of human immunodeficiency virus type 1 (HIV-1) DNA are associated with a faster progression to AIDS, an increased risk of death, and a higher risk of HIV RNA rebound in patients on highly active antiretroviral therapy. Our objective was to develop and assess a highly sensitive real-time multiplex PCR assay for the quantification of HIV-1 DNA (RTMP-HIV) based on molecular beacons. HIV-1 DNA quantification was carried out by RTMP in a LightCycler 2.0 apparatus. HIV-1 DNA was quantified in parallel with CCR5 as a reference gene, and reported values are numbers of HIV-1 DNA copies/10(6) peripheral blood mononuclear cells (PBMCs). The clinical sensitivity of the assay was assessed for 115 newly diagnosed HIV-1-infected individuals. The analytical sensitivity was estimated to be 12.5 copies of HIV-1 DNA per 10(6) PBMCs, while the clinical sensitivity was 100%, with levels ranging from 1.23 to 4.25 log(10) HIV-1 DNA copies/10(6) PBMCs. In conclusion, we developed and assessed a new RTMP-HIV assay based on molecular beacons, using a LightCycler 2.0 instrument. This multiplex assay has comparable sensitivity, reproducibility, and accuracy to single real-time PCR assays.

  19. Self-regulation of human brain activity using simultaneous real-time fMRI and EEG neurofeedback

    CERN Document Server

    Zotev, Vadim; Yuan, Han; Misaki, Masaya; Bodurka, Jerzy


    Neurofeedback is a promising approach for non-invasive modulation of human brain activity with applications for treatment of mental disorders and enhancement of brain performance. Neurofeedback techniques are commonly based on either electroencephalography (EEG) or real-time functional magnetic resonance imaging (rtfMRI). Advances in simultaneous EEG-fMRI have made it possible to combine the two approaches. Here we report the first implementation of simultaneous multimodal rtfMRI and EEG neurofeedback (rtfMRI-EEG-nf). It is based on a novel system for real-time integration of simultaneous rtfMRI and EEG data streams. We applied the rtfMRI-EEG-nf to training of emotional self-regulation in healthy subjects performing a positive emotion induction task based on retrieval of happy autobiographical memories. The participants were able to simultaneously regulate their BOLD fMRI activation of the left amygdala and frontal EEG power asymmetry in the high-beta band using the rtfMRI-EEG-nf. Our proof-of-concept results...

  20. Dose- and time-dependent benefits of iPad technology in an undergraduate human anatomy course. (United States)

    Raney, Marcella A


    This study examined the impact of iPad integration on performance in an undergraduate gross anatomy course. Two out of six course sections were assigned to one of the following conditions: control (no iPad, n = 61); limited access (laboratory iPads, n = 58); and unlimited access (personal iPads, n = 47). Student knowledge was assessed over time during the semester with two practical examinations in laboratory and four multiple choice/essay examinations in lecture. The same PowerPoint presentations and examinations were utilized for all conditions. Mixed ANOVA analysis identified an interaction effect between time and condition for both laboratory (F2,153  = 16.12; P higher by 3.0% in control and unlimited access conditions, respectively. Unlimited access students scored higher than control and limited access (82.8 ± 2.2 vs 71.5 ± 2.6 and 74.3 ± 1.7%; P higher than control students (78.7 ± 2.1 vs 70.6 ± 2.0%; P tablet devices and relevant applications can be useful tools in human anatomy courses. Anat Sci Educ 9: 367-377. © 2015 American Association of Anatomists.

  1. Functional Stability of the Human Kappa Opioid Receptor Reconstituted in Nanodiscs Revealed by a Time-Resolved Scintillation Proximity Assay (United States)

    Hansen, Randi Westh; Wang, Xiaole; Golab, Agnieszka; Bornert, Olivier; Oswald, Christine; Wagner, Renaud; Martinez, Karen Laurence


    Long-term functional stability of isolated membrane proteins is crucial for many in vitro applications used to elucidate molecular mechanisms, and used for drug screening platforms in modern pharmaceutical industry. Compared to soluble proteins, the understanding at the molecular level of membrane proteins remains a challenge. This is partly due to the difficulty to isolate and simultaneously maintain their structural and functional stability, because of their hydrophobic nature. Here we show, how scintillation proximity assay can be used to analyze time-resolved high-affinity ligand binding to membrane proteins solubilized in various environments. The assay was used to establish conditions that preserved the biological function of isolated human kappa opioid receptor. In detergent solution the receptor lost high-affinity ligand binding to a radiolabelled ligand within minutes at room temperature. After reconstitution in Nanodiscs made of phospholipid bilayer the half-life of high-affinity ligand binding to the majority of receptors increased 70-fold compared to detergent solubilized receptors—a level of stability that is appropriate for further downstream applications. Time-resolved scintillation proximity assay has the potential to screen numerous conditions in parallel to obtain high levels of stable and active membrane proteins, which are intrinsically unstable in detergent solution, and with minimum material consumption. PMID:27035823

  2. Time-dependent inhibition of CYP3A4 by gallic acid in human liver microsomes and recombinant systems. (United States)

    Pu, Qiang-Hong; Shi, Liang; Yu, Chao


    1.Gallic acid is a main polyphenol in various fruits and plants. Inhibitory characteristics of gallic acid on CYP3A4 were still unclear. The objective of this work is hence to investigate inhibitory characteristics of gallic acid on CYP3A4 using testosterone as the probe substrate in human liver microsomes (HLMs) and recombinant CYP3A4 (rCYP3A4) systems. 2.Gallic acid caused concentration-dependent loss of CYP3A4 activity with IC50 values of 615.2 μM and 669.5 μM in HLM and rCYP3A4 systems, respectively. IC50-shift experiments showed that pre-incubation with gallic acid in the absence of NADPH contributed to 12- or 14-fold reduction of IC50 in HLM and rCYP3A4 systems, respectively, supporting a time-dependent inhibition. In HLM, time-dependent inactivation variables KI and Kinact were 485.8 μM and 0.05 min(-1), respectively. 3.Compared with the presence of NADPH, pre-incubation of gallic acid in the absence of NADPH markedly increased its inhibitory effects in HLM and rCYP3A4 systems. Those results indicate that CYP3A4 inactivation by gallic acid was independent on NADPH and was mainly mediated its oxidative products. 4.In conclusion, we showed that gallic acid weakly and time-dependently inactivated CYP3A4 via its oxidative products.

  3. Comparison of real-time PCR and conventional PCR with two DNA targets for detection of Leishmania (Leishmania) infantum infection in human and dog blood samples. (United States)

    Mohammadiha, A; Mohebali, M; Haghighi, A; Mahdian, R; Abadi, A R; Zarei, Z; Yeganeh, F; Kazemi, B; Taghipour, N; Akhoundi, B


    Zoonotic visceral leishmaniasis (VL) is endemic in northwestern Iran. Real-time PCR, conventional PCR, and the direct agglutination test (DAT) were used to diagnose Leishmania infantum infection in blood samples from 100 domestic dogs and 100 humans. Based on clinical evaluation, 82 humans and 72 dogs from the endemic area were categorized as having asymptomatic infection, DAT positive with no clinical signs of VL, or symptomatic infection, DAT positive with at least one sign of VL. Eighteen human samples containing no Leishmania antibodies (DAT(-)) and 28 dog DAT(-) sera from non-endemic areas with no history of VL constituted negative controls. All 46 DAT(-) samples were also negative by Dipstick rK39. Bone marrow material was used for parasitological examinations in symptomatic VL, and peripheral blood samples were used for detection of L. infantum infection using conventional PCR and real-time PCR in non-symptomatic subjects. Two DNA targets (ITS1 kDNA) were used for conventional PCR. L. infantum antibodies in sera were detected by DAT. Parasitemia was measured by real-time PCR targeting kDNA using Taqman Assay. All 72 (100%) symptomatic (38/38) and asymptomatic (34/34) dog DAT(+)samples, 45 of 48 (93.8%) symptomatic human DAT(+) samples, and 32 of 34 (94.1%) human asymptomatic cases were identified by real-time PCR. The mean (59.19 vs 12.38 parasite equivalents/mL of blood) and median (16.15 vs 1 parasite equivalents/mL of blood) ranges of parasitemia were higher in dogs than in humans (Preal-time PCR and DAT (99% in dogs and 95% in humans). Sensitivity of 100% and 93.9%, specificity of 96.4% and 100%, positive predictive values of 98.6% and 100%, and negative predictive values of 100% and 78.3% were found by real-time PCR for dog and human samples, respectively.

  4. Natural vs human-induced changes at the Tauranga Harbour area (New Zealand): a time -series acoustic seabed classification comparison (United States)

    Capperucci, Ruggero Maria; Bartholomä, Alexander; Renken, Sabrina; De Lange, Willem


    The Tauranga Harbour Bay (New Zealand) is a mesotidal estuary system, enclosed by the Matakana barrier island. It hosts the leading export port in New Zealand and the second largest import port by value. Coastal changes are well documented over the last decades, mainly at the southern entrance of the area, between Matakana Island and Mt. Maunganui. It is an extremely dynamic environment, where natural processes are strongly influenced by human activities. In particular, the understanding of the recent evolution of the system is crucial for policymakers. In fact, the cumulative impact due to the maintenance of the port (mainly dredging activities, shipping, facilities construction, but also increasing tourism) and its already approved expansion clashes with the claim of the local Maori communities, which recently leaded to a court action. A hydroacoustic multiple-device survey (Side-scan Sonar SSS, Multibeam Echo-sounder MBES and Single Beam Echo-sounder) coupled with sediment sampling was carried out in March 2011 over an area of 0.8 km2, southern Matakana Island, along the Western Channel. The area is not directly impacted by dredging activities, resulting in an optimal testing site for assessing indirect effects of human disturbance on coastal dynamics. The main goals were: 1. To test the response of different acoustic systems in such a highly dynamic environment; 2. To study the influence of dredging activities on sediment dynamics and habitat changes, by means of comparing the current data with existing ones, in order to distinguish between natural and human induced changes Results demonstrate a good agreement between acoustic classifications from different systems. They seem to be mainly driven by the sediment distribution, with a distinctive fingerprint given by shells and shell fragments. Nevertheless, the presence of relevant topographic features (i.e. large bedform fields) influences swath-looking systems (SSS and MBES). SSS and MBES classifications tend

  5. TIMED: a computer program for calculating cumulated activity of a radionuclide in the organs of the human body at a given time, t, after deposition

    Energy Technology Data Exchange (ETDEWEB)

    Watson, S.B.; Snyder, W.S.; Ford, M.R.


    TIMED is a computer program designed to calculate cumulated radioactivity in the various source organs at various times after radionuclide deposition. TIMED embodies a system of differential equations which describes activity transfer in the lungs, gastrointestinal tract, and other organs of the body. This system accounts for delay of transfer of activity between compartments of the body and radioactive daughters.

  6. Climatic and human impacts on quasi-periodic and abrupt changes of sedimentation rate at multiple time scales in Lake Taihu, China (United States)

    Liu, Huiyu; Xu, Xiaojuan; Lin, Zhenshan; Zhang, Mingyang; Mi, Ying; Huang, Changchun; Yang, Hao


    With the ensemble Empirical Mode Decomposition Method (EEMD) and the non-parametric Mann-Kendall Test, the quasi-periodic and abrupt changes of sedimentation rate at multiple time scales, and their relations to climate changes and human activities from 1951 to 2010 in Meiliang Bay of Lake Taihu (China) were studied. The results showed the following. (1) The change in sedimentation rate can be completely decomposed into three quasi-periodic changes on 3.7, 6.4, and 24-yr time scales, and a long-term trend. (2) The quasi-periodic changes in sedimentation rate are significantly and positively related to changes in annual average temperature at 6.4 and 24-yr time scales and human activities at 3.7-yr time scales, and not significantly related to precipitation at these time scales. The trend of sedimentation rate has a negative relation with temperature, but positive relations with precipitation and human activities. As a whole, the total variance contribution of climate changes to the quasi-periodic changes of sedimentation rate is close to that of human activities; (3) Temperature and precipitation are possibly related to the abrupt change of sedimentation rate as a whole. Floods have significant impacts on abrupt changes in the sedimentation rate at 3.7, 6.4 and 24-yr time scales. Moreover, some abrupt changes of sedimentation rate at 3.7- and 6.4-yr time scales are partly related to the changes of precipitation at 3.1-yr time scale and temperature at 5-yr time scale. The results of this study will help identify the impacts of climate change and human activities on lake sedimentation at different time scales, and will be available for use as a guide for reasonable development and effective protection of lake resources.

  7. The susceptive alendronate-treatment timing and dosage for osteogenesis enhancement in human bone marrow-derived stem cells.

    Directory of Open Access Journals (Sweden)

    Chih-Hsiang Chang

    Full Text Available Recent studies indicated that alendronate enhanced osteogenesis in osteoblasts and human bone marrow-derived stem cells. However, the time- and dose-dependent effects of Aln on osteogenic differentiation and cytotoxicity of hBMSCs remain undefined. In present study, we investigated the effective dose range and timing of hBMSCs. hBMSCs were treated with various Aln doses (1, 5 and 10 µM according to the following groups: group A was treated with Aln during the first five days of bone medium, groups B, C and D were treated during the first, second, and final five days of osteo-induction medium and group E was treated throughout the entire experiment. The mineralization level and cytotoxicity were measured by quantified Alizarin Red S staining and MTT assay. In addition, the reversal effects of farnesyl pyrophosphate and geranylgeranyl pyrophosphate replenishment in group B were also investigated. The results showed that Aln treatment in groups A, B and E enhanced hBMSC mineralization in a dose-dependent manner, and the most pronounced effects were observed in groups B and E. The higher dose of Aln simultaneously enhanced mineralization and caused cytotoxicity in groups B, C and E. Replenishment of FPP or GGPP resulted in partial or complete reverse of the Aln-induced mineralization respectively. Furthermore, the addition of FPP or GGPP also eliminated the Aln-induced cytotoxicity. We demonstrated that hBMSCs are susceptible to 5 µM Aln during the initiation stage of osteogenic differentiation and that a 10 µM dose is cytotoxic.

  8. Comparison of DNA extraction kits for detection of Burkholderia pseudomallei in spiked human whole blood using real-time PCR.

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    Nicole L Podnecky

    Full Text Available Burkholderia pseudomallei, the etiologic agent of melioidosis, is endemic in northern Australia and Southeast Asia and can cause severe septicemia that may lead to death in 20% to 50% of cases. Rapid detection of B. pseudomallei infection is crucial for timely treatment of septic patients. This study evaluated seven commercially available DNA extraction kits to determine the relative recovery of B. pseudomallei DNA from spiked EDTA-containing human whole blood. The evaluation included three manual kits: the QIAamp DNA Mini kit, the QIAamp DNA Blood Mini kit, and the High Pure PCR Template Preparation kit; and four automated systems: the MagNAPure LC using the DNA Isolation Kit I, the MagNAPure Compact using the Nucleic Acid Isolation Kit I, and the QIAcube using the QIAamp DNA Mini kit and the QIAamp DNA Blood Mini kit. Detection of B. pseudomallei DNA extracted by each kit was performed using the B. pseudomallei specific type III secretion real-time PCR (TTS1 assay. Crossing threshold (C T values were used to compare the limit of detection and reproducibility of each kit. This study also compared the DNA concentrations and DNA purity yielded for each kit. The following kits consistently yielded DNA that produced a detectable signal from blood spiked with 5.5×10(4 colony forming units per mL: the High Pure PCR Template Preparation, QIAamp DNA Mini, MagNA Pure Compact, and the QIAcube running the QIAamp DNA Mini and QIAamp DNA Blood Mini kits. The High Pure PCR Template Preparation kit yielded the lowest limit of detection with spiked blood, but when this kit was used with blood from patients with confirmed cases of melioidosis, the bacteria was not reliably detected indicating blood may not be an optimal specimen.

  9. Full genotyping of a highly polymorphic human gene trait by time-resolved fluorescence resonance energy transfer.

    Directory of Open Access Journals (Sweden)

    Edoardo Totè

    Full Text Available The ability of detecting the subtle variations occurring, among different individuals, within specific DNA sequences encompassed in highly polymorphic genes discloses new applications in genomics and diagnostics. DQB1 is a gene of the HLA-II DQ locus of the Human Leukocyte Antigens (HLA system. The polymorphisms of the trait of the DQB1 gene including codons 52-57 modulate the susceptibility to a number of severe pathologies. Moreover, the donor-receiver tissue compatibility in bone marrow transplantations is routinely assessed through crossed genotyping of DQB and DQA. For the above reasons, the development of rapid, reliable and cost-effective typing technologies of DQB1 in general, and more specifically of the codons 52-57, is a relevant although challenging task. Quantitative assessment of the fluorescence resonance energy transfer (FRET efficiency between chromophores labelling the opposite ends of gene-specific oligonucleotide probes has proven to be a powerful tool to type DNA polymorphisms with single-nucleotide resolution. The FRET efficiency can be most conveniently quantified by applying a time-resolved fluorescence analysis methodology, i.e. time-correlated single-photon counting, which allows working on very diluted template specimens and in the presence of fluorescent contaminants. Here we present a full in-vitro characterization of the fluorescence responses of two probes when hybridized to oligonucleotide mixtures mimicking all the possible genotypes of the codons 52-57 trait of DQB1 (8 homozygous and 28 heterozygous. We show that each genotype can be effectively tagged by the combination of the fluorescence decay constants extrapolated from the data obtained with such probes.

  10. A two-step real-time PCR assay for quantitation and genotyping of human parvovirus 4. (United States)

    Väisänen, E; Lahtinen, A; Eis-Hübinger, A M; Lappalainen, M; Hedman, K; Söderlund-Venermo, M


    Human parvovirus 4 (PARV4) of the family Parvoviridae was discovered in a plasma sample of a patient with an undiagnosed acute infection in 2005. Currently, three PARV4 genotypes have been identified, however, with an unknown clinical significance. Interestingly, these genotypes seem to differ in epidemiology. In Northern Europe, USA and Asia, genotypes 1 and 2 have been found to occur mainly in persons with a history of injecting drug use or other parenteral exposure. In contrast, genotype 3 appears to be endemic in sub-Saharan Africa, where it infects children and adults without such risk behaviour. In this study, a novel straightforward and cost-efficient molecular assay for both quantitation and genotyping of PARV4 DNA was developed. The two-step method first applies a single-probe pan-PARV4 qPCR for screening and quantitation of this relatively rare virus, and subsequently, only the positive samples undergo a real-time PCR-based multi-probe genotyping. The new qPCR-GT method is highly sensitive and specific regardless of the genotype, and thus being suitable for studying the clinical impact and occurrence of the different PARV4 genotypes.

  11. Detection of human papillomavirus in normal oral cavity in a group of Pakistani subjects using real-time PCR. (United States)

    Gichki, Abdul Samad; Buajeeb, Waranun; Doungudomdacha, Sombhun; Khovidhunkit, Siribang-on Pibooniyom


    Since there is evidence that human papillomavirus (HPV) may play some role in oral carcinogenesis, we investigated the presence of HPV in a group of Pakistani subjects with normal oral cavity using real-time PCR analysis. Two-hundred patients attending the Dental Department, Sandaman Provincial Hospital, Balochistan, Pakistan, were recruited. After interview, oral epithelial cells were collected by scraping and subjected to DNA extraction. The HPV-positive DNA samples were further analyzed using primer sets specific for HPV-16 and -18. It was found that out of 200 DNA samples, 192 were PCR-positive for the β-globin gene and these were subsequently examined for the presence of HPV DNA. Among these, 47 (24.5%) were HPV-positive with the virus copy number ranged between 0.43-32 copies per 1 μg of total DNA (9-99 copies per PCR reaction). There were 4 and 11 samples containing HPV-16 and -18, respectively. Additionally, one sample harbored both types of HPV. Among the investigated clinical parameters, smoking habit was associated with the presence of HPV (p=0.001) while others indicated no significant association. The prevalence of HPV in normal oral cavity in our Pakistani subjects appears to be comparable to other studies. However, the association between the presence of HPV and smoking warrants further investigations whether both of these factors can cooperate in inducing oral cancer in this group of patients.

  12. Magnetization transfer contrast imaging in bovine and human cortical bone applying an ultrashort echo time sequence at 3 Tesla. (United States)

    Springer, Fabian; Martirosian, Petros; Machann, Jürgen; Schwenzer, Nina F; Claussen, Claus D; Schick, Fritz


    Magnetization transfer (MT) contrast imaging reveals interactions between free water molecules and macromolecules in a variety of tissues. The introduction of ultrashort echo time (UTE) sequences to clinical whole-body MR scanners expands the possibility of MT imaging to tissues with extremely fast signal decay such as cortical bone. The aim of this study was to investigate the MT effect of bovine cortical bone in vitro on a 3 Tesla whole-body MR unit. A 3D-UTE sequence with a rectangular-shaped on-resonant excitation pulse and a Gaussian-shaped off-resonant saturation pulse for MT preparation was applied. The flip angle and off-resonance frequency of the MT pulse was systematically varied. Measurements on various samples of bovine cortical bone, agar gel, aqueous manganese chloride solutions, and solid polymeric materials (polyurethane) were performed, followed by preliminary applications on human tibial bone in vivo. Direct on-resonant saturation effects of the MT prepulses were calculated numerically by means of Bloch's equations. Corrected for direct saturation effects dry and fresh bovine cortical bone showed "true" MTR values of 0.26 and 0.21, respectively. In vivo data were obtained from three healthy subjects and showed MTR values of 0.30 +/- 0.08. In vivo studies into MT of cortical bone might have the potential to give new insights in musculoskeletal pathologies.

  13. A magnetic nanoparticle-based time-resolved fluoroimmunoassay for determination of the cytokeratin 19 fragment in human serum. (United States)

    Lin, Guanfeng; Liu, Tiancai; Hou, Jingyuan; Ren, Zhiqi; Zhou, Jianwei; Liang, Qianni; Chen, Zhenhua; Dong, Wenqi; Wu, Yingsong


    A sensitive, rapid and novel measurement method for cytokeratin 19 fragment (CYFRA 21-1) in human serum by magnetic particle-based time-resolved fluoroimmunoassay (TRFIA) is described. Built on a sandwich-type immunoassay format, analytes in samples were captured by one monoclonal antibody coating onto the surface of magnetic beads and "sandwiched" by another monoclonal antibody labeled with europium chelates. The coefficient variations of the method were lower than 7%, and the recoveries were in the range of 90-110% for serum samples. The lower limit of quantitation of the present method for CYFRA 21-1 was 0.78 ng/ml. The correlation coefficient of CYFRA 21-1 values obtained by our novel TRFIA and CLIA was 0.980. The present novel TRFIA demonstrated high sensitivity, wider effective detection range and excellent reproducibility for determination of CYFRA 21-1 can be useful for early screening and prognosis evaluation of patients with non-small cell lung cancer.

  14. Cycling probe-based real-time PCR for the detection of Human herpesvirus 6A and B. (United States)

    Ihira, Masaru; Yamaki, Ayumi; Kato, Yuri; Higashimoto, Yuki; Kawamura, Yoshiki; Yoshikawa, Tetsushi


    Human herpesvirus 6 (HHV-6) is classified as two distinct species: HHV-6A and B. HHV-6B infection can cause several clinical manifestations in transplant recipients including encephalitis, bone marrow suppression, and pneumonitis. In contrast to HHV-6B, the clinical features of HHV-6A infection remain largely undefined. Herein, we developed a multiplex cycling probe real-time PCR that discriminated between HHV-6A and HHV-6B. The assay was HHV-6-specific and no cross amplification was demonstrated for other herpesviruses. Moreover, the assay had a broad, linear dynamic range of detection between 1 and 10(6) copies of viral DNA. The quantification of HHV-6A DNA was suppressed by an excess amount of HHV-6B DNA (1 × 10(6) copies/tube) in the multiplex PCR assay; however, 1 × 10(6) copies/tube of HHV-6A DNA did not affect the quantification of 1 × 10(4) copies/tube of HHV-6B DNA. To determine the reliability of the assay for analysis of clinical specimens, DNAs extracted from the peripheral blood of hematopoietic stem cell transplant recipients were assayed using our multiplex real-time PCR versus the standard TaqMan PCR. Strong correlations were demonstrated between the two different assay systems for both HHV-6A (R(2)  = 0.913) and HHV-6B (R(2)  = 0.909). Therefore, our multiplex HHV-6 species-specific cycling probe real-time PCR is useful for evaluating the precise copy numbers of HHV-6A and B in transplant recipients. However, as HHV-6A copy numbers was affected by presence of high copies of HHV-6B DNA (1 × 10(6) copies/tube), it may be difficult to measure precise copy numbers of HHV-6A in inherited chromosomally integrated HHV-6B patient. J. Med. Virol. 88:1628-1635, 2016. © 2016 Wiley Periodicals, Inc.

  15. Proton transfer reaction mass spectrometry and time intensity perceptual measurement of flavor release from lipid emulsions using trained human subjects. (United States)

    Frank, Damian; Appelqvist, Ingrid; Piyasiri, Udayasika; Wooster, Tim J; Delahunty, Conor


    The effect of the fat component of liquid emulsions on dynamic "in-nose" flavor release was examined using a panel of trained human subjects (n = 6), proton transfer reaction mass spectrometry (PTR-MS), and time intensity (TI) sensory evaluation. A rigorous breathing and consumption protocol was developed, which synchronized subjects' breathing cycles and also the timing of sample introduction. Temporal changes in volatile release were measured in exhaled nostril breath by real-time PTR-MS. Corresponding changes in the perceived odor intensity could also be simultaneously measured using a push button TI device. The method facilitated accurate examination of both "preswallow" and "postswallow" phases of volatile release and perception. Volatile flavor compounds spanning a range of octanol/water partition coefficient (K(o/w)) values (1-1380) were spiked into water (0% fat) or lipid emulsions with various fat contents (2, 5, 10, and 20% fat). Replicate samples for each fat level were consumed according to the consumption protocol by six subjects. Statistical comparisons were made at the individual level and across the group for the effects of changes in the food matrix, such as fat content, on both pre- and postswallow volatile release. Significant group differences in volatile release parameters including area under the concentration curve (AUC) and maximum concentration (I(max)) were measured according to the lipid content of emulsions and volatile K(o/w). In a second experiment, using single compounds (2-heptanone, ethyl butanoate, and ethyl hexanoate), significant decreases in both in-nose volatile release and corresponding perceived odor intensities were measured with increasing fat addition. Overall, the effect of fat on in vivo release conformed to theory; fat had little effect on compounds with low K(o/w) values, but increased for volatiles with higher lipophilicity. In addition, significant pre- and postswallow differences were observed in AUC and I(max), as

  16. A Paradigm for Systems Thinking as a Real-Time Approach for Human Adaptation in the 21st Century

    Directory of Open Access Journals (Sweden)

    Melissa J. Mills


    Full Text Available Contemporary neuroscientists, human anthropologists, biologists, and psychologists suggest that the human species is still evolving. The productivity of science, research, education and capital investment can be seen in the phenomenal growth of the human population. Yet the trajectories that have brought us to the present-day apex of material well-being and social health are not sustainable. How can we take the deep advances in distinct academic disciplines and bring them together in ways that inform and coordinate human ingenuity to meet and address the challenges of the 21st century? By taking contemporary research results from a broad range of disciplines and applying them to human dynamics through definable structures, humans are empowered to leverage their capacity to find solutions through joint intention.

  17. Recording human electrocorticographic (ECoG) signals for neuroscientific research and real-time functional cortical mapping. (United States)

    Hill, N Jeremy; Gupta, Disha; Brunner, Peter; Gunduz, Aysegul; Adamo, Matthew A; Ritaccio, Anthony; Schalk, Gerwin


    Neuroimaging studies of human cognitive, sensory, and motor processes are usually based on noninvasive techniques such as electroencephalography (EEG), magnetoencephalography or functional magnetic-resonance imaging. These techniques have either inherently low temporal or low spatial resolution, and suffer from low signal-to-noise ratio and/or poor high-frequency sensitivity. Thus, they are suboptimal for exploring the short-lived spatio-temporal dynamics of many of the underlying brain processes. In contrast, the invasive technique of electrocorticography (ECoG) provides brain signals that have an exceptionally high signal-to-noise ratio, less susceptibility to artifacts than EEG, and a high spatial and temporal resolution (i.e., intentions to enhance or improve communication and control. Nevertheless, human ECoG data are often hard to obtain because of the risks and limitations of the invasive procedures involved, and the need to record within the constraints of clinical settings. Still, clinical monitoring to localize epileptic foci offers a unique and valuable opportunity to collect human ECoG data. We describe our methods for collecting recording ECoG, and demonstrate how to use these signals for important real-time applications such as clinical mapping and brain-computer interfacing. Our example uses the BCI2000 software platform and the SIGFRIED method, an application for real-time mapping of brain functions. This procedure yields information that clinicians can subsequently use to guide the complex and laborious process of functional mapping by electrical stimulation. PREREQUISITES AND PLANNING: Patients with drug-resistant partial epilepsy may be candidates for resective surgery of an epileptic focus to minimize the frequency of seizures. Prior to resection, the patients undergo monitoring using subdural electrodes for two purposes: first, to localize the epileptic focus, and second, to identify nearby critical brain areas (i.e., eloquent cortex) where

  18. Developmental variations in environmental influences including endocrine disruptors on pubertal timing and neuroendocrine control: Revision of human observations and mechanistic insight from rodents. (United States)

    Parent, Anne-Simone; Franssen, Delphine; Fudvoye, Julie; Gérard, Arlette; Bourguignon, Jean-Pierre


    Puberty presents remarkable individual differences in timing reaching over 5 years in humans. We put emphasis on the two edges of the age distribution of pubertal signs in humans and point to an extended distribution towards earliness for initial pubertal stages and towards lateness for final pubertal stages. Such distortion of distribution is a recent phenomenon. This suggests changing environmental influences including the possible role of nutrition, stress and endocrine disruptors. Our ability to assess neuroendocrine effects and mechanisms is very limited in humans. Using the rodent as a model, we examine the impact of environmental factors on the individual variations in pubertal timing and the possible underlying mechanisms. The capacity of environmental factors to shape functioning of the neuroendocrine system is thought to be maximal during fetal and early postnatal life and possibly less important when approaching the time of onset of puberty.

  19. 时空压缩下的我国人力资本积累%Time-space Compression and Human Capital Accumulation in China

    Institute of Scientific and Technical Information of China (English)



    时空压缩下的我国人力资本积累呈现如下显著特征:时空压缩促使我国人力资本积累的快速增长;时空压缩加剧我国人力资本积累的区域差异;时空压缩导致我国人力资本积累面临更加严峻的国际竞争形势.从支撑我国未来现代化发展的长远看,我国人力资本积累需要充分考虑时空压缩的现实国情,不失时机地实施人力资本积累的跨越发展战略、协调发展战略与和平发展战略.%The time-space compression perspective outlines several notable features of human capital accumu-lation in China: time-space compression promoting rapid growth of human capital accumulation; time-space compression increasing the regional difference of human capital accumulation; and time-space compression leading to a more severe situation of international competition in human capital accumulation. From the view of supporting the long-term development of China's future modernization, human capital accumulation in China need to give full consideration to the actual situation of time-space compression, and lose no time to imple-ment the strategies of leap-forward, coordination and peace in the development of human capital accumulation.

  20. Real-time, transcranial monitoring of safe blood-brain barrier opening in non-human primates.

    Directory of Open Access Journals (Sweden)

    Fabrice Marquet

    Full Text Available The delivery of drugs to specific neural targets faces two fundamental problems: (1 most drugs do not cross the blood-brain barrier, and (2 those that do, spread to the entire brain. To date, there exists only one non-invasive methodology with the potential to solve these problems: selective blood-brain barrier (BBB opening using micro-bubble enhanced focused ultrasound. We have recently developed a single-element 500-kHz spherical transducer ultrasound setup for targeted BBB opening in the non-human primate that does not require simultaneous MRI monitoring. So far, however, the targeting accuracy that can be achieved with this system has not been quantified systematically. In this paper, the accuracy of this system was tested by targeting caudate nucleus and putamen of the basal ganglia in two macaque monkeys. The average lateral targeting error of the system was ∼2.5 mm while the axial targeting error, i.e., along the ultrasound path, was ∼1.5 mm. We have also developed a real-time treatment monitoring technique based on cavitation spectral analysis. This technique also allowed for delineation of a safe and reliable acoustic parameter window for BBB opening. In summary, the targeting accuracy of the system was deemed to be suitable to reliably open the BBB in specific sub-structures of the basal ganglia even in the absence of MRI-based verification of opening volume and position. This establishes the method and the system as a potentially highly useful tool for brain drug delivery.

  1. Uremic Toxins Induce ET-1 Release by Human Proximal Tubule Cells, which Regulates Organic Cation Uptake Time-Dependently

    Directory of Open Access Journals (Sweden)

    Carolien M. S. Schophuizen


    Full Text Available In renal failure, the systemic accumulation of uremic waste products is strongly associated with the development of a chronic inflammatory state. Here, the effect of cationic uremic toxins on the release of inflammatory cytokines and endothelin-1 (ET-1 was investigated in conditionally immortalized proximal tubule epithelial cells (ciPTEC. Additionally, we examined the effects of ET-1 on the cellular uptake mediated by organic cation transporters (OCTs. Exposure of ciPTEC to cationic uremic toxins initiated production of the inflammatory cytokines IL-6 (117 ± 3%, p < 0.001, IL-8 (122 ± 3%, p < 0.001, and ET-1 (134 ± 5%, p < 0.001. This was accompanied by a down-regulation of OCT mediated 4-(4-(dimethylaminostyryl-N-methylpyridinium-iodide (ASP+ uptake in ciPTEC at 30 min (23 ± 4%, p < 0.001, which restored within 60 min of incubation. Exposure to ET-1 for 24 h increased the ASP+ uptake significantly (20 ± 5%, p < 0.001. These effects could be blocked by BQ-788, indicating activation of an ET-B-receptor-mediated signaling pathway. Downstream the receptor, iNOS inhibition by (N(G‐monomethyl‐l‐arginine l-NMMA acetate or aminoguanidine, as well as protein kinase C activation, ameliorated the short-term effects. These results indicate that uremia results in the release of cytokines and ET-1 from human proximal tubule cells, in vitro. Furthermore, ET-1 exposure was found to regulate proximal tubular OCT transport activity in a differential, time-dependent, fashion.

  2. Optical tomography of human skin with subcellular spatial and picosecond time resolution using intense near infrared femtosecond laser pulses (United States)

    Koenig, Karsten; Wollina, Uwe; Riemann, Iris; Peukert, Christiane; Halbhuber, Karl-Juergen; Konrad, Helga; Fischer, Peter; Fuenfstueck, Veronika; Fischer, Tobias W.; Elsner, Peter


    We describe the novel high resolution imaging tool DermaInspect 100 for non-invasive diagnosis of dermatological disorders based on multiphoton autofluorescence imaging (MAI)and second harmonic generation. Femtosecond laser pulses in the spectral range of 750 nm to 850 nm have been used to image in vitro and in vivo human skin with subcellular spatial and picosecond temporal resolution. The non-linear induced autofluorescence originates mainly from naturally endogenous fluorophores/protein structures like NAD(P)H, flavins, keratin, collagen, elastin, porphyrins and melanin. Second harmonic generation was observed in the stratum corneum and in the dermis. The system with a wavelength-tunable compact 80 MHz Ti:sapphire laser, a scan module with galvo scan mirrors, piezoelectric objective positioner, fast photon detector and time-resolved single photon counting unit was used to perform optical sectioning and 3D autofluorescence lifetime imaging (t-mapping). In addition, a modified femtosecond laser scanning microscope was involved in autofluorescence measurements. Tissues of patients with psoriasis, nevi, dermatitis, basalioma and melanoma have been investigated. Individual cells and skin structures could be clearly visualized. Intracellular components and connective tissue structures could be further characterized by tuning the excitation wavelength in the range of 750 nm to 850 nm and by calculation of mean fluorescence lifetimes per pixel and of particular regions of interest. The novel non-invasive imaging system provides 4D (x,y,z,t) optical biopsies with subcellular resolution and offers the possibility to introduce a further optical diagnostic method in dermatology.

  3. Real-time imaging of ATP release induced by mechanical stretch in human airway smooth muscle cells. (United States)

    Takahara, Norihiro; Ito, Satoru; Furuya, Kishio; Naruse, Keiji; Aso, Hiromichi; Kondo, Masashi; Sokabe, Masahiro; Hasegawa, Yoshinori


    Airway smooth muscle (ASM) cells within the airway walls are continually exposed to mechanical stimuli, and exhibit various functions in response to these mechanical stresses. ATP acts as an extracellular mediator in the airway. Moreover, extracellular ATP is considered to play an important role in the pathophysiology of asthma and chronic obstructive pulmonary disease. However, it is not known whether ASM cells are cellular sources of ATP secretion in the airway. We therefore investigated whether mechanical stretch induces ATP release from ASM cells. Mechanical stretch was applied to primary human ASM cells cultured on a silicone chamber coated with type I collagen using a stretching apparatus. Concentrations of ATP in cell culture supernatants measured by luciferin-luciferase bioluminescence were significantly elevated by cyclic stretch (12 and 20% strain). We further visualized the stretch-induced ATP release from the cells in real time using a luminescence imaging system, while acquiring differential interference contrast cell images with infrared optics. Immediately after a single uniaxial stretch for 1 second, strong ATP signals were produced by a certain population of cells and spread to surrounding spaces. The cyclic stretch-induced ATP release was significantly reduced by inhibitors of Ca(2+)-dependent vesicular exocytosis, 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester, monensin, N-ethylmaleimide, and bafilomycin. In contrast, the stretch-induced ATP release was not inhibited by a hemichannel blocker, carbenoxolone, or blockade of transient receptor potential vanilloid 4 by short interfering RNA transfection or ruthenium red. These findings reveal a novel property of ASM cells: mechanically induced ATP release may be a cellular source of ATP in the airway.

  4. Reproducibility of creatine kinase reaction kinetics in human heart: a (31) P time-dependent saturation transfer spectroscopy study. (United States)

    Bashir, Adil; Gropler, Robert


    Creatine kinase (CK) is essential for the buffering and rapid regeneration of adenosine triphosphate (ATP) in heart tissue. Herein, we demonstrate a (31) P MRS protocol to quantify CK reaction kinetics in human myocardium at 3 T. Furthermore, we sought to quantify the test-retest reliability of the measured metabolic parameters. The method localizes the (31) P signal from the heart using modified one-dimensional image-selected in vivo spectroscopy (ISIS), and a time-dependent saturation transfer (TDST) approach was used to measure CK reaction parameters. Fifteen healthy volunteers (22 measurements in total) were tested. The CK reaction rate constant (kf ) was 0.32 ± 0.05 s(-1) and the coefficient of variation (CV) was 15.62%. The intrinsic T1 for phosphocreatine (PCr) was 7.36 ± 1.79 s with CV = 24.32%. These values are consistent with those reported previously. The PCr/ATP ratio was equal to 1.94 ± 0.15 with CV = 7.73%, which is within the range of healthy subjects. The reproducibility of the technique was tested in seven subjects and inferred parameters, such as kf and T1 , exhibited good reliability [intraclass correlation coefficient (ICC) of 0.90 and 0.79 for kf and T1 , respectively). The reproducibility data provided in this study will enable the calculation of the power and sample sizes required for clinical and research studies. The technique will allow for the examination of cardiac energy metabolism in clinical and research studies, providing insight into the relationship between energy deficit and functional deficiency in the heart.

  5. Probing orientation of immobilized humanized anti-lysozyme variable fragment by time-of-flight secondary-ion mass spectrometry. (United States)

    Baio, J E; Cheng, Fang; Ratner, Daniel M; Stayton, Patrick S; Castner, David G


    As methods to orient proteins are conceived, techniques must also be developed that provide an accurate characterization of immobilized protein orientation. In this study, X-ray photoelectron spectroscopy (XPS), surface plasmon resonance (SPR), and time-of-flight secondary ion mass spectrometry (ToF-SIMS) were used to probe the orientation of a surface immobilized variant of the humanized anti-lysozyme variable fragment (HuLys Fv, 26 kDa). This protein contained both a hexahistidine tag and a cysteine residue, introduced at opposite ends of the HuLys Fv, for immobilization onto nitrilotriacetic acid (NTA) and maleimide oligo(ethylene glycol) (MEG)-terminated substrates, respectively. The thiol group on the cysteine residue selectively binds to the MEG groups, while the his-tag selectively binds to the Ni-loaded NTA groups. XPS was used to monitor protein coverage on both surfaces by following the change in the nitrogen atomic %. SPR results showed a 10-fold difference in lysozyme binding between the two different HuLys Fv orientations. The ToF-SIMS data provided a clear differentiation between the two samples due to the intensity differences of secondary ions originating from asymmetrically located amino acids in HuLys Fv (histidine: 81, 82, and 110 m/z; phenylalanine: 120 and 131 m/z). An intensity ratio of the secondary ion peaks from the histidine and phenylalanine residues at either end of the protein was then calculated directly from the ToF-SIMS data. The 45% change in this ratio, observed between the NTA and MEG substrates with similar HuLys Fv surface coverages, indicates that the HuLys Fv fragment has opposite orientations on two different surfaces.

  6. Netrin-1, a urinary proximal tubular injury marker, is elevated early in the time course of human diabetes

    NARCIS (Netherlands)

    Jayakumar, Calpurnia; Nauta, Ferdau L.; Bakker, Stephan J. L.; Bilo, Henk; Gansevoort, Ron T.; Johnson, Maribeth H.; Ramesh, Ganesan


    Netrin-1 was recently identified as an early diagnostic biomarker of chronic kidney disease (CKD) in an experimental animal model. However, its usefulness for early diagnosis of CKD in humans is unknown. The current study evaluated whether netrin-1 is increased in urine from human diabetic patients.

  7. Effects of Age, Season, Gender and Urban-Rural Status on Time-Activity: Canadian Human Activity Pattern Survey 2 (CHAPS 2

    Directory of Open Access Journals (Sweden)

    Carlyn J. Matz


    Full Text Available Estimation of population exposure is a main component of human health risk assessment for environmental contaminants. Population-level exposure assessments require time-activity pattern distributions in relation to microenvironments where people spend their time. Societal trends may have influenced time-activity patterns since previous Canadian data were collected 15 years ago. The Canadian Human Activity Pattern Survey 2 (CHAPS 2 was a national survey conducted in 2010–2011 to collect time-activity information from Canadians of all ages. Five urban and two rural locations were sampled using telephone surveys. Infants and children, key groups in risk assessment activities, were over-sampled. Survey participants (n = 5,011 provided time-activity information in 24-hour recall diaries and responded to supplemental questionnaires concerning potential exposures to specific pollutants, dwelling characteristics, and socio-economic factors. Results indicated that a majority of the time was spent indoors (88.9%, most of which was indoors at home, with limited time spent outdoors (5.8% or in a vehicle (5.3%. Season, age, gender and rurality were significant predictors of time activity patterns. Compared to earlier data, adults reported spending more time indoors at home and adolescents reported spending less time outdoors, which could be indicative of broader societal trends. These findings have potentially important implications for assessment of exposure and risk. The CHAPS 2 data also provide much larger sample sizes to allow for improved precision and are more representative of infants, children and rural residents.

  8. A new method to study changes in microvascular blood volume in muscle and adipose tissue: Real time imaging in humans and rat

    DEFF Research Database (Denmark)

    Sjøberg, Kim Anker; Rattigan, Stephen; Hiscock, Natalie J;


    We employed and evaluated a new application of contrast enhanced ultrasound for real time imaging of changes in microvascular blood volume (MVB) in tissues in females, males and rat. Continuous real time imaging was performed using contrast enhanced ultrasound to quantify infused gas filled...... have demonstrated that real time imaging of changes in MBV is possible in human and rat muscle and in subcutaneous adipose tissue and that the method is sensitive enough to pick up relatively small changes in MBV when performed with due consideration of steady state microbubble concentration. Due...... to real time imaging the method has wide applications for determining MBV in different organs during various physiological or pathophysiological conditions....

  9. [Separation and identification of beta-casein from Chinese human milk by ion exchange chromatography-matrix-assisted laser desorption/ionization time of flight/time of flight mass spectrometry]. (United States)

    Huang, Yu; Ren, Haowei; Liu, Biao; Liu, Ning; Li, Meng; Wang, Dongmao


    The selective precipitation of whole casein from skimmed milk was achieved by the addition of calcium salt under acidic pH. The effects of pH, centrifugal force and final concentration of CaCl2 on the separation of casein were studied by measuring the purity of final products using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The results showed that casein with the highest purity could be obtained with the pH of 4.3, the centrifugal force of 10 400 g and the final concentration of CaCl2 of 60 mmol/L. The casein was processed with DEAE anion exchange chromatography and three peaks were obtained. Then the third peak (peak III) was identified with Western-Blot method and matrix-assisted laser desorption/ionization time of flight/time of flight mass spectrometry (MALDI-TOF/TOF MS). The identification of Western-Blot showed that peak III can combine with the specificity of human milk beta-casein antibody, and it is proved to be human milk beta-casein. The fingerprints of peak III were nalyzed by Mascot searching, and the sequence coverage was 50%, further supporting it is human milk beta-casein. In conclusion, an effective method to obtain human milk beta-casein from milk samples through DEAE anion exchange chromatography was established, and it is suitable for the proteomics research requirements of the beta-casein from human milk.

  10. Space-time variations of human capital assets across U.S. metropolitan areas, 1980 to 2000. (United States)

    Scott, Allen J


    This article examines the changing structure of human capital in U.S. metropolitan regions from 1980 to 2000. Data are drawn from the Dictionary of Occupational Titles and from the Integrated Public Use Microdata Series. Intensive empirical investigation leads to three main conclusions. First, forms of human capital in the United States are becoming more oriented to labor tasks that call for cognitive-cultural skills. Second, cognitive-cultural skills are accumulating most intensively in large metropolitan areas. Third, physical or practical forms of human capital are increasingly being relegated to smaller metropolitan areas. That said, important residues of human capital, focused on physical or practical tasks, remain a durable element of the economies of large metropolitan areas. I offer a brief theoretical explanation of these results.

  11. The effects of self-selected light-dark cycles and social constraints on human sleep and circadian timing: a modeling approach. (United States)

    Skeldon, Anne C; Phillips, Andrew J K; Dijk, Derk-Jan


    Why do we go to sleep late and struggle to wake up on time? Historically, light-dark cycles were dictated by the solar day, but now humans can extend light exposure by switching on artificial lights. We use a mathematical model incorporating effects of light, circadian rhythmicity and sleep homeostasis to provide a quantitative theoretical framework to understand effects of modern patterns of light consumption on the human circadian system. The model shows that without artificial light humans wakeup at dawn. Artificial light delays circadian rhythmicity and preferred sleep timing and compromises synchronisation to the solar day when wake-times are not enforced. When wake-times are enforced by social constraints, such as work or school, artificial light induces a mismatch between sleep timing and circadian rhythmicity ('social jet-lag'). The model implies that developmental changes in sleep homeostasis and circadian amplitude make adolescents particularly sensitive to effects of light consumption. The model predicts that ameliorating social jet-lag is more effectively achieved by reducing evening light consumption than by delaying social constraints, particularly in individuals with slow circadian clocks or when imposed wake-times occur after sunrise. These theory-informed predictions may aid design of interventions to prevent and treat circadian rhythm-sleep disorders and social jet-lag.

  12. Real-time tracking of CO migration and binding in the α and β subunits of human hemoglobin via 150-ps time-resolved Laue crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Schotte, Friedrich; Cho, Hyun Sun [Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520 (United States); Soman, Jayashree [Department of Biochemistry and Cell Biology, and W.M. Keck Center for Computational Biology, Rice University, Houston, TX 77251-1892 (United States); Wulff, Michael [European Synchrotron Radiation Facility, BP 220, 38043 Grenoble Cedex (France); Olson, John S. [Department of Biochemistry and Cell Biology, and W.M. Keck Center for Computational Biology, Rice University, Houston, TX 77251-1892 (United States); Anfinrud, Philip A., E-mail: [Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520 (United States)


    Highlights: ► 150-ps Time-resolved Laue crystallography has unveiled ligand dynamics in hemoglobin. ► Significant kinetic differences are observed in the α and β subunits of hemoglobin. ► The B-site lifetime is ∼1.6 ns in β, and ∼18 ns in α. ► The B-site location in β is ∼0.25 Å closer to the binding site than in α. ► The correlation between CO position and rebinding rate suggests distal control. - Abstract: We have developed the method of picosecond Laue crystallography and used this capability to probe ligand dynamics in tetrameric R-state hemoglobin (Hb). Time-resolved, 2 Å-resolution electron density maps of photolyzed HbCO reveal the time-dependent population of CO in the binding (A) and primary docking (B) sites of both α and β subunits from 100 ps to 10 μs. The proximity of the B site in the β subunit is about 0.25 Å closer to its A binding site, and its k{sub BA} rebinding rate (∼300 μs{sup −1}) is six times faster, suggesting distal control of the rebinding dynamics. Geminate rebinding in the β subunit exhibits both prompt and delayed geminate phases. We developed a microscopic model to quantitatively explain the observed kinetics, with three states for the α subunit and four states for the β subunit. This model provides a consistent framework for interpreting rebinding kinetics reported in prior studies of both HbCO and HbO{sub 2}.

  13. Identification of fipronil metabolites by time-of-flight mass spectrometry for application in a human exposure study. (United States)

    McMahen, Rebecca L; Strynar, Mark J; Dagnino, Sonia; Herr, David W; Moser, Virginia C; Garantziotis, Stavros; Andersen, Erik M; Freeborn, Danielle L; McMillan, Larry; Lindstrom, Andrew B


    Fipronil is a phenylpyrazole insecticide commonly used in residential and agricultural applications. To understand more about the potential risks for human exposure associated with fipronil, urine and serum from dosed Long Evans adult rats (5 and 10mg/kg bw) were analyzed to identify metabolites as potential biomarkers for use in human biomonitoring studies. Urine from treated rats was found to contain seven unique metabolites, two of which had not been previously reported-M4 and M7 which were putatively identified as a nitroso compound and an imine, respectively. Fipronil sulfone was confirmed to be the primary metabolite in rat serum. The fipronil metabolites identified in the respective matrices were then evaluated in matched human urine (n=84) and serum (n=96) samples from volunteers with no known pesticide exposures. Although no fipronil or metabolites were detected in human urine, fipronil sulfone was present in the serum of approximately 25% of the individuals at concentrations ranging from 0.1 to 4ng/mL. These results indicate that many fipronil metabolites are produced following exposures in rats and that fipronil sulfone is a useful biomarker in human serum. Furthermore, human exposure to fipronil may occur regularly and require more extensive characterization.

  14. Comparison of microscopy, real-time PCR and a rapid immunoassay for the detection of Giardia lamblia in human stool specimens

    NARCIS (Netherlands)

    Schuurman, T.; Lankamp, P.; van Belkum, A.; Kooistra-Smid, M.; van Zwet, A.


    Giardia lamblia is one of the most common intestinal parasites worldwide, with microscopy being the diagnostic reference standard for use with human stools. However, microscopy is time-consuming, labour-intensive and lacks sensitivity when single stools are examined. In the present study, microscopy

  15. Vasoactive intestinal peptide induces cyclooxygenase-2 expression through nuclear factor-κB in human prostate cell lines. Differential time-dependent responses in cancer progression


    Fernández-Martínez, Ana B.; Collado, Beatriz; Bajo, Ana M.; Sánchez-Chapado, Manuel; Prieto,Juan C.; Carmena, María J.


    Vasoactive intestinal peptide induces cyclooxygenase-2 expression through nuclear factor-?B in human prostate cell lines. Differential time-dependent responses in cancer progression SPAIN (Fernandez-Martinez, Ana B.) SPAIN Received: 2006-09-11 Revised: 2007-01-11 Accepted: 2007-01-11

  16. Time constants for temperature elevation in human models exposed to dipole antennas and beams in the frequency range from 1 to 30 GHz (United States)

    Morimoto, Ryota; Hirata, Akimasa; Laakso, Ilkka; Ziskin, Marvin C.; Foster, Kenneth R.


    This study computes the time constants of the temperature elevations in human head and body models exposed to simulated radiation from dipole antennas, electromagnetic beams, and plane waves. The frequency range considered is from 1 to 30 GHz. The specific absorption rate distributions in the human models are first computed using the finite-difference time-domain method for the electromagnetics. The temperature elevation is then calculated by solving the bioheat transfer equation. The computational results show that the thermal time constants (defined as the time required to reach 63% of the steady state temperature elevation) decrease with the elevation in radiation frequency. For frequencies higher than 4 GHz, the computed thermal time constants are smaller than the averaging time prescribed in the ICNIRP guidelines, but larger than the averaging time in the IEEE standard. Significant differences between the different head models are observed at frequencies higher than 10 GHz, which is attributable to the heat diffusion from the power absorbed in the pinna. The time constants for beam exposures become large with the increase in beam diameter. The thermal time constant in the brain is larger than that in the superficial tissues at high frequencies, because the brain temperature elevation is caused by the heat conduction of energy absorbed in the superficial tissue. The thermal time constant is minimized with an ideal beam with a minimum investigated diameter of 10 mm this minimal time constant is approximately 30 s and is almost independent of the radiation frequency, which is supported by analytic methods. In addition, the relation between the time constant, as defined in this paper, and ‘averaging time’ as it appears in the exposure limits is discussed, especially for short intense pulses. Similar to the laser guidelines, provisions should be included in the limits to limit the fluence for such pulses.

  17. Three Experiments Examining the Use of Electroencephalogram,Event-Related Potentials, and Heart-Rate Variability for Real-Time Human-Centered Adaptive Automation Design (United States)

    Prinzel, Lawrence J., III; Parasuraman, Raja; Freeman, Frederick G.; Scerbo, Mark W.; Mikulka, Peter J.; Pope, Alan T.


    Adaptive automation represents an advanced form of human-centered automation design. The approach to automation provides for real-time and model-based assessments of human-automation interaction, determines whether the human has entered into a hazardous state of awareness and then modulates the task environment to keep the operator in-the-loop , while maintaining an optimal state of task engagement and mental alertness. Because adaptive automation has not matured, numerous challenges remain, including what the criteria are, for determining when adaptive aiding and adaptive function allocation should take place. Human factors experts in the area have suggested a number of measures including the use of psychophysiology. This NASA Technical Paper reports on three experiments that examined the psychophysiological measures of event-related potentials, electroencephalogram, and heart-rate variability for real-time adaptive automation. The results of the experiments confirm the efficacy of these measures for use in both a developmental and operational role for adaptive automation design. The implications of these results and future directions for psychophysiology and human-centered automation design are discussed.

  18. A personal reflection on the replicon theory: from R1 plasmid to replication timing regulation in human cells. (United States)

    Masai, Hisao


    Fifty years after the Replicon Theory was originally presented, detailed mechanistic insight into prokaryotic replicons has been obtained and rapid progress is being made to elucidate the more complex regulatory mechanisms of replicon regulation in eukaryotic cells. Here, I present my personal perspectives on how studies of model replicons have contributed to our understanding of the basic mechanisms of DNA replication as well as the evolution of replication regulation in human cells. I will also discuss how replication regulation contributes to the stable maintenance of the genome and how disruption of replication regulation leads to human diseases.

  19. Quantitative Real-Time PCR Analysis of YKL-40 and Its Comparison with Mammalian Chitinase mRNAs in Normal Human Tissues Using a Single Standard DNA

    Directory of Open Access Journals (Sweden)

    Misa Ohno


    Full Text Available YKL-40 (YKL for the first three N-terminal residues of a 40 kDa protein belongs to a group of human chitinase-like proteins (CLPs, which are similar to chitinases but lack chitinolytic activity. YKL-40 mRNA and its protein levels have been reported elevated in multiple disorders including asthma, cystic fibrosis, rheumatoid arthritis and malignant tumors. Here, we quantified the YKL-40 mRNA levels and compared them with chitinases and housekeeping genes in normal human tissues. To establish the quantitative real-time PCR (qPCR system for evaluation of relative YKL-40 mRNA levels, we constructed a human standard DNA molecule by ligating cDNAs of YKL-40, two mammalian chitinases and two housekeeping genes in a one-to-one ratio. We generated cDNAs from various normal human tissues and analyzed the YKL-40 mRNA expression levels using a qPCR system with the standard DNA. We found that YKL-40 mRNA is present widely in human tissues while its expression patterns exhibit clear tissue specificity. Highest YKL-40 mRNA levels were detected in the liver, followed by kidney, trachea and lung. The levels of YKL-40 mRNA in the kidney and liver were more than 100-times higher than those of chitotriosidase mRNA. Our study provides for the first time a comprehensive analysis of the relative expression levels of YKL-40 mRNA versus mammalian chitinases in normal human tissues.

  20. Real-time PCR-based assay to quantify the relative amount of human and mouse tissue present in tumor xenografts

    Directory of Open Access Journals (Sweden)

    Alcoser Sergio Y


    Full Text Available Abstract Background Xenograft samples used to test anti-cancer drug efficacies and toxicities in vivo contain an unknown mix of mouse and human cells. Evaluation of drug activity can be confounded by samples containing large amounts of contaminating mouse tissue. We have developed a real-time quantitative polymerase chain reaction (qPCR assay using TaqMan technology to quantify the amount of mouse tissue that is incorporated into human xenograft samples. Results The forward and reverse primers bind to the same DNA sequence in the human and the mouse genome. Using a set of specially designed fluorescent probes provides species specificity. The linearity and sensitivity of the assay is evaluated using serial dilutions of single species and heterogeneous DNA mixtures. We examined many xenograft samples at various in vivo passages, finding a wide variety of human:mouse DNA ratios. This variation may be influenced by tumor type, number of serial passages in vivo, and even which part of the tumor was collected and used in the assay. Conclusions This novel assay provides an accurate quantitative assessment of human and mouse content in xenograft tumors. This assay can be performed on aberrantly behaving human xenografts, samples used in bioinformatics studies, and periodically for tumor tissue frequently grown by serial passage in vivo.

  1. Prospects of a mathematical theory of human behavior in complex man-machine systems tasks. [time sharing computer analogy of automobile driving (United States)

    Johannsen, G.; Rouse, W. B.


    A hierarchy of human activities is derived by analyzing automobile driving in general terms. A structural description leads to a block diagram and a time-sharing computer analogy. The range of applicability of existing mathematical models is considered with respect to the hierarchy of human activities in actual complex tasks. Other mathematical tools so far not often applied to man machine systems are also discussed. The mathematical descriptions at least briefly considered here include utility, estimation, control, queueing, and fuzzy set theory as well as artificial intelligence techniques. Some thoughts are given as to how these methods might be integrated and how further work might be pursued.

  2. Effect of treatment with human chorionic gonadotropin on day 5 after timed artificial insemination on fertility of lactating dairy cows. (United States)

    Nascimento, A B; Bender, R W; Souza, A H; Ayres, H; Araujo, R R; Guenther, J N; Sartori, R; Wiltbank, M C


    Reproductive management programs that synchronize ovulation can ovulate a smaller than normal follicle, potentially resulting in inadequate progesterone (P4) concentrations after artificial insemination (AI). Ovulation of the dominant follicle of the first follicular wave with human chorionic gonadotropin (hCG) treatment can produce an accessory corpus luteum and increase circulating P4 concentrations. This manuscript reports the results of 2 separate analyses that evaluated the effect of hCG treatment post-AI on fertility in lactating dairy cows. The first study used meta-analysis to combine the results from 10 different published studies that used hCG treatment on d 4 to 9 post-AI in lactating dairy cows. Overall, pregnancies per artificial insemination (P/AI) were increased 3.0% by hCG treatment post-AI [34% (752/2,213) vs. 37% (808/2,184); Control vs. hCG-treated, respectively]. The second study was a field research trial in which lactating Holstein cows (n=2,979) from 6 commercial dairy herds were stratified by parity and breeding number and then randomly assigned to one of 2 groups: control (no further treatment, n=1,519) or hCG [Chorulon i.m.: 2,000 IU (in 3 of the herds) or 3,300 IU (in 3 herds); n=1,460] on d 5 after a timed AI (ovulation synchronized with Ovsynch, Presynch-Ovsynch, or Double-Ovsynch). In a subset of cows, the hCG profile and P4 changes were determined. Treatment with hCG increased P4 (4.3 vs. 5.3 ng/mL on d 12). Pregnancies per AI were greater in cows treated with hCG (40.8%; 596/1,460) than control (37.3%; 566/1,519) cows. Interestingly, an interaction among treatment and parity was observed; primiparous cows had greater P/AI after hCG (49.7%; 266/535) than controls (39.5%; 215/544). In contrast, older cows receiving hCG (35.7%; 330/925) had similar P/AI to controls (36.0%; 351/975).Thus, targeted use of hCG on d 5 after TAI enhances fertility about 3.0% (based on meta-analysis) to 3.5% (based on our field trial). Surprisingly, this

  3. The rhesus macaque is three times as diverse but more closely equivalent in damaging coding variation as compared to the human

    Directory of Open Access Journals (Sweden)

    Yuan Qiaoping


    Full Text Available Abstract Background As a model organism in biomedicine, the rhesus macaque (Macaca mulatta is the most widely used nonhuman primate. Although a draft genome sequence was completed in 2007, there has been no systematic genome-wide comparison of genetic variation of this species to humans. Comparative analysis of functional and nonfunctional diversity in this highly abundant and adaptable non-human primate could inform its use as a model for human biology, and could reveal how variation in population history and size alters patterns and levels of sequence variation in primates. Results We sequenced the mRNA transcriptome and H3K4me3-marked DNA regions in hippocampus from 14 humans and 14 rhesus macaques. Using equivalent methodology and sampling spaces, we identified 462,802 macaque SNPs, most of which were novel and disproportionately located in the functionally important genomic regions we had targeted in the sequencing. At least one SNP was identified in each of 16,797 annotated macaque genes. Accuracy of macaque SNP identification was conservatively estimated to be >90%. Comparative analyses using SNPs equivalently identified in the two species revealed that rhesus macaque has approximately three times higher SNP density and average nucleotide diversity as compared to the human. Based on this level of diversity, the effective population size of the rhesus macaque is approximately 80,000 which contrasts with an effective population size of less than 10,000 for humans. Across five categories of genomic regions, intergenic regions had the highest SNP density and average nucleotide diversity and CDS (coding sequences the lowest, in both humans and macaques. Although there are more coding SNPs (cSNPs per individual in macaques than in humans, the ratio of dN/dS is significantly lower in the macaque. Furthermore, the number of damaging nonsynonymous cSNPs (have damaging effects on protein functions from PolyPhen-2 prediction in the macaque is more

  4. Timing, rather than the concentration of cyclic AMP, correlates to osteogenic differentiation of human mesenchymal stem cells

    NARCIS (Netherlands)

    Siddappa, Ramakrishnaiah; Doorn, Joyce; Liu, Jun; Langerwerf, Eli; Arends, Roel; Blitterswijk, van Clemens; Boer, de Jan


    Previously, we demonstrated that protein kinase A (PKA) activation using dibutyryl-cAMP in human mesenchymal stem cells (hMSCs) induces in vitro osteogenesis and bone formation in vivo. To further investigate the physiological role of PKA in hMSC osteogenesis, we tested a selection of G-protein-coup

  5. The Best Time to Acquire New Skills: Age-Related Differences in Implicit Sequence Learning across the Human Lifespan (United States)

    Janacsek, Karolina; Fiser, Jozsef; Nemeth, Dezso


    Implicit skill learning underlies obtaining not only motor, but also cognitive and social skills through the life of an individual. Yet, the ontogenetic changes in humans' implicit learning abilities have not yet been characterized, and, thus, their role in acquiring new knowledge efficiently during development is unknown. We investigated such…

  6. Antimicrobial and antiviral effect of high-temperature short-time (HTST) pasteurization apllied to human milk

    NARCIS (Netherlands)

    Terpstra, F.G.; Rechtman, D.J.; Lee, M.L.; Hoeij, K. van; Berg, H.; Engelenberg, F.A.C. van; Wout, A.B. van 't


    In the United States, concerns over the transmission of infectious diseases have led to donor human milk generally being subjected to pasteurization prior to distribution and use. The standard method used by North American milk banks is Holder pasteurization (63°C for 30 minutes). The authors undert

  7. Real-Time Human Pose Estimation and Gesture Recognition from Depth Images Using Superpixels and SVM Classifier

    Directory of Open Access Journals (Sweden)

    Hanguen Kim


    Full Text Available In this paper, we present human pose estimation and gesture recognition algorithms that use only depth information. The proposed methods are designed to be operated with only a CPU (central processing unit, so that the algorithm can be operated on a low-cost platform, such as an embedded board. The human pose estimation method is based on an SVM (support vector machine and superpixels without prior knowledge of a human body model. In the gesture recognition method, gestures are recognized from the pose information of a human body. To recognize gestures regardless of motion speed, the proposed method utilizes the keyframe extraction method. Gesture recognition is performed by comparing input keyframes with keyframes in registered gestures. The gesture yielding the smallest comparison error is chosen as a recognized gesture. To prevent recognition of gestures when a person performs a gesture that is not registered, we derive the maximum allowable comparison errors by comparing each registered gesture with the other gestures. We evaluated our method using a dataset that we generated. The experiment results show that our method performs fairly well and is applicable in real environments.

  8. Real-time human pose estimation and gesture recognition from depth images using superpixels and SVM classifier. (United States)

    Kim, Hanguen; Lee, Sangwon; Lee, Dongsung; Choi, Soonmin; Ju, Jinsun; Myung, Hyun


    In this paper, we present human pose estimation and gesture recognition algorithms that use only depth information. The proposed methods are designed to be operated with only a CPU (central processing unit), so that the algorithm can be operated on a low-cost platform, such as an embedded board. The human pose estimation method is based on an SVM (support vector machine) and superpixels without prior knowledge of a human body model. In the gesture recognition method, gestures are recognized from the pose information of a human body. To recognize gestures regardless of motion speed, the proposed method utilizes the keyframe extraction method. Gesture recognition is performed by comparing input keyframes with keyframes in registered gestures. The gesture yielding the smallest comparison error is chosen as a recognized gesture. To prevent recognition of gestures when a person performs a gesture that is not registered, we derive the maximum allowable comparison errors by comparing each registered gesture with the other gestures. We evaluated our method using a dataset that we generated. The experiment results show that our method performs fairly well and is applicable in real environments.

  9. Gender Homophily, Ph.D. Completion, and Time to Degree in the Humanities and Humanistic Social Sciences (United States)

    Main, Joyce B.


    Doctoral programs in the humanities and humanistic social sciences contend with relatively lower graduation rates and longer duration to degree. While reforming graduate education can include changes to financial aid awards and program requirements, enhancements in the area of advising can also improve student educational experiences and outcomes…

  10. Direct B0 field monitoring and real-time B0 field updating in the human breast at 7 Tesla

    NARCIS (Netherlands)

    Boer, V.O.; Bank, B.L. van de; Vliet, G. van; Luijten, P.R.; Klomp, D.W.J.


    Large dynamic fluctuations of the static magnetic field (B(0)) are observed in the human body during MR scanning, compromising image quality and detection sensitivity in several MR imaging and spectroscopy sequences. Partially, these dynamic B(0) fluctuations are due to physiological motion such as

  11. Soluble CD163 does not predict first-time myocardial infarction in patients infected with human immunodeficiency virus

    DEFF Research Database (Denmark)

    Knudsen, Andreas; Møller, Holger Jon; Katzenstein, Terese Lea;


    BACKGROUND: Soluble CD163 (sCD163) has been associated with arterial inflammation and non-calcified plaques in human immunodeficiency virus (HIV)-infected individuals and has therefore been suggested as a predictive biomarker of myocardial infarction (MI). METHODS: We conducted a nested case...

  12. Identification of fipronil metabolites in rodents by time-of-flight mass spectrometry for application in a human exposure study (United States)

    Fipronil is a phenylpyrazole insecticide commonly used in residential and agricultural applications. To understand more about the potential risks associated with fipronil, dosed Long Evans rats were evaluated for metabolites to develop a set of biomarkers for use in human exposur...

  13. Human body reaction time measurement instrument and application%人体全身反应时间测量仪研制与应用

    Institute of Scientific and Technical Information of China (English)

    顾信文; 高俊; 张笑昆; 陶成


    为提高人体全身反应时间测量的效率和准确度,研制了人体全身反应时间测量仪。该仪器由信号发出装置、承重装置、时间和压力纪录装置以及反应判断装置组成。实验表明,利用该仪器可以完成人体反应时信号的测量、纪录与判别处理等过程,能够满足运动科研实验及教学的需要。%In order to improve the human body reaction time measurement efficiency and accuracy ,this paper discusses how to develop the human body reaction time measuring instrument . The system consists of a signaling device ,and bearing device ,time pressure recording device and reaction judging device .Experimental results show that the system can complete the human reaction time signal measurement ,record and judging process ,and can meet the needs of teaching and scientific research experiment of movement .

  14. European Contribution to Human Aspect Investigations for Future Planetary Habitat Definition Studies: Field Tests at MDRS on Crew Time Utilisation and Habitat Interfaces (United States)

    Pletser, Vladimir; Foing, Bernard


    Human factors are a dominant aspect in space missions, which may strongly influence work results and efficiency. To assess their impact on future long term space missions and to attempt a general quantification, the environmental and technical conditions to which astronauts may be confronted need to be reproduced as closely as possible. Among the stressors that occur during space missions, limited resources, limited social interactions, long term living and working in confined and isolated areas are among the most important for future planetary exploration. The European Space Agency (ESA) has a strong interest in obtaining data and insights in human aspects to prepare for future studies on the definition of future Lunar and Martian planetary habitats. In this frame, ESA's Directorate of Human Space Flight was associated to the EuroGeoMars campaign conducted by the Crews 76 and 77 in February 2009 in The Mars Society's `Mars Desert Research Station' (MDRS) in the Desert of Utah. The EuroGeoMars Campaign lasted 5 weeks and encompassed two groups of experiments, on human crew related aspects and field experiments in geology, biology and astronomy/astrophysics. The human crew related aspects covered (1) crew time organization in a planetary habitat, (2) an evaluation of the different functions and interfaces of this habitat, (3) an evaluation of man-machine interfaces of science and technical equipment. Several forms and questionnaires were filled in by all crew members: time and location evaluation sheets and two series of questionnaires. In addition, the crew participated in another on-going food study where the type of food was imposed and crew impressions were collected via questionnaires. The paper recalls the objectives of the human crew related experiments of the EuroGeoMars project and presents the first results of these field investigations. Some recommendations and lessons learnt will be presented and used as first inputs for future planetary habitat

  15. Feedback effect of human physical and psychological adaption on time period of thermal adaption in naturally ventilated building

    DEFF Research Database (Denmark)

    liu, weiwei; Huangfu, Hao; Xiong, Jing


    This study proposed a method to determine time period of thermal adaption for occupants in naturally ventilated building, and analyzed the synergistic and separate feedback effect of the physical and psychological adaption modes on the time period of thermal adaption. Using the method, the values......, under the synergistic feedback effect of the physical and psychological adaption modes. The time period of thermal adaption increased to 13 days, if only the feedback effect of the physical adaption mode was accounted for. The difference between the two values of the time period of thermal adaption...... of the time period of thermal adaption were obtained on the basis of the data from a long-term field survey conducted in two typical naturally ventilated offices located in Changsha, China. The results showed that the occupants need to take 4.25 days to fully adapt to a step-change in outdoor air temperature...

  16. Searching for anthropogenic contaminants in human breast adipose tissues using gas chromatography-time-of-flight mass spectrometry


    Hernández Hernández, Félix; Portolés Nicolau, Tania; Pitarch Arquimbau, María Elena; López Benet, Francisco José


    The potential of GC-TOF MS for screening anthropogenic organic contaminants in human breast adipose tissues has been investigated. Initially a target screening was performed for a list of 125 compounds which included persistent halogen pollutants (OC pesticides, PCBs, PBDEs), PAHs, alkylphenols, and a notable number of pesticides from the different fungicide, herbicide and insecticide families. Searching for target pollutants was done by evaluating the presence of up to five representative io...

  17. Spatial- and time-explicit human damage modeling of ozone depleting substances in life cycle impact assessment. (United States)

    Struijs, Jaap; van Dijk, Arjan; Slaper, Harry; van Wijnen, Harm J; Velders, Guus J M; Chaplin, George; Huijbregts, Mark A J


    Depletion of the stratospheric ozone layer is mainly caused by emissions of persistent halocarbons of anthropogenic origin. The resulting increase of solar ultraviolet radiation at the Earth's surface is associated with increased exposure of humans and increased human health damage. Here we assessed the change in human health damage caused by three types of skin cancer and cataract in terms of (healthy) years of life lost per kiloton emission reduction of an ozone-depleting substance (ODS). This so-called characterization factor is used in Life Cycle Assessments (LCAs). Characterization factors are provided for the emissions of five chlorofluorocarbons, three hydrochlorofluorocarbons, three (bromine-containing) halons, carbon tetrachloride, methyl chloroform, and anthropogenic emissions of methyl bromide. We employed dynamic calculations on a global scale for this purpose, taking physical and social geographic data into account such as skin tones, population density, average age, and life expectancy. When emission rates of all ODSs in 2007 are multiplied by our characterization factors, the resulting number of years of life lost may be a factor of 5 higher than reported previously. This increase is merely explained through the global demographic development until 2100 we took into account.

  18. Assessment of the time-dependent inhibition (TDI) potential of test compounds with human liver microsomes by IC50 shift method using a nondilution approach. (United States)

    de Ron, Lian; Rajaraman, Ganesh


    Time-dependent inhibition (TDI) of hepatic cytochrome P450 (CYP) enzymes is increasingly implicated in the majority of clinically relevant drug-drug interactions (DDIs). A time-dependent inhibitor or its reactive metabolite irreversibly inactivates CYP enzymes, thereby inhibiting the metabolism of other drugs. As the majority of marketed drugs are metabolized by CYP enzymes, their inhibition has important clinical consequences, such as in decreasing the metabolic clearance of a co-administered drug (victim drug). This could be life threatening, as such an effect narrows the therapeutic index for drugs such as warfarin and other potentially toxic agents. Therefore, it is essential to examine new chemical entities for their potential to cause TDI to minimize adverse drug reactions during human studies and use. This unit presents an in vitro procedure utilizing a nondilution method in human liver microsomes for determining the TDI potential of test compounds.

  19. Human induced dryland degradation in Ordos Plateau, China, revealed by multilevel statistical modeling of normalized difference vegetation index and rainfall time-series

    Institute of Scientific and Technical Information of China (English)

    Jing ZHANG; JianMing NIU; Tongliga BAO; Alexander BUYANTUYEV; Qing ZHANG; JianJun DONG; XueFeng ZHANG


    Land degradation causes serious environmental problems in many regions of the world, and although it can be effectively assessed and monitored using a time series of rainfall and a normalized difference vegetation index (NDVI) from remotely-sensed imagery, dividing human-induced land degradation from vegetation dynamics due to climate change is not a trivial task. This paper presented a multilevel statistical modeling of the NDVI-rainfall relationship to detect human-induced land degradation at local and landscape scales in the Ordos Plateau of Inner Mongolia, China, and recognized that anthropogenic activities result in either positive (land restoration and re-vegetation) or negative (degradation) trends. Linear regressions were used to assess the accuracy of the multi-level statistical model. The results show that:(1) land restoration was the dominant process in the Ordos Plateau between 1998 and 2012;(2) the effect of the statistical removal of precipitation revealed areas of human-induced land degradation and improvement, the latter reflecting successful restoration projects and changes in land man-agement in many parts of the Ordos; (3) compared to a simple linear regression, multilevel statistical modeling could be used to analyze the relationship between the NDVI and rainfall and improve the accuracy of detecting the effect of human activities. Additional factors should be included when analyzing the NDVI-rainfall relationship and detecting human-induced loss of vegetation cover in drylands to improve the accuracy of the approach and elimi-nate some observed non-significant residual trends.

  20. Rapid detection of Opisthorchis viverrini and Strongyloides stercoralis in human fecal samples using a duplex real-time PCR and melting curve analysis. (United States)

    Janwan, Penchom; Intapan, Pewpan M; Thanchomnang, Tongjit; Lulitanond, Viraphong; Anamnart, Witthaya; Maleewong, Wanchai


    Human opisthorchiasis caused by the liver fluke Opisthorchis viverrini is an endemic disease in Southeast Asian countries including the Lao People's Democratic Republic, Cambodia, Vietnam, and Thailand. Infection with the soil-transmitted roundworm Strongyloides stercoralis is an important problem worldwide. In some areas, both parasitic infections are reported as co-infections. A duplex real-time fluorescence resonance energy transfer (FRET) PCR merged with melting curve analysis was developed for the rapid detection of O. viverrini and S. stercoralis in human fecal samples. Duplex real-time FRET PCR is based on fluorescence melting curve analysis of a hybrid of amplicons generated from two genera of DNA elements: the 162 bp pOV-A6 DNA sequence specific to O. viverrini and the 244 bp 18S rRNA sequence specific to S. stercoralis, and two pairs of specific fluorophore-labeled probes. Both O. viverrini and S. stercoralis can be differentially detected in infected human fecal samples by this process through their different fluorescence channels and melting temperatures. Detection limit of the method was as little as two O. viverrini eggs and four S. stercoralis larvae in 100 mg of fecal sample. The assay could distinguish the DNA of both parasites from the DNA of negative fecal samples and fecal samples with other parasite materials, as well as from the DNA of human leukocytes and other control parasites. The technique showed 100% sensitivity and specificity. The introduced duplex real-time FRET PCR can reduce labor time and reagent costs and is not prone to carry over contamination. The method is important for simultaneous detection especially in areas where both parasites overlap incidence and is useful as the screening tool in the returning travelers and immigrants to industrialized countries where number of samples in the diagnostic units will become increasing.

  1. HuGE Watch: tracking trends and patterns of published studies of genetic association and human genome epidemiology in near-real time. (United States)

    Yu, Wei; Wulf, Anja; Yesupriya, Ajay; Clyne, Melinda; Khoury, Muin Joseph; Gwinn, Marta


    HuGE Watch is a web-based application for tracking the evolution of published studies on genetic association and human genome epidemiology in near-real time. The application allows users to display temporal trends and spatial distributions as line charts and google maps, providing a quick overview of progress in the field.

  2. Real-Time Human in the Loop MBS Simulation in the Fraunhofer Robot-Based Driving Simulator

    Directory of Open Access Journals (Sweden)

    Kleer Michael


    Full Text Available The paper encompasses the overview of hardware architecture and the systems characteristics of the Fraunhofer driving simulator. First, the requirements of the real-time model and the real-time calculation hardware are defined and discussed in detail. Aspects like transport delay and the parallel computation of complex real-time models are presented. In addition, the interfacing of the models with the simulator system is shown. Two simulator driving tests, including a fully interactive rough terrain driving with a wheeled excavator and a test drive with a passenger car, are set to demonstrate system characteristics. Furthermore, the simulator characteristics of practical significance, such as simulator response time delay, simulator acceleration signal bandwidth obtained from artificial excitation and from the simulator driving test, will be presented and discussed.

  3. DNA replication timing is maintained genome-wide in primary human myoblasts independent of D4Z4 contraction in FSH muscular dystrophy.

    Directory of Open Access Journals (Sweden)

    Benjamin D Pope

    Full Text Available Facioscapulohumeral muscular dystrophy (FSHD is linked to contraction of an array of tandem 3.3-kb repeats (D4Z4 at 4q35.2 from 11-100 copies to 1-10 copies. The extent to which D4Z4 contraction at 4q35.2 affects overall 4q35.2 chromatin organization remains unclear. Because DNA replication timing is highly predictive of long-range chromatin interactions, we generated genome-wide replication-timing profiles for FSHD and control myogenic precursor cells. We compared non-immortalized myoblasts from four FSHD patients and three control individuals to each other and to a variety of other human cell types. This study also represents the first genome-wide comparison of replication timing profiles in non-immortalized human cell cultures. Myoblasts from both control and FSHD individuals all shared a myoblast-specific replication profile. In contrast, male and female individuals were readily distinguished by monoallelic differences in replication timing at DXZ4 and other regions across the X chromosome affected by X inactivation. We conclude that replication timing is a robust cell-type specific feature that is unaffected by FSHD-related D4Z4 contraction.

  4. Efficient diagnosis and treatment follow-up of human brucellosis by a novel quantitative TaqMan real-time PCR assay: a human clinical survey. (United States)

    Sohrabi, Majid; Mohabati Mobarez, Ashraf; Khoramabadi, Nima; Hosseini Doust, Reza; Behmanesh, Mehrdad


    Rapid and effective diagnosis of brucellosis is a challenge for clinicians. Even when diagnosis is on time and therapy is initiated, meticulous follow-up appointments are crucial for ensuring the efficacy of the treatment. Due to shortcomings of serological methods, molecular diagnosis, especially real-time PCR, is becoming a main approach in laboratory diagnostics. Thus, the development of efficient procedures and standardization of the PCR tests will have a great impact on the precise detection and quantification of bacterial DNA loads, which is valuable for the medical management of brucellosis patients. We developed a new TaqMan real-time PCR directed to bcsp31, a shared gene of the brucellae. The bcsp31 gene fragment was cloned into pJET1.2. Recombinant pJET1.2-bcsp31 was linearized by HindIII digestion, and the product was used for the preparation of a standard curve. A panel of Brucella spp. and non-Brucella pathogens was tested. No bacterial genomes other than those of the brucellae were detected. According to the results, specificity of the method was 100%. In a clinical assessment, the positive-control group comprised 37 patients with microbiologically confirmed brucellosis, and 25 healthy individuals served as the negative-control group. By the end of the treatment period, there was a significant decrease in the DNA load of the 37 brucellosis patients, which persisted for the 4 weeks of monitoring after treatment, suggesting that our proposed method is an efficient monitoring tool. Serum samples prior to any treatment were collected from the 25 serologically suspicious patients and assessed by our method; 72% of these patients tested positive for brucellosis.

  5. Simultaneous determination of nabumetone and its principal metabolite in medicines and human urine by time-resolved fluorescence. (United States)

    Murillo Pulgarín, José Antonio; Alañón Molina, Aurelia; Martínez Ferreras, Fernando


    A simple fluorescent methodology for the simultaneous determination of nabumetone and its main metabolite, 6-methoxy-2-naphthylacetic acid (6-MNA), in pharmaceutical preparations and human urine is proposed. Due to the strong overlapping between the fluorescence spectra of both analytes, the use of fluorescence decay curves to resolve their mixture is proposed, since these curves are more selective. Values of dependent instrumental variables affecting the signal-to-noise ratio were fixed using a simplex optimization procedure. A factorial design with three levels per factor coupled to a central composite design was selected to obtain a calibration matrix of thirteen standards plus one blank sample that was processed using a partial least-squares (PLS) analysis. In order to assess the goodness of the proposed method, a prediction set of ten synthetic samples was analyzed, obtaining recovery percentages between 97 and 105%. Limits of detection, calculated by means of a new criterion, were 0.96 μg L(-1) and 0.88 μg L(-1) for nabumetone and 6-MNA, respectively. The method was also tested in the pharmaceutical preparation Relif, which contains nabumetone, obtaining recovery percentages close to 100%. Finally, the simultaneous determination of both analytes in human urine samples was successfully carried out by the PLS-analysis of a matrix of fifteen standards plus four analyte blanks and the use of the standard addition technique. Although urine shows native fluorescence, no extraction method or prior separation of the analytes was needed.

  6. A real-time ITS1-PCR based method in the diagnosis and species identification of Leishmania parasite from human and dog clinical samples in Turkey. (United States)

    Toz, Seray Ozensoy; Culha, Gulnaz; Zeyrek, Fadile Yıldız; Ertabaklar, Hatice; Alkan, M Ziya; Vardarlı, Aslı Tetik; Gunduz, Cumhur; Ozbel, Yusuf


    Human visceral leishmaniasis (VL) caused by L. infantum and cutaneous leishmaniasis (CL) caused by L. tropica and L. infantum have been reported in Turkey. L. infantum is also responsible for canine leishmaniasis (CanL) and it is widely common in the country. The main aim of the present study was to design a real-time PCR method based on the internal transcribed spacer 1 (ITS1) region in the diagnosis of all clinical forms of leishmaniasis in Mediterranean, and to identify the species directly from clinical samples. Totally, 315 clinical specimens, human/canine visceral (blood, bone marrow, lymph node) and cutaneous (lesion aspiration) samples, and 51 Turkish Leishmania isolates typed by isoenzymatic method were included in the study. For optimization, DNA samples of the 34 strains were amplified by conventional ITS1-PCR and then sequenced for designing the primers and probes, allowing the species identification. Following the validation with the isolates, the test was applied on clinical samples and melting temperatures were used for genotyping. A group of PCR products were further sequenced for confirmation and assigning the inter- and intraspecies heterogeneity. The diagnosis of leishmaniasis is successfully achieved by the new real-time PCR method, and the test identified 80.43% of human and canine VL samples as L.infantum and 6.52% as L.tropica; 52.46% of CL samples as L. infantum and 26.90% as L. tropica. In 13.04% of visceral and 20.62% of cutaneous samples, two peaks were observed. However, the higher peak was found to be concordant with the sequencing results in 96.96%, in terms of species identification. The real-time ITS1 PCR assay clearly identified the leishmanial species in 81.58% of all clinical samples. Genotypic variations of Leishmania parasites in Turkey within species and intraspecies were observed, and L. tropica is also found as causative agent of human and canine VL in Turkey.

  7. A real-time ITS1-PCR based method in the diagnosis and species identification of Leishmania parasite from human and dog clinical samples in Turkey.

    Directory of Open Access Journals (Sweden)

    Seray Ozensoy Toz

    Full Text Available Human visceral leishmaniasis (VL caused by L. infantum and cutaneous leishmaniasis (CL caused by L. tropica and L. infantum have been reported in Turkey. L. infantum is also responsible for canine leishmaniasis (CanL and it is widely common in the country. The main aim of the present study was to design a real-time PCR method based on the internal transcribed spacer 1 (ITS1 region in the diagnosis of all clinical forms of leishmaniasis in Mediterranean, and to identify the species directly from clinical samples. Totally, 315 clinical specimens, human/canine visceral (blood, bone marrow, lymph node and cutaneous (lesion aspiration samples, and 51 Turkish Leishmania isolates typed by isoenzymatic method were included in the study. For optimization, DNA samples of the 34 strains were amplified by conventional ITS1-PCR and then sequenced for designing the primers and probes, allowing the species identification. Following the validation with the isolates, the test was applied on clinical samples and melting temperatures were used for genotyping. A group of PCR products were further sequenced for confirmation and assigning the inter- and intraspecies heterogeneity. The diagnosis of leishmaniasis is successfully achieved by the new real-time PCR method, and the test identified 80.43% of human and canine VL samples as L.infantum and 6.52% as L.tropica; 52.46% of CL samples as L. infantum and 26.90% as L. tropica. In 13.04% of visceral and 20.62% of cutaneous samples, two peaks were observed. However, the higher peak was found to be concordant with the sequencing results in 96.96%, in terms of species identification. The real-time ITS1 PCR assay clearly identified the leishmanial species in 81.58% of all clinical samples. Genotypic variations of Leishmania parasites in Turkey within species and intraspecies were observed, and L. tropica is also found as causative agent of human and canine VL in Turkey.

  8. (31)P-MRS of healthy human brain: ATP synthesis, metabolite concentrations, pH, and T1 relaxation times. (United States)

    Ren, Jimin; Sherry, A Dean; Malloy, Craig R


    The conventional method for measuring brain ATP synthesis is (31)P saturation transfer (ST), a technique typically dependent on prolonged pre-saturation with γ-ATP. In this study, ATP synthesis rate in resting human brain is evaluated using EBIT (exchange kinetics by band inversion transfer), a technique based on slow recovery of γ-ATP magnetization in the absence of B1 field following co-inversion of PCr and ATP resonances with a short adiabatic pulse. The unidirectional rate constant for the Pi → γ-ATP reaction is 0.21 ± 0.04 s(-1) and the ATP synthesis rate is 9.9 ± 2.1 mmol min(-1)  kg(-1) in human brain (n = 12 subjects), consistent with the results by ST. Therefore, EBIT could be a useful alternative to ST in studying brain energy metabolism in normal physiology and under pathological conditions. In addition to ATP synthesis, all detectable (31)P signals are analyzed to determine the brain concentration of phosphorus metabolites, including UDPG at around 10 ppm, a previously reported resonance in liver tissues and now confirmed in human brain. Inversion recovery measurements indicate that UDPG, like its diphosphate analogue NAD, has apparent T1 shorter than that of monophosphates (Pi, PMEs, and PDEs) but longer than that of triphosphate ATP, highlighting the significance of the (31)P-(31)P dipolar mechanism in T1 relaxation of polyphosphates. Another interesting finding is the observation of approximately 40% shorter T1 for intracellular Pi relative to extracellular Pi, attributed to the modulation by the intracellular phosphoryl exchange reaction Pi ↔ γ-ATP. The sufficiently separated intra- and extracellular Pi signals also permit the distinction of pH between intra- and extracellular environments (pH 7.0 versus pH 7.4). In summary, quantitative (31)P MRS in combination with ATP synthesis, pH, and T1 relaxation measurements may offer a promising tool to detect biochemical alterations at early stages of brain dysfunctions and diseases.

  9. Shortening of alkaline DNA unwinding time does not interfere with detecting DNA damage to mouse and human spermatozoa in the comet assay

    Institute of Scientific and Technical Information of China (English)

    Hirokazu Kusakabe; Hiroyuki Tateno


    The comet assay was performed on mouse and human spermatozoa to examine the effect of alkaline DNA unwinding time.The spermatozoa were treated in vitrowith the DNA-damaging agents,methyl methanesulfonate(MMS)or hydrogen peroxide(H2O2),and then embedded in agarose gel on glass slides.The slides were immersed in alkaline solution(>pH 1.3)for 1,5,10 and 20 min,and then subjected to the electrophoresis under neutral conditions.In mouse spermatozoa,comet tails seen in solvent controls became brighter and longer as the alkaline DNA unwinding time increased.However,in the MMS-treated mouse spermatozoa,a smaller difference in the damage from that in the solvent control was seen with time within a dose.DNA damage induced by H2O2 could also be detected accurately after alkali treatment for 1-20 min.In human spermatozoa,DNA damage induced by MMS and H2O2 could be detected in a dose-dependent manner after alkali treatment for 1 min.The ability of the comet assay to detect DNA damage was not adversely affected by the short period(1 min)of the alkaline DNA unwinding time.

  10. Comparison of different pulse sequences for in vivo determination of T1 relaxation times in the human brain

    DEFF Research Database (Denmark)

    Kjaer, L; Henriksen, O


    (PSIR) sequence with TR varying between 0.24 and 8.0 s. The median T1 relaxation times obtained in cortical grey matter and cerebrospinal fluid were significantly shorter in the IR experiments at TR = 2 s than in those carried out at TR = 4 s. Concerning white matter the discrepancy was much less...

  11. Combined use of real-time PCR and nested sequence-based typing in survey of human Legionella infection. (United States)

    Qin, T; Zhou, H; Ren, H; Shi, W; Jin, H; Jiang, X; Xu, Y; Zhou, M; Li, J; Wang, J; Shao, Z; Xu, X


    Legionnaires' disease (LD) is a globally distributed systemic infectious disease. The burden of LD in many regions is still unclear, especially in Asian countries including China. A survey of Legionella infection using real-time PCR and nested sequence-based typing (SBT) was performed in two hospitals in Shanghai, China. A total of 265 bronchoalveolar lavage fluid (BALF) specimens were collected from hospital A between January 2012 and December 2013, and 359 sputum specimens were collected from hospital B throughout 2012. A total of 71 specimens were positive for Legionella according to real-time PCR focusing on the 5S rRNA gene. Seventy of these specimens were identified as Legionella pneumophila as a result of real-time PCR amplification of the dotA gene. Results of nested SBT revealed high genetic polymorphism in these L. pneumophila and ST1 was the predominant sequence type. These data revealed that the burden of LD in China is much greater than that recognized previously, and real-time PCR may be a suitable monitoring technology for LD in large sample surveys in regions lacking the economic and technical resources to perform other methods, such as urinary antigen tests and culture methods.

  12. The Timing of Prenatal Exposure to Maternal Cortisol and Psychosocial Stress Is Associated with Human Infant Cognitive Development (United States)

    Davis, Elysia P.; Sandman, Curt A.


    The consequences of prenatal maternal stress for development were examined in 125 full-term infants at 3, 6, and 12 months of age. Maternal cortisol and psychological state were evaluated 5 times during pregnancy. Exposure to elevated concentrations of cortisol early in gestation was associated with a slower rate of development over the 1st year…

  13. Cadmium-free quantum dots as time-gated bioimaging probes in highly-autofluorescent human breast cancer cells. (United States)

    Mandal, Gopa; Darragh, Molly; Wang, Y Andrew; Heyes, Colin D


    We report cadmium-free, biocompatible (Zn)CuInS(2) quantum dots with long fluorescence lifetimes as superior bioimaging probes using time-gated detection to suppress cell autofluorescence and improve the signal : background ratio by an order of magnitude. These results will be important for developing non-toxic fluorescence imaging probes for ultrasensitive biomedical diagnostics.

  14. Rapid, sensitive, and specific detection of Mycobacterium tuberculosis complex by real-time PCR on paraffin-embedded human tissues. (United States)

    Lee, Hye Seung; Park, Kyoung Un; Park, Jung Ok; Chang, Ho Eun; Song, Junghan; Choe, Gheeyoung


    The detection of Mycobacterium tuberculosis complex (MTB) in clinical specimens is important for diagnosing and caring for patients in whom tuberculosis is clinically suspected. We collected 129 FFPE specimens, including 56 nontuberculosis cases, 63 MTB cases, and 10 nontuberculous mycobacteria (NTM) cases determined by acid-fast bacilli (AFB) culture. We performed AFB staining; nested MTB PCR, targeting the IS6110 gene; and real-time MTB PCR, targeting the senX3-regX3 intergenic region in the 129 FFPE specimens. The sensitivity and specificity of AFB staining were 37.0% and 98.2%, respectively, using AFB culture results as the reference standard. The sensitivity and specificity of detecting MTB were 68.3% and 98.5%, respectively, by nested PCR; and 74.6% and 98.5% by real-time PCR, respectively. Among the 129 specimens, four were positive by AFB staining but negative by nested or real-time PCR. NTM grew in all four of these cases by AFB culture. AFB density in FFPE tissue sections significantly correlated with MTB DNA load. Thus, real-time PCR is a useful diagnostic tool for rapid and sensitive MTB detection in FFPE specimens, whereas NTM should be included in differential diagnoses of cases positive by AFB staining but negative by PCR.

  15. Detection and identification of human Plasmodium species with real-time quantitative nucleic acid sequence-based amplification

    NARCIS (Netherlands)

    P.F. Mens; G.J. Schoone; P.A. Kager; H.D.F.H. Schallig


    Background: Decisions concerning malaria treatment depend on species identification causing disease. Microscopy is most frequently used, but at low parasitaemia (< 20 parasites/mu l) the technique becomes less sensitive and time consuming. Rapid diagnostic tests based on Plasmodium antigen detection

  16. Complexities in the Use of Bomb-Curve Radiocarbon to Determine Time Since Death of Human Skeletal Remains

    Energy Technology Data Exchange (ETDEWEB)

    Ubelaker, D H; Buchholz, B A


    Atmospheric testing of nuclear weapons during the 1950s and early 1960s doubled the level of radiocarbon ({sup 14}C) in the atmosphere. From the peak in 1963, the level of {sup 14}CO{sub 2} has decreased exponentially with a mean life of about 16 years, not due to radioactive decay, but due to mixing with large marine and terrestrial carbon reservoirs. Since radiocarbon is incorporated into all living things, the bomb-pulse is an isotopic chronometer of the past half century. The absence of bomb radiocarbon in skeletonized human remains generally indicates a date of death before 1950. Comparison of the radiocarbon values with the post 1950 bomb-curve may also help elucidate when in the post 1950 era, the individual was still alive. Such interpretation however, must consider the age at death of the individual and the type of tissue sampled.

  17. Relaxation and phase space singularities in time series of human magnetoencephalograms can serve as an indicator of the photosensitive epilepsy

    CERN Document Server

    Yulmetyev, R M; Hänggi, P; Khusaenova, E V; Shimojo, S; Yulmetyeva, D G


    To analyze the crucial role of the fluctuation and relaxational effects in the human brain functioning we have studied a some statistical quantifiers that support the informational characteristics of neuromagnetic responses of magnetoencephalographic (MEG) signals. The signals to a flickering stimulus of different color combinations has been obtained from a group of control subjects which is contrasted with those for a patient with photosensitive epilepsy (PSE). We have revealed that the existence of the specific stratification of the phase clouds and the concomitant relaxation singularities of the corresponding nonequilibrium processes of chaotic behavior of the signals in the separate areas for a patient most likely shows the pronounced zones responsible the appearance of PSE.

  18. Targeted profiling of oral bacteria in human saliva and in vitro biofilms with quantitative real-time PCR. (United States)

    Price, R R; Viscount, H B; Stanley, M C; Leung, K-P


    An in vitro plaque model based on the use of human salivary bacteria and tooth-like surfaces was previously developed for studying the formation of oral biofilm and its use for pre-clinical testing of candidate antimicrobial or antiplaque agents. In this study, a quantitative Taqman PCR assay (QPCR) was developed to compare the bacterial compositions of in vitro biofilms to parent saliva samples, and to determine the relative contributions of different species in the formation of the oral biofilm. In addition, the growth inhibition of saliva-derived plaque was evaluated by chlorhexidine. With this assay, which consisted of primer/probe sets targeting either 16S rDNA sequences present in public databases or cloned ribosomal intergenic spacer region (ISR) sequences, 15 oral bacteria derived from saliva as well as those that were responsible for biofilm formation in an in vitro plaque model were rapidly identified and quantified. Among the target organisms were Actinobacillus actinomycetemcomitans, Eikenella corrodens, Fusobacterium nucleatum, Lactobacillus acidophilus, Micromonas micros, Porphyromonas gingivalis, Prevotella intermedia, Streptococcus mutans, Streptococcus sobrinus, Tannerella forsythensis, and Veillonella parvula. Primer and probe sets developed were both sensitive and specific. The relative profiles of a number of bacteria in 45-h-old biofilms were determined and, when compared to saliva samples, it was found that most of the bacteria identified in saliva also populated the in vitro plaque, including some anaerobes. Brief exposure of biofilms to chlorhexidine resulted in significant losses in viability. This new broad spectrum QPCR assay in combination with the in vitro plaque model will be of significant value in the quantitative study of the microbial composition of human saliva, saliva-derived plaque, and pre-clinical evaluation of potential antimicrobial and antiplaque molecules.

  19. Age-Related Changes to Human Stratum Corneum Lipids Detected Using Time-of-Flight Secondary Ion Mass Spectrometry Following in Vivo Sampling. (United States)

    Starr, Nichola J; Johnson, Daniel J; Wibawa, Judata; Marlow, Ian; Bell, Mike; Barrett, David A; Scurr, David J


    This work demonstrates the ability to detect changes in both quantity and spatial distribution of human stratum corneum (SC) lipids from samples collected in vivo. The SC functions as the predominant barrier to the body, protecting against the penetration of xenobiotic substances. Changes to the SC lipid composition have been associated with barrier impairment and consequent skin disorders, and it is therefore important to monitor and quantify changes to this structure. This work demonstrates the first reported use of time-of-flight secondary ion mass spectrometry (ToF-SIMS) to assess physiological changes to human SC as a function of depth. This technique provides exceptional sensitivity and chemical specificity, allowing analysis of single tape stripped samples taken from volunteers. Using this methodology we were able to successfully identify chemical differences in human SC resulting from both intrinsic and extrinsic (photo) aging. Samples were collected from women of two age groups (under 27 and postmenopausal) and from two body sites with varying UV exposure (inner forearm and dorsal hand), and differences were identified using multivariate data analysis. The key finding was the significant aged-related increase and change in spatial distribution of the sterol cholesterol sulfate, a membrane stabilizing lipid. Significant changes in the prevalence of both lignoceric acid (C24:0) and hexacosanoic acid (C26:0) were also observed. This work describes previously unreported age-related chemical changes to human SC, providing an insight into aging mechanisms which may improve the design of both pharmaceutical and cosmetic topical products.

  20. Uric acid promotes neuronal differentiation of human placenta-derived mesenchymal stem cells in a time- and concentration-dependent manner

    Institute of Scientific and Technical Information of China (English)

    Nailong Yang; Lili Xu; Peng Lin; Jing Cui


    Uric acid is an important, naturally occurring serum antioxidant. The present study investigates the use of uric acid for promoting proliferation and neuronal differentiation of mesenchymal stem cells derived from human placenta tissue. Human placenta-derived mesenchymal stem cells were pre-induced in the presence of either 0, 0.2, 0.4 or 0.8 mM uric acid in combination with 1 mM β-mercaptoethanol for 24 hours, followed by exposure to identical uric acid concentrations and 5 mM β-mercaptoethanol for 6 and 10 hours. Cells developed a neuronal-like morphology, with formation of interconnected process extensions, typical of neural cells. Immunocytochemistry and immunofluorescence staining showed neuron specific enolase positive cells were present in each group except the control group. A greater number of neuron specific enolase positive cells were observed in 0.8 mM uric acid in combination with 5 mM β-mercaptoethanol at 10 hours. After 24 hours of induction, Nissl bodies were detected in the cytoplasm of all differentiated cell groups except the control group and Nissl body numbers were greatest in human placenta-derived mesenchymal stem cells grown in the presence of 0.8 mM uric acid and 5 mM β-mercaptoethanol. These results suggest uric acid accelerates differentiation of human placenta-derived mesenchymal stem cells into neuronal-like cells in a time- and concentration-dependent manner.

  1. The advantages, disadvantages, and policies for part-time radiologists: report of the ACR Commission on Human Resources. (United States)

    Harolds, Jay A; Coleman, Beverly G; Recht, Michael P; Bluth, Edward I


    The employment of part-time radiologists (PTRs) has both advantages and disadvantages in various practice settings. The authors examine the pros and cons of PTRs and review the literature regarding PTRs both within and outside the specialty of radiology. The complexity of this issue is manifested in our inability to reach consensus on many policy issues for PTRs. Nevertheless, this article should be helpful in offering an objective, nonbiased background to initiating a discussion on employing PTRs in various radiology practices.

  2. Does Quality Time Produce Quality Children? Evidence on the Intergenerational Transmission of Human Capital using Parental Deaths



    This paper uses variation created by parental deaths in the amount of time children spend with each parent to examine whether the parent-child correlation in schooling outcomes stems from a causal relationship. Using a large sample of Israeli children who lost one parent during childhood, we find a series of striking patterns which show that the relationship is largely causal. Relative to children who did not lose a parent, the education of the deceased parent is less important in determining...

  3. Circadian regulation of human sleep and age-related changes in its timing, consolidation and EEG characteristics (United States)

    Dijk, D. J.; Duffy, J. F.


    The light-entrainable circadian pacemaker located in the suprachiasmatic nucleus of the hypothalamus regulates the timing and consolidation of sleep by generating a paradoxical rhythm of sleep propensity; the circadian drive for wakefulness peaks at the end of the day spent awake, ie close to the onset of melatonin secretion at 21.00-22.00 h and the circadian drive for sleep crests shortly before habitual waking-up time. With advancing age, ie after early adulthood, sleep consolidation declines, and time of awakening and the rhythms of body temperature, plasma melatonin and cortisol shift to an earlier clock hour. The variability of the phase relationship between the sleep-wake cycle and circadian rhythms increases, and in old age sleep is more susceptible to internal arousing stimuli associated with circadian misalignment. The propensity to awaken from sleep advances relative to the body temperature nadir in older people, a change that is opposite to the phase delay of awakening relative to internal circadian rhythms associated with morningness in young people. Age-related changes do not appear to be associated with a shortening of the circadian period or a reduction of the circadian drive for wake maintenance. These changes may be related to changes in the sleep process itself, such as reductions in slow-wave sleep and sleep spindles as well as a reduced strength of the circadian signal promoting sleep in the early morning hours. Putative mediators and modulators of circadian sleep regulation are discussed.

  4. Reference gene selection for quantitative real-time PCR analysis in virus infected cells: SARS corona virus, Yellow fever virus, Human Herpesvirus-6, Camelpox virus and Cytomegalovirus infections

    Directory of Open Access Journals (Sweden)

    Müller Marcel A


    Full Text Available Abstract Ten potential reference genes were compared for their use in experiments investigating cellular mRNA expression of virus infected cells. Human cell lines were infected with Cytomegalovirus, Human Herpesvirus-6, Camelpox virus, SARS coronavirus or Yellow fever virus. The expression levels of these genes and the viral replication were determined by real-time PCR. Genes were ranked by the BestKeeper tool, the GeNorm tool and by criteria we reported previously. Ranking lists of the genes tested were tool dependent. However, over all, β-actin is an unsuitable as reference gene, whereas TATA-Box binding protein and peptidyl-prolyl-isomerase A are stable reference genes for expression studies in virus infected cells.

  5. Characterization of ornidazole metabolites in human bile after intraveneous doses by ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry

    Directory of Open Access Journals (Sweden)

    Jiangbo Du


    Full Text Available Ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS was used to characterize ornidazole metabolites in human bile after intravenous doses. A liquid chromatography tandem mass spectrometry (LC–MS/MS assay was developed for the determination of the bile level of ornidazole. Bile samples, collected from four patients with T-tube drainage after biliary tract surgery, were prepared by protein precipitation with acetonitrile before analysis. A total of 12 metabolites, including 10 novel metabolites, were detected and characterized. The metabolites of ornidazole in human bile were the products of hydrochloride (HCl elimination, oxidative dechlorination, hydroxylation, sulfation, diastereoisomeric glucuronation, and substitution of NO2 or Cl atom by cysteine or N-acetylcysteine, and oxidative dechlorination followed by further carboxylation. The bile levels of ornidazole at 12 h after multiple intravenous infusions were well above its minimal inhibitory concentration for common strains of anaerobic bacteria.

  6. Apta-biosensors for nonlabeled real time detection of human IgE based on carbon nanotube field effect transistors. (United States)

    Kim, Jun Pyo; Hong, Seunghun; Sim, Sang Jun


    In this study, we demonstrated the aptamer-based biosensor (apta-biosensor) using CNT-FET devices for label free detection of allergy diagnosis by IgE detection. In order to detect the IgE, two kinds of receptor (monoclonal IgE antibody and anti-IgE aptamer)-modified CNT-FET devices were fabricated. The binding event of the target IgE onto receptors was detected by monitoring the gating effect caused by the charges of the target proteins. Since the CNT-FET biosensors were used in buffer solution, it was crucial to use small-size receptors like aptamers than whole antibodies so that the charged target IgE could approach the CNT surface within the Debye length distance to give a large gating effect. The results show that CNT-FET biosensors using monoclonal IgE antibody had very low sensitivity (minimum detectable level 1000 ng/mL), while those based on anti-IgE aptamer could detect 50 ng/mL. Moreover, the aptamer-modified CNT-FET herein could successfully block non-target proteins and could selectively detect the target protein in an environment similar to human serum electrolyte. Therefore, aptamer-based CNT-FET devices enable the production of label-free ultrasensitive electronic biosensors to detect clinically important biomarkers for disease diagnosis.

  7. Identification of appropriate reference genes for human mesenchymal stem cell analysis by quantitative real-time PCR. (United States)

    Li, Xiuying; Yang, Qiwei; Bai, Jinping; Xuan, Yali; Wang, Yimin


    Normalization to a reference gene is the method of choice for quantitative reverse transcription-PCR (RT-qPCR) analysis. The stability of reference genes is critical for accurate experimental results and conclusions. We have evaluated the expression stability of eight commonly used reference genes found in four different human mesenchymal stem cells (MSC). Using geNorm, NormFinder and BestKeeper algorithms, we show that beta-2-microglobulin and peptidyl-prolylisomerase A were the optimal reference genes for normalizing RT-qPCR data obtained from MSC, whereas the TATA box binding protein was not suitable due to its extensive variability in expression. Our findings emphasize the significance of validating reference genes for qPCR analyses. We offer a short list of reference genes to use for normalization and recommend some commercially-available software programs as a rapid approach to validate reference genes. We also demonstrate that the two reference genes, β-actin and glyceraldehyde-3-phosphate dehydrogenase, are frequently used are not always successful in many cases.

  8. A UWB Radar Signal Processing Platform for Real-Time Human Respiratory Feature Extraction Based on Four-Segment Linear Waveform Model. (United States)

    Hsieh, Chi-Hsuan; Chiu, Yu-Fang; Shen, Yi-Hsiang; Chu, Ta-Shun; Huang, Yuan-Hao


    This paper presents an ultra-wideband (UWB) impulse-radio radar signal processing platform used to analyze human respiratory features. Conventional radar systems used in human detection only analyze human respiration rates or the response of a target. However, additional respiratory signal information is available that has not been explored using radar detection. The authors previously proposed a modified raised cosine waveform (MRCW) respiration model and an iterative correlation search algorithm that could acquire additional respiratory features such as the inspiration and expiration speeds, respiration intensity, and respiration holding ratio. To realize real-time respiratory feature extraction by using the proposed UWB signal processing platform, this paper proposes a new four-segment linear waveform (FSLW) respiration model. This model offers a superior fit to the measured respiration signal compared with the MRCW model and decreases the computational complexity of feature extraction. In addition, an early-terminated iterative correlation search algorithm is presented, substantially decreasing the computational complexity and yielding negligible performance degradation. These extracted features can be considered the compressed signals used to decrease the amount of data storage required for use in long-term medical monitoring systems and can also be used in clinical diagnosis. The proposed respiratory feature extraction algorithm was designed and implemented using the proposed UWB radar signal processing platform including a radar front-end chip and an FPGA chip. The proposed radar system can detect human respiration rates at 0.1 to 1 Hz and facilitates the real-time analysis of the respiratory features of each respiration period.

  9. Simple Real-Time PCR and Amplicon Sequencing Method for Identification of Plasmodium Species in Human Whole Blood. (United States)

    Lefterova, Martina I; Budvytiene, Indre; Sandlund, Johanna; Färnert, Anna; Banaei, Niaz


    Malaria is the leading identifiable cause of fever in returning travelers. Accurate Plasmodium species identification has therapy implications for P. vivax and P. ovale, which have dormant liver stages requiring primaquine. Compared to microscopy, nucleic acid tests have improved specificity for species identification and higher sensitivity for mixed infections. Here, we describe a SYBR green-based real-time PCR assay for Plasmodium species identification from whole blood, which uses a panel of reactions to detect species-specific non-18S rRNA gene targets. A pan-Plasmodium 18S rRNA target is also amplified to allow species identification or confirmation by sequencing if necessary. An evaluation of assay accuracy, performed on 76 clinical samples (56 positives using thin smear microscopy as the reference method and 20 negatives), demonstrated clinical sensitivities of 95.2% for P. falciparum (20/21 positives detected) and 100% for the Plasmodium genus (52/52), P. vivax (20/20), P. ovale (9/9), and P. malariae (6/6). The sensitivity of the P. knowlesi-specific PCR was evaluated using spiked whole blood samples (100% [10/10 detected]). The specificities of the real-time PCR primers were 94.2% for P. vivax (49/52) and 100% for P. falciparum (51/51), P. ovale (62/62), P. malariae (69/69), and P. knowlesi (52/52). Thirty-three specimens were used to test species identification by sequencing the pan-Plasmodium 18S rRNA PCR product, with correct identification in all cases. The real-time PCR assay also identified two samples with mixed P. falciparum and P. ovale infection, which was confirmed by sequencing. The assay described here can be integrated into a malaria testing algorithm in low-prevalence areas, allowing definitive Plasmodium species identification shortly after malaria diagnosis by microscopy.

  10. Timing and modality of the sclerosing agents binding to the human proteins: laboratory analysis and clinical evidences

    Directory of Open Access Journals (Sweden)

    Lorenzo Tessari


    Full Text Available Sclerosing agents (SA are blood inactivated. Nevertheless, investigations concerning the interaction among SA and blood components have never been deeply investigated. Aim of the study is to precisely identify SA blood ligands, to determine their binding time and to highlight the clinical consequences. Thirty-one blood samples were collected from chronic venous disease patients and tested by capillary and agarose gel (AGE electrophoresis before and after adding polidocanol (POL and sodiumtetradecylsulphate (STS. The two different types of electrophoresis allowed an evaluation of the blood proteins binding with the sclerosing agents, with a reaction time lower than 8 seconds for the AGE. Subsequently six patients underwent foam sclerotherapy and then were subdivided in group A (4 patients and B (2 patients. In group A blood sample was obtained from the ipsilateral brachial vein immediately before (T0 and repeated 1, 3, 5, and 10 minutes after injection of STS 3% injection into the GSV. In group B, the same procedure was performed with the same timing from the ipsilateral femoral vein. Free STS (fSTS and total proteinbound STS (bSTS were measured. POL mainly binds to β-globulins (11%, while STS to albumin and α-globulins (62.6% and 30.7% on the protidogram, respectively. Both in the brachial and in the femoral vein, the average fSTS was always 0. STS binds to albumin (62.6% and α-globulins (30.7%, while POL is bound mainly by the b-globulins (11%. The present paper demonstrates how the vast majority of the sclerosing agent is bound to the blood proteins, suggesting the need to look for possible sclerotherapy complications factors also in the used gas and/or in the subsequent cathabolites release.

  11. Real-time upper-body human pose estimation from depth data using Kalman filter for simulator (United States)

    Lee, D.; Chi, S.; Park, C.; Yoon, H.; Kim, J.; Park, C. H.


    Recently, many studies show that an indoor horse riding exercise has a positive effect on promoting health and diet. However, if a rider has an incorrect posture, it will be the cause of back pain. In spite of this problem, there is only few research on analyzing rider's posture. Therefore, the purpose of this study is to estimate a rider pose from a depth image using the Asus's Xtion sensor in real time. In the experiments, we show the performance of our pose estimation algorithm in order to comparing the results between our joint estimation algorithm and ground truth data.

  12. The current crisis in human resources for health in Africa: the time to adjust our focus is now. (United States)

    Dalton, Simon C


    The challenges as we strive towards universal health coverage are many, but the need for an improved health workforce is chief among them. Unfortunately the global deficit in skilled professionals continues to increase. Nevertheless, there are potential solutions, and success stories are well documented when the approach is on system building and sustainability. As we approach 2015 and the Millennium Development Goals, we must shift our focus to a more distant time point in order to achieve the dramatic gains in global health that are possible. However, we must understand that there can be no health without a workforce.

  13. Time Management (United States)

    Stoilov, Todor, Ed.


    The time management is worthy goal of many human activities. It concerns variety problems related to goals definition, assessment of available resources, control of management policies, scheduling of decisions. This book is an attempt to illustrate the decision making process in time management for different success stories, which can be used as…

  14. [Relaxation times T1, T2, and T2* of apples, pears, citrus fruits, and potatoes with a comparison to human tissues]. (United States)

    Werz, Karin; Braun, Hans; Vitha, Dominik; Bruno, Graziano; Martirosian, Petros; Steidle, Günter; Schick, Fritz


    The aim of the project was a systematic assessment of relaxation times of different fruits and vegetables and a comparison to values of human tissues. Results provide an improved basis for selection of plant phantoms for development of new MR techniques and sequences. Vessels filled with agar gel are mostly used for this purpose, preparation of which is effortful and time-consuming. In the presented study apples, (malus, 8 species), pears, (pyrus, 2 species), citrus fruits (citrus, 5 species) and uncooked potatoes (solanum tuberosum, 8 species) from the supermarket were examined which are easily available nearly all-the-year. T1, T2 and T2* relaxation times of these nature products were measured on a 1.5 Tesla MR system with adapted examination protocols and mono-exponential fitting, and compared to literature data of human parenchyma tissues, fatty tissue and body fluid (cerebrospinal fluid). Resulting values were as follows: apples: T1: 1486-1874 ms, T2: 163-281 ms, T2*: 2.3-3.2 ms; pears: T1: 1631-1969 ms, T2: 119-133 ms, T2* : 10.1-10.6 ms, citrus fruits (pulp) T1: 2055-2632 ms, T2: 497-998 ms, T2* : 151-182 ms; citrus fruits (skin) T1: 561-1669 ms, T2: 93-119 ms; potatoes: T1: 1011-1459 ms, T2: 166 - 210 ms, T2* : 20 - 30 ms. All T1-values of the examined objects (except for potatoes and skins of citrus fruits) were longer than T1 values of human tissues. Also T2 values (except for pears and skins of citrus fruits) of the fruits and the potatoes tended to be longer. T2* values of apples, pears and potatoes were shorter than in healthy human tissue. Results show relaxation values of many fruits to be not exactly fitting to human tissue, but with suitable selection of the fruits and optionally with an adaption of measurement parameters one can achieve suitable contrast and signal characteristics for some purposes.

  15. About time

    CERN Document Server

    Frank, Adam


    From Stonehenge to beyond the Big Bang, an exhilarating scientific exploration of how we make time Time is the grandest conception of the universe that we humans have been able to imagine – and its most intimate, the very frame of human life. In About Time, astrophysicist and award-winning writer Adam Frank tells the scientific story of this wonderful and tyrannical invention. A Palaeolithic farmer moved through the sun-fuelled day and star-steered night in a radically different way than the Elizabethan merchants who set their pace to the clocks newly installed in their town squares. Since th

  16. Comparison of real time RT-PCR and flow cytometry methods for evaluation of biological activity of recombinant human erythropoietin

    Directory of Open Access Journals (Sweden)

    Sepehrizadeh Z


    Full Text Available Background: Evaluation of bioactivity of recombinant erythropoietin is essential for pharmaceutical industry, quality control authorities and researchers. The purpose of this study was to compare real time RT-PCR and flow cytometry for the assay of biological activity of recombinant erythropoietin. Methods: Three concentrations of recombinant erythropoietin BRP (80, 40 and 20 IU/ml were injected subcutaneously to mice. After 4 days the blood was collected and used for reticulocyte counts by flow cytometry and also for the RNA extraction. Real time RT-PCR amplification was carried out for β-globin. Results and conclusion: There was a significant correlation between the total RNA amounts (R2= 0.9995, relative quantity of β-globin mRNA (R2= 0.984 and reticulocyte counts (R2= 0.9742 with rhEpo concentrations. Total RNA and quantitative RT-PCR showed significant dose dependent results as well the reticulocyte counts by flow cytometry for the biological activity assay of rhEpo and so these methods could be considered as alternatives for flow cytometry.

  17. Comparison of data transformation procedures to enhance topographical accuracy in time-series analysis of the human EEG. (United States)

    Hauk, O; Keil, A; Elbert, T; Müller, M M


    We describe a methodology to apply current source density (CSD) and minimum norm (MN) estimation as pre-processing tools for time-series analysis of single trial EEG data. The performance of these methods is compared for the case of wavelet time-frequency analysis of simulated gamma-band activity. A reasonable comparison of CSD and MN on the single trial level requires regularization such that the corresponding transformed data sets have similar signal-to-noise ratios (SNRs). For region-of-interest approaches, it should be possible to optimize the SNR for single estimates rather than for the whole distributed solution. An effective implementation of the MN method is described. Simulated data sets were created by modulating the strengths of a radial and a tangential test dipole with wavelets in the frequency range of the gamma band, superimposed with simulated spatially uncorrelated noise. The MN and CSD transformed data sets as well as the average reference (AR) representation were subjected to wavelet frequency-domain analysis, and power spectra were mapped for relevant frequency bands. For both CSD and MN, the influence of noise can be sufficiently suppressed by regularization to yield meaningful information, but only MN represents both radial and tangential dipole sources appropriately as single peaks. Therefore, when relating wavelet power spectrum topographies to their neuronal generators, MN should be preferred.

  18. New potential biomarkers for mesterolone misuse in human urine by liquid chromatography quadrupole time-of-flight mass spectrometry. (United States)

    Lu, Jianghai; Fernández-Álvarez, María; Yang, Sheng; He, Genye; Xu, Youxuan; Aguilera, Rodigo


    In this paper, mesterolone metabolic profiles were investigated carefully. Mesterolone was administered to one healthy male volunteer. Urinary extracts were analyzed by liquid chromatography quadruple time-of-flight mass spectrometry (LC-QTOFMS) for the first time. Liquid-liquid extraction was applied to processing urine samples, and dilute-shoot analyses of intact metabolites were also presented. In LC-QTOFMS analysis, chromatographic peaks for potential metabolites were hunt down by using the theoretical [M-H](-) as target ions in full scan experiment, and their actual deprotonated ions were analyzed in targeted MS/MS mode. Ten metabolites including seven new sulfate and three glucuronide conjugates were found for mesterolone. Because of no useful fragment ion for structural elucidation, gas chromatography-mass spectrometry instrumentation was employed to obtain structural details of the trimethylsilylated phase I metabolite released after solvolysis. Thus, their potential structures were proposed particularly by a combined MS approach. All the metabolites were also evaluated in terms of how long they could be detected, and S1 (1α-methyl-5α-androst-3-one-17β-sulfate) together with S2 (1α-methyl-5α-androst-17-one-3β-sulfate) was detected up to 9 days after oral administration, which could be the new potential biomarkers for mesterolone misuse.

  19. Comparative Study on Real-time PCR and RT-PCR Testing Methods for Detecting human Metapneumo Virus%Real-time PCR与RT-PCR检测儿童人偏肺病毒

    Institute of Scientific and Technical Information of China (English)

    郭鑫; 崔玉霞; 诸葛姝芮; 刘兴梅


    目的:比较荧光定量PCR( real-time PCR)与普通反转录酶-聚合酶链锁反应( RT-PCR)对人偏肺病毒( hMPV)的检测价值。方法:Real-time PCR和RT-PCR同时对500例急性下呼吸道感染( ALRTI)患儿鼻咽部分泌物进行hMPV检测,分析两种方法的特异性和灵敏性。结果:Real-time PCR和RT-PCR的检出率分别为16%及9.8%,RT-PCR与Real-time PCR比较,灵敏度为31.3%(25/80),特异度为94.3%(396/420)。结论:Real-time PCR检测hMPV敏感性高于RT-PCR,是临床检测儿童鼻咽部分泌物hMPV感染的有效的方法。%Objective:To investigate the effect of real-time quantitative PCR and RT-PCR in detec-tion of human metapneumo virus. Methods:Real-time PCR and RT-PCR are adopted to test hMPV on throat exudate of 500 acute lower respiratory tract infection( ALRTI)child patients,analyzing the spe-cificity and sensitivity of both assays. Results:Comparing Real-time PCR and RT-PCR,the detection rates were 16 % to 9. 8%. Comparing Real-time PCR and RT-PCR,the sensitivity and specificity were 31. 3 %(25/80)and 94. 3%(396/420)respectively. Conclusion:The sensitivity of Real-time PCR is significantly higher than RT-PCR in detection of hMPV,which provid an effective method for detection of hMPV.

  20. Diagnosis of human herpes virus 1 and 2 (HHV-1 and HHV-2): use of a synthetic standard curve for absolute quantification by real time polymerase chain reaction. (United States)

    Lima, Lyana Rodrigues Pinto; Silva, Amanda Perse da; Schmidt-Chanasit, Jonas; Paula, Vanessa Salete de


    The use of quantitative real time polymerase chain reaction (qPCR) for herpesvirus detection has improved the sensitivity and specificity of diagnosis, as it is able to detect shedding episodes in the absence of clinical lesions and diagnose clinical specimens that have low viral loads. With an aim to improve the detection and quantification of herpesvirus by qPCR, synthetic standard curves for human herpesvirus 1 and 2 (HHV-1 and HHV-2) targeting regions gD and gG, respectively, were designed and evaluated. The results show that synthetic curves can replace DNA standard curves in diagnostic herpes qPCR.

  1. Diagnosis of human herpes virus 1 and 2 (HHV-1 and HHV-2): use of a synthetic standard curve for absolute quantification by real time polymerase chain reaction (United States)

    Lima, Lyana Rodrigues Pinto; da Silva, Amanda Perse; Schmidt-Chanasit, Jonas; de Paula, Vanessa Salete


    The use of quantitative real time polymerase chain reaction (qPCR) for herpesvirus detection has improved the sensitivity and specificity of diagnosis, as it is able to detect shedding episodes in the absence of clinical lesions and diagnose clinical specimens that have low viral loads. With an aim to improve the detection and quantification of herpesvirus by qPCR, synthetic standard curves for human herpesvirus 1 and 2 (HHV-1 and HHV-2) targeting regions gD and gG, respectively, were designed and evaluated. The results show that synthetic curves can replace DNA standard curves in diagnostic herpes qPCR. PMID:28225902

  2. Time pattern of exercise-induced changes in type I collagen turnover after prolonged endurance exercise in humans

    DEFF Research Database (Denmark)

    Langberg, Henning; Skovgaard, D; Asp, S;


    Type I collagen is known to adapt to physical activity, and biomarkers of collagen turnover indicate that synthesis can be influenced by a single intense exercise bout, but the exact time pattern of these latter changes are largely undescribed. In the present study, 17 healthy young males had...... indicate that type I collagen synthesis is accelerated in response to prolonged strenuous exercise, reaching a peak after 3 days and returning to preexercising levels 5 days after the completion of a marathon run....... their plasma concentrations of the carboxyterminal propeptide of type I procollagen (PICP), a marker of collagen formation, and the immunoactive carboxyterminal cross-linked telopeptide (ICTP), a marker of collagen resorption, measured before and immediately postexercise, as well as 1, 2, 3, 4, 5, and 6 days...

  3. Real-time PCR for detection of Streptococcus suis serotype 2 in cerebrospinal fluid of human patients with meningitis (United States)

    Nga, Tran Vu Thieu; Nghia, Ho Dang Trung; Tu, Le Thi Phuong; Diep, To Song; Mai, Nguyen Thi Hoang; Chau, Tran Thi Hong; Sinh, Dinh Xuan; Phu, Nguyen Hoan; Nga, Tran Thi Thu; Chau, Nguyen Van Vinh; Campbell, James; Hoa, Ngo Thi; Chinh, Nguyen Tran; Hien, Tran Tinh; Farrar, Jeremy; Schultsz, Constance


    Streptococcus suis serotype 2 is an emerging zoonotic pathogen and is the main cause of acute bacterial meningitis in adult patients in Vietnam. We developed an internally controlled real-time PCR for detection of S. suis serotype 2 in cerebrospinal fluid (CSF) samples targeted at the cps2J gene. Sensitivity and specificity in culture-confirmed clinical samples were 100%. The PCR detected S. suis serotype 2 infection in 101 of 238 (42.4%) prospectively collected CSF samples, of which 55 (23%) were culture positive. Culture-negative but PCR-positive CSF samples were significantly associated with the use of antimicrobial agents before admission. S. suis serotype 2 infection was more common than infections with Streptococcus pneumoniae and Neisseria meningitidis combined. Our results strikingly illustrate the additional diagnostic value of PCR in patients who are pretreated with antimicrobial agents and demonstrate the extremely high prevalence of S. suis infections among Vietnamese adult patients with bacterial meningitis. PMID:21767702

  4. Real-time PCR strategy for the identification of Trypanosoma cruzi discrete typing units directly in chronically infected human blood. (United States)

    Muñoz-San Martín, Catalina; Apt, Werner; Zulantay, Inés


    The protozoan Trypanosoma cruzi is the causative agent of Chagas disease, a major public health problem in Latin America. This parasite has a complex population structure comprised by six or seven major evolutionary lineages (discrete typing units or DTUs) TcI-TcVI and TcBat, some of which have apparently resulted from ancient hybridization events. Because of the existence of significant biological differences between these lineages, strain characterization methods have been essential to study T. cruzi in its different vectors and hosts. However, available methods can be laborious and costly, limited in resolution or sensitivity. In this study, a new genotyping strategy by real-time PCR to identify each of the six DTUs in clinical blood samples have been developed and evaluated. Two nuclear (SL-IR and 18S rDNA) and two mitochondrial genes (COII and ND1) were selected to develop original primers. The method was evaluated with eight genomic DNA of T. cruzi populations belonging to the six DTUs, one genomic DNA of Trypanosoma rangeli, and 53 blood samples from individuals with chronic Chagas disease. The assays had an analytical sensitivity of 1-25fg of DNA per reaction tube depending on the DTU analyzed. The selectivity of trials with 20fg/μL of genomic DNA identified each DTU, excluding non-targets DTUs in every test. The method was able to characterize 67.9% of the chronically infected clinical samples with high detection of TcII followed by TcI. With the proposed original genotyping methodology, each DTU was established with high sensitivity after a single real-time PCR assay. This novel protocol reduces carryover contamination, enables detection of each DTU independently and in the future, the quantification of each DTU in clinical blood samples.

  5. Immunohistochemistry and real-time PCR as diagnostic tools for detection of Borrelia burgdorferi sensu lato in ticks collected from humans. (United States)

    Briciu, Violeta T; Sebah, Daniela; Coroiu, Georgiana; Lupşe, Mihaela; Cârstina, Dumitru; Ţăţulescu, Doina F; Mihalca, Andrei D; Gherman, Călin M; Leucuţa, Daniel; Meyer, Fabian; Hizo-Teufel, Cecilia; Fingerle, Volker; Huber, Ingrid


    The objective of this study was to evaluate different methods used for detection of Borrelia burgdorferi sensu lato (s.l.) in ticks: immunohistochemistry followed by focus floating microscopy (FFM) and real-time polymerase chain reaction (real-time PCR) targeting the ospA and hbb genes. Additionally, an optimized ospA real-time PCR assay was developed with an integrated internal amplification control (IAC) for the detection of inhibition in the PCR assay and was validated as an improved screening tool for B. burgdorferi. One hundred and thirty-six ticks collected from humans in a hospital from Cluj-Napoca, Romania, were investigated regarding genus, stage of development and sex, and then tested by all three assays. A poor quality of agreement was found between FFM and each of the two real-time PCR assays, as assessed by concordance analysis (Cohen's kappa), whereas the agreement between the two real-time PCR assays was moderate. The present study argues for a low sensitivity of FFM and underlines that discordant results of different assays used for detection of B. burgdorferi in ticks are frequent.

  6. Investigations of the lysophospholipid composition of human neutrophils under different stimulation conditions by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

    Directory of Open Access Journals (Sweden)



    Full Text Available Matrix-assisted laser desorption / ionization time-of-flight mass spectrometry (MALDI-TOF MS is usually used for the analyses of proteins, carbohydrates and oligonucleotides. In spite of the number of advantages that MALDI-TOF MS exhibits for lipid analysis, this method has not often been applied in this field. In this paper we have extended our previous studies on the suitability of MALDI-TOF MS for the investigation of changes in the content of lipid-derived second messengers in organic extracts of human neutrophils. Qualitative differences in the lysophospholipid composition in organic extracts of the human neutrophils under different stimulation conditions could be easily observed by MALDI-TOF MS. Although there are still some methodological problems to be solved before this method can be routinely applied for the quantification of different lipid classes in complex biological mixtures (such as organic extracts of human neutrophils it is shown here that MALDI-TOF MS possesses the capability to be used as a simple screening method for the investigation of the content of lipid-derived second messengers and of signalling pathways in cells.

  7. Analyzing time-dependent microarray data using independent component analysis derived expression modes from human macrophages infected with F. tularensis holartica. (United States)

    Lutter, D; Langmann, Th; Ugocsai, P; Moehle, C; Seibold, E; Splettstoesser, W D; Gruber, P; Lang, E W; Schmitz, G


    The analysis of large-scale gene expression profiles is still a demanding and extensive task. Modern machine learning and data mining techniques developed in linear algebra, like Independent Component Analysis (ICA), become increasingly popular as appropriate tools for analyzing microarray data. We applied ICA to analyze kinetic gene expression profiles of human monocyte derived macrophages (MDM) from three different donors infected with Francisella tularensis holartica and compared them to more classical methods like hierarchical clustering. Results were compared using a pathway analysis tool, based on the Gene Ontology and the MeSH database. We could show that both methods lead to time-dependent gene regulatory patterns which fit well to known TNFalpha induced immune responses. In comparison, the nonexclusive attribute of ICA results in a more detailed view and a higher resolution in time dependent behavior of the immune response genes. Additionally, we identified NFkappaB as one of the main regulatory genes during response to F. tularensis infection.

  8. Real-time swept source optical coherence tomography imaging of the human airway using a microelectromechanical system endoscope and digital signal processor. (United States)

    Su, Jianping; Zhang, Jun; Yu, Lingfeng; G Colt, Henri; Brenner, Matthew; Chen, Zhongping


    A fast-scan-rate swept laser for optical coherence tomography (OCT) is suitable to record and analyze a 3-D image volume. However, the whole OCT system speed is limited by data streaming, processing, and storage. In this case, postprocessing is a common technique. Endoscopic clinical applications prefer onsite diagnosis, which requires a real-time technique. Parallel digital signal processors were applied to stream and process data directly from a data digitizer. A real-time system with 20-kHz axial line speed, which was limited only by our swept laser scan rate, was implemented. To couple with the system speed, an endoscope based on an improved 3-D microelectromechanical motor (diameter 1.5 mm, length 9.4 mm) was developed. In vivo 3-D imaging of the human airway was demonstrated.

  9. Effect of 50% human serum on the killing activity of micafungin against eight Candida species using time-kill methodology. (United States)

    Földi, Richárd; Szilágyi, Judit; Kardos, Gábor; Berényi, Réka; Kovács, Renátó; Majoros, László


    Micafungin activity was determined against 24 wild-type clinical isolates and 5 American Type Culture Collection strains belonging to 8 Candida species in RPMI-1640 with and without 50% serum using broth microdilution and time-kill methodology. MIC values increased from 4- to 128-folds in 50% serum for all Candida species. Micafungin was not fungicidal against C. albicans, C. tropicalis, and against 2 of 3 C. metapsilosis at ≥0.25, 1, and 1 μg/mL, respectively, after 48 h with 50% serum, showing good fungistatic activity. Fungicidal activity at ≥2, 4, and 32 μg/mL was noticed against C. glabrata, C. inconspicua, and C. krusei isolates, respectively. Micafungin at 8-32 μg/mL showed fungistatic activity against C. parapsilosis and C. orthopsilosis. Serum decreased the in vitro activity of micafungin. With serum binding of echinocandins taken into account, safely fungistatic or fungicidal concentrations seem to require elevated doses against some Candida species, including C. parapsilosis, C. orthopsilosis, and C. krusei.

  10. The Relationship between Cell Number, Division Behavior and Developmental Potential of Cleavage Stage Human Embryos: A Time-Lapse Study. (United States)

    Kong, Xiangyi; Yang, Shuting; Gong, Fei; Lu, Changfu; Zhang, Shuoping; Lu, Guangxiu; Lin, Ge


    Day 3 cleavage embryo transfer is routine in many assisted reproductive technology centers today. Embryos are usually selected according to cell number, cell symmetry and fragmentation for transfer. Many studies have showed the relationship between cell number and embryo developmental potential. However, there is limited understanding of embryo division behavior and their association with embryo cell number and developmental potential. A retrospective and observational study was conducted to investigate how different division behaviors affect cell number and developmental potential of day 3 embryos by time-lapse imaging. Based on cell number at day 3, the embryos (from 104 IVF/intracytoplasmic sperm injection (ICSI) treatment cycles, n = 799) were classified as follows: less than 5 cells (10C; n = 42). Division behavior, morphokinetic parameters and blastocyst formation rate were analyzed in 5 groups of day 3 embryos with different cell numbers. In 10C embryos increased compared to 7-8C embryos (45.8%, 33.3% vs. 11.1%, respectively). In ≥5C embryos, FR and DC significantly reduced developmental potential, whereas division behaviors. In NB embryos, the blastocyst formation rate increased with cell number from 7.4% (10C). In NB embryos, the cell cycle elongation or shortening was the main cause for abnormally low or high cell number, respectively. After excluding embryos with abnormal division behaviors, the developmental potential, implantation rate and live birth rate of day 3 embryos increased with cell number.

  11. Influence of blood collection systems on the prothrombin time and international sensitivity index determined with human and rabbit thromboplastin reagents. (United States)

    van den Besselaar, Anton M H P; Hoekstra, Martha M C L; Witteveen, Evelina; Didden, Jan H; van der Meer, Felix J M


    Three brands of blood collection tubes were studied for their influence on the prothrombin time (PT) and international sensitivity index (ISI) for 5 commercial thromboplastin reagents. With all reagents, PTs were shorter in Vacutainer (Becton Dickinson Vacutainer Systems, Plymouth, England) samples than in S-Monovette (Sarstedt, Nümbrecht, Germany) or Venosafe (Terumo Europe, Leuven, Belgium) samples. ISI values were higher with Vacutainer samples than with S-Monovette or Venosafe samples. The ISI differences between the tubes were small for Thromborel-S (2.1%; Dade Behring, Marburg, Germany) and Hepato Quick (1.1%; Diagnostica Stago, Asnières, France; Roche Diagnostics Nederland, Almere, the Netherlands) but greater for Neoplastin Plus (5.5%; Diagnostica Stago; Roche Diagnostics Nederland), Simplastin HTF (8.3%; bioMérieux, Durham, NC), and Innovin (8.8%; Dade Behring). The PT and ISI differences between the tubes could be explained mostly by the effect of magnesium ion contamination in the sodium citrate solutions. When PT ratios were transformed into international normalized ratios (INRs) using crossover ISI (ie, samples collected with one type of tube and ISI determined with another collection system for the PT reagent), the differences in mean INRs could be approximately 10%. For ISI calibration of reference thromboplastins, blood collection tubes should be used with minimal divalent metal ion contamination of the citrate solution.

  12. 一种深度图像中人体的实时跟踪算法%A Human Body Real-time Tracking Algorithm in Depth Image

    Institute of Scientific and Technical Information of China (English)

    曹昊; 诸宸辰; 李杨


    This paper proposes an improving Camshift algorithm based on depth data in order to realize real-time human body objects tracking in depth image. This algorithm computes depth probability distribution function of human body objects, combining the morphological characteristics of people. Different weight factors are given to the different part of human on depth probability distribution function. It finds human body objects in a frame after several times of iterations, uses the modified Camshift algorithm. Kalman filter is also applied in this work to predict the position of people in 3D space. Doing experiments on 1 200 frames of depth image, results present that this algorithm are effective to track moving human body on depth image even though the objects are partly covered or the shapes are regular changed. For the common one or two people situation, the tracking accuracy rate is over 95%, which is better than traditional Camshift algorithm.%针对深度图像中的人体目标跟踪问题,提出一种基于深度图像的改进Camshift算法。利用人体目标的深度信息计算概率分布,结合人体形态学特征,对深度的概率分布赋予不同的权重,通过Camshift算法进行迭代,从而寻找目标,使用卡尔曼滤波器在三维空间中对运动人体目标的位置实现预测和更新。采集1200帧图像进行测试,结果表明,该算法能实时准确地跟踪深度图像中的运动人体目标,有效克服遮挡等干扰,单人和双人跟踪准确率均在95%以上,高于传统Camshift算法。

  13. Characterization of human coronavirus etiology in Chinese adults with acute upper respiratory tract infection by real-time RT-PCR assays.

    Directory of Open Access Journals (Sweden)

    Roujian Lu

    Full Text Available BACKGROUND: In addition to SARS associated coronaviruses, 4 non-SARS related human coronaviruses (HCoVs are recognized as common respiratory pathogens. The etiology and clinical impact of HCoVs in Chinese adults with acute upper respiratory tract infection (URTI needs to be characterized systematically by molecular detection with excellent sensitivity. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we detected 4 non-SARS related HCoV species by real-time RT-PCR in 981 nasopharyngeal swabs collected from March 2009 to February 2011. All specimens were also tested for the presence of other common respiratory viruses and newly identified viruses, human metapneumovirus (hMPV and human bocavirus (HBoV. 157 of the 981 (16.0% nasopharyngeal swabs were positive for HCoVs. The species detected were 229E (96 cases, 9.8%, OC43 (42 cases, 4.3%, HKU1 (16 cases, 1.6% and NL63 (11 cases, 1.1%. HCoV-229E was circulated in 21 of the 24 months of surveillance. The detection rates for both OC43 and NL63 were showed significantly year-to-year variation between 2009/10 and 2010/11, respectively (P<0.001 and P = 0.003, and there was a higher detection frequency of HKU1 in patients aged over 60 years (P = 0.03. 48 of 157(30.57% HCoV positive patients were co-infected. Undifferentiated human rhinoviruses and influenza (Flu A were the most common viruses detected (more than 35% in HCoV co-infections. Respiratory syncytial virus (RSV, human parainfluenza virus (PIV and HBoV were detected in very low rate (less than 1% among adult patients with URTI. CONCLUSIONS/SIGNIFICANCE: All 4 non-SARS-associated HCoVs were more frequently detected by real-time RT-PCR assay in adults with URTI in Beijing and HCoV-229E led to the most prevalent infection. Our study also suggested that all non-SARS-associated HCoVs contribute significantly to URTI in adult patients in China.

  14. Computerized video time-lapse (CVTL) analysis of cell death kinetics in human bladder carcinoma cells (EJ30) X-irradiated in different phases of the cell cycle. (United States)

    Chu, Kenneth; Leonhardt, Edith A; Trinh, Maxine; Prieur-Carrillo, Geraldine; Lindqvist, Johan; Albright, Norman; Ling, C Clifton; Dewey, William C


    The purpose of this study was to quantify the modes and kinetics of cell death for EJ30 human bladder carcinoma cells irradiated in different phases of the cell cycle. Asynchronous human bladder carcinoma cells were observed in multiple fields by computerized video time-lapse (CVTL) microscopy for one to two cell divisions before irradiation (6 Gy) and for 6-11 days afterward. By analyzing time-lapse movies collected from these fields, pedigrees were constructed showing the behaviors of 231 cells irradiated in different phases of the cell cycle (i.e. at different times after mitosis). A total of 219 irradiated cells were determined to be non-colony-forming over the time spans of the experiments. In these nonclonogenic pedigrees, cells died primarily by necrosis either without entering mitosis or over 1 to 10 postirradiation generations. A total of 105 giant cells developed from the irradiated cells or their progeny, and 30% (31/105) divided successfully. Most nonclonogenic cells irradiated in mid-S phase (9-12 h after mitosis) died by the second generation, while those irradiated either before or after this short period in mid-S phase had cell deaths occurring over one to nine postirradiation generations. The nonclonogenic cells irradiated in mid-S phase also experienced the longest average delay before their first division. Clonogenic cells (11/12 cells) divided sooner after irradiation than the average nonclonogenic cells derived from the same phase of the cell cycle. The early death and long division delay observed for nonclonogenic cells irradiated in mid-S phase could possibly result from an increase in damage induced during the transition from the replication of euchromatin to the replication of heterochromatin.

  15. Glyphosate in German adults - Time trend (2001 to 2015) of human exposure to a widely used herbicide. (United States)

    Conrad, André; Schröter-Kermani, Christa; Hoppe, Hans-Wolfgang; Rüther, Maria; Pieper, Silvia; Kolossa-Gehring, Marike


    The broadband herbicide glyphosate (N-[phosphonomethyl]-glycine) and its main metabolite aminomethylphosphonic acid (AMPA) were analyzed by GC-MS-MS in 24h-urine samples cryo-archived by the German Environmental Specimen Bank (ESB). Samples collected in 2001, 2003, 2005, 2007, 2009, 2011, 2012, 2013, 2014, and 2015 were chosen for this retrospective analysis. All urine samples had been provided by 20 to 29 years old individuals living in Greifswald, a city in north-eastern Germany. Out of the 399 analyzed urine samples, 127 (=31.8%) contained glyphosate concentrations at or above the limit of quantification (LOQ) of 0.1μg/L. For AMPA this was the case for 160 (=40.1%) samples. The fraction of glyphosate levels at or above LOQ peaked in 2012 (57.5%) and 2013 (56.4%) after having discontinuously increased from 10.0% in 2001. Quantification rates were lower again in 2014 and 2015 with 32.5% and 40.0%, respectively. The overall trend for quantifiable AMPA levels was similar. Glyphosate and AMPA concentrations in urine were statistically significantly correlated (spearman rank correlation coefficient=0.506, p≤0.001). Urinary glyphosate and AMPA levels tended to be higher in males. The possible reduction in exposure since 2013 indicated by ESB data may be due to changes in glyphosate application in agricultural practice. The ESB will continue monitoring internal exposures to glyphosate and AMPA for following up the time trend, elucidating inter-individual differences, and contributing to the ongoing debate on the further regulation of glyphosate-based pesticides.

  16. [The validation of kit of reagents for quantitative detection of DNA of human cytomegalovirus in biological material using polymerase chain reaction technique in real time operation mode]. (United States)

    Sil'veĭstrova, O Iu; Domonova, É A; Shipulina, O Iu


    The validation of kit of reagents destined to detection and quantitative evaluation of DNA of human cytomegalovirus in biological material using polymerase chain reaction technique in real time operation mode was implemented. The comparison was made against international WHO standard--The first WHO international standard for human cytomegalovirus to implement measures the kit of reagents "AmpliSens CMV-screen/monitor-FL" and standard sample of enterprise DNA HCMV (The central research institute of epidemiology of Rospotrebnadzor) was applied. The fivefold dilution of international WHO standard and standard sample of enterprise were carried out in concentrations of DNA HCMV from 106 to 102. The arrangement of polymerase chain reaction and analysis of results were implemented using programed amplifier with system of detection of fluorescent signal in real-time mode "Rotor-Gene Q" ("Qiagen", Germany). In the total of three series of experiments, all stages of polymerase chain reaction study included, the coefficient of translation of quantitative evaluation of DNA HCMV from copy/ml to ME/ml equal to 0.6 was introduced for this kit of reagents.

  17. Stratification of the phase clouds and statistical effects of the non-Markovity in chaotic time series of human gait for healthy people and Parkinson patients

    CERN Document Server

    Yulmetyev, R M; Emelyanova, N; Gafarov, F; Hänggi, P; Yulmetyev, Renat; Demin, Sergey; Emelyanova, Natalya; Gafarov, Fail; Hanggi, Peter


    In this work we develop a new method of diagnosing the nervous system diseases and a new approach in studying human gait dynamics with the help of the theory of discrete non-Markov random processes. The stratification of the phase clouds and the statistical non-Markov effects in the time series of the dynamics of human gait are considered. We carried out the comparative analysis of the data of four age groups of healthy people: children (from 3 to 10 year olds), teenagers (from 11 to 14 year oulds), young people (from 21 up to 29 year oulds), elderly persons (from 71 to 77 year olds) and Parkinson patients. The full data set are analyzed with the help of the phase portraits of the four dynamic variables, the power spectra of the initial time correlation function and the memory functions of junior orders, the three first points in the spectra of the statistical non-Markov parameter. The received results allow to define the predisposition of the probationers to deflections in the central nervous system caused b...

  18. Stratification of the phase clouds and statistical effects of the non-Markovity in chaotic time series of human gait for healthy people and Parkinson patients (United States)

    Yulmetyev, Renat; Demin, Sergey; Emelyanova, Natalya; Gafarov, Fail; Hänggi, Peter


    In this work we develop a new method of diagnosing the nervous system diseases and a new approach in studying human gait dynamics with the help of the theory of discrete non-Markov random processes (Phys. Rev. E 62 (5) (2000) 6178, Phys. Rev. E 64 (2001) 066132, Phys. Rev. E 65 (2002) 046107, Physica A 303 (2002) 427). The stratification of the phase clouds and the statistical non-Markov effects in the time series of the dynamics of human gait are considered. We carried out the comparative analysis of the data of four age groups of healthy people: children (from 3 to 10 year olds), teenagers (from 11 to 14 year olds), young people (from 21 up to 29 year olds), elderly persons (from 71 to 77 year olds) and Parkinson patients. The full data set are analyzed with the help of the phase portraits of the four dynamic variables, the power spectra of the initial time correlation function and the memory functions of junior orders, the three first points in the spectra of the statistical non-Markov parameter. The received results allow to define the predisposition of the probationers to deflections in the central nervous system caused by Parkinson's disease. We have found out distinct differences between the five submitted groups. On this basis we offer a new method of diagnostics and forecasting Parkinson's disease.


    Institute of Scientific and Technical Information of China (English)

    PENG Mian; YU Xue-tao; CHEN Shu; CAI Xiao-hua; PENG Yi-chao; PENG Xiao-rong


    Objective To investigate the direct effect of leptin on osteoblast-like cell line MG63. Methods Human osteoblast-like cell line MG63 was incubated with leptin of different doses for 24, 48 and 72 h, respectively.The proliferation of MG63 was determined by methylene blue assay. Alpha1 (Ⅰ) collagen gene expression in MG63was determined by real time flourescence quantitive PCR (FQ-PCR), both with 17β-E2 as positive control.Results Leptin accelerated the proliferation and differentiation of MG63 in dose and time-dependent manners,with the best effect at 10-7 mol/L at 72 h. Compared with 17β-E2 , leptin showed a weaker promoting effect at all of the three time point: 24, 48 and 72 h. While the effects of the two hormones have an approaching trend the time prolonged. Conclusion Leptin has the effects of accelerating the proliferation and differentiation of MG63 cells in vitro, which is more enduring and later than that of 17β-E2.

  20. Human epidermal membrane constant conductance iontophoresis: alternating current to obtain reproducible enhanced permeation and reduced lag times of a nonionic polar permeant. (United States)

    Song, Yang; Li, S Kevin; Peck, Kendall D; Zhu, Honggang; Ghanem, Abdel-Halim; Higuchi, William I


    An experimental protocol, using an initial 1 min direct current (DC) applied potential of 4 V followed by alternating current (AC), was established to: (a) increase conductance and permeability and decrease lag time for human epidermal membrane (HEM) relative to unaltered HEM and; (b) maintain constant conductance and permeability during flux studies. The protocol allowed specific permeation parameters of the membrane to be characterized under electrically enhanced, constant flux conditions. The permeability, lag time, and effective membrane thickness were determined using a nonionic polar permeant, urea, while the enhanced conductance was maintained at a constant level with AC. A tortuous pore pathway model was employed to analyze the data. The AC protocol increased membrane permeability, and decreased lag time and effective membrane thickness relative to similar parameters obtained in previous studies from unaltered HEM. Lag times ranged from 32.0 to 105.5 min, and permeability coefficients calculated from steady state fluxes ranged from 1.68 to 6.03x10(-7) cm/s for HEM samples with electrical resistance values during transport of 2.3-8.0 kOmega x cm2. Effective membrane thicknesses were calculated to range from 0.34 to 0.61 cm during AC iontophoresis. Significant additional results were obtained when the protocol was applied for two consecutive runs using the same HEM sample, with time for the HEM sample to recover between runs. During the second run, the applied potential was adjusted to reproduce the conductance obtained on the first run. Under these conditions, the consecutive runs yielded essentially the same lag time, permeability and effective membrane thickness values. These results suggest that constant fluxes can be achieved by keeping HEM electrical conductance constant during AC iontophoresis.


    Institute of Scientific and Technical Information of China (English)


    Objective: Even though radiotherapy plays a major role in the local treatment of non-small cell lung cancer (NSCLC), little is known about the molecular effects of irradiation in this tumor. In the present study, we examined two NSCLC cell lines for their endogenous production of TNF-α after irradiation. To investigate the radiation-induced TNF-α production in NSCLC cell lines. Methods: Two human NSCLC cell lines (A549: squamous; NCI-H596: adenosquamous) were investigated for their TNF-α mRNA (real-time RT-PCR) after exposure to different irradiation doses (2, 5, 10, 20, 30, 40 Gy) and time intervals (1, 3, 6, 12, 24, 48 or 72 h). The TNF-α mRNA expression was quantified by real-time RT-PCR. The clonogenic survival was evaluated after irradiation with 2, 4, 6 and 8 Gy. Results: Non-irradiated NSCLC cells exhibited no or very low TNF-α expression. For the NCI-H596 cell line, TNF-α expression was significantly elevated 1~12 h (maximum 6h: 568fold increase relative to unirradiated cells) in a time-dependent manner. The radiation-induced increase could be observed after irradiation with 2 Gy reaching maximal at 40 Gy, with 83 times higher than normal controls. The clonogenic survival of these cell lines was nearly identical. Conclusion: NCI-H596 cells produce significant quantities of TNF-α following irradiation in a time- and dose-dependent manner. The pro-inflammatory cytokine TNF-α is a key mediator for the pathogenesis of radiation pneumonitis. Radiation-induced endogenous TNF-α expression in NSCLC cells may affect the normal lung adjacent to the tumor and may be associated with an adverse clinical outcome of the patient.

  2. Studies on time of death estimation in the early post mortem period -- application of a method based on eyeball temperature measurement to human bodies. (United States)

    Kaliszan, Michał


    This paper presents a verification of the thermodynamic model allowing an estimation of the time of death (TOD) by calculating the post mortem interval (PMI) based on a single eyeball temperature measurement at the death scene. The study was performed on 30 cases with known PMI, ranging from 1h 35min to 5h 15min, using pin probes connected to a high precision electronic thermometer (Dostmann-electronic). The measured eye temperatures ranged from 20.2 to 33.1°C. Rectal temperature was measured at the same time and ranged from 32.8 to 37.4°C. Ambient temperatures which ranged from -1 to 24°C, environmental conditions (still air to light wind) and the amount of hair on the head were also recorded every time. PMI was calculated using a formula based on Newton's law of cooling, previously derived and successfully tested in comprehensive studies on pigs and a few human cases. Thanks to both the significantly faster post mortem decrease of eye temperature and a residual or nonexistent plateau effect in the eye, as well as practically no influence of body mass, TOD in the human death cases could be estimated with good accuracy. The highest TOD estimation error during the post mortem intervals up to around 5h was 1h 16min, 1h 14min and 1h 03min, respectively in three cases among 30, while for the remaining 27 cases it was not more than 47min. The mean error for all 30 cases was ±31min. All that indicates that the proposed method is of quite good precision in the early post mortem period, with an accuracy of ±1h for a 95% confidence interval. On the basis of the presented method, TOD can be also calculated at the death scene with the use of a proposed portable electronic device (TOD-meter).

  3. Network Dynamics with BrainX3: A Large-Scale Simulation of the Human Brain Network with Real-Time Interaction

    Directory of Open Access Journals (Sweden)

    Xerxes D. Arsiwalla


    Full Text Available BrainX3 is a large-scale simulation of human brain activity with real-time interaction, rendered in 3D in a virtual reality environment, which combines computational power with human intuition for the exploration and analysis of complex dynamical networks. We ground this simulation on structural connectivity obtained from diffusion spectrum imaging data and model it on neuronal population dynamics. Users can interact with BrainX3 in real-time by perturbing brain regions with transient stimulations to observe reverberating network activity, simulate lesion dynamics or implement network analysis functions from a library of graph theoretic measures. BrainX3 can thus be used as a novel immersive platform for real-time exploration and analysis of dynamical activity patterns in brain networks, both at rest or in a task-related state, for discovery of signaling pathways associated to brain function and/or dysfunction and as a tool for virtual neurosurgery. Our results demonstrate these functionalities and shed insight on the dynamics of the resting-state attractor. Specifically, we found that a noisy network seems to favor a low firing attractor state. We also found that the dynamics of a noisy network is less resilient to lesions. Our simulations on TMS perturbations show that even though TMS inhibits most of the network, it also sparsely excites a few regions. This is presumably, due to anti-correlations in the dynamics and suggests that even a lesioned network can show sparsely distributed increased activity compared to healthy resting-state, over specific brain areas.

  4. CyProQuant-PCR: a real time RT-PCR technique for profiling human cytokines, based on external RNA standards, readily automatable for clinical use

    Directory of Open Access Journals (Sweden)

    Mercereau-Puijalon Odile


    Full Text Available Abstract Background Real-time PCR is becoming a common tool for detecting and quantifying expression profiling of selected genes. Cytokines mRNA quantification is widely used in immunological research to dissect the early steps of immune responses or pathophysiological pathways. It is also growing to be of clinical relevancy to immuno-monitoring and evaluation of the disease status of patients. The techniques currently used for "absolute quantification" of cytokine mRNA are based on a DNA standard curve and do not take into account the critical impact of RT efficiency. Results To overcome this pitfall, we designed a strategy using external RNA as standard in the RT-PCR. Use of synthetic RNA standards, by comparison with the corresponding DNA standard, showed significant variations in the yield of retro-transcription depending the target amplified and the experiment. We then developed primers to be used under one single experimental condition for the specific amplification of human IL-1β, IL-4, IL-10, IL-12p40, IL-13, IL-15, IL-18, IFN-γ, MIF, TGF-β1 and TNF-α mRNA. We showed that the beta-2 microglobulin (β2-MG gene was suitable for data normalisation since the level of β2-MG transcripts in naïve PBMC varied less than 5 times between individuals and was not affected by LPS or PHA stimulation. The technique, we named CyProQuant-PCR (Cytokine Profiling Quantitative PCR was validated using a kinetic measurement of cytokine transcripts under in vitro stimulation of human PBMC by lipopolysaccharide (LPS or Staphylococcus aureus strain Cowan (SAC. Results obtained show that CyProQuant-PCR is powerful enough to precociously detect slight cytokine induction. Finally, having demonstrated the reproducibility of the method, it was applied to malaria patients and asymptomatic controls for the quantification of TGF-β1 transcripts and showed an increased capacity of cells from malaria patients to accumulate TGF-β1 mRNA in response to LPS. Conclusion

  5. Time, Concentration, and pH-Dependent Transport and Uptake of Anthocyanins in a Human Gastric Epithelial (NCI-N87) Cell Line (United States)

    Atnip, Allison A.; Sigurdson, Gregory T.; Bomser, Joshua; Giusti, M. Mónica


    Anthocyanins are the largest class of water soluble plant pigments and a common part of the human diet. They may have many potential health benefits, including antioxidant, anti-inflammatory, anti-cancer, and cardioprotective activities. However, anthocyanin metabolism is not well understood. Studies suggest that anthocyanins absorption may occur in the stomach, in which the acidic pH favors anthocyanin stability. A gastric epithelial cell line (NCI-N87) has been used to study the behavior of anthocyanins at a pH range of 3.0–7.4. This work examines the effects of time (0–3 h), concentration (50–1500 µM), and pH (3.0, 5.0, 7.4) on the transport and uptake of anthocyanins using NCI-N87 cells. Anthocyanins were transported from the apical to basolateral side of NCI-N87 cells in time and dose dependent manners. Over the treatment time of 3 h the rate of transport increased, especially with higher anthocyanin concentrations. The non-linear rate of transport may suggest an active mechanism for the transport of anthocyanins across the NCI-N87 monolayer. At apical pH 3.0, higher anthocyanin transport was observed compared to pH 5.0 and 7.4. Reduced transport of anthocyanins was found to occur at apical pH 5.0. PMID:28218720

  6. Time, Concentration, and pH-Dependent Transport and Uptake of Anthocyanins in a Human Gastric Epithelial (NCI-N87 Cell Line

    Directory of Open Access Journals (Sweden)

    Allison A. Atnip


    Full Text Available Anthocyanins are the largest class of water soluble plant pigments and a common part of the human diet. They may have many potential health benefits, including antioxidant, anti-inflammatory, anti-cancer, and cardioprotective activities. However, anthocyanin metabolism is not well understood. Studies suggest that anthocyanins absorption may occur in the stomach, in which the acidic pH favors anthocyanin stability. A gastric epithelial cell line (NCI-N87 has been used to study the behavior of anthocyanins at a pH range of 3.0–7.4. This work examines the effects of time (0–3 h, concentration (50–1500 µM, and pH (3.0, 5.0, 7.4 on the transport and uptake of anthocyanins using NCI-N87 cells. Anthocyanins were transported from the apical to basolateral side of NCI-N87 cells in time and dose dependent manners. Over the treatment time of 3 h the rate of transport increased, especially with higher anthocyanin concentrations. The non-linear rate of transport may suggest an active mechanism for the transport of anthocyanins across the NCI-N87 monolayer. At apical pH 3.0, higher anthocyanin transport was observed compared to pH 5.0 and 7.4. Reduced transport of anthocyanins was found to occur at apical pH 5.0.

  7. Heading date 1 (Hd1), an ortholog of Arabidopsis CONSTANS, is a possible target of human selection during domestication to diversify flowering times of cultivated rice. (United States)

    Takahashi, Yasuyuki; Shimamoto, Ko


    During the domestication of rice (Oryza sativa L.), diversification of flowering time was important in expanding the areas of cultivation. Rice is a facultative short day (SD) plant and requires certain periods of dark to induce flowering. Heading date 1 (Hd1), a regulator of the florigen gene Hd3a, is one of the main factors used to generate diversity in flowering. Loss-of-function alleles of Hd1 are common in cultivated rice and cause the diversity of flowering time. However, it is unclear how these functional nucleotide polymorphisms of Hd1 accumulated in the course of evolution. Nucleotide polymorphisms within Hd1 and Hd3a were analyzed in 38 accessions of ancestral wild rice Oryza rufipogon and compared with those of cultivated rice. In contrast to cultivated rice, no nucleotide changes affecting Hd1 function were found in 38 accessions of wild rice ancestors. No functional changes were found in Hd3a in either cultivated or ancestral rice. A phylogenetic analysis indicated that evolution of the Hd1 alleles may have occurred independently in cultivars descended from various accessions of ancestral rice. The non-functional Hd1 alleles found in cultivated rice may be selected during domestication, because they were not found or very rare in wild ancestral rice. In contrast with Hd3a, which has been highly conserved, Hd1 may have undergone human selection to diversify the flowering times of rice during domestication or the early stage of the cultivation period.

  8. Acute Infections, Cost per Infection and Turnaround Time in Three United States Hospital Laboratories Using Fourth-Generation Antigen-Antibody Human Immunodeficiency Virus Immunoassays. (United States)

    Wesolowski, Laura G; Nasrullah, Muazzam; Coombs, Robert W; Rosenberg, Eric; Ethridge, Steven F; Hutchinson, Angela B; Dragavon, Joan; Rychert, Jennifer; Nolte, Frederick S; Madory, James E; Werner, Barbara G


    Background.  To improve clinical and public health outcomes through early human immunodeficiency virus (HIV) detection, fourth-generation antigen/antibody immunoassay (4IA) and supplemental testing results must be returned rapidly. Methods.  We examined HIV testing data at Harborview Medical Center (HMC), Massachusetts General Hospital (MGH), and the Medical University of South Carolina (MUSC), which used 4IA and supplemental antibody and nucleic acid tests (NATs). At MGH and MUSC, HIV-1 Western blot (WB) and HIV-2 testing were conducted at a reference laboratory. We compared time from specimen collection to laboratory result for established (positive WB) and acute infections (reactive 4IA, negative/indeterminate WB, detectable NAT), and we calculated testing cost per positive-test result. Results.  From 3731 (MUSC) to 19 774 (MGH) tests were conducted; 0.01% (MGH) to 0.05% (HMC) were acute infections. Each laboratory had reactive 4IA, WB-negative, or indeterminate specimens without NAT (ie, potential acute infections). Time to result was 1.5 (HMC) to 5.2 days (MGH) for acute and 1.0 (HMC) to 5.2 days (MGH) for established infections. Costs were $1054 (MGH) to $1521 (MUSC). Conclusions.  Conducting supplemental testing in-house lowered turnaround times, which may be further reduced with rapid HIV-1/HIV-2 differentiation tests. Hospitals may benefit from quantitative NATs not requiring physician orders, so all potential acute infections receive NAT.

  9. Quantification of human telomerase reverse transcriptase mRNA in testicular germ cell tumors by quantitative fluorescence real-time RT-PCR. (United States)

    Schrader, Mark; Burger, Angelika M; Müller, Markus; Krause, Hans; Straub, Bernd; Smith, Gilian L; Newlands, Eward S; Miller, Kurt


    Telomerase is a ribonucleoprotein enzyme which is endogenously expressed in germ, stem and tumor cells, but absent in benign somatic cells. The two major telomerase components are human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT). It has been shown that hTERT is rate-limiting for telomerase activity and that it plays a central role in human carcinogenesis. Here, we investigated the potential of hTERT and hTR gene expression as diagnostic markers in testicular germ cell tumors (TGCT). hTERT mRNA and hTR expression were quantified in 55 testicular germ cell tumors comprising 36 primary and 19 germ cell tumors from retroperitonal sides by fluorescence real-time RT-PCR using the LightCycler technology. Porphobilinogen deaminase (PBGD) was used as housekeeping gene and to enable relative quantification. For comparison to TGCTs, 38 benign testicular biopsies from patients with fertility disorders were assayed. hTERT expression was detected in all examined undifferentiated TGCTs and in the benign testicular tissue specimens with germ cell content (N(hTERT) 38-127). In contrast, mature teratomas from primary and post-chemotherapy masses, which are characterized by well-differentiated tissue components showed a nearly complete downregulation of hTERT expression (N(hTERT) 2-4, pmRNA is expressed in all undifferentiated TGCTs but repressed in mature teratomas. This suggests an inverse correlation between the differentiation status of germ cell tumors and hTERT expression. Thus, detection of hTERT expression in tumors histopathologically classified as mature teratomas enables a molecular-diagnostic confirmation and might aid decision making for treatment of patients presenting with this tumor subtype.

  10. Hyperspectral Imaging Using Intracellular Spies: Quantitative Real-Time Measurement of Intracellular Parameters In Vivo during Interaction of the Pathogenic Fungus Aspergillus fumigatus with Human Monocytes (United States)

    Mohebbi, Sara; Erfurth, Florian; Hennersdorf, Philipp; Brakhage, Axel A.; Saluz, Hans Peter


    Hyperspectral imaging (HSI) is a technique based on the combination of classical spectroscopy and conventional digital image processing. It is also well suited for the biological assays and quantitative real-time analysis since it provides spectral and spatial data of samples. The method grants detailed information about a sample by recording the entire spectrum in each pixel of the whole image. We applied HSI to quantify the constituent pH variation in a single infected apoptotic monocyte as a model system. Previously, we showed that the human-pathogenic fungus Aspergillus fumigatus conidia interfere with the acidification of phagolysosomes. Here, we extended this finding to monocytes and gained a more detailed analysis of this process. Our data indicate that melanised A. fumigatus conidia have the ability to interfere with apoptosis in human monocytes as they enable the apoptotic cell to recover from mitochondrial acidification and to continue with the cell cycle. We also showed that this ability of A. fumigatus is dependent on the presence of melanin, since a non-pigmented mutant did not stop the progression of apoptosis and consequently, the cell did not recover from the acidic pH. By conducting the current research based on the HSI, we could measure the intracellular pH in an apoptotic infected human monocyte and show the pattern of pH variation during 35 h of measurements. As a conclusion, we showed the importance of melanin for determining the fate of intracellular pH in a single apoptotic cell. PMID:27727286

  11. Past Holocene detritism quantification and modeling from lacustrine archives in order to deconvoluate human-climate interactions on natural ecosystem over long time-scale (United States)

    Simonneau, Anaëlle; Chapron, Emmanuel; Di Giovanni, Christian; Galop, Didier; Darboux, Frédéric


    Water budget is one of the main challenges to paleoclimate researchers in relation to present-day global warming and its consequences for human societies. Associated soil degradation and erosion are thereby becoming a major concern in many parts of the world and more particularly in the Alps. Moreover, humans are considered as geomorphologic agents since few thousand years and it is now recognized that such an impact on natural ecosystem profoundly modified soils properties as well as aquatic ecosystems dynamics over long-term periods. The quantification of such inference over long time-scale is therefore essential to establish new policies to reduce mechanic soil erosion, which is one of the dominant processes in Europe, and anticipate the potential consequences of future climate change on hydric erosion. The mechanical erosion of continental surfaces results from climatic forcing, but can be amplified by the anthropogenic one. We therefore suggest that quantifying and modelling soil erosion processes within comparable Holocene lacustrine archives, allows to estimate and date which and when past human activities have had an impact on soil fluxes over the last 10000 years. Based on the present-day geomorphology of the surrounding watershed and the evolution of the vegetation cover during the Holocene, we develop an interdisciplinary approach combining quantitative organic petrography (i.e. optical characterization and quantification of soil particles within lake sediments) with high-resolution seismic profiling, age-depth models on lacustrine sediment cores and soil erosional susceptibility modeling, in order to estimate the annual volume of soil eroded over the last 10000 years, and in fine to quantify the volume of human-induced soil erosion during the Holocene period. This method is applied to close but contrasted mountainous lacustrine environments from the western French Alps: lakes Blanc Huez and Paladru, sensitive to same climatic influences but where past

  12. Quantitative Real-Time Reverse Transcription-PCR Assay for the Expression of Tob mRNA in Human Colorectal Cancer

    Institute of Scientific and Technical Information of China (English)

    Dian-chao WU


    OBJECTIVE Tob is a member of Tob/BTG antiproliferative family. To date, Tob expression in human carcinoma using clinical specimens has not been studied in depth except for lung carcinoma and thyroid carcinoma. This study is the first to investigate the expression levels of Tob gene in human colorectal cancer tissues,and their corresponding para-cancerous tissues. The correlation of expression of the Tob gene with clinicopathological characteristics of colorectal cancer was also analyzed.METHODS Quantitative real time RT-PCR was used to detect the expression of Tob mRNA in 31 colorectal cancers.RESULTS Compared with normal tissues, up-regulation of Tob mRNA was observed in 31 colorectal cancer tissues (P = 0.020).The expression level of Tob at Dukes C + D phase was higher than Dukes A + B phase, and the difference was signifi cant (P < 0.05).However, in this study, it was found that the expression of Tob mRNA was not related with age, gender, and pathological type of colorectal cancer.CONCLUSION The up-regulation of Tob may be closely associated with tumorigenesis of colorectal carcinoma.

  13. Real-time monitoring of geosmin and 2-methylisoborneol, representative odor compounds in water pollution using bioelectronic nose with human-like performance. (United States)

    Son, Manki; Cho, Dong-guk; Lim, Jong Hyun; Park, Juhun; Hong, Seunghun; Ko, Hwi Jin; Park, Tai Hyun


    A bioelectronic nose for the real-time assessment of water quality was constructed with human olfactory receptor (hOR) and single-walled carbon nanotube field-effect transistor (swCNT-FET). Geosmin (GSM) and 2-methylisoborneol (MIB), mainly produced by bacteria, are representative odor compounds and also indicators of contamination in the water supply system. For the screening of hORs which respond to these compounds, we performed CRE-luciferase assays of the two odorants in heterologous cell system. Human OR51S1 for GSM and OR3A4 for MIB were selected, and nanovesicles expressing the hORs on surface were produced from HEK-293 cell. Carbon nanotube field-effect transistor was functionalized with the nanovesicles. The bioelectronic nose was able to selectively detect GSM and MIB at concentrations as low as a 10 ng L(-1). Furthermore, detection of these compounds from the real samples such as tap water, bottled water and river water was available without any pretreatment processes.

  14. Sb(V) and Sb(III) distribution in human erythrocytes: speciation methodology and the influence of temperature, time and anticoagulants. (United States)

    Quiroz, Waldo; Aguilar, Luis; Barría, Macarena; Veneciano, Jocelyn; Martínez, Daniel; Bravo, Manuel; Lobos, María Gabriela; Mercado, Luis


    In this research a new method was developed and optimized for the determination of Sb(V) and Sb(III) in human erythrocytes fractions (plasma and cytoplasm) by high performance liquid chromatography with hydride generation atomic fluorescence spectrometry. The method considers the first step of samples cleaning by protein precipitation by salting out followed by C18 solid phase extraction, EDTA elution, and finally a chromatographic separation by using anion exchange PRPX-100 (100 mm × 4.1mm) and EDTA 20 mmol L(-1) as mobile phase. The method was optimized by experimental design with a recovery of 90% for Sb(V) and 55-75% for Sb(III) approximately. The analytical method was applied to study the distribution of Sb(V) and Sb(III) in human erythrocytes considering temperature and time of incubations and with special attention about the influence of the anticoagulant. Results showed that both Sb(V) and Sb(III) are capable to enter the red blood cell in a proportion of approximately 40-60%. On the other hand, both species are then excreted from the interior of the cell, where the percentage considerably decreased from approximately 60 to less than 30% within the cell. An increase in the culture temperature increases the capacity of Sb(V) and Sb(III) to penetrate the membrane barrier and reach the cytoplasm. In order to preserve the original distribution of Sb in blood, heparin seems to be the best anticoagulant for sample preservation.

  15. Unmanned Aircraft Systems Human-in-the-Loop Controller and Pilot Acceptability Study: Collision Avoidance, Self-Separation, and Alerting Times (CASSAT) (United States)

    Comstock, James R., Jr.; Ghatas, Rania W.; Vincent, Michael J.; Consiglio, Maria C.; Munoz, Cesar; Chamberlain, James P.; Volk, Paul; Arthur, Keith E.


    The Federal Aviation Administration (FAA) has been mandated by the Congressional funding bill of 2012 to open the National Airspace System (NAS) to Unmanned Aircraft Systems (UAS). With the growing use of unmanned systems, NASA has established a multi-center "UAS Integration in the NAS" Project, in collaboration with the FAA and industry, and is guiding its research efforts to look at and examine crucial safety concerns regarding the integration of UAS into the NAS. Key research efforts are addressing requirements for detect-and-avoid (DAA), self-separation (SS), and collision avoidance (CA) technologies. In one of a series of human-in-the-loop experiments, NASA Langley Research Center set up a study known as Collision Avoidance, Self-Separation, and Alerting Times (CASSAT). The first phase assessed active air traffic controller interactions with DAA systems and the second phase examined reactions to the DAA system and displays by UAS Pilots at a simulated ground control station (GCS). Analyses of the test results from Phase I and Phase II are presented in this paper. Results from the CASSAT study and previous human-in-the-loop experiments will play a crucial role in the FAA's establishment of rules, regulations, and procedures to safely, efficiently, and effectively integrate UAS into the NAS.

  16. Biotransformation and metabolic profile of catalpol with human intestinal microflora by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. (United States)

    Tao, Jin-hua; Zhao, Min; Wang, Dong-geng; Yang, Chi; Du, Le-Yue; Qiu, Wen-qian; Jiang, Shu


    Traditional Chinese medicine (TCM) has been used in clinical practice for thousands of years. Catalpol, an iridoid glucoside, abundantly found in the root of the common used herb medicine Rehmannia glutinosa Libosch, has been reported to show various biological effects and pharmacological activities. After oral administration, the active ingredient might have interactions with the intestinal bacteria, which could help unravel how the medicine was processed in vivo. In this work, different pure bacteria from healthy human feces were isolated and used to bioconvert catalpol. Ultra performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) technique combined with Metabolynx(™) software was applied to analyze catalpol metabolites. Compared with blank samples, parent compound (M0) and four metabolites (M1-M4) were detected and tentatively identified based on the characteristics of their protonated ions. The metabolites were likely to be: catalpol aglycone (M1), acetylated catalpol (M2), dimethylated and hydroxylated catalpol aglycone (M3), nitrogen-containing catalpol aglycone (M4). M1 and M4 were generated in the majority of the samples like Bacteroides sp. 45. M3 was obtained in several bacterial samples like Enterococcus sp. 8-2 and M2 was detected only in the sample of Enterococcus sp. 43-1. To our knowledge, the metabolic routes and metabolites of catalpol produced by human intestinal bacteria were all firstly reported.

  17. Chemical and biological differentiation of three human breast cancer cell types using time-of-flight secondary ion mass spectrometry (TOF-SIMS)

    Energy Technology Data Exchange (ETDEWEB)

    Kulp, K S; Berman, E F; Knize, M G; Shattuck, D L; Nelson, E J; Wu, L; Montgomery, J L; Felton, J S; Wu, K J


    We use Time-of-Flight Secondary Ion Mass Spectrometry (TOF-SIMS) to image and classify individual cells based on their characteristic mass spectra. Using statistical data reduction on the large data sets generated during TOF-SIMS analysis, similar biological materials can be differentiated based on a combination of small changes in protein expression, metabolic activity and cell structure. We apply this powerful technique to image and differentiate three carcinoma-derived human breast cancer cell lines (MCF-7, T47D and MDA-MB-231). In homogenized cells, we show the ability to differentiate the cell types as well as cellular compartments (cytosol, nuclear and membrane). These studies illustrate the capacity of TOF-SIMS to characterize individual cells by chemical composition, which could ultimately be applied to detect and identify single aberrant cells within a normal cell population. Ultimately, we anticipate characterizing rare chemical changes that may provide clues to single cell progression within carcinogenic and metastatic pathways.

  18. AMS {sup 14}C chronology of woolly mammoth (Mammuthus primigenius Blum.) remains from the Shestakovo upper paleolithic site, western Siberia: Timing of human-mammoth interaction

    Energy Technology Data Exchange (ETDEWEB)

    Zenin, V.N.; Plicht, J. van der E-mail:; Orlova, L.A.; Kuzmin, Y.V


    We present a series of AMS {sup 14}C dates from the upper paleolithic site of Shestakovo, southwestern Siberia. The {sup 14}C ages range between 21 and 26 ka BP, corresponding to the so-called Sartan Glacial and Karginian Interglacial in Siberia. The majority of dates are from woolly mammoth bones, obtained from several discrete cultural layers, and range from ca. 25,700 to 21,600 BP. One charcoal date, ca. 23,300 BP, pinpoints the timing of at least one phase of site occupation by humans. The overlap of this date with the mammoth bone dates shows clearly that paleolithic people scavenged bones from natural death accumulations near the site. Mammoth hunting was most probably of limited scale. Conventional {sup 14}C dates from Shestakovo are also discussed.

  19. Recovery of distortion product otoacoustic emissions (DPOAE) with high time-resolution from a moderate monaural-exposure to 2-kHz in human subjects

    DEFF Research Database (Denmark)

    de Toro, Miguel Angel Aranda; Ordoñez, Rodrigo Pizarro; Reuter, Karen


    The amplitude of distortion product otoacoustic emissions (DPOAE) decreases temporarily after exposure to a sound of moderate level. These changes show similarities to the changes observed in absolute hearing thresholds after similar sound exposures. This paper presents the experimental protocol...... to study how DPOAEs in human subjects are affected after a monaural exposure of ten minutes to a pure tone of 2 kHz. The experimental protocol allows to measure fine structures of the DPOAE with high time-resolution in a limited frequency range. Thus, the results give a detailed description of the DPOAE...... recovery process and can be used to develop a mathematical model of the recovery. This is the first approximation to study the recovery of more complex exposures. [Work supported by the Danish Research Council for Technology and Production.]...

  20. Triple Quadrupole Versus High Resolution Quadrupole-Time-of-Flight Mass Spectrometry for Quantitative LC-MS/MS Analysis of 25-Hydroxyvitamin D in Human Serum (United States)

    Geib, Timon; Sleno, Lekha; Hall, Rabea A.; Stokes, Caroline S.; Volmer, Dietrich A.


    We describe a systematic comparison of high and low resolution LC-MS/MS assays for quantification of 25-hydroxyvitamin D3 in human serum. Identical sample preparation, chromatography separations, electrospray ionization sources, precursor ion selection, and ion activation were used; the two assays differed only in the implemented final mass analyzer stage; viz. high resolution quadrupole-quadrupole-time-of-flight (QqTOF) versus low resolution triple quadrupole instruments. The results were assessed against measured concentration levels from a routine clinical chemiluminescence immunoassay. Isobaric interferences prevented the simple use of TOF-MS spectra for extraction of accurate masses and necessitated the application of collision-induced dissociation on the QqTOF platform. The two mass spectrometry assays provided very similar analytical figures of merit, reflecting the lack of relevant isobaric interferences in the MS/MS domain, and were successfully applied to determine the levels of 25-hydroxyvitamin D for patients with chronic liver disease.

  1. Standardization of a TaqMan-based real-time PCR for the detection of Mycobacterium tuberculosis-complex in human sputum. (United States)

    Barletta, Francesca; Vandelannoote, Koen; Collantes, Jimena; Evans, Carlton A; Arévalo, Jorge; Rigouts, Leen


    Real-time polymerase chain reaction (qPCR) was optimized for detecting Mycobacterium tuberculosis in sputum. Sputum was collected from patients (N = 112) with suspected pulmonary tuberculosis, tested by smear microscopy, decontaminated, and split into equal aliquots that were cultured in Löwenstein-Jensen medium and tested by qPCR for the small mobile genetic element IS6110. The human ERV3 sequence was used as an internal control. 3 of 112 (3%) qPCR failed. For the remaining 109 samples, qPCR diagnosed tuberculosis in 79 of 84 patients with culture-proven tuberculosis, and sensitivity was greater than microscopy (94% versus 76%, respectively, P tuberculosis mycobacteria. The qPCR cost ∼5US$ per sample and provided same-day results compared with 2-6 weeks for culture.

  2. Interaction of Cm(III) and Am(III) with human serum transferrin studied by time-resolved laser fluorescence and EXAFS spectroscopy. (United States)

    Bauer, Nicole; Fröhlich, Daniel R; Panak, Petra J


    The complexation of Cm(III) with human serum transferrin was investigated in a pH range from 3.5 to 11.0 using time-resolved laser fluorescence spectroscopy (TRLFS). At pH ≥ 7.4 Cm(III) is incorporated at the Fe(III) binding site of transferrin whereas at lower pH a partially bound Cm(III) transferrin species is formed. At physiological temperature (310 K) at pH 7.4, about 70% of the partially bound and 30% of the incorporated Cm(III) transferrin species are present in solution. The Cm(III) results obtained by TRLFS are in very good agreement with Am(III) EXAFS results, confirming the incorporation of Am(III) at the Fe(III) binding site at pH 8.5.

  3. Crank-Nicholson Scheme for the Estimation of Thermal Disturbance on the Peripheral Tissues of Human Body Subjected to Oscillatory Boundary Condition and Time Dependent Heat Source (United States)

    Khanday, M. A.; Hussain, Fida


    To predict the behaviour of thermal physiology of a finite biological tissue in severe cold climatic conditions, a mathematical model has been established based on Pennes' bio-heat transfer equation with oscillatory boundary condition and time dependent heat source term. Crank-Nicholson scheme has been employed to obtain the solution of the boundary value problem to understand the change in stable temperature profiles at the peripheral tissues of human body subjected to forced convection due to cold. Thermal stress at these regions with respect to different input parameters has been computed under extreme environmental conditions using MATLAB Software. The results have shown a relative significance and provide a reasonable outcome in terms of variable metabolic heat generation and oscillatory heat source. The oscillations of the temperature profiles from the mean temperatures were computed in relation with tissue medium and other physiological parameters.

  4. Resveratrol metabolism in a non-human primate, the grey mouse lemur (Microcebus murinus, using ultra-high-performance liquid chromatography-quadrupole time of flight.

    Directory of Open Access Journals (Sweden)

    Marie-Claude Menet

    Full Text Available The grey mouse lemur (Microcebus murinus is a non-human primate used to study the ageing process. Resveratrol is a polyphenol that may increase lifespan by delaying age-associated pathologies. However, no information about resveratrol absorption and metabolism is available for this primate. Resveratrol and its metabolites were qualitatively and quantitatively analyzed in male mouse-lemur plasma (after 200 of oral resveratrol by ultra-high performance liquid chromatography (UHPLC, coupled to a quadrupole-time-of-flight (Q-TOF mass spectrometer used in full-scan mode. Data analyses showed, in MSE mode, an ion common to resveratrol and all its metabolites: m/z 227.072, and an ion common to dihydro-resveratrol metabolites: m/z 229.08. A semi-targeted study enabled us to identify six hydrophilic resveratrol metabolites (one diglucurono-conjugated, two monoglucurono-conjugated, one monosulfo-conjugated and two both sulfo- and glucurono-conjugated derivatives and three hydrophilic metabolites of dihydro-resveratrol (one monoglucurono-conjugated, one monosulfo-conjugated, and one both sulfo- and glucurono-conjugated derivatives. The presence of such metabolites has been already detected in the mouse, rat, pig, and humans. Free resveratrol was measurable for several hours in mouse-lemur plasma, and its two main metabolites were trans-resveratrol-3-O-glucuronide and trans-resveratrol-3-sulfate. Free dihydro-resveratrol was not measurable whatever the time of plasma collection, while its hydrophilic metabolites were present at 24 h after intake. These data will help us interpret the effect of resveratrol in mouse lemurs and provide further information on the inter-species characteristics of resveratrol metabolism.

  5. Simultaneous detection and differentiation of human rhino- and enteroviruses in clinical specimens by real-time PCR with locked nucleic Acid probes. (United States)

    Osterback, Riikka; Tevaluoto, Tuire; Ylinen, Tiina; Peltola, Ville; Susi, Petri; Hyypiä, Timo; Waris, Matti


    Human rhinoviruses (HRVs) and human enteroviruses (HEVs) are significant respiratory pathogens. While HRV infections are restricted to the respiratory tract, HEV infections may spread to secondary target organs. The method of choice for sensitive specific detection of these viruses is reverse transcription (RT)-PCR with primers targeting the conserved 5' noncoding region of the viral RNA. On the other hand, sequence similarities between HRVs and HEVs complicate their differential detection. In this study, we describe the use of locked nucleic acid (LNA) analogues in short double-dye probes which contained only two selectively HRV- or HEV-specific bases. The double-stranded DNA dye BOXTO (4-[6-(benzoxazole-2-yl-(3-methyl-)-2,3-dihydro-(benzo-1,3-thiazole)-2-methylidene)]-1-methyl-quinolinium chloride) was used with the LNA probes in a tricolor real-time PCR assay to allow specific detection of HRVs (probes labeled with 6-carboxyfluorescein [FAM] [green]) and HEVs (Cy5 [red]) with additional melting curve analysis (BOXTO [yellow]). The functionality of the probes was validated in PCR and RT-PCR assays using plasmids containing viral cDNA, quantified viral RNA transcripts, cultivated rhino- and enterovirus prototypes, and clinical specimens. Of 100 HRV and 63 HEV prototypes, the probes correctly identified all HEVs except one that produced only a BOXTO signal. Among 118 clinical specimens with sequencing results, concordant results were obtained for 116 specimens. Two specimens were reactive with both probes, but sequencing yielded only a single virus. Real-time PCR with LNA probes allowed sensitive group-specific identification of HRVs and HEVs and would enable relative copy number determination. The assay is suitable for rapid and accurate differential detection of HRVs and HEVs in a diagnostic laboratory setting.

  6. Cathelicidin LL-37 induces time-resolved release of LTB4 and TXA2 by human macrophages and triggers eicosanoid generation in vivo. (United States)

    Wan, Min; Soehnlein, Oliver; Tang, Xiao; van der Does, Anne M; Smedler, Erik; Uhlén, Per; Lindbom, Lennart; Agerberth, Birgitta; Haeggström, Jesper Z


    In humans, LL-37 and eicosanoids are important mediators of inflammation and immune responses. Here we report that LL-37 promotes leukotriene B4 (LTB4) and thromboxane A2 (TXA2) generation by human monocyte-derived macrophages (HMDMs). LL-37 evokes calcium mobilization apparently via the P2X7 receptor (P2X7R), activation of ERK1/2 and p38 MAPKs, as well as cytosolic phospholipase A2 (cPLA2) and 5-lipoxygenase in HMDMs, leading to an early (1 h) release of LTB4. Similarly, TXA2 production at an early time involved the same signaling sequence along an LL-37-P2X7R-cPLA2-cyclooxygenase-1 (COX-1) axis. However, at later (6-8 h) time points, internalized LL-37 up-regulates COX-2 expression, promoting TXA2 production. Furthermore, intraperitoneal injection of mice with murine cathelicidin-related antimicrobial peptide (mCRAMP) induces significantly higher levels of LTB4 and TXA2 in mouse ascites rich in macrophages. Conversely, cathelicidin-deficient (Cnlp(-/-)) mice produce much less LTB4 and TXB2 in vivo in response to TNF-α compared with control mice. We conclude that LL-37 elicits a biphasic release of eicosanoids in macrophages with early, Ca(2+)-dependent formation of LTB4 and TXA2 followed by a late peak of TXA2, generated via induction of COX-2 by internalized LL-37, thus allowing eicosanoid production in a temporally controlled manner. Moreover, our findings provide evidence that LL-37 is an endogenous regulator of eicosanoid-dependent inflammatory responses in vivo.

  7. Time series analysis performed on nephropathia epidemica in humans of northern Sweden in relation to bank vole population dynamic and the NAO index. (United States)

    Palo, R Thomas


    Time series analysis was performed on two data series of human nephropathia epidemica (NE) infections in northern Sweden between the years 1959-1975 and 1985-2006. The analysis confirms that the bank vole (Myodes glareolus), the main reservoir species, shows regular peaks in population density approximately every fourth year. The periodicity in NE cases of the more recent time period (1985-2006) is 2.8-3.3 years and the older period shows a periodicity ranging 3.4-4.2 years, but this is not significantly different from that expected by vole dynamics. A comparison of North Atlantic Oscillation (NAO) index between the two periods reveals higher mean winter NAO index in the period 1985-2006 than in 1959-1975. No difference was found in frequency of the NAO index between the older period (2.8-3.4 years) compared with the recent period (2.4-2.8 years). Cross-correlation revealed a delayed effect by NAO index on vole abundance but a multivariate model showed that NAO index did not explain the variation in NE cases. Vole index was the only factor that contributed significantly to the variation in numbers of NE cases and that no climate effect could be detected. The climate signal from NAO index does not appear to significantly affect the human NE cases and this suggests that the transmission of disease to man is not particularly sensitive to variations in weather factors. The results favour the hypothesis that higher NAO index will not increase the likelihood of virus transmission from voles to man in northern Sweden under present climatic conditions.

  8. Detection of the pediocin gene pedA in strains from human faeces by real-time PCR and characterization of Pediococcus acidilactici UVA1

    Directory of Open Access Journals (Sweden)

    Cereghetti Tania


    Full Text Available Abstract Background Bacteriocin-producing lactic acid bacteria are commonly used as natural protective cultures. Among them, strains of the genus Pediococcus are particularly interesting for their ability to produce pediocin, a broad spectrum antimicrobial peptide with a strong antagonistic activity against the food-borne pathogen Listeria monocytogenes. Furthermore, there is increasing interest in isolating new bacteriocin-producing strains of human intestinal origin that could be developed for probiotic effects and inhibition of pathogenic bacteria in the gut. In this work, we typed a new strain, co-isolated from baby faeces together with a Bifidobacterium thermophilum strain, and characterized its proteinaceous compound with strong antilisterial activity. Results The newly isolated strain UVA1 was identified as a Pediococcus acidilactici by carbohydrate fermentation profile, growth at 50°C and 16S rDNA sequencing. The partially purified bacteriocin was heat resistant up to 100°C, active over a wide range of pH (2 to 9 and susceptible to proteolytic enzymes. The molecular weight, estimated by SDS-PAGE, was similar to that of pediocin AcH/PA-1 (4.5 kDa. P. acidilactici UVA1 harboured a 9.5-kb plasmid that could be cured easily, which resulted in the loss of the antimicrobial activity. Southern hybridization using the DIG-labelled pedA-probe established that the bacteriocin gene was plasmid-borne as for all pediocin described so far. Nucleotide sequence of the whole operon (3.5 kb showed almost 100 % similarity to the pediocin AcH/PA-1 operon. The mRNA transcript for pedA could be detected in P. acidilactici UVA1 but not in the cured derivative, confirming the expression of the pedA-gene in UVA1. Using a new real-time PCR assay, eleven out of seventeen human faecal samples tested were found to contain pedA-DNA. Conclusion We identified and characterised the first pediocin produced by a human intestinal Pediococcus acidilactici isolate and

  9. 均衡时间压力的人机界面信息编码%Encoding Information of Human-Computer Interface for Equilibrium of Time Pressure

    Institute of Scientific and Technical Information of China (English)

    李晶; 薛澄岐; 王海燕; 周蕾; 牛亚峰


    It is a studying worthy problem in interface design whether the operator can deal with lots of information quickly and correctly under time pressure in human-computer interaction of a complex system.How to use reasonable encoding models to optimize interface design is researched in this paper,according to the influences of time pressures on cognitive behaviors.According to the variablelevel description of the Subject Workload Assessment Technique and vision gaze,time pressures is divided into three levels as high,medium,low,and the presentation time of each level corresponds to 200,600 and 1000 ms.With the help of the experiment,the influences of time pressures on color and shape cognition are analyzed.The results show that the cognition of color was more and quicker than the cognition of shape under time pressures within 1000 ms.Finally,the improved effect of color encoding on rapid recognition of multiple messages was tested and verified,with the emulational interface design of A320 airplane Electronic Centralized Aircraft Monitor system as demonstrative object.%复杂系统人机交互中,在紧迫的时间压力下,操作者能否迅速而准确地对界面承载的大量信息作出反应是界面设计中有待研究的课题.文中针对时间压力对认知行为的影响,研究如何合理地使用编码方式达到界面优化设计.基于主观工作负荷测量法中变量的水平描述和视觉凝视,将时间压力设定为大、适中和小3种水平,对应的呈现时间分别为200 ms,600 ms和1 000 ms;通过实验分析时间压力对颜色和形状编码的认知影响,结果表明,在1000 ms以内的时间压力下,颜色编码比形状编码的认知容量大、认知速度快.最后以A320飞机的电子集成监控系统仿真界面设计为例,验证了颜色编码在多个信息量快速识别中的改进作用.

  10. Simultaneous determination of six toxic alkaloids in human plasma and urine using capillary zone electrophoresis coupled to time-of-flight mass spectrometry. (United States)

    Yu, Zhuhong; Wu, Zhongping; Gong, Feijun; Wong, Rong; Liang, Chen; Zhang, Yurong; Yu, Yunqiu


    A novel capillary zone electrophoresis separation coupled to electro spray ionization time-of-flight mass spectrometry method was developed for the simultaneous analysis of six toxic alkaloids: brucine, strychnine, atropine sulfate, anisodamine hydrobromide, scopolamine hydrobromide and anisodine hydrobromide in human plasma and urine. To obtain optimal sensitivity, a solid-phase extraction method using Oasis MCX cartridges (1 mL, 30 mg; Waters, USA) for the pretreatment of samples was used. All compounds were separated by capillary zone electrophoresis at 25 kV within 12 min in an uncoated fused-silica capillary of 75 μm id × 100 cm and were detected by time-of-flight mass spectrometry. This method was validated with regard to precision, accuracy, sensitivity, linear range, limit of detection (LOD), and limit of quantification (LOQ). In the plasma and urine samples, the linear calibration curves were obtained over the range of 0.50-100 ng/mL. The LOD and LOQ were 0.2-0.5 ng/mL and 0.5-1.0 ng/mL, respectively. The intra- and interday precision was better than 12% and 13%, respectively. Electrophoretic peaks could be identified by mass analysis.

  11. The timing of hepatitis B virus (HBV) immunization relative to human immunodeficiency virus (HIV) diagnosis and the risk of HBV infection following HIV diagnosis. (United States)

    Landrum, Michael L; Hullsiek, Katherine Huppler; Chun, Helen M; Crum-Cianflone, Nancy F; Ganesan, Anuradha; Weintrob, Amy C; Barthel, R Vincent; O'Connell, Robert J; Agan, Brian K


    To assess associations between the timing of hepatitis B virus (HBV) immunization relative to human immunodeficiency virus (HIV) diagnosis and vaccine effectiveness, US Military HIV Natural History Study cohort participants without HBV infection at the time of HIV diagnosis were grouped by vaccination status, retrospectively followed from HIV diagnosis for incident HBV infection, and compared using Cox proportional hazards models. A positive vaccine response was defined as hepatitis B surface antibody level ≥ 10 IU/L. Of 1,877 participants enrolled between 1989 and 2008, 441 (23%) were vaccinated prior to HIV diagnosis. Eighty percent of those who received vaccine doses only before HIV diagnosis had a positive vaccine response, compared with 66% of those who received doses both before and after HIV and 41% of those who received doses only after HIV (P HIV only). Compared with the unvaccinated, persons vaccinated only before HIV had reduced risk of HBV infection after HIV diagnosis (hazard ratio = 0.38, 95% confidence interval: 0.20, 0.75). No reduction in HBV infection risk was observed for other vaccination groups. These data suggest that completion of the vaccine series prior to HIV infection may be the optimal strategy for preventing this significant comorbid infection in HIV-infected persons.

  12. Microelectrical Impedance Spectroscopy for the Differentiation between Normal and Cancerous Human Urothelial Cell Lines: Real-Time Electrical Impedance Measurement at an Optimal Frequency

    Directory of Open Access Journals (Sweden)

    Yangkyu Park


    Full Text Available Purpose. To distinguish between normal (SV-HUC-1 and cancerous (TCCSUP human urothelial cell lines using microelectrical impedance spectroscopy (μEIS. Materials and Methods. Two types of μEIS devices were designed and used in combination to measure the impedance of SV-HUC-1 and TCCSUP cells flowing through the channels of the devices. The first device (μEIS-OF was designed to determine the optimal frequency at which the impedance of two cell lines is most distinguishable. The μEIS-OF trapped the flowing cells and measured their impedance at a frequency ranging from 5 kHz to 1 MHz. The second device (μEIS-RT was designed for real-time impedance measurement of the cells at the optimal frequency. The impedance was measured instantaneously as the cells passed the sensing electrodes of μEIS-RT. Results. The optimal frequency, which maximized the average difference of the amplitude and phase angle between the two cell lines (p<0.001, was determined to be 119 kHz. The real-time impedance of the cell lines was measured at 119 kHz; the two cell lines differed significantly in terms of amplitude and phase angle (p<0.001. Conclusion. The μEIS-RT can discriminate SV-HUC-1 and TCCSUP cells by measuring the impedance at the optimal frequency determined by the μEIS-OF.

  13. 应用real-time PCR法快速定量人类粪便中双歧杆菌的研究%A fast quantification for Bifidobacteria in human feces by real-time PCR

    Institute of Scientific and Technical Information of China (English)

    于静; 文姝; 唐立


    Objective To build a fast and accurate method of quantification for Bifidobacteria in human feces. Method Traditional culture, common PCR, real-time PCR were used. Result (1) The inhibitors in the feces samples were removed when the samples were centrifuged, washed and diluted,so that the Bifidobacteria in the feces samples could be directly quantitated by PCR and real-time PCR. (2) The direct semiquantitation by PCR established in this study showed a satisfactory distinguishability when Bifidobacteria in feces samples was between 10~3 ~10~7CFU /ml. There was no obvious difference between the result from RT-PCR quantification and that from cultured method (P > 0.05); The direct quantita-tion by PCR showed a satisfactory distinguishability when Bifidobacteria in feces samples was between 10~1 ~ 10~7CFU /ml, without obvious difference between the result from RT-PCR and that from cultured method (P > 0. 05). Conclusion Bifidobacteria in feces samples can be directly quantitated or semiquantitated by real-time PCR method or common PCR method.%目的 建立快速、准确从粪便标本中定量双歧杆菌的RT-PCR技术.方法 传统培养定量法,普通PCR定量法,real-time PCR 比较测量.结果 (1)粪便标本前处理采取简单的离心和清洗、稀释步骤能去除粪便标本中的抑制物,实现不提取 DNA直接进行PCR、real-time定量粪便中双歧杆菌.(2)本实验建立的PCR方法直接半定量粪便双歧杆菌技术在双歧杆菌值介于10~3~10~7CFU/ml时具有较好的分辨率,粪便标本普通PCR得理论菌数与培养得菌数值之间差异无显著性(P>0.05);real-time PCR直接定量双歧杆菌技术在双歧杆菌值介于10~1~10~7CFU /ml时具有较好的分辨率,粪便标本RT-PCR得理论菌数与培养得菌数值之间差异无显著性(P>0.05).结论 利用PCR、real-time PCR直接半定量和定量粪便中的双歧杆菌可行.

  14. Real-time growth kinetics measuring hormone mimicry for ToxCast chemicals in T-47D human ductal carcinoma cells. (United States)

    Rotroff, Daniel M; Dix, David J; Houck, Keith A; Kavlock, Robert J; Knudsen, Thomas B; Martin, Matthew T; Reif, David M; Richard, Ann M; Sipes, Nisha S; Abassi, Yama A; Jin, Can; Stampfl, Melinda; Judson, Richard S


    High-throughput screening (HTS) assays capable of profiling thousands of environmentally relevant chemicals for in vitro biological activity provide useful information on the potential for disrupting endocrine pathways. Disruption of the estrogen signaling pathway has been implicated in a variety of adverse health effects including impaired development, reproduction, and carcinogenesis. The estrogen-responsive human mammary ductal carcinoma cell line T-47D was exposed to 1815 ToxCast chemicals comprising pesticides, industrial chemicals, pharmaceuticals, personal care products, cosmetics, food ingredients, and other chemicals with known or suspected human exposure potential. Cell growth kinetics were evaluated using real-time cell electronic sensing. T-47D cells were exposed to eight concentrations (0.006-100 μM), and measurements of cellular impedance were repeatedly recorded for 105 h. Chemical effects were evaluated based on potency (concentration at which response occurs) and efficacy (extent of response). A linear growth response was observed in response to prototypical estrogen receptor agonists (17β-estradiol, genistein, bisphenol A, nonylphenol, and 4-tert-octylphenol). Several compounds, including bisphenol A and genistein, induced cell growth comparable in efficacy to that of 17β-estradiol, but with decreased potency. Progestins, androgens, and corticosteroids invoked a biphasic growth response indicative of changes in cell number or cell morphology. Results from this cell growth assay were compared with results from additional estrogen receptor (ER) binding and transactivation assays. Chemicals detected as active in both the cell growth and ER receptor binding assays demonstrated potencies highly correlated with two ER transactivation assays (r = 0.72; r = 0.70). While ER binding assays detected chemicals that were highly potent or efficacious in the T-47D cell growth and transactivation assays, the binding assays lacked sensitivity in detecting

  15. Real-time imaging of resident T cells in human lung and ovarian carcinomas reveals how different tumor microenvironments control T lymphocyte migration

    Directory of Open Access Journals (Sweden)

    Houcine eBougherara


    Full Text Available T cells play a key role in the battle against cancer. To perform their antitumor activities, T cells need to adequately respond to tumor antigens by establishing contact with either malignant cells or antigen-presenting cells. These latter functions rely on a series of migratory steps that go from entry of T cells into the tumor followed by their locomotion in the tumor stroma. Our knowledge of how T cells migrate within tumors mainly comes from experiments performed in mouse models. Whereas such systems have greatly advanced our understanding, they do not always faithfully recapitulate the disease observed in cancer patients. We previously described a technique based on tissue slices that enables to track with real-time imaging microscopy the motile behavior of fluorescent T cells plated onto fresh sections of human lung tumors. We have now refined this approach to monitor the locomotion of resident tumor-infiltrating CD8 T cells labeled with fluorescently-coupled antibodies. Using this approach, our findings reveal that CD8 T cells accumulate in the stroma of ovarian and lung carcinomas but move slowly in this compartment. Conversely, even though less populated, tumors islets were found to be zones of faster migration for resident CD8 T cells. We also confirm the key role played by collagen fibers which, by their orientation, spacing and density, control the distribution and migration of resident CD8 T cells within the tumor stroma. We have subsequently demonstrated that under some physical tissue constraints CD8 T cells exhibited a mode of migration characterized by alternate forward and backward movements. In sum, using an ex vivo assay to track CD8 T cells in fresh human tumor tissues, we have identified the extracellular matrix as a major stromal component in influencing T cell migration, thereby impacting control of tumor growth. This approach will aid in the development and testing of novel immunotherapy strategies to promote T cell

  16. An Undergraduate Laboratory Experiment for Upper-Level Forensic Science, Biochemistry, or Molecular Biology Courses: Human DNA Amplification Using STR Single Locus Primers by Real-Time PCR with SYBR Green Detection (United States)

    Elkins, Kelly M.; Kadunc, Raelynn E.


    In this laboratory experiment, real-time polymerase chain reaction (real-time PCR) was conducted using published human TPOX single-locus DNA primers for validation and various student-designed short tandem repeat (STR) primers for Combined DNA Index System (CODIS) loci. SYBR Green was used to detect the amplification of the expected amplicons. The…

  17. Capillary electrophoresis-time of flight-mass spectrometry using noncovalently bilayer-coated capillaries for the analysis of amino acids in human urine. (United States)

    Ramautar, Rawi; Mayboroda, Oleg A; Derks, Rico J E; van Nieuwkoop, Cees; van Dissel, Jaap T; Somsen, Govert W; Deelder, André M; de Jong, Gerhardus J


    A capillary electrophoresis-time of flight-mass spectrometry (CE-TOF-MS) method for the analysis of amino acids in human urine was developed. Capillaries noncovalently coated with a bilayer of Polybrene (PB) and poly(vinyl sulfonate) (PVS) provided a considerable EOF at low pH, thus facilitating the fast separation of amino acids using a BGE of 1 M formic acid (pH 1.8). The PB-PVS coating proved to be very consistent yielding stable CE-MS patterns of amino acids in urine with favorable migration time repeatability (RSDs capillary preconcentration step based on pH-mediated stacking allowing 100-nL sample injection (i.e. ca. 4% of capillary volume). As a result, LODs for amino acids were down to 20 nM while achieving satisfactory separation efficiencies. Preliminary validation of the method with urine samples showed good linear responses for the amino acids (R(2) >0.99), and RSDs for peak areas were <10%. Special attention was paid to the influence of matrix effects on the quantification of amino acids. The magnitude of ion suppression by the matrix was similar for different urine samples. The CE-TOF-MS method was used for the analysis of urine samples of patients with urinary tract infection (UTI). Concentrations of a subset of amino acids were determined and compared with concentrations in urine of healthy controls. Furthermore, partial least squares-discriminant analysis (PLS-DA) of the CE-TOF-MS dataset in the 50-450 m/z region showed a distinctive grouping of the UTI samples and the control samples. Examination of score and loadings plot revealed a number of compounds, including phenylalanine, to be responsible for grouping of the samples. Thus, the CE-TOF-MS method shows good potential for the screening of body fluids based on the analysis of endogenous low-molecular weight metabolites such as amino acids and related compounds.

  18. Application of europium(III) chelates-bonded silica nanoparticle in time-resolved immunofluorometric detection assay for human thyroid stimulating hormone

    Energy Technology Data Exchange (ETDEWEB)

    Zhou Yulin [Xiamen Branch of Fujian Newborn Screening Centre and Xiamen Prenatal Diagnosis Centre, Xiamen Maternal and Children' s Health Care Hospital, Xiamen, Fujian 361003 (China); Xia Xiaohu; Xu Ye; Ke Wei [Engineering Research Centre of Molecular Diagnostics Laboratory, MOE, Department of Biomedical Sciences and the Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005 (China); Yang Wei, E-mail: [Engineering Research Centre of Molecular Diagnostics Laboratory, MOE, Department of Biomedical Sciences and the Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005 (China); Li Qingge, E-mail: [Engineering Research Centre of Molecular Diagnostics Laboratory, MOE, Department of Biomedical Sciences and the Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005 (China)


    Highlights: Black-Right-Pointing-Pointer A rapid and ultrasensitive TSH immunoassay was developed using fluorescent silica nanoparticles-based TrIFA. Black-Right-Pointing-Pointer The assay is of high sensitivity with short period time request. Black-Right-Pointing-Pointer method can be potentially used at hospitals for daily clinical practice in hTSH screening. - Abstract: Eu(III) chelate-bonded silica nanoparticle was used as a fluorescent label to develop a highly sensitive time-resolved immunofluorometric assay (TrIFA) for human thyroid stimulating hormone (hTSH). The limit of detection of the assay calculated according to the 2SD method was 0.0007 mIU L{sup -1} and became 0.003 mIU L{sup -1} when serum-based matrix was used for calibrators, indicating that this TrIFA is comparable with the most sensitive assays. The linear range was from 0.005 to 100 mIU L{sup -1} of hTSH with coefficient of variation between 1.9% and 8.3%. The correlation study using 204 blood spot samples from newborns showed that the results from this new method were coincident with that of the commercial dissociation-enhanced lanthanide fluorescence immunoassay (DELFIA) system, with a correlation coefficient of 0.938. The fluorescent nanoparticle label allows directly reading the fluorescent signal, omitting the signal development step required for the DELFIA system, and the whole procedure of this assay is fulfilled within 2 h. Thus, we developed a novel, sensitive, quantitative and simple nanoparticle label-based TrIFA assay, suitable for routine application in hTSH screening of neonatal hypothyroidism.

  19. No effect of an UMTS mobile phone-like electromagnetic field of 1.97 GHz on human attention and reaction time. (United States)

    Unterlechner, Manuela; Sauter, Cornelia; Schmid, Gernot; Zeitlhofer, Josef


    Several studies in the past reported influences of electromagnetic emissions of GSM phones on reaction time in humans. However, there are currently only a few studies available dealing with possible effects of the electromagnetic fields emitted by UMTS mobile phones. In our study, 40 healthy volunteers (20 female, 20 male), aged 26.0 years (range 21-30 years) underwent four different computer tests measuring reaction time and attention under three different UMTS mobile phone-like exposure conditions (two exposure levels plus sham exposure). Exposure of the subjects was accomplished by small helical antennas operated close to the head and fed by a generic signal representing the emissions of a UMTS mobile phone under constant receiving conditions as well as under a condition of strongly varying transmit power. In the high exposure condition the resulting peak spatial average exposure of the test subjects in the cortex of the left temporal lobe of the brain was 0.63 W/kg (min. 0.25 W/kg, max. 1.49 W/kg) in terms of 1 g averaged SAR and 0.37 W/kg (min. 0.16 W/kg, max. 0.84 W/kg) in terms of 10 g averaged SAR, respectively. Low exposure condition was one-tenth of high exposure and sham was at least 50 dB below low exposure. Statistical analysis of the obtained test parameters showed that exposure to the generic UMTS signal had no statistically significant immediate effect on attention or reaction. Therefore, this study does not provide any evidence that exposure of UMTS mobiles interferes with attention under short-term exposure conditions.

  20. The perfect time to be stressed: a differential modulation of human memory by stress applied in the morning or in the afternoon. (United States)

    Maheu, Françoise S; Collicutt, Patrick; Kornik, Rachel; Moszkowski, Robin; Lupien, Sonia J


    We measured the effects of a stressful experience on memory for emotionally arousing and neutral material learned after exposure to a stressor which induces a significant increase in corticosteroid stress hormones. Because memory performance can be influenced by circadian changes in corticosteroid levels, subjects were tested either in the morning or in the afternoon. Nineteen healthy men (9 in the morning group and 10 in the afternoon group) were submitted to a psychological stress task before viewing a story composed of emotionally negative and neutral segments, while another 20 healthy males (10 in the morning group and 10 in the afternoon group) viewed the story without being exposed to the psychological stressor. Salivary cortisol levels were measured before and after the stressor. Memory performance was assessed by a one week post learning delayed recall. Results show that stress-induced increases in salivary cortisol levels impaired delayed free recall of emotionally arousing material in the morning group, but not in the afternoon group. There was no effect of stress on memory for neutral material. Altogether, these findings suggest that stressing participants in the morning, at a time of high circulating levels of corticosteroids, over stimulated the corticosteroid receptors in the brain, impairing declarative memory for emotionally arousing material unrelated to the stressor. These findings suggest that the experimental context, i.e., time of day at which the experiment occurs, the nature of the to-be-remembered material (remembering the stressful event itself or material unrelated to the stressor) and the valence of the to-be-remembered material (emotionally arousing vs. neutral), modulates the effects of stress on human declarative memory.

  1. Development of Human Face Detection System Based on Real-time Camera Image%摄像头实时图像人脸检测系统开发

    Institute of Scientific and Technical Information of China (English)

    孙雅琪; 刘羽


    人脸检测是计算机视觉领域中一个重要的研究热点,也是人脸识别、表情识别等研究的基础.论文首先通过截取摄像头实时图像,然后通过转换彩色空间、人脸肤色建模、图像处理和人脸定位算法实现了人脸检测功能.详细介绍了基于摄像头的人脸图像采集开发和人脸检测等主要步骤,并由此开发了摄像头实时图像的人脸检测系统.试验结果表明,论文提出的方法是可行的.%Human face detection is an important research in the field of computer vision.It also is a basic research of face recognition and expression recognition etc.Firstly,the camera real-time image is captured,and then the face detection function is realized through conversing of color space,skin color model,image processing and face location algorithm are built.The main steps of developing the face images acquisition based on camera and face detection are introduced in detail.At last,the face detection system based on real-time camera image is developed.The test results show that,the proposed method is feasible.

  2. Modeling high resolution space-time variations in energy demand/CO2 emissions of human inhabited landscapes in the United States under a changing climate (United States)

    Godbole, A. V.; Gurney, K. R.


    With urban and exurban areas now accounting for more than 50% of the world's population, projected to increase 20% by 2050 (UN World Urbanization Prospects, 2009), urban-climate interactions are of renewed interest to the climate change scientific community (Karl et. al, 1988; Kalnay and Cai, 2003; Seto and Shepherd, 2009). Until recently, climate modeling efforts treated urban-human systems as independent of the earth system. With studies pointing to the disproportionately large influence of urban areas on their surrounding environment (Small et. al, 2010), modeling efforts have begun to explicitly account for urban processes in land models, like the CLM 4.0 urban layer, for example ( al, 2008, 2010). A significant portion of the urban energy demand comes from the space heating and cooling requirement of the residential and commercial sectors - as much as 51% (DOE, RECS 2005) and 11% (Belzer, D. 2006) respectively, in the United States. Thus, these sectors are both responsible for a significant fraction of fossil fuel CO2 emissions and will be influenced by a changing climate through changes in energy use and energy supply planning. This points to the possibility of interactive processes and feedbacks with the climate system. Space conditioning energy demand is strongly driven by external air temperature (Ruth, M., 2006) in addition to other socio-economic variables such as building characteristics (age of structure, activity cycle, weekend/weekday usage profile), occupant characteristics (age of householder, household income) and energy prices (Huang, 2006; Santin et. al, 2009; Isaac and van Vuuren, 2009). All of these variables vary both in space and time. Projections of climate change have begun to simulate changes in temperature at much higher resolution than in the past (Diffenbaugh et. al, 2005). Hence, in order to understand how climate change and variability will potentially impact energy use/emissions and energy planning, these two

  3. Prevalence of human papillomavirus in 5,072 consecutive cervical SurePath samples evaluated with the Roche cobas HPV real-time PCR assay

    DEFF Research Database (Denmark)

    Preisler, Sarah; Rebolj, Matejka; Untermann, Anette;


    New commercially available Human Papillomavirus (HPV) assays need to be evaluated in a variety of cervical screening settings. Cobas HPV Test (cobas) is a real-time PCR-based assay allowing for separate detection of HPV genotypes 16 and 18 and a bulk of 12 other high-risk genotypes. The aim...... of the present study, Horizon, was to assess the prevalence of high-risk HPV infections in an area with a high background risk of cervical cancer, where women aged 23-65 years are targeted for cervical screening. We collected 6,258 consecutive cervical samples from the largest cervical screening laboratory...... in Denmark serving the whole of Copenhagen. All samples were stored in SurePath media. In total, 5,072 samples were tested with cobas, Hybrid Capture 2 High Risk HPV DNA test (HC2) and liquid-based cytology. Of these, 27% tested positive on cobas. This proportion decreased by age, being 43% in women aged 23...

  4. Extreme patterns of variance in small populations: placing limits on human Y-chromosome diversity through time in the Vanuatu Archipelago. (United States)

    Cox, M


    Small populations are dominated by unique patterns of variance, largely characterized by rapid drift of allele frequencies. Although the variance components of genetic datasets have long been recognized, most population genetic studies still treat all sampling locations equally despite differences in sampling and effective population sizes. Because excluding the effects of variance can lead to significant biases in historical reconstruction, variance components should be incorporated explicitly into population genetic analyses. The possible magnitude of variance effects in small populations is illustrated here via a case study of Y-chromosome haplogroup diversity in the Vanuatu Archipelago. Deme-based modelling is used to simulate allele frequencies through time, and conservative confidence bounds are placed on the accumulation of stochastic variance effects, including diachronic genetic drift and contemporary sampling error. When the information content of the dataset has been ascertained, demographic models with parameters falling outside the confidence bounds of the variance components can then be accepted with some statistical confidence. Here I emphasize how aspects of the demographic history of a population can be disentangled from stochastic variance effects, and I illustrate the extreme roles of genetic drift and sampling error for many small human population datasets.

  5. Technical advance: introducing a novel metric, directionality time, to quantify human neutrophil chemotaxis as a function of matrix composition and stiffness. (United States)

    O'Brien, Xian M; Loosley, Alex J; Oakley, Katie E; Tang, Jay X; Reichner, Jonathan S


    A direct consequence of cellular movement and navigation, migration incorporates elements of speed, direction, and persistence of motion. Current techniques to parameterize the trajectory of a chemotaxing cell most commonly pair migration speed with some measure of persistence by calculating MSD, RMS speed, TAD, and/or CI. We address inherent limitations in TAD and CI for comparative analysis by introducing two new analytical tools to quantify persistence: directionality index and directionality time. With the use of these tools, we show that the mechanical properties of the underlying substrate contribute significantly to the regulation of human neutrophil chemotaxis toward fMLP on Fgn-, Col-, and Fn-coated gels of varying elasticity. The β₁-integrin ligand Col demonstrated mechanosensitive speed. In contrast, β₂-integrin ligand Fgn supported mechanosensitive persistence. Fn, recognized by β₁ and β₂ integrins, mechanoregulated speed and persistence. Blocking β₂ integrins of cells migrating on Fn identified an underlying β₂-integrin-directed modulation of persistence. These data demonstrate that individual components of the neutrophil chemotactic response show integrin dependence and are finely tunable with different ligand, mechanotactic, and chemotactic cues, underscoring the need for sensitive analytical methods.

  6. Building vulnerability and human loss assessment in different earthquake intensity and time: a case study of the University of the Philippines, Los Baños (UPLB) Campus (United States)

    Rusydy, I.; Faustino-Eslava, D. V.; Muksin, U.; Gallardo-Zafra, R.; Aguirre, J. J. C.; Bantayan, N. C.; Alam, L.; Dakey, S.


    Study on seismic hazard, building vulnerability and human loss assessment become substantial for building education institutions since the building are used by a lot of students, lecturers, researchers, and guests. The University of the Philippines, Los Banos (UPLB) located in an earthquake prone area. The earthquake could cause structural damage and injury of the UPLB community. We have conducted earthquake assessment in different magnitude and time to predict the posibility of ground shaking, building vulnerability and estimated the number of casualty of the UPLB community. The data preparation in this study includes the earthquake scenario modeling using Intensity Prediction Equations (IPEs) for shallow crustal shaking attenuation to produce intensity map of bedrock and surface. Earthquake model was generated from the segment IV and the segment X of the Valley Fault System (VFS). Building vulnerability of different type of building was calculated using fragility curve of the Philippines building. The population data for each building in various occupancy time, damage ratio, and injury ratio data were used to compute the number of casualties. The result reveals that earthquake model from the segment IV and the segment X of the VFS could generate earthquake intensity between 7.6 – 8.1 MMI in the UPLB campus. The 7.7 Mw earthquake (scenario I) from the segment IV could cause 32% - 51% damage of building and 6.5 Mw earthquake (scenario II) occurring in the segment X could cause 18% - 39% structural damage of UPLB buildings. If the earthquake occurs at 2 PM (day-time), it could injure 10.2% - 18.8% for the scenario I and could injure 7.2% - 15.6% of UPLB population in scenario II. The 5 Pm event, predicted will injure 5.1%-9.4% in the scenario I, and 3.6%-7.8% in scenario II. A nighttime event (2 Am) cause injury to students and guests who stay in dormitories. The earthquake is predicted to injure 13 - 66 students and guests in the scenario I and 9 - 47 people in

  7. Use of surface plasmon resonance for real-time measurements of the global conformational transition in human phenylalanine hydroxylase in response to substrate binding and catalytic activation. (United States)

    Flatmark, T; Stokka, A J; Berge, S V


    In the present study the optical biosensor technique, based on the surface plasmon resonance (SPR) phenomenon, was used for real-time measurements of the reversible binding of the pterin cofactor (6R)-l-erythro-5,6,7,8-tetrahydrobiopterin (BH(4)) and l-phenylalanine (l-Phe) to human phenylalanine hydroxylase (hPAH). When BH(4) (241 Da) was injected over the sensor chip with immobilized tetrameric wt-hPAH a positive DeltaRU response was observed with a square-wave type of sensorgram and a saturable response (about 25 RU/(pmol subunit/mm(2)) with a [S](0.5) value of 5.6 +/- 0.8 microM for the pterin cofactor. The rapid on-and-off rates were, however, not possible to determine. By contrast, when l-Phe (165 Da) was injected a time-dependent increase in RU (up to about 3 min) and a much higher saturable DeltaRU response (about 75 RU/(pmol subunit/mm(2)) at 2 mM l-Phe) than expected (i.e., <5 RU/(pmol subunit/mm(2))) from the low molecular mass of l-Phe were observed in the sensorgram. The half-time for the on-and-off rates were 6 +/- 2 and 9 +/- 1 s, respectively, at 2 mM l-Phe. The steady-state (apparent equilibrium) response revealed a hyperbolic concentration dependence with a [S](0.5) value of 98 +/- 7 microM. The [S](0.5) values of both pterin cofactor and l-Phe were lower than those determined by steady-state enzyme kinetic analysis. Evidence is presented that the DeltaRU response to l-Phe is accounted for by the global conformational transition which occurs in the enzyme upon l-Phe binding, i.e., by the slow reversible transition from a low activity state ("T"-state) to a high activity state ("R"-state) characteristic of this hysteretic enzyme.

  8. The limits of human endurance: what is the greatest endurance performance of all time? Which factors regulate performance at extreme altitude? (United States)

    Noakes, Timothy David


    Humans evolved as an athletic species able to run in the midday heat, to throw with exquisite accuracy and to strike powerfully despite relatively weak upper arms compared to those of the great apes. The true extent to which humans could run long distances was first tested in a unique series of 6-day foot races contested between 1874 and 1888 by professional athletes from England and the United States. These athletes typically would have expended approximately 60,000 kcal (24.12 MJ) of energy during these races. The discovery of the bicycle soon caused the replacement of these races by 6-day cycling races which, in turn, led to the modern day Tour de France, the cycling race across America (RaAM) and two running races across the width of the United States in 1928 and 1929. The total energy expenditures during these different events can be estimated at approximately 168,000, 180,000 and 340,000 kcal respectively. But, in terms of the total energy expenditure, all these performances pale somewhat when compared to that of Robert Falcon Scott's Polar party during the 1911/12 British Antarctic Expedition. For most of 159 consecutive days, Scott's team man-hauled for 10 hours a day to the South Pole and back covering a distance of 2500 km. Their predicted total energy expenditure per individual would have been about 1 million kcal, making theirs, by some margin, the greatest sustained endurance athletic performance of all time. Interestingly, the dogs that provided the pulling power for Norwegian